The driver landscape of sporadic chordoma

Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma

Prevalence and risk factors of viral diseases in broiler farms contracted to multifactorial respiratory syndrome

Newcastle, Influenza H9N2 and Infectious Bronchitis are the major respiratory diseases in broiler poultry farming in Iran. This study aims to investigate prevalence and risk factors of these viral diseases in commercial broiler chicken farms contracted to multi-factorial respiratory syndrome in Iran. In this cross-sectional study, 157 affected commercial broiler chicken farms in Iran were sampled during 2017 to 2019. Samples were examined for avian influenza H9N2, Newcastle, and infectious bronchitis by performing reverse transcription polymerase chain reaction. Possible risk factors for the occurrence of viral diseases were investigated by comparing the mean and frequency of the factors, as well as performing univariate and multivariate regression analysis. Highest frequency of investigated viral diseases was due to Newcastle disease with 98 cases (62.43%, CI 95%= 54.35-70.01). Frequency of avian influenza H9N2 and infectious bronchitis was respectively 74 cases (47.13%, CI 95%= 39.13-55.25) and 22 cases (14.1%, CI 95%= 8.99-20.44). Flock age (Odd Ratio: 2.65, P value: 0.030) and first week mortality (Odd Ratio: 10.12, P value: 0.014) respectively had significant effect on occurrence of influenza H9N2 and co-infection of influenza H9N2. Control strategies must be implemented on the broiler farms. Continuous monitoring of the farms and investigation of the the farm vaccination programs every year are among the necessary control strategies measures and must be implemented

Tumour Cell Heterogeneity.

The population of cells that make up a cancer are manifestly heterogeneous at the genetic, epigenetic, and phenotypic levels. In this mini-review, we summarise the extent of intra-tumour heterogeneity (ITH) across human malignancies, review the mechanisms that are responsible for generating and maintaining ITH, and discuss the ramifications and opportunities that ITH presents for cancer prognostication and treatment

Exploration of neural correlates of movement intention based on characterisation of temporal dependencies in electroencephalography

Brain computer interfaces (BCIs) provide a direct communication channel by using brain signals, enabling patients with motor impairments to interact with external devices. Motion intention detection is useful for intuitive movement-based BCI as movement is the fundamental mode of interaction with the environment. The aim of this paper is to investigate the temporal dynamics of brain processes using electroencephalography (EEG) to explore novel neural correlates of motion intention. We investigate the changes in temporal dependencies of the EEG by characterising the decay of autocorrelation during asynchronous voluntary finger tapping movement. The evolution of the autocorrelation function is characterised by its relaxation time, which is used as a robust marker for motion intention. We observed that there was reorganisation of temporal dependencies in EEG during motion intention. The autocorrelation decayed slower during movement intention and faster during the resting state. There was an increase in temporal dependence during movement intention. The relaxation time of the autocorrelation function showed significant (p < 0.05) discrimination between movement and resting state with the mean sensitivity of 78.37 ± 8.83%. The relaxation time provides movement related information that is complementary to the well-known event-related desynchronisation (ERD) by characterising the broad band EEG dynamics which is frequency independent in contrast to ERD. It can also detect motion intention on average 0.51s before the actual movement onset. We have thoroughly compared autocorrelation relaxation time features with ERD in four frequency bands. The relaxation time may therefore, complement the well-known features used in motion-based BCI leading to more robust and intuitive BCI solutions. The results obtained suggest that changes in autocorrelation decay may involve reorganisation of temporal dependencies of brain activity over longer duration during motion intention. This opens the possibilities of investigating further the temporal dynamics of fundamental neural processes underpinning motion intention

Phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations.

Several studies using genome-wide molecular techniques have reported various degrees of genetic heterogeneity between primary tumours and their distant metastases. However, it has been difficult to discern patterns of dissemination owing to the limited number of patients and available metastases. Here, we use phylogenetic techniques on data generated using whole-exome sequencing and copy number profiling of primary and multiple-matched metastatic tumours from ten autopsied patients to infer the evolutionary history of breast cancer progression. We observed two modes of disease progression. In some patients, all distant metastases cluster on a branch separate from their primary lesion. Clonal frequency analyses of somatic mutations show that the metastases have a monoclonal origin and descend from a common 'metastatic precursor'. Alternatively, multiple metastatic lesions are seeded from different clones present within the primary tumour. We further show that a metastasis can be horizontally cross-seeded. These findings provide insights into breast cancer dissemination

The simultaneous presence of three different Newcastle Disease Virus Genotypes in various bird species in a public bird garden

Newcastle disease (ND) is one of the most important contagious bird diseases. Not only it continuously causes significant economic damage to the commercial poultry industry, but also it is of clinical importance as it occurs in a wide range of free-living and captive birds. Although different types of commercial vaccines are extensively used, the disease has not been eradicated. Between October 2018 and March 2019, three different outbreaks of ND were observed in three different captive bird species of pigeons, peafowls, and pheasants at the Saei public bird garden in Tehran. Genetic identification of viral isolates of AMMM116 (pheasant), AMMM122 (peafowl), and AMMM160 (pigeon) indicated the presence of genotypes VII.1.1, II, and VI.2.1.2, respectively. The virus isolated from the pheasants was closely related to the VII.1.1 subgenotypes obtained from commercial poultry farms in different parts of Iran. Moreover, the VI.2.1.2 isolate obtained from the ND outbreak in pigeons was related to the isolates obtained from pigeons in Nigeria and Kenya. Lastly, we isolated a genotype II NDV, identical to the common vaccine strains, from immature peacocks that had an acute death. The peacocks were not vaccinated, therefore, we speculated that the presence of genotype II could be because of the spillover of vaccine strains from commercial poultry flocks to wild birds that had visited the park and landed in the roofless aviary. The results of this study indicate the simultaneous circulation of different NDV genotypes in a small geographic location and emphasize the importance of imposing more restricted biosecurity measures

Immune activation in irritable bowel syndrome: can neuroimmune interactions explain symptoms?

Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal (GI) tract characterized by pain or discomfort from the lower abdominal region, which is associated with altered bowel habit. Despite its prevalence, there is currently a lack of effective treatment options for patients. IBS has long been considered as a neurological condition resulting from alterations in the brain gut axis, but immunological alterations are increasingly reported in IBS patients, consistent with the hypothesis that there is a chronic, but low-grade, immune activation. Mediators released by immune cells act to either dampen or amplify the activity of GI nerves. Release of a number of these mediators correlates with symptoms of IBS, highlighting the importance of interactions between the immune and the nervous systems. Investigation of the role of microbiota in these interactions is in its early stages, but may provide many answers regarding the mechanisms underlying activation of the immune system in IBS. Identifying what the key changes in the GI immune system are in IBS and how these changes modulate viscerosensory nervous function is essential for the development of novel therapies for the underlying disorder.Patrick A. Hughes, Heddy Zola, Irmeli A. Penttila, L. Ashley Blackshaw, Jane M. Andrews, and Doreen Krumbiege

Ovarian cancer

Ovarian cancer is not a single disease and can be subdivided into at least five different histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents and poly(ADP-ribose) polymerase inhibitors are used, and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and at diagnosis is typically very responsive to platinum-based chemotherapy. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy. Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Substantial progress has been made in identifying genes that are associated with a high risk of ovarian cancer (such as BRCA1 and BRCA2), as well as a precursor lesion of HGSC called serous tubal intraepithelial carcinoma, which holds promise for identifying individuals at high risk of developing the disease and for developing prevention strategies

Single Balloon Enteroscopy in the Elderly

Background: Single-balloon enteroscopy (SBE) is a minimally invasive procedure to assess and treat small bowel pathologies. The most common use is to detect suspected small bowel bleeding: Insignificant gastrointestinal (GI) bleeding or iron deficiency anaemia (IDA). The safety and feasibility of SBE in the elderly has not been adequately studied. Aim: To assess the safety and feasibility of both antegrade and retrograde SBE in elderly patients. Methods: We performed a retrospective cohort study of all antegrade and retrograde SBE done at our center from March 2011 through May 2020. We collected patient\u27s data including demographics, indications, findings, therapeutic interventions, and complications. The cohort was divided into 3 groups: Patients younger than 65 years (group 1), patients 65-75 years (group 2), and patients older than 75 years (group 3). We used 1-way one way analysis of variance, a χ 2 test, and logistic regression to compare study outcomes. The primary aim was to assess diagnostic yield, therapeutic yield and rates of complications from SBE among study groups. Results: A total of 284 SBE were performed in 227 patients. In the 227 patients, we analyzed 194 antegrade (19 in gastric bypass patients) and 33 retrograde procedures. Mean age was 62.0 (SD: 16.7), 130 patients were women (57.3%), 98 were Hispanic (43.4%), and mean body mass index was 28 (SD: 6.3). The number of patients in each group were: Group 1 (117, 51.3%), group 2 (57, 25.0%) and group 3 (53, 23.7%). Gender, ethnicity, body mass index and proportions of antegrade and retrograde were comparable between age groups. The most common indications for procedure were: Obscure GI bleeding (48%), IDA (48%), abdominal pain (14%), and others (abnormal capsule, 43%; abnormal imaging, 9.7%; diarrhea 5.3%). The elderly (group 3) were more likely to have GI bleed as the indication (42.7%, 40.4%, 67.9%, P = 0.004) without difference in IDA (44.4%, 56.1%, 47.2%, P = 0.35). Diagnostic yield was significantly higher in the elderly group (48.2%, 53.7%, 68.0%), particularly in antegrade (48.5%, 53.3%, 72.1%, P = 0.033). Angioectasias were the most common finding (21.0%) and present more often in the elderly (10.9%, 20.4%, 44%) (P \u3c 0.001). Therapeutic interventions were also more in the elderly group (35.0%, 33.3%, 58.5%, P = 0.007). There were only 2 (0.9%) complications, including minor oropharyngeal hemorrhage and esophageal trauma and no deaths, with no difference among groups. Conclusion: In a retrospective analysis of SBE, we found this procedure safe and feasible in the elderly. SBE has higher diagnostic and therapeutic yields in the elderly vs the other age groups, mainly because of the increased small bowel angioectasias

Feature-based classifiers for somatic mutation detection in tumour–normal paired sequencing data

Motivation: The study of cancer genomes now routinely involves using next-generation sequencing technology (NGS) to profile tumours for single nucleotide variant (SNV) somatic mutations. However, surprisingly few published bioinformatics methods exist for the specific purpose of identifying somatic mutations from NGS data and existing tools are often inaccurate, yielding intolerably high false prediction rates. As such, the computational problem of accurately inferring somatic mutations from paired tumour/normal NGS data remains an unsolved challenge