Miracle-dz/UniFAR-FTUs huggingface dataset:
The roles of inter- and intra-sexual selection in behavioral isolation between native and invasive pupfishes

Abstract Male–male competition and female mate choice may both play important roles in driving and maintaining reproductive isolation between species. When previously allopatric species come into secondary contact with each other due to introductions, they provide an opportunity to evaluate the identity and strength of reproductive isolating mechanisms. If reproductive isolation is not maintained, hybridization may occur. We examined how reproductive isolating mechanisms mediate hybridization between endemic populations of the Red River pupfish Cyprinodon rubrofluviatilis and the recently introduced sheepshead minnow C. variegatus. In lab-based dominance trials, males of both species won the same number of competitions. However, male C. rubrofluviatilis that won competitions were more aggressive than C. variegatus winners, and more aggression was needed to win against competitor C. variagatus than allopatric C. rubrofluviatilis. Duration of fights also differed based on the relatedness of the competitor. In dichotomous mate choice trials, there were no conspecific or heterospecific preferences expressed by females of either species. Our findings that male–male aggression differs between closely and distantly related groups, but female choice does not suggest that male–male competition may be the more likely mechanism to impede gene flow in this system.
Exploring autophagy with Gene Ontology

ABSTRACT Autophagy is a fundamental cellular process that is well conserved among eukaryotes. It is one of the strategies that cells use to catabolize substances in a controlled way. Autophagy is used for recycling cellular components, responding to cellular stresses and ridding cells of foreign material. Perturbations in autophagy have been implicated in a number of pathological conditions such as neurodegeneration, cardiac disease and cancer. The growing knowledge about autophagic mechanisms needs to be collected in a computable and shareable format to allow its use in data representation and interpretation. The Gene Ontology (GO) is a freely available resource that describes how and where gene products function in biological systems. It consists of 3 interrelated structured vocabularies that outline what gene products do at the biochemical level, where they act in a cell and the overall biological objectives to which their actions contribute. It also consists of ‘annotations’ that associate gene products with the terms. Here we describe how we represent autophagy in GO, how we create and define terms relevant to autophagy researchers and how we interrelate those terms to generate a coherent view of the process, therefore allowing an interoperable description of its biological aspects. We also describe how annotation of gene products with GO terms improves data analysis and interpretation, hence bringing a significant benefit to this field of study.
Toxicity and drug exposure in a quadruple drug regimen in HIV–1 infected patients participating in the ADAM study

ObjectiveTo study the relationship between toxicity and the exposure to nelfinavir and saquinavir as part of a quadruple drug regimen. DesignThe ADAM study is a randomized study to investigate the feasibility of induction-maintenance therapy in HIV-1 infection. MethodsHIV-1-infected patients with no prior use of antiretroviral treatment started induction therapy consisting of stavudine + lamivudine + nelfinavir + saquinavir for a period of 26 weeks. Data regarding toxicity of the quadruple regimen and exposure to the protease inhibitors were collected. ResultsSeven of the 65 patients enrolled had to switch therapy for reasons of toxicity within the first 26 weeks. Diarrhoea was frequently reported (49 of 65, one discontinuation), but could be relieved by using antidiarrhoeal agents. Laboratory monitoring revealed elevated liver enzymes (leading to four discontinuations) and mild to moderate elevations of triglycerides and cholesterol (nine and 23 of 65, respectively). The exposure to saquinavir and nelfinavir was lower than expected. Abdominal pain was associated with a higher exposure to nelfinavir or saquinavir. The association of nausea and abdominal distension with drug exposure appeared to vary over time. ConclusionsThe quadruple drug regimen was quite well tolerated. Diarrhoea was frequently reported but could be relieved by the use of antidiarrhoeal agents. In comparison with other protease inhibitor combinations, lipid abnormalities in plasma were infrequent and mild. With the exception of diarrhoea, all gastrointestinal complaints observed were found to be associated with the level of exposure to nelfinavir or saquinavir. The exposure to the protease inhibitors was relatively low, although the virologic efficacy of the regimen used was satisfactory.
Scenes, Spaces, and Memory Traces

The hippocampus is one of the most closely scrutinized brain structures in neuroscience. While traditionally associated with memory and spatial cognition, in more recent years it has also been linked with other functions, including aspects of perception and imagining fictitious and future scenes. Efforts continue apace to understand how the hippocampus plays such an apparently wide-ranging role. Here we consider recent developments in the field and in particular studies of patients with bilateral hippocampal damage. We outline some key findings, how they have subsequently been challenged, and consider how to reconcile the disparities that are at the heart of current lively debates in the hippocampal literature.
Quantification of the tug-back by measuring the pulling force and micro computed tomographic evaluation

Objectives The aims of this study were to quantify tug-back by measuring the pulling force and investigate the correlation of clinical tug-back pulling force with in vitro gutta-percha (GP) cone adaptation score using micro-computed tomography (µCT). Materials and Methods Twenty-eight roots from human single-rooted teeth were divided into 2 groups. In the ProTaper Next (PTN) group, root canals were prepared with PTN, and in the ProFile (PF) group, root canals were prepared using PF (n = 14). The degree of tug-back was scored after selecting taper-matched GP cones. A novel method using a spring balance was designed to quantify the tug-back by measuring the pulling force. The correlation between tug-back scores, pulling force, and percentage of the gutta-percha occupied area (pGPOA) within apical 3 mm was investigated using µCT. The data were analyzed using Pearson's correlation analysis, one-way analysis of variance (ANOVA) and Tukey's test. Results Specimens with a strong tug-back had a mean pulling force of 1.24 N (range, 0.15–1.70 N). This study showed a positive correlation between tug-back score, pulling force, and pGPOA. However, there was no significant difference in these factors between the PTN and PF groups. Regardless of the groups, pGPOA and pulling force were significantly higher in the specimens with a higher tug-back score (p < 0.05). Conclusions The degree of subjective tug-back was a definitive determinant for master cone adaptation in the root canal. The use of the tug-back scoring system and pulling force allows the interpretation of subjective tug-back in a more objective and quantitative manner.
p38 Mitogen-activated protein kinase (MAPK) increases arginase activity and contributes to endothelial dysfunction in corpora cavernosa from angiotensin-II-treated mice.

INTRODUCTION Angiotensin II (AngII) activates p38 mitogen-activated protein kinase (MAPK) and elevates arginase activity in endothelial cells. Upregulation of arginase activity has been implicated in endothelial dysfunction by reducing nitric oxide (NO) bioavailability. However, signaling pathways activated by AngII in the penis are largely unknown. AIM We hypothesized that activation of p38 MAPK increases arginase activity and thus impairs penile vascular function in AngII-treated mice. METHODS Male C57BL/6 mice were implanted with osmotic minipumps containing saline or AngII (42 µg/kg/h) for 14 days and cotreated with p38 MAPK inhibitor, SB 203580 (5 µg/kg/day), beginning 2 days before minipump implantation. Systolic blood pressure (SBP) was measured. Corpus cavernosum (CC) tissue was used for vascular functional studies and protein expression levels of p38 MAPK, arginase and constitutive NO synthase (NOS), and arginase activity. MAIN OUTCOME MEASURES Arginase expression and activity; expression of phospho-p38 MAPK, endothelial NOS (eNOS) and neuronal NOS proteins; endothelium-dependent and nitrergic nerve-mediated relaxations were determined in CC from control and AngII-infused mice. RESULTS AngII increased SBP (22%) and increased CC arginase activity and expression (∼twofold), and phosphorylated P38 MAPK levels (30%) over control. Treatment with SB 203580 prevented these effects. Endothelium-dependent NO-mediated relaxation to acetylcholine was significantly reduced by AngII and this effect was prevented by SB 203580 (P < 0.01). AngII (2 weeks) did not alter nitrergic function. However, SB 203580 significantly increased nitrergic relaxation in both control and AngII tissue at lower frequencies. Maximum contractile responses for phenylephrine and electrical field stimulation were increased by AngII (56% and 171%, respectively) and attenuated by SB 203580 treatment. AngII treatment also decreased eNOS phosphorylation at Ser-1177 compared to control. Treatment with SB 203580 prevented all these changes. CONCLUSION p38 MAPK inhibition corrects penile arginase activity and protects against erectile dysfunction caused by AngII.
MicroRNA-34a inhibits liver cancer cell growth by reprogramming glucose metabolism

MicroRNAs (miRs) have been proposed as minimally invasive prognostic markers for various types of cancer, including liver cancer, which is one of the most common cancers worldwide. In the present study, the expression of miR-34a in human liver cancer tissues and cell lines was evaluated and the effects of miR-34a on cell proliferation, invasion and glycolysis in hepatocellular carcinoma (HCC) cells were determined. The results indicated that miR-34a was downregulated in human liver cancer tissues. Overexpression of miR-34a significantly inhibited liver cancer cell proliferation and clone formation. In terms of the underlying mechanism, miR-34a was indicated to negatively regulate the expression of lactate dehydrogenase A (LDHA), which consequently inhibited LDHA-dependent glucose uptake in the cancer cells, as well as cell proliferation and invasion. Collectively, these data suggest that miR-34a functions as a negative regulator of glucose metabolism and may serve as a novel marker for liver cancer prognosis.
Modelling the large-scale yellow fever outbreak in Luanda, Angola, and the impact of vaccination

Background Yellow fever (YF), transmitted via bites of infected mosquitoes, is a life-threatening viral disease endemic to tropical and subtropical regions of Africa and South America. YF has largely been controlled by widespread national vaccination campaigns. Nevertheless, between December 2015 and August 2016, YF resurged in Angola, quickly spread and became the largest YF outbreak for the last 30 years. Recently, YF resurged again in Brazil (December 2016). Thus, there is an urgent need to gain better understanding of the transmission pattern of YF. Model The present study provides a refined mathematical model, combined with modern likelihood-based statistical inference techniques, to assess and reconstruct important epidemiological processes underlying Angola’s YF outbreak. This includes the outbreak’s attack rate, the reproduction number (R0), the role of the mosquito vector, the influence of climatic factors, and the unusual but noticeable appearance of two-waves in the YF outbreak. The model explores actual and hypothetical vaccination strategies, and the impacts of possible human reactive behaviors (e.g., response to media precautions). Findings While there were 73 deaths reported over the study period, the model indicates that the vaccination campaign saved 5.1-fold more people from death and saved from illness 5.6-fold of the observed 941 cases. Delaying the availability of the vaccines further would have greatly worsened the epidemic in terms of increased cases and deaths. The analysis estimated a mean R0≈2.6-3.4 and an attack rate of 0.09-0.15% (proportion of population infected) over the whole period from December 2015 to August 2016. Our estimated lower and upper bounds of R0 are in line with previous studies. Unusually, R0 oscillated in a manner that was “delayed” with the reported deaths. High recent number of deaths were associated (followed) with periods of relatively low disease transmission and low R0, and vice-versa. The time-series of Luanda’s YF cases suggest the outbreak occurred in two waves, a feature that would have become far more prominent had there been no mass vaccination. The waves could possibly be due to protective reactive behavioral changes of the population affecting the mosquito population. The second wave could well be an outcome of the March-April rainfall patterns in the 2016 El Niño year by creating ideal conditions for the breeding of the mosquito vectors. The modelling framework is a powerful tool for studying future YF epidemic outbreaks, and provides a basis for future vaccination campaign evaluations.
A global analysis of parenchyma tissue fractions in secondary xylem of seed plants

Summary Parenchyma is an important tissue in secondary xylem of seed plants, with functions ranging from storage to defence and with effects on the physical and mechanical properties of wood. Currently, we lack a large‐scale quantitative analysis of ray parenchyma (RP) and axial parenchyma (AP) tissue fractions. Here, we use data from the literature on AP and RP fractions to investigate the potential relationships of climate and growth form with total ray and axial parenchyma fractions (RAP). We found a 29‐fold variation in RAP fraction, which was more strongly related to temperature than with precipitation. Stem succulents had the highest RAP values (mean ± SD: 70.2 ± 22.0%), followed by lianas (50.1 ± 16.3%), angiosperm trees and shrubs (26.3 ± 12.4%), and conifers (7.6 ± 2.6%). Differences in RAP fraction between temperate and tropical angiosperm trees (21.1 ± 7.9% vs 36.2 ± 13.4%, respectively) are due to differences in the AP fraction, which is typically three times higher in tropical than in temperate trees, but not in RP fraction. Our results illustrate that both temperature and growth form are important drivers of RAP fractions. These findings should help pave the way to better understand the various functions of RAP in plants.
Genomic evolution, recombination, and inter-strain diversity of chelonid alphaherpesvirus 5 from Florida and Hawaii green sea turtles with fibropapillomatosis

Chelonid alphaherpesvirus 5 (ChHV5) is a herpesvirus associated with fibropapillomatosis (FP) in sea turtles worldwide. Single-locus typing has previously shown differentiation between Atlantic and Pacific strains of this virus, with low variation within each geographic clade. However, a lack of multi-locus genomic sequence data hinders understanding of the rate and mechanisms of ChHV5 evolutionary divergence, as well as how these genomic changes may contribute to differences in disease manifestation. To assess genomic variation in ChHV5 among five Hawaii and three Florida green sea turtles, we used high-throughput short-read sequencing of long-range PCR products amplified from tumor tissue using primers designed from the single available ChHV5 reference genome from a Hawaii green sea turtle. This strategy recovered sequence data from both geographic regions for approximately 75% of the predicted ChHV5 coding sequences. The average nucleotide divergence between geographic populations was 1.5%; most of the substitutions were fixed differences between regions. Protein divergence was generally low (average 0.08%), and ranged between 0 and 5.3%. Several atypical genes originally identified and annotated in the reference genome were confirmed in ChHV5 genomes from both geographic locations. Unambiguous recombination events between geographic regions were identified, and clustering of private alleles suggests the prevalence of recombination in the evolutionary history of ChHV5. This study significantly increased the amount of sequence data available from ChHV5 strains, enabling informed selection of loci for future population genetic and natural history studies, and suggesting the (possibly latent) co-infection of individuals by well-differentiated geographic variants.
Liquid Profiling of Circulating Tumor DNA in Plasma of Melanoma Patients for Companion Diagnostics and Monitoring of BRAF Inhibitor Therapy.

BACKGROUND The current standard for determining eligibility of patients with metastatic melanoma for BRAF-targeted therapy is tissue-based testing of BRAF mutations. As patients are rarely rebiopsied, detection in blood might be advantageous by enabling a comprehensive assessment of tumor mutational status in real time and thereby representing a noninvasive biomarker for monitoring BRAF therapy. METHODS In all, 634 stage I to IV melanoma patients were enrolled at 2 centers, and 1406 plasma samples were prospectively collected. Patients were assigned to 3 separate study cohorts: study 1 for assessment of circulating tumor DNA (ctDNA) as part of companion diagnostics, study 2 for assessment of ctDNA for patients with low tumor burden and for follow-up, and study 3 for monitoring of resistance to BRAF inhibitor (BRAFi) or mitogen-activated protein kinase inhibitor therapy. RESULTS Overall, a high degree of concordance between plasma and tissue testing results was observed at 90.9% (study 1) and 90.1% (study 2), respectively. Interestingly, discrepant results were in some cases associated with nonresponse to BRAFi (n = 3) or a secondary BRAF-mutant malignancy (n = 5). Importantly, ctDNA results correlated with the clinical course of disease in 95.7% and with response to treatment. Significantly, the detection of BRAF mutant ctDNA preceded relapse assessed by Response Evaluation Criteria in Solid Tumors, and was more specific than serum S100 and lactate dehydrogenase. CONCLUSIONS Blood-based testing compares favorably with standard-of-care tissue-based BRAF mutation testing. Importantly, blood-based BRAF testing correlates with the clinical course, even for early-stage patients, and may be used to predict response to treatment, recurrence, and resistance before radioimaging under BRAFi therapy, thereby enabling considerable improvements in patient treatment.
Risk Factors for Bone Loss in Patients Having Clinical Conditions That Restrict Physical Activity

Purpose: The purpose of this study was to identify the effect of sleep duration, depression, and other factors on the risk for low bone mineral density (BMD) in patients having physical restrictions due to chronic obstructive pulmonary disease, cardiovascular disease, stroke, or asthma. Design: A cross-sectional survey. Methods: The 2008–2011 Korea National Health and Nutrition Examination Survey assesses sociodemographic, physiological, and behavioral factors, including depression and sleep duration. The records of 512 individuals were examined in the present survey. Findings: Among men, absence of a depressive mood was associated with greater lumbar spine BMD, and among women, adequate sleep duration was associated with greater lumbar spine BMD. Conclusions: This study of individuals having restricted physical activity due to a respiratory or circulatory problem indicated that men without depression and women with adequate sleep had greater BMD. Clinical Relevance: Interventions that improve sleep duration and provide a stable psychological state may help to prevent declines of BMD in this population.
Patterns of antiplatelet drug use after a first myocardial infarction during a 10‐year period

Aims The aims of the present study were to assess antiplatelet drug use patterns after a first myocardial infarction (MI) and to evaluate the determinants of antiplatelet nonpersistence. Methods The present study was conducted in 4690 patients from the Utrecht Cardiovascular Pharmacogenetics cohort with a first MI between 1986 and 2010, who were followed for a maximum of 10 years. Medication use and event diagnosis were obtained from the Dutch PHARMO Record Linkage System. Antiplatelet drug users were classified as persistent users (gap between prescriptions ≤90 days), nonpersistent users (>90‐day gap and no refills), and restarters (a new prescription after a >90‐day gap). The association between potential determinants and antiplatelet nonpersistence was analysed using Cox regression. Results The proportions of persistent users decreased from 84.0% at the 1‐year follow‐up to 32.8% at 10 years for any antiplatelet drug, and 77.3% to 27.5% for aspirin; and 39.0% to 6.4% for clopidogrel at 6 years. Most nonpersistent users restarted antiplatelet drugs later, leading to 89.3% overall antiplatelet drug users at 10 years after MI. Diabetes (hazard ratio [HR] 0.44; 0.32–0.60), hypertension (HR 0.77; 0.60–0.99), hypercholesterolaemia (HR 0.49; 0.39–0.62) and more recent MI diagnosis period (2003–2007: HR 0.69, 0.61–0.79; 2008–2010: HR 0.38, 0.19–0.77, compared to ≤ 2002 period) lowered the risk of antiplatelet nonpersistence, while vitamin K antagonist (VKA) comedication (HR 18.97; 16.91–21.28) increased this risk. Conclusions A large proportion of patients with a first MI still used antiplatelet drugs after 10 years. The frequent discontinuations during this time frame are expected to reduce the effectiveness of antiplatelet drugs as secondary prevention of cardiovascular diseases. Diabetes, hypertension, hypercholesterolaemia, VKA comedication and MI diagnosis period were determinants of antiplatelet nonpersistence.
Accuracy of data in abstracts of published research articles.

CONTEXT The section of a research article most likely to be read is the abstract, and therefore it is particularly important that the abstract reflect the article faithfully. OBJECTIVE To assess abstracts accompanying research articles published in 6 medical journals with respect to whether data in the abstract could be verified in the article itself. DESIGN Analysis of simple random samples of 44 articles and their accompanying abstracts published during 1 year(July 1, 1996-June 30, 1997) in each of 5 major general medical journals (Annals of Internal Medicine, BMJ, JAMA, Lancet, and New England Journal of Medicine) and a consecutive sample of 44 articles published during 15 months (July 1, 1996-August 15, 1997) in the CMAJ. MAIN OUTCOME MEASURE Abstracts were considered deficient if they contained data that were either inconsistent with corresponding data in the article's body (including tables and figures) or not found in the body at all. RESULTS The proportion of deficient abstracts varied widely (18%-68%) and to a statistically significant degree (P<.001) among the 6 journals studied. CONCLUSIONS Data in the abstract that are inconsistent with or absent from the article's body are common, even in large-circulation general medical journals.
Comparison of quality of life between open and endoscopic thyroidectomy for papillary thyroid cancer

Recently, various endoscopic thyroidectomy techniques have been introduced for cosmetic purposes. However, few reports have compared the quality of life (QOL) between post–endoscopic thyroidectomy and post–conventional open thyroidectomy. In this study, we investigated whether endoscopic thyroidectomy was comparable to conventional open thyroidectomy with respect to QOL.