Miracle-dz/UniFAR-FTUs huggingface dataset:
College students’ use of transportation networking companies: An opportunity to decrease substance-impaired driving

Abstract Objective: To examine the use of transportation networking companies (TNCs) (eg, Uber) among substance-using students in rural and urban college settings. Participants: Students at two large state universities were randomly selected and screened for substance use. Participants reported use of TNCs generally and after substance use and whether TNC use was on or near campus or in other environments. Methods: Data were evaluated using chi-square test, t-tests, and Fisher’s exact tests. Results: Most (85%) participants (n = 99, 61% response rate) had used a TNC. Among students who used TNCs on/near campus, 98% of rural students used them after substance use compared to 85% of urban students (p = .037). We did not detect differences in TNC use by gender or age. Conclusions: Results indicate that TNC use is common after college student substance use and may play a particularly important role in preventing impaired driving for rural campuses where existing transportation options are limited.
Phylogeography of Swertia perennis in Europe based on cpDNA markers

Background Swertia perennis(Gentianaceae) is a perennial diploid and clonal plant species that is discontinuously distributed in peat bogs in the mountains of Europe, Asia and North America as well as in the lowlands of Europe. The current geographical dispersion of S. perennis is probably the result of quaternary climatic changes that have played an important role in determining the distribution of Swertia and other plant and animal species. Methods In this study we used molecular techniques and combined data from chloroplast DNA markers (trnLF region and trnH-psbA spacer) to elucidate the phylogeography of S. perennis in Europe. Plants were collected from 28 populations in different locations in the lowlands and mountainous areas of Europe (e.g., the Carpathians, Sudetes, Bohemian Forest and Alps). cDNA was analysed to detect the genetic relationship between specimens from different locations. Results A total of 20 haplotypes were identified across the dataset. They were characterised by a high level of genetic variability but showed a lack of phylogeographical structure. This pattern may be the result of repeated recolonization and expansion from several areas. Such genetic differentiation may also be attributed to the relatively long-term isolation of S. perennis in Pleistocene refugia in Europe, which resulted in independent separation of different cpDNA phylogenetic lineages and variation in the nucleotide composition of cpDNA. Discussion The lack of strong phylogeographical structure makes it impossible to indicate the centre of haplotype diversity; however, refugia located in the Carpathians, Sudetes or Alps are the most probable sites where S. perennis existed in Europe. This lack of structure may also indicate a high level of gene flow in times when the landscape and fen systems were not fragmented in numerous geographically-isolated populations. This makes it difficult to speculate about the relationships between Asiatic and European plant populations and the origin and distribution of this species in Europe. Today, it seems to be restricted due to the occurrence of plants which clearly reflects the genetic variability from the ancient period.
The Kaplan–Meier method for estimating and comparing proportions in a randomized controlled trial with dropouts

ABSTRACT We propose a method for estimating and comparing proportions of study participants who reached an event of interest during a randomized controlled trial. Standard methods for estimating this proportion include the intent-to-treat method, which counts the number who reached the event of interest divided by the total number of participants, and the completers-only method, which counts the number who reached the event only among those who completed the entire study. When participants drop out of the study early, however, these methods will either be biased or inefficient. We propose to use the Kaplan–Meier method from survival analysis to estimate the proportion of interest in this non-survival setting. We show through extensive simulation studies that the Kaplan–Meier method has less bias and is more efficient than the standard methods. We demonstrate the performance of all methods for estimating proportions in one sample and for comparing proportions across two samples. Finally, we apply the proposed method to a data-set for estimating and comparing proportions of patients who achieved treatment response during a Parkinson's disease trial for the treatment of impulse control disorders.
Commissural communication allows mouse intergeniculate leaflet and ventral lateral geniculate neurons to encode interocular differences in irradiance

Unlike other visual thalamic regions, the intergeniculate leaflet and ventral lateral geniculate nucleus (IGL/vLGN) possess extensive reciprocal commissural connections, the functions of which are unknown. Using electrophysiological approaches, it is shown that commissural projecting IGL/vLGN cells are primarily activated by light increments to the contralateral eye while cells receiving commissural input typically exhibit antagonistic binocular responses. Across antagonistic cells, the nature of the commissural input (excitatory or inhibitory) corresponds to the presence of ipsilateral ON or OFF visual responses and in both cases antagonistic responses disappear following inactivation of the contralateral thalamus. The steady state firing rates of antagonistic cells uniquely encode interocular differences in irradiance. There is a pivotal role for IGL/vLGN commissural signalling in generating new sensory properties that are potentially useful for the proposed contributions of these nuclei to visuomotor/vestibular and circadian control.
Multiple upstream start codons (AUG) in 5′ untranslated region enhance translation efficiency of cry2Ac11 without helper protein

Cry2Ac11, a 65 kDa insecticidal protein produced by Bacillus thuringiensis, shows toxicity against dipteran and lepidopteran larvae. It is encoded by cry2Ac11 gene ( orf3), which is part of an operon comprising orf1, orf2, and orf3. Orf2, a helper protein, helps in proper folding and prevents aberrant aggregation of newly produced molecules. In this study, we have elucidated the effect of different mutations in translation initiation region (TIR), particularly the ribosomal binding site and the start codon (RBS‐ATG) on cry2Ac11 gene expression without helper protein. All recombinant constructs were expressed in acrystalliferous B. thuringiensis subsp israelensis 4Q7 under the control of strong chimeric promoter cyt1AP/STAB. Of all the mutants, mut/RBS2, with two consecutive AUGs after the spacer region in TIR, exhibited 89‐ and 2246‐fold higher transcript levels compared with 4Q7‐operSalI/RBS ( cry2Ac11 operon) and 4Q7‐w‐RBS ( cry2Ac11 gene), respectively. The analysis of mut/RBS2 messenger RNA (mRNA) structure in the RBS‐AUG region showed the presence of RBS in the single‐stranded part of the moderately stable hairpin loop. The high expression efficiency of Cry2Ac11 mutant without helper protein is a cumulative and cooperative result of chimeric promoter cyt1AP/STAB‐SD with the optimal context of RBS‐AUG region provided by multiple AUGs and stabilizer sequence at 3′ ends.
Extracting software product line feature models from natural language specifications

The specification of a family of software products may include documents written in natural language. Automatically extracting knowledge from these documents is a challenging problem that requires using Natural Language Processing (NLP) techniques. This knowledge can be formalized as a Feature Model (FM), a diagram capturing the key features and the relationships among them. In this paper, we first review previous works that have presented tools for extracting FMs from textual specifications and compare their strengths and limitations. Then, we propose a framework for feature and relationship extraction, which overcomes the identified limitations and is built upon state-of-the-art open-source NLP tools. This framework is evaluated against previous works using several case studies, showing improved results.
Prss56 expression in the rodent hypothalamus: Inverse correlation with pro‐opiomelanocortin suggests oscillatory gene expression in adult rat tanycytes

We recently reported that the number of hypothalamic tanycytes expressing pro‐opiomelanocortin (Pomc) is highly variable among brains of adult rats. While its cause and significance remain unknown, identifying other variably expressed genes in tanycytes may help understand this curious phenomenon. In this in situ hybridization study, we report that the Prss56 gene, which encodes a trypsin‐like serine protease and is expressed in neural stem/progenitor cells, shows a similarly variable mRNA expression in tanycytes of adult rats and correlates inversely with tanycyte Pomc mRNA. Prss56 was expressed in α1, β1, subsets of α2, and some median eminence γ tanycytes, but virtually absent from β2 tanycytes. Prss56 was also expressed in vimentin positive tanycyte‐like cells in the parenchyma of the ventromedial and arcuate nuclei, and in thyrotropin beta subunit‐expressing cells of the pars tuberalis of the pituitary. In contrast to adults, Prss56 expression was uniformly high in tanycytes in adolescent rats. In mice, Prss56‐expressing tanycytes and parenchymal cells were also observed but fewer in number and without significant variations. The results identify Prss56 as a second gene that is expressed variably in tanycytes of adult rats. We propose that the variable, inversely correlating expression of Prss56 and Pomc reflect periodically oscillating gene expression in tanycytes rather than stable expression levels that vary between individual rats. A possible functional link between Prss56 and POMC, and Prss56 as a potential marker for migrating tanycytes are discussed.
Complex formation of sphingomyelin synthase 1 with glucosylceramide synthase increases sphingomyelin and decreases glucosylceramide levels

Sphingolipids, including sphingomyelin (SM) and glucosylceramide (GlcCer), are generated by the addition of a polar head group to ceramide (Cer). Sphingomyelin synthase 1 (SMS1) and glucosylceramide synthase (GCS) are key enzymes that catalyze the conversion of Cer to SM and GlcCer, respectively. GlcCer synthesis has been postulated to occur mainly in cis-Golgi, and SM synthesis is thought to occur in medial/trans-Golgi; however, SMS1 and GCS are known to partially co-localize in cisternae, especially in medial/trans-Golgi. Here, we report that SMS1 and GCS can form a heteromeric complex, in which the N terminus of SMS1 and the C terminus of GCS are in close proximity. Deletion of the N-terminal sterile α-motif of SMS1 reduced the stability of the SMS1–GCS complex, resulting in a significant reduction in SM synthesis in vivo. In contrast, chemical-induced heterodimerization augmented SMS1 activity, depending on an increase in the amount and stability of the complex. Fusion of the SMS1 N terminus to the GCS C terminus via linkers of different lengths increased SM synthesis and decreased GlcCer synthesis in vivo. These results suggest that formation of the SMS1–GCS heteromeric complex increases SM synthesis and decreases GlcCer synthesis. Importantly, this regulation of relative Cer levels by the SMS1–GCS complex was confirmed by CRISPR/Cas9–mediated knockout of SMS1 or GCS combined with pharmacological inhibition of Cer transport protein in HEK293T cells. Our findings suggest that complex formation between SMS1 and GCS is part of a critical mechanism controlling the metabolic fate of Cer in the Golgi.
Dose reduction in breast CT by spectrum switching

Purpose: To evaluate whether combining a polychromatic reconstruction algorithm for breast CT with projection data acquired using alternating high and low energy spectra allows a significant dose reduction while maintaining image quality. Materials and Methods: A breast phantom was scanned on a clinical breast CT scanner using the automatic exposure control selected exposure at the regular spectrum with a tube voltage of 49 kV and a 1.576 mm aluminum filter and with a second, higher energy spectrum created by adding a 0.254 mm copper filter. An acquisition with spectrum switching was simulated by interleaving projections from the standard and high energy datasets, and a previously developed polychromatic reconstruction algorithm was modified to reconstruct the breast CT images. Image quality was assessed using the signal difference-to-noise ratio (SDNR) of a high and a low contrast target present in the phantom. A Monte Carlo simulation was performed to determine the mean glandular dose (MGD) of each scan. Results: Acquisition of the simulated scan with spectrum switching would result in an MGD of 6.57 mGy, compared to the standard acquisition MGD of 10.4 mGy, a reduction of 37%. At the same time, the measured SDNR of the mixed spectrum reconstructions was slightly higher than that of the standard acquisition, with an increase in SDNR of 6.6% (p < 0.01) for the high contrast target and 5.3% (p = 0.12) for the low contrast target. Conclusion: Our approach combining a polychromatic reconstruction algorithm for breast CT with an advanced acquisition protocol using alternating high and low energy spectra can lower dose by at least a third without loss of target SDNR
The neurophysiological basis of developmental changes during sequential cognitive flexibility between adolescents and adults

Cognitive flexibility is a major facet of executive functions and often refers to sequential task control; that is, it is very likely that one may re‐encounter a task that has previously been abandoned to carry out a different task. In the context of sequential cognitive flexibility, the “backward inhibition (BI) effect” has been studied quite extensively. Here we ask whether there are age‐related differences between adolescents and adults to overcome BI and what system‐neurophysiological mechanisms underlie these modulations. This was examined using a system neurophysiological study procedure combining event‐related potentials data with source localization and EEG signal decomposition methods. We show that sequential cognitive flexibility, and the ability overcome backward inhibition, is inferior in adolescents compared with adults. Accounting for intra‐individual variability in the neurophysiological data, this data suggest that two partly inter‐related processes underlie the differences between adolescents than adults to overcome backward inhibition: One process refers to the suppression of the inhibitory effect of the n‐1 trial on the n‐2 trial during perceptual categorization of incoming information that is associated with right inferior frontal regions. The other process refers to immature response selection and conflict monitoring mechanisms associated with regions in the medial frontal cortex.
Ophthalmology Patient Perceptions of Open Payments Information

Importance Since 2014, medical industry payment data to physicians have been public via the Open Payments database. Patient opinions regarding these data help us to understand concerns and policymakers to improve reporting mechanisms for such payments. Objective To assess patient perceptions of Open Payments information. Design, Setting, and Participants This cross-sectional, questionnaire-based study was conducted in 3 ophthalmology clinic sites of an academic institution in Manhattan, New York City, New York. All patients older than 18 years who were waiting for appointments were eligible. Data were collected from January to June 2016 and analyzed from June to September 2016. Exposures Participants answered 27 questions about the Open Payments database in English or Spanish. Demographic information was also collected. Main Outcomes and Measures Key questionnaire results included patient awareness of the Open Payments database and perceptions of physicians’ financial relationships. Cronbach &agr; validation of the survey was performed, and Poisson multivariable regression analysis was performed to evaluate the association between patient characteristics and responses. Results A total of 407 individuals participated. The mean (SD) age of study participants was 58.8 (17.9) years, and 220 (54.2%) were women. Of these, 30 (7.3% [95% CI, 5.1%-19.4%]) were aware of the Open Payments database, and 109 (26.8% [95% CI, 24.8%-34.0%]) planned to access it. More than half (n = 212; 53.5% [95% CI, 48.6%-58.5%]) wanted to know if their physician receives industry payments. Regarding payments of any kind valuing $100, 161 (41.9% [95% CI, 37.0%-46.9%]) disapproved. Similarly, 178 (45.8% [95% CI, 40.8%-50.7%]) disapproved of $500 payments, and 221 (57.0% [95% CI, 52.0%-61.9%]) disapproved of $25 000 payments. Poisson multivariable regression analysis demonstrated that participants who took the survey in Spanish were 38% more likely to approve of physicians receiving payments than were those who took the survey in English (incidence rate ratio [IRR], 1.38 [95% CI, 1.19-1.59]; P < .001). For every 1 year of age, the likelihood of approval for a physician receiving payments decreased by 1% (IRR, 0.995 [95% CI, 0.99-1.00]; P = .007). Participants with graduate degrees were 20% less likely to approve of physicians receiving payments, compared with those with less than a high school degree (IRR, 0.80 [95% CI, 0.66-0.97]; P = .02). Conclusions and Relevance If the survey is validated, and if these results are generalizable outside of the 3 academic centers in ophthalmology surveyed, the findings suggest that many patients disapprove of physicians receiving payments from industry. However, few patients had accessed the Open Payments database or planned to access it. Further investigation is required to determine if these results can be generalized for other settings.
School Bag Weight as a Barrier to Active Transport to School among New Zealand Adolescents

Background: Excessive school bag weight is a barrier to active transport to school (ATS). This study examined parents’ and adolescents’ perceptions of school bag weights and actual school bag weights for adolescents in New Zealand. Methods: Parents (n = 331; 76.7% women) completed a survey. Adolescents (n = 682; age 15.1 ± 1.4 years; 57.3% boys) completed a survey, underwent anthropometry, and had their school bags weighed. Results: Overall, 68.3% of parents perceived that adolescents’ school bags were too heavy to carry to school. This parental perception differed by adolescents’ mode of transport to school (active/motorized/combined: 35.1%/78.4%/68.8%, p < 0.001). Adolescents perceived that their school bags were too heavy to carry to walk (57.8%) or cycle (65.8%) to school. Adolescent perceptions differed by mode of transport to school (for walking (active/motorized/combined): 30.9%/69.2%/55.9% agree, p < 0.001; for cycling: 47.9%/72.8%/67.7%; p < 0.001). Actual school bag weight was, on average, 5.6 ± 2.1 kg. Relative school bag weight (% of body weight) was higher for boys and underweight adolescents compared to their counterparts. Neither absolute nor relative school bag weight differed by mode of transport to school. Conclusions: School bag weight was perceived a barrier to ATS and was a greater perceived barrier among users of motorized versus active transport. Perceptions of school bag weights should be considered in future ATS interventions.
Investigating Functional Roles for Positive Feedback and Cellular Heterogeneity in the Type I Interferon Response to Viral Infection

Secretion of type I interferons (IFN) by infected cells mediates protection against many viruses, but prolonged or excessive type I IFN secretion can lead to immune pathology. A proper type I IFN response must therefore maintain a balance between protection and excessive IFN secretion. It has been widely noted that the type I IFN response is driven by positive feedback and is heterogeneous, with only a fraction of infected cells upregulating IFN expression even in clonal cell lines, but the functional roles of feedback and heterogeneity in balancing protection and excessive IFN secretion are not clear. To investigate the functional roles for feedback and heterogeneity, we constructed a mathematical model coupling IFN and viral dynamics that extends existing mathematical models by accounting for feedback and heterogeneity. We fit our model to five existing datasets, reflecting different experimental systems. Fitting across datasets allowed us to compare the IFN response across the systems and suggested different signatures of feedback and heterogeneity in the different systems. Further, through numerical experiments, we generated hypotheses of functional roles for IFN feedback and heterogeneity consistent with our mathematical model. We hypothesize an inherent tradeoff in the IFN response: a positive feedback loop prevents excessive IFN secretion, but also makes the IFN response vulnerable to viral antagonism. We hypothesize that cellular heterogeneity of the IFN response functions to protect the feedback loop from viral antagonism. Verification of our hypotheses will require further experimental studies. Our work provides a basis for analyzing the type I IFN response across systems.
An Ab Initio QM/MM Study of the Electrostatic Contribution to Catalysis in the Active Site of Ketosteroid Isomerase

The electric field in the hydrogen-bond network of the active site of ketosteroid isomerase (KSI) has been experimentally measured using vibrational Stark effect (VSE) spectroscopy, and utilized to study the electrostatic contribution to catalysis. A large gap was found in the electric field between the computational simulation based on the Amber force field and the experimental measurement. In this work, quantum mechanical (QM) calculations of the electric field were performed using an ab initio QM/MM molecular dynamics (MD) simulation and electrostatically embedded generalized molecular fractionation with conjugate caps (EE-GMFCC) method. Our results demonstrate that the QM-derived electric field based on the snapshots from QM/MM MD simulation could give quantitative agreement with the experiment. The accurate calculation of the electric field inside the protein requires both the rigorous sampling of configurations, and a QM description of the electrostatic field. Based on the direct QM calculation of the electric field, we theoretically confirmed that there is a linear correlation relationship between the activation free energy and the electric field in the active site of wild-type KSI and its mutants (namely, D103N, Y16S, and D103L). Our study presents a computational protocol for the accurate simulation of the electric field in the active site of the protein, and provides a theoretical foundation that supports the link between electric fields and enzyme catalysis.