bluuebunny/crossref_metadata_2025_split huggingface dataset:
Choice of appropriate beam model and gantry rotational angle for low-dose gradient-based craniospinal irradiation using volumetric-modulated arc therapy
Authors: Sarkar Biplab , Pradhan Anirudh 
Published: November 2016

AbstractObjectivesWe aimed to assess the impact of advanced multileaf collimator (MLC) models and flattening filter-free (3F) beam in volumetric-modulated arc therapy (VMAT)-based craniospinal irradiation (CSI).MethodsCT scans of five medulloblastoma patients who previously received CSI at our hospital were used for the present study. Patients were planned for a prescription dose of 35 Gy to craniospinal axis. A three-dimensional conformal radiotherapy (3DCRT) plan and a VMAT plan using 1 cm MLC leaf width were generated as the gold standard (reference arm). Test VMAT plans were generated using Agility MLC model (MLC leaf width 5 mm) for various combinations of flattened beam (F) and 3F beam for treating the brain and spine planning target volume (PTV). Organs at risks (OARs) were analysed for dose 5, 50, 75 and 90% volumes, mean dose and maximum dose.ResultsAll 3DCRT plans and VMAT plans were aimed to cover 95% of PTV by at least 95% prescription dose. VMAT demonstrated lesser dose spillage than 3DCRT to body volume minus PTV (NTID: non tumor integral dose) for a dose threshold above 7·5 Gy. For the low-dose range (1–7 Gy), variation between the dose coverage between all VMAT plans (for either spine or brain PTV) was <1%. Intra-VMAT plan dose variation for all OAR’s for all tested parameters was <1 Gy. Average monitor unit (MU) difference among different VMAT plans ranged between 1·52 and 2·13 when normalised to 3DCRT MU. For VMAT plans, flat beam with 1 cm MLC showed the highest MU, whereas Agility MLC with 3F beam had the least MU values for intra-VMAT plans. No statistical significance variation (p) was observed in between reference arm and test arm plans except for mean dose and V107% for PTV spine. When compared between reference arm 3DCRT and test arm VMAT plans. For OAR’s, no statistical difference was observed between reference and test arm VMAT plans.ConclusionsReference arm plans and test arm plans exhibit no statistically significant difference. However, as compared with 3DCRT, VMAT plans are more conformal and produce lesser dose to OAR at the cost of higher delivered MU. 3F beams or finer width MLC’s (width <5 mm) have no advantage over the conventional 1 cm MLC and flat beam except that 3F beams have a shorter beam delivery time. This study demonstrate a significantly lesser spillage dose to NTID/body that of the reported literature, which is attributed to limited rotational arc length used for VMAT plans.
Coinhibition of the deubiquitinating enzymes, USP14 and UCHL5, with VLX1570 is lethal to ibrutinib- or bortezomib-resistant Waldenstrom macroglobulinemia tumor cells
Authors: Paulus A , Akhtar S , Caulfield T R , Samuel K , Yousaf H , Bashir Y , Paulus S M , Tran D , Hudec R , Cogen D , Jiang J , Edenfield B , Novak A , Ansell S M , Witzig T , Martin P , Coleman M , Roy V , Ailawadhi S , Chitta K , Linder S , Chanan-Khan A 
Published: November 2016

AbstractThe survival of Waldenstrom macroglobulinemia (WM) tumor cells hinges on aberrant B-cell receptor (BCR) and MYD88 signaling. WM cells upregulate the proteasome function to sustain the BCR-driven growth while maintaining homeostasis. Clinically, two treatment strategies are used to disrupt these complementary yet mutually exclusive WM survival pathways via ibrutinib (targets BTK/MYD88 node) and bortezomib (targets 20 S proteasome). Despite the success of both agents, WM patients eventually become refractory to treatment, highlighting the adaptive plasticity of WM cells and underscoring the need for development of new therapeutics. Here we provide a comprehensive preclinical report on the anti-WM activity of VLX1570, a novel small-molecule inhibitor of the deubiquitinating enzymes (DUBs), ubiquitin-specific protease 14 (USP14) and ubiquitin carboxyl-terminal hydrolase isozyme L5 (UCHL5). Both DUBs reside in the 19 S proteasome cap and their inhibition by VLX1570 results in rapid and tumor-specific apoptosis in bortezomib- or ibrutinib-resistant WM cells. Notably, treatment of WM cells with VLX1570 downregulated BCR-associated elements BTK, MYD88, NFATC, NF-κB and CXCR4, the latter whose dysregulated function is linked to ibrutinib resistance. VLX1570 administered to WM-xenografted mice resulted in decreased tumor burden and prolonged survival (P=0.0008) compared with vehicle-treated mice. Overall, our report demonstrates significant value in targeting USP14/UCHL5 with VLX1570 in drug-resistant WM and carries a high potential for clinical translation.
Vital staining for cell death identifies Atg9a-dependent necrosis in developmental bone formation in mouse
Authors: Imagawa Yusuke , Saitoh Tatsuya , Tsujimoto Yoshihide 
Published: November 2016

AbstractProgrammed cell death has a crucial role in various biological events, including developmental morphogenesis. Recent evidence indicates that necrosis contributes to programmed cell death in addition to apoptosis, but it is unclear whether necrosis acts as a compensatory mechanism for failure of apoptosis or has an intrinsic role during development. In contrast to apoptosis, there have been no techniques for imaging physiological necrosis in vivo. Here we employ vital staining using propidium iodide to identify cells with plasma membrane disruption (necrotic cells) in mouse embryos. We discover a form of necrosis at the bone surface, which does not occur in embryos with deficiency of the autophagy-related gene Atg9a, although it is unaffected by Atg5 knockout. We also find abnormalities of the bone surface in Atg9a knockout mice, suggesting an important role of Atg9a-dependent necrosis in bone surface formation. These findings suggest that necrosis has an active role in developmental morphogenesis.
Differential Canalograms Detect Outflow Changes from Trabecular Micro-Bypass Stents and Ab Interno Trabeculectomy
Authors: Parikh Hardik A. , Loewen Ralitsa T. , Roy Pritha , Schuman Joel S. , Lathrop Kira L. , Loewen Nils A. 
Published: November 2016

AbstractRecently introduced microincisional glaucoma surgeries that enhance conventional outflow offer a favorable risk profile over traditional surgeries, but can be unpredictable. Two paramount challenges are the lack of an adequate training model for angle surgeries and the absence of an intraoperative quantification of surgical success. To address both, we developed an ex vivo training system and a differential, quantitative canalography method that uses slope-adjusted fluorescence intensities of two different chromophores to avoid quenching. We assessed outflow enhancement by trabecular micro-bypass (TMB) implantation or by ab interno trabeculectomy (AIT). In this porcine model, TMB resulted in an insignificant (p > 0.05) outflow increase of 13 ± 5%, 14 ± 8%, 9 ± 3%, and 24 ± 9% in the inferonasal, superonasal, superotemporal, and inferotemporal quadrant, respectively. AIT caused a 100 ± 50% (p = 0.002), 75 ± 28% (p = 0.002), 19 ± 8%, and 40 ± 21% increase in those quadrants. The direct gonioscopy and tactile feedback provided a surgical experience that was very similar to that in human patients. Despite the more narrow and discontinuous circumferential drainage elements in the pig with potential for underperformance or partial stent obstruction, unequivocal patterns of focal outflow enhancement by TMB were seen in this training model. AIT achieved extensive access to outflow pathways beyond the surgical site itself.
Hydrogen separation through tailored dual phase membranes with nominal composition BaCe0.8Eu0.2O3-δ:Ce0.8Y0.2O2-δ at intermediate temperatures
Authors: Ivanova Mariya E. , Escolástico Sonia , Balaguer Maria , Palisaitis Justinas , Sohn Yoo Jung , Meulenberg Wilhelm A. , Guillon Olivier , Mayer Joachim , Serra Jose M. 
Published: November 2016

AbstractHydrogen permeation membranes are a key element in improving the energy conversion efficiency and decreasing the greenhouse gas emissions from energy generation. The scientific community faces the challenge of identifying and optimizing stable and effective ceramic materials for H2 separation membranes at elevated temperature (400–800 °C) for industrial separations and intensified catalytic reactors. As such, composite materials with nominal composition BaCe0.8Eu0.2O3-δ:Ce0.8Y0.2O2-δ revealed unprecedented H2 permeation levels of 0.4 to 0.61 mL·min−1·cm−2 at 700 °C measured on 500 μm-thick-specimen. A detailed structural and phase study revealed single phase perovskite and fluorite starting materials synthesized via the conventional ceramic route. Strong tendency of Eu to migrate from the perovskite to the fluorite phase was observed at sintering temperature, leading to significant Eu depletion of the proton conducing BaCe0.8Eu0.2O3-δ phase. Composite microstructure was examined prior and after a variety of functional tests, including electrical conductivity, H2-permeation and stability in CO2 containing atmospheres at elevated temperatures, revealing stable material without morphological and structural changes, with segregation-free interfaces and no further diffusive effects between the constituting phases. In this context, dual phase material based on BaCe0.8Eu0.2O3-δ:Ce0.8Y0.2O2-δ represents a very promising candidate for H2 separating membrane in energy- and environmentally-related applications.
Association of LRRK2 R1628P variant with Parkinson’s disease in Ethnic Han-Chinese and subgroup population
Authors: Zhang Pei , Wang Qingzhi , Jiao Fengjuan , Yan Jianguo , Chen Lijun , He Feng , Zhang Qian , Tian Bo 
Published: November 2016

AbstractRecent studies have linked certain single nucleotide polymorphisms in the leucine-rich repeat kinase 2 (LRRK2) gene with Parkinson’s disease (PD). The R1628P variant of LRRK2 may be a specific risk factor for PD in ethnic Han-Chinese populations. This study is to elucidate the epidemiological feature of R1628P in ethnic Han-Chinese population with PD. A comprehensive meta-analysis was performed to evaluate the precise association between R1628P variant and the risk for PD in ethnic Han-Chinese and subgroups stratified by gender, onset age, or family history. The analysis assessing the role of R1628P on the risk of PD in ethnic Han-Chinese supported a significant association, and the odds ratio was 1.86. We further estimate the specific prevalence in relevant ethnic Han-Chinese subgroups. After stratifying the eligible data by gender, onset age, or family history, significant associations were found in all male, female, early-onset, late-onset, familial and sporadic subgroups, and the odds ratio were 1.90, 1.94, 2.12, 1.75, 6.71 and 1.81 respectively. In conclusion, our meta-analysis suggests that R1628P variant of LRRK2 has a significant association with the risk of PD in ethnic Han-Chinese and subgroup population.
IL-25 attenuates rheumatoid arthritis through suppression of Th17 immune responses in an IL-13-dependent manner
Authors: Liu Dan , Cao Tuanping , Wang Na , Liu Chengfei , Ma Ning , Tu Ran , Min Xiaoyun 
Published: November 2016

AbstractIL-25, a new member of the IL-17 cytokine family, is involved in type 2 immunity initiation and has been associated with the pathogenesis of rheumatoid arthritis (RA). However, its exact role remains unclear. Here, we aimed to analyse IL-25 expression in the serum and synovial fluid of RA patients and evaluated the correlations between serum IL-25 levels, clinical and laboratory values and inflammation cytokines. Additionally, we investigated whether IL-25 can suppress Th1/Th17 responses involved in RA pathogenesis. We further determined whether IL-25 can alleviate collagen-induced arthritis (CIA) development in mice and the underlying mechanisms using in vitro and in vivo experiments. Our results showed that IL-25 was upregulated in the serum and synovial fluid of RA patients. Increased serum IL-25 levels were associated with disease severity and inflammatory response in RA patients. Furthermore, IL-25 inhibited CD4+ T-cell activation and differentiation into Th17 cells, without affecting Th1 cells in human RA and CIA models. Administration of IL-25 could attenuate CIA development by Th17 suppression in an IL-13-dependent manner. Our findings indicate that IL-25 plays a potent immunosuppressive role in the pathogenesis of RA and CIA by downregulating Th17 cell response, and thus, may be a potential therapeutic agent for RA.
Very Short Mitochondrial DNA Fragments and Heteroplasmy in Human Plasma
Authors: Zhang Ruoyu , Nakahira Kiichi , Guo Xiaoxian , Choi Augustine M.K. , Gu Zhenglong 
Published: November 2016

AbstractCell free DNA (cfDNA) has received increasing attention and has been studied in a broad range of clinical conditions. However, few studies have focused on mitochondrial DNA (mtDNA) in the cell free form. We optimized DNA isolation and sequencing library preparation protocols to better retain short DNA fragments from plasma, and applied these optimized methods to plasma samples from patients with sepsis. Our methods can retain substantially shorter DNA, resulting in an average of 11.5 fold increase in short DNA fragments yield (DNA <100bp). We report that cf-mtDNA in plasma is highly enriched in short-size cfDNA (30~60 bp). Motivated by this unique size distribution, we size-selected short cfDNA, which further increased the mtDNA recovery rate by an average of 10.4 fold. We then detected mtDNA heteroplasmy in plasma from 3 patients. In one patient who previously received bone marrow transplantation, different minor allele frequencies were observed between plasma and leukocytes at heteroplasmic sites, consistent with mixed-tissue origin for cfDNA. For the other two patients, the heteroplasmy pattern is also different between plasma and leukocyte. Our study shed new lights into the architecture of the cfDNA, and mtDNA heteroplasmy identified in plasma provides new potential for biomarker discovery.
Membrane glycerolipidome of soybean root hairs and its response to nitrogen and phosphate availability
Authors: Wei Fang , Fanella Brian , Guo Liang , Wang Xuemin 
Published: November 2016

AbstractRoot hairs are tubular extensions of specific root epidermal cells important in plant nutrition and water absorption. To determine membrane glycerolipids in root hairs and roots may differ, as well as their respective response to nutrient availability, this study analyzed the membrane glycerolipid species in soybean root hairs and in roots stripped of root hairs, and their response to nitrogen (N) and phosphate (Pi) supplementation. The ratio of phospholipids to galactolipids was 1.5 fold higher in root hairs than in stripped roots. Under Pi deficiency, the ratio of phospholipids to galactolipids in stripped roots decreased with the greatest decrease found in the level of phosphatidylethanolamine (PE) in root hairs and stripped roots, and root hairs had an increased level of phosphatidic acid (PA). When seedlings were not supplied with N, the level of the N-containing lipids PE and phosphatidylserine in root hairs decreased whereas the level of non-N-containing lipids galactolipids and PA increased compared to N-supplied conditions. In stripped roots, the level of major membrane lipids was not different between N-sufficient and -deficient conditions. The results indicate that the membrane glycerolipidomes in root hairs are more responsive to nutrient availability than are the rest of roots.
In Vivo Bioluminescence Tomography for Monitoring Breast Tumor Growth and Metastatic Spreading: Comparative Study and Mathematical Modeling
Authors: Mollard Séverine , Fanciullino Raphaelle , Giacometti Sarah , Serdjebi Cindy , Benzekry Sebastien , Ciccolini Joseph 
Published: November 2016

AbstractThis study aimed at evaluating the reliability and precision of Diffuse Luminescent Imaging Tomography (DLIT) for monitoring primary tumor and metastatic spreading in breast cancer mice, and to develop a biomathematical model to describe the collected data. Using orthotopic mammary fat pad model of breast cancer (MDAMB231-Luc) in mice, we monitored tumor and metastatic spreading by three-dimensional (3D) bioluminescence and cross-validated it with standard bioluminescence imaging, caliper measurement and necropsy examination. DLIT imaging proved to be reproducible and reliable throughout time. It was possible to discriminate secondary lesions from the main breast cancer, without removing the primary tumor. Preferential metastatic sites were lungs, peritoneum and lymph nodes. Necropsy examinations confirmed DLIT measurements. Marked differences in growth profiles were observed, with an overestimation of the exponential phase when using a caliper as compared with bioluminescence. Our mathematical model taking into account the balance between living and necrotic cells proved to be able to reproduce the experimental data obtained with a caliper or DLIT imaging, because it could discriminate proliferative living cells from a more composite mass consisting of tumor cells, necrotic cell, or inflammatory tissues. DLIT imaging combined with mathematical modeling could be a powerful and informative tool in experimental oncology.
Resistive Switching in All-Printed, Flexible and Hybrid MoS2-PVA Nanocomposite based Memristive Device Fabricated by Reverse Offset
Authors: Rehman Muhammad Muqeet , Siddiqui Ghayas Uddin , Gul Jahan Zeb , Kim Soo-Wan , Lim Jong Hwan , Choi Kyung Hyun 
Published: November 2016

AbstractOwing to the increasing interest in the nonvolatile memory devices, resistive switching based on hybrid nanocomposite of a 2D material, molybdenum disulphide (MoS2) and polyvinyl alcohol (PVA) is explored in this work. As a proof of concept, we have demonstrated the fabrication of a memory device with the configuration of PET/Ag/MoS2-PVA/Ag via an all printed, hybrid, and state of the art fabrication approach. Bottom Ag electrodes, active layer of hybrid MoS2-PVA nanocomposite and top Ag electrode are deposited by reverse offset, electrohydrodynamic (EHD) atomization and electrohydrodynamic (EHD) patterning respectively. The fabricated device displayed characteristic bistable, nonvolatile and rewritable resistive switching behavior at a low operating voltage. A decent off/on ratio, high retention time, and large endurance of 1.28 × 102, 105 sec and 1000 voltage sweeps were recorded respectively. Double logarithmic curve satisfy the trap controlled space charge limited current (TCSCLC) model in high resistance state (HRS) and ohmic model in low resistance state (LRS). Bendability test at various bending diameters (50-2 mm) for 1500 cycles was carried out to show the mechanical robustness of fabricated device.
The mutation p.E113K in the Schiff base counterion of rhodopsin is associated with two distinct retinal phenotypes within the same family
Authors: Reiff Charlotte , Owczarek-Lipska Marta , Spital Georg , Röger Carsten , Hinz Hebke , Jüschke Christoph , Thiele Holger , Altmüller Janine , Nürnberg Peter , Da Costa Romain , Neidhardt John 
Published: November 2016

AbstractThe diagnoses of retinitis pigmentosa (RP) and stationary night blindness (CSNB) are two distinct clinical entities belonging to a group of clinically and genetically heterogeneous retinal diseases. The current study focused on the identification of causative mutations in the RP-affected index patient and in several members of the same family that reported a phenotype resembling CSNB. Ophthalmological examinations of the index patient confirmed a typical form of RP. In contrast, clinical characterizations and ERGs of another affected family member showed the Riggs-type CSNB lacking signs of RP. Applying whole exome sequencing we detected the non-synonymous substitution c.337G > A, p.E113 K in the rhodopsin (RHO) gene. The mutation co-segregated with the diseases. The identification of the pathogenic variant p.E113 K is the first description of a naturally-occurring mutation in the Schiff base counterion of RHO in human patients. The heterozygous mutation c.337G > A in exon 1 was confirmed in the index patient as well as in five CSNB-affected relatives. This pathogenic sequence change was excluded in a healthy family member and in 199 ethnically matched controls. Our findings suggest that a mutation in the biochemically well-characterized counterion p.E113 in RHO can be associated with RP or Riggs-type CSNB, even within the same family.
Dynamically sculpturing plasmonic vortices: from integer to fractional orbital angular momentum
Authors: Wang Yu , Zhao Peng , Feng Xue , Xu Yuntao , Liu Fang , Cui Kaiyu , Zhang Wei , Huang Yidong 
Published: November 2016

AbstractAs a fundamental tool for light-matter interactions, plasmonic vortex (PV) is extremely useful due to the unique near field property. However, it is a pity that, up to now, the orbital angular momentum (OAM) carried by PVs could not be dynamically and continuously tuned in practice as well as the properties of fractional PVs are still not well investigated. By comparing with two previously reported methods, it is suggested that our proposal of utilizing the propagation induced radial phase gradient of incident Laguerre-Gaussian (LG) beam is a promising candidate to sculpture PVs from integer to fractional OAM dynamically. Consequently, the preset OAM of PVs could have four composing parts: the incident spin and orbital angular momentum, the geometric contribution of chiral plasmonic structure, and the radial phase gradient dependent contribution. Moreover, an analytical expression for the fractional PV is derived as a linear superposition of infinite numbers of integer PVs described by Bessel function of the first kind. It is also shown that the actual mean OAM of a fractional PV would deviate from the preset value, which is similar with previous results for spatial fractional optical vortices.
EGFR tyrosine kinase inhibitors versus chemotherapy as first-line therapy for non-small cell lung cancer patients with the L858R point mutation
Authors: Xu Jianlin , Yang Haitang , Jin Bo , Lou Yuqing , Zhang Yanwei , Zhang Xueyan , Zhong Hua , Wang Huiming , Wu Dan , Han Baohui 
Published: November 2016

AbstractThe efficacy of EGFR tyrosine kinase inhibitors (TKIs) varies among different EGFR mutations. Here, we directly compared the efficacy of first-line TKIs to chemotherapy for non-small cell lung cancer (NSCLC) patients with the L858R mutation. The progression-free survival (PFS) for patients receiving TKIs as first-line therapy was longer than those who received chemotherapy (hazard ratio [HR]: 0.44, P < 0.001). Subgroup analyses showed that first-line TKI therapy resulted in longer PFS among non-smokers (HR: 0.41, P < 0.001), male (HR: 0.49, P = 0.002), female (HR: 0.39, P < 0.001), and patients with adenocarcinoma histology (HR: 0.41, P < 0.001). However, among patients with non-adenocarcinoma histology (HR: 1.11, P = 0.824) and those who used to smoke (HR: 0.55, P = 0.093), first-line TKI therapy failed to demonstrate statistically longer PFS compared to chemotherapy. Our results demonstrated that for patients with L858R mutation, first-line TKI therapy provided better survival benefits. However, among non-adenocarcinoma patients and those who used to smoke, the PFS in cohorts receiving first-line chemotherapy or TKI were not significantly different. The results of the current study will be helpful for decision-making in the treatment of patients with L858R mutation.