bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal pacing of outcomes for improving patient flow: Design science research in a National Health Service hospital
Authors: Johnson Mark , Burgess Nicola , Sethi Simon 
Published: December 2019

AbstractImproving patient flow in hospitals is a contemporary challenge in the UK National Health Service (NHS). When patients remain in a hospital bed for longer than clinically necessary, hospital performance is dramatically impacted, quality of care is reduced, and elective surgeries are cancelled at great cost to both hospital and patient. This research explains how one UK hospital employed design science research to improve patient flow after other process improvement techniques had failed. The work focused on improving patient flow through the creation of a set of interconnected, temporally paced routines that successfully engaged doctors and nurses in new, outcome‐specific ways of working. These routines were both independent and interdependent, were relationally coordinated through time, and systematically and unambiguously engaged all levels of staff at specific temporal junctures. We discover that the successful adoption of these routines was cumulative rather than iterative and was aligned with ongoing efforts supporting the social aspects of change. Through this work, our case hospital saw performance improvements that moved them from being below average to the best in the country, combining improvements in patient care with savings of over £3 million in the first 12 months. The contribution of this research is twofold; first, we explain how the development of outcome‐specific routines can facilitate process improvement, and second, we illustrate how design science research can successfully bridge theory and practice to promote swift and even flow in healthcare.
Predictive validity of radiographic signs of complete discoid lateral meniscus in children using machine learning techniques
Authors: Ha Chul‐Won , Kim Seong Hwan , Lee Dong‐Hoon , Kim Hyojoon , Park Yong‐Beom 
Published: December 2019

AbstractThe diagnostic utility of radiographic signs of complete discoid lateral meniscus remains controversial. This study aimed to investigate the diagnostic accuracy and determine which sign is most reliably detects the presence of a complete discoid lateral meniscus in children. A total of 141 knees (age 7‐16) with complete discoid lateral meniscus and 141 age‐ and sex‐matched knees with normal meniscus were included. The following radiographic signs were evaluated: lateral joint (LJ) space, fibular head (FH) height, lateral tibial spine (LTS) height, lateral tibial plateau (LTP) obliquity, lateral femoral condyle (LFC) squaring, LTP cupping, LFC notching, and prominence ratio of the femoral condyle. Prediction models were constructed using logistic regressions, decision trees, and random forest analyses. Receiver operating characteristic curves and area under the curve (AUC) were estimated to compare the diagnostic accuracy of the radiographic signs and model fit. The random forest model yielded the best diagnostic accuracy (AUC: 0.909), with 86.5% sensitivity and 82.2% specificity. LJ space height, FH height, and prominence ratio showed statistically large AUC compared with LTS height and LTP obliquity (P < .05 in all). The cut‐off values for diagnosing discoid meniscus to be <12.55 mm for FH height, <0.804 for prominence ratio, and >6.6 mm for LJ space height when using the random forest model. On the basis of the results of this study, in clinical practice, LJ space height, FH height and prominence ratio could be easily used as supplementary tools for complete discoid lateral meniscus in children.
SOX2 upregulates side population cells and enhances their chemoresistant ability by transactivating ABCC1 expression contributing to intrinsic resistance to paclitaxel in melanoma
Authors: Si Xiaoqiang , Gao Zhengjun , Xu Feihua , Zheng Yawen 
Published: December 2019

AbstractPaclitaxel is the last choice for the treatment of advanced melanoma as a second‐line chemotherapeutic agent, but there are still many cases of intrinsic resistance to paclitaxel in melanoma and the reasons that cause paclitaxel resistance remain unclear. Here, we identified that high expression of SRY‐box transcription factor 2 (SOX2) and high ratio of side population (SP) cells reduced the sensitivity to paclitaxel in melanoma cells. The knockout and the induction of SOX2 completely depleted and significantly upregulated the ratios of melanoma SP cells, respectively. These data suggest that SOX2, a pluripotent transcription factor for inducing cancer stem cells in melanoma, is also sufficient and necessary for the induction of melanoma SP cells. ATP‐binding cassette (ABC) subfamily C member 1 (ABCC1) is one of ABC transporters which causes SP cells to be resistance to chemotherapeutic agents by efficiently pumping drugs out of cells. The knockout and the induction of ABCC1 significantly increased and decreased the sensitivity of melanoma cells to paclitaxel. High expression of ABCC1 was identified in melanoma cell lines with high expression of SOX2 and in their SP cells. SOX2 was identified to induce ABCC1 transcription. Taken together, SOX2 upregulates SP cells and enhances their chemoresistant ability by increasing ABCC1 expression, which contributes to intrinsic resistance to paclitaxel in melanoma. Our findings will lead to new insights into melanoma biology and therapy resistance, and eventually to new therapeutic targets.
Noonan syndrome‐associated biallelic LZTR1 mutations cause cardiac hypertrophy and vascular malformations in zebrafish
Authors: Nakagama Yu , Takeda Norihiko , Ogawa Seishi , Takeda Hiroyuki , Furutani Yoshiyuki , Nakanishi Toshio , Sato Tatsuyuki , Hirata Yoichiro , Oka Akira , Inuzuka Ryo 
Published: December 2019

AbstractBackgroundVariants in the LZTR1 (leucine‐zipper‐like transcription regulator 1) gene (OMIM #600574) have been reported in recessive Noonan syndrome patients. In vivo evidence from animal models to support its causative role is lacking.MethodsBy CRISPR‐Cas9 genome editing, we generated lztr1‐mutated zebrafish (Danio rerio). Analyses of histopathology and downstream signaling were performed to investigate the pathogenesis of cardiac and extracardiac abnormalities in Noonan syndrome.ResultsA frameshift deletion allele was created in the zebrafish lztr1. Crosses of heterozygotes obtained homozygous lztr1 null mutants that modeled LZTR1 loss‐of‐function. Histological analyses of the model revealed ventricular hypertrophy, the deleterious signature of Noonan syndrome‐associated cardiomyopathy. Further, assessment for extracardiac abnormalities documented multiple vascular malformations, resembling human vascular pathology caused by RAS/MAPK activation. Due to spatiotemporal regulation of LZTR1, its downstream function was not fully elucidated from western blots of adult tissue.ConclusionOur novel zebrafish model phenocopied human recessive Noonan syndrome and supported the loss‐of‐function mechanism of disease‐causing LZTR1 variants. The discovery of vascular malformations in mutants calls for the clinical follow‐up of patients to monitor for its emergence. The model will serve as a novel platform for investigating the pathophysiology linking RAS/MAPK signaling to cardiac and vascular pathology.
Spline curve deformation model with prior shapes for identifying adhesion boundaries between large lung tumors and tissues around lungs in CT images
Authors: Zhang Xin , Wang Jie , Yang Ying , Wang Bing , Gu Lixu 
Published: December 2019

PurposeAutomated segmentation of lung tumors attached to anatomic structures such as the chest wall or mediastinum remains a technical challenge because of the similar Hounsfield units of these structures. To address this challenge, we propose herein a spline curve deformation model that combines prior shapes to correct large spatially contiguous errors (LSCEs) in input shapes derived from image‐appearance cues.The model is then used to identify the adhesion boundaries between large lung tumors and tissue around the lungs.MethodsThe deformation of the whole curve is driven by the transformation of the control points (CPs) of the spline curve, which are influenced by external and internal forces. The external force drives the model to fit the positions of the non‐LSCEs of the input shapes while the internal force ensures the local similarity of the displacements of the neighboring CPs. The proposed model corrects the gross errors in the lung input shape caused by large lung tumors, where the initial lung shape for the model is inferred from the training shapes by shape group‐based sparse prior information and the input lung shape is inferred by adaptive‐thresholding‐based segmentation followed by morphological refinement.ResultsThe accuracy of the proposed model is verified by applying it to images of lungs with either moderate large‐sized (ML) tumors or giant large‐sized (GL) tumors. The quantitative results in terms of the averages of the dice similarity coefficient (DSC) and the Jaccard similarity index (SI) are 0.982 ± 0.006 and 0.965 ± 0.012 for segmentation of lungs adhered by ML tumors, and 0.952 ± 0.048 and 0.926 ± 0.059 for segmentation of lungs adhered by GL tumors, which give 0.943 ± 0.021 and 0.897 ± 0.041 for segmentation of the ML tumors, and 0.907 ± 0.057 and 0.888 ± 0.091 for segmentation of the GL tumors, respectively. In addition, the bidirectional Hausdorff distances are 5.7 ± 1.4 and 11.3 ± 2.5 mm for segmentation of lungs with ML and GL tumors, respectively.ConclusionsWhen combined with prior shapes, the proposed spline curve deformation can deal with large spatially consecutive errors in object shapes obtained from image‐appearance information. We verified this method by applying it to the segmentation of lungs with large tumors adhered to the tissue around the lungs and the large tumors. Both the qualitative and quantitative results are more accurate and repeatable than results obtained with current state‐of‐the‐art techniques.
High spatial resolution inorganic scintillator detector for high‐energy X‐ray beam at small field irradiation
Authors: Debnath Sree Bash Chandra , Fauquet Carole , Tallet Agnes , Goncalves Anthony , Lavandier Sébastien , Jandard Franck , Tonneau Didier , Darreon Julien 
Published: December 2019

PurposeSmall field dosimetry for radiotherapy is one of the major challenges due to the size of most dosimeters, for example, sufficient spatial resolution, accurate dose distribution and energy dependency of the detector. In this context, the purpose of this research is to develop a small size scintillating detector targeting small field dosimetry and compare its performance with other commercial detectors.MethodAn inorganic scintillator detector (ISD) of about 200 µm outer diameter was developed and tested through different small field dosimetric characterizations under high‐energy photons (6 and 15 MV) delivered by an Elekta Linear Accelerator (LINAC). Percentage depth dose (PDD) and beam profile measurements were compared using dosimeters from PTW namely, microdiamond and PinPoint three‐dimensional (PP3D) detector. A background fiber method has been considered to quantitate and eliminate the minimal Cerenkov effect from the total optical signal magnitude. Measurements were performed inside a water phantom under IAEA Technical Reports Series recommendations (IAEA TRS 381 and TRS 483).ResultsSmall fields ranging from 3 × 3 cm2, down to 0.5 × 0.5 cm2 were sequentially measured using the ISD and commercial dosimeters, and a good agreement was obtained among all measurements. The result also shows that, scintillating detector has good repeatability and reproducibility of the output signal with maximum deviation of 0.26% and 0.5% respectively. The Full Width Half Maximum (FWHM) was measured 0.55 cm for the smallest available square size field of 0.5 × 0.5 cm2, where the discrepancy of 0.05 cm is due to the scattering effects inside the water and convolution effect between field and detector geometries. Percentage depth dose factor dependence variation with water depth exhibits nearly the same behavior for all tested detectors. The ISD allows to perform dose measurements at a very high accuracy from low (50 cGy/min) to high dose rates (800 cGy/min) and was found to be independent of dose rate variation. The detection system also showed an excellent linearity with dose; hence, calibration was easily achieved.ConclusionsThe developed detector can be used to accurately measure the delivered dose at small fields during the treatment of small volume tumors. The author's measurement shows that despite using a nonwater‐equivalent detector, the detector can be a powerful candidate for beam characterization and quality assurance in, for example, radiosurgery, Intensity‐Modulated Radiotherapy (IMRT), and brachytherapy. Our detector can provide real‐time dose measurement and good spatial resolution with immediate readout, simplicity, flexibility, and robustness.
A deep learning method for producing ventilation images from 4DCT: First comparison with technegas SPECT ventilation
Authors: Liu Zhiqiang , Miao Junjie , Huang Peng , Wang Wenqing , Wang Xin , Zhai Yirui , Wang Jingbo , Zhou Zongmei , Bi Nan , Tian Yuan , Dai Jianrong 
Published: December 2019

PurposeThe purpose of this study is to develop a deep learning (DL) method for producing four‐dimensional computed tomography (4DCT) ventilation imaging and to evaluate the accuracy of the DL‐based ventilation imaging against single‐photon emission‐computed tomography (SPECT) ventilation imaging (SPECT‐VI). The performance of the DL‐based method is assessed by comparing with density change‐ and Jacobian‐based (HU and JAC) methods.Materials and methodsFifty patients with esophagus or lung cancer who underwent thoracic radiotherapy were enrolled in this study. For each patient, 4DCT scans paired with 99mTc‐Technegas SPECT/CT were acquired before the first radiotherapy treatment. 4DCT and SPECT/CT were first rigidly registered using MIMvista and converted to data matrix using MATLAB, and then transferred to a DL model based on U‐net for correlating 4DCT features and SPECT‐VI. Two forms of 4DCT dataset [(a) ten phases and (b) two phases of peak‐exhalation and peak‐inhalation] as input are studied. Tenfold cross‐validation procedure was used to evaluate the performance of the DL model. For comparative evaluation, HU and JAC methodologies are used to calculate specific ventilation imaging based on 4DCT (CTVI) for each patient. The voxel‐wise Spearman’s correlation was evaluated over the whole lung between each of CTVI and corresponding SPECT‐VI. The SPECT‐VI and produced CTVIs were segmented into high, median, and low functional lung (HFL, MFL, and LFL) regions. The spatial overlap of corresponding HFL, MFL, and LFL for each CTVI against SPECT‐VI was also evaluated using the dice similarity coefficient (DSC). The averaged DSC of functional lung regions was calculated and statistically analyzed with a one‐factor ANONA model among different methods.ResultsThe voxel‐wise Spearman rs values were (0.22 ± 0.31), (−0.09 ± 0.18), and (0.73 ± 0.16)/(0.71 ± 0.17) for the CTVIHU, CTVIJAC, and CTVIDL(1)/CTVIDL(2). These results showed the DL method yielded the strongest correlation with SPECT‐VI. Using the DSC as the spatial overlap metric, we found that the CTVIHU, CTVIJAC, and CTVIDL(1)/CTVIDL(2) methods achieved averaged DSC values for all patients to be (0.45 ± 0.08), (0.33 ± 0.04), and (0.73 ± 0.09)/(0.71 ± 0.09), respectively. The results demonstrated that the DL method yielded the highest similarity with SPECT‐VI with the prominently significant difference (P < 10−7).ConclusionsThis study developed a DL method for producing CTVI and performed a validation against SPECT‐VI. The results demonstrated that DL method can derive CTVI with greatly improved accuracy in comparison to HU and JAC methods. The produced ventilation images can be more accurate and useful for lung functional avoidance radiotherapy and treatment response modeling.
Elucidating heteroatom influence on homonuclear 4J(H,H) coupling constants by DFT/NMR approach
Authors: Chini Maria Giovanna , Urbani Daniele , Dambruoso Paolo , Riccio Raffaele , Bifulco Giuseppe 
Published: December 2019

AbstractWe report the structural dependency of long range scalar J‐coupling constant across four bonds as function of the dihedral angles Φ1 and Φ3. The calculated homonuclear coupling constants 4J(H,H), obtained at a density functional theory level, were measured between C(1)─X(2) and X(2)─C(3) bonds in three‐term models, where C, N, O, and S were systematically used as the second atom of the alkyl structures (1‐4).The 4J(H,H) calculated values, tabulated for variation of 30° for both Φ1 and Φ3, have disclosed an unexpected detectable coupling constant (4J(H,H) ≥ 1 Hz) across heteroatoms, useful to provide valuable structural information. A 2‐methyl‐1,3‐dithiane sulfide (5) was used as a case study to prove the applicability and reliability of the calculated values to real issues. The 4J(H,H) values obtained at density functional theory for the system 4 have reproduced with good accuracy an unexpected experimental 4J(H2ax‐H4ax) = 1.01 Hz of sulfide molecule (5), suggesting these calculated coupling constant values as a new powerful tool for the organic synthesis and stereochemical analysis.
Solvent optimization and conformational flexibility effects on 1H and 13C NMR scaling factors
Authors: Merrill Amy T. , Tantillo Dean J. 
Published: December 2019

AbstractThe effects of including (a) implicit solvent in geometry optimizations, (b) conformationally flexible molecules in test sets, and (c) empirical dispersion D3(BJ) on scaling factors for predicting 1H and 13C NMR chemical shifts were explored. Scaling factors with optimizations performed in the gas phase and with a Polarizable Continuum Model (PCM) solvent model were obtained for 12 organic solvents, including 2,2,2‐trifluroethanol and chlorobenzene, for which scaling factors have been developed for the first time. Scaling factors for aromatic solvents were split into primary and secondary scaling factors to account for CH–π effects. Including empirical dispersion D3(BJ) did not lead to significant improvement.
Thermo‐acoustic ultrasound for noninvasive temperature monitoring at lead tips during MRI
Authors: Dixit Neerav , Pauly John M. , Scott Greig C. 
Published: December 2019

PurposeWe explore the use of thermo‐acoustic ultrasound (TAUS) to monitor temperature at the tips of conductive device leads during MRI.TheoryIn TAUS, rapid radiofrequency (RF) power deposition excites an acoustic signal via thermoelastic expansion. Coupling of the MRI RF transmit to device leads causes SAR amplification at lead tips, allowing MRI RF transmitters to excite significant lead tip TAUS signals. Because the amplitude of the TAUS signal depends on temperature, it becomes feasible to monitor the lead tip temperature during MRI by tracking the TAUS amplitude.MethodsThe TAUS temperature dependence was characterized in a phantom and in tissue. To perform TAUS acquisitions in an MRI scanner, amplitude modulated RF chirps were transmitted by the body coil, and the lead tip TAUS signal was detected by an ultrasonic transducer. The TAUS signal level was correlated with the RF current induced on the lead and the associated artifacts in MRI. TAUS signals acquired during RF‐induced heating were used to estimate the lead tip temperature.ResultsThe TAUS signal exhibited strong dependence on temperature, increasing over 30% with C of heating both in the phantom and in tissue. A lead tip TAUS signal was observed for a 100 mA rms current induced on a lead. During RF‐induced heating, the TAUS signal appeared to accurately approximate the peak lead tip temperature.ConclusionsTAUS allows for noninvasive monitoring of lead tip temperature in an MRI environment. With further development, TAUS opens new avenues to improve RF device safety during MRI scans.
Spin‐lock imaging of intrinsic susceptibility gradients in tumors
Authors: Zu Zhongliang , Janve Vaibhav , Gore John C. 
Published: December 2019

PurposePrevious studies have shown that diffusion of water through intrinsic susceptibility gradients produces a dispersion of the spin‐lattice relaxation rate in the rotating frame (R1ρ) over a low range of spin‐locking amplitudes (0 < ω1 < 100 Hz), whereas at higher ω1 and high magnetic fields, a second dispersion arises due to chemical exchange. Here, we separated these different effects and evaluated their contributions in tumors.MethodsMaps of R1ρ and its changes with locking field were acquired on intracranial 9‐L tumor models. The R1ρ changes due to diffusion () were calculated by subtracting maps of R1ρ at 100 Hz (R1ρ[100 Hz]) from those at 0 Hz (R1ρ[0 Hz]). The R1ρ changes due to exchange () were calculated by subtracting maps of R1ρ at 5620 Hz (R1ρ[5620 Hz]) from those of R1ρ at 100 Hz (R1ρ[100 Hz]). Measurements of vascular dimensions and spacing were performed ex vivo using 3D confocal microscopy.ResultsThe R1ρ changes at low ω1 in tumors (5.24 ± 1.78 s−1) are substantially (p = 3.76) greater than those in normal tissues (1.36 ± 0.70 s−1), which we suggest are due to greater contributions from diffusion through susceptibility gradients. Tumor vessels were larger and spaced less closely compared with normal brain, which may be 1 factor contributing the susceptibility within 9‐L tumors. The contrast between tumor and normal tissues for is larger than for and for the apparent R2w.ConclusionImages that are sensitive to the variations of spin‐lock relaxation rates at low ω1 provide a novel form of contrast that reflects the heterogeneous nature of intrinsic variations within tumors.
Interleukin‐6 secretion by fibroblasts in carpal tunnel syndrome patients is associated with trigger finger and inhibited by tranilast
Authors: Kawamoto Hiroya , Iwatsuki Katsuyuki , Kurimoto Shigeru , Yamamoto Michiro , Tatebe Masahiro , Morita Akimasa , Kinoshita Fumie , Hirata Hitoshi 
Published: December 2019

AbstractIntroductionIn this study we aimed to clarify the association between interleukin‐6 (IL‐6) secretion in fibroblasts in carpal tunnel syndrome (CTS) patients and their biophysical parameters, including association with trigger finger and whether tranilast inhibits IL‐6 secretion in fibroblasts.MethodsFibroblasts were obtained from tenosynovial tissue harvested from idiopathic CTS patients undergoing carpal tunnel release and tenosynovectomy and cultured in media containing tranilast with or without tumor necrosis‐α (TNF‐α) or interleukin‐1β (IL‐1β). Their proliferation was evaluated and secreted IL‐6 levels and IL‐6 mRNA expression were quantified. Correlations between IL‐6 concentration and patient characteristics were examined.ResultsIL‐6 secretion was significantly associated with trigger finger (P = .001). Tranilast inhibited fibroblast proliferation in a dose‐dependent manner and suppressed IL‐6 secretion.DiscussionIL‐6 overproduction in tenosynovial tissue may account for the association between CTS and trigger finger. Future studies should investigate whether tranilast can be used to treat patients with CTS.