bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimized rectification of fiber orientation density function
Authors: Moss Hunter G. , Jensen Jens H. 
Published: July 2020

PurposeTo demonstrate an optimized rectification strategy for fiber orientation density functions (fODFs).Theory and MethodsIn white matter, fODFs can be estimated with diffusion MRI. However, because of signal noise, imaging artifacts and other factors, experimentally determined fODFs may take on unphysical negative values in some directions. Here, we show how to rectify such fODFs to eliminate all negative values while minimizing the mean square difference between the original and rectified fODFs. The method is demonstrated for a mathematical model and for fODFs estimated from experimental human data using both constrained spherical deconvolution and fiber ball imaging. Comparison with an alternative nonoptimized rectification approach is also provided.ResultsFor the mathematical model, it is found that the optimized rectification procedure removes negative fODF values while at the same time reducing the mean square error. Relative to the alternative rectification approach, the optimized fODFs are substantially more accurate. For the experimental data, the optimized fODFs have a lower average fractional anisotropy axonal and often fewer small peaks than the original, unrectified fODFs. The calculation of optimized fODFs is straightforward where the main step is the finding of the root to an equation in one variable, as may be efficiently accomplished with the bisection method.ConclusionUnphysical negative fODF values can be easily eliminated in a manner that minimizes the mean square difference between the original and rectified fODFs. Optimized fODF rectification may be useful in applications for which negative values are problematic.
Hamiltonian direct differentiation and adjoint approaches for multibody system sensitivity analysis
Authors: Maciąg Paweł , Malczyk Paweł , Frączek Janusz 
Published: July 2020

SummaryThe design of multibody systems involves high fidelity and reliable techniques and formulations that should help the analyst to make reasonable decisions. Given that constrained equations of motion for the simplest of multibody systems are highly nonlinear, determining the sensitivity terms is a computationally intensive and complex process that requires the application of special procedures. In this article, two novel Hamiltonian‐based approaches are presented for efficient sensitivity analysis of general multibody systems. The developed direct differentiation and the adjoint methods are based on constrained Hamilton's canonical equations of motion. This formulation provides solutions, which are more stable as compared to the results of direct integration of equations of motion expressed in terms of accelerations due to a reduced differential index of the underlying system of differential‐algebraic equations and explicit constraint imposition at the velocity level.The proposed Hamiltonian based methods are both capable of calculating the sensitivity derivatives and keeping the growth of constraint violation errors at a reasonable rate. The Hamiltonian‐based procedures derived herein appear to be good alternatives to existing methods for sensitivity analysis of general multibody systems.
Examining whether order of instruction matters in an experiential learning activity
Authors: Higley Corrine , Hayes Daniel 
Published: July 2020

AbstractExperiential learning is a pedagogical technique that places students in direct contact with the material being studied. Students progress through four stages in a continuous cycle of learning. Because it is conceptualized as a continuous cycle, we question whether student comprehension varies according to where in the learning cycle they begin. Using an experiential outdoor survival shelter building activity, we tested whether student comprehension of experiential course material varied when receiving instruction prior to the activity vs. interactive discussion after the activity. Our results indicate that students who received advance instruction created significantly higher quality survival shelters during the activity, but there was no difference in post‐activity summative learning assessments between groups. Furthermore, prior outdoor survival experience was the only covariate in our analysis that affected student comprehension. No other covariates considered (treatment, gender, class rank, and participation in various outdoor activities) in our analysis affected student comprehension in this activity. Although the order of instruction did not influence student comprehension in this activity, more research is needed to explore whether instructional order matters in other experiential learning activities. Researchers are encouraged to apply this approach to other situations to further understand the ramifications of instructional order on experiential learning outcomes.
Association between end‐induction response according to the revised International Neuroblastoma Response Criteria (INRC) and outcome in high‐risk neuroblastoma patients
Authors: Barr Erin K. , Laurie Kathryn , Wroblewski Kristen , Applebaum Mark A. , Cohn Susan L. 
Published: July 2020

AbstractBackgroundThe 1993 International Neuroblastoma Response Criteria (INRC) were revised in 2017 to include modern functional imaging studies and methods for quantifying disease in bone marrow. We hypothesized the 2017 INRC would enable more precise assessment of response to treatment and provide superior prognostic information compared with the 1993 criteria.MethodsHigh‐risk (HR) neuroblastoma patients from two institutions in Chicago diagnosed between 2006 and 2016 were identified. Patients were assessed post induction chemotherapy via the 1993 and 2017 INRC and classified as responder (≥ mixed response [MXR] or ≥ minor response [MR], respectively) or nonresponder (< MXR or < MR). Event‐free survival (EFS) and overall survival (OS) for responders versus nonresponders were determined from end induction and stratified by Cox regression. Patients with progressive disease at end induction were eliminated from the EFS analyses but included in the OS analysis.ResultsThe 1993 criteria classified 52 of the 60 HR patients as responders, whereas 54 responders were identified using the 2017 criteria (Spearman correlation r = 0.82, P < 0.001). No statistically significant difference in EFS was observed for responders versus nonresponders using either criteria (P = 0.48 and P = 0.08). However, superior OS was observed for responders (P = 0.01) using either criteria. Both criteria were sensitive in identifying responders among those with good outcomes. The specificity to identify nonresponders among those with poor outcomes was poor.ConclusionsIn HR neuroblastoma, end‐induction response defined by the 1993 or 2017 INRC is associated with survival. Larger cohorts are needed to determine if the 2017 INRC provides more precise prognostication.
Cost‐effectiveness of levofloxacin prophylaxis against bacterial infection in pediatric patients with acute myeloid leukemia
Authors: McCormick Meghan , Friehling Erika , Kalpatthi Ramasubramanian , Siripong Nalyn , Smith Kenneth 
Published: July 2020

AbstractBackgroundInfections are the leading cause of therapy‐related mortality in pediatric patients with acute myeloid leukemia (AML). Although effectiveness of levofloxacin antibacterial prophylaxis in oncology patients is recognized, its cost‐effectiveness is unknown. This study evaluated epidemiologic data regarding levofloxacin use and the cost‐effectiveness of this strategy as the cost per bacteremia episode, intensive care unit (ICU) admission, and death avoided in children with AML.ProcedureA retrospective cohort study using the Pediatric Health Information System (PHIS) database compared demographic and clinical characteristics and receipt of levofloxacin prophylaxis in children with AML admitted for chemotherapy from January 1, 2014, through December 31, 2018. We then developed a decision analysis model in this population that compared costs associated with bacteremia, ICU admission, or death secondary to bacteremia to levofloxacin prophylaxis cost from a healthcare perspective. Time horizon is one chemotherapy cycle. Probabilistic and one‐way sensitivity analyses evaluated model uncertainty.ResultsProphylaxis cost $8491 per bacteremia episode prevented compared with an average added hospital cost of $119 478. Prophylaxis cost $81 609 per ICU admission avoided, compared with an average added hospital cost of $94 181. Prophylaxis cost $220 457 per death avoided. In sensitivity analysis, at a willingness‐to‐pay threshold of $100 000 per bacteremia episode avoided, prophylaxis remained cost‐effective in 94.6% of simulations. Prophylaxis use was more common in recent years in patients with relapsed disease and with chemotherapy regimens considered more intensive.ConclusionProphylaxis is cost‐effective in preventing bacterial infections in patients with AML. Findings support increased use in patients considered at high risk of bacterial infection secondary to myelosuppression.
Chest computed tomography findings for a cohort of children with pulmonary Langerhans cell histiocytosis
Authors: Della Valle Valeria , Donadieu Jean , Sileo Chiara , Barkaoui Mohamed Aziz , Héritier Sébastien , Brisse Hervé , Boutry Nathalie , Tréguier Catherine , Chateil Jean‐François , Petit Philippe , Pracros Jean‐Pierre , Chastagner Pascal , Boyer Corinne , Veillon Francis , Durand Chantal , Mounayer Charbel , Kambouchner Marianne , Brauner Michel , Tazi Abdellatif , Epaud Ralp , Ducou le Pointe Hubert 
Published: July 2020

ABSTRACTObjectiveThis study was undertaken to describe the spectrum of lung computed‐tomography (CT) findings in children with pulmonary Langerhans cell histiocytosis (PLCH) and to evaluate for this population the CT‐scan nodule and cyst scores proposed by adult pulmonologists at diagnosis and during follow‐up.MethodsAmong 175 children with PLCH identified in the French national population‐based Langerhans cell histiocytosis cohort, 60 were retrospectively selected by the availability of CT for a central review by three pediatric radiologists. These 60 patients are representative of childhood PLCH for almost all clinical aspects, except a lower percentage of risk organ involvement (38% vs 54%; P = 0.05).ResultsThe 60 children's chest CT scans (n = 218) were reviewed. At diagnosis, 63% of them had nodules, 53% had cysts, and 29% had both. The percentages of patients with nodules or cysts increased from diagnosis to peak disease activity, respectively, from 63% to 73% and from 53% to 66%. The costophrenic angle was involved in 71%. Patients with pneumothorax (25%) had a higher median cyst score. Alveolar consolidation was observed in 34%. Patients with low CT‐scan nodule and cyst scores had no long‐term pulmonary sequelae.ConclusionsWell‐known characteristics of adult PLCH (nodules and cysts) were observed in children. The chest CT scores proposed by adult pulmonologists could easily be applied to childhood PLCH. Lesions in children, unlike those in adults, are frequently located near the costophrenic angles. Alveolar consolidation might be considered an atypical feature of childhood PLCH.
Microbiology and radiographic features of osteomyelitis in children and adolescents with sickle cell disease
Authors: Kao Carol M. , Yee Marianne E. , Maillis Alexander , Lai Kristina , Bakshi Nitya , Rostad Bradley S. , Jerris Robert C. , Lane Peter A. , Yildirim Inci 
Published: July 2020

AbstractBackgroundChildren with sickle cell disease (SCD) are at increased risk for bacterial infections including osteomyelitis (OM). Fever and bone pain, key presenting symptoms of OM, are common in SCD, thus complicating diagnosis. We reviewed presentation, imaging features, and microbiologic etiologies of children with SCD treated for OM.MethodsThe comprehensive SCD clinical database of children and adolescents with SCD followed at a single, large tertiary pediatric center were searched to identify all diagnostic coding for potential cases of osteomyelitis in children ages 6 months to 21 years from 2010 to 2019. Medical charts were reviewed to determine OM diagnostic probability based on radiographic and microbiologic findings and the duration of prescribed antibiotic treatment for OM.ResultsReview of 3553 patients (18 039 person‐years) identified 20 episodes of probable OM in 19 children. Magnetic resonance imaging (MRI) findings to support OM were definitive in 4/19 (21%), probable in 10/19 (53%), suspected in 5/19 (26%), based on blinded radiologist review. Blood and/or operative cultures from bone and tissue debridement isolated Salmonella species in seven (35%) cases and methicillin‐susceptible Staphylococcus aureus (MSSA) in two (10%). Six patients received antibiotic treatment prior to obtainment of cultures. Of culture‐positive cases, MRI findings for OM were definitive or probable in six of nine (67%), suspected in three of nine (33%).ConclusionsDistinction between OM and sickle‐related bone infarct or vasoocclusion is difficult based on imaging findings alone. Early attainment of blood and operative cultures increases the likelihood of identifying and adequately treating OM.
Prolongation of radiotherapy duration is associated with inferior overall survival in patients with pediatric medulloblastoma and central nervous system primitive neuroectodermal tumors
Authors: Baliga Sujith , Bajaj Benjamin V. M. , Kabarriti Rafi , Grassberger Clemens , Patteson Brooke , Yeap Beow , Fox Jana L. , Garg Madhur K. , Yock Torunn I. 
Published: July 2020

AbstractBackgroundThe importance of radiotherapy (RT) duration in medulloblastoma in the modern era of chemotherapy has not been well elucidated. The aim of this study was to determine the impact of RT treatment duration on overall survival (OS) in pediatric medulloblastoma and cenral nervous system neuroectodermal tumors (PNETs).MethodsThe National Cancer Database (NCDB) was queried to identify patients with newly diagnosed medulloblastoma and CNS PNETs diagnosed between 2004 and 2014. Patients were excluded if they had extraneural metastasis, did not receive standard craniospinal irradiation dose, had a nonstandard total dose outside of 54 or 55.8 Gy, did not receive adjuvant chemotherapy, or if the RT duration was outside of the expected range of 37 to 80 days. The Kaplan‐Meier estimator was used to estimate the association between RT duration (≤45 days or >45 days) and OS. Multivariate Cox regression was used to assess other confounders of OS.ResultsSix‐hundred twenty‐five patients met inclusion criteria, of which 181 were assigned to the “RT long" (>45 days) cohort (29.0%) and 444 (71.0%) to the “RT short” group (≤45 days). The five‐year OS for the “RT short” compared with “RT long” cohort was 82.2% versus 70.9%, respectively (log‐rank, P < 0.0037). For average risk patients, the five‐year OS was 84.6% versus 86.4% for “RT short” and “RT long,” respectively (log‐rank, P = 0.40). However, for high‐risk patients, five‐year OS was 77.7% versus 51.0% (log‐rank, P < 0.0001) in the “RT short” and “RT long” cohorts.ConclusionFor patients with high‐risk medulloblastoma and CNS PNETs, RT duration >45 days was associated with inferior OS.
Comprehensive promotion of mechanical properties of epoxy by electrical insulating filler of Si3N4 whiskers at low content
Authors: Zhang Dian , Liu Jing , Liu Xuan , Liu Yijun , Yang Xiaofeng , Gao Yunqin , Ma Aiqiong 
Published: July 2020

AbstractThe improvement of the mechanical properties of brittle epoxies by various fillers, especially by carbon‐related materials, has attracted significant attention and achieved impressive results. However, the dielectric properties of an epoxy may be compromised along with the improvement, and there is an urgent need to develop electrical insulating fillers to address this issue. In this study, Si3N4 whiskers (Si3N4w) are first introduced as the filler used to prepare a composite of Si3N4w/epoxy. The results indicate that Si3N4w has an outstanding capability to comprehensively improve the mechanical properties of an epoxy. The maximal reinforcing and toughening effect could be obtained at a low filler content of 3.0%. The bending strength, Young's modulus, KIC and work of fracture of the composite can be augmented by 34.05%, 23.00%, 57.53%, and 513.50%, respectively, in comparison with those of the neat epoxy. The abundant energy dissipation mechanisms responsible for these effects are observed and interpreted. Finally, a brief phenomenological fracture process of Si3N4w/epoxy is proposed.
Using physical features of protein core packing to distinguish real proteins from decoys
Authors: Grigas Alex T. , Mei Zhe , Treado John D. , Levine Zachary A. , Regan Lynne , O'Hern Corey S. 
Published: July 2020

AbstractThe ability to consistently distinguish real protein structures from computationally generated model decoys is not yet a solved problem. One route to distinguish real protein structures from decoys is to delineate the important physical features that specify a real protein. For example, it has long been appreciated that the hydrophobic cores of proteins contribute significantly to their stability. We used two sources to obtain datasets of decoys to compare with real protein structures: submissions to the biennial Critical Assessment of protein Structure Prediction competition, in which researchers attempt to predict the structure of a protein only knowing its amino acid sequence, and also decoys generated by 3DRobot, which have user‐specified global root‐mean‐squared deviations from experimentally determined structures. Our analysis revealed that both sets of decoys possess cores that do not recapitulate the key features that define real protein cores. In particular, the model structures appear more densely packed (because of energetically unfavorable atomic overlaps), contain too few residues in the core, and have improper distributions of hydrophobic residues throughout the structure. Based on these observations, we developed a feed‐forward neural network, which incorporates key physical features of protein cores, to predict how well a computational model recapitulates the real protein structure without knowledge of the structure of the target sequence. By identifying the important features of protein structure, our method is able to rank decoy structures with similar accuracy to that obtained by state‐of‐the‐art methods that incorporate many additional features. The small number of physical features makes our model interpretable, emphasizing the importance of protein packing and hydrophobicity in protein structure prediction.
Drivers of recombinant soluble influenza A virus hemagglutinin and neuraminidase expression in mammalian cells
Authors: van der Woude Roosmarijn , Turner Hannah L. , Tomris Ilhan , Bouwman Kim M. , Ward Andrew B. , de Vries Robert P. 
Published: July 2020

AbstractRecombinant soluble trimeric influenza A virus hemagglutinins (HA) and tetrameric neuraminidases (NAs) have proven to be excellent tools to decipher biological properties. Receptor binding and sialic acid cleavage by recombinant proteins correlate satisfactorily compared to whole viruses. Expression of HA and NA can be achieved in a plethora of different laboratory hosts. For immunological and receptor interaction studies however, insect and mammalian cell expressed proteins are preferred due to the presence of N‐linked glycosylation and disulfide bond formation. Because mammalian‐cell expression is widely applied, an increased expression yield is an important goal. Here we report that using codon‐optimized genes and sfGFP fusions, the expression yield of HA can be significantly improved. sfGFP also significantly increased expression yields when fused to the N‐terminus of NA. In this study, a suite of different hemagglutinin and neuraminidase constructs are described, which can be valuable tools to study a wide array of different HAs, NAs and their mutants.
Calibration of computational Mössbauer spectroscopy to unravel active sites in FeNC catalysts for the oxygen reduction reaction
Authors: Gallenkamp Charlotte , Kramm Ulrike I. , Proppe Jonny , Krewald Vera 
Published: July 2020

AbstractSingle‐atom catalysts with iron ions in the active site, known as FeNC catalysts, show high activity for the oxygen reduction reaction and hence hold promise for access to low‐cost fuel cells. Because of the amorphous, multiphase structure of the FeNC catalysts, the iron environment and its electronic structure are poorly understood. While it is widely accepted that the catalytically active site contains an iron ion ligated by several nitrogen donors embedded in a graphene‐like plane, the exact structural details, such as the presence or nature of axial ligands, are unknown. Computational chemistry in combination with Mössbauer spectroscopy can help unravel the geometric and electronic structures of the active sites. As a first step toward this goal, we present a calibration of computational Mössbauer spectroscopy for FeN4‐like environments. The uncertainty of both the isomer shift and the quadrupole splitting prediction is determined, from which trust regions for the Mössbauer parameter predictions of computational FeNC models are derived. We find that TPSSh, B3LYP, and PBE0 perform equally well; the trust regions with B3LYP are 0.13 mm s−1for the isomer shift and 0.36 mm s−1for the quadrupole splitting. The calibration data is made publicly available in an interactive notebook that provides predicted Mössbauer parameters with individual uncertainty estimates from computed contact densities and quadrupole splitting values. We show that a differentiation of common FeNC Mössbauer signals by a separate analysis of isomer shift and quadrupole splitting will most likely be insufficient, whereas their simultaneous evaluation will allow the assignment to adequate computational FeNC models.