5,150 research outputs found

    Leveraging technology-driven strategies to untangle omics big data: circumventing roadblocks in clinical facets of oral cancer

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    Oral cancer is one of the 19most rapidly progressing cancers associated with significant mortality, owing to its extreme degree of invasiveness and aggressive inclination. The early occurrences of this cancer can be clinically deceiving leading to a poor overall survival rate. The primary concerns from a clinical perspective include delayed diagnosis, rapid disease progression, resistance to various chemotherapeutic regimens, and aggressive metastasis, which collectively pose a substantial threat to prognosis. Conventional clinical practices observed since antiquity no longer offer the best possible options to circumvent these roadblocks. The world of current cancer research has been revolutionized with the advent of state-of-the-art technology-driven strategies that offer a ray of hope in confronting said challenges by highlighting the crucial underlying molecular mechanisms and drivers. In recent years, bioinformatics and Machine Learning (ML) techniques have enhanced the possibility of early detection, evaluation of prognosis, and individualization of therapy. This review elaborates on the application of the aforesaid techniques in unraveling potential hints from omics big data to address the complexities existing in various clinical facets of oral cancer. The first section demonstrates the utilization of omics data and ML to disentangle the impediments related to diagnosis. This includes the application of technology-based strategies to optimize early detection, classification, and staging via uncovering biomarkers and molecular signatures. Furthermore, breakthrough concepts such as salivaomics-driven non-invasive biomarker discovery and omics-complemented surgical interventions are articulated in detail. In the following part, the identification of novel disease-specific targets alongside potential therapeutic agents to confront oral cancer via omics-based methodologies is presented. Additionally, a special emphasis is placed on drug resistance, precision medicine, and drug repurposing. In the final section, we discuss the research approaches oriented toward unveiling the prognostic biomarkers and constructing prediction models to capture the metastatic potential of the tumors. Overall, we intend to provide a bird’s eye view of the various omics, bioinformatics, and ML approaches currently being used in oral cancer research through relevant case studies

    Application of Machine Learning algorithms for experimental data processing and estimation of

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    In this paper, Machine learning techniques have been employed for preparation and estimation of 96 Mo (n, p) 96Nb reaction data. The experimental data of 96 Mo (n, p) 96Nb reaction available in the EXFOR database was retrieved, analyzed and processed using renormalization and data cleaning techniques. Estimation of the renormalized experimental data with outlier and without outlier, over the entire neutron energy range, was then performed using machine learning regression algorithms of Ordinary Least square, Ridge, Least Absolute Shrinkage and Selection Operator (LASSO) and Support Vector Regressor. The results obtained were then compared and it was observed that the data preparation plays a significant role in data quality

    Feasibility of comparing medical management and surgery (with neurosurgery or stereotactic radiosurgery) with medical management alone in people with symptomatic brain cavernoma - protocol for the Cavernomas: A Randomised Effectiveness (CARE) pilot trial

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    IntroductionThe top research priority for cavernoma, identified by a James Lind Alliance Priority setting partnership was 'Does treatment (with neurosurgery or stereotactic radiosurgery) or no treatment improve outcome for people diagnosed with a cavernoma?' This pilot randomised controlled trial (RCT) aims to determine the feasibility of answering this question in a main phase RCT.Methods and analysisWe will perform a pilot phase, parallel group, pragmatic RCT involving approximately 60 children or adults with mental capacity, resident in the UK or Ireland, with an unresected symptomatic brain cavernoma. Participants will be randomised by web-based randomisation 1:1 to treatment with medical management and with surgery (neurosurgery or stereotactic radiosurgery) versus medical management alone, stratified by prerandomisation preference for type of surgery. In addition to 13 feasibility outcomes, the primary clinical outcome is symptomatic intracranial haemorrhage or new persistent/progressive focal neurological deficit measured at 6‚ÄČmonthly intervals. An integrated QuinteT Recruitment Intervention (QRI) evaluates screening logs, audio recordings of recruitment discussions, and interviews with recruiters and patients/parents/carers to identify and address barriers to participation. A Patient Advisory Group has codesigned the study and will oversee its progress.Ethics and disseminationThis study was approved by the Yorkshire and The Humber-Leeds East Research Ethics Committee (21/YH/0046). We will submit manuscripts to peer-reviewed journals, describing the findings of the QRI and the Cavernomas: A Randomised Evaluation (CARE) pilot trial. We will present at national specialty meetings. We will disseminate a plain English summary of the findings of the CARE pilot trial to participants and public audiences with input from, and acknowledgement of, the Patient Advisory Group.Trial registration numberISRCTN41647111

    Taxane chemotherapy induces stromal injury that leads to breast cancer dormancy escape.

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    A major cause of cancer recurrence following chemotherapy is cancer dormancy escape. Taxane-based chemotherapy is standard of care in breast cancer treatment aimed at killing proliferating cancer cells. Here, we demonstrate that docetaxel injures stromal cells, which release protumor cytokines, IL-6 and granulocyte colony stimulating factor (G-CSF), that in turn invoke dormant cancer outgrowth both in vitro and in vivo. Single-cell transcriptomics shows a reprogramming of awakened cancer cells including several survival cues such as stemness, chemoresistance in a tumor stromal organoid (TSO) model, as well as an altered tumor microenvironment (TME) with augmented protumor immune signaling in a syngeneic mouse breast cancer model. IL-6 plays a role in cancer cell proliferation, whereas G-CSF mediates tumor immunosuppression. Pathways and differential expression analyses confirmed MEK as the key regulatory molecule in cancer cell outgrowth and survival. Antibody targeting of protumor cytokines (IL-6, G-CSF) or inhibition of cytokine signaling via MEK/ERK pathway using selumetinib prior to docetaxel treatment prevented cancer dormancy outgrowth suggesting a novel therapeutic strategy to prevent cancer recurrence

    Quantifying a spectrum of clinical response in atrial tachyarrhythmias using spatiotemporal synchronization of electrograms

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    Aims There is a clinical spectrum for atrial tachyarrhythmias wherein most patients with atrial tachycardia (AT) and some with atrial fibrillation (AF) respond to ablation, while others do not. It is undefined if this clinical spectrum has pathophysiological signatures. This study aims to test the hypothesis that the size of spatial regions showing repetitive synchronized electrogram (EGM) shapes over time reveals a spectrum from AT, to AF patients who respond acutely to ablation, to AF patients without acute response. Methods and results We studied n = 160 patients (35% women, 65.0 +/- 10.4 years) of whom (i) n = 75 had AF terminated by ablation propensity matched to (ii) n = 75 without AF termination and (iii) n = 10 with AT. All patients had mapping by 64-pole baskets to identify areas of repetitive activity (REACT) to correlate unipolar EGMs in shape over time. Synchronized regions (REACT) were largest in AT, smaller in AF termination, and smallest in non-termination cohorts (0.63 +/- 0.15, 0.37 +/- 0.22, and 0.22 +/- 0.18, P < 0.001). Area under the curve for predicting AF termination in hold-out cohorts was 0.72 +/- 0.03. Simulations showed that lower REACT represented greater variability in clinical EGM timing and shape. Unsupervised machine learning of REACT and extensive (50) clinical variables yielded four clusters of increasing risk for AF termination (P < 0.01, chi(2)), which were more predictive than clinical profiles alone (P < 0.001). Conclusion The area of synchronized EGMs within the atrium reveals a spectrum of clinical response in atrial tachyarrhythmias. These fundamental EGM properties, which do not reflect any predetermined mechanism or mapping technology, predict outcome and offer a platform to compare mapping tools and mechanisms between AF patient groups

    Neurocognitive basis of model-based decision making and its metacontrol in childhood

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    Human behavior is supported by both goal-directed (model-based) and habitual (model-free) decision-making, each differing in its flexibility, accuracy, and computational cost. The arbitration between habitual and goal-directed systems is thought to be regulated by a process known as metacontrol. However, how these systems emerge and develop remains poorly understood. Recently, we found that while children between 5 and 11 years displayed robust signatures of model-based decision-making, which increased during this developmental period, there were substantial individual differences in the display of metacontrol. Here, we inspect the neurocognitive basis of model-based decision-making and metacontrol in childhood and focus this investigation on executive functions, fluid reasoning, and brain structure. A total of 69 participants between the ages of 6-13 completed a two-step decision-making task and an extensive behavioral test battery. A subset of 44 participants also completed a structural magnetic resonance imaging scan. We find that individual differences in metacontrol are specifically associated with performance on an inhibition task and individual differences in thickness of dorsolateral prefrontal, temporal, and superior-parietal cortices. These brain regions likely reflect the involvement of cognitive processes crucial to metacontrol, such as cognitive control and contextual processing

    Global, regional, and national incidence of six major immune-mediated inflammatory diseases: findings from the global burden of disease study 2019Research in context

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    Summary: Background: The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to¬†2019. Methods: We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. Findings: In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of¬†‚ąí0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC¬†=¬†‚ąí0.41), inflammatory bowel disease (AAPC¬†=¬†‚ąí0.72), multiple sclerosis (AAPC¬†=¬†‚ąí0.26), psoriasis (AAPC¬†=¬†‚ąí0.77), and atopic dermatitis (AAPC¬†=¬†‚ąí0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. Interpretation: The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. Funding: The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital (2022QN38)

    Studies on colchicine induced changes in bajra napier hybrid (Pennisetum glaucum x P. purpureum)

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    An experiment was conducted to estimate the lethal concentration of the polyploidy inducing chemical Colchicine in two genotypes of Bajra Napier hybrid CO 6 and TNCN 1534. Single nodded setts of the genotypes CO 6 and TNCN 1534 were treated with colchicine using two different methods viz., whole immersion with concentrations of 0.05%, 0.10%, 0.15%, 0.20% and 0.25% for 3 and 6 hours and the cotton swab method using the same five different concentrations. The LC50 values were observed based on growth reduction of seedlings after the planting of treated setts by the two methods. The sprouting percentage and survival percentage of both genotypes gradually reduced with increasing doses of colchicine and it also differed based on the method used. The LC50 values differed for both the methods used. The cotton swab method had the LC50 value of 0.21% for the genotype CO 6 and 0.19% for TNCN 1534. The whole immersion method had the LC50 value of 0.14% in case of CO 6 and 0.15% colchicine concentration was found to be optimum for TNCN 1534 indicating the differential response of genotypes for colchicine treatment. Correlation between different concentrations and stomatal parameters indicated positive correlation when the varieties were treated for 3 hours duration and a negative correlation was observed when they were treated for 6 hour duration in case of whole immersion method. As the duration of exposure increased, the parameters showed decreased growth. In case of cotton swab method, both the varieties showed positive correlation for stomatal width with the increasing concentration while stomatal length was seen having negative correlation when the concentrations were increased
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