bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intra-arterial thrombolytics during endovascular thrombectomy for acute ischaemic stroke in the MR CLEAN Registry
Authors: Collette Sabine L , Bokkers Reinoud P H , Mazuri Aryan , Lycklama à Nijeholt Geert J , van Oostenbrugge Robert J , LeCouffe Natalie E , Benali Faysal , Majoie Charles B L M , de Groot Jan Cees , Luijckx Gert Jan R , Uyttenboogaart Maarten 
Published: August 2022

IntroductionThe efficacy and safety of local intra-arterial (IA) thrombolytics during endovascular thrombectomy (EVT) for large-vessel occlusions is uncertain. We analysed how often IA thrombolytics were administered in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry, whether it was associated with improved functional outcome and assessed technical and safety outcomes compared with EVT without IA thrombolytics.MethodsIn this observational study, we included patients undergoing EVT for an acute ischaemic stroke in the anterior circulation from the MR CLEAN Registry (March 2014–November 2017). The primary endpoint was favourable functional outcome, defined as an modified Rankin Scale score ≤2 at 90 days. Secondary endpoints were reperfusion status, early neurological recovery and symptomatic intracranial haemorrhage (sICH). Subgroup analyses for IA thrombolytics as primary versus adjuvant revascularisation attempt were performed.ResultsOf the 2263 included patients, 95 (4.2%) received IA thrombolytics during EVT. The IA thrombolytics administered were urokinase (median dose, 250 000 IU (IQR, 1 93 750–2 50 000)) or alteplase (median dose, 20 mg (IQR, 12–20)). No association was found between IA thrombolytics and favourable functional outcome (adjusted OR (aOR), 1.16; 95% CI 0.71 to 1.90). Successful reperfusion was less often observed in those patients treated with IA thrombolytics (aOR, 0.57; 95% CI 0.36 to 0.90). The odds of sICH (aOR, 0.82; 95% CI 0.32 to 2.10) and early neurological recovery were comparable between patients treated with and without IA thrombolytics. For primary and adjuvant revascularisation attempts, IA thrombolytics were more often administered for proximal than for distal occlusions. Functional outcomes were comparable for patients receiving IA thrombolytics as a primary versus adjuvant revascularisation attempt.ConclusionLocal IA thrombolytics were rarely used in the MR CLEAN Registry. In the relatively small study sample, no statistical difference was observed between groups in the rate of favourable functional outcome or sICH. Patients whom required and underwent IA thrombolytics were patients less likely to achieve successful reperfusion, probably due to selection bias.
Self-consistent numerical evaluation of concrete shielding activation for proton therapy systems
Authors: Ramoisiaux E. , Tesse R. , Hernalsteens C. , Boogert S. T. , Gnacadja E. , Nevay L. J. , Pauly N. , Shields W. , Stichelbaut F. , Vanwelde M. 
Published: August 2022

AbstractDue to the advancement of proton therapy for cancer treatment, there has been a worldwide increase in the construction of treatment facilities. Therapy centres are often coupled with clinical, biological or material-science research programs. Research activities require proton beams at energies spanning an extensive range with higher beam currents and longer irradiation times than clinical conditions. Additionally, next-generation proton therapy systems are evolving towards more compact designs. In addition to the increased centres’ workloads, reducing the system in size produces a more significant number of secondary particles per unit volume and time. Therefore, the activation level of materials constituting those future proton therapy centres is expected to be higher, increasing the ambient dose and the amount of radioactive waste collected at the end of a centre’s lifetime. These operating conditions pose new challenges for the shielding design and the reduction of the concrete activation. To tackle them, we propose a novel approach to seamlessly simulate all the processes relevant for the evaluation of the concrete shielding activation using, as an illustration, the Ion Beam Applications Proteus$$^\circledR $$

®

One system. A realistic model of the system is developed using Beam Delivery Simulation (BDSIM), a Geant4-based particle tracking code. It allows a single model to simulate primary and secondary particle tracking in the beamline, its surroundings, and all particle-matter interactions. The code system and library database FISPACT-II allows the computation of the shielding activation by solving the rate equations using ENDF-compliant group library data for nuclear reactions, particle-induced or spontaneous fission yields, and radioactive decay. As input, FISPACT-II is provided with the secondary particle fluences scored using the BDSIM Monte Carlo simulations. This approach is applied to the proton therapy research centre of Charleroi, Belgium. Results compare the evolution of the clearance level and the long-lived nuclide concentrations throughout the facility lifetime when using regular concrete or the newly developed Low Activation Concrete (LAC). A comparison with the initial shielding dimensioning has been performed for all the shielding walls to validate the methodology and highlight the clear benefits of integrating LAC inserts in the shielding design. The effectiveness of coupling BDSIM and FISPACT-II gives a glimpse of the possibility of a complete activation study following the actual workloads of the centre, allowing a better assessment of the shielding activation level at any time of the facility lifespan.
FDA Approval Summary: Pembrolizumab for Neoadjuvant and Adjuvant Treatment of Patients with High-Risk Early-Stage Triple-Negative Breast Cancer
Authors: Shah Mirat , Osgood Christy L. , Amatya Anup K. , Fiero Mallorie H. , Pierce William F. , Nair Abhilasha , Herz Jonathan , Robertson Kim J. , Mixter Bronwyn D. , Tang Shenghui , Pazdur Richard , Beaver Julia A. , Amiri-Kordestani Laleh 
Published: August 2022

Abstract
On July 26, 2021, the FDA granted approval to pembrolizumab in combination with chemotherapy for neoadjuvant treatment and then continued as a single agent for adjuvant treatment following surgery for patients with high-risk, early-stage triple-negative breast cancer. Approval was based on results from KEYNOTE-522, an ongoing randomized (2:1) trial evaluating pembrolizumab or placebo in combination with chemotherapy for neoadjuvant treatment and then as a single agent for adjuvant treatment. The co-primary endpoints were pathological complete response (pCR) rate and event-free survival (EFS). The trial demonstrated an improvement in pCR and EFS in the pembrolizumab arm compared with the control arm. The number of patients who experienced an EFS event was 123 (16%) and 93 (24%), respectively [HR: 0.63, 95% confidence interval (CI), 0.48–0.82, P = 0.00031]. Patients on the pembrolizumab arm experienced EFS benefit regardless of tumor PD-L1 status. The absolute pCR rate improvement with the addition of pembrolizumab was 7.5% (95% CI, 1.6–13.4). Among patients receiving pembrolizumab, 44% experienced an immune-related adverse reaction. This article summarizes FDA's review of pembrolizumab and the data supporting the favorable benefit–risk assessment.
A Druggable UHRF1/DNMT1/GLI Complex Regulates Sonic Hedgehog–Dependent Tumor Growth
Authors: Yang Fan , Rodriguez-Blanco Jezabel , Long Jun , Swiderska-Syn Marzena , Wynn Daniel T. , Li Bin , Shen Chen , Nayak Anmada , Ban Yuguang , Sun Xiaodian , Suter Robert K. , McCrea Heather J. , Capobianco Anthony J. , Ayad Nagi G. , Robbins David J. 
Published: August 2022

Abstract

Dysregulation of Sonic hedgehog (SHH) signaling drives the growth of distinct cancer subtypes, including medulloblastoma (MB). Such cancers have been treated in the clinic with a number of clinically relevant SHH inhibitors, the majority of which target the upstream SHH regulator, Smoothened (SMO). Despite considerable efficacy, many of these patients develop resistance to these drugs, primarily due to mutations in SMO. Therefore, it is essential to identify druggable, signaling components downstream of SMO to target in SMO inhibitor resistant cancers. We utilized an integrated functional genomics approach to identify epigenetic regulators of SHH signaling and identified a novel complex of Ubiquitin-like with PHD and RING finger domains 1 (UHRF1), DNA methyltransferase 1 (DNMT1), and GLI proteins. We show that this complex is distinct from previously described UHRF1/DNMT1 complexes, suggesting that it works in concert to regulate GLI activity in SHH driven tumors. Importantly, we show that UHRF1/DNMT1/GLI complex stability is targeted by a repurposed FDA-approved therapy, with a subsequent reduction in the growth of SHH-dependent MB ex vivo and in vivo.

Implications:
This work describes a novel, druggable UHRF1/DNMT1/GLI complex that regulates SHH-dependent tumor growth, and highlights an FDA-approved drug capable of disrupting this complex to attenuate tumor growth.
Quantitative anatomy or macroscopic parameters of compression wood of Picea abies (L.) H. Karst.? Defining the optimal parameters for dendrogeomorphic purposes
Authors: Wiśniewská Kristýna , Šilhán Karel 
Published: August 2022

Summary
The quantification of the intensities of tree growth responses to the impact of geomorphic processes is a modern research trend in dendrogeomorphology. It enables a more sensitive assessment of the activity of the studied geomorphic process compared to the traditional use of growth disturbances. The advanced definitions of individual intensity classes of growth disturbances are based exclusively on macroscopic observations. This study evaluates the possibility of anatomical quantification of compression wood (CW) intensity in the case of common spruce (Picea abies (L.) Karst.) and compares it with subjective macroscopic evidence of CW with respect to stem tilting intensity. In total, 25 disturbed (tilted) individuals of P. abies occupying a landslide active during July 1997 were sampled, and 21 of them were analysed. The intensity of external disturbance (stem tilting) was compared against the macroscopic (intensity and duration) and microscopic (quantitative change of the tracheid lumen area and the cell wall proportion) parameters of compression wood suitable for practical application in common dendrogeomorphic analysis. Generally, the macroscopic indices of CW were strongly correlated with stem tilting. The intensity of the anatomical growth response was stronger in the earlywood zone than in the latewood zone. Nevertheless, their dependence on stem tilting was not detected. Results suggest that CW classification based on the quantification of anatomical changes is not possible for dendrogeomorphic purposes. Nevertheless, based on the obtained results, the present study suggests preferring the most intensively tilted trees during future dendrogeomorphic research to obtain the most intensive macroscopic and subjective observable anatomical evidence for studying compression wood.
Archetypal Analysis of Geophysical Data Illustrated by Sea Surface Temperature
Authors: Black Amanda S. , Monselesan Didier P. , Risbey James S. , Sloyan Bernadette M. , Chapman Christopher C. , Hannachi Abdelwaheb , Richardson Doug , Squire Dougal T. , Tozer Carly R. , Trendafilov Nikolay 
Published: August 2022

Abstract
The ability to find and recognize patterns in high-dimensional geophysical data is fundamental to climate science and critical for meaningful interpretation of weather and climate processes. Archetypal analysis (AA) is one technique that has recently gained traction in the geophysical science community for its ability to find patterns based on extreme conditions. While traditional empirical orthogonal function (EOF) analysis can reveal patterns based on data covariance, AA seeks patterns from the points located at the edges of the data distribution. The utility of any objective pattern method depends on the properties of the data to which it is applied and the choices made in implementing the method. Given the relative novelty of the application of AA in geophysics it is important to develop experience in applying the method. We provide an assessment of the method, implementation, sensitivity, and interpretation of AA with respect to geophysical data. As an example for demonstration, we apply AA to a 39-yr sea surface temperature (SST) reanalysis dataset. We show that the decisions made to implement AA can significantly affect the interpretation of results, but also, in the case of SST, that the analysis is exceptionally robust under both spatial and temporal coarse graining.

Significance Statement
Archetypal analysis (AA), when applied to geophysical fields, is a technique designed to find typical configurations or modes in underlying data. This technique is relatively new to the geophysical science community and has been shown to be beneficial to the interpretation of extreme modes of the climate system. The identification of extreme modes of variability and their expression in day-to-day weather or state of the climate at longer time scales may help in elucidating the interplay between major teleconnection drivers and their evolution in a changing climate. The purpose of this work is to bring together a comprehensive report of the AA methodology using an SST reanalysis for demonstration. It is shown that the AA results are significantly affected by each implementation decision, but also can be resilient to spatiotemporal averaging. Any application of AA should provide a clear documentation of the choices made in applying the method.
Global Mesoscale Ocean Variability from Multiyear Altimetry: An Analysis of the Influencing Factors
Authors: Yu Yao , Gille Sarah T. , Sandwell David T. , McAuley Julian 
Published: August 2022

Abstract
Sea surface slope (SSS) responds to oceanic processes and other environmental parameters. This study aims to identify the parameters that influence SSS variability. We use SSS calculated from multiyear satellite altimeter observations and focus on small resolvable scales in the 30–100-km wavelength band. First, we revisit the correlation of mesoscale ocean variability with seafloor roughness as a function of depth, as proposed by Gille et al. Our results confirm that in shallow water there is statistically significant positive correlation between rough bathymetry and surface variability, whereas the opposite is true in the deep ocean. In the next step, we assemble 27 features as input variables to fit the SSS with a linear regression model and a boosted trees regression model, and then we make predictions. Model performance metrics for the linear regression model are R2 = 0.381 and mean square error = 0.010 μrad2. For the boosted trees model, R2 = 0.563 and mean square error = 0.007 μrad2. Using the hold-out data, we identify the most important influencing factors to be the distance to the nearest thermocline boundary, significant wave height, mean dynamic topography gradient, and M2 tidal speed. However, there are individual regions, that is, the Amazon outflow, that cannot be predicted by our model, suggesting that these regions are governed by processes that are not represented in our input features. The results highlight both the value of machine learning and its shortcomings in identifying mechanisms governing oceanic phenomena.
Automated Identification of Characteristic Droplet Size Distributions in Stratocumulus Clouds Utilizing a Data Clustering Algorithm
Authors: Allwayin Nithin , Larsen Michael L. , Shaw Alexander G. , Shaw Raymond A. 
Published: August 2022

Abstract
Droplet-level interactions in clouds are often parameterized by a modified gamma fitted to a “global” droplet size distribution. Do “local” droplet size distributions of relevance to microphysical processes look like these average distributions? This paper describes an algorithm to search and classify characteristic size distributions within a cloud. The approach combines hypothesis testing, specifically, the Kolmogorov–Smirnov (KS) test, and a widely used class of machine learning algorithms for identifying clusters of samples with similar properties: density-based spatial clustering of applications with noise (DBSCAN) is used as the specific example for illustration. The two-sample KS test does not presume any specific distribution, is parameter free, and avoids biases from binning. Importantly, the number of clusters is not an input parameter of the DBSCAN-type algorithms but is independently determined in an unsupervised fashion. As implemented, it works on an abstract space from the KS test results, and hence spatial correlation is not required for a cluster. The method is explored using data obtained from the Holographic Detector for Clouds (HOLODEC) deployed during the Aerosol and Cloud Experiments in the Eastern North Atlantic (ACE-ENA) field campaign. The algorithm identifies evidence of the existence of clusters of nearly identical local size distributions. It is found that cloud segments have as few as one and as many as seven characteristic size distributions. To validate the algorithm’s robustness, it is tested on a synthetic dataset and successfully identifies the predefined distributions at plausible noise levels. The algorithm is general and is expected to be useful in other applications, such as remote sensing of cloud and rain properties.

Significance Statement
A typical cloud can have billions of drops spread over tens or hundreds of kilometers in space. Keeping track of the sizes, positions, and interactions of all of these droplets is impractical, and, as such, information about the relative abundance of large and small drops is typically quantified with a “size distribution.” Droplets in a cloud interact locally, however, so this work is motivated by the question of whether the cloud droplet size distribution is different in different parts of a cloud. A new method, based on hypothesis testing and machine learning, determines how many different size distributions are contained in a given cloud. This is important because the size distribution describes processes such as cloud droplet growth and light transmission through clouds.
A Method for Correcting Staggered Pulse Repetition Time (PRT) and Dual Pulse Repetition Frequency (PRF) Processor Errors in Research Radar Datasets
Authors: Alford A. Addison , Biggerstaff Michael I. , Ziegler Conrad L. , Jorgensen David P. , Carrie Gordon D. 
Published: August 2022

Abstract
Mobile weather radars at high frequencies (C, X, K, and W bands) often collect data using staggered pulse repetition time (PRT) or dual pulse repetition frequency (PRF) modes to extend the effective Nyquist velocity and mitigate velocity aliasing while maintaining a useful maximum unambiguous range. These processing modes produce widely dispersed “processor” dealiasing errors in radial velocity estimates. The errors can also occur in clusters in high shear areas. Removing these errors prior to quantitative analysis requires tedious manual editing and often produces “holes” or regions of missing data in high signal-to-noise areas. Here, data from three mobile weather radars were used to show that the staggered PRT errors are related to a summation of the two Nyquist velocities associated with each of the PRTs. Using observations taken during a mature mesoscale convective system, a landfalling tropical cyclone, and a tornadic supercell storm, an algorithm to automatically identify and correct staggered PRT processor errors has been developed and tested. The algorithm creates a smooth profile of Doppler velocities using a Savitzky–Golay filter independently in radius and azimuth and then combined. Errors are easily identified by comparing the velocity at each range gate to its smoothed counterpart and corrected based on specific error characteristics. The method improves past dual PRF correction methods that were less successful at correcting “grouped” errors. Given the success of the technique across low, moderate, and high radial shear regimes, the new method should improve research radar analyses by affording the ability to retain as much data as possible rather than manually or objectively removing erroneous velocities.
“In vitro” evaluation of bacterial biofilm formation on different cerclage systems
Authors: Veloso Margarita , Lopez Yuli , Bernaus Martí , Gabasa Yaiza , Angles Francesc , Font-Vizcarra Lluis , Soto Sara 
Published: August 2022

Cerclage wiring may be used for fracture fixation or osteotomy stabilization in revision arthroplasty. There is a lack of evidence regarding the potential risk of bacterial colonization for the different types of cerclages. The objective of our research is to study the adhesion and biofilm formation of S. epidermidis, S. aureus, and P. aeruginosa on two different cerclage cable models, comparing a polymer cable and a stainless steel metal cable. A two-cm cerclage piece of each material was submerged in 2 mL of tryptic soy broth (TSB) inoculated with 10 μL of a 0.5 McFarland bacterial culture, and incubated at 37°C during 2 h for adhesion and 48 h for biofilm formation. The cerclages were washed with 1xPBS and sonicated in a new culture medium. Aliquots of several dilutions of each sonicated culture were spread in TSB agar and incubated at 37°C for 24 h. The number of colonies was counted. The colony-forming units per ml (CFU/mL) and the percentage of reduction were calculated. Experiments were triplicated. For P. aeruginosa, a statistically significant reduction in biofilm formation was found on the polymer cerclage cable, compared to the metal cerclage cable. Reductions of 59% and 88%, after 2 h and 48 h, respectively, were observed. For S. epidermis and S. aureus, there was a trend towards lower bacterial adhesion and biofilm formation for the polymer cerclage cable. In summary, these results demonstrate that the braided polymer cerclage cable may be less prone to bacterial adherence and biofilm formation compared to the braided metal cerclage cable.
Acculturation, Physical Activity, and Metabolic Syndrome in Asian American Adults
Authors: Sheng Jingxi , Abshire Demetrius A. , Heiney Sue P. , Wirth Michael D. 
Published: August 2022

Introduction: Asian Americans (AsAms) have a high prevalence of metabolic syndrome (MetS) and are one of the least physically active racial groups in America. The purpose of this study was to examine the relationship between MetS and moderate-to-vigorous physical activity (MVPA) among AsAm adults and whether acculturation modifies this relationship. Method: Data were from 2,259 AsAms participating in the 2011–2016 National Health and Nutrition Examination Survey. Physical activity (PA) was self-reported as minutes of weekly MVPA. Acculturation included nativity, length of residency in America, and language preference. The International Diabetes Federation criteria was used to determine the presence of MetS. Results: About 64.4% of AsAms did not meet the PA recommendation (MVPA ≥150 min/week). The prevalence of MetS was 39.2%. The odds of having MetS were greater among AsAms who did not meet MVPA recommendations compared with those who did meet MVPA recommendations (odds ratio [OR] = 1.5, 95% confidence interval [CI] = [1.11, 2.07]). When stratified by acculturation, this association remained statistically significant in the groups who immigrated to America more than 15 years ago and who spoke English only. Conclusion: MVPA reduces MetS risk in AsAm adults, especially among more acculturated AsAms. Culturally adapted programs are warranted to promote PA and adequate knowledge of disease prevention in this population.