Miracle-dz/UniFAR-FTUs huggingface dataset:
Acute Exacerbations and Lung Function Loss in Smokers with and without Chronic Obstructive Pulmonary Disease

Rationale: Acute exacerbations of chronic obstructive pulmonary disease (COPD) increase the risk of death and drive healthcare costs, but whether they accelerate loss of lung function remains controversial. Whether exacerbations in subjects with mild COPD or similar acute respiratory events in smokers without airflow obstruction affect lung function decline is unknown. Objectives: To determine the association between acute exacerbations of COPD (and acute respiratory events in smokers without COPD) and the change in lung function over 5 years of follow‐up. Methods: We examined data on the first 2,000 subjects who returned for a second COPDGene visit 5 years after enrollment. Baseline data included demographics, smoking history, and computed tomography emphysema. We defined exacerbations (and acute respiratory events in those without established COPD) as acute respiratory symptoms requiring either antibiotics or systemic steroids, and severe events by the need for hospitalization. Throughout the 5‐year follow‐up period, we collected self‐reported acute respiratory event data at 6‐month intervals. We used linear mixed models to fit FEV1 decline based on reported exacerbations or acute respiratory events. Measurements and Main Results: In subjects with COPD, exacerbations were associated with excess FEV1 decline, with the greatest effect in Global Initiative for Chronic Obstructive Lung Disease stage 1, where each exacerbation was associated with an additional 23 ml/yr decline (95% confidence interval, 2‐44; P = 0.03), and each severe exacerbation with an additional 87 ml/yr decline (95% confidence interval, 23‐151; P = 0.008); statistically significant but smaller effects were observed in Global Initiative for Chronic Obstructive Lung Disease stage 2 and 3 subjects. In subjects without airflow obstruction, acute respiratory events were not associated with additional FEV1 decline. Conclusions: Exacerbations are associated with accelerated lung function loss in subjects with established COPD, particularly those with mild disease. Trials are needed to test existing and novel therapies in subjects with early/mild COPD to potentially reduce the risk of progressing to more advanced lung disease. Clinical trial registered with www.clinicaltrials. gov (NCT 00608764).
Co‐expression of NF‐κB‐p65 and phosphorylated NF‐κB‐p105 is associated with poor prognosis in surgically resectable non‐small cell lung cancer

Nuclear factor‐kappa B (NF‐κB) as a prognostic marker remains unclear in non‐small cell lung cancer (NSCLC). Here, we studied NF‐κB‐p65 (p65) expression and phosphorylated NF‐κB‐p105 (p‐p105) expression in NSCLC and correlated the finding with overall survival (OS) and clinicopathological features. A total of 186 archival samples from patients with surgically resectable NSCLC were probed with p65 and p‐p105 (Ser 932). The p65‐positive expression and p‐p105‐positive expression were defined as distinct nuclear p65 and cytoplasmic p‐p105 labelling in at least 1% of tumour cells, respectively. The positive staining of p65 alone, p‐p105 alone and co‐expression of p65 and p‐p105 were observed in 61 (32.8%), 90 (48.4%) and 35 (18.8%) patients, respectively. Co‐expression of p65 and p‐p105 but not of either p65 or p‐p105 alone was associated with a poor prognosis. Patients with co‐expression of p65 and p‐p105 had a shorter OS than others, median OS 26.5 months versus 64.1 months, HR 1.85 (95% CI: 1.18–2.91), P = 0.007. There was no statistically significant association between clinicopathological characteristics and either p65 or p‐p105 alone or co‐expression of p65 and p‐p105. This indicates that co‐expression of p65 and p‐p105 was a poor prognostic factor, and pathologic studies of NF‐κB expression could include multiple pathway components in NSCLC.
Frequency, trends, and antecedents of severe maternal depression after three million U.S. births

Background Postpartum depression carries adverse consequences for mothers and children, so widespread screening during primary care visits is recommended. However, the rates, timing, and factors associated with significant depressive episodes are incompletely understood. Methods and findings We examined the Healthcare Cost and Utilization Project (HCUP) State Inpatient, Emergency Department, and Ambulatory Surgery and Services Databases from California (2005–2011) and Florida (2005–2012). Within 203 million records, we identified 3,213,111 births and all mothers who had hospital encounters for severe depression within 40 weeks following delivery. We identified 15,806 episodes of postpartum depression after 11,103 deliveries among 10,883 unique women, and calculated an overall rate of 36.7 depression- associated hospital visits per 10,000 deliveries. Upward trends were observed in both states, with combined five-year increases of 34%. First depressive events were most common within 30 days of delivery, but continued for the entire observation period. About half (1,661/3,325) of PPD first episodes occurred within 34 days of delivery, 70% (2,329/3,325) by the end of the second month, and 87% (2,893/3,325) before four-months of the delivery. Women with private insurance were less likely to have hospital encounters for depression than women with public insurance and women with depression were much more likely to have had some kind of hospital encounter at some time during their pregnancies. Rates of depression increased with the number of prenatal hospital encounters in a “dose-dependent” fashion: the rate of depression was 17.2/10,000 for women with no prenatal hospital visits, doubling for women with at least one encounter (34.9/10,000), and increasing 7-fold to 126/10,000 for women with three or more encounters during their pregnancies. Conclusions Our findings suggest that (1) hospital encounters for post-partum depression are increasing, (2) screening should begin very early and continue for the first year after delivery, and (3) added attention should be given to women who had hospital encounters during their pregnancies.
Multiple resistance to glyphosate, paraquat and ACCase-inhibiting herbicides in Italian ryegrass populations from California: confirmation and mechanisms of resistance.

BACKGROUND Glyphosate, paraquat and acetyl CoA carboxylase (ACCase)-inhibiting herbicides are widely used in California annual and perennial cropping systems. Recently, glyphosate, paraquat, and ACCase- and acetolactate synthase (ALS)-inhibitor resistance was confirmed in several Italian ryegrass populations from the Central Valley of California. This research characterized the possible mechanisms of resistance. RESULTS Multiple-resistant populations (MR1, MR2) are resistant to several herbicides from at least three modes of action. Dose-response experiments revealed that the MR1 population was 45.9-, 122.7- and 20.5-fold, and the MR2 population was 24.8-, 93.9- and 4.0-fold less susceptible to glyphosate, sethoxydim and paraquat, respectively, than the susceptible (Sus) population. Accumulation of shikimate in Sus plants was significantly greater than in MR plants 32 h after light pretreatments. Glyphosate resistance in MR plants was at least partially due to Pro106-to-Ala and Pro106-to-Thr substitutions at site 106 of 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). EPSPS gene copy number and expression level were similar in plants from the Sus and MR populations. An Ile1781-to-Leu substitution in ACCase gene of MR plants conferred a high level of resistance to sethoxydim and cross-resistance to other ACCase-inhibitors. Radiolabeled herbicide studies and phosphorimaging indicated that MR plants had restricted translocation of 14 C-paraquat to untreated leaves compared to Sus plants. CONCLUSION This study shows that multiple herbicide resistance in Italian ryegrass populations in California, USA, is due to both target-site and non-target-site resistance mechanisms. © 2017 Society of Chemical Industry.
A novel DC-link voltage balancing algorithm for a 3-level neutral point clamped (NPC) traction inverter for an electric vehicle IPMSM drive

This paper presents a novel DC-link voltage balancing algorithm for a 3-level DC/AC traction inverter drive. In this topology, two DC-link capacitor voltages and three-phase line currents are measured, to generate the control pulses for the traction inverter, based on space-vector pulse width modulation (SV-PWM) scheme. Depending on the states of the two DC-link capacitors, redundant voltage vector sequences are used, to keep the capacitor voltages within a particular tolerance level. Phase current directions are also taken into account, because below a certain power factor level, it affects the capacitor voltage balancing capability. Simulation and experimental results are presented in this paper for a 6.0 kW interior permanent magnet synchronous machine (IPMSM) used for the electric vehicle (EV) traction applications. Both the simulation and experimental results show required performance of the proposed system.
Genomic evidence reveals a radiation of placental mammals uninterrupted by the KPg boundary

Significance We produced a genome-scale dataset from representatives of all placental mammal orders to infer diversification timing relative to the Cretaceous–Paleogene (KPg) boundary. Our sensitivity analyses show that divergence time estimates within placentals are considerably biased by the specific way in which a given dataset is processed. We examined the performance of various dating approaches using a comprehensive scheme of likelihood analyses and computational simulations, allowing us to identify the optimal molecular clock parameters, gene sets, and gene partitioning schemes for reliable dating. Based on the optimal methodology, we present a hypothesis of mammalian divergence timing that is more consistent with the fossil record than previous molecular clock reconstructions, suggesting that placental mammals underwent a continuous radiation across the KPg boundary. The timing of the diversification of placental mammals relative to the Cretaceous–Paleogene (KPg) boundary mass extinction remains highly controversial. In particular, there have been seemingly irreconcilable differences in the dating of the early placental radiation not only between fossil-based and molecular datasets but also among molecular datasets. To help resolve this discrepancy, we performed genome-scale analyses using 4,388 loci from 90 taxa, including representatives of all extant placental orders and transcriptome data from flying lemurs (Dermoptera) and pangolins (Pholidota). Depending on the gene partitioning scheme, molecular clock model, and genic deviation from molecular clock assumptions, extensive sensitivity analyses recovered widely varying diversification scenarios for placental mammals from a given gene set, ranging from a deep Cretaceous origin and diversification to a scenario spanning the KPg boundary, suggesting that the use of suboptimal molecular clock markers and methodologies is a major cause of controversies regarding placental diversification timing. We demonstrate that reconciliation between molecular and paleontological estimates of placental divergence times can be achieved using the appropriate clock model and gene partitioning scheme while accounting for the degree to which individual genes violate molecular clock assumptions. A birth-death-shift analysis suggests that placental mammals underwent a continuous radiation across the KPg boundary without apparent interruption by the mass extinction, paralleling a genus-level radiation of multituberculates and ecomorphological diversification of both multituberculates and therians. These findings suggest that the KPg catastrophe evidently played a limited role in placental diversification, which, instead, was likely a delayed response to the slightly earlier radiation of angiosperms.
Delays to Care in Pediatric Lupus Patients: Data From the Childhood Arthritis and Rheumatology Research Alliance Legacy Registry

Prompt treatment for lupus is important to prevent morbidity. A potential barrier to early treatment of pediatric lupus is delayed presentation to a pediatric rheumatologist. To better understand factors contributing to delayed presentation among pediatric lupus patients, we examined differences in demographic and clinical characteristics of lupus patients within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry with regard to time between symptom onset and presentation to a pediatric rheumatologist.
Histone Deacetylase Inhibitor (Trapoxin A) Enhances Stemness Properties in Adipose Tissue Derived Mesenchymal Stem Cells

Abstract Back ground Adipose tissue derived mesenchymal stem cells (ASCs) have unique potential for regenerative cell therapies. However, during ex-vivo cultivation, they undergo considerable quality loss regarding their phenotypic properties, stemness genes expression and differentiation potential. Recent studies reported that the loss of stemness properties of MSCs is a result of chromatin histone deacetylations through in-vitro cultivation. The present work aimed to study the effect of Trapoxin A (TPX) as a histone deacetylase inhibitor (HDACi) on overall stemness properties of ASCs. Methods First, the effects of TPX treatments on ASCs viability and proliferation were evaluated using MTT assay. Second, the desired doses of TPX supporting ASCs proliferation were determined and the lack of their negative effects was confirmed by DAPI staining. In addition, the influence of TPX on cell cycle of ASCs and the mRNA levels of stemness genes were measured by flowcytometry and qPCR, respectively. Finally, the effect of TPX treatment on osteogenic potential of ASCs was studied. Results The results indicated that short time TPX treatment (nM concentrations) caused stimulation of proliferation and considerable percentage of ASCs entered to S-phase of cell cycle (p<0.05). Moreover, the findings demonstrated significant up-regulation of stemness markers genes (Oct-4, Sox-2, Nanog, TERT, Klf-4, Rex-1) (p<0.05) and enhanced osteogenic differentiation potential of ASC after TPX treatment. Conclusion The addition of low dose of TPX to the expansion medium could possibly enhance the stemness properties and prevent the quality decline of ex-vivo cultured ASCs.
Viscous Properties of Thermoplastic Starches from Different Botanical Origin

Abstract Starches from various botanical origins were plasticized in a twin screw extruder with different glycerol contents (from 23 to 32%, total wet basis) in order to prepare pellets of amorphous thermoplastic starches (TPS) that can further be processed for manufacturing purposes. The viscous behaviour of these starches was studied with a capillary pre-shearing rheometer, which achieved an homogeneous molten phase under controlled thermomechanical conditions. After performing Bagley corrections and Rabinowitsch analysis, it was found that all samples exhibited a non-Newtonian shear-thinning behaviour, which could be modeled in the range 1 to 103 s−1 either by a simple power law or by a Herschel-Bulkley relationship. For the consistency index, the influence of temperature and plasticizer content was accounted for by Arrhenius-like laws, applying time-temperature and time-plasticizer superposition. For the same plasticizer content and temperature, comparison of starches from different botanical origins showed that shear viscosity values usually increased with the starch amylose content. This trend was partly confirmed for the elongational behaviour, estimated by the Cogswell's analysis of entrance effects. These results can be interpreted by the greater ability of linear molecules of amylose to entangle, compared to the more compact amylopectin molecules.
Evolved plasmid‐host interactions reduce plasmid interference cost

Antibiotic selection drives adaptation of antibiotic resistance plasmids to new bacterial hosts, but the molecular mechanisms are still poorly understood. We previously showed that a broad‐host‐range plasmid was poorly maintained in Shewanella oneidensis, but rapidly adapted through mutations in the replication initiation gene trfA1. Here we examined if these mutations reduced the fitness cost of TrfA1, and whether this was due to changes in interaction with the host's DNA helicase DnaB. The strains expressing evolved TrfA1 variants showed a higher growth rate than those expressing ancestral TrfA1. The evolved TrfA1 variants showed a lower affinity to the helicase than ancestral TrfA1 and were no longer able to activate the helicase at the oriV without host DnaA. Moreover, persistence of the ancestral plasmid was increased upon overexpression of DnaB. Finally, the evolved TrfA1 variants generated higher plasmid copy numbers than ancestral TrfA1. The findings suggest that ancestral plasmid instability can at least partly be explained by titration of DnaB by TrfA1. Thus under antibiotic selection resistance plasmids can adapt to a novel bacterial host through partial loss of function mutations that simultaneously increase plasmid copy number and decrease unfavorably high affinity to one of the hosts' essential proteins.
Outbreak of Legionnaire’s Disease Caused by Legionella pneumophila Serogroups 1 and 13

In Japan, hot springs and public baths are the major sources of legionellosis. In 2015, an outbreak of Legionnaires’ disease occurred among 7 patients who had visited a spa house. Laboratory investigation indicated that L. pneumophila serogroup 1 and 13 strains caused the outbreak and that these strains were genetically related.
Engineering and characterisation of chalcogenide-based photonic microstructures

Information and communication are playing a growing role in modern society. In this increasingly interconnected and networked world that we live in, it has become critically important to nd a way to have faster and more e cient storage and transmission of data. As the network capacity continues to grow, so does the need for fast signal regeneration and switching devices. It seems that electronics and semiconductor technology will not be able to keep up with the growing telecommunication market. The top speed at which integrated electronic circuits can operate is starting to level out. However, by transmitting signals with light rather than electrons, it is possible to obtain a larger bandwidth in both smaller and more energy e cient devices. To achieve this goal it is necessary to control and manipulate the propagation of light through so-called photonic crystals (PhCs). These materials are highly periodic structures with the optical equivalent to the energy gap in semiconductors. PhCs have the potential to address many of the problems that currently limit the speed and capacity of optical communication networks. They represent a new tool for the microscopic engineering of light and thus have recently received great attention in a variety of elds. However, to employ the high technology potential of PhCs, it is crucially important to achieve a dynamical tunability of their properties. As such, it is necessary to turn to PhCs made of nonlinear materials, in which the optical
Linear models of coregionalization for multivariate lattice data: a general framework for coregionalized multivariate CAR models

We present a general coregionalization framework for developing coregionalized multivariate Gaussian conditional autoregressive (cMCAR) models for Bayesian analysis of multivariate lattice data in general and multivariate disease mapping data in particular. This framework is inclusive of cMCARs that facilitate flexible modelling of spatially structured symmetric or asymmetric cross‐variable local interactions, allowing a wide range of separable or non‐separable covariance structures, and symmetric or asymmetric cross‐covariances, to be modelled. We present a brief overview of established univariate Gaussian conditional autoregressive (CAR) models for univariate lattice data and develop coregionalized multivariate extensions. Classes of cMCARs are presented by formulating precision structures. The resulting conditional properties of the multivariate spatial models are established, which cast new light on cMCARs with richly structured covariances and cross‐covariances of different spatial ranges. The related methods are illustrated via an in‐depth Bayesian analysis of a Minnesota county‐level cancer data set. We also bring a new dimension to the traditional enterprize of Bayesian disease mapping: estimating and mapping covariances and cross‐covariances of the underlying disease risks. Maps of covariances and cross‐covariances bring to light spatial characterizations of the cMCARs and inform on spatial risk associations between areas and diseases. Copyright © 2016 John Wiley & Sons, Ltd.
Formation of Spatial Presence: By Form or Content?

Spatial presence, among the many aspects of presence, is the sense of physical and concrete space, often dubbed as the sense of “being there. ” This paper theorizes on how “spatial” presence is formed by various types of artificial cues in a virtual environment, form or content. We believe that spatial presence is a product of an unconscious effort to correctly register oneself into the virtual environment in a consistent manner. We hypothesize that this process is perceptual, and bottomup in nature, and rooted in the reflexive and adaptive behavior to react and resolve the mismatch in the spatial cues between the physical space where the user is and the virtual space where the user looks at, hears from and interacts with. Hinted from the fact that our brain has two major paths for processing sensory input, the “where” path for determining object locations, and “what” path for identifying objects, we categorize the sensory stimulation cues in the virtual environment accordingly and investigate in their relationships as how they affect the user in adaptively registering oneself into the virtual environment, thus creating spatial presence. Based on the results of series of our experiments and other bodies of research, we postulate that while low level and perceptual spatial cues are sufficient for creating spatial presence, they can be affected and modulated by the spatial (whether form or content) factors. These results provide important insights into constructing a model of spatial presence, its measurement, and guidelines for configuring locationbased virtual reality applications.