Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of [18F]MC225 as a PET radiotracer for measuring P-glycoprotein function at the blood–brain barrier in rats: Kinetics, metabolism, and selectivity

P-glycoprotein is a protective efflux transporter at the blood–brain barrier showing altered function in many neurological disorders. The purpose of this study was to validate [18F]MC225 as a radiotracer for measuring P-glycoprotein function with positron emission tomography. Three groups of Sprague-Dawley rats were used to assess tracer uptake at baseline (group 1), after inhibition of P-glycoprotein (group 2), and after inhibition of both P-glycoprotein and breast cancer resistance protein (Bcrp, group 3). A two-tissue compartment model with a metabolite-corrected plasma input function provided the best fit to the positron emission tomography data, but parameter estimates were more reliable in a one-tissue compartment model, which was selected as the preferred model. Regional distribution volumes (VT) in the control group ranged from 6 to 11, which is higher than for other radiotracers. [18F]MC225 showed transporter selectivity, since inhibition of P-glycoprotein caused a two to fourfold increase in the cerebral VT values, but additional inhibition of Bcrp did not cause any further increase. Metabolic stability of [18F]MC225 was moderate (at 1 h post-injection 15% of plasma radioactivity and 76% of brain radioactivity represented intact parent). Thus, [18F]MC225 may be a useful radiotracer to measure especially increases of P-glycoprotein function at the blood–brain barrier.
The Bayesian New Statistics: Hypothesis testing, estimation, meta-analysis, and power analysis from a Bayesian perspective

In the practice of data analysis, there is a conceptual distinction between hypothesis testing, on the one hand, and estimation with quantified uncertainty on the other. Among frequentists in psychology, a shift of emphasis from hypothesis testing to estimation has been dubbed “the New Statistics” (Cumming 2014). A second conceptual distinction is between frequentist methods and Bayesian methods. Our main goal in this article is to explain how Bayesian methods achieve the goals of the New Statistics better than frequentist methods. The article reviews frequentist and Bayesian approaches to hypothesis testing and to estimation with confidence or credible intervals. The article also describes Bayesian approaches to meta-analysis, randomized controlled trials, and power analysis.
Contribution of Socioeconomic Status at 3 Life-Course Periods to Late-Life Memory Function and Decline: Early and Late Predictors of Dementia Risk

Both early life and adult socioeconomic status (SES) predict late-life level of memory; however, evidence is mixed on the relationship between SES and rate of memory decline. Further, the relative importance of different life-course periods for rate of late-life memory decline has not been evaluated. We examined associations between life-course SES and late-life memory function and decline. Health and Retirement Study participants (n = 10,781) were interviewed biennially from 1998-2012 (United States). SES measurements for childhood (composite score including parents' educational attainment), early adulthood (high-school or college completion), and older adulthood (income, mean age 66 years) were all dichotomized. Word-list memory was modeled via inverse-probability weighted longitudinal models accounting for differential attrition, survival, and time-varying confounding, with nonrespondents retained via proxy assessments. Compared to low SES at all 3 points (referent), stable, high SES predicted the best memory function and slowest decline. High-school completion had the largest estimated effect on memory (β = 0.19; 95% confidence interval: 0.15, 0.22), but high late-life income had the largest estimated benefit for slowing declines (for 10-year memory change, β = 0.35; 95% confidence interval: 0.24, 0.46). Both early and late-life interventions are potentially relevant for reducing dementia risk by improving memory function or slowing decline.
Patients' and Health Professionals' Experiences of Using Virtual Reality Technology for Upper Limb Training after Stroke: A Qualitative Substudy

Background In recent years, virtual reality (VR) therapy systems for upper limb training after stroke have been increasingly used in clinical practice. Therapy systems employing VR technology can enhance the intensity of training and can also boost patients' motivation by adding a playful element to therapy. However, reports on user experiences are still scarce. Methods A qualitative investigation of patients' and therapists' perspectives on VR upper limb training. Semistructured face-to-face interviews were conducted with six patients in the final week of the VR intervention. Therapists participated in two focus group interviews after the completion of the intervention. The interviews were analyzed from a phenomenological perspective emphasizing the participants' perceptions and interpretations. Results Five key themes were identified from the patients' perspectives: (i) motivational factors, (ii) engagement, (iii) perceived improvements, (iv) individualization, and (v) device malfunction. The health professionals described the same themes as the patients but less positively, emphasizing negative technical challenges. Conclusion Patients and therapists mainly valued the intensive and motivational character of VR training. The playful nature of the training appeared to have a significant influence on the patients' moods and engagement and seemed to promote a “gung-ho” spirit, so they felt that they could perform more repetitions.
A novel approach for superficial intraoperative radiotherapy (IORT) using a 50 kV X‐ray source: a technical and case report

The use of IORT as a treatment modality for patients with close or positive margins has increased over the past decade. For situations where a flat area (up to 6 cm in diameter) has to be treated intraoperatively, new applicators for superficial treatment with a miniature X‐ray source (INTRABEAM system) were developed. Here we report our evaluation of the dosimetric characteristics of these new applicators and their first clinical use. Each of these flat and surface applicators consists of a radiation protective metal tube and a flattening filter, which converts the spherical dose distribution of the X‐ray source into a flat one. The homogeneity of each dose distribution and depth‐dose measurements were evaluated using film dosimetry in a solid water phantom and a soft X‐ray ionization chamber in a water tank. The first patient was treated with 5 Gy delivered in 5 mm using a 4 cm FLAT applicator over 21 minutes. The flat applicators show the maximum homogeneity, with a uniformity ratio of 1.02‐1.08 in certain depths. In 1 mm depth surface applicators show a uniformity ratio of 1.15‐1.28. They also show a higher dose rate and a steeper dose gradient compared to the flat applicators. The results of this investigation demonstrated that the flat and surface applicators have unique dosimetric characteristics that need to be considered during the treatment planning stages. This work also showed that it is possible to perform a superficial localized IORT which provides new application possibilities for use of the INTRABEAM system. PACS number: 87.55. ne
Differential roles of two delayed rectifier potassium currents in regulation of ventricular action potential duration and arrhythmia susceptibility

Arrhythmias result from disruptions to cardiac electrical activity, although the factors that control cellular action potentials are incompletely understood. We combined mathematical modelling with experiments in heart cells from guinea pigs to determine how cellular electrical activity is regulated. A mismatch between modelling predictions and the experimental results allowed us to construct an improved, more predictive mathematical model. The balance between two particular potassium currents dictates how heart cells respond to perturbations and their susceptibility to arrhythmias.
Joint scheduling of MapReduce jobs with servers: Performance bounds and experiments

MapReduce has achieved tremendous success for large-scale data processing in data centers. A key feature distinguishing MapReduce from previous parallel models is that it interleaves parallel and sequential computation. Past schemes, and especially their theoretical bounds, on general parallel models are therefore, unlikely to be applied to MapReduce directly. There are many recent studies on MapReduce job and task scheduling. These studies assume that the servers are assigned in advance. In current data centers, multiple MapReduce jobs of different importance levels run together. In this paper, we investigate a schedule problem for MapReduce taking server assignment into consideration as well. We formulate a MapReduce server-job organizer problem (MSJO) and show that it is NP-complete. We develop a 3-approximation algorithm and a fast heuristic. We evaluate our algorithms through both simulations and experiments on Amazon EC2 with an implementation in Hadoop. The results confirm the advantage of our algorithms.
Water Exposure is a Common Risk Behavior Among Soft and Gas-Permeable Contact Lens Wearers

Purpose: To understand soft contact lens (SCL) and gas-permeable (GP) lens wearers' behaviors and knowledge regarding exposure of lenses to water. Methods: The Contact Lens Risk Survey (CLRS) and health behavior questions were completed online by a convenience sample of 1056 SCL and 85 GP lens wearers aged 20 to 76 years. Participants were asked about exposing their lenses to water and their understanding of risks associated with these behaviors. Chi-square analyses examined relationships between patient behaviors and perceptions. Results: GP lens wearers were more likely than SCL wearers to ever rinse or store lenses in water (rinsing: 91% GP, 31% SCL, P < 0.001; storing: 33% GP, 15% SCL P < 0.001). Among SCL wearers, men were more likely to store (24% vs. 13%, P = 0.003) or rinse (41% vs. 29%, P = 0.012) their lenses in water. Showering while wearing lenses was more common in SCL wearers (86%) than GP lens wearers (67%) (P < 0.0001). Swimming while wearing lenses was reported by 62% of SCL wearers and 48% of GP lens wearers (P = 0.027). Wearers who rinsed (SCL; P < 0.0001, GP; P = 0.11) or stored lenses in water (SCL; P < 0.0001, GP P = 0.007) reported that this behavior had little or no effect on their infection risk, compared with those who did not. Both SCL (P < 0.0001) and GP lens wearers (P < 0.0001) perceived that distilled water was safer than tap water for storing or rinsing lenses. Conclusions: Despite previously published evidence of Acanthamoeba keratitis' association with water exposure, most SCL, and nearly all GP lens wearers, regularly expose their lenses to water, with many unaware of the risk.
IGFBP3 Modulates Lung Tumorigenesis and Cell Growth through IGF1 Signaling

Insulin-like growth factor binding protein 3 (IGFBP3) modulates cell growth through IGF-dependent and -independent mechanisms. Reports suggest that the serum levels of IGFBP3 are associated with various cancers and that IGFBP3 expression is significantly decreased in cisplatin (CDDP)-resistant lung cancer cells. Based on these findings, we investigated whether Igfbp3 deficiency accelerates mouse lung tumorigenesis and if expression of IGFBP3 enhances CDDP response by focusing on the IGF1 signaling cascade. To this end, an Igfbp3-null mouse model was generated in combination with KrasG12D to compare the tumor burden. Then, IGF-dependent signaling was assessed after expressing wild-type or a mutant IGFBP3 without IGF binding capacity in non–small cell lung cancer (NSCLC) cells. Finally, the treatment response to CDDP chemotherapy was evaluated under conditions of IGFBP3 overexpression. Igfbp3-null mice had increased lung tumor burden (>2-fold) and only half of human lung cancer cells survived after expression of IGFBP3, which corresponded to increased cleaved caspase-3 (10-fold), inactivation of IGF1 and MAPK signaling. In addition, overexpression of IGFBP3 increased susceptibility to CDDP treatment in lung cancer cells. These results, for the first time, demonstrate that IGFBP3 mediates lung cancer progression in a KrasG12D mouse model. Furthermore, overexpression of IGFBP3 induced apoptosis and enhanced cisplatin response in vitro and confirmed that the suppression is in part by blocking IGF1 signaling. Implications: These findings reveal that IGFBP3 is effective in lung cancer cells with high IGF1 signaling activity and imply that relevant biomarkers are essential in selecting lung cancer patients for IGF1-targeted therapy. Mol Cancer Res; 15(7); 896–904. ©2017 AACR.
14 – Tin and copper oxides in corroded archaeological bronzes

Publisher Summary This chapter presents that tin bronzes have been materials in common use since archaeological times. Many factors, such as the composition and microstructure of bronzes and the corrosive environment features of the burial context, can influence the chemical and structural nature of patinas. In general, the corrosion compounds have been roughly identified by X-ray diffraction (performed on the surface directly or on powder produced from the patina). Bronze corrosion exhibits complex and heterogeneous structures. However, it is established that patinas of ancient bronze objects reveal numerous common morphological features, such as the presence of tin-enriched corrosion layers. Furthermore, the formation process of bronze patinas in natural environments is mainly related to a selective dissolution of copper. The understanding of bronze patinas is most often based on two types of corrosion structures, according to the presence or absence of an original surface preserving the original shape of the artefact. It is introduced and detailed in the chapter. One of the main goals of the study presented in the chapter is to obtain a structural characterization of the nature of the corrosion compounds of internal tin-enriched corrosion layers in the case of “type 2” patinas. In addition to the classical approaches (optical and electron microscopy, elemental analysis), the Raman microspectroscopy and the X-ray microdiffraction are used in the study to get a structural analysis of the compounds with a lateral resolution at the microscopic level. The chapter discusses the results achieved in the frame of a better understanding of bronze corrosion mechanisms.
Modeling and measurement of the variations of CT number distributions for mobile targets in cone‐beam computed tomographic imaging

The purpose of this study was to investigate quantitatively by measurement and modeling the variations in CT number distributions of mobile targets in cone‐beam CT (CBCT) imaging. CBCT images were acquired for three targets manufactured from homogenous water‐equivalent gel that was inserted into a commercial mobile thorax phantom. The phantom moved with a controlled cyclic motion in one‐dimension along the superior–inferior direction to simulate patient respiratory motion. Profiles of the CT number distributions of the static and mobile targets were obtained using CBCT images. A mathematical model was developed that predicted the variations in CT number distributions and their dependence on the motion parameters of targets moving in one‐dimension using CBCT imaging. The measured CT number distributions for the mobile targets varied considerably, depending on the motion parameters. The extension of the CT number distribution increased linearly with motion amplitude where maximum target elongation reached twice the motion amplitude. The CT number levels of the mobile targets were smeared over a longer distribution; for example, the CT number level for the 20 mm target dropped by nearly 30% at motion amplitude (A) equal to 20 mm in comparison with the CT number distribution of stationary targets. Frequency of motion played an important role in spatial and level variations of the CT number distributions. For example, the level of the CT number profile for the medium target (20 mm) decreased evenly by nearly 50% at A=20 mm with high motion frequencies. Motion phase did not affect the CT number distributions for prolonged projection acquisition that included several respiratory cycles. The mathematical model of the CT number distributions of mobile targets in CBCT reproduced well the measured CT number distributions and predicted their dependence on the target size and phantom motion parameters such as speed, amplitude, frequency, and phase. The CT number distributions varied considerably with motion in CBCT. A motion model of CT number distribution for mobile targets has been developed in this work that predicted well the variations in the measured CT number profiles and their dependence on motion parameters. The model corrected the CT number distribution retrospective to CT image reconstruction where it used a first‐order linear relationship between the number of projections collected in the imaging window of a mobile voxel to obtain the cumulative CT number. This model provides quantitative characterization of motion artifacts on CT number distributions in CBCT that is useful to determine the validity of CT numbers and the accuracy of localization and volume measurement of tumors in diagnostic imaging and interventional applications, such as radiotherapy. PACS number: 87.57. C‐
Deriving detector‐specific correction factors for rectangular small fields using a scintillator detector

The goal of this study was to investigate small field output factors (OFs) for flattening filter‐free (FFF) beams on a dedicated stereotactic linear accelerator‐based system. From this data, the collimator exchange effect was quantified, and detector‐specific correction factors were generated. Output factors for 16 jaw‐collimated small fields (from 0.5 to 2 cm) were measured using five different detectors including an ion chamber (CC01), a stereotactic field diode (SFD), a diode detector (Edge), Gafchromic film (EBT3), and a plastic scintillator detector (PSD, W1). Chamber, diodes, and PSD measurements were performed in a Wellhofer water tank, while films were irradiated in solid water at 100 cm source‐to‐surface distance and 10 cm depth. The collimator exchange effect was quantified for rectangular fields. Monte Carlo (MC) simulations of the measured configurations were also performed using the EGSnrc/DOSXYZnrc code. Output factors measured by the PSD and verified against film and MC calculations were chosen as the benchmark measurements. Compared with plastic scintillator detector (PSD), the small volume ion chamber (CC01) underestimated output factors by an average of ‐1.0%±4.9%(max.=‐11.7% for 0.5×0.5cm2 square field). The stereotactic diode (SFD) overestimated output factors by 2.5%±0.4%(max.=3.3% for 0.5×1cm2 rectangular field). The other diode detector (Edge) also overestimated the OFs by an average of 4.2%±0.9%(max.=6.0% for 1×1cm2 square field). Gafchromic film (EBT3) measurements and MC calculations agreed with the scintillator detector measurements within 0.6%±1.8% and 1.2%±1.5%, respectively. Across all the X and Y jaw combinations, the average collimator exchange effect was computed: 1.4%±1.1% (CC01), 5.8%±5.4% (SFD), 5.1%±4.8% (Edge diode), 3.5%±5.0% (Monte Carlo), 3.8%±4.7% (film), and 5.5%±5.1% (PSD). Small field detectors should be used with caution with a clear understanding of their behaviors, especially for FFF beams and small, elongated fields. The scintillator detector exhibited good agreement against Gafchromic film measurements and MC simulations over the range of field sizes studied. The collimator exchange effect was found to be important at these small field sizes. Detector‐specific correction factors were computed using the scintillator measurements as the benchmark. PACS number(s): 87.56. Fc
Genetic Variability of Myxoma Virus Genomes

ABSTRACT Myxomatosis is a recurrent problem on rabbit farms throughout Europe despite the success of vaccines. To identify gene variations of field and vaccine strains that may be responsible for changes in virulence, immunomodulation, and immunoprotection, the genomes of 6 myxoma virus (MYXV) strains were sequenced: German field isolates Munich-1, FLI-H, 2604, and 3207; vaccine strain MAV; and challenge strain ZA. The analyzed genomes ranged from 147.6 kb (strain MAV) to 161.8 kb (strain 3207). All sequences were affected by several mutations, covering 24 to 93 open reading frames (ORFs) and resulted in amino acid substitutions, insertions, or deletions. Only strains Munich-1 and MAV revealed the deletion of 10 ORFs (M007L to M015L) and 11 ORFs (M007L to M008.1L and M149R to M008.1R), respectively. Major differences were observed in the 27 immunomodulatory proteins encoded by MYXV. Compared to the reference strain Lausanne, strains FLI-H, 2604, 3207, and ZA showed the highest amino acid identity (>98.4%). In strains Munich-1 and MAV, deletion of 5 and 10 ORFs, respectively, was observed, encoding immunomodulatory proteins with ankyrin repeats or members of the family of serine protease inhibitors. Furthermore, putative immunodominant surface proteins with homology to vaccinia virus (VACV) were investigated in the sequenced strains. Only strain MAV revealed above-average frequencies of amino acid substitutions and frameshift mutations. Finally, we performed recombination analysis and found signs of recombination in vaccine strain MAV. Phylogenetic analysis showed a close relationship of strain MAV and the MSW strain of Californian MYXV. However, in a challenge model, strain MAV provided full protection against lethal challenges with strain ZA. IMPORTANCE Myxoma virus (MYXV) is pathogenic for European rabbits and two North American species. Due to sophisticated strategies in immune evasion and oncolysis, MYXV is an important model virus for immunological and pathological research. In its natural hosts, MYXV causes a benign infection, whereas in European rabbits, it causes the lethal disease myxomatosis. Since the introduction of MYXV into Australia and Europe for the biological control of European rabbits in the 1950s, a coevolution of host and pathogen has started, selecting for attenuated virus strains and increased resistance in rabbits. Evolution of viruses is a continuous process and influences the protective potential of vaccines. In our analyses, we sequenced 6 MYXV field, challenge, and vaccine strains. We focused on genes encoding proteins involved in virulence, host range, immunomodulation, and envelope composition. Genes affected most by mutations play a role in immunomodulation. However, attenuation cannot be linked to individual mutations or gene disruptions.