Miracle-dz/UniFAR-FTUs huggingface dataset:
A Phase Ib Open-Label Multicenter Study of AZD4547 in Patients with Advanced Squamous Cell Lung Cancers

Purpose: Squamous cell lung cancers (SQCLC) account for 25% of all NSCLCs, yet the prognosis of these patients is poor and treatment options are limited. Amplified FGFR1 is one of the most common oncogenic events in SQCLCs, occurring in approximately 20% of cases. AZD4547 is a potent and selective FGFR1-3 inhibitor with antitumor activity in FGFR1-amplified SQCLC cell lines and patient-derived xenografts. Experimental Design: On the basis of these data, we performed a phase I study of AZD4547 in patients with previously treated stage IV FGFR1-amplified SQCLCs (NCT00979134). FGFR1 amplification (FGFR1:CEP8 ≥ 2) was determined by FISH. The primary endpoint was safety/tolerability. Secondary endpoints included antitumor activity, pharmacokinetics, pharmacodynamics, and molecular analyses. Results: Fifteen FGFR1-amplified patients were treated. The most common related adverse events (AE) were gastrointestinal and dermatologic. Grade ≥3–related AEs occurred in 3 patients (23%). Thirteen patients were evaluable for radiographic response assessment. The overall response rate was 8% (1 PR). Two of 15 patients (13.3%) were progression-free at 12 weeks, and the median overall survival was 4.9 months. Molecular tests, including next-generation sequencing, gene expression analysis, and FGFR1 immunohistochemistry, showed poor correlation between gene amplification and expression, potential genomic modifiers of efficacy, and heterogeneity in 8p11 amplicon. Conclusions: AZD4547 was tolerable at a dosage of 80 mg oral twice a day, with modest antitumor activity. Detailed molecular studies show that these tumors are heterogeneous, with a range of mutational covariates and stark differences in gene expression of the 8p11 amplicon that likely explain the modest efficacy of FGFR inhibition in this disease. Clin Cancer Res; 23(18); 5366–73. ©2017 AACR.
Interactive Network Analytical Tool for Instantaneous Bespoke Interrogation of Food Safety Notifications

Background The globalization of food supply necessitates continued advances in regulatory control measures to ensure that citizens enjoy safe and adequate nutrition. The aim of this study was to extend previous reports on network analysis relating to food notifications by including an optional filter by type of notification and in cases of contamination, by type of contaminant in the notified foodstuff. Methodology/Principal Findings A filter function has been applied to enable processing of selected notifications by contaminant or type of notification to i) capture complexity, ii) analyze trends, and iii) identify patterns of reporting activities between countries. The program rapidly assesses nations' roles as transgressor and/or detector for each category of contaminant and for the key class of border rejection. In the open access demonstration version, the majority of notifications in the Rapid Alert System for Food and Feed were categorized by contaminant type as mycotoxin (50.4%), heavy metals (10.9%) or bacteria (20.3%). Examples are given demonstrating how network analytical approaches complement, and in some cases supersede, descriptive statistics such as frequency counts, which may give limited or potentially misleading information. One key feature is that network analysis takes the relationship between transgressor and detector countries, along with number of reports and impact simultaneously into consideration. Furhermore, the indices that compliment the network maps and reflect each country's transgressor and detector activities allow comparisons to be made between (transgressing vs. detecting) as well as within (e.g. transgressing) activities. Conclusions/significance This further development of the network analysis approach to food safety contributes to a better understanding of the complexity of the effort ensuring food is safe for consumption in the European Union. The unique patterns of the interplay between detectors and transgressors, instantly revealed by our approach, could supplement the intelligence gathered by regulatory authorities and inform risk based sampling protocols.
Identification of dysregulated modules based on network entropy in type 1 diabetes

Type 1 diabetes is a prevalent autoimmune disease of which the underlying mechanisms remain to be elucidated. The aim of the study was to identify dysregulated modules of type 1 diabetes. After microarray data were preprocessed, 20,545 genes were obtained. By integrating gene expression data and protein-protein interactions (PPI) data, 48,778 new networks were obtained, including 7,953 genes. After simplifying networks, we obtained 24 target networks. By ranking networks with P-values, two modules with P<0.05 were identified, including the genes, CCNB1, CDC45, GINS2, NDC80, FBXO5, NCAPG and DLGAP5. Module 2 was part of module 1. The identified modules and genes may provide new insights into the underlying biological mechanisms that drive the progression of type 1 diabetes.
Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome

Objective To evaluate the safety and preliminary pharmacokinetics of a pharmaceutical formulation of purified cannabidiol (CBD) in children with Dravet syndrome. Methods Patients aged 4–10 years were randomized 4:1 to CBD (5, 10, or 20 mg/kg/d) or placebo taken twice daily. The double-blind trial comprised 4-week baseline, 3-week treatment (including titration), 10-day taper, and 4-week follow-up periods. Completers could continue in an open-label extension. Multiple pharmacokinetic blood samples were taken on the first day of dosing and at end of treatment for measurement of CBD, its metabolites 6-OH-CBD, 7-OH-CBD, and 7-COOH-CBD, and antiepileptic drugs (AEDs; clobazam and metabolite N-desmethylclobazam [N-CLB], valproate, levetiracetam, topiramate, and stiripentol). Safety assessments were clinical laboratory tests, physical examinations, vital signs, ECGs, adverse events (AEs), seizure frequency, and suicidality. Results Thirty-four patients were randomized (10, 8, and 9 to the 5, 10, and 20 mg/kg/d CBD groups, and 7 to placebo); 32 (94%) completed treatment. Exposure to CBD and its metabolites was dose-proportional (AUC0–t). CBD did not affect concomitant AED levels, apart from an increase in N-CLB (except in patients taking stiripentol). The most common AEs on CBD were pyrexia, somnolence, decreased appetite, sedation, vomiting, ataxia, and abnormal behavior. Six patients taking CBD and valproate developed elevated transaminases; none met criteria for drug-induced liver injury and all recovered. No other clinically relevant safety signals were observed. Conclusions Exposure to CBD and its metabolites increased proportionally with dose. An interaction with N-CLB was observed, likely related to CBD inhibition of cytochrome P450 subtype 2C19. CBD resulted in more AEs than placebo but was generally well-tolerated. Classification of evidence This study provides Class I evidence that for children with Dravet syndrome, CBD resulted in more AEs than placebo but was generally well-tolerated.
Fitness Consequences of Boldness in Juvenile and Adult Largemouth Bass

To date, most studies investigating the relationship between personality traits and fitness have focused on a single measure of fitness (such as survival) at a specific life stage. However, many personality traits likely have multiple effects on fitness, potentially operating across different functional contexts and stages of development. Here, we address the fitness consequences of boldness, under seminatural conditions, across life stages and functional contexts in largemouth bass (Micropterus salmoides). Specifically, we report the effect of boldness on (1) juvenile survivorship in an outdoor pond containing natural prey and predators and (2) adult reproductive success in three outdoor ponds across three reproductive seasons (years). Juvenile survival was negatively affected by boldness, with bolder juveniles having a lower probability of survival than shyer juveniles. In contrast, bolder adult male bass had greater reproductive success than their shyer male counterparts. Female reproductive success was not affected by boldness. These findings demonstrate that boldness can affect fitness differently across life stages. Further, boldness was highly consistent across years and significantly heritable, which suggests that boldness has a genetic component. Thus, our results support theory suggesting that fitness trade-offs across life stages may contribute to the maintenance of personality variation within populations.
Reliability Evaluation Methodology of Complex Systems Based on Dynamic Object-Oriented Bayesian Networks

A novel reliability evaluation methodology of complex systems is proposed using dynamic object-oriented Bayesian networks (DOOBNs). This modeling methodology consists of two main phases, namely, construction phases for object-oriented Bayesian networks (OOBNs) and for DOOBNs. In the first phase, the network fragments with similar structures and parameters are divided into classes; these classes are then encapsulated. The construction of OOBNs is completed according to the relationship among the encapsulated classes. In the second phase, every fragment of the dynamic Bayesian networks that was constructed by the first phase is encapsulated as a class called DOOBN. The construction of DOOBNs is completed according to the relationship among the time fragments. The accuracy of this methodology is validated using the all-series, all-voting, voting-after-series, series-after-voting, parallel-after-series, and series-after-parallel systems. This methodology is further illustrated and verified by using deepwater blowout preventer system and can model the system from global to local levels, thereby effectively reducing modeling difficulty and adopting efficient arithmetic reasoning algorithms.
The Conceptual Framework of the National Diabetes Education Outcomes System (NDEOS)

PURPOSE this article describes the systems-based conceptual framework for the definition of diabetes education outcomes and the development of the National Diabetes Education Outcomes System (NDEOS). METHODS Development of the NDEOS was based on integrating diabetes education into the diabetes care system; identifying and tracking standardized learning, behavioral, and clinical outcomes measurements; and gathering data at the individual, program, and national levels. Each component was formulated based on available literature and through consensus with the American Association of Diabetes Educators (AADE) Outcomes Task Force and other multidisciplinary healthcare professionals. RESULTS Behavior change is the key outcome measurement for diabetes self-management education (DSME). In addition, diabetes educators should collect other immediate, intermediate, and long-term outcomes for monitoring the impact of DSME. The NDEOS system includes standardized data collection tools for the participant, the educator, and the program manager, and provides reports at the individual, program, and national levels. CONCLUSIONS By capturing outcomes data using valid, reliable, and evidence-based tools, the NDEOS strives to support diabetes educators and provide a uniform data set that can be used to influence public policy, support reimbursement negotiations, and assist researchers.
Acoustic emission characteristics of damage processes in self-reinforced polyethylene composites

Upon being subjected to the external load,acoustic emission(AE) may occur from matrix cracking,interface debonding,fiber fracture,etc in composite materials.UHMWPE/HDPE composite materials were experimented to determine the event amplitude content of AE signals under tensile loads.Special specimens,designed to fail under well-defined modes such as matrix plastic deformation and cracking,fiber-matrix debonding,fiber breakage,delamination,etc were tested under the loads from zero to failure.The fracture surfaces of the specimens were observed by a scanning electron microscope(SEM). The AE signals were distinguished as being released from(several) special types of damage.AE measurements were performed subsequently for different types of UHMWPE/HDPE quasi-isotropic laminates under the same loading conditions.The correlations are established between the damage modes and acoustic emission events amplitude of special specimens which exhibit the dominant damage mecha-nisms.The AE characteristics of damage growth processes and the fracture mechanisms in UHMWPE/HDPE(quasi-isotropic) laminates are revealed.Accumulative numbers of acoustic emission events for different types of(UHMWPE/HDPE) quasi-isotropic laminates vs tensile stress curves are different from each other;the corresponding loading levels of their same type of damage occurrence are not equal.The results show that ply stacking angles and(sequences) affect remarkably the damage growth process of these laminates.It is verified that the final fracture of these materials is caused by severe interlaminar delamination.
Comparison of objective quality models for adaptive bit-streaming services

As adaptive bit-streaming services are increasingly available, there is a greater need to monitor the perceptual quality of video services of networks. A number of objective video/image quality measurement methods have been proposed. In this paper, we performed several subjective tests using UHD signals that are reduced to various resolutions. Then, we applied several objective video/image quality measurement models to investigate the applicability of such models to monitor the perceptual quality of adaptive bit-stream services.
Functional near-infrared spectroscopy is in moderate accordance with functional MRI in determining lateralisation of frontal language areas

Purpose Understanding language dominance is crucial in pre-surgical evaluation of patients with epilepsy and in patients having a tumour close to the language area. Functional magnetic resonance imaging (fMRI) studies are well established in evaluating language dominance. Functional near-infrared spectroscopy (fNIRS) is a non-invasive optical imaging modality that offers a convenient and affordable technique to image language-related cortical areas. This study investigates the agreement between results from task-based fMRI and fNIRS in determining language lateralisation. Methods Language laterality indices LIs were calculated from both fMRI and fNIRS measurements of the same individual volunteers by using an identical paradigm. Statistical measures of percentage agreement and kappa value have been calculated for testing agreement and reliability. Results A correlation analysis of the LI values shows a good correlation with r = 0.677 at p < 0.05. Statistical comparison of both fMRI and fNIRS methods for language lateralisation yielded a percentage agreement of 90% and a moderate kappa value of κ = 0.621. Conclusion Our study suggests that fNIRS is in moderate accordance with fMRI in determining lateralisation of the frontal language areas. It implies that the optical imaging technique can provide additional information on functional lateralisation of frontal language areas.
Focus Section Health IT Usability: Applying a Task-Technology Fit Model to Adapt an Electronic Patient Portal for Patient Work

Abstract Objectives Although electronic patient portals are offered by most health care organizations, poor usability and poor fit to patient needs may pose barriers to adoption. We collaborated with an academic hospital to conduct iterative user evaluation of a newly deployed portal designed to deliver inpatient data upon hospital discharge. Methods Three evaluators applied heuristic usability evaluation and conducted 23 individual user testing sessions with patients with chronic disease or managing the care of family members with chronic disease. Evaluation and development/improvement were conducted iteratively. User testing and analysis of qualitative data were both conducted from the perspective of a task-technology fit framework, to assess the degree of fit between the portal and patient work. Results Ability to complete health information management tasks, perceived usability, and positive comments from users improved over the course of the iterative development. However, patients still encountered significant difficulties accomplishing certain tasks such as setting up proxy accounts. The problems were most severe when patients did not start with a clear understanding of tasks that they could accomplish. In exploring the portal, novice users frequently described anecdotes from their own medical history or constructed fictional narratives about a hypothetical patient. Conclusion Chronic illness imposes a significant workload on patients, and applying a task-technology framework for evaluation of a patient portal helped improve the portal's fit to patient needs. However, it also revealed that patients often lack a clear understanding of tasks that would help them accomplish personal health information management. Portal developers may need to educate patients about types of patient work involving medical centers, in a way that developers of clinical information systems do not need to do. An approach to doing this might be to provide narratives about hypothetical patients.
The intrinsic strength of triangular symmetrical composite eutectic

Composite ceramic has the excellent properties at normal and high temperatures, especially when the structure of the composite eutectic is triangular symmetrical. Obviously, mechanical behavior and fracture properties of composite ceramic closely relates to the micro-structure of symmetrical triangular eutectic. In order to reveal the mechanical properties of eutectic composite ceramic, it is necessary to determine the intrinsic strength of triangular composite eutectic. Since the fiber and matrix of triangular symmetrical composite eutectic sharing a same covalent bond, the theoretical cohesion strength of symmetrical triangular eutectic was obtained by the combination-separation displacement of intrinsic bond. Basing on micro-structure plastic deformation before fracture of composite eutectic matrix, the dislocation pile-up model of eutectic composite ceramics was established. And then intrinsic bond fracture shear stress of triangular symmetrical composite eutectic was given by using the theory of disl.
Realization of real time adaptive CFAR processor for homing application in marine environment

Airborne pulse Doppler radar operating against marine target has to detect the target in presence of severe interference which may be homogeneous or non homogeneous depending upon environmental conditions. This necessitates implementing an adaptive CFAR processor to maintain a constant false alarm rate. Considering large range-Doppler maps generated during signal processing, implementation of CFAR processor is crucial. In case of homing radars update rates to guidance algorithm are stringent; therefore real time signal processing is required. In this paper real time implementation of Ordered Statistics Adaptive CFAR processor for terminal guidance application is presented. Implementation is done on KCU105 FPGA evaluation platform using KINTEX-Ultrascale FPGA. Highly parallel architecture of FPGA is used effectively to give better throughput. Further, presented scheme is evaluated and validated with real experimental data collected by sea trials.
Comparative Transcriptome Profiling of Chilling Stress Responsiveness in Two Contrasting Rice Genotypes

Rice is sensitive to chilling stress, especially at the seedling stage. To elucidate the molecular genetic mechanisms of chilling tolerance in rice, comprehensive gene expressions of two rice genotypes (chilling-tolerant LTH and chilling-sensitive IR29) with contrasting responses to chilling stress were comparatively analyzed. Results revealed a differential constitutive gene expression prior to stress and distinct global transcription reprogramming between the two rice genotypes under time-series chilling stress and subsequent recovery conditions. A set of genes with higher basal expression were identified in chilling-tolerant LTH compared with chilling-sensitive IR29, indicating their possible role in intrinsic tolerance to chilling stress. Under chilling stress, the major effect on gene expression was up-regulation in the chilling- tolerant genotype and strong repression in chilling-sensitive genotype. Early responses to chilling stress in both genotypes featured commonly up-regulated genes related to transcription regulation and signal transduction, while functional categories for late phase chilling regulated genes were diverse with a wide range of functional adaptations to continuous stress. Following the cessation of chilling treatments, there was quick and efficient reversion of gene expression in the chilling-tolerant genotype, while the chilling-sensitive genotype displayed considerably slower recovering capacity at the transcriptional level. In addition, the detection of differentially-regulated TF genes and enriched cis-elements demonstrated that multiple regulatory pathways, including CBF and MYBS3 regulons, were involved in chilling stress tolerance. A number of the chilling-regulated genes identified in this study were co-localized onto previously fine-mapped cold-tolerance-related QTLs, providing candidates for gene cloning and elucidation of molecular mechanisms responsible for chilling tolerance in rice.
Coming of old age: understanding older adults’ engagement and needs in coproduction activities for healthy ageing

ABSTRACT We report an investigation of how older adults engage in social activities and community events in support of their mental, physical, and emotional health. We focus on personal and collaborative agency in a community context, and construe health as an outcome that is coproduced by a person and other engaged community members. Using qualitative methods, we investigated the coproduction of health among members of retirement communities and people who are ageing in place. We found that our participants, irrespective of living arrangements, engaged in a diverse range of coproduction activities, including physical, socialising, service, discussion, and interest-based activities. We also identified desired but less-supported coproduction opportunities, such as opportunistic activities and the need to better appropriate social resources to enable coproductions. We draw from these findings to consider design implications of technological support for facilitating older adults to coproduce.
Benchmarking Geant4 for spallation neutron source calculations

Geant4 is becoming increasingly used for radiation transport simulations of spallation neutron sources and related components. Historically, the code has seen little usage in this field and it is of general interest to investigate the suitability of Geant4 for such applications. For this purpose, we carried out Geant4 calculations based on simple spallation source geometries and also with the the European Spallation Source Technical Design Report target and moderator configuration. The results are compared to calculations performed with the Monte Carlo N- Particle extended code. The comparisons are carried out over the full spallation neutron source energy spectrum, from sub-eV energies up to thousands of MeV. Our preliminary results reveal that there is generally good agreement between the simulations using both codes. Additionally, we have also implemented a general weight-window generator for Geant4 based applications and present some results of the method applied to the ESS target model.