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  1. Article ; Online: A Novel Machine Learning Model for Dose Prediction in Prostate Volumetric Modulated Arc Therapy Using Output Initialization and Optimization Priorities

    P. James Jensen / Jiahan Zhang / Bridget F. Koontz / Q. Jackie Wu

    Frontiers in Artificial Intelligence, Vol

    2021  Volume 4

    Abstract: Treatment planning for prostate volumetric modulated arc therapy (VMAT) can take 5–30 min per plan to optimize and calculate, limiting the number of plan options that can be explored before the final plan decision. Inspired by the speed and accuracy of ... ...

    Abstract Treatment planning for prostate volumetric modulated arc therapy (VMAT) can take 5–30 min per plan to optimize and calculate, limiting the number of plan options that can be explored before the final plan decision. Inspired by the speed and accuracy of modern machine learning models, such as residual networks, we hypothesized that it was possible to use a machine learning model to bypass the time-intensive dose optimization and dose calculation steps, arriving directly at an estimate of the resulting dose distribution for use in multi-criteria optimization (MCO). In this study, we present a novel machine learning model for predicting the dose distribution for a given patient with a given set of optimization priorities. Our model innovates upon the existing machine learning techniques by utilizing optimization priorities and our understanding of dose map shapes to initialize the dose distribution before dose refinement via a voxel-wise residual network. Each block of the residual network individually updates the initialized dose map before passing to the next block. Our model also utilizes contiguous and atrous patch sampling to effectively increase the receptive fields of each layer in the residual network, decreasing its number of layers, increasing model prediction and training speed, and discouraging overfitting without compromising on the accuracy. For analysis, 100 prostate VMAT cases were used to train and test the model. The model was evaluated by the training and testing errors produced by 50 iterations of 10-fold cross-validation, with 100 cases randomly shuffled into the subsets at each iteration. The error of the model is modest for this data, with average dose map root-mean-square errors (RMSEs) of 2.38 ± 0.47% of prescription dose overall patients and all optimization priority combinations in the patient testing sets. The model was also evaluated at iteratively smaller training set sizes, suggesting that the model requires between 60 and 90 patients for optimal performance. This model may be used ...
    Keywords dose prediction ; multi-criterial optimization ; treatment planning ; prostate VMAT ; machine learning ; artificial intelligence ; Electronic computers. Computer science ; QA75.5-76.95
    Subject code 006
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Effectiveness of short, personalised student assistantships

    Amir H Sam / Chee Yeen Fung / Elizabeth Hughes / Emma Hatfield / Omid Halse / Niamh M Martin / Lesa Kearney / James Jensen-Martin

    BMJ Open, Vol 12, Iss

    an evaluative study across eight London hospitals

    2022  Volume 12

    Abstract: Objectives Student assistantships are recommended to prepare medical graduates for clinical practice. Traditionally, assistantships have consisted of longer placements, often up to 15 weeks. However, within the constraints of the final year, medical ... ...

    Abstract Objectives Student assistantships are recommended to prepare medical graduates for clinical practice. Traditionally, assistantships have consisted of longer placements, often up to 15 weeks. However, within the constraints of the final year, medical schools need to carefully balance the time required for specialty placements, assessments and the risk of student burnout. We set out to evaluate the effectiveness of shorter, personalised student assistantships.Design An evaluative study on the changes in final year student confidence in preparedness for practice after a 3-week assistantship with defined learning objectives and learning needs assessment.Setting Eight hospitals affiliated with Imperial College School of Medicine.Outcomes Student confidence in 10 learning outcomes including organising ward rounds, documentation, communication with colleagues, communication with patients and relatives, patient handover, practical procedures, patient management, acute care, prioritisation and out-of-hours clinical work.Results Two hundred and twenty final year medical students took part in the student assistantship, of whom 208 completed both the pre-assistantship and post-assistantship confidence rating questionnaires (95% completion rate). After the assistantship, 169 (81%) students expressed increased confidence levels in one or more learning objectives. For each individual learning objective, there was a significant change in the proportion of students who agreed or strongly agreed after the assistantship (p<0.0001).Conclusion Overall, the focused 3-week, personalised student assistantships led to significant improvement across all learning objectives related to preparedness for practice. The use of the pre-assistantship confidence rating questionnaire allowed students to identify and target areas of learning needs during their assistantship.
    Keywords Medicine ; R
    Subject code 370
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher BMJ Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Incidental Retroperitoneal Castleman’s Disease Found in Patient with Renal Cell Carcinoma

    Samantha Richardson / James Jensen / Niru Nahar / Nadim Bou Zgheib

    Marshall Journal of Medicine, Vol 5, Iss 3, Pp 11-

    a case report

    2019  Volume 15

    Abstract: This report briefly discusses a case of retroperitoneal Castleman’s disease in a 52 year old post-menopausal woman with renal cell carcinoma. ...

    Abstract This report briefly discusses a case of retroperitoneal Castleman’s disease in a 52 year old post-menopausal woman with renal cell carcinoma.
    Keywords Castleman's disease ; Medicine (General) ; R5-920
    Language English
    Publishing date 2019-07-01T00:00:00Z
    Publisher Marshall University
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: mTOR Regulation of N-Myc Downstream Regulated 1 (NDRG1) Phosphorylation in Clear Cell Renal Cell Carcinoma

    Anisha Valluri / Jessica Wellman / Chelsea L. McCallister / Kathleen C. Brown / Logan Lawrence / Rebecca Russell / James Jensen / James Denvir / Monica A. Valentovic / Krista L. Denning / Travis B. Salisbury

    International Journal of Molecular Sciences, Vol 24, Iss 9364, p

    2023  Volume 9364

    Abstract: The mechanistic target of rapamycin (mTOR) kinase is a component of two signaling complexes that are known as mTOR complex 1 (mTORC1) and mTORC2. We sought to identify mTOR-phosphorylated proteins that are differently expressed in clinically resected ... ...

    Abstract The mechanistic target of rapamycin (mTOR) kinase is a component of two signaling complexes that are known as mTOR complex 1 (mTORC1) and mTORC2. We sought to identify mTOR-phosphorylated proteins that are differently expressed in clinically resected clear cell renal cell carcinoma (ccRCC) relative to pair-matched normal renal tissue. Using a proteomic array, we found N-Myc Downstream Regulated 1 (NDRG1) showed the greatest increase (3.3-fold) in phosphorylation (on Thr346) in ccRCC. This was associated with an increase in total NDRG1. RICTOR is a required subunit in mTORC2, and its knockdown decreased total and phospho-NDRG1 (Thr346) but not NDRG1 mRNA. The dual mTORC1/2 inhibitor, Torin 2, significantly reduced (by ~100%) phospho-NDRG1 (Thr346). Rapamycin is a selective mTORC1 inhibitor that had no effect on the levels of total NDRG1 or phospho-NDRG1 (Thr346). The reduction in phospho-NDRG1 (Thr346) due to the inhibition of mTORC2 corresponded with a decrease in the percentage of live cells, which was correlated with an increase in apoptosis. Rapamycin had no effect on ccRCC cell viability. Collectively, these data show that mTORC2 mediates the phosphorylation of NDRG1 (Thr346) in ccRCC. We hypothesize that RICTOR and mTORC2-mediated phosphorylation of NDRG1 (Thr346) promotes the viability of ccRCC cells.
    Keywords N-Myc Downstream Regulated 1 ; NDRG1 ; clear cell renal cell carcinoma ; mTOR ; mTORC1 ; mTORC2 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 500
    Language English
    Publishing date 2023-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Genetic analysis of the Warburg effect in yeast.

    Olayanju, Bola / Hampsey, James Jensen / Hampsey, Michael

    Advances in biological regulation

    2015  Volume 57, Page(s) 185–192

    Abstract: We recently discovered that the Warburg effect, defined by the dramatically enhanced metabolism of glucose to pyruvate, even in well-oxygenated cancer cells, can occur as a consequence of mutations that enhance lipid biosynthesis at the expense of ... ...

    Abstract We recently discovered that the Warburg effect, defined by the dramatically enhanced metabolism of glucose to pyruvate, even in well-oxygenated cancer cells, can occur as a consequence of mutations that enhance lipid biosynthesis at the expense of respiratory capacity. Specifically, mutations in the E1 subunit of either of two respiratory enzymes, pyruvate dehydrogenase (PDC) or α-ketoglutarate dehydrogenase (KGDC), change substrate specificity from the 3-carbon α-ketoacid pyruvate, or the 5-carbon α-ketoacid α-ketoglutarate, to the 4-carbon α-ketoacid oxaloacetate (OADC). These mutations result in OADC-catalyzed synthesis of malonyl-CoA (MaCoA), the essential precursor of all fatty acids. These mutants arose as spontaneous suppressors of a yeast acc1(cs) cold-sensitive mutation encoding an altered form of AcCoA carboxylase (Acc1) that fails to produce MaCoA at the restrictive temperature (16 °C). Notably, these suppressors are respiratory defective as a result of the same nuclear mutations that suppress acc1(cs). These mutants also suppress sensitivity to Soraphen A, a potent inhibitor of Acc1 activity, at normal temperature (30 °C). To our knowledge, OADC activity has never been identified in eukaryotic cells. Our results offer a novel perspective on the Warburg effect: the reprogramming of energy metabolism in cancer cells as a consequence of mutational impairment of respiration to meet the fatty acid requirements of rapidly proliferating cells. We suggest OADC activity is a common feature of cancer cells and represents a novel target for the development of chemotherapeutics.
    MeSH term(s) Energy Metabolism/physiology ; Glucose/genetics ; Glucose/metabolism ; Mutation ; Pyruvic Acid/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism
    Chemical Substances Saccharomyces cerevisiae Proteins ; Pyruvic Acid (8558G7RUTR) ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2015-01
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2667413-0
    ISSN 2212-4934 ; 2212-4926
    ISSN (online) 2212-4934
    ISSN 2212-4926
    DOI 10.1016/j.jbior.2014.09.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: A Network of Conserved Synthetic Lethal Interactions for Exploration of Precision Cancer Therapy

    Srivas, Rohith / Ana Bojorquez-Gomez / Andrew M. Gross / Chih Cheng Yang / Daniel Pekin / Haico van Attikum / Huwate Yeerna / James Jensen / Jia L. Xu / Jianfeng Li / John Paul Shen / Justin Huang / Katherine Licon / Kristin Klepper / Leonie Kollenstart / Pedro Aza-Blanc / Robert W. Sobol / Su Ming Sun / Trey Ideker /
    Vignesh Sivaganesh

    Molecular cell. 2016 Aug. 04, v. 63, no. 3

    2016  

    Abstract: An emerging therapeutic strategy for cancer is to induce selective lethality in a tumor by exploiting interactions between its driving mutations and specific drug targets. Here we use a multi-species approach to develop a resource of synthetic lethal ... ...

    Abstract An emerging therapeutic strategy for cancer is to induce selective lethality in a tumor by exploiting interactions between its driving mutations and specific drug targets. Here we use a multi-species approach to develop a resource of synthetic lethal interactions relevant to cancer therapy. First, we screen in yeast ∼169,000 potential interactions among orthologs of human tumor suppressor genes (TSG) and genes encoding drug targets across multiple genotoxic environments. Guided by the strongest signal, we evaluate thousands of TSG-drug combinations in HeLa cells, resulting in networks of conserved synthetic lethal interactions. Analysis of these networks reveals that interaction stability across environments and shared gene function increase the likelihood of observing an interaction in human cancer cells. Using these rules, we prioritize ∼105 human TSG-drug combinations for future follow-up. We validate interactions based on cell and/or patient survival, including topoisomerases with RAD17 and checkpoint kinases with BLM.
    Keywords drugs ; genotoxicity ; humans ; mutation ; neoplasm cells ; neoplasms ; patients ; phosphotransferases (kinases) ; therapeutics ; tumor suppressor genes ; yeasts
    Language English
    Dates of publication 2016-0804
    Size p. 514-525.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2016.06.022
    Database NAL-Catalogue (AGRICOLA)

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