9,594 results match your criteria dose prediction

Prediction of fluoxetine and norfluoxetine pharmacokinetic profiles using physiologically based pharmacokinetic modeling.

J Clin Pharmacol 2021 Jun 12. Epub 2021 Jun 12.

College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, 41566, Republic of Korea.

Fluoxetine is a selective serotonin reuptake inhibitor that is metabolized to norfluoxetine by CYP2D6, CYP2C19, and CYP3A4. A physiologically based pharmacokinetic (PBPK) model for fluoxetine and norfluoxetine metabolism was developed to predict and investigate changes in concentration-time profiles according to fluoxetine dosage in the Korean population. The model was developed based on the Certara repository model and information gleaned from the literature. Read More

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Oral pH value predicts the incidence of radiotherapy related caries in nasopharyngeal carcinoma patients.

Sci Rep 2021 Jun 10;11(1):12283. Epub 2021 Jun 10.

Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, 169, Donghu Road, Wuchang District, Wuhan, 430071, Hubei Province, China.

Radiotherapy-related caries is a complication of radiotherapy for nasopharyngeal carcinoma; however, factors influencing the occurrence, accurate prediction of onset, and protective factors of radiotherapy-related caries remain unclear. This study analyzed risk factors, disease predictors, and protective factors for radiotherapy-related caries in nasopharyngeal carcinoma. This prospective study included 138 nasopharyngeal carcinoma patients receiving radical radiotherapy at our hospital during June 2012-December 2016 and were followed up for dental caries. Read More

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Early Exanthema Upon Vemurafenib Plus Cobimetinib Is Associated With a Favorable Treatment Outcome in Metastatic Melanoma: A Retrospective Multicenter DeCOG Study.

Front Oncol 2021 24;11:672172. Epub 2021 May 24.

Department of Dermatology, University Hospital Essen, German Cancer Consortium (DKTK), Essen, Germany.

Background: The combination of BRAF and MEK inhibitors has become standard of care in the treatment of metastatic BRAF V600-mutated melanoma. Clinical factors for an early prediction of tumor response are rare. The present study investigated the association between the development of an early exanthema induced by vemurafenib or vemurafenib plus cobimetinib and therapy outcome. Read More

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Considering lead-time bias in evaluating the effectiveness of lung cancer screening with real-world data.

Sci Rep 2021 Jun 9;11(1):12180. Epub 2021 Jun 9.

Department of Chronic Disease Epidemiology, Yale University School of Public Health, New Haven, CT, USA.

Low-dose computed tomography screening can be used to diagnose lung cancer at a younger age compared to no screening. Real-world studies observing mortality after lung cancer diagnosis are subject to lead-time bias. This study developed a method using a nationwide cancer registry and stage shift from trial for the adjustment of lead-time bias. Read More

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Population pharmacokinetic and exploratory exposure-response analysis of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive early breast cancer in the FeDeriCa study.

Cancer Chemother Pharmacol 2021 Jun 9. Epub 2021 Jun 9.

Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.

Purpose: To characterize pertuzumab pharmacokinetics (PK) in FeDeriCa (NCT03493854: fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection [PH FDC SC] versus intravenous pertuzumab plus trastuzumab); derive individual pertuzumab exposures in the PH FDC SC arm for subsequent pertuzumab exposure-response (ER) analyses; compare observed trastuzumab PK with predicted exposures from a previous SC trastuzumab model; assess whether pertuzumab affects trastuzumab PK; evaluate pertuzumab exposure-efficacy and -safety relationships and support the approved SC dosing regimen.

Methods: Population pharmacokinetic modeling and simulations were used to describe the data. Standard goodness-of-fit diagnostics and prediction-corrected visual predictive checks were used for model performance assessment. Read More

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A clinical decision support tool to find the best initial intravenous cyclosporine regimen in pediatric hematopoietic stem cell transplantation.

J Clin Pharmacol 2021 Jun 8. Epub 2021 Jun 8.

Targeted Therapies in Oncology, Faculté de Médecine et de Maïeutique Lyon-Sud Charles Mérieux, Université Claude Bernard Lyon 1, 165 chemin du Grand Revoyet-BP 12, Oullins, 69921 Cedex, France.

In order to optimize cyclosporine A (CsA) dosing regimen in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT), we aimed to provide clinicians with a validated decision support tool for determining the most suitable first dose of intravenous CsA.We used a 10-years monocentric dataset of pediatric patients undergoing HSCT. Discretization of all variables was performed according to literature or thanks to algorithms using Shannon entropy (from information theory) or equal width intervals. Read More

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Low-dose CDK4/6 inhibitors induce presentation of pathway specific MHC ligands as potential targets for cancer immunotherapy.

Oncoimmunology 2021 May 24;10(1):1916243. Epub 2021 May 24.

Molecular Pharmacology Program, Sloan Kettering Institute, New York, USA.

Cyclin dependent kinase 4/6 inhibitors (CDK4/6i) lead to cell-cycle arrest but also trigger T cell-mediated immunity, which might be mediated by changes in human leukocyte antigen (HLA) ligands. We investigated the effects of CDK4/6i, abemaciclib and palbociclib, on the immunopeptidome at nontoxic levels in breast cancer cell lines by biochemical identification of HLA ligands followed by network analyses. This treatment led to upregulation of HLA and revealed hundreds of induced HLA ligands in breast cancer cell lines. Read More

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Technical Note: A Cascade 3D U-Net for Dose Prediction in Radiotherapy.

Med Phys 2021 Jun 8. Epub 2021 Jun 8.

Key Laboratory of Intelligent Computing & Signal Processing, Ministry of Education/School of Electrical Engineering and Automation, Anhui University, HeFei, 230601, China.

Purpose: Although large datasets are available, to learn a robust dose prediction model from a limited dataset still remains challenging. This work employed cascaded deep-learning models and advanced training strategies with a limited dataset to precisely predict three-dimensional (3D) dose distribution.

Methods: A Cascade 3D (C3D) model is developed based on the cascade mechanism and 3D U-Net network units. Read More

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A Feasibility Study on Deep Learning-Based Individualized 3D Dose Distribution Prediction.

Med Phys 2021 Jun 5. Epub 2021 Jun 5.

Medical Artificial Intelligence and Automation (MAIA) Laboratory, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, 75235, USA.

Purpose: Radiation therapy treatment planning is a trial-and-error, often time-consuming process. An approximately optimal dose distribution corresponding to a specific patient's anatomy can be predicted by using pre-trained deep learning (DL) models. However, dose distributions are often optimized based not only on patient-specific anatomy but also on physicians' preferred trade-offs between planning target volume (PTV) coverage and organ at risk (OAR) sparing or among different OARs. Read More

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A Predictive Model for Reactive Tube Feeding in Head and Neck Cancer Patients Undergoing Definitive (Chemo) Radiotherapy.

Clin Oncol (R Coll Radiol) 2021 Jun 2. Epub 2021 Jun 2.

The Christie NHS Foundation Trust, Clinical Oncology, Proton Beam Therapy Centre, Manchester, UK; The University of Manchester, Division of Clinical Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester, UK.

Aims: Careful management of a patient's nutritional status during and after treatment for head and neck squamous cell cancers (HNSCC) is crucial for optimal outcomes. The aim of this study was to develop a model for stratifying a patient's risk of requiring reactive enteral feeding through a nasogastric tube during radiotherapy for HNSCC, based on clinical and treatment-related factors.

Materials And Methods: A cohort of consecutive patients treated with definitive (chemo)radiotherapy for HNSCC between January 2016 and January 2018 was identified in the institutional electronic database for retrospective analysis. Read More

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The entropy of chaotic transitions of EEG phase growth in bipolar disorder with lithium carbonate.

Sci Rep 2021 Jun 4;11(1):11888. Epub 2021 Jun 4.

Üsküdar University, NPİstanbul Brain Hospital, Ahmet Tevfik İleri C. N: 18 Ümraniye, İstanbul, Turkey.

The application of chaos measures the association of EEG signals which allows for differentiating pre and post-medicated epochs for bipolar patients. We propose a new approach on chaos necessary for proof of EEG metastability. Shannon entropies of concealed patterns of Schwarzian derivatives from absolute instantaneous frequency transformations of EEG signals after Hilbert transform are compared and found significantly statistically different between pre and post-medication periods when fitted to von Bertalanffy's functions. Read More

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Magnetic properties and its application in the prediction of potentially toxic elements in aquatic products by machine learning.

Sci Total Environ 2021 Aug 20;783:147083. Epub 2021 Apr 20.

School of Environment, Nanjing Normal University, Nanjing 210023, PR China. Electronic address:

Magnetic measurement was provided to substitute for time-consuming conventional methods for determination of potentially toxic elements. Both the concentrations of 12 elements and 9 magnetic parameters were determined in 700 muscle tissue samples from the snail Bellamya aeruginosa, shrimp species Exopalaemon modestus and Macrobrachium nipponense, and fish species Hemisalanx prognathous Regan, Coilia ectenes taihuensis, and Culer alburnus Basilewsky collected from Chaohu Lake during different hydrological periods. Spherical and irregular iron oxide particles were observed in the muscle tissues of the studied aquatic products. Read More

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Prediction of copper ions adsorption by attapulgite adsorbent using tuned-artificial intelligence model.

Chemosphere 2021 Aug 4;276:130162. Epub 2021 Mar 4.

New Era and Development in Civil Engineering Research Group, Scientific Research Center, Al-Ayen University, Thi-Qar, 64001, Iraq. Electronic address:

Copper (Cu) ion in wastewater is considered as one of the crucial hazardous elements to be quantified. This research is established to predict copper ions adsorption (Ad) by Attapulgite clay from aqueous solutions using computer-aided models. Three artificial intelligent (AI) models are developed for this purpose including Grid optimization-based random forest (Grid-RF), artificial neural network (ANN) and support vector machine (SVM). Read More

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Learning-based dose prediction for pancreatic stereotactic body radiation therapy using dual pyramid adversarial network.

Phys Med Biol 2021 Jun 4. Epub 2021 Jun 4.

Department of Radiology and Sciences Imaging Department of Radiology Oncology, Emory University, Atlanta, Georgia, UNITED STATES.

Treatment planning for pancreatic cancer stereotactic body radiation therapy (SBRT) is very challenging owing to vast spatial variations and close proximity of many organs-at-risk. Recently, deep learning (DL)-based methods have been applied in dose prediction tasks of various treatment sites with the aim of relieving planning challenges. Limited investigations, however, have been reported on DL-based dose prediction for pancreatic cancer SBRT. Read More

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Crowdsourced mapping of unexplored target space of kinase inhibitors.

Nat Commun 2021 06 3;12(1):3307. Epub 2021 Jun 3.

Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.

Despite decades of intensive search for compounds that modulate the activity of particular protein targets, a large proportion of the human kinome remains as yet undrugged. Effective approaches are therefore required to map the massive space of unexplored compound-kinase interactions for novel and potent activities. Here, we carry out a crowdsourced benchmarking of predictive algorithms for kinase inhibitor potencies across multiple kinase families tested on unpublished bioactivity data. Read More

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Microdosimetry modeling with auger emitters in generalized cell geometry.

Phys Med Biol 2021 Jun 3;66(11). Epub 2021 Jun 3.

Institute for Energy Technology (IFE), PO Box 40, NO-2027 Kjeller, Norway.

A microdosimetry model was developed for the prediction of cell viability for irregular non-spherical cells that were irradiated by low energy, short range auger electrons. Measured cell survival rates for LNCaP prostate cancer were compared to the computational results for the radioisotopesLu andTb (conjugated to PSMA). The cell geometries used for the computations were derived directly from the cell culture images. Read More

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Dose selection for intracerebroventricular cerliponase alfa in children with CLN2 disease, translation from animal to human in a rare genetic disease.

Clin Transl Sci 2021 Jun 2. Epub 2021 Jun 2.

BioMarin Pharmaceutical Inc., Novato, California, USA.

Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is an ultra-rare pediatric neurodegenerative disorder characterized by deficiency of the lysosomal enzyme tripeptidyl peptidase-1 (TPP1). In the absence of adequate TPP1, lysosomal storage material accumulation occurs in the central nervous system (CNS) accompanied by neurodegeneration and neurological decline that culminates in childhood death. Cerliponase alfa is a recombinant human TPP1 enzyme replacement therapy administered via intracerebroventricular infusion and approved for the treatment of CLN2 disease. Read More

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Correlation of Donor-Derived Cell-free DNA with Histology and Molecular Diagnoses of Kidney Transplant Biopsies.

Transplantation 2021 May 28. Epub 2021 May 28.

Division of Nephrology, Virginia Commonwealth University, Richmond, VA, United States Division of Transplant Surgery, Virginia Commonwealth University, Richmond, VA, United States Department of Biostatistics, Virginia Commonwealth University, Richmond, VA, United States Department of Pathology, Virginia Commonwealth University, Richmond, VA, United States Alberta Transplant Applied Genomics Center, Edmonton, Canada.

Background: Circulating donor-derived cell free DNA (cfDNA), a minimally invasive diagnostic tool for kidney transplant rejection, was validated using traditional histology. The Molecular Microscope (MMDx) tissue gene expression platform may provide increased precision to traditional histology.

Methods: In this single-center prospective study of 208 biopsies (median=5. Read More

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Drug Metab Dispos 2021 Jun 1. Epub 2021 Jun 1.

Department of Pharmaceutical Sciences, Washington State University, United States

Anticancer drug, irinotecan shows serious dose-limiting gastrointestinal toxicity regardless of intravenous dosing. Although enzymes and transporters involved in irinotecan disposition are known, quantitative contributions of these mechanisms in complex in vivo disposition of irinotecan are poorly understood. We explained intestinal disposition and toxicity of irinotecan by integrating i) in vitro metabolism and transport data of rinotecan and its metabolites, ii) ex vivo gut microbial activation of the toxic metabolite, SN-38, and iii) the tissue protein abundance data of enzymes and transporters relevant to irinotecan and its metabolites. Read More

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A Nomogram Predicting Progression Free Survival in Patients with Gastrointestinal Stromal Tumor Receiving Sunitinib: Incorporating Pre-Treatment and Post-Treatment Parameters.

Cancers (Basel) 2021 May 25;13(11). Epub 2021 May 25.

Department of Surgery and GIST Team, Chang Gung Memorial Hospital at Linkou, ChangGung University College of Medicine, Taoyuan 33305, Taiwan.

The present study aimed to construct a prognostic nomogram incorporating pre-treatment and post-treatment factors to predict progression-free survival (PFS) after use of sunitinib in patients with metastatic gastrointestinal stromal tumors (GISTs) following imatinib intolerance or failure. From 2007 to 2018, 109 metastatic GIST patients receiving sunitinib at Chang Gung Memorial Hospital, Taiwan, were enrolled. A prognostic nomogram to predict PFS was developed. Read More

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Enhancing Clinical Translation of Cancer Using Nanoinformatics.

Cancers (Basel) 2021 May 19;13(10). Epub 2021 May 19.

Faculty of Science, School of Optometry and Vision Science, University of Waterloo, Waterloo, ON N2L 3G1, Canada.

Application of drugs in high doses has been required due to the limitations of no specificity, short circulation half-lives, as well as low bioavailability and solubility. Higher toxicity is the result of high dosage administration of drug molecules that increase the side effects of the drugs. Recently, nanomedicine, that is the utilization of nanotechnology in healthcare with clinical applications, has made many advancements in the areas of cancer diagnosis and therapy. Read More

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Enrofloxacin Dose Optimization for the Treatment of Colibacillosis in Broiler Chickens Using a Drinking Behaviour Pharmacokinetic Model.

Antibiotics (Basel) 2021 May 19;10(5). Epub 2021 May 19.

Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.

Enrofloxacin is frequently administered via drinking water for the treatment of colibacillosis in broiler chickens. However, the EMA/CVMP has urged to re-evaluate historically approved doses, especially for antimicrobials administered via drinking water. In response, the objectives of this study were two-fold. Read More

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Current Evidence, Challenges, and Opportunities of Physiologically Based Pharmacokinetic Models of Atorvastatin for Decision Making.

Pharmaceutics 2021 May 13;13(5). Epub 2021 May 13.

Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46010 Valencia, Spain.

Atorvastatin (ATS) is the gold-standard treatment worldwide for the management of hypercholesterolemia and prevention of cardiovascular diseases associated with dyslipidemia. Physiologically based pharmacokinetic (PBPK) models have been positioned as a valuable tool for the characterization of complex pharmacokinetic (PK) processes and its extrapolation in special sub-groups of the population, leading to regulatory recognition. Several PBPK models of ATS have been published in the recent years, addressing different aspects of the PK properties of ATS. Read More

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Structural Analysis of the Novel Variants of SARS-CoV-2 and Forecasting in North America.

Viruses 2021 05 17;13(5). Epub 2021 May 17.

Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Miami Miller School of Medicine, Miami, FL 33146, USA.

Background: little is known about the forecasting of new variants of SARS-COV-2 in North America and the interaction of variants with vaccine-derived neutralizing antibodies.

Methods: the affinity scores of the spike receptor-binding domain (S-RBD) of B.1. Read More

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Radiomics Analysis of 3D Dose Distributions to Predict Toxicity of Radiotherapy for Cervical Cancer.

J Pers Med 2021 May 11;11(5). Epub 2021 May 11.

Radiation Oncology Department, University Hospital, CHRU Morvan, 2 avenue Foch, CEDEX, 29609 Brest, France.

Standard treatment for locally advanced cervical cancer (LACC) is chemoradiotherapy followed by brachytherapy. Despite radiation therapy advances, the toxicity rate remains significant. In this study, we compared the prediction of toxicity events after radiotherapy for locally advanced cervical cancer (LACC), based on either dose-volume histogram (DVH) parameters or the use of a radiomics approach applied to dose maps at the voxel level. Read More

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Robust and Accurate Mandible Segmentation on Dental CBCT Scans Affected by Metal Artifacts Using a Prior Shape Model.

J Pers Med 2021 May 1;11(5). Epub 2021 May 1.

Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.

Accurate mandible segmentation is significant in the field of maxillofacial surgery to guide clinical diagnosis and treatment and develop appropriate surgical plans. In particular, cone-beam computed tomography (CBCT) images with metal parts, such as those used in oral and maxillofacial surgery (OMFS), often have susceptibilities when metal artifacts are present such as weak and blurred boundaries caused by a high-attenuation material and a low radiation dose in image acquisition. To overcome this problem, this paper proposes a novel deep learning-based approach (SASeg) for automated mandible segmentation that perceives overall mandible anatomical knowledge. Read More

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Prediction of Life-Threatening Intracranial Hypertension During the Acute Phase of Traumatic Brain Injury Using Machine Learning.

IEEE J Biomed Health Inform 2021 Jun 1;PP. Epub 2021 Jun 1.

Intracranial hypertension (IH) following acute phase traumatic brain injury (TBI) is associated with high mortality. Objective: This study proposes a novel parameter that may identify a potentially life-threatening IH (LTH) event and designs a machine learning model to predict LTH. Continuous recordings of intracranial pressure (ICP) and arterial blood pressure (ABP) from 273 TBI patients were used as the development dataset. Read More

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Prediction of the minimum spacer thickness required for definitive radiotherapy with carbon ions and photons for pelvic tumors: an in silico planning study using virtual spacers.

J Radiat Res 2021 May 31. Epub 2021 May 31.

Department of Radiation Oncology, Yamagata University Faculty of Medicine, 2-2-2, Iida-Nishi, Yamagata 990-9585, Japan.

We aimed to predict the minimum distance between a tumor and the gastrointestinal (GI) tract that can satisfy the dose constraint by creating simulation plans with carbon-ion (C-ion) radiotherapy (RT) and photon RT for each case assuming insertion of virtual spacers of various thicknesses. We enrolled 55 patients with a pelvic tumor adjacent to the GI tract. Virtual spacers were defined as the overlap volume between the GI tract and the volume expanded 7-17 mm from the gross tumor volume (GTV). Read More

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High-throughput PBTK models for to extrapolation.

Expert Opin Drug Metab Toxicol 2021 May 31. Epub 2021 May 31.

Center for Computational Toxicology and Exposure, US Environmental Protection Agency, Research Triangle Park, NC, USA.

: Toxicity data are unavailable for many thousands of chemicals in commerce and the environment. Therefore, risk assessors need to rapidly screen these chemicals for potential risk to public health. High-throughput screening (HTS) for in vitro bioactivity, when used with high-throughput toxicokinetic (HTTK) data and models, allows characterization of these thousands of chemicals. Read More

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Investigation of the Multi-Target Mechanism of Guanxin-Shutong Capsule in Cerebrovascular Diseases: A Systems Pharmacology and Experimental Assessment.

Front Pharmacol 2021 13;12:650770. Epub 2021 May 13.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Guanxin-Shutong capsule (GXSTC), a combination of Mongolian medicines and traditional herbs, has been clinically proven to be effective in treating cerebrovascular diseases (CBVDs). However, the underlying pharmacological mechanisms of GXSTC in CBVDs remain largely unknown. In this study, a combination of systems pharmacology and experimental assessment approach was used to investigate the bioactive components, core targets, and possible mechanisms of GXSTC in the treatment of CBVDs. Read More

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