Miracle-dz/UniFAR-FTUs huggingface dataset:
Predictive and External Validity of a Pre-Market Study to Determine the Most Effective Pictorial Health Warning Label Content for Cigarette Packages.

INTRODUCTION Studies examining cigarette package pictorial health warning label (HWL) content have primarily used designs that do not allow determination of effectiveness after repeated, naturalistic exposure. This research aimed to determine the predictive and external validity of a pre-market evaluation study of pictorial HWLs. METHODS Data were analyzed from: (1) a pre-market convenience sample of 544 adult smokers who participated in field experiments in Mexico City before pictorial HWL implementation (September 2010); and (2) a post-market population-based representative sample of 1765 adult smokers in the Mexican administration of the International Tobacco Control Policy Evaluation Survey after pictorial HWL implementation. Participants in both samples rated six HWLs that appeared on cigarette packs, and also ranked HWLs with four different themes. Mixed effects models were estimated for each sample to assess ratings of relative effectiveness for the six HWLs, and to assess which HWL themes were ranked as the most effective. RESULTS Pre- and post-market data showed similar relative ratings across the six HWLs, with the least and most effective HWLs consistently differentiated from other HWLs. Models predicting rankings of HWL themes in post-market sample indicated: (1) pictorial HWLs were ranked as more effective than text-only HWLs; (2) HWLs with both graphic and "lived experience" content outperformed symbolic content; and, (3) testimonial content significantly outperformed didactic content. Pre-market data showed a similar pattern of results, but with fewer statistically significant findings. CONCLUSIONS The study suggests well-designed pre-market studies can have predictive and external validity, helping regulators select HWL content.
Toxoplasma gondii, Neospora caninum and Leishmania spp. serology and Leishmania spp. PCR in dogs from Pirassununga, SP.

We examined the presence of antibodies against the parasites Toxoplasma gondii, Neospora caninum, and Leishmania spp. , as well the presence of DNA from Leishmania spp. , in dogs from Pirassununga - SP. The seropositivity rate was compared with the animals' originating location. Three hundred seventy-three blood samples from the county's kennel and local veterinary clinics were collected and analyzed. A total of 300 samples were tested for T. gondii and N. caninum using an indirect immunofluorescence antibody test (IFAT); 45% (135/300) were positive for T. gondii and 24.3% (73/300) were positive for N. caninum. Three hundred seventy-three samples were tested for Leishmania spp. using the IFAT. Of these, 4.6% (17/373) were positive. Additionally, 145 samples were tested using a polymerase chain reaction (PCR); of these samples, 0.7% (1/145) was positive. Considering the results, we conclude that these parasites are present in the city of Pirassununga - SP and that the animals have contact with the protozoan. It is therefore necessary to create methods for disease prevention to maintain both animal and human health in regard to leishmaniasis and toxoplasmosis.
High-resolution phylogeography of zoonotic tapeworm Echinococcus granulosus sensu stricto genotype G1 with an emphasis on its distribution in Turkey, Italy and Spain

SUMMARY Echinococcus granulosus is the causative agent of cystic echinococcosis. The disease is a significant global public health concern and human infections are most commonly associated with E. granulosus sensu stricto (s. s.) genotype G1. The objectives of this study were to: (i) analyse the genetic variation and phylogeography of E. granulosus s. s. G1 in part of its main distribution range in Europe using 8274 bp of mtDNA; (ii) compare the results with those derived from previously used shorter mtDNA sequences and highlight the major differences. We sequenced a total of 91 E. granulosus s. s. G1 isolates from six different intermediate host species, including humans. The isolates originated from seven countries representing primarily Turkey, Italy and Spain. Few samples were also from Albania, Greece, Romania and from a patient originating from Algeria, but diagnosed in Finland. The analysed 91 sequences were divided into 83 haplotypes, revealing complex phylogeography and high genetic variation of E. granulosus s. s. G1 in Europe, particularly in the high-diversity domestication centre of western Asia. Comparisons with shorter mtDNA datasets revealed that 8274 bp sequences provided significantly higher phylogenetic resolution and thus more power to reveal the genetic relations between different haplotypes.
Outdoor Reproducibility of a 1-km Treadmill Walking Test to Predict Peak Oxygen Uptake in Cardiac Patients

Introduction: The aim of this study was to determine whether the 1-km treadmill walking test, previously developed to predict peak oxygen uptake ( O2peak) in stable cardiac outpatients, could be reproduced outdoors. Methods: Fifty male cardiac outpatients performed the 1-km walking test on a treadmill and on a flat track within 1 week. O2peak was estimated for both testing conditions considering age, height, weight, walking speed, and heart rate. Results: Average walking speed was slightly higher during outdoor conditions (5.73 ± 0.77 km/h vs 5.55 ± 0.84 km/h), whereas mean heart rates were similar for both testing conditions (102 ± 18 beats/min vs 103 ± 16 beats/min). O2peak values for treadmill and outdoor tests were not significantly different (26.4 ± 4.1 mL/kg/min vs 26.8 ± 4.5 mL/kg/min) and were strongly correlated (r = 0.93, P < .0001). The slope and the intercept of the O2peak values were not different from the line of identity. Conclusions: This moderate and perceptually regulated 1-km walking test administered outdoors gives similar results compared with a similar test performed on a treadmill. Therefore, O2peak can be reasonably estimated using both testing modalities. This suggests that the outdoor 1-km test can be applied for indirect estimations of cardiorespiratory fitness in an outpatient setting.
Novel Molecular Insights into Classical and Alternative Activation States of Microglia as Revealed by Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC)-based Proteomics*

Microglia, the resident immune cells of the brain, have been shown to display a complex spectrum of roles that span from neurotrophic to neurotoxic depending on their activation status. Microglia can be classified into four stages of activation, M1, which most closely matches the classical (pro-inflammatory) activation stage, and the alternative activation stages M2a, M2b, and M2c. The alternative activation stages have not yet been comprehensively analyzed through unbiased, global-scale protein expression profiling. In this study, BV2 mouse immortalized microglial cells were stimulated with agonists specific for each of the four stages and total protein expression for 4644 protein groups was quantified using SILAC-based proteomic analysis. After validating induction of the various stages through a targeted cytokine assay and Western blotting of activation states, the data revealed novel insights into the similarities and differences between the various states. The data identify several protein groups whose expression in the anti-inflammatory, pro-healing activation states are altered presumably to curtail inflammatory activation through differential protein expression, in the M2a state including CD74, LYN, SQST1, TLR2, and CD14. The differential expression of these proteins promotes healing, limits phagocytosis, and limits activation of reactive nitrogen species through toll-like receptor cascades. The M2c state appears to center around the down-regulation of a key member in the formation of actin-rich phagosomes, SLP-76. In addition, the proteomic data identified a novel activation marker, DAB2, which is involved in clathrin-mediated endocytosis and is significantly different between M2a and either M1 or M2b states. Western blot analysis of mouse primary microglia stimulated with the various agonists of the classical and alternative activation states revealed a similar trend of DAB2 expression compared with BV2 cells.
Association between advanced glycation end-products and functional performance in Alzheimer's disease and mixed dementia

ABSTRACT Background: People with Alzheimer's disease (AD) experience, in addition to the progressive loss of cognitive functions, a decline in functional performance such as mobility impairment and disability in activities of daily living (ADL). Functional decline in dementia is mainly linked to the progressive brain pathology. Peripheral biomechanical changes by advanced glycation end-products (AGEs) have been suggested but have yet to be thoroughly studied. Methods: A multi-center, longitudinal, one-year follow-up cohort study was conducted in 144 people with early stage AD or mixed Alzheimer's/Vascular dementia. Linear mixed model analyses was used to study associations between AGE-levels (AGE reader) and mobility (Timed Up and Go), and ADL (Groningen Activity Restriction Scale and Barthel index), respectively. Results: A significant association between AGE levels and mobility (β = 3.57, 95%CI: 1.43–5.73) was revealed; however, no significant association between AGE levels and ADL was found. Over a one-year time span, mean AGE levels significantly increased, and mobility and ADL performance decreased. Change in AGE levels was not significantly correlated with change in mobility. Conclusions: This study indicates that high AGE levels could be a contributing factor to impaired mobility but lacks evidence for an association with ADL decline in people with early stage AD or mixed dementia. Future research is necessary on the reduction of functional decline in dementia regarding the effectiveness of interventions such as physical activity programs and dietary advice possibly in combination with pharmacologic strategies targeting AGE accumulation.
An evolutionary tipping point in a changing environment

Populations can persist in directionally changing environments by evolving. Quantitative genetic theory aims to predict critical rates of environmental change beyond which populations go extinct. Here, we point out that all current predictions effectively assume the same specific fitness function. This function causes selection on the standing genetic variance of quantitative traits to become increasingly strong as mean trait values depart from their optima. Hence, there is no bound on the rate of evolution and persistence is determined by the critical rate of environmental change at which populations cease to grow. We then show that biologically reasonable changes to the underlying fitness function can impose a qualitatively different extinction threshold. In particular, inflection points caused by weakening selection create local extrema in the strength of selection and thus in the rate of evolution. These extrema can produce evolutionary tipping points, where long‐run population growth rates drop from positive to negative values without ever crossing zero. Generic early‐warning signs of tipping points are found to have little power to detect imminent extinction, and require hard‐to‐gather data. Furthermore, we show how evolutionary tipping points produce evolutionary hysteresis, creating extinction debts.
An augmented reality tool for learning spatial anatomy on mobile devices

Augmented Realty (AR) offers a novel method of blending virtual and real anatomy for intuitive spatial learning. Our first aim in the study was to create a prototype AR tool for mobile devices. Our second aim was to complete a technical evaluation of our prototype AR tool focused on measuring the system's ability to accurately render digital content in the real world. We imported Computed Tomography (CT) data derived virtual surface models into a 3D Unity engine environment and implemented an AR algorithm to display these on mobile devices. We investigated the accuracy of the virtual renderings by comparing a physical cube with an identical virtual cube for dimensional accuracy. Our comparative study confirms that our AR tool renders 3D virtual objects with a high level of accuracy as evidenced by the degree of similarity between measurements of the dimensions of a virtual object (a cube) and the corresponding physical object. We developed an inexpensive and user‐friendly prototype AR tool for mobile devices that creates highly accurate renderings. This prototype demonstrates an intuitive, portable, and integrated interface for spatial interaction with virtual anatomical specimens. Integrating this AR tool with a library of CT derived surface models provides a platform for spatial learning in the anatomy curriculum. The segmentation methodology implemented to optimize human CT data for mobile viewing can be extended to include anatomical variations and pathologies. The ability of this inexpensive educational platform to deliver a library of interactive, 3D models to students worldwide demonstrates its utility as a supplemental teaching tool that could greatly benefit anatomical instruction. Clin. Anat. 30:736–741, 2017. © 2017Wiley Periodicals, Inc.
Blood-brain barrier, cytotoxic chemotherapies and glioblastoma

ABSTRACT Introduction: Glioblastomas (GBM) are the most common and aggressive primary malignant brain tumors in adults. The blood brain barrier (BBB) is a major limitation reducing efficacy of anti-cancer drugs in the treatment of GBM patients. Areas covered: Virtually all GBM recur after the first-line treatment, at least partly, due to invasive tumor cells protected from chemotherapeutic agents by the intact BBB in the brain adjacent to tumor. The passage through the BBB, taken by antitumor drugs, is poorly and heterogeneously documented in the literature. In this review, we have focused our attention on: (i) the BBB, (ii) the passage of chemotherapeutic agents across the BBB and (iii) the strategies investigated to overcome this barrier. Expert commentary: A better preclinical knowledge of the crossing of the BBB by antitumor drugs will allow optimizing their clinical development, alone or combined with BBB bypassing strategies, towards an increased success rate of clinical trials.
A spiral attractor network drives rhythmic locomotion

The joint activity of neural populations is high dimensional and complex. One strategy for reaching a tractable understanding of circuit function is to seek the simplest dynamical system that can account for the population activity. By imaging Aplysia’s pedal ganglion during fictive locomotion, here we show that its population-wide activity arises from a low-dimensional spiral attractor. Evoking locomotion moved the population into a low-dimensional, periodic, decaying orbit −a spiral −in which it behaved as a true attractor, converging to the same orbit when evoked, and returning to that orbit after transient perturbation. We found the same attractor in every preparation, and could predict motor output directly from its orbit, yet individual neurons’ participation changed across consecutive locomotion bouts. From these results, we propose that only the low-dimensional dynamics for movement control, and not the high-dimensional population activity, are consistent within and between nervous systems.
Pharmacokinetics of Jaspine B and Enhancement of Intestinal Absorption of Jaspine B in the Presence of Bile Acid in Rats

We aimed to investigate the pharmacokinetics and the underlying mechanisms of the intestinal absorption, distribution, metabolism, and excretion of Jaspine B in rats. The oral bioavailability of Jaspine B was 6.2%, but it decreased to 1.6% in bile-depleted rats and increased to 41.2% (normal) and 23.5% (bile-depleted) with taurocholate supplementation (60 mg/kg). Consistent with the increased absorption in the presence of bile salts, rat intestinal permeability of Jaspine B also increased in the presence of 10 mM taurocholate or 20% bile. Further studies demonstrated that the enhanced intestinal permeability with bile salts was due to increased lipophilicity and decreased membrane integrity. Jaspine B was designated as a highly tissue-distributed compound, because it showed large tissue to plasma ratios in the brain, kidney, heart, and spleen. Moreover, the recovery of Jaspine B from the feces and urine after an intravenous administration was about 6.3%, suggesting a substantial metabolism of Jaspine B. Consistent with this observation, 80% of the administered Jaspine B was degraded after 1 h incubation with rat liver microsomes. In conclusion, the facilitated intestinal permeability in the presence of bile salts could significantly increase the bioavailability of Jaspine B and could lead to the development of oral formulations of Jaspine B with bile salts. Moreover, the highly distributed features of Jaspine B in the brain, kidney, heart, and spleen should be carefully considered in the therapeutic effect and toxicity of this compound.
The life course model as a framework for post-conflict health analysis: reflections on the Gulf War critical period

Abstract In the Kuwait context, from January 1991 to December 1991, there were a series of chemical and psychological Gulf War-era exposures that left persistent, long-term damage. Extreme stress from a critical event speeds up the usual disease latency period, and may be part of a synergistic effect that leads to higher disease rates over a shorter period of time. I am interested in the impact of armed conflict on health outcomes over the life course in Kuwait, and particularly the pathways through which armed conflict causes changes in health on a population level. In this paper, I propose a culturally sensitive, post-conflict socio-ecological model that informs a three-pronged health study. I propose a macro–micro mix that includes an ecological study, a case-control study and a qualitative study to investigate Kuwait’s post-conflict health concerns. Thus, I revise the concept of ‘post-conflict health’ as a trajectory that is mediated through different, complex social levels and develops over time during the latency period. The main advantage of a macro–micro mix approach for post-conflict health is that it contextualizes the Gulf War as an environmental health issue.
The role of ZIP transporters and group F bZIP transcription factors in the Zn‐deficiency response of wheat (Triticum aestivum)

Summary Understanding the molecular basis of zinc (Zn) uptake and transport in staple cereal crops is critical for improving both Zn content and tolerance to low‐Zn soils. This study demonstrates the importance of group F bZIP transcription factors and ZIP transporters in responses to Zn deficiency in wheat (Triticum aestivum). Seven group F TabZIP genes and 14 ZIPs with homeologs were identified in hexaploid wheat. Promoter analysis revealed the presence of Zn‐deficiency‐response elements (ZDREs) in a number of the ZIPs. Functional complementation of the zrt1/zrt2 yeast mutant by TaZIP3, ‐6, ‐7, ‐9 and ‐13 supported an ability to transport Zn. Group F TabZIPs contain the group‐defining cysteine–histidine‐rich motifs, which are the predicted binding site of Zn2+ in the Zn‐deficiency response. Conservation of these motifs varied between the TabZIPs suggesting that individual TabZIPs may have specific roles in the wheat Zn‐homeostatic network. Increased expression in response to low Zn levels was observed for several of the wheat ZIPs and bZIPs; this varied temporally and spatially suggesting specific functions in the response mechanism. The ability of the group F TabZIPs to bind to specific ZDREs in the promoters of TaZIPs indicates a conserved mechanism in monocots and dicots in responding to Zn deficiency. In support of this, TabZIPF1‐7DL and TabZIPF4‐7AL afforded a strong level of rescue to the Arabidopsis hypersensitive bzip19 bzip23 double mutant under Zn deficiency. These results provide a greater understanding of Zn‐homeostatic mechanisms in wheat, demonstrating an expanded repertoire of group F bZIP transcription factors, adding to the complexity of Zn homeostasis.
Use of Nitrogen‐15‐Enriched Escherichia coli as a Bacterial Tracer in Karst Aquifers

Karst aquifers are susceptible to contamination by microorganisms, but relatively few studies have used bacteria as tracers. We demonstrate the utility of Escherichia coli enriched in the stable isotope nitrogen‐15 (15N) as a novel bacterial tracer. Nonpathogenic E. coli from two springs in central Kentucky were grown on 15N‐enriched media. Survival of E. coli and persistence of the isotopic signal were assessed in two sets of laboratory experiments conducted with sterilized spring water in dark microcosms at 14 °C. First, isotopically labeled bacteria survived for 130 d at concentrations within one log unit of the average initial value, and there was no significant difference in δ15N values from Day 1 to Day 130. Second, water samples with E. coli were inoculated with either of two different species of protozoa (Tetrahymena pyriformis or Colpoda steinii). During 7 d, δ15N values increased in T. pyriformis while bacterial populations decreased. In a field test, following a 2.1‐cm rainfall, 15N‐labeled E. coli, solutes (rhodamine WT dye and bromide), and latex microspheres were injected into a sinkhole approximately 530 m upgradient of a spring. Breakthrough of all tracers coincided, but microspheres were remobilized by subsequent storms, unlike other tracers. Enriched E. coli exhibited more tailing than solute tracers during the initial storm‐flow recession. These results indicate that 15N‐enriched E. coli is a viable tracer of bacterial transport in karst aquifers, although predation may attenuate the isotopic signal in systems that are not rapidly flushed.
Neighborhood Diversity, Economic Health, and The Role of the Arts

ABSTRACT Policymakers pursue a range of strategies aimed at diversifying neighborhoods despite research indicating the complicated and potentially damaging results of these efforts. One increasingly common approach is to incorporate the arts into planning efforts in the hope of enhancing diversity and catalyzing positive neighborhood change. Using data from the Cultural Data Project, the authors determine where newly established New York City arts organizations locate in terms of neighborhood racial, income, and industry diversity. They then analyze how diverse contexts interact with an arts presence to impact neighborhood economic health over time. They find that neighborhoods with high levels of racial diversity and low levels of income and industry diversity benefit most from an arts presence. However, the arts are attracted predominantly to neighborhoods with moderate levels of racial diversity and high levels of income and industry diversity. This complicates the use of the arts as a tool in urban revitalization policy.