bluuebunny/crossref_metadata_2025 huggingface dataset:
MCPIP1 Exogenous Overexpression Inhibits Pathways Regulating MYCN Oncoprotein Stability in Neuroblastoma
Authors: Boratyn Elżbieta , Nowak Iwona , Durbas Małgorzata , Horwacik Irena , Sawicka Anna , Rokita Hanna
Published: December 2016

The main physiological function of MCPIP1 (regnase‐1) is negative regulation of inflammation. Moreover, roles of regnase‐1 in apoptosis and differentiation have also been described, but its involvement in cancer is yet to be fully recognized. Earlier, we showed a lack of expression of MCPIP1 in both primary tumors and several neuroblastoma cell lines. Additionally, we reported that levels of MCPIP1 and the key neuroblastoma oncoprotein—MYCN were inversely correlated in BE(2)‐C clones overexpressing the MCPIP1 gene. Here, we show that exogenous expression of the MCPIP1 protein decreases MYCN mRNA and protein levels without changing the MYCN mRNA half‐life. Furthermore, it was shown that MCPIP1‐wt exogenous expression affects levels and phosphorylation of MYCN partners such as Aurora A (Thr288), CDC2 (Tyr15 and Thr161), GSK3β (Ser9), and key cellular components of Akt/mTOR signaling, which regulate MYCN stability and activation. In accordance with the obtained results, we found increased phosphorylation of MYCN protein at Thr58 that causes destabilization of the oncoprotein. Moreover, it is shown that exogenous expression of MCPIP1 does not cause apoptosis. Our data extend knowledge on roles of MCPIP1 in our model and link the protein to regulation of expression and stability of MYCN through decrease of signaling via Akt/mTOR pathway. J. Cell. Biochem. 118: 1741–1755, 2017. © 2016 Wiley Periodicals, Inc.
Macroporous hydroxyapatite ceramic beads for fluoride removal from drinking water
Authors: Nijhawan Anisha , Butler Elizabeth C , Sabatini David A
Published: December 2016

BACKGROUND

This study evaluates the capacity of hydroxyapatite ceramics to remove fluoride from drinking water. Porous hydroxyapatite ceramic beads approximately 5 mm in diameter were fabricated using soluble potato starch as well as insoluble rice starch, wheat starch, corn starch, and cellulose as pore‐forming agents.

RESULTS

Calcination of hydroxyapatite particles, followed by mixing with starches and water, compaction, and sintering at 1200 °C resulted in the formation of macroporous ceramic beads with maximum fluoride adsorption capacities ranging from 7 to 12 mg g−1, depending on the relative proportions of different pore‐forming agents. Increasing the insoluble starch content from 0 to 25% by volume in ceramics with 50% by volume hydroxyapatite led to a marked improvement in fluoride adsorption by creating interconnected macropores, as evidenced by scanning electron microscopy (SEM). Calcination of hydroxyapatite powder at or above 400 °C before ceramic preparation was required to obtain a ceramic material with sufficient structural integrity to withstand operation and handling after sintering.

CONCLUSION

This study evaluates the potential of using porous hydroxyapatite ceramics to remove fluoride from drinking water. An increase in fluoride adsorption capacity was consistent with the observation of macropores in SEM images as well as an increase in open porosity and specific surface area (SSA) measurements as the insoluble starch content was increased from 0 to 25%. © 2016 Society of Chemical Industry
Retracted: MicroRNA‐4656 is a prognostic factor and tumor suppressor in human pancreatic cancer through a downstream target of TrkA
Authors: Tan Xianglong , Lv Jinyong , Zhao Guodong , Zhao Zhiming , Li Chenggang , Xu Yong , Hu Minggen
Published: December 2016

Background

In the present study, we investigated the expression profile and functional mechanism of microRNA‐4656 in human pancreatic cancer (PC).

Methods

MiR‐4656 expression in PC tumors was examined using a quantitative reverse transcriptase‐polymerase chain reaction in 134 patients. Associations between tumorous miR‐4656 expression and clinicopathological parameters of patients, as well as overall survival, were analyzed. MiR‐4656 expression was also examined in PC in vitro cell lines. In Capan‐1 and AsPC‐1 PC cells, lentivirus‐induced miR‐4656 overexpression or downregulation was applied to investigate its functional regulations on PC in vitro proliferation and invasion, as well as in vivo transplant growth. The association of miR‐4656 and its downstream target, the tropomyosin receptor kinase A (TrkA) gene, was investigated in both cell line and clinical pancreatic tumors. In miR‐4656‐overerxpressed PC cells, TrkA was overexpressed with the aim of investigating its role in miR‐4656‐induced functional regulation in PC.

Results

MiR‐4656 was downregulated in PC. Low tumorous miR‐4656 expression was associated with a poor prognosis and overall survival of patients. MiR‐4656 was also found to be downregulated in PC cell lines. MiR‐4656 overexpression in Capan‐1 and AsPC‐1 cells significantly inhibited cancer proliferation and invasion in vitro, as well as explant growth in vivo, whereas miR‐4656 downregulation had no effect on cancer development. The TrkA gene was directly bound by miR‐4656, and reversely expressed in PC tumors as miR‐4656. TrkA overexpression reversed the inhibitory effect of miR‐4656‐overexpression on PC proliferation and invasion.

Conclusions

MiR‐4656 is expressed to a low extent and is a potential biomarker in PC. Overexpressing miR‐4656 has tumor suppressive effects on PC development both in vitro and in vivo, likely through its downstream target of the TrkA gene.
A biophysical and computational study unraveling the molecular interaction mechanism of a new Janus kinase inhibitor Tofacitinib with bovine serum albumin
Authors: Abdelhameed Ali Saber , Nusrat Saima , Ajmal Mohammad Rehan , Zakariya Syed Mohammad , Zaman Masihuz , Khan Rizwan Hasan
Published: December 2016

The interaction of a recently certified kinase inhibitor Tofacitinib (TFB) with bovine serum albumin (BSA) has been studied, by spectroscopic and molecular docking studies. Spectrofluorimetric measurements at 3 different temperatures (288, 298, and 310 K) showed that TFB quench the intrinsic fluorescence of BSA upon forming a nonfluorescent complex. The intrinsic fluorescence data showed that TFB binds to BSA with binding constant (Kb) of approximately 104M−1, affirming a significant affinity of TFB with BSA. The decrease in Stern‐Volmer quenching constant with increasing temperature exhibited the static mechanism of quenching. Negative value of ΔG (−6.94 ± 0.32 kcal·mol−1), ΔH (−7.87 ± 0.52 kcal·mol−1), and ΔS (−3.14 ± 0.42 cal·mol−1·K−1) at all 3 temperatures declared the reaction between BSA and TFB to be spontaneous and exothermic. Far‐UV circular dichroism spectroscopy results demonstrated an increase in helical content of BSA in the presence of TFB. Moreover, dynamic light scattering measurements showed that TFB resulted into a decrease in the hydrodynamic radii (from 3.6 ± 0.053 to 2.9 ± 0.02 nm) of BSA. Molecular docking studies confirmed that TFB binds near site II on BSA, hydrogen bonding, and hydrophobic interaction were involved in the BSA‐TFB complex formation. The present study characterizing the BSA‐TFB interaction could be significant towards gaining an insight into the drug pharmacokinetics and pharmacodynamics and also in the direction of rational drug designing with better competence, against emerging immune‐mediated diseases, ie, alopecia and rheumatoid arthritis.
Characterization of polyaniline‐coated stationary phases by using the linear solvation energy relationship in the hydrophilic interaction liquid chromatography mode using capillary liquid chromatography
Authors: Taraba Lukáš , Křížek Tomáš , Hodek Ondřej , Kalíková Květa , Coufal Pavel
Published: December 2016

A polyaniline coating was used to modify the surface of bare silica gel and octadecyl silica stationary phases to characterize the properties of altered materials. It was assumed that the mixed‐mode retention was established on the basis of the polyaniline chemical structure and its combination with the original sorbents. Polyaniline was deposited onto the original surfaces during the chemical polymerization of aniline hydrochloride. The prepared materials were slurry packed into capillary columns and systematic chromatographic characterization was performed using the linear solvation energy relationship, also employing descriptors that allow inclusion of ionic interactions in the proposed retention mechanism. The retention times of 80 solutes with various chemical structures were measured in the hydrophilic interaction liquid chromatography mode. The obtained results demonstrated the significant contribution of the polyaniline coating to the retention mechanism under the given conditions; the assumed mixed‐mode retention was confirmed. The dominant retention interaction for both modified stationary phases was based on the protonation of nitrogen atoms in the polyaniline structure, leading to suitable retention and selectivity for the hydrophilic analytes, especially anionic and zwitterionic species. Thus, especially, the polyaniline‐coated bare silica gel sorbent seems to be promising for potential applications related to the separation of polar compounds.
Laryngeal pacing for bilateral vocal fold paralysis: Voice and respiratory aspects
Authors: Mueller Andreas H. , Hagen Rudolf , Pototschnig Claus , Foerster Gerhard , Grossmann Wilma , Baumbusch Katrin , Gugatschka Markus , Nawka Tadeus
Published: December 2016

Objective

To evaluate the effects of neurostimulation with the laryngeal pacemaker (LP) system in patients with bilateral vocal fold paralysis (BVFP) in terms of voice quality and respiratory function.

Study Design

Feasibility study, first‐in‐human, single‐arm, open‐label, prospective, multicenter study with group‐sequential design and 6‐month follow‐up period, as described in details in our previous publication.

Methods

Nine symptomatic BVFP subjects were unilaterally implanted with the LP system at three study sites in Germany and Austria. Subjective and objective voice function, spirometric parameters other than peak expiratory/inspiratory flow (PEF/PIF), and PEF‐meter self‐assessment were evaluated pre‐ and 6 months postimplantation.

Results

In general, the LP system did not considerably change the voice quality of the implanted patients. Only the sound pressure level range improved significantly 6 months postimplantation (P = 0.018). The LP system implantation did not affect the glottal closure configuration, the duration of the closed phase, and the mucosal wave of the implanted side. The evaluated spirometric parameters were not significantly affected by laryngeal pacing, whereas PEF meter self‐assessment showed a stable and significant (P = 0.028) improvement of the PEF within a week upon activation of the LP system.

Conclusion

Neurostimulation with the LP system results in an immediate and stable PEF improvement, without negative effects on the voice quality. The PEF meter self‐assessment confirmed the spirometry results of the PEF. The stimulated abduction did not affect the glottal closure during phonation. These results should be confirmed in larger and more homogenous patient cohorts.

Level of Evidence

2b Laryngoscope, 127:1838–1844, 2017
Parameterization of the Effect of Bench Terraces on Runoff and Sediment Yield by Swat Modeling in a Small Semi‐arid Watershed in Northern Tunisia
Authors: Khelifa Walid Ben , Hermassi Taoufik , Strohmeier Stefan , Zucca Claudio , Ziadat Feras , Boufaroua Mohamed , Habaieb Hamadi
Published: December 2016

In Tunisia, soil and water conservation interventions are among the most practicable strategies to prevent and mitigate rainwater losses through surface runoff and consequential erosion of fertile soils. In this study, a small and terraced agricultural catchment (Sbaihia) was used as an experimental site to analyze and parameterize the effects of bench terraces on water and sediment yield using the Soil and Water Assessment Tool. Model calibration and validation was performed, taking advantage from high‐quality daily runoff data from 1994 to 2000 and a high‐resolution bathymetric survey of the hill lake at the watershed outlet. Soil and Water Assessment Tool indicated that the local terraces, established on approximately 50% of the watershed area, reduced surface runoff by around 19% and sediment yield by around 22%, decelerating the siltation of the hill lake. Targeted model calibration delivered concise parameter set describing bench terrace impacts on runoff (Soil Conservation Service curve number method) and sediment yield (Modified Universal Soil Loss Equation) crucial for outscaling of soil and water conservation impacts and suitable watershed management. Copyright © 2016 John Wiley & Sons, Ltd.
Four‐dimensional diffusion‐weighted MR imaging (4D‐DWI): a feasibility study
Authors: Liu Yilin , Zhong Xiaodong , Czito Brian G. , Palta Manisha , Bashir Mustafa R. , Dale Brian M. , Yin Fang‐Fang , Cai Jing
Published: December 2016

Purpose

Diffusion‐weighted Magnetic Resonance Imaging (DWI) has been shown to be a powerful tool for cancer detection with high tumor‐to‐tissue contrast. This study aims to investigate the feasibility of developing a four‐dimensional DWI technique (4D‐DWI) for imaging respiratory motion for radiation therapy applications.

Materials/Methods

Image acquisition was performed by repeatedly imaging a volume of interest (VOI) using an interleaved multislice single‐shot echo‐planar imaging (EPI) 2D‐DWI sequence in the axial plane. Each 2D‐DWI image was acquired with an intermediately low b‐value (b = 500 s/mm2) and with diffusion‐encoding gradients in x, y, and z diffusion directions. Respiratory motion was simultaneously recorded using a respiratory bellow, and the synchronized respiratory signal was used to retrospectively sort the 2D images to generate 4D‐DWI. Cine MRI using steady‐state free precession was also acquired as a motion reference. As a preliminary feasibility study, this technique was implemented on a 4D digital human phantom (XCAT) with a simulated pancreas tumor. The respiratory motion of the phantom was controlled by regular sinusoidal motion profile. 4D‐DWI tumor motion trajectories were extracted and compared with the input breathing curve. The mean absolute amplitude differences (D) were calculated in superior–inferior (SI) direction and anterior–posterior (AP) direction. The technique was then evaluated on two healthy volunteers. Finally, the effects of 4D‐DWI on apparent diffusion coefficient (ADC) measurements were investigated for hypothetical heterogeneous tumors via simulations.

Results

Tumor trajectories extracted from XCAT 4D‐DWI were consistent with the input signal: the average D value was 1.9 mm (SI) and 0.4 mm (AP). The average D value was 2.6 mm (SI) and 1.7 mm (AP) for the two healthy volunteers.

Conclusion

A 4D‐DWI technique has been developed and evaluated on digital phantom and human subjects. 4D‐DWI can lead to more accurate respiratory motion measurement. This has a great potential to improve the visualization and delineation of cancer tumors for radiotherapy.
Experimental evaluation of x‐ray acoustic computed tomography for radiotherapy dosimetry applications
Authors: Hickling Susannah , Lei Hao , Hobson Maritza , Léger Pierre , Wang Xueding , El Naqa Issam
Published: December 2016

Purpose

The aim of this work was to experimentally demonstrate the feasibility of x‐ray acoustic computed tomography (XACT) as a dosimetry tool in a clinical radiotherapy environment.

Methods

The acoustic waves induced following a single pulse of linear accelerator irradiation in a water tank were detected with an immersion ultrasound transducer. By rotating the collimator and keeping the transducer stationary, acoustic signals at varying angles surrounding the field were detected and reconstructed to form an XACT image. Simulated XACT images were obtained using a previously developed simulation workflow. Profiles extracted from experimental and simulated XACT images were compared to profiles measured with an ion chamber. A variety of radiation field sizes and shapes were investigated.

Results

XACT images resembling the geometry of the delivered radiation field were obtained for fields ranging from simple squares to more complex shapes. When comparing profiles extracted from simulated and experimental XACT images of a 4 cm × 4 cm field, 97% of points were found to pass a 3%/3 mm gamma test. Agreement between simulated and experimental XACT images worsened when comparing fields with fine details. Profiles extracted from experimental XACT images were compared to profiles obtained through clinical ion chamber measurements, confirming that the intensity of XACT images is related to deposited radiation dose. Seventy‐seven percent of the points in a profile extracted from an experimental XACT image of a 4 cm × 4 cm field passed a 7%/4 mm gamma test when compared to an ion chamber measured profile. In a complicated puzzle‐piece shaped field, 86% of the points in an XACT extracted profile passed a 7%/4 mm gamma test.

Conclusions

XACT images with intensity related to the spatial distribution of deposited dose in a water tank were formed for a variety of field sizes and shapes. XACT has the potential to be a useful tool for absolute, relative and in vivo dosimetry.
Evaluation of motion mitigation using abdominal compression in the clinical implementation of pencil beam scanning proton therapy of liver tumors
Authors: Lin Liyong , Souris Kevin , Kang Minglei , Glick Adam , Lin Haibo , Huang Sheng , Stützer Kristin , Janssens Guillaume , Sterpin Edmond , Lee John A. , Solberg Timothy D. , McDonough James E. , Simone Charles B. , Ben‐Josef Edgar
Published: December 2016

Purpose

To determine whether individual liver tumor patients can be safely treated with pencil beam scanning proton therapy. This study reports a planning preparation workflow that can be used for beam angle selection and the evaluation of the efficacy of abdominal compression (AC) to mitigate motion.

Methods

Four‐dimensional computed tomography scans (4DCT) with and without AC were available from 10 liver tumor patients with fluoroscopy‐proven motion reduction by AC, previously treated using photons. For each scan, the motion amplitudes and the motion‐induced variation of water‐equivalent thickness (ΔWET) in each voxel of the target volume were evaluated during treatment plan preparation. Optimal proton beam angles were selected after volume analysis of the respective beam‐specific planning target volume (BSPTV). M⊥80 and ΔWET80 derived from the 80th percentiles of perpendicular motion amplitude (M⊥) and ΔWET were compared with and without AC. Proton plans were created on the average CT to achieve target coverage similar to that of the conventional photon treatments. 4D dynamic dose calculation was performed postplan by synchronizing proton beam delivery timing patterns to the 4DCT phases to assess interplay and fractionation effects, and to determine motion criteria for subsequent patient treatment.

Results

Selected coplanar beam angles ranged between 180° and 39°, primarily from right lateral (oblique) and posterior (oblique) directions. While AC produced a significant reduction in mean Liver‐GTV dose, any reduction in mean heart dose was patient dependent and not significant. Similarly, AC resulted in reductions in M⊥, ΔWET, and BSPTV volumes and improved dose degradation (ΔD95 and ΔD1) within the CTV. For small motion (M⊥80 < 7 mm and ΔWET80 < 5 mm), motion mitigation was not needed. For moderate motion (M⊥80 7–10 mm or ΔWET80 5–7 mm), AC produced a modest improvement. For large motion (M⊥80 > 10 mm or ΔWET80 > 7 mm), AC and/or some other form of mitigation strategies were required.

Conclusion

A workflow for screening patients’ motion characteristics and optimizing beam angle selection was established for the pencil beam scanning proton therapy treatment of liver tumors. Abdominal compression was found to be useful at mitigation of moderate and large motion.
Segmentation of organs‐at‐risks in head and neck CT images using convolutional neural networks
Authors: Ibragimov Bulat , Xing Lei
Published: December 2016

Purpose

Accurate segmentation of organs‐at‐risks (OARs) is the key step for efficient planning of radiation therapy for head and neck (HaN) cancer treatment. In the work, we proposed the first deep learning‐based algorithm, for segmentation of OARs in HaN CT images, and compared its performance against state‐of‐the‐art automated segmentation algorithms, commercial software, and interobserver variability.

Methods

Convolutional neural networks (CNNs)—a concept from the field of deep learning—were used to study consistent intensity patterns of OARs from training CT images and to segment the OAR in a previously unseen test CT image. For CNN training, we extracted a representative number of positive intensity patches around voxels that belong to the OAR of interest in training CT images, and negative intensity patches around voxels that belong to the surrounding structures. These patches then passed through a sequence of CNN layers that captured local image features such as corners, end‐points, and edges, and combined them into more complex high‐order features that can efficiently describe the OAR. The trained network was applied to classify voxels in a region of interest in the test image where the corresponding OAR is expected to be located. We then smoothed the obtained classification results by using Markov random fields algorithm. We finally extracted the largest connected component of the smoothed voxels classified as the OAR by CNN, performed dilate–erode operations to remove cavities of the component, which resulted in segmentation of the OAR in the test image.

Results

The performance of CNNs was validated on segmentation of spinal cord, mandible, parotid glands, submandibular glands, larynx, pharynx, eye globes, optic nerves, and optic chiasm using 50 CT images. The obtained segmentation results varied from 37.4% Dice coefficient (DSC) for chiasm to 89.5% DSC for mandible. We also analyzed the performance of state‐of‐the‐art algorithms and commercial software reported in the literature, and observed that CNNs demonstrate similar or superior performance on segmentation of spinal cord, mandible, parotid glands, larynx, pharynx, eye globes, and optic nerves, but inferior performance on segmentation of submandibular glands and optic chiasm.

Conclusion

We concluded that convolution neural networks can accurately segment most of OARs using a representative database of 50 HaN CT images. At the same time, inclusion of additional information, for example, MR images, may be beneficial to some OARs with poorly visible boundaries.
Feasibility of external beam radiation therapy to deep‐seated targets with kilovoltage x‐rays
Authors: Bazalova‐Carter Magdalena , Weil Michael D. , Breitkreutz Dylan Yamabe , Wilfley Brian P. , Graves Edward E.
Published: December 2016

Purpose

Radiation therapy to deep‐seated targets is typically delivered with megavoltage x‐ray beams generated by medical linear accelerators or 60Co sources. Here, we used computer simulations to design and optimize a lower energy kilovoltage x‐ray source generating acceptable dose distributions to a deep‐seated target.

Methods

The kilovoltage arc therapy (KVAT) x‐ray source was designed to treat a 4‐cm diameter target located at a 10‐cm depth in a 40‐cm diameter homogeneous cylindrical phantom. These parameters were chosen as an example of a clinical scenario for testing the performance of the kilovoltage source. A Monte Carlo (MC) model of the source was built in the EGSnrc/BEAMnrc code and source parameters, such as beam energy, tungsten anode thickness, beam filtration, number of collimator holes, collimator hole size and thickness, and source extent were varied. Dose to the phantom was calculated in the EGSnrc/DOSXYZnrc code for varying treatment parameters, such as the source‐to‐axis distance and the treatment arc angle. The quality of dose distributions was quantified by means of target‐to‐skin ratio and dose output expressed in D50 (50% isodose line) for a 30‐min irradiation in the homogeneous phantom as well as a lung phantom. Additionally, a patient KVAT dose distribution to a left pararenal lesion (~1.6 cm in diameter) was calculated and compared to a 15 MV volumetric modulated arc therapy (VMAT) plan.

Results

In the design of the KVAT x‐ray source, the beam energy, beam filtration, collimator hole size, source‐to‐isocenter distance, and treatment arc had the largest effect on the source output and the quality of dose distributions. For the 4‐cm target at 10‐cm depth, the optimized KVAT dose distribution generated a conformal plan with target‐to‐skin ratio of 5.1 and D50 in 30 min of 24.1 Gy in the homogeneous phantom. In the lung phantom, a target‐to‐skin ratio of 7.5 and D50 in 30 min of 25.3 Gy were achieved. High dose conformity of the 200 kV KVAT left pararenal plan was comparable to the 15 MV VMAT plan. The volume irradiated to at least 10% (<240 cGy) of the prescription dose was 2.2 × larger in the 200 kV KVAT plan than in the 15 MV VMAT plan, but considered clinically insignificant.

Conclusions

This study demonstrated that conformal treatments of deep‐seated targets were achievable with kilovoltage x‐rays with dose distributions comparable to MV beams. However, due to the larger volumes irradiated to clinically tolerated low doses, KVAT x‐ray source usage for deep‐seated lesions will be further evaluated to determine optimal target size.
A feasibility study of a deuterium–deuterium neutron generator‐based boron neutron capture therapy system for treatment of brain tumors
Authors: Hsieh Mindy , Liu Yingzi , Mostafaei Farshad , Poulson Jean M. , Nie Linda H.
Published: December 2016

Purpose

Boron neutron capture therapy (BNCT) is a binary treatment modality that uses high LET particles to achieve tumor cell killing. Deuterium–deuterium (DD) compact neutron generators have advantages over nuclear reactors and large accelerators as the BNCT neutron source, such as their compact size, low cost, and relatively easy installation. The purpose of this study is to design a beam shaping assembly (BSA) for a DD neutron generator and assess the potential of a DD‐based BNCT system using Monte Carlo (MC) simulations.

Methods

The MC model consisted of a head phantom, a DD neutron source, and a BSA. The head phantom had tally cylinders along the centerline for computing neutron and photon fluences and calculating the dose as a function of depth. The head phantom was placed at 4 cm from the BSA. The neutron source was modeled to resemble the source of our current DD neutron generator. A BSA was designed to moderate and shape the 2.45‐MeV DD neutrons to the epithermal (0.5 eV to 10 keV) range. The BSA had multiple components, including moderator, reflector, collimator, and filter. Various materials and configurations were tested for each component. Each BSA layout was assessed in terms of the in‐air and in‐phantom parameters. The maximum brain dose was limited to 12.5 Gray‐Equivalent (Gy‐Eq) and the skin dose to 18 Gy‐Eq.

Results

The optimized BSA configuration included 30 cm of lead for reflector, 45 cm of LiF, and 10 cm of MgF2 for moderator, 10 cm of lead for collimator, and 0.1 mm of cadmium for thermal neutron filter. Epithermal flux at the beam aperture was 1.0 × 105 nepi/cm2‐s; thermal‐to‐epithermal neutron ratio was 0.05; fast neutron dose per epithermal was 5.5 × 10−13 Gy‐cm2/φepi, and photon dose per epithermal was 2.4 × 10−13 Gy‐cm2/φepi. The AD, AR, and the advantage depth dose rate were 12.1 cm, 3.7, and 3.2 × 10−3 cGy‐Eq/min, respectively. The maximum skin dose was 0.56 Gy‐Eq. The DD neutron yield that is needed to irradiate in reasonable time was 4.9 × 1013 n/s.

Conclusions

Results demonstrated that a DD‐based BNCT system could be designed to produce neutron beams that have acceptable in‐air and in‐phantom characteristics. The parameter values were comparable to those of existing BNCT facilities. Continuing efforts are ongoing to improve the DD neutron yield.
Commissioning of the Leksell Gamma Knife® Icon™
Authors: Zeverino Michele , Jaccard Maud , Patin David , Ryckx Nick , Marguet Maud , Tuleasca Constantin , Schiappacasse Luis , Bourhis Jean , Levivier Marc , Bochud Francois O. , Moeckli Raphaël
Published: December 2016

Purpose

The Leksell Gamma Knife (LGK) Icon has been recently introduced to provide Gamma Knife technology with frameless stereotactic treatments which use an additional cone‐beam CT (CBCT) imaging system and a motion tracking system (IFMM, Intra‐Fraction Motion Management). The system was commissioned for the treatment unit itself as well as the imaging system.

Methods

The LGK Icon was calibrated using an A1SL ionization chamber. EBT3 radiochromic films were employed to independently check the machine calibration, to measure the relative output factors (ROFs) and to collect dose distributions. Coincidence between CBCT isocenter and radiological focus was evaluated by means of EBT3 films. CBCT image quality was investigated in terms of spatial resolution, contrast‐to‐noise ratio (CNR), and uniformity for the two presets available (low dose and high dose). Computed Tomography Dose Index (CTDI) was also measured for both presets.

Results

The absolute dose rate of the LGK Icon was 3.86 ± 0.09 Gy/min. This result was confirmed by EBT3 readings. ROF were found to be 0.887 ± 0.035 and 0.797 ± 0.032 for the 8 mm and 4 mm collimators, respectively, which are within 2% of the Monte Carlo‐derived ROF values. Excellent agreement was found between calculated and measured dose distribution with the gamma pass rate >95% of points for the nine dose distributions analyzed with 3%/1 mm criteria. CBCT isocenter was found to be within 0.2 mm with respect to radiological focus. Image quality parameters were found to be well within the manufacturer's specifications with the high‐dose preset being superior in terms of CNR and uniformity. CTDI values were 2.41 mGy and 6.32 mGy, i.e. −3.6% and 0.3% different from the nominal values for the low‐dose and high‐dose presets, respectively.

Conclusions

The LGK Icon was successfully commissioned for clinical use. The use of the EBT3 to characterize the treatment unit was demonstrated to be feasible. The CBCT imaging system operates well within the manufacturer's specifications and provides good geometrical accuracy.
Dihedral angle study in Hesperidin using NMR Spectroscopy
Authors: Jadeja Yashwantsinh S. , Kapadiya Khushal M. , Jebaliya Hetal J. , Shah Anamik K. , Khunt Ranjan C.
Published: December 2016

Hesperidin is flavonoid molecule found in citrus fruits (Citrus reticulata), especially difficult to extract, classify and characterize. Present work is to study the unresolved relative configuration of Hesperidin through the dihedral angle, coupling constant and different NMR techniques. The Karplus equation and its modifications have been originated from the valence bond theory and associated with dihedral angle and coupling constant. The result data set of calculated dihedral angle can probe significant method to assign the virtual configuration of natural products and also resolved stereochemistry of Hesperidin at C‐2 position in. Copyright © 2016 John Wiley & Sons, Ltd.
White Paper on Natural Products
Authors: Gabay Michael , Smith Judith A. , Chavez Mary L. , Goldwire Micheline , Walker Scot , Coon Scott A. , Gosser Rena , Hume Anne L. , Musselman Megan , Phillips Jennifer , Abe Andrew M.
Published: December 2016

The American College of Clinical Pharmacy (ACCP) published an initial white paper on herbal products in 2000. Since then, the global market for natural products has continued to expand, with tens of millions of consumers using such products on an annual basis in the United States alone. However, despite this expansion, natural products remain largely unregulated compared with prescription medications, have moderate‐ to low‐level clinical evidence for efficacy, and continue to have safety concerns, including adulteration and misbranding. As comprehensive medication management experts, clinical pharmacists are uniquely qualified to navigate these concerns and advise patients appropriately. To develop and recommend a suitable care plan involving natural products, clinical pharmacists must establish a strong pharmacist‐patient relationship, assess the appropriateness of therapy, educate the patient regarding key issues, and continuously monitor and follow up on the effectiveness of the care plan. This process should not only occur in an individual community or hospital setting, but also whenever a patient transitions from one care setting to another in cooperation with other clinicians.
A systematic review of dyadic studies examining relationship quality in couples facing colorectal cancer together
Authors: Kayser Karen , Acquati Chiara , Reese Jennifer Barsky , Mark Kristen , Wittmann Daniela , Karam Eli
Published: December 2016

Background

Despite the adverse effects that treatment for colorectal cancer can have on patients' quality of life and, in particular, their intimate relationships, very little research has been conducted on the psychosocial adjustment for both patients and their partners/spouses.

Objectives

The aim of this systematic review was to examine dyadic studies of adjustment in couples in which one partner has been diagnosed with colorectal cancer.

Methods

Pub Med, PsychINFO, MEDLINE, Social Sciences Abstracts (EBSCO), and the Cochrane Library were systematically searched for studies reporting quality of life outcomes for colorectal cancer patients and their partners/spouses. Only studies that included dyads in the sample were eligible for inclusion. The Quality Assessment Tool for Quantitative Studies was used to evaluate each study.

Results

A total of 277 studies were identified, of which 9 studies met the inclusion criteria (N = 388 couples). The methodological quality of the studies was high in that they used standardized instruments validated with their samples, conducted dyadic data analyses (when appropriate), and used longitudinal designs. A synthesis of the studies revealed that (1) relationship factors (eg, support, communication, dyadic coping, and relationship satisfaction) affect adjustment to cancer; (2) cancer‐related distress impacts each partner's adjustment or the relationship; and (3) gender, role (patient/caregiver), and clinical characteristics (treatment, mental health) can mediate adjustment to cancer.

Conclusion

The quality of the relationship can influence patients' and their partners' adjustment to colorectal cancer. Psychosocial interventions that address relationship issues may be beneficial to couples facing the challenges of colorectal cancer.
Balancing give and take between patients and their spousal caregivers in hematopoietic stem cell transplantation
Authors: Beattie Sara , Lebel Sophie , Petricone‐Westwood Danielle , Wilson Keith G. , Harris Cheryl , Devins Gerald , Huebsch Lothar , Tay Jason
Published: December 2016

Objective

Hematopoietic stem cell transplantation (HSCT) is a demanding treatment. Spouses of HSCT patients assume caregiving responsibilities that can induce feelings of burden and disrupt relationship equity. On the basis of equity theory, we propose a conceptual framework examining the individual and dyadic experience of HSCT patients and their caregivers. The model includes feelings of inequity, patient self‐perceived burden, caregiver burden, and distress.

Methods

The HSCT patients and their spousal caregivers were recruited prior to HSCT between March 2011 and September 2012. Each member of the dyad self‐administered a questionnaire package.

Results

Seventy‐two dyads were included in the path analyses. Our model demonstrated an inadequate statistical fit; however, with one modification, an adequate to good fit was obtained: χ2(df) = 6.01(5), normed χ2 = 1.20, standardized root mean square residual = 0.048, comparative fit index = 0.99, Tucker‐Lewis index = 0.96, and root‐mean‐square error of approximation = 0.05 (90% CI, 0.00‐0.18). As hypothesized, pre‐HSCT caregiver burden mediates the relationship between caregiver underbenefit and caregiver distress. However, patient self‐perceived burden was not associated with patient distress; rather, patient perception of overbenefit was related to patient distress. In our modified model, the results demonstrate that patient overbenefit influenced caregiver burden; however, there was not a reciprocal influence, because caregiver variables did not affect patient variables.

Conclusions

Our proposed theoretical framework describes patients' and caregivers' individual experience of distress before HSCT but does not as clearly encompass the dyadic experience. Addressing perceived imbalances and providing psycho‐education on role changes within HSCT dyads before transplantation may be a useful prehabilitation strategy for preventing distress.
Trajectories of quality of life, life satisfaction, and psychological adjustment after prostate cancer
Authors: Chambers Suzanne K. , Ng Shu Kay , Baade Peter , Aitken Joanne F. , Hyde Melissa K. , Wittert Gary , Frydenberg Mark , Dunn Jeff
Published: December 2016

Background

To describe trajectories of health‐related quality of life (QoL), life satisfaction, and psychological adjustment for men with prostate cancer over the medium to long term and identify predictors of poorer outcomes using growth mixture models.

Methods

One‐thousand sixty‐four (82.4% response) men diagnosed with prostate cancer were recruited close to diagnosis and assessed over a 72‐month (6‐year) period with self‐report assessment of health‐related QoL, life satisfaction, cancer‐related distress, and prostate specific antigen anxiety. Urinary, bowel, and sexual function were also assessed using validated questionnaires.

Results

Poorer physical QOL was predicted by older age, lower education, lower income, comorbidities, and receiving hormone therapy. Lower life satisfaction was related to younger age, lower income, not being partnered, and comorbidities. Poorer psychological trajectories were predicted by younger age, lower income, comorbidities, and receiving radical prostatectomy or brachytherapy. Better urinary, bowel, and sexual function were related to better global outcomes over time. Anxiety about prostate specific antigen testing was rare.

Conclusions

Distinct trajectories exist for medium‐ to long‐term QoL, life satisfaction, and psychological adjustment after prostate cancer; with age and socioeconomic deprivation playing a differential role in men's survivorship profile and the impact of functional status on outcomes increasing over time. These results reinforce the need for an appraisal of men's life course in addition to treatment side effects when planning survivorship care after cancer.
Posttraumatic growth in breast cancer survivors and their husbands based on the actor‐partner interdependence model
Authors: Lee MyoSuk , Kim Kyunghee , Lim Changwon , Kim Ji‐Su
Published: December 2016

Objective

This study aimed to verify actor and partner effects, by examining the effects of self‐esteem, relationship quality, and subjective distress on posttraumatic growth in breast cancer survivors and their spouses, and involved a structural analysis of descriptive cause‐and‐effect relationships to verify the suitability of the actor‐partner interdependence model.

Methods

A structured questionnaire was used to collect data from breast cancer survivors and their spouses at outpatient centers, wards, and patient meetings in 4 general hospitals in Seoul between April 13 and September 20, 2015. Data for 336 individuals (168 couples) were analyzed. The suitability of the hypothetical model was assessed via SPSS Win 21.0 and AMOS 21.0. Actor and partner effects on posttraumatic growth in breast cancer survivors and their spouses were examined.

Results

Self‐esteem, relationship quality, and subjective distress exerted significant actor effects, and subjective distress exerted a significant partner effect on posttraumatic growth in breast cancer survivors. Relationship quality and support exerted significant actor effects, and self‐esteem, relationship quality, and subjective distress exerted significant partner effects on posttraumatic growth in spouses.

Conclusions

Posttraumatic growth in breast cancer survivors was influenced by not only relationship quality and spouses' self‐ esteem but also subjective distress; therefore, solidarity between breast cancer survivors and their spouses was important and should be maintained to provide healthy relationship support and enhance posttraumatic growth. Further, health care providers should include spouses in health‐related education and involve them in interventions and family support programs for couples.
A comparison of attitudes toward length and quality of life between community‐dwelling older adults and patients with advanced cancer
Authors: Malhotra Chetna , Xiang Ling , Ozdemir Semra , Kanesvaran Ravindran , Chan Noreen , Finkelstein Eric Andrew
Published: December 2016

Objective

Applying prospect theory to end‐of‐life decision making, we hypothesize that community‐dwelling older adults (CDOAs) will be relatively less inclined towards extending length over improving quality of life compared with patients. We also hypothesize that differences in relative inclination for length over quality of life between the 2 groups will decrease with advancing age.

Methods

We tested these hypotheses by administering the quality‐quantity questionnaire to 1067 CDOAs and 320 stage IV cancer patients and applying a linear regression model to assess whether relative inclination for length over quality of life, as estimated by the questionnaire, differed between CDOAs and patients after controlling for differences in sociodemographic characteristics. We also assessed the effect of interaction between age and participant status (CDOA compared to patient) on relative inclination for length over quality of life.

Results

Consistent with prospect theory, a lower proportion of CDOAs (26%) than patients (42%) were relatively more inclined towards length over quality of life. Results were significant even after adjusting for differences in sociodemographics (P < .01). With increasing age, the difference in relative inclination between CDOAs and patients increased (P = .01).

Conclusions

Findings indicate that attitudes towards length and quality of life differ by life stage. This has implications for end‐of‐life care decisions made by CDOAs, such as purchasing health or disability insurance and signing advance directives or care plans.
Cross‐resistance to three phenylpyrazole insecticides and A2′N mutation detection of GABA receptor subunit in fipronil‐resistant Laodelphax striatellus (Hemiptera: Delphacidae)
Authors: Wei Qi , Mu Xi‐Chao , Wu Shun‐Fan , Wang Li‐Xiang , Gao Cong‐Fen
Published: December 2016

BACKGROUND

Laodelphax striatellus (Fallén) is an important pest of crops in East Asia. Over the past decade, phenylpyrazole insecticides, which target the insect GABA receptor, have increasingly been used as alternatives against rice planthoppers.

RESULTS

Cross‐resistance to ethiprole and butene‐fipronil was detected in a laboratory‐selected fipronil‐resistant strain of L. striatellus (LsFR). Compared with a fipronil‐susceptible strain (LsFS), LsFR had obtained a high‐level resistance to fipronil (112.1‐fold) and moderate resistance to ethiprole (24.5‐fold) and butene‐fipronil (14.7‐fold). For the resistance of field populations, LC50 values of ethiprole were remarkably higher than the other two analogues in Gaochun and Yancheng populations in 2016. Significant correlations were demonstrated between the LC50 values of three phenylpyrazole insecticides (R = 0.944‐0.998, P = 0.007–0.016). Additionally, an AS‐PCR assay was developed to detect the A2′N mutant GABA receptor in L. striatellus strains or populations. It was noteworthy that mutation frequencies of 19.2 and 3.6% appeared in Lujiang and Gaochun populations in 2016, respectively. Furthermore, there was an extremely significant difference in genomic expression of Lsrdl between the LsFS and LsFR individuals (1.85‐fold, F = 26.8, P = 0.0008).

CONCLUSIONS

This study could help us better understand the cross‐resistance mechanisms in L. striatellus, and be beneficial for proposing effective pest management strategies of phenylpyrazole resistance. © 2016 Society of Chemical Industry
Characterization of Contributing Factors to Variability in Morphine Clearance Through PBPK Modeling Implemented With OCT1 Transporter
Authors: Emoto C , Fukuda T , Johnson TN , Neuhoff S , Sadhasivam S , Vinks AA
Published: December 2016

Morphine shows large interindividual variability in its pharmacokinetics; however, the cause of this has not been fully addressed. The variability in morphine disposition is considered to be due to a combination of pharmacogenetic and physiological determinants related to morphine disposition. We previously reported the effect of organic cation transporter (OCT1) genotype on morphine disposition in pediatric patients. To further explore the underlying mechanisms for variability arising from relevant determinants, including OCT1, a physiologically based pharmacokinetic (PBPK) model of morphine was developed. The PBPK model predicted morphine concentration‐time profiles well, in both adults and children. Almost all of the observed morphine clearances in pediatric patients fell within a twofold range of median predicted values for each OCT1 genotype in each age group. This PBPK modeling approach quantitatively demonstrates that OCT1 genotype, age‐related growth, and changes in blood flow as important contributors to morphine pharmacokinetic (PK) variability.
Toward more efficient density‐based adaptive QM/MM methods
Authors: Zheng Min , Kuriappan Jissy A. , Waller Mark P.
Published: December 2016

Adaptive QM/MM (quantum mechanical/molecular mechanical) methods repartition molecules on‐the‐fly into the QM and MM regions based on a partitioning criterion. A density‐based partitioning scheme offers a unique way of carrying out QM and MM assignments on the presence/absence of (non) covalent interactions between non‐QM core molecules and the QM core. Here, we present two improvements to promote our density‐based adaptive partitioning strategy for adaptive QM/MM calculations. First, bond formation/breaking processes between non‐QM core molecules and the QM core are monitored using a density‐based descriptor, to define an adaptive QM core region on the fly. Second, the density‐based adaptive QM/MM partitioning scheme is made efficient enough for large systems by utilizating an adaptive search region and a Voronoi style‐partitioning scheme. The adaptive search region is used to preselect the subset of molecules that may interact strongly enough with the QM core region, and then a density‐based interaction calculation is only carried out on this subset. A Voronoi style‐partitioning scheme achieves an efficient assignment of the density‐based interactions.