Miracle-dz/UniFAR-FTUs huggingface dataset:
tracer for in vivo monitoring of HER2 expression by positron emission tomography

Purpose The expression of human epidermal growth factor receptor-2 (HER2) receptors in cancers is correlated with a poor prognosis. If assessed in vivo, it could be used for selection of appropriate therapy for individual patients and for monitoring of the tumor response to targeted therapies. We have radiolabeled a HER2-binding Affibody molecule with fluorine-18 for in vivo monitoring of the HER2 expression by positron emission tomography (PET). Materials and methods The HER2-binding ZHER2:342–Cys Affibody molecule was conjugated with N-2-(4-[ 18 F]fluorobenzamido)ethyl]maleimide([ 18 F]FBEM). The in vitro binding of the resulting radioconjugate was characterized by receptor saturation and competition assays. For in vivo studies, the radioconjugate was injected into the tail vein of mice bearing subcutaneousHER2-positiveorHER2-negativetumors.Some of the mice were pre-treated with non-labeled ZHER2:342�Cys. The animals were sacrificed at different times post-injection, and the radioactivity in selected tissues was measured. PET images were obtained using an animal PET scanner. Results In vitro experiments indicated specific, high-affinity binding to HER2. PET imaging revealed a high accumulation of the radioactivity in the tumor as early as 20 min after injection, with a plateau being reached after 60 min. These results were confirmed by biodistribution studies demonstrating that, as early as 1 h post-injection, the tumor to blood concentration ratio was 7.5 and increased to 27 at 4 h. Presaturation of the receptors with unlabeled ZHER2:342–Cys lowered the accumulation of radioactivity in HER2-positive tumors to the levels observed in HER2-negative ones. Conclusion Our results suggest that the [ 18 F]FBEM-ZHER2:342 radioconjugate can be used to assess HER2 expression in vivo.
Co-evolution and morphogenetic systems

The emerging field of morphogenetic engineering proposes to design complex heterogeneous system focused on the paradigm of emergence. Necessarily at the interface of disciplines, its concepts can be defined through multiple viewpoints. This contribution aims at linking a co-evolutionary perspective on such systems with morphogenesis, and therein at bringing a novel conceptual approach to the bottom-up design of complex systems which allows to fully consider co-evolutive processes. We first situate systems of interest at the interface between biological and social systems, and introduce a multidisciplinary perspective on co-evolution. Building on Holland's signals and boundaries theory of complex adaptive systems, we finally suggest that morphogenetic systems are equivalent to combinations of co-evolutionary niches. This introduces an entry to morphogenetic engineering focused on co-evolution between components of a system. Applications can be found in a broad range of subjects, which we illustrate with the example of planning in territorial systems, suggesting an extended scope for the relevance of morphogenetic engineering concepts.
Colorectal cancer screening prevalence and predictors among Asian American subgroups using Medical Expenditure Panel Survey National Data

Asian American (AA) ethnic subgroups are diverse in socio‐economic status, years in the United States, English proficiency, and cultures with different health seeking behaviors and health care access. Fifty‐two percent of AAs age ≥50 years had colorectal cancer screening (CRCS) in 2013, compared with 61% of non‐Hispanic whites. We hypothesized that CRCS prevalence among AA ethnicities is heterogeneous and that the reasons related to CRCS among AA subgroups are associated with demographic characteristics, acculturation, health care access, and health attitudes.
Experiences of severe childhood maltreatment, depression, anxiety and alcohol abuse among adults in Finland

Childhood maltreatment increases the risk of subsequent depression, anxiety and alcohol abuse, but the rate of resilient victims is unknown. Here, we investigated the rate of victims that do not suffer from clinical levels of these problems after severe maltreatment in a population-based sample of 10980 adult participants. Compared to men, women reported more severe emotional and sexual abuse, as well as more severe emotional neglect. For both genders, severe emotional abuse (OR = 3.80 [2.22, 6.52]); severe physical abuse (OR = 3.97 [1.72, 9.16]); severe emotional neglect (OR = 3.36 [1.73, 6.54]); and severe physical neglect (OR = 11.90 [2.66, 53.22]) were associated with depression and anxiety while only severe physical abuse (OR = 3.40 [1.28, 9.03]) was associated with alcohol abuse. Looking at men and women separately, severe emotional abuse (OR = 6.05 [1.62, 22.60] in men; OR = 3.74 [2.06, 6.81] in women) and severe physical abuse (OR = 6.05 [1.62, 22.60] in men; OR = 3.03 [0.99, 9.33] in women) were associated with clinical levels of depression and anxiety. In addition, in women, severe sexual abuse (OR = 2.40 [1.10, 5.21]), emotional neglect (OR = 4.78 [2.40, 9.56]), and severe physical neglect (OR = 9.86 [1.99, 48.93]) were associated with clinical levels of depression and anxiety. Severe emotional abuse in men (OR = 3.86 [0.96, 15.48]) and severe physical abuse in women (OR = 5.18 [1.48, 18.12]) were associated with alcohol abuse. Concerning resilience, the majority of severely maltreated participants did not report clinically significant levels of depression or anxiety (72%), or alcohol abuse (93%) in adulthood. Although the majority of severely abused or neglected individuals did not show clinical levels of depression, anxiety or alcohol use, severe childhood maltreatment increased the risk for showing clinical levels of psychopathology in adulthood.
Preparation, Characterization and Optimization of Poloxamer Solid Dispersions of a Poorly Water Soluble Drug Aprepitant

Aim: The aim of the present investigation was to enhance the dissolution rate of a poorly water soluble drug, aprepitant, by preparation of solid dispersion with hydrophilic carrier, poloxamer 188, using solvent evaporation method. Place and Duration of Study: Department of Pharmaceutical Sciences and Department of Emerging Life Sciences, Guru Nanak Dev University, Amritsar, Punjab, between Original Research Article British Journal of Pharmaceutical Research, 4(20): 2436-2454, 2014 2437 August 2012 and July 2013. Study Design: Designs of experiments were carried out with two input variables, drug to carrier ratio (X1) and amount of solvent (X2). A total of 7 experiments were performed (4 factorial runs and 3 centre points) as per full factorial design. Percent dissolution efficiency at 60 min (DE60) was selected as the response variable. Pareto chart along with half probability plot were studied for determining the most significant process variables, which were modelled using ANOVA. Methodology: Solid dispersions of aprepitant with poloxamer 188 were prepared using the solvent evaporation method and studied systematically using an optimization technique. A 2 2 full factorial design approach was used for the optimization of process variables on dissolution characteristics. The optimized solid dispersion was characterized by dissolution studies, Fourier Transform Infrared Spectroscopy, Differential Scanning Calorimetry, X-ray powder Diffraction studies and Scanning Electron Microscopy. Results: The results of the experimental study confirm that the factors like drug to carrier ratio and solvent amount significantly influence the dependent variable DE60. A high level of drug to carrier ratio and low level of solvent amount were found to be suitable for maximum DE60. The use of factorial design approach helped in the optimization of the solid dispersion. The characterization of optimized solid dispersion (F5) demonstrated that the decrease in crystallinity of aprepitant and poloxamer 188 might be responsible for the enhanced dissolution rate. Analysis of dissolution data indicated the best fitting with firstorder model. Conclusion: Dissolution enhancement of aprepitant was successfully obtained by preparing its solid dispersion with poloxamer 188 using solid evaporation method.
Hospitality Industry Expectations of Entry-Level College Graduates: Attitude over Aptitude

Executive Summary his article reports on the findings of an empirical study conducted with senior hiring executives who represent various sectors of the hospitality and tourism industry in the Metropolitan Statistical Area (MSA) of Orlando, Florida. The geographic area was chosen for its representation of a number of hospitality and tourism sectors. While the sample represented various sectors, the purpose of the study was to identify perceptions of attributes preferred for entry-level workers primarily in the lodging and restaurant sectors. The article presents background information from the literature, methodologies employed within the study, as well as conclusions and recommendations for future education/industry initiatives in the MSA. The article presents a follow-up to a prior study to determine whether practitioners view embedded attitudinal factors as strongly as had been reported five years prior within the same MSA. T
Exploratory Structural Equation Modeling, Integrating CFA and EFA: Application to Students' Evaluations of University Teaching

This study is a methodological-substantive synergy, demonstrating the power and flexibility of exploratory structural equation modeling (ESEM) methods that integrate confirmatory and exploratory factor analyses (CFA and EFA), as applied to substantively important questions based on multidimentional students' evaluations of university teaching (SETs). For these data, there is a well established ESEM structure but typical CFA models do not fit the data and substantially inflate correlations among the nine SET factors (median rs = .34 for ESEM, .72 for CFA) in a way that undermines discriminant validity and usefulness as diagnostic feedback. A 13-model taxonomy of ESEM measurement invariance is proposed, showing complete invariance (factor loadings, factor correlations, item uniquenesses, item intercepts, latent means) over multiple groups based on the SETs collected in the first and second halves of a 13-year period. Fully latent ESEM growth models that unconfounded measurement error from communality showed almost no linear or quadratic effects over this 13-year period. Latent multiple indicators multiple causes models showed that relations with background variables (workload/difficulty, class size, prior subject interest, expected grades) were small in size and varied systematically for different ESEM SET factors, supporting their discriminant validity and a construct validity interpretation of the relations. A new approach to higher order ESEM was demonstrated, but was not fully appropriate for these data. Based on ESEM methodology, substantively important questions were addressed that could not be appropriately addressed with a traditional CFA approach.
Reoperation Rates After Surgery for Degenerative Cervical Spine Disease According to Different Surgical Procedures: National Population-based Cohort Study

Study Design. National population-based cohort study. Objective. To evaluate reoperation rates of cervical spine surgery for cervical degenerative conditions utilizing a national population database. Summary of Background Data. There is an inherently low incidence of reoperation after surgery for cervical degenerative disease. Therefore, it is difficult to sufficiently power studies to detect differences between reoperation rates of different cervical surgical procedures. National population-based databases provide large, longitudinally followed cohorts that may help overcome this challenge. Methods. We used the Korean Health Insurance Review and Assessment Service national database to select our study population. We included patients with diagnosis of cervical spondylotic radiculopathy or myelopathy who underwent cervical surgeries from January 2009 to June 2014. We separated patients into three groups based on surgical procedures: discectomy or corpectomy with anterior fusion, laminoplasty, or laminectomy with posterior fusion. Age, sex, presence of diabetes, osteoporosis, associated comorbidities, number of operated cervical disc levels, and hospital types were considered potential confounding factors. Reoperation rates were analyzed over early and late periods. Results. The reoperation rate over the entire follow-up period was 3.31%. Overall, the reoperation rate was significantly higher after laminectomy with posterior fusion or laminoplasty than after discectomy or corpectomy with anterior fusion. A similar pattern was seen during the late period. In the early period, rates were higher only after laminectomy with posterior fusion than after discectomy or corpectomy with anterior fusion. Sex, presence of diabetes, associated comorbidities, and hospital types were noted to be risk factors for reoperation. Conclusion. The reoperation rate was higher after laminectomy with posterior fusion or laminoplasty. Given clinical scenarios in which either anterior or posterior approaches can be utilized, risk of reoperation can be another variable to consider in surgical planning and patient education. Level of Evidence: 3
Physical interactions among flavonoid enzymes in snapdragon and torenia reveal the diversity in the flavonoid metabolon organization of different plant species

Flavonoid metabolons (weakly-bound multi-enzyme complexes of flavonoid enzymes) are believed to occur in diverse plant species. However, how flavonoid enzymes are organized to form a metabolon is unknown for most plant species. We analyzed the physical interaction partnerships of the flavonoid enzymes from two lamiales plants (snapdragon and torenia) that produce flavones and anthocyanins. In snapdragon, protein-protein interaction assays using yeast and plant systems revealed the following binary interactions: flavone synthase II (FNSII)/chalcone synthase (CHS); FNSII/chalcone isomerase (CHI); FNSII/dihydroflavonol 4-reductase (DFR); CHS/CHI; CHI/DFR; and flavonoid 3'-hydroxylase/CHI. These results along with the subcellular localizations and membrane associations of snapdragon flavonoid enzymes suggested that FNSII serves as a component of the flavonoid metabolon tethered to the endoplasmic reticulum (ER). The observed interaction partnerships and temporal gene expression patterns of flavonoid enzymes in red snapdragon petal cells suggested the flower stage-dependent formation of the flavonoid metabolon, which accounted for the sequential flavone and anthocyanin accumulation patterns therein. We also identified interactions between FNSII and other flavonoid enzymes in torenia, in which the co-suppression of FNSII expression was previously reported to diminish petal anthocyanin contents. The observed physical interactions among flavonoid enzymes of these plant species provided further evidence supporting the long-suspected organization of flavonoid metabolons as enzyme complexes tethered to the ER via cytochrome P450, and illustrated how flavonoid metabolons mediate flower coloration. Moreover, the observed interaction partnerships were distinct from those previously identified in other plant species (Arabidopsis thaliana and soybean), suggesting that the organization of flavonoid metabolons may differ among plant species.
Optical Music Recognition with Convolutional Sequence-to-Sequence Models

Optical Music Recognition (OMR) is an important technology within Music Information Retrieval. Deep learning models show promising results on OMR tasks, but symbol-level annotated data sets of sufficient size to train such models are not available and difficult to develop. We present a deep learning architecture called a Convolutional Sequence-to-Sequence model to both move towards an end-to-end trainable OMR pipeline, and apply a learning process that trains on full sentences of sheet music instead of individually labeled symbols. The model is trained and evaluated on a human generated data set, with various image augmentations based on real-world scenarios. This data set is the first publicly available set in OMR research with sufficient size to train and evaluate deep learning models. With the introduced augmentations a pitch recognition accuracy of 81% and a duration accuracy of 94% is achieved, resulting in a note level accuracy of 80%. Finally, the model is compared to commercially available methods, showing a large improvements over these applications.
Anti–Herpes Simplex Virus Type-1 Activity and Phenolic Content of Crude Ethanol Extract and Four Corresponding Fractions of Quercus brantii L Acorn

This research was aimed to evaluate anti–herpes simplex virus type-1 (anti-HSV-1) activity of crude ethanol extract and 4 corresponding fractions of Quercus brantii acorn in vitro. Crude ethanol extract was prepared and subjected to fractionation with different polarity. Anti-HSV-1 activity was evaluated on baby hamster kidney cell line using MTT assay. The inhibitory effect of the plant materials on adsorption and/or post-adsorption stages of HSV-1 replication cycle were determined. Regression analysis was used to determine 50% inhibitory concentration and 50% cytotoxicity concentration, from which selective index was calculated. Based on our results, the chloroform fraction and the crude extract had the highest effect against HSV-1 with selectivity indices of 53.8 and 48.4, respectively. The n-hexane, n-butanol, and chloroform fractions inhibited HSV-1 replication in postadsorption stage (P < .001). The results obtained indicated that the chloroform fraction of Q brantii acorn with high inhibitory effect against HSV-1 replication could be a new promising anti-HSV-1 agent.
IGF2 mRNA binding protein 3 (IMP3) promotes glioma cell migration by enhancing the translation of RELA/p65

The diffusely infiltrative nature of glioblastoma (GBM) makes them highly recurrent. IGF2 mRNA-binding protein 3 (IMP3), a GBM upregulated RNA binding protein, promotes glioma cell migration. An integrative bioinformatics analysis identified p65 (RELA), a subunit of NF-κB heterodimer as a target and an important mediator of IMP3 promoted glioma cell migration. IMP3 increased p65 protein levels without any change in p65 transcript levels, but promoted its polysome association. RIP-PCR demonstrated the binding of IMP3 to p65 transcript. UV crosslinking experiments with in vitro transcribed RNA confirmed the specific and direct binding of IMP3 to sites on p65 3′UTR. Further, IMP3 induced luciferase activity from p65 3′UTR reporter carrying wild type sites but not mutated sites. Exogenous overexpression of p65 from a 3′UTR-less construct rescued the reduced migration of glioma cells in IMP3 silenced condition. In addition, IMP3 silencing inhibited glioma stem-like cell maintenance and migration. The exogenous overexpression of 3′UTR-less p65 significantly alleviated the inhibition of neurosphere formation observed in IMP3 silenced glioma stem-like cells. Further, we show that IMP3 is transcriptionally activated by NF-κB pathway indicating the presence of a positive feedback loop between IMP3 and p65. This study establishes p65 as a novel target of IMP3 in increasing glioma cell migration and underscores the significance of IMP3-p65 feedback loop for therapeutic targeting in GBM.
Incidence and Risk Factors of Adjacent Cranial Facet Joint Violation Following Pedicle Screw Insertion Using Cortical Bone Trajectory Technique

Study Design. Retrospective study evaluating cranial facet joint violation (FJV) by pedicle screws. Objective. The aim of the study was to determine the incidence and risk factors of FJV following screw placement via cortical bone trajectory (CBT). Summary of Background Data. CBT is a new minimally invasive technique for lumbar pedicle screw insertion that minimizes muscle dissection. Inserting a screw from a more caudal entry point can reduce iatrogenic damage to the cranial facet joint; however, no previous reports exist describing the incidence of FJV secondary to the CBT technique. Methods. We reviewed 202 consecutive patients who underwent lumbar pedicle screw instrumentation using CBT from October 2011 to June 2015. Postoperative CT scans were obtained to determine the degree and incidence of FJV. Clinical and imaging data were analyzed to clarify the risk factors of FJV. The detailed positions of the proximal screws were also investigated and compared between the FJV and non-FJV groups. Results. The incidence of FJV by the proximal screws was 11.8% (48/404), with no occurrence of intra-articular FJV. Multiple logistic regression analysis revealed that age >70 years, vertebral slip >10%, and adjacent facet joint degeneration (Pathria's grade 2 or 3) were independent factors significantly affecting FJV. There were statistically significant differences between the FJV and non-FJV groups in the facet-screw distance (3.2 ± 1.0 vs. 8.1 ± 2.3 mm, P < 0.01), the cranial angle (25.8 ± 6.3° vs. 29.9 ± 7.6°, P < 0.01), and the lamina-screw head distance (5.6 ± 1.6 vs. 6.4 ± 1.9 mm, P < 0.01). Conclusion. Lumbar pedicle screw placement via CBT would reduce FJV; however, special care should be taken in patients with age >70 years, vertebral slip >10%, and facet degeneration. Level of Evidence: 3
Deep Salience Representations for F0 Estimation in Polyphonic Music

Estimating fundamental frequencies in polyphonic music remains a notoriously difﬁcult task in Music Information Retrieval. While other tasks, such as beat tracking and chord recognition have seen improvement with the application of deep learning models, little work has been done to apply deep learning methods to fundamental frequency related tasks including multi-f 0 and melody tracking, primarily due to the scarce availability of labeled data. In this work, we describe a fully convolutional neural network for learning salience representations for estimating fundamental frequencies, trained using a large, semi-automatically generated f 0 dataset. We demonstrate the effectiveness of our model for learning salience representations for both multi-f 0 and melody tracking in polyphonic audio, and show that our models achieve state-of-the-art performance on several multi-f 0 and melody datasets. We conclude with directions for future research.
NLR Nod1 signaling promotes survival of BCR-engaged mature B cells through up-regulated Nod1 as a positive outcome

Although B cell development requires expression of the B cell antigen receptor (BCR), it remains unclear whether engagement of self-antigen provides a positive impact for most B cells. Here, we show that BCR engagement by self-ligand during development in vivo results in up-regulation of the Nod-like receptor member Nod1, which recognizes the products of intestinal commensal bacteria. In anti-thymocyte/Thy-1 autoreactive BCR knock-in mice lacking self–Thy-1 ligand, immunoglobulin light chain editing occurred, generating B cells with up-regulated Nod1, including follicular and marginal zone B cells with natural autoreactivity. This BCR editing with increased Nod1 resulted in preferential survival. In normal adult mice, most mature B cells are enriched for Nod1 up-regulated cells, and signaling through Nod1 promotes competitive survival of mature B cells. These findings demonstrate a role for microbial products in promoting survival of mature B cells through up-regulated Nod1, providing a positive effect of BCR engagement on development of most B cells.