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Background: This study aims to explore the role of four-dimensional (4D) transperineal ultrasound (TPUS) in the contouring of prostate gland with planning computed tomography (CT) images, in the absence of magnetic resonance imaging (MRI)., Materials and Methods: Five radiation oncologists (ROs) performed two rounds of prostate gland contouring (single-blinded) on CT-alone and CT/TPUS datasets obtained from 10 patients who underwent TPUS-guided external beam radiotherapy. Parameters include prostate volume, DICE similarity coefficient (DSC) and centroid position. Wilcoxon signed-rank test assessed the significance of inter-modality differences, and the intraclass correlation coefficient (ICC ) reflected inter- and intra-observer reliability of parameters., Results: Inter-modality analysis revealed high agreement (based on DSC and centroid position) of prostate gland contours between CT-alone and CT/TPUS. Statistical significant difference was observed in the superior-inferior direction of the prostate centroid position (p = 0.011). All modalities yielded excellent inter-observer reliability of delineated prostate volume with ICC > 0.9, mean DSC > 0.8 and centroid position: CT-alone (ICC = 1.000) and CT/TPUS (ICC = 0.999) left-right (L/R); CT-alone (ICC = 0.999) and CT/TPUS (ICC = 0.998) anterior-posterior (A/P); CT-alone (ICC = 0.999) and CT/TPUS (ICC = 1.000) superior-inferior (S/I). Similarly, all modalities yielded excellent intra-observer reliability of delineated prostate volume, ICC > 0.9 and mean DSC > 0.8. Lastly, intra-observer reliability was excellent on both imaging modalities for the prostate centroid position, ICC > 0.9., Conclusion: TPUS does not add significantly to the amount of anatomical information provided by CT images. However, TPUS can supplement planning CT to achieve a higher positional accuracy in the S/I direction if access to CT/MRI fusion is limited., Competing Interests: Conflict of interest The authors do not have any conflict of interest to declare., (© 2022 Greater Poland Cancer Centre.)

Inter-fraction organ variations cause deviations between planned and delivered doses in patients receiving radiotherapy for prostate cancer. This study compared planned (D P ) vs accumulated doses (D A ) obtained from daily cone-beam computed tomography (CBCT) scans in high-risk- prostate cancer with pelvic lymph nodes irradiation. An intensity-based deformable image registration algorithm used to estimate contours for D A was validated using geometrical agreement between radiation oncologist's and deformable image registration algorithm propagated contours. Spearman rank correlations (r s ) between geometric measures and changes in organ volumes were evaluated for 20 cases. Dose-volume (DV) differences between D A and D P were compared (Wilcoxon rank test, p < 0.05). A novel region-of-interest (ROI) method was developed and mean doses were analyzed. Geometrical measures for the prostate and organ-at-risk contours were within clinically acceptable criteria. Inter-group mean (± SD) CBCT volumes for the rectum were larger compared to planning CT (pCT) (51.1 ± 11.3 cm 3 vs 46.6 ± 16.1 cm 3 ), and were moderately correlated with variations in pCT volumes, rs = 0.663, p < 0.01. Mean rectum DV for D A was higher at V30-40 Gy and lower at V70-75 Gy, p < 0.05. Mean bladder CBCT volumes were smaller compared to pCT (198.8 ± 55 cm 3 vs 211.5 ± 89.1 cm 3 ), and was moderately correlated with pCT volumes, rs = 0.789, p < 0.01. Bladder D A was higher at V30-65 Gy and lower at V70-75 Gy (p < 0.05). For the ROI method, rectum and bladder D A were lower at 5 to 10 mm (p < 0.01) as compared to D P , whilst bladder D A was higher than D P at 20 to 50 mm (p < 0.01). Generated D A demonstrated significant differences in organ-at-risk doses as compared to D P . A well-constructed workflow incorporating a ROI DV-extraction method has been validated in terms of efficiency and accuracy designed for seamless integration in the clinic to guide future plan adaptation., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

In addition to genomic alterations, aberrant changes in post-transcriptional regulation can modify gene function and drive cancer development. RNA-binding proteins (RBPs) are a large class of post-transcriptional regulators that have been increasingly implicated in carcinogenesis. By integrating multi-omics data, we identify LARP1 as one of the most upregulated RBPs in colorectal cancer (CRC) and demonstrate its oncogenic properties. We perform LARP1:RNA interactome profiling and unveil a previously unexplored role for LARP1 in targeting the 3'UTR of oncogenes in CRC. Notably, we identify the proto-oncogenic transcription factor MYC as a key LARP1-regulated target. Our data show that LARP1 positively modulates MYC expression by associating with its 3'UTR. In addition, antisense oligonucleotide-mediated blocking of the interaction between LARP1 and the MYC 3'UTR reduces MYC expression and in vitro CRC growth. Furthermore, a systematic analysis of LARP1:protein interactions reveals IGF2BP3 and YBX1 as LARP1-interacting proteins that also regulate MYC expression and CRC development. Finally, we demonstrate that MYC reciprocally modulates LARP1 expression by targeting its enhancer. In summary, our data reveal a critical, previously uncharacterized role of LARP1 in promoting CRC tumorigenesis, validate its direct regulation of the proto-oncogene MYC and delineate a model of the positive feedback loop between MYC and LARP1 that promotes CRC growth and development., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: Relative biological effectiveness (RBE) uncertainties have been a concern for treatment planning in proton therapy, particularly for treatment sites that are near organs at risk (OARs). In such a clinical situation, the utilization of variable RBE models is preferred over constant RBE model of 1.1. The problem, however, lies in the exact choice of RBE model, especially when current RBE models are plagued with a host of uncertainties. This paper aims to determine the influence of RBE models on treatment planning, specifically to improve the understanding of the influence of the RBE models with regard to the passing and failing of treatment plans. This can be achieved by studying the RBE-weighted dose uncertainties across RBE models for OARs in cases where the target volume overlaps the OARs. Multi-field optimization (MFO) and single-field optimization (SFO) plans were compared in order to recommend which technique was more effective in eliminating the variations between RBE models., Methods: Fifteen brain tumor patients were selected based on their profile where their target volume overlaps with both the brain stem and the optic chiasm. In this study, 6 RBE models were analyzed to determine the RBE-weighted dose uncertainties. Both MFO and SFO planning techniques were adopted for the treatment planning of each patient. RBE-weighted dose uncertainties in the OARs are calculated assuming ( α β ) x of 3 Gy and 8 Gy. Statistical analysis was used to ascertain the differences in RBE-weighted dose uncertainties between MFO and SFO planning. Additionally, further investigation of the linear energy transfer (LET) distribution was conducted to determine the relationship between LET distribution and RBE-weighted dose uncertainties., Results: The results showed no strong indication on which planning technique would be the best for achieving treatment planning constraints. MFO and SFO showed significant differences ( P <.05) in the RBE-weighted dose uncertainties in the OAR. In both clinical target volume (CTV)-brain stem and CTV-chiasm overlap region, 10 of 15 patients showed a lower median RBE-weighted dose uncertainty in MFO planning compared with SFO planning. In the LET analysis, 8 patients (optic chiasm) and 13 patients (brain stem) showed a lower mean LET in MFO planning compared with SFO planning. It was also observed that lesser RBE-weighted dose uncertainties were present with MFO planning compared with SFO planning technique., Conclusions: Calculations of the RBE-weighted dose uncertainties based on 6 RBE models and 2 different ( α β ) x revealed that MFO planning is a better option as opposed to SFO planning for cases of overlapping brain tumor with OARs in eliminating RBE-weighted dose uncertainties. Incorporation of RBE models failed to dictate the passing or failing of a treatment plan. To eliminate RBE-weighted dose uncertainties in OARs, the MFO planning technique is recommended for brain tumor when CTV and OARs overlap., (© 2021 The Authors.)

Correlative imaging and quantification of intracellular nanoparticles with the underlying ultrastructure is crucial for understanding cell-nanoparticle interactions in biological research. However, correlative nanoscale imaging of whole cells still remains a daunting challenge. Here, we report a straightforward nanoscopic approach for whole-cell correlative imaging, by simultaneous ionoluminescence and ultrastructure mapping implemented with a highly focused beam of alpha particles. We demonstrate that fluorescent nanodiamonds exhibit fast, ultrabright and stable emission upon excitation by alpha particles. Thus, by using fluorescent nanodiamonds as imaging probes, our approach enables quantification and correlative localization of single nanodiamonds within a whole cell at sub-30 nm resolution. As an application example, we show that our approach, together with Monte Carlo simulations and radiobiological experiments, can be employed to provide unique insights into the mechanisms of nanodiamond radiosensitization at the single whole-cell level. These findings may benefit clinical studies of radio-enhancement effects by nanoparticles in charged-particle cancer therapy., (© 2021. The Author(s).)

An automated dose accumulation and contour propagation workflow using daily cone beam computed tomography (CBCTs) images for prostate cases that require pelvic lymph nodes irradiation (PLNs) was developed. This workflow was constructed using MIM® software with the intention to provide accurate dose transformations for plans with two different isocentres, whereby two sequential treatment phases were prescribed. The pre-processing steps for data extractions from treatment plans, CBCTs, determination of couch shift information and management of missing CBCTs are described. To ensure that the imported translational couch shifts were in the correct orientation and readable in MIM, phantom commissioning was performed. For dose transformation, rigid registration with corrected setup shifts and scaled fractional dose was performed for pCT to daily CBCTs, which were then deformed onto CBCT 1 . Fractional dose summation resulted in the final accumulated dose for the patient allowing differences in dosimetry between the planned and accumulated dose to be analysed. Contour propagations of the prostate, bladder and rectum were performed within the same workflow. Transformed contours were then deformed onto daily CBCTs to generate trending reports for analysis, including Dice Similarity Coefficient (DSC) and Mean Distance to Agreement (MDA). Results obtained from phantom commissioning (DSC = 0.96, MDA = 0.89 mm) and geometrical analysis of the propagated contours for twenty patients; prostate (DSC: 0.9 ± 0.0, MDA: 1.0 ± 0.3 mm), rectum (DSC: 0.8 ± 0.1, mm, MDA: 1.7 ± 0.6 mm) and bladder (DSC: 0.8 ± 0.1, MDA: 2.8 ± 1.0 mm) were within clinically accepted tolerances for both DSC (>0.8) and MDA (< 0.3 mm). The developed workflow is being performed on a larger patient cohort for predictive model building, with the goal of correlating observed toxicity with the actual accumulated dose received by the patient., (© 2020 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.)

Background: Phytophthora capsici root rot (PRR) is a disastrous disease in peppers (Capsicum spp.) caused by soilborne oomycete with typical symptoms of necrosis and constriction at the basal stem and consequent plant wilting. Most studies on the QTL mapping of P. capsici resistance suggested a consensus broad-spectrum QTL on chromosome 5 named Pc.5.1 regardless of P. capsici isolates and resistant resources. In addition, all these reports proposed NBS-ARC domain genes as candidate genes controlling resistance., Results: We screened out 10 PRR-resistant resources from 160 Capsicum germplasm and inspected the response of locus Pc.5.1 and NBS-ARC genes during P. capsici infection by comparing the root transcriptomes of resistant pepper 305R and susceptible pepper 372S. To dissect the structure of Pc.5.1, we anchored genetic markers onto pepper genomic sequence and made an extended Pc5.1 (Ext-Pc5.1) located at 8.35 Mb-38.13 Mb on chromosome 5 which covered all Pc5.1 reported in publications. A total of 571 NBS-ARC genes were mined from the genome of pepper CM334 and 34 genes were significantly affected by P. capsici infection in either 305R or 372S. Only 5 inducible NBS-ARC genes had LRR domains and none of them was positioned at Ext-Pc5.1. Ext-Pc5.1 did show strong response to P. capsici infection and there were a total of 44 differentially expressed genes (DEGs), but no candidate genes proposed by previous publications was included. Snakin-1 (SN1), a well-known antimicrobial peptide gene located at Pc5.1, was significantly decreased in 372S but not in 305R. Moreover, there was an impressive upregulation of sugar pathway genes in 305R, which was confirmed by metabolite analysis of roots. The biological processes of histone methylation, histone phosphorylation, DNA methylation, and nucleosome assembly were strongly activated in 305R but not in 372S, indicating an epigenetic-related defense mechanism., Conclusions: Those NBS-ARC genes that were suggested to contribute to Pc5.1 in previous publications did not show any significant response in P. capsici infection and there were no significant differences of these genes in transcription levels between 305R and 372S. Other pathogen defense-related genes like SN1 might account for Pc5.1. Our study also proposed the important role of sugar and epigenetic regulation in the defense against P. capsici.

Background: Acute decompensated heart failure (ADHF) contributes millions of emergency department (ED) visits and it is associated with high in-hospital mortality. The aim of this study was to develop and validate a multiparametric score for critically-ill ADHF patients., Methods: In this single-center, retrospective study, a total of 1268 ADHF patients in China were enrolled and divided into derivation (n = 1014) and validation (n = 254) cohorts. The primary endpoint was any in-hospital death, cardiac arrest or utilization of mechanical support devices. Logistic regression model was preformed to identify risk factors and build the new scoring system. The assigning point of each parameter was determined according to its β coefficient. The discrimination was validated internally using C statistic and calibration was evaluated by the Hosmer-Lemeshow goodness-of-fit test., Results: We constructed a predictive score based on six significant risk factors [systolic blood pressure (SBP), white blood cell (WBC) count, hematocrit (HCT), total bilirubin (TBIL), estimated glomerular filtration rate (eGFR) and NT-proBNP]. This new model was computed as (1 × SBP < 90 mmHg) + (2 × WBC > 9.2 × 10 9 /L) + (1 × HCT ≤ 0.407) + (2 × TBIL > 34.2 μmol/L) + (2 × eGFR < 15 ml/min/1.73 m 2 ) + (1 × NTproBNP ≥ 10728.9 ng/ml). The C statistic for the new score was 0.758 (95% CI 0.667-0.838) higher than APACHE II, AHEAD and ADHERE score. It also demonstrated good calibration for detecting high-risk patients in the validation cohort (χ 2  = 6.681, p = 0.463)., Conclusions: The new score including SBP, WBC, HCT, TBIL, eGFR and NT-proBNP might be used to predict short-term prognosis of Chinese critically-ill ADHF patients.

Objective: We aimed to evaluate the association between plasma big endothelin-1 (ET-1) at admission and short-term outcomes in acute decompensated heart failure (ADHF) patients. Methods: In this single-center, retrospective study, a total of 746 ADHF patients were enrolled and divided into three groups according to baseline plasma big ET-1 levels: tertile 1 (<0.43 pmol/L, n = 250), tertile 2 (between 0.43 and 0.97 pmol/L, n = 252), and tertile 3 (>0.97 pmol/L, n = 244). The primary outcomes were all-cause death, cardiac arrest, or utilization of mechanical support devices during hospitalization. Logistic regression analysis and net reclassification improvement approach were applied to assess the predictive power of big ET-1 on short-term outcomes. Results: During hospitalization, 92 (12.3%) adverse events occurred. Etiology, arterial pH, lactic acid, total bilirubin, serum creatine, serum uric acid, presence of atrial fibrillation and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were positively correlated with plasma big ET-1 level, whereas systolic blood pressure, serum sodium, hemoglobin, albumin, and estimated glomerular filtration rate were negatively correlated. In multivariate logistic regression, tertile 3 compared with tertile 1 had a 3.68-fold increased risk of adverse outcomes [odds ratio (OR) = 3.681, 95% confidence interval (CI) 1.410-9.606, p = 0.008]. However, such adverse effect did not exist between tertile 2 and tertile 1 (OR = 0.953, 95% CI 0.314-2.986, p = 0.932). As a continuous variable, big ET-1 level was significantly associated with primary outcome (OR = 1.756, 95% CI 1.413-2.183, p < 0.001). The C statistic of baseline big ET-1 was 0.66 (95% CI 0.601-0.720, p < 0.001). Net reclassification index (NRI) analysis showed that big ET-1 provided additional predictive power when combining it to NT-proBNP (NRI = 0.593, p < 0.001). Conclusion: Elevated baseline big ET-1 is an independent predictor of short-term adverse events in ADHF patients and may provide valuable information for risk stratification., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mo, Yang, Yu, Tan and Zhu.)

Noble metal nanoparticles (NMNPs) with excellent catalytic activity and stability play an important role in the field of environmental governance. A uniform distribution and a strong binding force with the carriers of the noble metal nanoparticles are important, but avoidance of the use of additional reducing agents is a promising direction of research. Herein, 2D ultrathin surfactant-encapsulating polyoxometalate (SEP) nanosheets constructed by the self-assembly of dodecyldimethylammonium bromide (DODA) and molybdophosphate (H3PMo12O40, PMo12) are designed to be versatile carriers for Ag nanoparticles. Under the synergistic effect of the well-arranged PMo12 units, encapsulating hydrophobic oleic acid (OA) and reductive molybdophosphate under Xe lamp irradiation, the silver oleate (AgOA)-derived Ag nanoparticles (5 ± 2 nm) are monodispersed on the DODA-PMo12 assemblies and form the Agx/DODA-PMo12 composite. The optimized Ag4.89/DODA-PMo12 composite exhibits high catalytic activity and stability in the degradation of 4-nitrophenol (4-NP), which reaches a superior rate constant of 6.49 × 10-3 s-1 and without significant deterioration after three recycles. This technique can be facilely promoted to other noble metal nanoparticles with excellent catalytic activity and stability.

The reasonable construction of heterojunction photocatalysts with clear nanostructures and a good interface contact especially the one-dimensional/two-dimensional (1D/2D) composite heterojunction with unique morphology is considered one of the most effective strategies for designing highly efficient photocatalysts. Herein, a series of the 1D β-keto-enamine-based covalent organic framework (COF)/2D g-C 3 N 4 composite materials COF-CN (1: x ; where 1: x represents the mass ratio of COF and g-C 3 N 4 , x = 2.5, 5, 10, 15, 20) is prepared through the in situ reaction of 2,4,6-triformylphloroglucinol (Tp) and benzidine (BD) in stripped g-C 3 N 4 suspension. A series of characterizations, such as X-ray diffraction (XRD), Fourier transform infrared (FT-IR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM), have verified their 1D/2D heterojunction structure. With the introduction of 1D COF nanobelts, the absorption of the composite is largely extended to 560 nm. Photocatalytic experiments reveal that the composite COF/CN shows evidently superior photocatalytic performance than individual COF and g-C 3 N 4 . The optimized COF-CN (1:10) exhibits a H 2 production rate of 12.8 mmol g -1 ·h -1 under visible-light (λ ≥ 420 nm) irradiation, which is about 62 and 284 times higher than those of COF and g-C 3 N 4 , respectively. The apparent quantum efficiency (AQE) of COF-CN (1:10) is about 15.09% under 500 nm light irradiation, which is one of the highest among previous COF- or g-C 3 N 4 -based materials. This work provides important strategies for designing and constructing high-efficiency heterojunction photocatalysts with multidimensional features.

Background: Lactate dehydrogenase (LDH) is a known prognostic biomarker for the endemic variant of nasopharyngeal carcinoma (NPC). Here, we investigate whether serial changes in LDH level between chemotherapy (CT) cycles are associated with tumour response to CT., Methods: Patients with biopsy-proven, recurrent or treatment-naïve metastatic NPC (mNPC) were recruited. All patients had received at least two cycles of platinum-based doublet or triplet CT, with serial assessment of LDH prior to every cycle of chemotherapy (CT1-6). Patients harbouring conditions that affect LDH levels (IU/L) were excluded. Tumour response was assessed after every two cycles of CT by RECIST v1.1., Results: A total of 158 patients were analysed, including 77 with recurrent and 81 with treatment-naïve mNPC. High pre-CT LDH was associated with an inferior overall survival [hazard ratio 1.93 for ⩾240 versus <240 (1.34-2.77), p  < 0.001], which is consistent with published literature. We found that both absolute LDH levels and LDH ratios (LDH CTn : LDH CTn-1 ) were associated with tumour response [partial response versus progressive disease: median value across CT1-6 = 168-190 versus 222-398 (absolute); 0.738-0.988 versus 1.039-1.406 (ratio)], albeit LDH ratio had a tighter variance between patients. Finally, we showed that an LDH ratio cut-off of 1.0 at CT1, CT3 and CT5 was predictive of progressive disease at CT2, CT4, CT6 [area under the curve of 0.73 (0.65-0.80)]., Conclusion: Herein, we characterised the longitudinal variation of LDH in response to CT in mNPC. Our findings suggest the potential utility of interval LDH ratio to predict subsequent tumour response to CT., Competing Interests: Conflict of interest statement: MC reports personal fees from Astellas, Janssen, Bayer, Pfizer, MSD, personal fees and non-financial support from AstraZeneca, personal fees and grants from Ferring, personal fees and non-financial support from Varian, non-financial support from Decipher Biosciences, non-financial support from Medlever, and consults for immunoSCAPE Inc., outside the submitted work., (© The Author(s), 2020.)

Purpose: The Willis covered stent (WCS) is used to treat complex vascular diseases of the internal carotid artery; however, its performance requires further investigation. This study aimed to present our single-center clinical results and experience of endovascular repair of complex vascular diseases of the internal carotid artery using the WCS. Methods: Patients who presented with complex vascular diseases of the internal carotid artery and who were treated with the WCS from December 2013 to September 2018 were retrospectively reviewed. Procedural results, perioperative complications, incidence of endoleak, and follow-up outcomes were analyzed. Results: Sixty-five patients were enrolled. A total of 25 large aneurysms, 10 pseudoaneurysms, 14 blood blister-like aneurysms, 11 carotid-cavernous fistulas, and 5 surgical injuries were assessed. WCS placement was successful in all patients. Immediate angiography showed that complete repair of the target artery was achieved in 56 patients (86.2%). Endoleak was observed in nine patients, including seven type I endoleaks and two type II endoleaks. Occlusion of a side-branch vessel occurred in four patients. Acute in-stent thrombosis occurred in one patient. No ischemic or hemorrhagic events or other complications developed during the perioperative and follow-up periods. Angiographic follow-up (mean duration, 12 ± 3.29 months) was performed in 60 patients and showed complete target artery repair in 58 patients, and asymptomatic mild to moderate in-stent stenosis was observed in four patients. Slight endoleak persisted in two patients without enlargement or rupture of the residual lumen. Conclusion: WCS implantation is safe, feasible, and efficacious for endovascular repair in patients with complex vascular diseases of the internal carotid artery, showing excellent short-term target artery patency and clinical outcomes., (Copyright © 2020 Ma, Feng, Yan, Xu, Tan and Fang.)

Objective: Dose-averaged linear energy transfer (LET D ) is one of the factors which determines relative biological effectiveness (RBE) for treatment planning in proton therapy. It is usually determined from Monte Carlo (MC) simulation. However, no standard simulation protocols were established for sampling of LET D . Simulation parameters like maximum step length and range cut will affect secondary electrons production and have an impact on the accuracy of dose distribution and LET D . We aim to show how different combinations of step length and range cut in GEANT4 will affect the result in sampling of LET D using different MC scoring methods., Methods: In this work, different step length and range cut value in a clinically relevant voxel geometry were used for comparison. Different LET D scoring methods were established and the concept of covariance between energy deposition per step and step length is used to explain the differences between them., Results: We recommend a maximum step length of 0.05 mm and a range cut of 0.01 mm in MC simulation as this yields the most consistent LET D value across different scoring methods. Different LET D scoring methods are also compared and variation up to 200% can be observed at the plateau of 80 MeV proton beam. Scoring Method one has one of the lowest percentage differences compared across all simulation parameters., Conclusion: We have determined a set of maximum step length and range cut parameters to be used for LET D scoring in a 1 mm voxelized geometry. LET D scoring method should also be clearly defined and standardized to facilitate cross-institutional studies., Advances in Knowledge: Establishing a standard simulation protocol for sampling LET D would reduce the discrepancy when comparing data across different centres, and this can improve the calculation for RBE.

There is an increasing number of radiobiological experiments being conducted with low energy protons (less than 5 MeV) for radiobiological studies due to availability of sub-millimetre focused beam. However, low energy proton has broad microdosimetric spectra which can introduce dosimetric uncertainty. In this work, we quantify the impact of this dosimetric uncertainties on the cell survival curve and how it affects the estimation of the alpha and beta parameters in the LQ formalism. Monte Carlo simulation is used to generate the microdosimetric spectra in a micrometer-sized water sphere under proton irradiation. This is modelled using radiobiological experiment set-up at the Centre of Ion Beam Application (CIBA) in National University of Singapore. Our results show that the microdosimetric spectra can introduce both systematic and random shifts in dose and cell survival; this effect is most pronounced with low energy protons. The alpha and beta uncertainties can be up to 10% and above 30%, respectively for low energy protons passing through thin cell target (about 10 microns). These uncertainties are non-negligible and show that care must be taken in using the cell survival curve and its derived parameters for radiobiological models., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

RNA editing introduces nucleotide changes in RNA sequences. Recent studies have reported that aberrant A-to-I RNA editing profiles are implicated in cancers. Albeit changes in expression and activity of ADAR genes are thought to have been responsible for the dysregulated RNA editome in diseases, they are not always correlated, indicating the involvement of secondary regulators. Here, we uncover DAP3 as a potent repressor of editing and a strong oncogene in cancer. DAP3 mainly interacts with the deaminase domain of ADAR2 and represses editing via disrupting association of ADAR2 with its target transcripts. PDZD7 , an exemplary DAP3-repressed editing target, undergoes a protein recoding editing at stop codon [Stop →Trp (W)]. Because of editing suppression by DAP3, the unedited PDZD7 WT , which is more tumorigenic than edited PDZD7 Stop518W , is accumulated in tumors. In sum, cancer cells may acquire malignant properties for their survival advantage through suppressing RNA editome by DAP3., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Objective: To explore the occurrence of cognitive impairment in Chinese heart failure (HF) patients and it's impact on prognosis. Methods: In this prospective observational study, a total of 990 HF patients were enrolled from 24 hospitals in China during December 2012 to November 2014. All patients were administrated with the interview-format Montreal Cognitive Assessment (MoCA), according to which they were divided into MoCA<26 (with cognitive impairment) group and MoCA≥26 (without cognitive impairment) group. Baseline data were collected and a 1-year follow up was carried out. Univariate and multivariate logistic or Cox regression were performed for 1-year outcomes. Results: Cognitive impairment was evidenced in 628 patients (63.4%) and they were more likely to be older, female, and with higher proportion of New York Heart Association(NYHA) class Ⅲ-Ⅳ, chronic obstructive pulmonary disease (COPD), ischemic heart disease, while body mass index (BMI), education level, and medical insurance rate were lower (all P< 0.05) as compared to patients in MoCA≥26 group. The rate of percutaneous intervention, device implantation, cardiac surgery and evidence-based medications were significantly lower in MoCA<26 group than in MoCA≥26 group (all P< 0.05). During the 1-year follow up, patients in the MoCA<26 group had higher all-cause mortality (10.2%(64/628) vs. 2.2%(8/362), P< 0.01), cardiovascular mortality (5.9%(37/628) vs. 0.8%(3/362), P< 0.01) and major adverse cardiac and cerebrovascular events (MACCE) (9.6%(60/628) vs. 2.5%(8/362), P< 0.01) than patients in the MoCA≥26 group. In univariate regression, MoCA<26 was associated with increased all-cause mortality ( HR (95 %CI ):4.739(2.272-9.885), P< 0.01), cardiovascular mortality ( HR (95 %CI ):7.258(2.237-23.548), P= 0.001) and MACCE ( OR (95 %CI ):4.143(2.031-8.453), P< 0.01). After adjustment by multivariate regression, MoCA<26 was indicated as an independent risk factor for all-cause mortality ( HR (95 %CI ): 6.387(2.533-16.104), P< 0.01), cardiovascular mortality ( HR (95 %CI ): 10.848(2.586-45.506), P= 0.001) and MACCE ( OR (95 %CI ): 4.081(1.299-12.816), P= 0.016), while not for re-hospitalization for HF ( OR (95 %CI ):1.010(0.700-1.457), P= 0.957). Conclusions: Cognitive impairment is common in HF patients,and it is an independent prognostic factor for 1-year outcomes. Routine cognitive function assessment and active intervention are thus recommended for HF patients.

The electrocatalytic carbon dioxide (CO 2 ) reduction reaction (CO 2 RR) involves a variety of electron transfer pathways, resulting in poor reaction selectivity, limiting its use to meet future energy requirements. Polyoxometalates (POMs) can both store and release multiple electrons in the electrochemical process, and this is expected to be an ideal "electron switch" to match with catalytically active species, realize electron transfer modulation and promote the activity and selectivity of the electrocatalytic CO 2 RR. Herein, we report a series of new POM-based manganese-carbonyl (MnL) composite CO 2 reduction electrocatalysts, whereby SiW 12 -MnL exhibits the most remarkable activity and selectivity for CO 2 RR to CO, resulting in an increase in the faradaic efficiency (FE) from 65% (MnL) to a record-value of 95% in aqueous electrolyte. A series of control electrochemical experiments, photoluminescence spectroscopy (PL), transient photovoltage (TPV) experiments, and density functional theory (DFT) calculations revealed that POMs act as electronic regulators to control the electron transfer process from POM to MnL units during the electrochemical reaction, enhancing the selectivity of the CO 2 RR to CO and depressing the competitive hydrogen evolution reaction (HER). This work demonstrates the significance of electron transfer modulation in the CO 2 RR and suggests a new idea for the design of efficient electrocatalysts towards CO 2 RR., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: To investigate the epidemiological characteristics and clinic symptoms of an outbreak of infectious diarrhea caused by Sapovirus, in CT community, Zhaoqing, Guangdong province. Methods: Retrospective study of field epidemiology investigation was carried out and Chi-square test was used enteroviruses were detected by RT-PCR in swab, fecal specimens and water samples. Results: A total of 422 cases were identified in this outbreak, with the prevalence as 11.95 % . Cases mainly concentrated between 21 and 24, December, with curves noticed by point- source and peaked on the 22(nd). Symptoms mainly appeared as vomiting, with watery stool. Patients were founded in every village, with the highest prevalence appeared in the elderly (25.20 % ) but involved in every age group. Sapovirus infection was most frequently seen in the population under 25 years of age, with overall prevalence as 16.41 % . People older than 50 years of age took the second place (12.05 % ), and the lowest was seen between 25 to 49 years age group (8.42 % ). Sapovirus was detected in both swab and fecal specimens, with the positive rate as 38.78 % . Both general and heat- resistant coliformed-bacteria were detected in the 24 monitored water samples, with the qualification rates as 95.83 % , 45.83 % and 50.00 % , respectively. However, Sapovirus was not detected in any of the water samples. Conclusions: Our findings confirmed that an outbreak, caused by sapovirus infection in CT community was most likely related to the central water supply. The surveillance system for infectious diarrheal diseases should be improved and both public health awareness and surveillance programs on drinking water should be strengthened.

Background: Mycobacterium tuberculosis (TB) is a pathogen that consequently leads to TB infection, which remains a significant global health concern. Programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling pathway is critical for terminating immune responses. The present study aimed to elucidate the regulatory role of the PD-1/PD-L1 signaling pathway in alveolar macrophages against Mycobacterium TB in mice., Methods: Specific pathogen free mice were initially prepared for Mycobacterium TB model establishment. The alveolar macrophages of the successfully modeled rats were evaluated to determine the levels of PD-1, PD-L1, AKT, mTOR, TNF-α, NF-κB, IL-2, IL-4, IL-6, IL-10, IL-17, IL-17A, and IFN-γ. The surface makers of macrophages (CD11c, CD16, CD86, CD163, CD206, CX3CR-1 and CSF-1R), level of ROS, apoptosis and cell cycle, were all assessed., Results: Elevated levels of PD-1 and PD-L1, decreased levels of AKT and mTOR, along with elevated levels of TNF-α, NF-κB, IL-17, IL-2, IL-6, IL-17A and IFN-γ were identified in the alveolar macrophages infected with Mycobacterium TB, while an opposite trend was observed when PD-1/PD-L1 signaling pathway was inhibited. Additionally, elevated protein levels of CD11c, CD16 and CD86, as well as an increased rate of positive ROS and cell apoptosis, levels of Bax, and a diminished percentage of alveolar macrophages at the S and G2/M stages were detected in the event of Mycobacterium TB infection. A contrasting trend to the aforementioned findings was detected when the PD-1/PD-L1 signaling pathway was inhibited., Conclusion: Taken together, these results suggested that inhibition of the PD-1/PD-L1 signaling pathway enhanced the innate immune response of alveolar macrophages to Mycobacterium TB in mice., (Copyright © 2019. Published by Elsevier Ltd.)

The oxidized platinum (Pt) can exhibit better electrocatalytic activity than metallic Pt 0 in the hydrogen evolution reaction (HER), which has aroused great interest in exploring the role of oxygen in Pt-based catalysts. Herein, we select two structurally well-defined polyoxometalates Na 5 [H 3 Pt (IV) W 6 O 24 ] (PtW 6 O 24 ) and Na 3 K 5 [Pt (II) 2 (W 5 O 18 ) 2 ] (Pt 2 (W 5 O 18 ) 2 ) as the platinum oxide model to investigate the HER performance. Electrocatalytic experiments show the mass activities of PtW 6 O 24 /C and Pt 2 (W 5 O 18 ) 2 /C are 20.175 A mg -1 and 10.976 A mg -1 at 77 mV, respectively, which are better than that of commercial 20% Pt/C (0.398 A mg -1 ). The in situ synchrotron radiation experiments and DFT calculations suggest that the elongated Pt-O bond acts as the active site during the HER process, which can accelerate the coupling of proton and electron and the rapid release of H 2 . This work complements the knowledge boundary of Pt-based electrocatalytic HER, and suggests another way to update the state-of-the-art electrocatalyst.

The nitrogen (N 2 ) reduction to generate ammonia (NH 3 ) is a prerequisite for inputting fixed nitrogen (N) into a global biogeochemical cycle. Developing highly efficient photocatalysts for N 2 fixation under mild conditions is still a challenge. Herein, we first report three kinds of reduction states of graphene oxide (GO)@polyoxometalate (POM) composite nanomaterials, which have outstanding photocatalytic N 2 fixation activities in pure water without any other electronic sacrificial agents and cocatalysts at atmospheric pressure and room temperature. A lot of experiments show that the remarkable photocatalytic N 2 fixation performance of these three nanocatalysts is due to three factors that doping the reduced POMs (also called heteropoly blues) into the reduce GO (rGO) reduces the aggregation state of rGO (from 5 to 2 nm), resulting in rGO exposing many active sites to enhance the N 2 adsorption amount, these three nanocatalysts possess a wide absorption spectrum and strong reducibility, which facilitate absorb light energy exciting abundant photoelectrons to activate N 2 , and rGO can effectively suppress the electrons recombination and rapidly transfer electrons to the absorbed N 2 to accelerate NH 3 production. Among them, r-GO@H 5 [PMo 10 V 2 O 40 ] (PMo 10 V 2 ) exhibits the highest NH 3 generation efficiency of 130.3 μmol L -1 h -1 , which is improved by 65.9 and 97.3% compared to the reduced PMo 10 V 2 (rPMo 10 V 2 ) and PMo 10 V 2 . Introduction of POMs provides a new perspective in the design of high-performance photocatalytic N 2 fixation nanomaterials.

Rectal temperature is an important physiological indicator used to characterize the reproductive and health status of sows. Infrared thermography, a surface temperature measurement technology, was investigated in this study to explore its feasibility in non-invasive detection of rectal temperature in sows. A total of 124 records of rectal temperature and surface temperature in various body regions of 99 Landrace × Yorkshire crossbred sows were collected. These surface temperatures together with ambient temperature, ambient humidity, and wind speed in pig pens were correlated with the real rectal temperature of sows to establish rectal temperature prediction models by introducing chemometrics algorithms. Two types of models, i.e., full feature models and selected feature models, were established by applying the partial least squares regression (PLSR) method. The optimal model was attained when 7 important features were selected by LARS-Lasso, where correlation coefficients and root mean squared errors of calibration were 0.80 and 0.30 °C, respectively. Particularly, the validity and stability of established simplified models were further evaluated by applying the model to an independent prediction set, where correlation coefficients and root mean squared errors for prediction were 0.80 and 0.35 °C, respectively. The validation of established models is scarce in previous similar studies. Above all, this study demonstrated that introduction of chemometrics methodologies would lead to more reliable and accurate model for predicting sow rectal temperature, thus the potential for ensuring animal welfare in a broader view if extended to more applications.

Objective: Radiomics pipelines have been developed to extract novel information from radiological images, which may help in phenotypic profiling of tumours that would correlate to prognosis. Here, we compared two publicly available pipelines for radiomics analyses on head and neck CT and MRI in nasopharynx cancer (NPC)., Methods and Materials: 100 biopsy-proven NPC cases stratified by T- and N-categories were enrolled in this study. Two radiomics pipeline, Moddicom (v. 0.51) and Pyradiomics (v. 2.1.2) were used to extract radiomics features of CT and MRI. Segmentation of primary gross tumour volume was performed using Velocity v. 4.0 by consensus agreement between three radiation oncologists. Intraclass correlation between common features of the two pipelines was analysed by Spearman's rank correlation. Unsupervised hierarchical clustering was used to determine association between radiomics features and clinical parameters., Results: We observed a high proportion of correlated features in the CT data set, but not for MRI; 76.1% (51 of 67 common between Moddicom and Pyradiomics) of CT features and 28.6% (20 of 70 common) of MRI features were significantly correlated. Of these, 100% were shape-related for both CT and MRI, 100 and 23.5% were first-order-related, 61.9 and 19.0% were texture-related, respectively. This interpipeline heterogeneity affected the downstream clustering with known prognostic clinical parameters of cTN-status and GTVp. Nonetheless, shape features were the most reproducible predictors of clinical parameters among the different radiomics modules., Conclusion: Here, we highlighted significant heterogeneity between two publicly available radiomics pipelines that could affect the downstream association with prognostic clinical factors in NPC., Advances in Knowledge: The present study emphasized the broader importance of selecting stable radiomics features for disease phenotyping, and it is necessary prior to any investigation of multicentre imaging datasets to validate the stability of CT-related radiomics features for clinical prognostication.

Ninety years after the discovery of the virus causing the influenza disease, this malady remains one of the biggest public health threats to mankind. Currently available drugs and vaccines only partially reduce deaths and hospitalizations. Some of the reasons for this disturbing situation stem from the sophistication of the viral machinery, but another reason is the lack of a complete understanding of the molecular and physiological basis of viral infections and host-pathogen interactions. Even the functions of the influenza proteins, their mechanisms of action and interaction with host proteins have not been fully revealed. These questions have traditionally been studied in mammalian animal models, mainly ferrets and mice (as well as pigs and non-human primates) and in cell lines. Although obviously relevant as models to humans, these experimental systems are very complex and are not conveniently accessible to various genetic, molecular and biochemical approaches. The fact that influenza remains an unsolved problem, in combination with the limitations of the conventional experimental models, motivated increasing attempts to use the power of other models, such as low eukaryotes, including invertebrate, and primary cell cultures. In this review, we summarized the efforts to study influenza in yeast, Drosophila , zebrafish and primary human tissue cultures and the major contributions these studies have made toward a better understanding of the disease. We feel that these models are still under-utilized and we highlight the unique potential each model has for better comprehending virus-host interactions and viral protein function.

Two-dimensional (2D) heteromaterials with large interface contact and intimate interfacial charge transition have been considered to be an ideal model for constructing highly efficient photocatalysts. However, few studies have reported on these 2D heterojunctions. Herein, we report a series of new 2D heterojunctions comprising polyimide (PI) and perylene-3,4,9,10-tetracarboxylic dianhydride (TD). These heterojunctions, denoted as PI-TD x (where x represents the amount of TD added, i.e., x = 0.13, 0.18, 0.27, 0.54, and 1.08 g), were prepared by the solid thermal copolymerization of melamine (MA), pyromellitic dianhydride (PD), and different amounts of TD. FT-IR spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and transmission electron microscopy analyses were used to verify the 2D heterojunction structure. Photocatalytic experiments reveal that PI-TD x exhibit excellent and stable photocatalytic performance for the degradation of the organic dyes rhodamine B (RhB) and methyl violet (MV), as well as for the photoreduction of Cr(vi), under visible-light irradiation. Among the samples, PI-TD 0.18 exhibits the best photocatalytic performance. Its activity is about 2.7 times and 7.5 times higher than that of individual PI MP (formed by MA and PD) and PI MT (formed by MA and TD) for RhB degradation, respectively. Notably, PI-TD 0.18 retains a certain photocatalytic activity under light irradiation at 600 nm. The photocatalytic-mechanism study demonstrates that PI-TD 0.18 has a classic type-II heterojunction. Its 2D heterojunction greatly enhances the visible-light absorption of the composites and effectively suppresses the radiation recombination of photogenerated carriers, thereby improving its charge transfer and separation abilities and providing excellent photocatalytic performance. This work may serve as an important reference for the design and construction of new highly efficient 2D organic conjugated-polymer photocatalysts.

Purpose: This study aimed to report the clinical findings and initial clinical experience of endovascular recanalization for symptomatic subacute/chronic intracranial large artery occlusion (ILAO) of the anterior circulation., Methods: From October 2015 to December 2017, 13 patients with symptomatic subacute/chronic ILAO of the anterior circulation were enrolled in this study and underwent endovascular recanalization. We collected the initial procedural results, including the rate of successful recanalization and periprocedural complications, and data pertaining to angiographic and clinical follow-up., Results: Recanalization was successful in 11 of 13 patients (84.6%). Intraoperative complications occurred in four cases, including symptomatic distal embolism in three cases; one of which was simultaneously complicated with artery dissection. Intracerebral hemorrhage occurred in one case. Eleven patients underwent angiographic follow-up, and 12 patients underwent clinical follow-up. The results of the angiography follow-up (mean 6 ± 3.29 months) showed that in-stent restenosis occurred in one of the 11 successfully recanalized patients. However, the artery was occluded again in the patient who achieved thrombolysis in cerebral infarction (TICI) grade of 2a after treatment. Clinical follow-up (mean 5.8 ± 2.25 months) showed no recurrence of transient ischemic attack (TIA) or stroke in ten successfully recanalized cases. However, the patient who developed in-stent stenosis suffered TIA., Conclusions: Endovascular recanalization for symptomatic subacute/chronic ILAO of anterior circulation is feasible, relatively safe, and efficacious in highly selected cases, improving patients' symptoms in the short-term. However, further larger scale pilot studies are needed to determine the efficacy and long-term outcome associated with this treatment.

Background: Desminopathy, a hereditary myofibrillar myopathy, mainly results from the desmin gene (DES) mutations. Desminopathy involves various phenotypes, mainly including different cardiomyopathies, skeletal myopathy, and arrhythmia. Combined with genotype, it helps us precisely diagnose and treat for desminopathy., Methods: Sanger sequencing was used to characterize DES variation, and then a minigene assay was used to verify the effect of splice-site mutation on pre-mRNA splicing. Phenotypes were analyzed based on clinical characteristics associated with desminopathy., Results: A splicing mutation (c.735+1G>T) in DES was detected in the proband. A minigene assay revealed skipping of the whole exon 3 and transcription of abnormal pre-mRNA lacking 32 codons. Another affected family member who carried the identical mutation, was identified with a novel phenotype of desminopathy, non-compaction of ventricular myocardium. There were 2 different phenotypes varied in cardiomyopathy and skeletal myopathy among the 2 patients, but no significant correlation between genotype and phenotype was identified., Conclusions: We reported a novel phenotype with a splicing mutation in DES, enlarging the spectrum of phenotype in desminopathy. Molecular studies of desminopathy should promote our understanding of its pathogenesis and provide a precise molecular diagnosis of this disorder, facilitating clinical prevention and treatment at an early stage.

Objective: To report the clinical results and initial clinical experience of endovascular isolation with the Willis covered stent for carotid siphon aneurysms., Methods: Between November 2013 and December 2016, a total of 57 patients who presented with carotid siphon aneurysms were treated with the Willis covered stent. Results of the procedures, technical events, and complications were recorded. Clinical and imaging follow-ups were performed at 3 months following the endovascular procedures., Results: Placement of the Willis covered stent was successful in all patients. Immediate angiography revealed complete exclusion of aneurysms in 48 patients (84%), while endoleak occurred in nine patients (16%). Procedure-related complications occurred in three cases, including displacement of the covered stent in one patient, acute in-stent thrombosis in one patient, and microwire-related intracranial hemorrhage in one patient. Angiographic follow-ups were done in 49 patients, with complete exclusion of aneurysms in 47 patients. Endoleak was present in two patients. No aneurysm recurrence occurred. Forty-four patients showed good parent artery patency, while the other five patients showed mild to moderate asymptomatic in-stent stenosis. During the follow-up period, no ischemic or hemorrhagic event occurred. The modified Rankin Scale scores at follow-up were 0-2 in 56 patients and >2 in one patient., Conclusions: The treatment of siphon aneurysms with Willis covered stent implantation resulted in satisfactory clinical outcomes. The Willis covered stent seems safe and feasible for the treatment of siphon aneurysms, which still needs to be confirmed by longer follow-up periods and controlled studies with larger samples., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

We present a simple and universal approach to calculate the total ionization cross section (TICS) for electron impact ionization in DNA bases and other biomaterials in the condensed phase. Evaluating the electron impact TICS plays a vital role in ion-beam radiobiology simulation at the cellular level, as secondary electrons are the main cause of DNA damage in particle cancer therapy. Our method is based on extending the dielectric formalism. The calculated results agree well with experimental data and show a good comparison with other theoretical calculations. This method only requires information of the chemical composition and density and an estimate of the mean binding energy to produce reasonably accurate TICS of complex biomolecules. Because of its simplicity and great predictive effectiveness, this method could be helpful in situations where the experimental TICS data are absent or scarce, such as in particle cancer therapy.

Chemoprevention-the use of medication to prevent cancer-can be augmented by the consumption of produce enriched with natural metabolites. However, chemopreventive metabolites are typically inactive and have low bioavailability and poor host absorption. Here, we show that engineered commensal microbes can prevent carcinogenesis and promote the regression of colorectal cancer through a cruciferous vegetable diet. The engineered commensal Escherichia coli bound specifically to the heparan sulphate proteoglycan on colorectal cancer cells and secreted the enzyme myrosinase to transform host-ingested glucosinolates-natural components of cruciferous vegetables-to sulphoraphane, an organic small molecule with known anticancer activity. The engineered microbes coupled with glucosinolates resulted in >95% proliferation inhibition of murine, human and colorectal adenocarcinoma cell lines in vitro. We also show that murine models of colorectal carcinoma fed with the engineered microbes and the cruciferous vegetable diet displayed significant tumour regression and reduced tumour occurrence.

The aim of this study was to determine whether low dose doxycycline as an anti-inflammatory agent could improve glucose metabolism in diabetic animals. Therefore, doxycycline was supplemented in drinking water to 6-week-old male db/db mice for 10 weeks. Doxycycline reduced perirenal/epididymal fat, Lee's index, and liver cholesterol. Blood HDL-cholesterol increased, but total cholesterol and aspartate transaminase decreased. Glucose and insulin tolerances were improved, accompanying with reduced fasting blood glucose, insulin, HOMA-IR and advanced glycation end products. Islet number, β-cell percentage and mass increased, while islet size decreased. Consistently, less apoptosis but more β-cell proliferation were found in islets of treated mice. Freshly isolated islets from treated mice showed higher insulin content and enhanced glucose stimulated insulin secretion (GSIS). In addition, purified islets of Balb/c mice showed increased GSIS after cultivation in vitro with doxycycline, but not with chloramphenicol and levofloxacin. Inflammation markers, including lipopolysaccharides (LPS) and C-reactive protein (CRP) in serum as well as CD68-positive cells in treated islets, decreased significantly. Finally, LPS stimulated the production of inflammatory factors but inhibited GSIS of MIN6 cells; however, the effects were completely reversed by doxycycline. The results support further study of possible long-term usage of sub-antimicrobial doxycycline in diabetic patients.

Objective: Intracranial blood blister-like aneurysm (BBA) is a rare type of aneurysm that lacks all layers of the arterial wall. These fragile aneurysms have the propensity to rupture with minimal manipulation, which makes them hazardous and difficult to treat. The present study evaluated the safety and feasibility of endovascular treatment of BBAs with the Willis covered stent., Materials: Thirteen patients (7 men and 6 women, age range 28-68 years) who presented with ruptured BBAs and were treated with the Willis covered stent were retrospectively reviewed. Results of the procedures and treatment-related complications were recorded. Angiographic and clinical follow-ups were performed 4-6 months after the procedure., Results: Placement of the covered stent was successful in all patients. Immediate angiography showed complete aneurysm occlusion in 12 patients while one patient showed a mild endoleak. This high rate of aneurysm exclusion ensured the security of postoperative antiplatelet treatment. Occlusion of the ophthalmic artery occurred in two patients and occlusion of the anterior choroidal artery occurred in one patient; however, none of them showed acute or delayed clinical symptoms. Thrombosis, aneurysm rupture, and other complications did not develop in any case. Angiographic follow-up showed complete aneurysm exclusion without aneurysm recurrence in any patients. Only two patients showed asymptomatic mild to moderate in-stent stenosis. All patients had satisfactory clinical outcomes (modified Rankin Scale score ≤1)., Conclusions: Willis covered stent implementation may be safe and feasible for BBAs. This strategy might be a promising option for this high-risk type of aneurysm., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

During the exploration of highly efficient noble-metal-free electrocatalysts for the hydrogen evolution reaction (HER), a promising and challenging strategy is to fabricate composite nanocatalysts by finely tuning metal and/or nonmetal element components. Herein, we report a new HER electrocatalyst, which is composed of molybdenum phosphide and molybdenum carbide composite nanoparticles (NPs) coated by few-layer N-doped graphitic carbon shells (denoted as MoP/Mo 2 C@C). Such a new combination mode of electrocatalysts is realized by a one-step annealing route with the mixture of a Mo/P-based polyoxometalate (POM) and dicyandiamide. On the basis of this method, the simultaneous phosphorization and carbonization in a nanoscale confined space can be easily achieved by the use of POM as the molecular-element-regulating platform. MoP/Mo 2 C@C exhibits more remarkable HER performance over the whole pH range than those of MoP, Mo 2 C, and the physical mixture of MoP and Mo 2 C. The low overpotentials of 89, 136, and 75 mV were obtained at a current density of 10 mA cm -2 in the media of pH = 0, 7, and 14, respectively. Furthermore, MoP/Mo 2 C@C shows a long-term durability for 14 h over the entire pH range (0-14). Because of the protection of carbon shells, such composite electrocatalyst also possesses better transition-metal tolerance exemplified by Fe 2+ , Co 2+ , and Ni 2+ than that of 20% commercial Pt/C. This work demonstrates the advantage of POM precursors in adjusting the component and properties of nanoscale composite electrocatalysts for HER, which may suggest new options for the fabrication of highly efficient composite electrocatalysts.

The objective of this study was to formulate a novel gene delivery system based on the erythrocyte ghost (EG) integrated with fusogenic viral glycoprotein vesicular stomatitis virus glycoprotein G (VSV-G). VSV-G proteins were harvested as condition medium of Ad293 cells carrying a VSV-G transgene and then incorporated into EG. Plasmid DNA was condensed by various transfection reagents. A luciferase expression construct (pGL3-control) and a DsRed expression cassette (pCMV-DsRed) were used to evaluate the delivery efficiency of DNA/EG/VSV-G complexes. VSV-G proteins could be incorporated into EG in static incubation under acidic conditions as evidenced by the Western blot analysis. Condensed plasmid DNA was bound mostly to the outer surface of EG, which could be detected by electromicroscopy and measured by electrophoresis. EG/VSV-G complexes stimulated the delivery of pGL3-control into Ad293 cells significantly with the luciferase activity increased about 4-fold as compared to that of the control. The delivery of pCMV-DsRed was also enhanced with the percentage of DsRed-positive Ad293 cells increased from 55 % to about 80 %. Moreover, the transfection efficiency in 3T3, HeLa, INS-1, and bone marrow stem cell (BMSC) cells increased about 2-3-fold. Finally, confocal microscopy analysis showed that incorporation of VSV-G significantly enhanced the endocytosis of EG into target cells. In the present study, a novel type of non-viral DNA delivery vehicle consisting of EG and fusogenic VSV-G proteins was formulated, which showed superior transfection efficiency even in cells resistant to classical transfection.

Photocatalysis, a promising technology platform to address the environmental problems, has been attracting considerable attention. In this paper, Ag/Ag x H 3-x PMo 12 O 40 (simplified as Ag/AgHPMo 12 ) nanowires have been synthesized by a facile solid reaction route and in situ photodeposited method. The results of SEM and TEM indicate that the diameters of AgHPMo 12 nanowires are about 45 ± 10 nm, and Ag nanoparticles with diameters in the range of 5-15 nm are uniformly anchored on the surface of AgHPMo 12 nanowires. The Ag content in the Ag/AgHPMo 12 composite was manipulated by the light irradiation time (Ag/AgHPMo 12 -x; x stands for the irradiation time; x = 2, 4, 6, 8 h, respectively). With increasing irradiation time, the light absorption of as-synthesized samples in the visible region was gradually enhanced. The Ag/AgHPMo 12 -4 exhibits the best photocatalytic performance for the degradation of methyl orange and reduction of Cr 2 O 7 2- under visible-light (λ > 420 nm) irradiation. The study of the photocatalytic mechanism reveals that both Ag and AgHPMo 12 can be excited by visible light. The photoinduced electrons were transferred from AgHPMo 12 to metallic Ag, and combined with the Ag plasmonic holes. The Ag plasmonic electrons were trapped by O 2 to form ·O 2 - , or directly reduced Cr 2 O 7 2- to Cr 3+ . Meanwhile, the ·O 2 - species and the photogenerated holes of AgHPMo 12 were used to oxidize MO or i-PrOH; thus, they showed highly efficient and recyclable photocatalytic performance for removing the organic and inorganic pollutants.

Objective: This analysis was performed to evaluate the efficacy in stroke prevention and safety of dabigatran in Chinese nonvalvular atrial fibrillation(NVAF) patients enrolled in RE-LY trial. Methods: RE-LY was an prospective, open-label, randomized, multicenter study. From March 2006 to March 2009, 541 atrial fibrillation patients at risk of stroke were recruited from 13 medical centers in China. Patients randomly received, in a blinded fashion, fixed doses of dabigatran-110 mg or 150 mg twice daily or, in an unblinded fashion, adjusted-dose warfarin. The primary efficacy endpoint was stroke or systemic embolism. The primary safety endpoint was major bleeding. Results: The incidence of stroke in the Chinese subpopulation was 1.94% per year(7 cases) in the group that received 110 mg of dabigatran (dabigatran 110) and 1.10% per year(4 cases) in the group that received 150 mg of dabigatran (dabigatran 150), as compared with 2.87% per year (10 cases) in warfarin group . Incidence of ischemic stroke was 1.11% per year(4 patients) in dabigatran 110 group, 0.82% per year(3 cases) in dabigatran 150 group and 2.01% per year(7 patients) in warfarin group. Incidence of hemorrhagic stroke was 0.28% per year(1 case) in dabigatran 110 group, 0.27% per year(1 case) in dabigatran 150 group and 0.57% per year(2 cases) in warfarin group. All-cause mortality was similar among the three treatment groups: 3.33% per year(12 cases) in dabigatran 110, 2.19% per year(8 cases) in dabigatran 150 and 2.58% per year(9 cases) in warfarin group. Incidence of major bleeding event was 0.56% per year(2 cases) in both dabigatran groups, as compared with 1.43% per year(5 cases) in warfarin group. Gastrointestinal disorders such as dyspepsia occurred in 12.8% patients of both dabigatran groups, and in 5.6% patients of warfarin group. Conclusions: Despite the descriptive statistical analysis in nature of present study due to the limited number of subjects, our subgroup analysis implies that like warfarin, dabigatran is efficacious and safe for thromboembolism prevention in Chinese patients with atrial fibrillation at risk of stroke. Clinical Trail Registry National Institutes of Health(http: //www.clinicaltrials.gov), CT00262600.

The loading of noble-metal nanoparticles (NMNPs) onto various carriers to obtain stable and highly efficient catalysts is currently an important strategy in the development of noble metal (NM)-based catalytic reactions and their applications. We herein report a nanowire supramolecular assembly constructed from the surfactant-encapsulating polyoxometalates (SEPs) CTAB-PW 12 , which can act as new carriers for NMNPs. In this case, the Ag NPs are loaded onto the SEP nanowire assembly with a narrow size distribution from 5 to 20 nm in diameter; the average size is approximately 10 nm. The Ag NPs on the nanowire assemblies are well stabilized and the over agglomeration of Ag NPs is avoided owing to the existence of well-arranged polyoxometalate (POM) units in the SEP assembly and the hydrophobic surfactant on the surface of the nanowire assembly. Furthermore, the loading amount of the Ag NPs can be adjusted by controlling the concentration of the AgNO 3 aqueous solution. The resultant Ag/CTAB-PW 12 composite materials exhibit high activity and good stability for the catalytic reduction of 4-nitrophenol (4-NP) with NaBH 4 in isopropanol/H 2 O solution. The NMNPs-loaded SEP nanoassembly may represent a new composite catalyst system for application in NM-based catalysis., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Rational design of earth-abundant photocatalysts is an important issue for solar energy conversion and storage. Polyoxometalate (POM)@Co 3 O 4 composites doped with highly dispersive molecular metal-oxo clusters, synthesized by loading a single Keggin-type POM cluster into each confined space of a metal-organic framework (MOF), exhibit significantly improved photocatalytic activity in water oxidation compared to the pure MOF-derived nanostructure. The systematic synthesis of these composite nanocrystals allows the conditions to be tuned, and their respective water oxidation catalytic performance can be efficiently adjusted by varying the thermal treatment temperature and the feeding amount of the POM. This work not only provides a modular and tunable synthetic strategy for preparing molecular cluster@TM oxide (TM=transition metal) nanostructures, but also showcases a universal strategy that is applicable to design and construct multifunctional nanoporous metal oxide composite materials., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Atrial fibrillation (AF) and coronary artery disease (CAD) often coexist, however, the clinical characteristics and the impact of stable CAD on the outcomes in Chinese patients with AF has not been well understood., Methods: Consecutive AF patients in 20 hospitals in China from November 2008 to October 2011 were enrolled. The primary endpoints included 1-year all-cause mortality, stroke, non-central nervous system (non-CNS) embolism, and major bleeding., Results: A total of 1947 AF patients were analyzed, of whom 40.5% had stable CAD. The mean CHADS 2 scores in CAD patients were significantly higher than that of non-CAD patients (2.4 ± 1.4 vs . 1.4 ± 1.2, P < 0.001). During follow-up period, warfarin use is low in both groups, with relatively higher proportion in non-CAD patients compared with CAD patients (22.3% vs . 10.7%, P < 0.001). Compared with non-CAD patients, CAD patients had higher one-year all-cause mortality (16.8% vs . 12.9%, P = 0.017) and incidence of stroke (9.0% vs . 6.4%, P = 0.030), while the non-CNS embolism and major bleeding rates were comparable between the two groups. After multivariate adjustment, stable CAD was independently associated with increased risk of 1-year all-cause mortality (HR = 1.35, 95% CI: 1.01-1 .80, P = 0.040), but not associated with stroke (HR = 1.07, 95% CI: 0.72-1.58, P = 0.736)., Conclusions: Stable CAD was prevalent in Chinese AF patients and was independently associated with increased risk of 1-year all-cause mortality. Chinese AF patients with stable CAD received inadequate antithrombotic therapy and this grim status of antithrombotic therapy needed to be improved urgently.

Black-colored ZnO nanowires have been prepared in a metal-organic chemical vapor deposition system by employing a relatively low growth temperature and oxygen-deficient conditions. X-ray photoelectron spectroscopy reveals the incorporation of carbon into the nanowires. The photocatalytic hydrogen evolution activity of the black-colored ZnO nanowires is over 2.5 times larger than that of the pristine ZnO nanowires under simulated solar illumination conditions, and the enhanced photocatalytic activity can be attributed to the higher absorption of visible light by the black color and better carrier separation at the ZnO/carbon interface.

Mimicking proton conduction mechanism of Nafion to construct novel proton-conducting materials with low cost and high proton conductivity is of wide interest. Herein, we have designed and synthesized a cationic covalent organic framework with high thermal and chemical stability by combining a cationic monomer, ethidium bromide (EB) (3,8-diamino-5-ethyl-6-phenylphenanthridinium bromide), with 1,3,5-triformylphloroglucinol (TFP) in Schiff base reactions. This is the first time that the stable cationic crystalline frameworks allowed for the fabrication of a series of charged COFs (EB-COF:X, X = F, Cl, Br, I) through ion exchange processes. Exchange of the extra framework ions can finely modulate the COFs' porosity and pore sizes at nanoscale. More importantly, by introducing PW12O40(3-) into this porous cationic framework, we can greatly enhance the proton conductivity of ionic COF-based material. To the best of our knowledge, EB-COF:PW12 shows the best proton conductivity at room temperature among ever reported porous organic materials.

Three hybrid coordination networks that were constructed from ɛ-Keggin polyoxometalate building units and imidazole-based bridging ligands were prepared under hydrothermal conditions, that is, H[(Hbimb)2 (bimb){Zn4 PMo(V8) Mo(VI) 4O40}]⋅6 H2O(1), [Zn(Hbimbp)(bimbp)3 {Zn4 PMo(V8) Mo(VI) 4O40}]⋅DMF⋅3.5 H2O(2), and H[Zn2 (timb)2 (bimba)2 Cl2 {Zn4 PMo(V8) Mo(VI) 4O40}]⋅7 H2O(3) (bimb=1,4-bis(1-imidazolyl)benzene, bimbp=4,4'-bis(imidazolyl)biphenyl, timb=1,3,5-tris(1-imidazolyl)benzene, bimba=3,5-bis(1-imidazolyl)benzenamine). All three compounds were characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis, and single-crystal X-ray diffraction. The mixed valence of the Mo centers was analyzed by XPS spectroscopy and bond-valence sum calculations. In all three compounds, the ɛ-Keggin polyoxometalate (POM) units acted as nodes that were connected by rigid imidazole-based bridging ligands to form hybrid coordination networks. In compound 1, 1D zigzag chains extended to form a 3D supramolecular architecture through intermolecular hydrogen-bonding interactions. Compound 2 consisted of 2D curved sheets, whilst compound 3 contained chiral 2D networks. Because of the intrinsic reducing properties of ɛ-Keggin POM species, noble-metal nanoparticles were loaded onto these POM-based coordination networks. Thus, compounds 1-3 were successfully loaded with Ag nanoparticles, and the corresponding composite materials exhibited high catalytic activities for the reduction of 4-nitrophenol., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: We compared admission systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP) in predicting 30-day all-cause mortality in patients with ST-segment elevation myocardial infarction (STEMI) without cardiogenic shock., Methods: A retrospective study was performed in 7,033 consecutive STEMI patients. Multivariate-adjusted hazard ratios (HRs) with a 10mm Hg increment and quartiles of each blood pressure were determined by Cox proportional hazard analyses; Wald χ (2) tests were used to compare the strength of relationships., Results: Totally 593 (8.4%) patients died during follow-up. Of 4 indexes, only SBP (HR 0.94 per 10mm Hg, 95% confidence interval (CI) 0.91 to 0.98; P = 0.001) and PP (HR 0.89 per 10 mmHg, 95% CI 0.85 to 0.94; P < 0.001) were significantly associated with 30-day all-cause mortality; these in the highest vs. lowest quartiles of SBP (≥140 vs. <110mm Hg) and PP (≥60 vs. <40mm Hg) had HRs of mortality of 0.70 (95% CI 0.55 to 0.87; P = 0.003) and 0.60 (95% CI 0.47 to 0.75; P < 0.001), respectively. Compared with SBP, PP was a better predictor for mortality no matter in men (χ (2) = 5.9 for per 10mm Hg, χ (2) = 10.8 for quartiles) or women (χ (2) = 15.1 for per 10mm Hg, χ (2) = 19.5 for quartiles), and the relationship remained significant after adjustment of SBP. There was a pattern of declining risk with increasing blood pressures for mortality, and this trend was mainly observed in age groups of more than 70 years., Conclusions: Pulse pressure was an independent predictor of mortality in patients with STEMI, and low admission blood pressure should serve as a warning sign., (© American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The combination of an optical microscope and a luminescent probe plays a pivotal role in biological imaging because it allows for probing subcellular structures. However, the optical resolutions are largely constrained by Abbe's diffraction limit, and the common dye probes often suffer from photobleaching. Here we present a new method for subwavelength imaging by combining lanthanide-doped upconversion nanocrystals with the ionoluminescence imaging technique. We experimentally observed that the ion beam can be used as a new form of excitation source to induce photon upconversion in lanthanide-doped nanocrystals. This approach enables luminescence imaging and simultaneous mapping of cellular structures with a spatial resolution of sub-30 nm.

The reaction of Keggin-type polyoxometalate (POM) units, transition-metal (TM) ions, and a rigid bis(imidazole) ligand (1,4-bis(1-imidazolyl)benzene (bimb)) in a hydrothermal environment led to the isolation of four new POM-based metal-organic networks, [H2 L][CuL][SiW12 O40 ]⋅2 H2 O (1), [H2 L]2 [Co(H2 O)3 L][SiW11 CoO39 ]⋅6 H2 O (2), KH[CuL]2 [SiW11 CoO39 (H2 O)]⋅2 H2 O (3), and [CuL]4 [GeW12 O40 ]⋅H2 O (4; L=bimb). All four compounds were characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis, powder X-ray diffraction, and single-crystal X-ray diffraction. Compounds 1 and 3 are new 3D networks with 1D channels. Compounds 2 and 4 contain 2D networks, which further stack into 3D supramolecular networks. The contributions of pH value, the negative charge of the POM, and the TM coordination modes to the construction of 3D networks were elucidated by comparing the synthetic conditions and structures of compounds 1-4. The photocatalytic properties of compounds 1-4 were investigated using methylene blue (MB) degradation under UV light. All compounds showed good catalytic activity and structural stability. The possible catalytic mechanism was discussed on the basis of active-species trapping experiments. The different photocatalytic activities of compounds 1-4 were explained by comparison of the band gaps of different POM species and different packing modes of POM units in these hybrid compounds., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A series of polynuclear metal-oxo clusters have been constructed from the dynamic polyoxometalate (POM) building block {B-α-Sb(III)W9O33} and lanthanide (Ln) linkers via a stepwise synthetic strategy with the molecular formulas of [Ln2(H2O)4{WO2(pic)}2(SbW8O30)2](10-) (Na4Li6[La-1]·28H2O, Na3Li7[Pr-2]·30H2O) and [{Ln(H2O)}{Ln(pic)}(Sb3O4)(SbW8O31)(SbW10O35)]2(24-) (K2Na6Li16[Tb-3]·63H2O, Na9Li15[Dy-4]·61H2O, Na7Li17[Ho-5]·53H2O) (Hpic = picolinic acid). The five compounds have been characterized by FT-IR, elemental analysis, TG, powder X-ray diffraction (PXRD) and single crystal X-ray diffraction. In compounds 1-5, various POM moieties, such as {B-β-SbW8O30}, {B-α-SbW8O31} and {B-α-SbW10O35}, were formed through a series of disassembling and re-assembling processes of the dynamic {B-α-SbW9O33} precursor with specific pH, reaction temperature and time. Furthermore, the use of oxytropic Ln(3+) ions as linkers, together with auxiliary organic pic ligands and/or inorganic Sb(3+) ions, led to diverse connection modes between the POM building blocks and Ln linkers and the assembly of new polynuclear metal-oxo clusters. The polyoxoanions of La-1 and Pr-2 possess the same structural feature, which can be viewed as a sandwich-type cluster composed of two {B-β-SbW8O30} units connected by two {WO2(pic)} fragments and two hydrated Ln ions. These sandwich-type polyoxoanions are further linked by the hydrated Ln ions to form a 1-D helical chain. The polyoxoanions of Tb-3, Dy-4 and Ho-5 display the same structural features, although they contain different counter-cations and lattice water molecules. In the polyoxoanions of 3-5, one {B-α-SbW8O31} POM moiety and one {B-α-SbW10O35} POM unit are connected by one {Sb3O4} fragment and one {Ln(pic)} linker, forming an asymmetric sandwich-type metal-oxo cluster. Two of these sandwich-type clusters are further fused together by extra two hydrated Ln ions, leading to an isolated polynuclear metal-oxo cluster with a size of 16.4 × 28.5 Å. The photoluminescence properties of Tb-3 and Dy-4 were investigated. Both compounds exhibit characteristic Tb(3+) and Dy(3+) luminescence. The relationship between the luminescence properties and the crystal structure of the polyoxoanion was discussed.

Three new polyoxometalate(POM)-based polynuclear nickel clusters, Na24[Ni12(OH)9(CO3)3(PO4)(SiW9O34)3]·56H2O (1), Na25[Ni13(H2O)3(OH)9(PO4)4(SiW9O34)3]·50H2O (2), and Na50[Ni25(H2O)2OH)18(CO3)2(PO4)6(SiW9O34)6]·85H2O (3) were synthesized and structurally characterized. Compounds 1-3 contain {Ni12}, {Ni13} and {Ni25} core, respectively, connected by the inorganic {OH}, {PO4} and/or {CO3} linkers and encapsulated by the lacunary A-α-{SiW9O34} POM units. Compound 3 represents the currently largest POM-based Ni clusters. All three compounds contain {Ni3O3} quasi-cubane or {Ni4O4} cubane units, which are similar to the natural oxygen-evolving center {Mn4O5Ca} in photosystem II (PSII). Visible light-driven water oxidation experiments with compounds 1-3 as the homogeneous catalysts indicate that all three compounds show good photocatalytic activities. The O2 evolution amount corresponds to a high TON of 128.2 for 1, 147.6 for 2, and 204.5 for 3, respectively. Multiple experiments including dynamic light-scattering, UV-vis absorption, catalysts aged experiments, tetra-n-heptylammonium nitrate (THpANO3) toluene extraction, and capillary electrophoretic measurements results confirm that compounds 1-3 are dominant active catalysts but not Ni(2+) ions(aq) or nickel oxide under the photocatalytic conditions. The above research results indicate a new and all-inorganic polynuclear Ni-based structural model as the visible light-driven water oxidation catalysts.

Purpose: To compare the feasibility and efficacy of recanalizing below-the-knee (BTK) chronic total occlusions (CTOs) between patients with good or poor distal runoff based on magnetic resonance angiography (MRA) scans., Methods: Two hundred long-segment BTK CTOs in 171 limbs of 113 diabetic patients (58 men; mean age 69.8±1.9 years) were divided into good distal runoff (GDR: 119 lesions, 98 limbs) or poor distal runoff groups (PDR: 81 lesions, 73 limbs) based on baseline MRA findings. After angioplasty, modified thrombolysis in myocardial ischemia (mTIMI) grades and ankle-brachial index (ABI) were used to assess immediate outcomes. Regularly scheduled duplex or MRA imaging was performed in follow-up. The restenosis and limb salvage rates were compared., Results: The success rates were 93.3% and 87.7% in the GDR and PDR groups, respectively (p=0.21); subintimal angioplasty was more common in the PDR group (93.0% vs. 63.1%, p<0.01). Completion angiography indicated an mTIMI grade 3 blood flow in 71.2% lesions in the GDR patients and in 52.1% in the PDR (p=0.01) group. Improvement in the ABI was greater in the GDR limbs (p<0.001 vs. PDR). Mean imaging follow-up was 10.8±6.9 months in the GDR group and 11.1±6.6 months in the PDR group. Kaplan-Meier analysis showed a better restenosis-free rate in the GDR group (80.6% vs. 61.7%; p=0.02) at 12 months and for lesions with mTIMI grade 3 flow (p<0.01). At 24 months, Kaplan-Meier analysis revealed a better limb salvage rate in the GDR group (84.2% vs. 54.6%; p=0.02)., Conclusion: Distal runoff detected using MRA could be a predictor for successful intraluminal recanalization, better distal tissue perfusion, improved long-term patency, and better limb salvage for patients with BTK CTOs., (© The Author(s) 2015.)