Miracle-dz/UniFAR-FTUs huggingface dataset:
Validation of a Minimum Outcome Core Set in the Evaluation of Patients With Back Pain

Study Design. Prospective study of patients with subacute osteoporotic fracture (SOF) or chronic low back pain (CLBP). Objective. To evaluate reliability, validity, and responsiveness of a purposefully brief outcome instrument. Summary of Background Data. A minimum standardized “core set” was proposed for monitoring patients with low back pain in 1998, but an assessment of metric properties was still lacking. Methods. The Core Set, SF-36, and Oswestry questionnaires were completed by 154 patients. Test–retest reproducibility was evaluated in a subsample of 43 stable patients with CLBP. Responsiveness was evaluated by estimating effect size (ES) of pre-postsurgery changes in 50 patients with SOF and 23 with CLBP. Results. The total Core Set showed good reproducibility with intraclass correlation coefficients on test–retest near the highest standard of 0.9, whereas internal consistency differed between patients with CLBP and those with SOF (Cronbach’s alpha of 0.92 and 0.64, respectively). Most correlations of the Core Set with SF-36 and Oswestry, previously hypothesized as high, were >0.65, demonstrating good construct validity. Sensitivity to change of the Core Set (ES 0.4–2.3) is similar to the Oswestry (ES 0.7 and 2.3). Conclusions. These findings support the potential usefulness of the Core Set when respondent burden is a major concern. However, subscale scores need to be further tested in other populations before they can be widely recommended.
Designing for deeper learning in a blended computer science course for middle school students

The focus of this research was to create and test an introductory computer science course for middle school. Titled “Foundations for Advancing Computational Thinking” (FACT), the course aims to prepare and motivate middle school learners for future engagement with algorithmic problem solving. FACT was also piloted as a seven-week course on Stanford’s OpenEdX MOOC platform for blended in-class learning. Unique aspects of FACT include balanced pedagogical designs that address the cognitive, interpersonal, and intrapersonal aspects of “deeper learning”; a focus on pedagogical strategies for mediating and assessing for transfer from block-based to text-based programming; curricular materials for remedying misperceptions of computing; and “systems of assessments” (including formative and summative quizzes and tests, directed as well as open-ended programming assignments, and a transfer test) to get a comprehensive picture of students’ deeper computational learning. Empirical investigations, accomplished over two iterations of a design-based research effort with students (aged 11–14 years) in a public school, sought to examine student understanding of algorithmic constructs, and how well students transferred this learning from Scratch to text-based languages. Changes in student perceptions of computing as a discipline were measured. Results and mixed-method analyses revealed that students in both studies (1) achieved substantial learning gains in algorithmic thinking skills, (2) were able to transfer their learning from Scratch to a text-based programming context, and (3) achieved significant growth toward a more mature understanding of computing as a discipline. Factor analyses of prior computing experience, multivariate regression analyses, and qualitative analyses of student projects and artifact-based interviews were conducted to better understand the factors affecting learning outcomes. Prior computing experiences (as measured by a pretest) and math ability were found to be strong predictors of learning outcomes.
Walking Impairment Questionnaire Improves Mortality Risk Prediction Models in a High-Risk Cohort Independent of Peripheral Arterial Disease Status

Background— The Walking Impairment Questionnaire (WIQ) is a subjective measure of patient-reported walking performance developed for peripheral arterial disease. The purpose of this study is to examine whether this simple tool can improve the predictive capacity of established risk models and whether the WIQ can be used in patients without peripheral arterial disease. Methods and Results— At baseline we assessed the walking distance, stair-climbing, and walking speed WIQ category scores among individuals who were undergoing coronary angiography. During a median follow-up of 5.0 years, there were 172 mortalities among 1417 study participants. Adjusted Cox proportional hazards models showed that all 3 WIQ categories independently predicted future all-cause and cardiovascular mortality, including among individuals without peripheral arterial disease (P<0.001). Compared with the cardiovascular risk factors model, we observed significantly increased risk discrimination with a C-index of 0.741 (change in C-index, 0.040; 95% confidence interval, 0.011–0.068) and 0.832 (change in C-index, 0.080; 95% confidence interval, 0.034–0.126) for all-cause and cardiovascular mortality, respectively. Examination of risk reclassification using the net reclassification improvement index showed a 48.4% (P<0.001) improvement for all-cause mortality and a 77.4% (P<0.001) improvement for cardiovascular mortality compared with the cardiovascular risk factors model. Conclusions— All 3 WIQ categories independently predicted future all-cause and cardiovascular mortality. Importantly, we found that this subjective measure of walking ability could be extended to patients without peripheral arterial disease. The addition of the WIQ scores to established cardiovascular risk models significantly improved risk discrimination and reclassification, suggesting broad clinical use for this simple, inexpensive test.
Global Myocardial Ischemia in the Newborn, Juvenile, and Adult Isolated Isovolumic Rabbit Heart: Age‐Related Differences in Systolic Function, Diastolic Stiffness, Coronary Resistance, Myocardial Oxygen Consumption, and Extracellular pH

Controversy persists over the relative tolerance of the immature myocardium to global ischemia. Thus, we evaluated the physiologic effects of 30, 60, and 180 minutes of global ischemia in an isolated, isovolumic rabbit heart model, at 3 different ages: newborns (less than 1 week of age) (n = 36), juveniles (4 to 6 weeks old) (n = 36), and adults (5 to 7 months old) (n = 36). Following 30 and 60 minutes of ischemia, respectively, adults recovered 87 ± 4% (mean ± SEM) and 90 ± 7% of baseline systolic function, and juveniles recovered 91 ± 10% and 85 ± 8%. In contrast, newborns recovered only 27 ± 6% and 28 ± 4% of baseline systolic function (p<0.05 compared to adults and juveniles). During ischemia, newborn hearts became stiff more rapidly, reaching 361 ± 46% of baseline stiffness by 60 minutes, whereas adults and juveniles were at 122 ± 33% and 92 ± 18% of baseline stiffness (p<0.05 newborns compared to adults and juveniles). With reperfusion after 60 minutes of ischemia, the work efficiency of the newborn heart deteriorated to 39 ± 7% of baseline, compared with 95 ± 7% and 91 ± 7% of baseline efficiency in the adult and juvenile hearts (p<0.05, newborns compared to adults and juveniles). The ratio of tissue wet-to-dry weights were similar in all age groups after ischemia. However, tissue pH was significantly higher in newborns during ischemia (6.54 ± 0.06, 6.69 ± 0.07, and 6.85 ± 0.09 in adults, juveniles, and newborns, after 60 minutes of ischemia) (p<0.05 newborns versus adults). We conclude that the newborn rabbit hearts are more susceptible to ischemic injury than the juvenile and adult hearts. (Circulation Research 1987;61:609-615)
Molecular Mechanism of the Hydration of Candida antarctica Lipase B in the Gas Phase: Water Adsorption Isotherms and Molecular Dynamics Simulations

Hydration is a major determinant of activity and selectivity of enzymes in organic solvents or in gas phase. The molecular mechanism of the hydration of Candida antarctica lipase B (CALB) and its dependence on the thermodynamic activity of water (aw) was studied by molecular dynamics simulations and compared to experimentally determined water sorption isotherms. Hydration occurred in two phases. At low water activity, single water molecules bound to specific water binding sites at the protein surface. As the water activity increased, water networks gradually developed. The number of protein‐bound water molecules increased linearly with aw, until at aw=0.5 a spanning water network was formed consisting of 311 water molecules, which covered the hydrophilic surface of CALB, with the exception of the hydrophobic substrate‐binding site. At higher water activity, the thickness of the hydration shell increased up to 10 Å close to aw=1. Above a limit of 1600 protein‐bound water molecules the hydration shell becomes unstable and the formation of pure water droplets occurs in these oversaturated simulation conditions. While the structure and the overall flexibility of CALB was independent of the hydration state, the flexibility of individual loops was sensitive to hydration: some loops, such as those part of the substrate‐binding site, became more flexible, while other parts of the protein became more rigid upon hydration. However, the molecular mechanism of how flexibility is related to activity and selectivity is still elusive.
Marked effects of intracranial volume correction methods on sex differences in neuroanatomical structures: a HUNT MRI study

To date, there is no consensus whether sexual dimorphism in the size of neuroanatomical structures exists, or if such differences are caused by choice of intracranial volume (ICV) correction method. When investigating volume differences in neuroanatomical structures, corrections for variation in ICV are used. Commonly applied methods are the ICV-proportions, ICV-residuals and ICV as a covariate of no interest, ANCOVA. However, these different methods give contradictory results with regard to presence of sex differences. Our aims were to investigate presence of sexual dimorphism in 18 neuroanatomical volumes unrelated to ICV-differences by using a large ICV-matched subsample of 304 men and women from the HUNT-MRI general population study, and further to demonstrate in the entire sample of 966 healthy subjects, which of the ICV-correction methods gave results similar to the ICV-matched subsample. In addition, sex-specific subsamples were created to investigate whether differences were an effect of head size or sex. Most sex differences were related to volume scaling with ICV, independent of sex. Sex differences were detected in a few structures; amygdala, cerebellar cortex, and 3rd ventricle were larger in men, but the effect sizes were small. The residuals and ANCOVA methods were most effective at removing the effects of ICV. The proportions method suffered from systematic errors due to lack of proportionality between ICV and neuroanatomical volumes, leading to systematic mis-assignment of structures as either larger or smaller than their actual size. Adding additional sexual dimorphic covariates to the ANCOVA gave opposite results of those obtained in the ICV-matched subsample or with the residuals method. The findings in the current study explain some of the considerable variation in the literature on sexual dimorphisms in neuroanatomical volumes. In conclusion, sex plays a minor role for neuroanatomical volume differences; most differences are related to ICV.
CarSpeak: a content-centric network for autonomous driving

This paper introduces CarSpeak, a communication system for autonomous driving. CarSpeak enables a car to query and access sensory information captured by other cars in a manner similar to how it accesses information from its local sensors. CarSpeak adopts a content-centric approach where information objects -- i.e., regions along the road -- are first class citizens. It names and accesses road regions using a multi-resolution system, which allows it to scale the amount of transmitted data with the available bandwidth. CarSpeak also changes the MAC protocol so that, instead of having nodes contend for the medium, contention is between road regions, and the medium share assigned to any region depends on the number of cars interested in that region. CarSpeak is implemented in a state-of-the-art autonomous driving system and tested on indoor and outdoor hardware testbeds including an autonomous golf car and 10 iRobot Create robots. In comparison with a baseline that directly uses 802.11, CarSpeak reduces the time for navigating around obstacles by 2.4x, and reduces the probability of a collision due to limited visibility by 14x.
Evaluation of combined dynamic compression and single channel noise reduction for hearing aid applications

Abstract Objective: Single-channel noise reduction (SCNR) and dynamic range compression (DRC) are important elements in hearing aids. Only relatively few studies have addressed interaction effects and typically used real hearing aids with limited knowledge about the integrated algorithms. Here the potential benefit of different combinations and integration of SCNR and DRC was systematically assessed. Design: Ten different systems combining SCNR and DRC were implemented, including five serial arrangements, a parallel and two multiplicative approaches. In an instrumental evaluation, signal-to-noise ratio (SNR) improvement and spectral contrast enhancement (SCE) were assessed. Quality ratings at 0 and +6 dB SNR, and speech reception thresholds (SRTs) in noise were measured using stationary and babble noise. Study sample: Thirteen young normal-hearing (NH) listeners and 12 hearing-impaired (HI) listeners participated. Results: In line with an increased segmental SNR and spectral contrast compared to a serial concatenation, the parallel approach significantly reduced the perceived noise annoyance for both subject groups. The proposed multiplicative approaches could partly counteract increased speech distortions introduced by DRC and achieved the best overall quality for the HI listeners. Conclusions: For high SNRs well above the individual SRT, the specific combination of SCNR and DRC is perceptually relevant and the integrative approaches were preferred.
Genetic Structure and Demographic History Should Inform Conservation: Chinese Cobras Currently Treated as Homogenous Show Population Divergence

An understanding of population structure and genetic diversity is crucial for wildlife conservation and for determining the integrity of wildlife populations. The vulnerable Chinese cobra (Naja atra) has a distribution from the mouth of the Yangtze River down to northern Vietnam and Laos, within which several large mountain ranges and water bodies may influence population structure. We combined 12 microsatellite loci and 1117 bp of the mitochondrial cytochrome b gene to explore genetic structure and demographic history in this species, using 269 individuals from various localities in Mainland China and Vietnam. High levels of genetic variation were identified for both mtDNA and microsatellites. mtDNA data revealed two main (Vietnam + southern China + southwestern China; eastern + southeastern China) and one minor (comprising only two individuals from the westernmost site) clades. Microsatellite data divided the eastern + southeastern China clade further into two genetic clusters, which include individuals from the eastern and southeastern regions, respectively. The Luoxiao and Nanling Mountains may be important barriers affecting the diversification of lineages. In the haplotype network of cytchrome b, many haplotypes were represented within a “star” cluster and this and other tests suggest recent expansion. However, microsatellite analyses did not yield strong evidence for a recent bottleneck for any population or genetic cluster. The three main clusters identified here should be considered as independent management units for conservation purposes. The release of Chinese cobras into the wild should cease unless their origin can be determined, and this will avoid problems arising from unnatural homogenization.
Discretization and Learning of Bayesian Networks using Stochastic Search, with Application to Base Realignment and Closure (BRAC)

DISCRETIZATION AND LEARNING OF BAYESIAN NETWORKS USING STOCHASTIC SEARCH, WITH APPLICATION TO BASE REALIGNMENT AND CLOSURE (BRAC) Pamela J. Hoyt, PhD. George Mason University, 2008 Dissertation Director: Dr. Kathryn B. Laskey The need for automated Bayesian Network (BN) construction from data has increased for a variety of reasons. Elicitation of networks from experts can be time consuming and expensive. With large, complex problems, construction of an accurate network, which ‘best’ describe the probability distribution of the training data can be difficult. The learning process is further complicated by missing or incomplete data, and mixed data. In light of these issues BN construction cannot rely on experts alone, rather experts can be used to enhance the network after the automated process. The closer technology comes to building models that reflect the real world the more their power as an inference tool will increase. This research is an empirical approach on determining how well a stochastic search discretizes continuous variables and learns structure. This study also has the added complexity of missing data. Our approach interleaves discretization with a stochastic search process to find a population of solutions for learning BNs. We compared our process to other methods that discretize as a preprocessing step. Learning BN structure as well as the parameters increases in difficulty when the variables are continuous or mixed (both continuous and discrete). Real world datasets are not generally discrete and missing data is common. Continuous variables are often discretized in order to use one of the established and well-known learning algorithms. Therefore, to handle the continuous variable the two common approaches are to apply a discretization method or use one of the families of parametric distributions. The novel approach we developed is a dynamic process that interleaves partitioning of continuous variables with learning using a stochastic search method called PopMCMC. We applied our new methodology to data from the U.S. Army’s recent Base Realignment and Closure (BRAC) study from 1988 to 1995, which consists primarily of both continuous and discrete variables complicated by missing data. The desired outcome was to develop a method to model the BRAC data as a BN. A BN offered a natural way to represent the uncertainties associated with the data and would then permit us to make queries relevant to the BRAC decision making issues.
Intratumor IL-17-Positive Mast Cells Are the Major Source of the IL-17 That Is Predictive of Survival in Gastric Cancer Patients

Interleukin-17 (IL-17) is prevalent in tumor tissue and suppresses effective anti-tumor immune responses. However, the source of the increased tumor-infiltrating IL-17 and its contribution to tumor progression in human gastric cancer remain poorly understood. In this study, we enrolled 112 gastric cancer patients, immunofluorescence was used to evaluate the colocalization of CD3, CD4, CD56, CD20, CD68, and mast cell tryptase (MCT) with IL-17. Immunohistochemistry was used to evaluate the distribution of microvessel density (CD34), CD66b+, CD68+, and FoxP3+ cells in different microanatomical areas. Prognostic value was determined by Kaplan-Meier analysis and a Cox regression model. The results showed that mast cells, but not T cells or macrophages, were the predominant cell type producing IL-17 in gastric cancer. Significant positive correlations were detected between densities of mast cell-derived IL-17 and microvessels, neutrophils, and regulatory T cells (Tregs). Futhermore, we found that the majority of vascular endothelial cells expressing Interleukin-17 receptor (IL-17R). Kaplan-Meier analysis revealed that increasing intratumor infiltrated mast cells and IL-17+ cells, as well as MCT+ IL-17+ cells, were significantly associated with worse overall survival. These findings indicated that mast cells were the major source of IL-17 in gastric cancer, and intratumor IL-17 infiltration may have promoted tumor progression by enhancing angiogenesis in the tumor microenvironment through the axis of IL-17/IL-17R. IL-17-positive mast cells showed a prognostic factor in gastric cancer, indicating that immunotherapy targeting mast cells might be an effective strategy to control intratumor IL-17 infiltration, and consequently reverse immunosuppression in the tumor microenvironment, facilitating cancer immunotherapy.
Turoctocog alfa (NovoEight®) – from design to clinical proof of concept

Turoctocog alfa (NovoEight®) is a recombinant factor VIII (rFVIII) with a truncated B‐domain made from the sequence coding for 10 amino acids from the N‐terminus and 11 amino acids from the C‐terminus of the naturally occurring B‐domain. Turoctocog alfa is produced in Chinese hamster ovary (CHO) cells without addition of any human‐ or animal‐derived materials. During secretion, some rFVIII molecules are cleaved at the C‐terminal of the heavy chain (HC) at amino acid 720, and a monoclonal antibody binding C‐terminal to this position is used in the purification process allowing isolation of the intact rFVIII. Viral inactivation is ensured by a detergent inactivation step as well as a 20‐nm nano‐filtration step. Characterisation of the purified protein demonstrated that turoctocog alfa was fully sulphated at Tyr346 and Tyr1664, which is required for optimal proteolytic activation by thrombin. Kinetic assessments confirmed that turoctocog alfa was activated by thrombin at a similar rate as seen for other rFVIII products fully sulphated at these positions. Tyr1680 was also fully sulphated in turoctocog alfa resulting in strong affinity (low nm Kd) for binding to von Willebrand factor (VWF). Half‐lives of 7.2 ± 0.9 h in F8‐KO mice and 8.9 ± 1.8 h haemophilia A dogs supported that turoctocog alfa bound to VWF after infusion. Functional studies including thromboelastography analysis of human haemophilia A whole blood with added turoctocog alfa and effect studies in mice bleeding models demonstrated a dose‐dependent effect of turoctocog alfa. The non‐clinical data thus confirm the haemostatic effect of turoctocog alfa and, together with the comprehensive clinical evaluation, support the use as FVIII replacement therapy in patients with haemophilia A.