Tag: pubmed

Behav Res Methods. 2021 Apr 14. doi: 10.3758/s13428-021-01579-5. Online ahead of print.

ABSTRACT

Ongoing goal-directed movements can be rapidly adjusted following new environmental information, e.g., when chasing pray or foraging. This makes movement trajectories in go-before-you-know decision-making a suitable behavioral readout of the ongoing decision process. Yet, existing methods of movement analysis are often based on statistically comparing two groups of trial-averaged trajectories and are not easily applied to three-dimensional data, preventing them from being applicable to natural free behavior. We developed and tested the cone method to estimate the point of overt commitment (POC) along a single two- or three-dimensional trajectory, i.e., the position where the movement is adjusted towards a newly selected spatial target. In Experiment 1, we established a “ground truth” data set in which the cone method successfully identified the experimentally constrained POCs across a wide range of all but the shallowest adjustment angles. In Experiment 2, we demonstrate the power of the method in a typical decision-making task with expected decision time differences known from previous findings. The POCs identified by cone method matched these expected effects. In both experiments, we compared the cone method’s single trial performance with a trial-averaging method and obtained comparable results. We discuss the advantages of the single-trajectory cone method over trial-averaging methods and possible applications beyond the examples presented in this study. The cone method provides a distinct addition to existing tools used to study decisions during ongoing movement behavior, which we consider particularly promising towards studies of non-repetitive free behavior.

PMID:33852130 | DOI:10.3758/s13428-021-01579-5

Eur J Drug Metab Pharmacokinet. 2021 Apr 14. doi: 10.1007/s13318-021-00671-7. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Population pharmacokinetic analysis explored the pharmacokinetics of sunitinib and its primary active metabolite, SU012662, in children and evaluated the sunitinib dose(s) that produce comparable plasma exposures to adults receiving the approved daily dose.

METHODS: Data were from 65 children with gastrointestinal stromal tumors (GIST) or solid tumors. Pharmacokinetic models of sunitinib and SU012662 were developed using a systematic multi-step approach employing nonlinear mixed-effects modeling. The effect of predefined covariates on pharmacokinetic parameters was assessed. Final models were validated using visual predictive check and statistical techniques.

RESULTS: The final dataset comprised 439 sunitinib and 417 SU012662 post-baseline plasma observations. Base models were characterized by two-compartment models with first-order absorption and lag time. Body surface area (BSA) was the only covariate that affected (P < 0.001) pharmacokinetic parameters for sunitinib and SU012662 and was incorporated into the final models. Bootstrap results indicated that the final models represented the final dataset adequately. Based on the final models, a sunitinib dose of ~ 20mg/m²/day in children with GIST aged 6-17 years would be expected to lead to similar total plasma exposures of sunitinib and SU012661 as a dose of 50 mg/day in an adult with GIST on schedule 4/2.

CONCLUSIONS: In children with GIST or solid tumors receiving sunitinib, population pharmacokinetic analysis identified BSA as the only covariate that affected pharmacokinetic parameters and predicted a dose of ~ 20 mg/m²/day as achieving equivalent exposure to 50 mg/day in adults with GIST on schedule 4/2.

TRIAL REGISTRATION: ClinicalTrials.gov identifiers (date registered): NCT01396148 (July 2011); NCT01462695 (October 2011); NCT00387920 (October 2006).

PMID:33852135 | DOI:10.1007/s13318-021-00671-7

Clin Oral Investig. 2021 Apr 14. doi: 10.1007/s00784-021-03880-1. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the effects of epidermal growth factor (EGF)-coated titanium (Ti) discs on the adhesion and metabolism of keratinocytes and gingival fibroblasts exposed to nitrogen-containing bisphosphonates.

MATERIALS AND METHODS: Keratinocytes and fibroblasts were seeded (1 × 10⁵ cells/disc) on Ti discs coated with EGF (100 nM). After 24 h, cells were exposed or not to sodium alendronate (SA) or zoledronic acid (ZA) at different concentrations (0 = control, 0.5, 1, or 5 μM) for 48 h. Cell adhesion to the substrates was evaluated by fluorescence microscopy. Cell viability (alamarBlue, n = 6) and synthesis of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), and keratinocytes growth factor (KGF) (ELISA, n = 6) were assessed. Data were statistically analyzed by one-way ANOVA and Tukey tests (α = 0.05).

RESULTS: Higher cell adhesion rate was observed when keratinocytes and fibroblasts were seeded onto EGF-coated discs in comparison to uncoated discs. ZA treatment hindered the adhesion of both cell lines on the Ti discs as well as reduced the viability and synthesis of VEGF, KGF and MMP-2 by cells (p < 0.05). SA treatment did not affect cell viability, but interfered negatively on the adhesion and synthesis of EGF and KGF by the cells (p < 0.05). EGF-coated surface increased cell viability and synthesis of growth factors as well as downregulated the synthesis of MMP-2 in comparison to control (p < 0.05).

CONCLUSION: EGF applied on Ti surface improves the biological responses of oral mucosa cells exposed to SA and ZA.

CLINICAL RELEVANCE: EGF-coating on titanium may be a suitable strategy to improve oral mucosa cellular events related to biological sealing, especially for patients under bisphosphonate therapy.

PMID:33852064 | DOI:10.1007/s00784-021-03880-1

Eur J Nutr. 2021 Apr 14. doi: 10.1007/s00394-021-02556-6. Online ahead of print.

ABSTRACT

PURPOSE: The burden of non-communicable diseases (NCDs) has increased in China. However, the contribution of dietary risks to the NCD burden has not been evaluated. This study aimed to estimate the burden of ischemic heart disease (IHD) and colorectal cancer (CRC) attributable to a diet low in fiber in China from 1990 to 2017.

METHODS: China data from the Global Burden of Disease Study (GBD) 2017 were used to assess the age-, sex-, and province-specific mortality and disability-adjusted life-years (DALYs) of IHD and CRC related to a diet low in fiber.

RESULTS: In 2017, a diet low in fiber contributed 170,143 [95% uncertainty interval (UI): 99,623-256,806] IHD deaths and 25,561 (95% UI: 13,726-39,215) CRC deaths, with the population attributable fractions (PAFs) were 9.7 and 13.7%, respectively. Males had higher risk-attributable mortality and DALY rates for IHD and CRC than females. An upward trend with age in rates of mortality and DALY was observed. All-age risk-attributable mortality and DALY rates increased significantly by 111.4 and 53.2% for IHD, and 94.4 and 59.6% for CRC from 1990 to 2017, respectively; however, the corresponding age-standardized rates for IHD and CRC showed relatively stable trends. Heilongjiang, Xinjiang, and Inner Mongolia were ranked as the top three provinces in terms of total risk-attributable NCD burden in 2017.

CONCLUSIONS: China has a large and growing NCD burden attributable to a diet low in fiber. Greater priority in disease prevention and control should be given to male and older adults throughout China, particularly in some western provinces.

PMID:33852070 | DOI:10.1007/s00394-021-02556-6

Breast Cancer Res Treat. 2021 Apr 14. doi: 10.1007/s10549-021-06221-8. Online ahead of print.

ABSTRACT

PURPOSE: To compare efficacy and safety of capecitabine and lapatinib with or without IMC-A12 (cituxumumab) in patients with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab.

PATIENTS AND METHODS: Following an initial safety run-in cohort, patients were randomized 1:2 to Arm A (capecitabine and lapatinib) or to Arm B (capecitabine, lapatinib, and cituxumumab). Given the frequency of non-hematologic grade ≥ 3 adverse events in those receiving the three-drug combination in the safety cohort, lapatinib and capecitabine doses were reduced in Arm B only. The primary objective was to determine if the addition of cituxumumab to capecitabine and lapatinib improved progression-free survival (PFS) compared with capecitabine and lapatinib. Secondary objectives included a comparison between arms of other clinical endpoints, safety, change in overall quality of life (QOL) and self-assessed fatigue, rash, diarrhea, and hand-foot syndrome.

RESULTS: From July 2008 to March 2012, 68 patients (out of 142 planned) were enrolled and 63 were evaluable, including 8 for the safety run-in and 55 for the randomized cohort. Study enrollment was stopped early due to slow accrual. The addition of cituxumumab to capecitabine and lapatinib did not improve PFS (HR 0.93, 95% CI: 0.52-1.64). Furthermore, no difference in objective response rate or overall survival (OS) was observed. No difference between arms was observed in grade ≥ 3 adverse events, overall QOL change from baseline after 4 cycles of treatment.

CONCLUSION: The addition of cituxumumab to lapatinib and capecitabine did not improve PFS or OS compared with lapatinib and capecitabine in patients with HER2-positive MBC.

CLINICAL TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT00684983.

PMID:33852121 | DOI:10.1007/s10549-021-06221-8

Eur J Nucl Med Mol Imaging. 2021 Apr 14. doi: 10.1007/s00259-021-05354-8. Online ahead of print.

ABSTRACT

PURPOSE: Prostate-specific membrane antigen (PSMA) PET/CT is increasingly used in patients with biochemical recurrence post prostatectomy to detect local recurrence and metastatic disease at low PSA levels. The aim of this study was to assess patterns of disease detection, predictive factors and safety using [¹⁸F]DCFPyL PET/CT versus diagnostic CT in patients being considered for salvage radiotherapy with biochemical recurrence post prostatectomy.

METHODS: We conducted a prospective trial recruiting 100 patients with detectable PSA post prostatectomy (PSA 0.2-2.0 ng/mL) and referred for salvage radiotherapy from August 2018 to July 2020. All patients underwent a PSMA PET/CT using the [¹⁸F]DCFPyL tracer and a diagnostic CT. The detection rates of [¹⁸F]DCFPyL PET/CT vs diagnostic CT were compared and patterns of disease are reported. Clinical patient and tumour characteristics were analysed for predictive utility. Thirty-day post-scan safety is reported.

RESULTS: Of 100 patients recruited, 98 were suitable for analysis with a median PSA of 0.32 ng/mL. [¹⁸F]DCFPyL PET/CT was positive 46.4% and equivocal 5.2%, compared to 15.5% positivity for diagnostic CT. Local recurrence was detected on [¹⁸F]DCFPyL PET/CT in 28.5%, nodal disease in 27.5% and bony metastases in 6.1% of patients. Both ISUP grade group (p < 0.001) and pre-scan PSA (p = 0.029) were significant predictors of [¹⁸F]DCFPyL PET/CT positivity, and logistic regression generated probabilities combining the two showed improved prediction rates. No significant safety events were reported post [¹⁸F]DCFPyL administration.

CONCLUSIONS: [¹⁸F]DCFPyL PET/CT increases detection of disease in patients with biochemical recurrence post prostatectomy compared to diagnostic CT. Patients being considered for salvage radiotherapy with a PSA >0.2 ng/mL should be considered for [¹⁸F]DCFPyL PET/CT scan.

TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Number: ACTRN12618001530213 ( http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375932&isReview=true ).

PMID:33852051 | DOI:10.1007/s00259-021-05354-8

Surg Endosc. 2021 Apr 14. doi: 10.1007/s00464-021-08433-x. Online ahead of print.

ABSTRACT

BACKGROUND: Endoscopic submucosal dissection (ESD) for remnant gastric cancer (RGC) after distal gastrectomy (DG) is considered technically challenging due to the narrow working space, and severe fibrosis and staples from the previous surgery. Technical difficulties of ESD for RGC after DG have not been thoroughly investigated. This study aimed to develop and validate a risk-scoring system for assessing the technical difficulty of ESD for RGC after DG in a large multicenter cohort.

METHODS: We investigated patients who underwent ESD for RGC after DG in 10 institutions between April 2008 and March 2018. A difficult case was defined as ESD lasting ≥ 120 min, involving piecemeal resection, or the occurrence of perforation during the procedure. A risk-scoring system for the technical difficulty of the procedure was developed based on multiple logistic regression analyses, and its performance was internally validated using bootstrapping.

RESULTS: A total of 197 consecutive patients with 201 lesions were analyzed. There were 90 and 111 difficult and non-difficult cases, respectively. The scoring model consisted of four independent risk factors and points of risk scores were assigned for each as follows: tumor size > 20 mm: 2 points; anastomosis site: 2 points; suture line: 1 point; and non-expert endoscopist: 2 points. The C-statistics of the scoring system for technical difficulty was 0.72.

CONCLUSIONS: We developed a validated risk-scoring model for predicting the technical difficulty of ESD for RGC after DG that can contribute to its safer and more reliable performance.

PMID:33852062 | DOI:10.1007/s00464-021-08433-x

J Orofac Orthop. 2021 Apr 14. doi: 10.1007/s00056-021-00292-4. Online ahead of print.

ABSTRACT

PURPOSE: Main goal of the study was the identification and quantitative analysis of monomer elution from materials commonly used in fixed orthodontic therapy. Studies have shown severe health effects of monomers including cytotoxic, allergenic or mutagenic potential and endocrine changes. This in vitro study focusses primarily on five resins which are usually processed intraorally and remain in the oral cavity long-term.

METHODS: We tested the elution of monomers from specimens (7.5 mm × 1.5 mm) immersed in artificial saliva at body temperature (37 °C) for 30 min to 5 weeks. The used method is in accordance with DIN EN ISO 10993-13. The five tested materials were BrackFix® (Voco GmbH, Cuxhaven, Germany), Triad®Gel (DeguDent GmbH, Hanau, Germany), and Transbond™ XT, LR and Plus (3M Unitek, Monrovia, CA, USA). All aliquots were analyzed using high performance liquid chromatography (HPLC). Data were statistically analyzed.

RESULTS: All five analyzed materials eluted substances over a period of 5 weeks. Identified substances included bisphenol A (BPA), triethylene glycol dimethacrylate (TEGDMA) and urethane dimethacrylate (UDMA). BPA eluted from Transbond™ Plus, XT, LR and BrackFix®. The cumulated mean values after 35 days ranged from 16.04 to 64.83 ppm, depending on the material. TEGDMA eluted with a mean of 688.61 ppm from Transbond™ LR. UDMA with a mean of 1682.00 ppm from Triad®Gel. For each material the highest concentrations of all these substances were found in the first elution period. Other substances that were not equivocally identified or of low concentration also eluted.

CONCLUSION: Using the described method, it is possible to qualitatively and quantitatively determine the in vitro elution of monomers from orthodontic materials. The concentrations of the substances identified were below the current maximum recommended intake. However, a cumulative effect and low-dose effects should be considered for both patients and dental professionals, especially for young patients. Measures to reduce exposure patients and practitioners are suggested.

PMID:33852039 | DOI:10.1007/s00056-021-00292-4

Eur Radiol. 2021 Apr 14. doi: 10.1007/s00330-021-07918-6. Online ahead of print.

ABSTRACT

OBJECTIVES: To develop an objective quantitative method to characterize and visualize meningioma-brain adhesion using MR elastography (MRE)-based slip interface imaging (SII).

METHODS: This retrospective study included 47 meningiomas (training dataset: n = 35; testing dataset: n = 12) with MRE/SII examinations. Normalized octahedral shear strain (NOSS) values were calculated from the acquired MRE displacement data. The change in NOSS at the tumor boundary (ΔNOSS_bdy) was computed, from which a 3D ΔNOSS_bdy map of the tumor surface was created and the probability distribution of ΔNOSS_bdy over the entire tumor surface was calculated. Statistical features were calculated from the probability histogram. After eliminating highly correlated features, the capability of the remaining feature for tumor adhesion classification was assessed using a one-way ANOVA and ROC analysis.

RESULTS: The magnitude and location of the tumor adhesion can be visualized by the reconstructed 3D ΔNOSS_bdy surface map. The entropy of the ΔNOSS_bdy histogram was significantly different between adherent tumors and partially/completely non-adherent tumors in both the training (AUC: 0.971) and testing datasets (AUC: 0.900). Based on the cutoff values obtained from the training set, the ΔNOSS_bdy entropy in the testing dataset yielded an accuracy of 0.83 for distinguishing adherent versus partially/non-adherent tumors, and 0.67 for distinguishing non-adherent versus completely/partially adherent tumors.

CONCLUSIONS: SII-derived ΔNOSS_bdy values are useful for quantification and classification of meningioma-brain adhesion. The reconstructed 3D ΔNOSS_bdy surface map presents the state and location of tumor adhesion in a “clinician-friendly” manner, and can identify meningiomas with a high risk of adhesion to adjacent brain parenchyma.

KEY POINTS: • MR elastography (MRE)-based slip interface imaging shows promise as an objective tool to preoperatively discriminate meningiomas with a high risk of intraoperative adhesion. • Measurement of the change of shear strain at meningioma boundaries can provide quantitative metrics depicting the state of adhesion at the tumor-brain interface. • The surface map of tumor adhesion shows promise in assisting precise adhesion localization, using a comprehensible, “clinician-friendly” 3D visualization.

PMID:33852045 | DOI:10.1007/s00330-021-07918-6

Eur Radiol. 2021 Apr 14. doi: 10.1007/s00330-021-07943-5. Online ahead of print.

ABSTRACT

OBJECTIVES: Quantum noise is a random process in X-ray-based imaging systems. We addressed and measured the uncertainty of radiomics features against this quantum noise in computed tomography (CT) images.

METHODS: A clinical multi-detector CT scanner, two homogeneous phantom sets, and four heterogeneous samples were used. A solid tumor tissue removed from a male BALB/c mouse was included. We the placed phantom sets on the CT scanning table and repeated 20 acquisitions with identical imaging settings. Regions of interest were delineated for feature extraction. Statistical quantities-average, standard deviation, and percentage uncertainty-were calculated from these 20 repeated scans. Percentage uncertainty was used to measure and quantify feature stability against quantum noise. Twelve radiomics features were measured. Random noise was added to study the robustness of machine learning classifiers against feature uncertainty.

RESULTS: We found the ranges of percentage uncertainties from homogeneous soft tissue phantoms, homogeneous bone phantoms, and solid tumor tissue to be 0.01-2138%, 0.02-15%, and 0.18-16%, respectively. Overall, it was found that the CT features ShortRunHighGrayLevelEmpha (SRHGE) (0.01-0.18%), ShortRunLowGrayLevelEmpha (SRLGE) (0.01-0.41%), LowGrayLevelRunEmpha (LGRE) (0.01-0.39%), and LongRunLowGrayLevelEmpha (LRLGE) (0.02-0.66%) were the most stable features against the inherent quantum noise. The most unstable features were cluster shade (1-2138%) and max probability (1-16%). The impact of random noise to the prediction accuracy by different machine learning classifiers was found to be between 0 and 12%.

CONCLUSIONS: Twelve features were used for uncertainty measurements. The upper and lower bounds of percentage uncertainties were determined. The quantum noise effect on machine learning classifiers is model dependent.

KEY POINTS: • Quantum noise is a random process and is intrinsic to X-ray-based imaging systems. This inherent quantum noise creates unpredictable fluctuations in the gray-level intensities of image pixels. Extra cautions and further validations are strongly recommended when unstable radiomics features are selected by a predictive model for disease classification or treatment outcome prognosis. • We addressed and used the statistical quantity of percentage uncertainty to measure the uncertainty of radiomics features against the inherent quantum noise in computed tomography (CT) images. • A clinical multi-detector CT scanner, two homogeneous phantom sets, and four heterogeneous samples were used in the stability measurement. A solid tumor tissue removed from a male BALB/c mouse was included in the heterogeneous sample.

PMID:33852047 | DOI:10.1007/s00330-021-07943-5