bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Reliability of the Joint Tissue Activity and Damage Examination for Quantitation of Structural Abnormalities by Musculoskeletal Ultrasound in Hemophilic Joints
Authors: Volland Lena M. , Zhou Jenny Y. , Barnes Richard F. W. , Kruse‐Jarres Rebecca , Steiner Bruno , Quon Doris V. , Bailey Cindy , Hughes Tudor H. , Moore Randy E. , Chang Eric Y. , von Drygalski Annette 
Published: October 2018

ObjectivesMusculoskeletal ultrasound (US) is used increasingly to examine hemophilic arthropathy. However, quantitative algorithms to document findings are lacking. We developed and sought to validate a protocol quantifying hemophilic joint abnormalities.MethodsThirty‐one patients with hemophilia were examined serially for 2 years with musculoskeletal US (≈600 joint examinations and ≈6000 images). Based on the spectrum of pathologies, a quantitative algorithm, named Joint Tissue Activity and Damage Examination (JADE), was developed for soft tissue and osteochondral measurements, including power Doppler, using nominal group techniques. To study intra‐ and inter‐rater reliability, 8 musculoskeletal US–experienced hemophilia providers performed anatomic landmark recognition and tissue measurements on 86 images with arthropathic changes, with repetition 1 month later. Twenty‐three musculoskeletal US–inexperienced providers performed similar assessments. Inter‐operator reliability was established by 6 musculoskeletal US–experienced hemophilia providers, each acquiring images and JADE assessments of 3 hemophilic arthropathic joints. A radiologist and musculoskeletal sonographer functioned as adjudicators. The statistical analysis was performed with the intraclass correlation coefficient (ICC), Fleiss κ, and Cohen κ where appropriate.ResultsThe musculoskeletal US–experienced providers showed excellent intra‐and inter‐rater reliability for tissue measurements (ICCs, 0.94–0.96). Agreement was good to excellent for landmark recognition (Fleiss κ, 0.87‐0.94). Inter‐operator reliability was excellent for measurements and landmark recognition (ICC, 0.90; Fleiss κ, 1.0). Agreement with adjudicators was mostly good to excellent. Musculoskeletal US–inexperienced providers showed excellent inter‐rater reliability for measurements (ICC, 0.96) and moderate agreement for landmark recognition (Fleiss κ, 0.58).ConclusionsThe JADE protocol appears feasible for quantifying hemophilic intra‐articular abnormalities. Musculoskeletal US–trained hemophilia providers showed high intra‐rater, inter‐rater, and inter‐operator reliability, supporting JADE as a protocol for clinical management and research.
Flattening filter free in intensity‐modulated radiotherapy (IMRT) – Theoretical modeling with delivery efficiency analysis
Authors: Ma Chaoqiong , Chen Mingli , Long Troy , Parsons David , Gu Xuejun , Jiang Steve , Hou Qing , Lu Weiguo 
Published: October 2018

PurposeThe flattening filter (FF) has traditionally been used to flatten beams or create uniform fields in conformal and intensity‐modulated radiation therapy (IMRT) but reduces the dose rate. Many studies have confirmed improvement in delivery efficiency by removing the FF, also known as flattening filter free (FFF), especially for small field stereotactic body radiation therapy (SBRT); but it is unclear if large treatment fields still favor the FFF beam. We propose a novel, unified approach to quantify delivery efficiency of the FFF and flattened beams.MethodsWe modeled the FF effect by inverse conical filters and systematically studied delivery efficiency (beam‐on time, BOT) by varying the filter thickness, including the FF and FFF mode. We formulated the BOT of different beams for any arbitrary fluence map in linear programming to solve the optimal inverse conical filter that minimizes the BOT. One‐dimensional optimal filters of minimum BOT were also derived in closed form for conical fluence to gain insight for arbitrary clinical fluence maps. We evaluated the BOT of the FFF beam and flattened beam for conformal treatment fields of various dimensions ranging from 5 cm × 5 cm to 25 cm × 25 cm. We also analyzed the BOT for 698 clinical IMRT prostate fluence maps of field size 10 cm × 10 cm, 17 head‐and‐neck fluence maps of field size 15 cm × 15 cm, and additional realistic test data from 90° rotation and up to 40 cm × 40 cm enlargement of these clinical fluence maps, which were all initially generated with flattened beams.ResultsThe FFF beam minimized the BOT for A field size less than 20 cm in single leaf pair cases and for conformal fields of dimension less than 20 cm × 20 cm. The FFF beam also minimized the BOT for all tested prostate and head‐and‐neck cases. The median BOT ratios of the FFF beam to the flattened beam were 0.56 and 0.61 for prostate and head‐and‐neck cases, respectively. The FFF beam minimized the BOT for field size up to 30 cm × 30 cm and had similar BOTs to those of the flattened beam for field size greater than 30 cm × 30 cm in those clinically realistic test data.ConclusionThe filter modeling and BOT calculation enable us to quantify delivery efficiency of the FFF beam and flattened beam in a unified approach. The FFF beam minimized the BOT both theoretically and in simulations for all clinically relevant field sizes and fluence maps in IMRT. The results for conformal fields imply that the FFF beam requires less BOT than the flattened beam for volumetric modulated arc therapy (VMAT) treatments. The delivery efficiency consideration favors the FFF beam in intensity‐modulated treatments and may eventually lead to removal of the FF in all future linear accelerator head designs.
Estimating picking errors in near‐surface seismic data to enable their time‐lapse interpretation of hydrosystems
Authors: Dangeard M. , Bodet L. , Pasquet S. , Thiesson J. , Guérin R. , Jougnot D. , Longuevergne L. 
Published: October 2018

ABSTRACTTime‐lapse applications of seismic methods have been recently suggested in the near‐surface scale to track hydrological properties variations due to climate, water level changes, or permafrost thaw, for instance. But when it comes to traveltime tomography or surface‐wave dispersion inversion, a careful estimation of the data variability associated with the picking process must be considered prior to any time‐lapse interpretation. In this study, we propose to estimate picking errors that are due to the inherent subjectivity of human operators, using statistical analysis based on picking repeatability. Two seismic datasets were collected along the same profile under distinct hydrological conditions across a granite–micaschist contact at the Ploemeur hydrological observatory (France). Both datasets were recorded using identical equipment and acquisition parameters. A thorough statistical analysis is conducted to estimate picking uncertainties, at the 99% confidence level, for both P‐wave first arrival time and surface‐wave phase velocity. With the suggested workflow, we are able to identify 33% of the P‐wave traveltimes and 16% of the surface‐wave dispersion data, which can be considered significant enough for time‐lapse interpretations. In this selected portion of the data, point‐by‐point differences highlight important variations linked to different hydrogeological properties of the subsurface. These variations show strong contrasts with a non‐monotonous behaviour along the line, offering new insights to better constrain the dynamics of this hydrosystem.
GASP and FASP are Complementary for LC–MS/MS Proteomic Analysis of Drug‐Metabolizing Enzymes and Transporters in Pig Liver
Authors: Howard Martyn , Achour Brahim , Al‐Majdoub Zubida , Rostami‐Hodjegan Amin , Barber Jill 
Published: October 2018

AbstractSample preparation is a critical step in the proteomic workflow. Numerous different approaches are used, tailored to the type of sample, the aims of the experiment, analytical method, and to an extent, user preference. This has resulted in large variation in reported protein abundances. In this study, the complementarity of two different sample preparation techniques is demonstrated for the study of absorption, distribution, metabolism, and excretion (ADME) related proteins from pig liver tissue. Filter‐aided sample preparation (FASP) is a well‐established and widely used method, while gel‐aided sample preparation (GASP) is a relatively new method optimized and simplified from previous gel‐associated digestion techniques. To investigate each method, the number of peptides and proteins characterized, reproducibility of results, and their real‐time application are examined. While both methods have their merits and limitations, for example, FASP is the less technical of the two methods, while GASP is time efficient, ultimately the two methods show significant differences in the peptides identified and therefore, the use of both methods should be considered when examining and quantifying ADME related proteins. Data are available via ProteomeXchange with identifier PXD011324.
SAXSMoW 2.0: Online calculator of the molecular weight of proteins in dilute solution from experimental SAXS data measured on a relative scale
Authors: Piiadov Vassili , Ares de Araújo Evandro , Oliveira Neto Mario , Craievich Aldo Felix , Polikarpov Igor 
Published: October 2018

AbstractKnowledge of molecular weight, oligomeric states, and quaternary arrangements of proteins in solution is fundamental for understanding their molecular functions and activities. We describe here a program SAXSMoW 2.0 for robust and quick determination of molecular weight and oligomeric state of proteins in dilute solution, starting from a single experimental small‐angle scattering intensity curve, I(q), measured on a relative scale. The first version of this calculator has been widely used during the last decade and applied to analyze experimental SAXS data of many proteins and protein complexes. SAXSMoW 2.0 exhibits new features which allow for the direct input of experimental intensity curves and also automatic modes for quick determinations of the radius of gyration, volume, and molecular weight. The new program was extensively tested by applying it to many experimental SAXS curves downloaded from the open databases, corresponding to proteins with different shapes and molecular weights ranging from ~10 kDa up to about ~500 kDa and different shapes from globular to elongated. These tests reveal that the use of SAXSMoW 2.0 allows for determinations of molecular weights of proteins in dilute solution with a median discrepancy of about 12% for globular proteins. In case of elongated molecules, discrepancy value can be significantly higher. Our tests show discrepancies of approximately 21% for the proteins with molecular shape aspect ratios up to 18.
Tyrosine kinase inhibitor therapy prescribed for non‐urologic diseases can modify PSA titers in urology patients
Authors: Sasaki Takeshi , Franco Omar E. , Ohishi Kohshi , Filipovich Yana , Ishii Kenichiro , Crawford Susan E. , Takahashi Naoto , Katayama Naoyuki , Sugimura Yoshiki , Hayward Simon W. 
Published: October 2018

BackgroundThe tyrosine kinase inhibitors (TKI), imatinib and nilotinib, are used to treat chronic myelogenous leukemia (CML). In three CML patients being monitored for urologic diseases, we observed that switching of TKI therapy affected prostate‐specific antigen (PSA) titers. Urologists and other medical professionals need to be aware of the potential side‐effects of drugs that patients may be receiving for other indications to modify this important prostate diseases indicator. TKIs may affect PSA titers independent of prostate growth or volume.Materials and MethodsWe followed PSA levels in urology patients who were also undergoing TKI treatment for CML. We determined the effects of nilotinib and imatinib on proliferation, AR and PSA expression in the LNCaP and 22Rv1 prostate cancer (PCa) cell lines using real‐time PCR and Western blotting.ResultsClinically, nilotinib and dasatinib reversibly reduced PSA titers compared to imatinib. At high doses nilotinib and imatinib both demonstrated antiproliferative effects in the PCa cells. At low doses expression of AR and PSA was decreased by both drugs, at mRNA and protein levels. Nilotinib exerted greater effects at lower doses than imatinib.ConclusionsNilotinib down‐regulates serum PSA in patients being treated for non‐urological indications, potentially masking a clinical useful marker, we cannot exclude a similar but smaller effect of imatinib. Nilotinib and imatinib both decreased AR and PSA expression in PCa cell lines with the nilotinib effect evident at lower doses. Urologists must appreciate the effects of drugs provided for other diseases on PSA titers and be aware that sudden changes may not reflect underlying prostatic disease.
Molecular cloning and characterization of TRPVs in two rice pests: Nilaparvata lugens (Stål) and Nephotettix cincticeps (Uhler)
Authors: Mao Fen , Guo Lei , Jin Miao , Qiao Xiao‐mu , Ye Gong‐yin , Huang Jia 
Published: October 2018

AbstractBACKGROUDInsect TRPV is a subfamily of transient receptor potential (TRP) ion channels, including two genes, nanchung and inactive. It has recently been found that two commercial insecticides, pymetrozine and pyrifluquinazon, target the heteromeric TRPV ion channel complex which is specifically expressed in the chordotonal organ neurons in Drosophila. However, information on the TRPV genes in agricultural insects is still limited.RESULTSIn this study, we cloned and characterized two TRPV genes from Nilaparvata lugens (NlNan and NLIav) and Nephotettix cincticeps (NcNan and NcIav), two serious rice pests throughout Asia. The deduced amino acid sequences share highly identity with other insect homologues (58–85%) and have the characteristic TRPV domain architecture: five ankyrin repeats and six transmembrane domains. These TRPV transcripts were expressed in all developmental stages and expression levels in male adults were significantly higher than in female adults. Moreover, expression levels in antennae were much higher than in heads and legs.CONCLUSIONNlNan, NlIav, NcNan and NcIav may have roles in male‐specific behaviors, and the sequence information lays the foundation for further study on the structural and functional characterization of TRPVs in agricultural pests. © 2018 Society of Chemical Industry
Strategies for composite estimands in confirmatory clinical trials: Examples from trials in nasal polyps and steroid reduction
Authors: Keene Oliver N. 
Published: October 2018

SummaryThe draft addendum to the ICH E9 regulatory guideline asks for explicit definition of the treatment effect to be estimated in clinical trials. The draft guideline also introduces the concept of intercurrent events to describe events that occur post‐randomisation that may affect efficacy assessment. Composite estimands allow incorporation of intercurrent events in the definition of the endpoint. A common example of an intercurrent event is discontinuation of randomised treatment and use of a composite strategy would assess treatment effect based on a variable that combines the outcome variable of interest with discontinuation of randomised treatment. Use of a composite estimand may avoid the need for imputation which would be required by a treatment policy estimand. The draft guideline gives the example of a binary approach for specifying a composite estimand. When the variable is measured on a non‐binary scale, other options are available where the intercurrent event is given an extreme unfavourable value, for example comparison of median values or analysis based on categories of response. This paper reviews approaches to deriving a composite estimand and contrasts the use of this estimand to the treatment policy estimand. The benefits of using each strategy are discussed and examples of the use of the different approaches are given for a clinical trial in nasal polyposis and a steroid reduction trial in severe asthma.
Can cytoplasmic donation rescue aged oocytes?
Authors: Tanaka Atsushi , Watanabe Seiji 
Published: October 2018

AbstractBackgroundThe pregnancy and delivery rates following assisted reproductive technology (ART) start to decrease and that the miscarriage rate increases rapidly from 35 years old. The miscarriage rate exceeds 50% at 43 years old. The number of aneuploid fetuses in miscarriages increases according to female age, reaching more than 90% when women are over 40 years old.MethodsDifferent cytoplasmic donation technologies used to rescue aged oocytes with high percentage of aneuploidy were analyzed, and their efficacy compared.Main findings (Results)Germinal vesicle transfer (GVT) might be superior to spindle chromosome transfer (ST) theoretically from the point of higher capability of rescuing the disjunction at meiosis I which cannot be helped by ST. However, actually, in vitro maturation (IVM) of oocyte after GVT has not yet been totally completed. ST among other nuclear donations showed the higher possibility to rescue them, due to the fact it does not require in vitro maturation and it has an ethical advantage over pronuclear transfer (PNT) which requires the destruction of an embryo.ConclusionSpindle chromosome transfer has the potential to rescue aged oocytes to some extent, but we have to continue the basic study further to establish the clinical application of cytoplasmic donation to rescue aged oocytes.
Robust fault and icing diagnosis in unmanned aerial vehicles using LPV interval observers
Authors: Rotondo Damiano , Cristofaro Andrea , Johansen Tor Arne , Nejjari Fatiha , Puig Vicenç 
Published: October 2018

SummaryThis paper proposes a linear parameter varying (LPV) interval unknown input observer for the robust fault diagnosis of actuator faults and ice accretion in unmanned aerial vehicles (UAVs) described by an uncertain model. The proposed interval observer evaluates the set of values for the state, which are compatible with the nominal fault‐free and icing‐free operation and can be designed in such a way that some information about the nature of the unknown inputs affecting the system can be obtained, thus allowing the diagnosis to be performed. The proposed strategy has several advantages. First, the LPV paradigm allows taking into account operating point variations. Second, the noise rejection properties are enhanced by the presence of the integral term. Third, the interval estimation property guarantees the absence of false alarms. Linear matrix inequality–based conditions for the analysis/design of these observers are provided in order to guarantee the interval estimation of the state and the boundedness of the estimation. The developed theory is supported by simulation results, obtained with the uncertain model of a Zagi Flying Wing UAV, which illustrate the strong appeal of the methodology for identifying correctly unexpected changes in the system dynamics due to actuator faults or icing.
Sphere–Tubule Superstructures through Supramolecular and Supracolloidal Assembly Pathways
Authors: Cautela J. , Lattanzi V. , Månsson L. K. , Galantini L. , Crassous J. J. 
Published: October 2018

AbstractWhile colloids have been widely employed as models for atoms and molecules, the current study proposes to extend their use as building blocks for supracolloidal frameworks. Hereby, the self‐assembly between highly anisotropic supramolecular microtubules and soft spherical fluorescent microgels is explored using confocal laser scanning microscopy. The influence of the particle size and charge with respect to the catanionic tubule composition, which consists of two oppositely charged bile salt derivatives, is investigated. Under certain conditions, microgel particles are found to specifically interact with the extremities of the tubular aggregates and hierarchically self‐assemble into various superstructures varying from virus‐like assemblies to supracolloidal networks. The reported approach is envisioned to open new self‐assembly routes toward ordered hybrid superstructures where the spherical colloids act as responsive linkers of tubular structures.
Efficient Inverted Perovskite Solar Cells by Employing N‐Type (D–A1–D–A2) Polymers as Electron Transporting Layer
Authors: Said Ahmed Ali , Xie Jian , Wang Yang , Wang Zongrui , Zhou Yu , Zhao Kexiang , Gao Wei‐Bo , Michinobu Tsuyoshi , Zhang Qichun 
Published: October 2018

AbstractIt is highly desirable to employ n‐type polymers as electron transporting layers (ETLs) in inverted perovskite solar cells (PSCs) due to their good electron mobility, high hydrophobicity, and simplicity of film forming. In this research, the capability of three n‐type donor–acceptor1–donor–acceptor2 (D–A1–D–A2) conjugated polymers (pBTT, pBTTz, and pSNT) is first explored as ETLs because these polymers possess electron mobilities as high as 0.92, 0.46, and 4.87 cm2 (Vs)−1 in n‐channel organic transistors, respectively. The main structural difference among pBTT, pBTTz, and pSNT is the position of sp2‐nitrogen atoms (sp2‐N) in the polymer main chains. Therefore, the effect of different substitution positions on the PSC performances is comprehensively studied. The as‐fabricated p–i–n PSCs with pBTT, pBTTz, and pSNT as ETLs show the maximum photoconversion efficiencies of 12.8%, 14.4%, and 12.0%, respectively. To be highlighted, pBTTz‐based device can maintain 80% of its stability after ten days due to its good hydrophobicity, which is further confirmed by a contact angle technique. More importantly, the pBTTz‐based device shows a neglected hysteresis. This study reveals that the n‐type polymers can be promising candidates as ETLs to approach solution‐processed highly‐efficient inverted PSCs.
Improving Gene Editing Outcomes in Human Hematopoietic Stem and Progenitor Cells by Temporal Control of DNA Repair
Authors: Lomova Anastasia , Clark Danielle N. , Campo-Fernandez Beatriz , Flores-Bjurström Carmen , Kaufman Michael L. , Fitz-Gibbon Sorel , Wang Xiaoyan , Miyahira Eric Y. , Brown Devin , DeWitt Mark A. , Corn Jacob E. , Hollis Roger P. , Romero Zulema , Kohn Donald B. 
Published: October 2018

Abstract
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated system (Cas9)-mediated gene editing of human hematopoietic stem cells (hHSCs) is a promising strategy for the treatment of genetic blood diseases through site-specific correction of identified causal mutations. However, clinical translation is hindered by low ratio of precise gene modification using the corrective donor template (homology-directed repair, HDR) to gene disruption (nonhomologous end joining, NHEJ) in hHSCs. By using a modified version of Cas9 with reduced nuclease activity in G1 phase of cell cycle when HDR cannot occur, and transiently increasing the proportion of cells in HDR-preferred phases (S/G2), we achieved a four-fold improvement in HDR/NHEJ ratio over the control condition in vitro, and a significant improvement after xenotransplantation of edited hHSCs into immunodeficient mice. This strategy for improving gene editing outcomes in hHSCs has important implications for the field of gene therapy, and can be applied to diseases where increased HDR/NHEJ ratio is critical for therapeutic success. Stem Cells 2019;37:284–294