Miracle-dz/UniFAR-FTUs huggingface dataset:
Recent Trends in the Epidemiology of Hepatocellular Carcinoma in Olmsted County, Minnesota: A US Population-based Study

Background/Aim: The epidemiology of hepatocellular carcinoma (HCC) has changed in the United States recently. The aim of this study is to evaluate the recent trends of HCC epidemiology in Olmsted County, MN. Methods: Residents aged over 20 with newly diagnosed HCC were identified using the Rochester Epidemiology Project database. Clinical information was compared among patients diagnosed between 2000 and 2009 (era 1) and 2010 to 2014 (era 2). Results: Over 1.6 million person years of follow-up, 93 residents were diagnosed with HCC. The mean age was 67 and 71% were male. The age-adjusted and sex-adjusted incidence rates were 6.3 and 7.0 per 100,000 person years in the first and second eras (P=0.64). The proportion with hepatitis B virus etiology increased from 4% to 21% between the 2 eras (P<0.01), whereas there was a trend toward a decreasing proportion of hepatitis C virus etiology from 42% to 29% (P=0.20). Only 39% of HCC surveillance candidates had HCCs detected under surveillance and 41% of cirrhotic patients had unrecognized cirrhosis at the time of HCC diagnosis. Nonalcoholic fatty liver disease was associated with unrecognized cirrhosis and absence of cirrhosis at HCC diagnosis. More than half (56%) of patients presented at Barcelona Clinic Liver Cancer stage C or D and the median survival was 9.7 months. The overall survival had not changed over time. Conclusions: The incidence of HCC remained stable after 2010 in Olmsted County. The proportion of hepatitis B virus-induced HCC increased, whereas there was a trend of decreasing proportion of hepatitis C virus-induced HCC. The overall survival in community residents with HCC remains poor.
Time in a Bottle: The Evolutionary Fate of Species Discrimination in Sibling Drosophila Species

Disadvantageous hybridization favors the evolution of prezygotic isolating behaviors, generating a geographic pattern of interspecific mate discrimination where members of different species drawn from sympatric populations exhibit stronger preference for members of their own species than do individuals drawn from allopatric populations. Geographic shifts in species' boundaries can relax local selection against hybridization; under such scenarios the fate of enhanced species preference is unknown. Lineages established from populations in the region of sympatry that have been maintained as single-species laboratory cultures represent cases where allopatry has been produced experimentally. Using such cultures dating from the 1950s, we assess how Drosophila pseudoobscura and D. persimilis mate preferences respond to relaxed natural selection against hybridization. We found that the propensity to hybridize generally declines with increasing time in experimental allopatry, suggesting that maintaining enhanced preference for conspecifics may be costly. However, our data also suggest a strong role for drift in determining mating preferences once secondary allopatry has been established. Finally, we discuss the interplay between populations in establishing the presence or absence of patterns consistent with reinforcement.
Rac1 and Rac3 GTPases Regulate the Development of Hilar Mossy Cells by Affecting the Migration of Their Precursors to the Hilus

We have previously shown that double deletion of the genes for Rac1 and Rac3 GTPases during neuronal development affects late developmental events that perturb the circuitry of the hippocampus, with ensuing epileptic phenotype. These effects include a defect in mossy cells, the major class of excitatory neurons of the hilus. Here, we have addressed the mechanisms that affect the loss of hilar mossy cells in the dorsal hippocampus of mice depleted of the two Rac GTPases. Quantification showed that the loss of mossy cells was evident already at postnatal day 8, soon after these cells become identifiable by a specific marker in the dorsal hilus. Comparative analysis of the hilar region from control and double mutant mice revealed that synaptogenesis was affected in the double mutants, with strongly reduced presynaptic input from dentate granule cells. We found that apoptosis was equally low in the hippocampus of both control and double knockout mice. Labelling with bromodeoxyuridine at embryonic day 12.5 showed no evident difference in the proliferation of neuronal precursors in the hippocampal primordium, while differences in the number of bromodeoxyuridine-labelled cells in the developing hilus revealed a defect in the migration of immature, developing mossy cells in the brain of double knockout mice. Overall, our data show that Rac1 and Rac3 GTPases participate in the normal development of hilar mossy cells, and indicate that they are involved in the regulation of the migration of the mossy cell precursor by preventing their arrival to the dorsal hilus.
Effects of Preview on Human Control Behavior in Tracking Tasks With Various Controlled Elements

This paper investigates how humans use a previewed target trajectory for control in tracking tasks with various controlled element dynamics. The human’s hypothesized “near” and “far” control mechanisms are first analyzed offline in simulations with a quasi-linear model. Second, human control behavior is quantified by fitting the same model to measurements from a human-in-the-loop experiment, where subjects tracked identical target trajectories with a pursuit and a preview display, each with gain, single-, and double-integrator controlled element dynamics. Results show that target-tracking performance improves with preview, primarily due to the far-viewpoint response, which allows humans to cancel their own and the controlled element’s lags, without additional control activity. The near-viewpoint response yields better target tracking at higher frequencies, but requires substantially more control activity. The control-theoretic approach adopted in this paper provides unique quantitative insights into human use of preview, which can help to explain human behavior observed in other preview control tasks, like driving.
The Impact of Obesity on the Clinical Course of Inflammatory Bowel Disease: A Meta-Analysis

Background Obesity has been linked with a pro-inflammatory state and the development of inflammatory diseases, including inflammatory bowel disease (IBD). However, there is some controversy regarding whether obesity is associated with an adverse clinical course in patients with IBD. The aim of this meta-analysis was to assess the association between obesity and clinical outcomes in IBD patients. Material/Methods Electronic databases (PubMed, Embase, Cochrane Library, and Web of Science) were systematically searched for studies investigating the association between obesity and clinical outcomes in patients with IBD. A meta-analysis was performed using Review Manager software. Results Among the 4,798 articles identified, seven met the inclusion criteria for our meta-analysis. The pooled data revealed that obese patients were significantly less likely to undergo IBD-related surgery, receive hormone therapy, and experience hospitalization compared with non-obese patients. However, no statistically significant difference was observed in perianal disease, anti-TNF use, and immunomodulator use between the two groups. Conclusions Our meta-analysis indicated that clinical outcomes were significantly different in obese versus non-obese patients with IBD. We found that obesity was associated with a less severe disease course of IBD. Future prospective studies are needed to confirm the relationship between obesity and the clinical course of IBD.
False Discovery Rate Control via Debiased Lasso

We consider the problem of variable selection in high-dimensional statistical models where the goal is to report a set of variables, out of many predictors $X_1, \dotsc, X_p$, that are relevant to a response of interest. For linear high-dimensional model, where the number of parameters exceeds the number of samples $(p>n)$, we propose a procedure for variables selection and prove that it controls the \emph{directional} false discovery rate (FDR) below a pre-assigned significance level $q\in [0,1]$. We further analyze the statistical power of our framework and show that for designs with subgaussian rows and a common precision matrix $\Omega\in\mathbb{R}^{p\times p}$, if the minimum nonzero parameter $\theta_{\min}$ satisfies $$\sqrt{n} \theta_{\min} - \sigma \sqrt{2(\max_{i\in [p]}\Omega_{ii})\log\left(\frac{2p}{qs_0}\right)} \to \infty\,,$$ then this procedure achieves asymptotic power one. Our framework is built upon the debiasing approach and assumes the standard condition $s_0 = o(\sqrt{n}/(\log p)^2)$, where $s_0$ indicates the number of true positives among the $p$ features. Notably, this framework achieves exact directional FDR control without any assumption on the amplitude of unknown regression parameters, and does not require any knowledge of the distribution of covariates or the noise level. We test our method in synthetic and real data experiments to asses its performance and to corroborate our theoretical results.
Automatic large-scale classification of bird sounds is strongly improved by unsupervised feature learning

Automatic species classification of birds from their sound is a computational tool of increasing importance in ecology, conservation monitoring and vocal communication studies. To make classification useful in practice, it is crucial to improve its accuracy while ensuring that it can run at big data scales. Many approaches use acoustic measures based on spectrogram-type data, such as the Mel-frequency cepstral coefficient (MFCC) features which represent a manually-designed summary of spectral information. However, recent work in machine learning has demonstrated that features learnt automatically from data can often outperform manually-designed feature transforms. Feature learning can be performed at large scale and “unsupervised”, meaning it requires no manual data labelling, yet it can improve performance on “supervised” tasks such as classification. In this work we introduce a technique for feature learning from large volumes of bird sound recordings, inspired by techniques that have proven useful in other domains. We experimentally compare twelve different feature representations derived from the Mel spectrum (of which six use this technique), using four large and diverse databases of bird vocalisations, classified using a random forest classifier. We demonstrate that in our classification tasks, MFCCs can often lead to worse performance than the raw Mel spectral data from which they are derived. Conversely, we demonstrate that unsupervised feature learning provides a substantial boost over MFCCs and Mel spectra without adding computational complexity after the model has been trained. The boost is particularly notable for single-label classification tasks at large scale. The spectro-temporal activations learned through our procedure resemble spectro-temporal receptive fields calculated from avian primary auditory forebrain. However, for one of our datasets, which contains substantial audio data but few annotations, increased performance is not discernible. We study the interaction between dataset characteristics and choice of feature representation through further empirical analysis.
Endocrine-Disrupting Chemicals and Oil and Natural Gas Operations: Potential Environmental Contamination and Recommendations to Assess Complex Environmental Mixtures

Background Hydraulic fracturing technologies, developed over the last 65 years, have only recently been combined with horizontal drilling to unlock oil and gas reserves previously deemed inaccessible. Although these technologies have dramatically increased domestic oil and natural gas production, they have also raised concerns for the potential contamination of local water supplies with the approximately 1,000 chemicals that are used throughout the process, including many known or suspected endocrine-disrupting chemicals. Objectives We discuss the need for an endocrine component to health assessments for drilling-dense regions in the context of hormonal and antihormonal activities for chemicals used. Methods We discuss the literature on a) surface and groundwater contamination by oil and gas extraction operations, and b) potential human exposure, particularly in the context of the total hormonal and antihormonal activities present in surface and groundwater from natural and anthropogenic sources; we also discuss initial analytical results and critical knowledge gaps. Discussion In light of the potential for environmental release of oil and gas chemicals that can disrupt hormone receptor systems, we recommend methods for assessing complex hormonally active environmental mixtures. Conclusions We describe a need for an endocrine-centric component for overall health assessments and provide information supporting the idea that using such a component will help explain reported adverse health trends as well as help develop recommendations for environmental impact assessments and monitoring programs. Citation Kassotis CD, Tillitt DE, Lin CH, McElroy JA, Nagel SC. 2016. Endocrine-disrupting chemicals and oil and natural gas operations: potential environmental contamination and recommendations to assess complex environmental mixtures. Environ Health Perspect 124:256–264; http://dx.doi. org/10.1289/ehp.1409535
CD1c(+) myeloid dendritic cells in myeloid neoplasia

We determined the normal level and phenotype of CD1c(+) myeloid dendritic cells (MDCs) in blood and bone marrow and evaluated the level of CD1c(+) MDCs in 295 myeloid neoplasms. CD1c(+) MDCs were increased above the mean level of non‐neoplastic hospital controls in 18.0% (53/295) of myeloid malignancies, increased three standard deviations above the control mean in 14.2% (42/295) with a 10‐fold or more increase compared to mean in 6.8% (20/295). Increased CD1c(+) MDCs were associated with chronic myelomonocytic leukemia (CMML) (12/24, 50%) and acute myeloid leukemia (AML) (31/140, 22%) with a strong association with AML with the inv(16) cytogenetic abnormality. The cells were not increased in chronic myelogenous leukemia (CML) and rarely increased in non‐CML myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS). Immunohistochemical staining of cases with increased CD1c(+) MDCs did not reveal clustering of the cells unlike that observed with myeloid neoplasms associated with increased plasmacytoid dendritic cells. Our findings indicate CD1c(+) MDC elevations are not uncommon in myeloid leukemias and are associated with CMML and AML, particularly AML with inv(16). © 2015 International Clinical Cytometry Society
One Problem, Many Solutions: Simple Statistical Approaches Help Unravel the Complexity of the Immune System in an Ecological Context

The immune system is a complex collection of interrelated and overlapping solutions to the problem of disease. To deal with this complexity, researchers have devised multiple ways to measure immune function and to analyze the resulting data. In this way both organisms and researchers employ many tactics to solve a complex problem. One challenge facing ecological immunologists is the question of how these many dimensions of immune function can be synthesized to facilitate meaningful interpretations and conclusions. We tackle this challenge by employing and comparing several statistical methods, which we used to test assumptions about how multiple aspects of immune function are related at different organizational levels. We analyzed three distinct datasets that characterized 1) species, 2) subspecies, and 3) among- and within-individual level differences in the relationships among multiple immune indices. Specifically, we used common principal components analysis (CPCA) and two simpler approaches, pair-wise correlations and correlation circles. We also provide a simple example of how these techniques could be used to analyze data from multiple studies. Our findings lead to several general conclusions. First, relationships among indices of immune function may be consistent among some organizational groups (e.g. months over the annual cycle) but not others (e.g. species); therefore any assumption of consistency requires testing before further analyses. Second, simple statistical techniques used in conjunction with more complex multivariate methods give a clearer and more robust picture of immune function than using complex statistics alone. Moreover, these simpler approaches have potential for analyzing comparable data from multiple studies, especially as the field of ecological immunology moves towards greater methodological standardization.
Epstein-Barr Virus gp350 Can Functionally Replace the Rhesus Lymphocryptovirus Major Membrane Glycoprotein and Does Not Restrict Infection of Rhesus Macaques

ABSTRACT Primary Epstein-Barr virus (EBV) infection is the most common cause of infectious mononucleosis, and persistent infection is associated with multiple cancers. EBV vaccine development has focused on the major membrane glycoprotein, gp350, since it is the major target for antibodies that neutralize infection of B cells. However, EBV has tropism for both B cells and epithelial cells, and it is unknown whether serum neutralizing antibodies against B cell infection will provide sufficient protection against virus infection initiated at the oral mucosa. This could be stringently tested by passive antibody transfer and oral virus challenge in the rhesus macaque model for EBV infection. However, only neutralizing monoclonal antibodies (MAbs) against EBV are available, and EBV is unable to infect rhesus macaques because of a host range restriction with an unknown mechanism. We cloned the prototypic EBV-neutralizing antibody, 72A1, and found that recombinant 72A1 did not neutralize rhesus lymphocryptovirus (rhLCV) infection of macaque B cells. Therefore, we constructed a chimeric rhLCV in which the native major membrane glycoprotein was replaced with EBV gp350. This chimeric rhLCV became sensitive to neutralization by the 72A1 MAb, efficiently immortalized macaque B cells in vitro, and successfully established acute and persistent infection after oral inoculation of rhesus macaques. Thus, EBV gp350 can functionally replace rhLCV gp350 and does not restrict rhLCV infection in vitro or in vivo. The chimeric rhLCV enables direct use of an EBV-specific MAb to investigate the effects of serum neutralizing antibodies against B cell infection on oral viral challenge in rhesus macaques. IMPORTANCE This study asked whether the EBV major membrane glycoprotein could functionally replace the rhLCV major membrane glycoprotein. We found that an rhLCV humanized with EBV gp350 is capable of efficiently immortalizing monkey B cells in vitro and reproduces acute and persistent infection after oral inoculation of macaques. These results advance our understanding of why EBV cannot infect rhesus macaques by proving that viral attachment through gp350 is not the mechanism for EBV host range restriction. Humanization of rhLCV with EBV gp350 also confers susceptibility to a potent EBV-neutralizing MAb and provides a novel and significant enhancement to the rhesus macaque animal model where both the clinical utility and biological role of neutralizing MAbs against B cell or epithelial cell infection can now be directly tested in the most accurate animal model for EBV infection.
Mitochondrial DNA multiplex real‐time polymerase chain reaction inhibition assay for quality control of pathogen inactivation by ultraviolet C light in platelet concentrates

Several ultraviolet (UV) light‐based pathogen inactivation (PI) technologies for platelet (PLT) products have been developed or are under development. Upon implementation of PI technologies, quality control measures are required to ensure consistent efficiency of the treatment process. Previous reports showed that amotosalen/UVA and riboflavin/UV‐based PI technologies induce modifications of the PLT‐derived mitochondrial DNA (mtDNA) that can be detected by polymerase chain reaction (PCR) inhibition assays. In this study, we sought to establish a PCR inhibition assay to document the impact of ultraviolet C (UVC) treatment with the THERAFLEX UV‐Platelets system on the mitochondrial genome in PLT concentrates (PCs).
THE HAT-P-13 EXOPLANETARY SYSTEM: EVIDENCE FOR SPIN–ORBIT ALIGNMENT AND A THIRD COMPANION

We present new radial velocity (RV) measurements of HAT-P-13, a star with two previously known companions: a transiting giant planet “b” with an orbital period of 3 days and a more massive object “c” on a 1.2 yr, highly eccentric orbit. For this system, dynamical considerations would lead to constraints on planet b's interior structure, if it could be shown that the orbits are coplanar and apsidally locked. By modeling the Rossiter–McLaughlin effect, we show that planet b's orbital angular momentum vector and the stellar spin vector are well aligned on the sky (λ = 1.9 ± 8.6 deg). The refined orbital solution favors a slightly eccentric orbit for planet b (e = 0.0133 ± 0.0041), although it is not clear whether it is apsidally locked with c's orbit (Δω = 36+27−36 deg). We find a long-term trend in the star's RV and interpret it as evidence for an additional body “d,” which may be another planet or a low-mass star. Predictions are given for the next few inferior conjunctions of c, when transits may happen.
Longitudinal imaging of Caenorhabditis elegans in a microfabricated device reveals variation in behavioral decline during aging

The roundworm C. elegans is a mainstay of aging research due to its short lifespan and easily manipulable genetics. Current, widely used methods for long-term measurement of C. elegans are limited by low throughput and the difficulty of performing longitudinal monitoring of aging phenotypes. Here we describe the WorMotel, a microfabricated device for long-term cultivation and automated longitudinal imaging of large numbers of C. elegans confined to individual wells. Using the WorMotel, we find that short-lived and long-lived strains exhibit patterns of behavioral decline that do not temporally scale between individuals or populations, but rather resemble the shortest and longest lived individuals in a wild type population. We also find that behavioral trajectories of worms subject to oxidative stress resemble trajectories observed during aging. Our method is a powerful and scalable tool for analysis of C. elegans behavior and aging. DOI: http://dx.doi. org/10.7554/eLife.26652. 001
HPLC profiling of phenolics and flavonoids of Adonidia merrillii fruits and their antioxidant and cytotoxic properties

Abstract In this study the antioxidant and cytotoxicity activity of the Adonidia merrillii fruits were investigated using different solvent polarities (methanol, ethyl acetate and water). The results showed that the total phenolic and flavonoid contents of the methanolic extract was higher compare with other extract with respective values of 17.80 ± 0.45 mg gallic acid equivalents/g dry weight (DW) and 5.43 ± 0.33 mg rutin equivalents/g DW. Beside that The RP-HPLC analyses indicated the presence of gallic acid, pyrogallol, caffeic acid, vanillic acid, syringic acid, naringin and rutin. In the DPPH, NO2 and ABTS scavenging assays, the methanolic extract exhibited higher antioxidant activity as compared to the ethyl acetate and water extracts. The extracts exhibited moderate to weak cytotoxic activity in the assays using human hepatocytes (Chang liver cells) and NIH/3T3 (fibroblasts cell) cell lines. The findings showed the Adonidia merrillii fruit extracts to possess considerable antioxidant and cytotoxicity properties. The fruit, therefore, is a potential candidate for further work to discover antioxidant and cytotoxic drugs from natural sources.