Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular impact of juvenile hormone agonists on neonatal Daphnia magna

Daphnia magna has been used extensively to evaluate organism‐ and population‐level responses to pollutants in acute toxicity and reproductive toxicity tests. We have previously reported that exposure to juvenile hormone (JH) agonists results in a reduction of reproductive function and production of male offspring in a cyclic parthenogenesis, D. magna. Recent advances in molecular techniques have provided tools to understand better the responses to pollutants in aquatic organisms, including D. magna. DNA microarray was used to evaluate gene expression profiles of neonatal daphnids exposed to JH agonists: methoprene (125, 250 and 500 ppb), fenoxycarb (0.5, 1 and 2 ppb) and epofenonane (50, 100 and 200 ppb). Exposure to these JH analogs resulted in chemical‐specific patterns of gene expression. The heat map analyses based on hierarchical clustering revealed a similar pattern between treatments with a high dose of methoprene and with epofenonane. In contrast, treatment with low to middle doses of methoprene resulted in similar profiles to fenoxycarb treatments. Hemoglobin and JH epoxide hydrolase genes were clustered as JH‐responsive genes. These data suggest that fenoxycarb has high activity as a JH agonist, methoprene shows high toxicity and epofenonane works through a different mechanism compared with other JH analogs, agreeing with data of previously reported toxicity tests. In conclusion, D. magna DNA microarray is useful for the classification of JH analogs and identification of JH‐responsive genes. Copyright © 2013 John Wiley & Sons, Ltd.
Partial Occlusion of the Descending Aorta Increases Cerebral Blood Flow in a Nonstroke Porcine Model

Background: We studied the effect of partial aortic occlusion on cerebral perfusion and cardiac performance using the intra-aortic NeuroFlo™ catheter. Methods: Adult pigs were instrumented to determine cardiac parameters; unique isotope-labeled microspheres were used to determine cerebral blood flow (CBF) before, during and after sequential partial aortic occlusion. Results: Six pigs were studied; there was no relevant change in cardiac output, and the desired pressure drop of 10–15 mm Hg across the balloons was achieved. CBF increased significantly with inflation of the suprarenal balloon and remained elevated 90 min after deflation. Conclusions:Partial aortic occlusion with the NeuroFlo catheter significantly increased cerebral perfusion without adversely affecting cardiac performance.
A Single-Institution Experience With Treatment of Severe Acute Chest Syndrome: Lack of Rebound Pain With Dexamethasone Plus Transfusion Therapy

The use of corticosteroid therapy for the treatment of acute chest syndrome (ACS) in patients with sickle cell disease has been infrequently used owing to concerns for rebound pain. Here, we report a cohort of patients <21 years of age with sickle cell disease treated between January 2001 and June 2006 for severe ACS with both corticosteroids and transfusion therapy. We reviewed 53 episodes of severe ACS with an average hospital duration of 4.9 days. Only 1 patient out of 6 who were transferred to the intensive care unit required intubation. None of the ACS episodes resulted in death and none of the 4 readmissions after discharge were due to pain. There was no acute toxicity related to either corticosteroid or transfusion therapy.
Influenza A Virus Host Shutoff Disables Antiviral Stress-Induced Translation Arrest

Influenza A virus (IAV) polymerase complexes function in the nucleus of infected cells, generating mRNAs that bear 5′ caps and poly(A) tails, and which are exported to the cytoplasm and translated by host machinery. Host antiviral defences include mechanisms that detect the stress of virus infection and arrest cap-dependent mRNA translation, which normally results in the formation of cytoplasmic aggregates of translationally stalled mRNA-protein complexes known as stress granules (SGs). It remains unclear how IAV ensures preferential translation of viral gene products while evading stress-induced translation arrest. Here, we demonstrate that at early stages of infection both viral and host mRNAs are sensitive to drug-induced translation arrest and SG formation. By contrast, at later stages of infection, IAV becomes partially resistant to stress-induced translation arrest, thereby maintaining ongoing translation of viral gene products. To this end, the virus deploys multiple proteins that block stress-induced SG formation: 1) non-structural protein 1 (NS1) inactivates the antiviral double-stranded RNA (dsRNA)-activated kinase PKR, thereby preventing eIF2α phosphorylation and SG formation; 2) nucleoprotein (NP) inhibits SG formation without affecting eIF2α phosphorylation; 3) host-shutoff protein polymerase-acidic protein-X (PA-X) strongly inhibits SG formation concomitant with dramatic depletion of cytoplasmic poly(A) RNA and nuclear accumulation of poly(A)-binding protein. Recombinant viruses with disrupted PA-X host shutoff function fail to effectively inhibit stress-induced SG formation. The existence of three distinct mechanisms of IAV-mediated SG blockade reveals the magnitude of the threat of stress-induced translation arrest during viral replication.
Shipment Impairs Lymphocyte Proliferative Responses to Microbial Antigens

ABSTRACT Lymphocyte proliferation assays (LPAs) are widely used to assess T-lymphocyte function of patients with human immunodeficiency virus infection and other primary and secondary immunodeficiency disorders. Since these assays require expertise not readily available at all clinical sites, specimens may be shipped to central labs for testing. We conducted a large multicenter study to evaluate the effects of shipping on assay performance and found significant loss of LPA activity. This may lead to erroneous results for individual subjects and introduce bias into multicenter trials.
Dietary pattern and risk of multiple sclerosis

Background It has been suggested that nutrition might play a role in the etiology of multiple sclerosis (MS). However, dietary patterns associated with MS risk are unknown. This study was conducted to compare the dietary patterns of patients with MS and healthy controls to find the relationship between dietary patterns and MS. Methods Usual dietary intake of 75 women with relapsing/remitting MS (RRMS) and 75 healthy controls were assessed with a food frequency questionnaire consisting of 168 food items. To define major dietary patterns, we used factor analysis. Multivariate logistic regression was used to assess the relationship between dietary patterns and risk of MS. Results Traditional pattern (high in low-fat dairy products, red meat, vegetable oil, onion, whole grain, soy, refined grains, organ meats, coffee, and legumes) was inversely related to the risk of MS [odds ratio (OR) = 0.15; 95% confidence interval (CI): 0.03-0.18; P = 0.028]. A similar inverse relationship was noted between MS risk and lacto-vegetarian (high in nuts, fruits, French fries, coffee, sweets and desserts, vegetables, and high-fat dairy products) and vegetarian (high in green leafy vegetables, hydrogenated fats, tomato, yellow vegetables, fruit juices, onion, and other vegetables) patterns (OR = 0.31; 95% CI: 0.12-0.82; P = 0.018 and OR = 0.42; 95% CI: 0.19-0.90; P = 0.026, respectively). In contrast, the prevalence of MS was higher in those who had high animal fat dietary pattern (high in animal fats, potato, meat products, sugars, and hydrogenated fats and low in whole grains) (OR = 1.99; 95% CI: 1.63-2.94; P < 0.005). Conclusion Our findings showed that the risk of RRMS can be affected by major dietary patterns.
Anatomy of the Facial Danger Zones: Maximizing Safety during Soft-Tissue Filler Injections

Summary: With limited downtime and immediate results, facial filler injections are becoming an ever more popular alternative to surgical rejuvenation of the face. The results, and the complications, can be impressive. To maximize safety during injections, the authors have outlined general injection principles followed by pertinent anatomy within six different facial danger zones. Bearing in mind the depth and the location of the vasculature within each zone, practitioners can tailor their injection techniques to prevent vessel injury and avoid cannulation.
Hidden Conditional Random Fields with Distributed User Embeddings for Ad Targeting

Estimating a user's propensity to click on a display ad or purchase a particular item is a critical task in targeted advertising, a burgeoning online industry worth billions of dollars. Better and more accurate estimation methods result in improved online user experience, as only relevant and interesting ads are shown, and may also lead to large benefits for advertisers, as targeted users are more likely to click or make a purchase. In this paper we address this important problem, and propose an approach for improved estimation of ad click or conversion prob- ability based on a sequence of user's online actions, modeled using Hidden Conditional Random Fields (HCRF) model. In addition, in order to address the sparsity issue at the input side of the HCRF model, we propose to learn distributed, low-dimensional representations of user actions through a directed skip-gram, a neural architecture suitable for sequential data. Experimental results on a real-world data set comprising thousands of user sessions collected at Yahoo servers clearly indicate the benefits and the potential of the proposed approach, which outperformed competing state-of-the-art algorithms and obtained significant improvements in terms of retrieval measures.
Geographic variations of the prevalence and distribution of COPD phenotypes in Spain: “the ESPIRAL-ES study”

Purpose The purpose of this study was to assess the prevalence of COPD phenotypes at a national level and to determine their geographic distribution among different autonomous communities in Spain. Patients and methods A total of 1,610 patients (82% men, median age 67 years) recruited in primary care centers and pneumology services participated in an observational, cross-sectional, and multicenter study. Phenotypes evaluated were the non-exacerbator phenotype, the asthma–COPD overlap syndrome (ACOS), the exacerbator phenotype with emphysema, and the exacerbator phenotype with chronic bronchitis. Results The non-exacerbator phenotype was the most common (46.7%) followed by exacerbator with chronic bronchitis (22.4%) and exacerbator with emphysema (16.4%). The ACOS phenotype accounted for the lowest rate (14.5%). For each phenotype, the highest prevalence rates were concentrated in two or three autonomous communities, with relatively similar rates for the remaining regions. Overall prevalence rates were higher for the non-exacerbator and the exacerbator with chronic bronchitis phenotypes than for ACOS and the exacerbator with chronic bronchitis phenotypes. Differences in the distribution of COPD phenotypes according to gender, age, physician specialty, smoking habit, number of comorbidities, quality of life assessed with the COPD Assessment Test, and BODEx index (body mass index, airflow obstruction, dyspnea, and exacerbations) were all statistically significant. Conclusion Differences in the prevalence rates of COPD phenotypes among the Spanish autonomous communities have been documented. Mapping the distribution of COPD phenotypes is useful to highlight regional differences as starting point for comparisons across time. This geographic analysis provides health-care planners a valuable platform to assess changes in COPD burden at nationwide and regional levels.
The translocation kinetics of antibiotics through porin OmpC: Insights from structure‐based solvation mapping using WaterMap

Poor permeability of the lipopolysaccharide‐based outer membrane of Gram‐negative bacteria is compensated by the existence of protein channels (porins) that selectively admit low molecular weight substrates, including many antibiotics. Improved understanding of the translocation mechanisms of porin substrates could help guide the design of antibiotics capable of achieving high intracellular exposure. Energy barriers to channel entry and exit govern antibiotic fluxes through porins. We have previously reported a hypothesis that the costs of transferring protein solvation to and from bulk medium underlie the barriers to protein‐ligand association and dissociation, respectively, concomitant with the gain and loss of protein‐ligand interactions during those processes. We have now applied this hypothesis to explain the published rates of entry (association) and exit (dissociation) of six antibiotics to/from reconstituted E. coli porin OmpC. WaterMap was used to estimate the total water transfer energies resulting from transient occupation by each antibiotic. Our results suggest that solvation within the porin cavity is highly energetically favorable, and the observed moderately fast entry rates of the antibiotics are consistent with replacement of protein‐water H‐bonds. The observed ultrafast exit kinetics is consistent with the lack of intrachannel solvation sites that convey unfavorable resolvation during antibiotic dissociation. These results are aligned with known general relationships between antibiotic efficacy and physicochemical properties, namely unusually low logP, reflecting an abundance of H‐bond partners. We conclude that antibiotics figuratively “melt” their way through porin solvation at a rate determined by the cost of exchanging protein‐solvent for protein‐antibiotic H‐bonds. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Meter and Periodicity in Musical Performance

This paper presents a psychoacoustically based method of data reduction motivated by the desire to analyze the rhythm of musical performances. The resulting information is then analyzed by the “Periodicity Transform” (which is based on a projection onto “periodic subspaces”) to locate periodicities in the resulting data. These periodicities represent the rhythm at several levels, including the “pulse”, the “measure”, and larger structures such as musical “phrases. ” The implications (and limitations) of such automated grouping of rhythmic features is discussed. The method is applied to a number of musical examples, its output is compared to that of the Fourier Transform, and both are compared to a more traditional “musical” analysis of the rhythm. Unlike many methods of rhythm analysis, the techniques can be applied directly to the digitized performance (i.e., a sound- file) and do not require a musical score or a MIDI transcription. Several examples are presented that highlight both the strengths and weaknesses of the approach.
Rotenone-induced Impairment of Mitochondrial Electron Transport Chain Confers a Selective Priming Signal for NLRP3 Inflammasome Activation*

Background: Mitochondrial dysfunction is considered crucial for triggering NLRP3 inflammasome activation. Results: Rotenone-induced impairment of mitochondrial electron transport chain promotes NLRP3 inflammasome activation exclusively with ATP but not with other NLRP3-activating stimulators. Conclusion: High-grade mROS and hyperpolarization are essential for NLRP3 inflammasome activation upon rotenone-induced mitochondrial dysfunction. Significance: Mitochondrial impairment may selectively prime NLRP3 inflammasome activation, leading to many degenerative diseases. Mitochondrial dysfunction is considered crucial for NLRP3 inflammasome activation partly through its release of mitochondrial toxic products, such as mitochondrial reactive oxygen species (mROS)2 and mitochondrial DNA (mtDNA). Although previous studies have shown that classical NLRP3-activating stimulations lead to mROS generation and mtDNA release, it remains poorly understood whether and how mitochondrial damage-derived factors may contribute to NLRP3 inflammasome activation. Here, we demonstrate that impairment of the mitochondrial electron transport chain by rotenone primes NLRP3 inflammasome activation only upon costimulation with ATP and not with nigericin or alum. Rotenone-induced priming of NLRP3 in the presence of ATP triggered the formation of specklike NLRP3 or ASC aggregates and the association of NLRP3 with ASC, resulting in NLRP3-dependent caspase-1 activation. Mechanistically, rotenone confers a priming signal for NLRP3 inflammasome activation only in the context of aberrant high-grade, but not low-grade, mROS production and mitochondrial hyperpolarization. By contrast, rotenone/ATP-mediated mtDNA release and mitochondrial depolarization are likely to be merely an indication of mitochondrial damage rather than triggering factors for NLRP3 inflammasome activation. Our results provide a molecular insight into the selective contribution made by mitochondrial dysfunction to the NLRP3 inflammasome pathway.
Constraint-Induced Movement Therapy for the Upper Paretic Limb in Acute or Sub-Acute Stroke: A Systematic Review

Abstract Constraint-induced movement therapy is a commonly used intervention to improve upper limb function after stroke. However, the effectiveness of constraint-induced movement therapy and its optimal dosage during acute or sub-acute stroke is still under debate. To examine the literature on the effects of constraint-induced movement therapy in acute or sub-acute stroke. A literature search was performed to identify randomized, controlled trials; studies with the same outcome measure were pooled by calculating the mean difference. Separate quantitative analyses for high-intensity and low-intensity constraint-induced movement therapy were applied when possible. Five randomized, controlled trials were included, comprising 106 participants. The meta-analysis demonstrated significant mean differences in favor of constraint-induced movement therapy for the Fugl–Meyer arm, the Action Research Arm Test, the Motor Activity Log, Quality of Movement and the Grooved Pegboard Test. Nonsignificant mean difference in favor of constraint-induced movement therapy were found for the Motor Activity Log, Amount of Use. Separate analyses for high-intensity and low-intensity constraint-induced movement therapy resulted in significant favorable mean differences for low-intensity constraint-induced movement therapy for all outcome measures, in contrast to high-intensity constraint-induced movement therapy. This meta-analysis demonstrates a trend toward positive effects of high-intensity and low-intensity constraint-induced movement therapy in acute or sub-acute stroke, but also suggests that low-intensity constraint-induced movement therapy may be more beneficial during this period than high-intensity constraint-induced movement therapy. However, these results were based on a small number of studies. Therefore, more trials are needed applying different doses of therapy early after stroke and a better understanding is needed about the different time windows in which underlying mechanisms of recovery operate.
Nonhuman gamblers: lessons from rodents, primates, and robots

The search for neuronal and psychological underpinnings of pathological gambling in humans would benefit from investigating related phenomena also outside of our species. In this paper, we present a survey of studies in three widely different populations of agents, namely rodents, non-human primates, and robots. Each of these populations offers valuable and complementary insights on the topic, as the literature demonstrates. In addition, we highlight the deep and complex connections between relevant results across these different areas of research (i.e., cognitive and computational neuroscience, neuroethology, cognitive primatology, neuropsychiatry, evolutionary robotics), to make the case for a greater degree of methodological integration in future studies on pathological gambling.
Interaction of Programmed Death-1 and Programmed Death-1 Ligand-1 Contributes to Testicular Immune Privilege

Background. Immune responses are tempered in immunologically privileged sites including the testis. Previous studies have shown that islet transplantation in the testis significantly prolongs islet allograft survival. However, mechanisms underlying testicular immune privilege and intratesticular allograft survival remain unclear. Methods. Allogeneic murine islets were transplanted in the testis. Programmed death-1 ligand-1 (PD-L1) expression was detected by immunohistochemstry and real-time polymerase chain reaction. Infiltrating T-cell proliferation was measured by bromodeoxyuridine uptakes, whereas their apoptosis was quantified by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling methods. Transgenic T cells were used to track allospecific memory T-cell generation. Results. We found that programmed death-1 (PD-1):PD-L1 negative costimulation is essential for prolonged survival of intratesticular islet allografts, as blocking PD-L1 or PD-1, but not PD-L2 and cytotoxic T-lymphocyte antigen 4, abrogated long-term survival of intratesticular islet allografts. As controls, blocking PD-1 or PD-L1 did not significantly accelerate the acute rejection of islet allografts transplanted under the renal capsule, a conventional islet-grafting site. We also found for the first time that PD-L1 is constitutively expressed mainly by spermatocytes and spermatids in seminiferous tubules of the testis. Moreover, infiltrating T cells underwent less vigorous proliferation but faster apoptosis in the testis than in the kidney. Blocking PD-1:PD-L1 costimulation largely abolished the suppression of T-cell proliferation and acceleration of T-cell apoptosis. Importantly, testicular immune privilege significantly suppressed the generation and proliferation of donor-specific memory CD8+ T cells. Conclusions. The constitutive expression of PD-L1 in the testis is an important mechanism underlying testicular immune privilege and long-term survival of intratesticular islet allografts.
On the Edge-Expansion of Graphs

It is shown that if n>n0(d) then any d-regular graph G=(V, E) on n vertices contains a set of u=[lfloor ]n/2[rfloor ] vertices which is joined by at most (d/2−c√d)u edges to the rest of the graph, where c>0 is some absolute constant. This is tight, up to the value of c.
Anti‐infective potential of Citrus bergamia Risso et Poiteau (bergamot) derivatives: a systematic review

Infectious diseases remain among the leading causes of morbidity and mortality worldwide, mainly because of the increase of resistance to chemotherapeutic drugs. Nature is the major source of anti‐infective drugs and could represent a font of medicines that may help overcome antibiotic resistance. Recently, the potential antimicrobial effect of certain plant extracts has attracted attention within the scientific community as alternatives to synthetic drugs. Here, we present a systematic review on the anti‐infective properties of bergamot derivatives that highlight the activity of bergamot essential oil against bacteria, mycetes and larvae, as well as the anti‐Helicobacter pylori effect of bergamot juice and the antimicrobial properties of extracts from bergamot peel. Findings presented herein could be used to develop novel and alternative preventive and therapeutic strategies aimed to overcome antibiotic resistance. Copyright © 2016 John Wiley & Sons, Ltd.