Miracle-dz/UniFAR-FTUs huggingface dataset:
Coffee Consumption Enhances High-Density Lipoprotein–Mediated Cholesterol Efflux in Macrophages

Rationale: Association of habitual coffee consumption with coronary heart disease morbidity and mortality has not been established. We hypothesized that coffee may enhance reverse cholesterol transport (RCT) as the antiatherogenic properties of high-density lipoprotein (HDL). Objective: This study was to investigate whether the phenolic acids of coffee and coffee regulates RCT from macrophages in vitro, ex vivo and in vivo. Methods and Results: Caffeic acid and ferulic acid, the major phenolic acids of coffee, enhanced cholesterol efflux from THP-1 macrophages mediated by HDL, but not apoA-I. Furthermore, these phenolic acids increased both the mRNA and protein levels of ATP-binding cassette transporter (ABC)G1 and scavenger receptor class B type I (SR-BI), but not ABCA1. Eight healthy volunteers were recruited for the ex vivo study, and blood samples were taken before and 30 minutes after consumption of coffee or water in a crossover study. The mRNA as well as protein levels of ABCG1, SR-BI, and cholesterol efflux by HDL were increased in the macrophages differentiated under autologous sera obtained after coffee consumption compared to baseline sera. Finally, effects of coffee and phenolic acid on in vivo RCT were assessed by intraperitoneally injecting [3H]cholesterol-labeled acetyl low-density lipoprotein–loaded RAW264.7 cells into mice, then monitoring appearance of 3H tracer in plasma, liver, and feces. Supporting in vitro and ex vivo data, ferulic acid was found to significantly increase the levels of 3H tracer in feces. Conclusions: Coffee intake might have an antiatherogenic property by increasing ABCG1 and SR-BI expression and enhancing HDL-mediated cholesterol efflux from the macrophages via its plasma phenolic acids.
Hemispheric asymmetries in phonological processing of tones versus segmental units

The aim of this functional magnetic resonance imaging study is to identify neuroanatomical substrates underlying phonological processing of segmental (consonant, rhyme) and suprasegmental (tone) units. An auditory verbal recognition paradigm was used in which native speakers of Mandarin Chinese were required to match a phonological unit that occurs in a list of three syllables to the corresponding unit of a following probe. The results show that hemispheric asymmetries arise depending on the type of phonological unit. In direct contrasts between phonological units, tones, relative to consonants and rhymes, yield increased activation in frontoparietal areas of the right hemisphere. This finding indicates that the cortical circuitry subserving lexical tones differs from that of consonants or rhymes.
Endothelial Progenitor Cell Fraction Contained in Bone Marrow-Derived Mesenchymal Stem Cell Populations Impairs Osteogenic Differentiation

In bone tissue engineering (TE) endothelial cell-osteoblast cocultures are known to induce synergies of cell differentiation and activity. Bone marrow mononucleated cells (BMCs) are a rich source of mesenchymal stem cells (MSCs) able to develop an osteogenic phenotype. Endothelial progenitor cells (EPCs) are also present within BMC. In this study we investigate the effect of EPCs present in the BMC population on MSCs osteogenic differentiation. Human BMCs were isolated and separated into two populations. The MSC population was selected through plastic adhesion capacity. EPCs (CD34+ and CD133+) were removed from the BMC population and the resulting population was named depleted MSCs. Both populations were cultured over 28 days in osteogenic medium (Dex+) or medium containing platelet lysate (PL). MSC population grew faster than depleted MSCs in both media, and PL containing medium accelerated the proliferation for both populations. Cell differentiation was much higher in Dex+ medium in both cases. Real-time RT-PCR revealed upregulation of osteogenic marker genes in depleted MSCs. Higher values of ALP activity and matrix mineralization analyses confirmed these results. Our study advocates that absence of EPCs in the MSC population enables higher osteogenic gene expression and matrix mineralization and therefore may lead to advanced bone neoformation necessary for TE constructs.
Doppler ultrasound and tibial tuberosity maturation status predicts pain in adolescent male athletes with Osgood-Schlatter's disease: a case series with comparison group and clinical interpretation

Background The pathogenesis of the Osgood-Schlatter's disease (OSD) is still debated. The fragmentation of the ossification centre has been questioned as a definitive sign of OSD and has been seen as a normal development of the anterior tibial tubercle (ATT). Objectives It is unknown if such changes are present in the presumed pathological tendon insertion seen in OSD, nor the relation of Doppler-positive changes to pain on clinical examination. Methods A prospective analysis was carried out on 20 consecutive symptomatic male athletes (13.9 years±1.3) and a comparison group of asymptomatic subjects. All underwent a comparative clinical assessment and ultrasound with colour Doppler scan on both knees. Subjective pain was recorded with a visual analogue scale (VAS) during provocative manoeuvres: palpation, resisted contraction and single leg squat. Results Positive Doppler US (within the distal end of the patellar tendon) was associated with higher pain on palpation (47±24.5 vs 18±11.4, p<0.01) and resisted static contraction (59±20.2 vs 27±12.5, p<0.001) compared with Doppler-negative subjects. No Doppler activity was found in the comparison group. VAS for palpation and resisted contraction of the athletes graded as stage 2 (51.1±22.0 and 60.0±21.2) were significantly higher than stage 3 (17.8±12.0 and 18.9±16.9) and stage 4 (15.0±7.1 and 25.0±7.1; p<0.01). Conclusions More painful OSD is associated with the presence of neo-vessels. This may be linked with a particular stage of ATT maturation and applied compressive forces. A Doppler ultrasound scan adds practical information to develop the care plan of the patient.
Lenalidomide and Rituximab in Waldenstrom's Macroglobulinemia

Purpose: Thalidomide and its more potent immunomodulatory derivative lenalidomide enhance rituximab-mediated antibody-dependent cell-mediated cytotoxicity. We therefore evaluated lenalidomide and rituximab in symptomatic Waldenstrom's macroglobulinemia (WM) patients naive to either agent. Experimental Design: Intended therapy consisted of 48 weeks of lenalidomide (25 mg/d for 3 weeks and then 1 week off) along with rituximab (375 mg/m2/wk) dosed on weeks 2 to 5 and 13 to 16. Sixteen patients were enrolled, 12 of whom were previously untreated. Results: Unexpectedly, we observed an acute decrease in hematocrit in 13 of 16 patients (median hematocrit decrease, 4.8%), which was attributable to lenalidomide patients and which led to cessation of further enrollment on this study. Lenalidomide-related anemia was observed even at doses as low as 5 mg/d and occurred in the absence of hemolysis or other cytopenias. The overall response and major response (<50% decrease in serum IgM) rates were 50% and 25%, respectively, on an intent-to-treat basis. With a median follow-up of 31.3 months, 4 of 8 responding patients have progressed with a median time to progression of 18.9 months. Conclusion: Lenalidomide produces unexpected but clinically significant acute anemia in patients with WM. In comparison with our previous study with thalidomide and rituximab in an analogous patient population, the responses achieved in WM patients with lenalidomide and rituximab appear less favorable.
Adverse health behaviours are associated with depression and anxiety in multiple sclerosis: A prospective multisite study

Background: Depression and anxiety are common among people with multiple sclerosis (MS), as are adverse health behaviours, but the associations between these factors are unclear. Objective: To evaluate the associations between cigarette smoking, alcohol use, and depression and anxiety in MS in a cross-Canada prospective study. Methods: From July 2010 to March 2011 we recruited consecutive MS patients from four MS clinics. At three visits over two years, clinical and demographic information was collected, and participants completed questionnaires regarding health behaviours and mental health. Results: Of 949 participants, 75.2% were women, with a mean age of 48.6 years; most had a relapsing−remitting course (72.4%). Alcohol dependence was associated with increased odds of anxiety (OR: 1.84; 95% CI: 1.32–2.58) and depression (OR: 1.53; 95% CI: 1.05–2.23) adjusting for age, sex, Expanded Disability Status Scale (EDSS), and smoking status. Smoking was associated with increased odds of anxiety (OR: 1.29; 95% CI: 1.02–1.63) and depression (OR: 1.37; 95% CI: 1.04–1.78) adjusting for age, sex, EDSS, and alcohol dependence. Alcohol dependence was associated with an increased incidence of depression but not anxiety. Depression was associated with an increased incidence of alcohol dependence. Conclusion: Alcohol dependence and smoking were associated with anxiety and depression. Awareness of the effects of adverse health behaviours on mental health in MS might help target counselling and support for those ‘at risk’.
Varied presentations of moyamoya disease in a tertiary care hospital of north-east India

Introduction: Moyamoya disease is a chronic progressive cerebrovascular disorder, characterized by stenosis or occlusion of bilateral internal carotid arteries (ICAs), anterior cerebral arteries (ACAs) and middle cerebral arteries (MCAs), accompanied by a collateral network of vessels formed at the base of the brain. Ischemia and intracranial hemorrhage are the common typical manifestations. However moyamoya disease has been associated with atypical presentations like headache, seizures and involuntary movements. Although frequently reported from Asian countries like Japan, China and Korea, only few studies reported on clinical manifestations of moyamoya disease from India. Objectives: To study the varied presentations of moyamoya disease in a tertiary care hospital of north-east India. Material and Methods: Relevant investigations were done to rule out other causes of moyamoya syndrome. Results: We report 6 cases of moyamoya disease with varied presentations from a tertiary care referral government hospital. Case 1, 2 and 6 presented with alternating hemiparesis. Case 3 had amaurosis fugax. Case 4 had history suggestive of ischemic stroke and presented with hemichorea. Case 4 had focal seizure as the only manifestation. Cases 4 and 5 notably had stenosis of posterior cerebral artery (PCA) in addition to stenosis of bilateral ICAs, ACAs and MCAs. Conclusion: Owing to its low incidence in India, moyamoya disease is easily overlooked as a possible diagnosis. However, because of its progressive nature, it is imperative to diagnose this disease early and offer surgical treatment to the patients.
Growth-Associated Protein-43 Is Required for Commissural Axon Guidance in the Developing Vertebrate Nervous System

Growth-associated protein-43 (GAP-43) is a major growth cone protein whose phosphorylation by PKC in response to extracellular guidance cues can regulate F-actin behavior. Here we show that 100% of homozygote GAP-43 (−/−) mice failed to form the anterior commissure (AC), hippocampal commissure (HC), and corpus callosum (CC) in vivo. Instead, although midline fusion was normal, selective fasciculation between commissural axons was inhibited, and TAG-1-labeled axons tangled bilaterally into Probst's bundles. Moreover, their growth cones had significantly smaller lamellas and reduced levels of F-actin in vitro. Likewise, 100% of GAP-43 (+/−) mice with one disrupted allele also showed defects in HC and CC, whereas the AC was unaffected. Individual GAP-43 (+/−) mice could be assigned to two groups based on the amount that PKC phosphorylation of GAP-43 was reduced in neocortical neurons. In mice with ∼1% phosphorylation, the HC and CC were absent, whereas in mice with ∼10% phosphorylation, the HC and CC were smaller. Both results suggest that PKC-mediated signaling in commissural axons may be defective. However, although Probst's bundles formed consistently at the location of the glial wedge, both GAP-43 (−/−) and GAP-43 (+/+) cortical axons were still repulsed by Slit-2 in vitro, precluding failure of this deflective signal from the glial wedge as the source of the phenotype. Nonetheless, the data show that a functional threshold of GAP-43 is required for commissure formation and suggests that failure to regulate F-actin in commissural growth cones may be related to inhibited PKC phosphorylation of GAP-43.
Functional heterogeneity of colony‐stimulating factor‐induced human monocyte‐derived macrophages

Objectives: Macrophages (Mφs) have various functions and play a critical role in host defense and the maintenance of homeostasis. Mφs exist in every tissue in the body, but Mφs from different tissues exhibit a wide range of phenotypes with regard to their morphology, cell surface antigen expression and function, and are called by different names. However, the precise mechanism of the generation of macrophage heterogeneity is not known. In the present study, the authors examined the functional heterogeneity of Mφs generated from human monocytes under the influence of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and macrophage‐CSF (M‐CSF).
Directed Evaluation of Enterotoxigenic Escherichia coli Autotransporter Proteins as Putative Vaccine Candidates

Background Enterotoxigenic Escherichia coli (ETEC) is a major diarrheal pathogen in developing countries, where it accounts for millions of infections and hundreds of thousands of deaths annually. While vaccine development to prevent diarrheal illness due to ETEC is feasible, extensive effort is needed to identify conserved antigenic targets. Pathogenic Escherichia coli, including ETEC, use the autotransporter (AT) secretion mechanism to export virulence factors. AT proteins are comprised of a highly conserved carboxy terminal outer membrane beta barrel and a surface-exposed amino terminal passenger domain. Recent immunoproteomic studies suggesting that multiple autotransporter passenger domains are recognized during ETEC infection prompted the present studies. Methodology Available ETEC genomes were examined to identify AT coding sequences present in pathogenic isolates, but not in the commensal E. coli HS strain. Passenger domains of the corresponding autotransporters were cloned and expressed as recombinant antigens, and the immune response to these proteins was then examined using convalescent sera from patients and experimentally infected mice. Principal Findings Potential AT genes shared by ETEC strains, but absent in the E. coli commensal HS strain were identified. Recombinant passenger domains derived from autotransporters, including Ag43 and an AT designated pAT, were recognized by antibodies from mice following intestinal challenge with H10407, and both Ag43 and pAT were identified on the surface of ETEC by flow cytometry. Likewise, convalescent sera from patients with ETEC diarrhea recognized Ag43 and pAT, suggesting that these proteins are expressed during both experimental and naturally occurring ETEC infections and that they are immunogenic. Vaccination of mice with recombinant passenger domains from either pAT or Ag43 afforded protection against intestinal colonization with ETEC. Conclusions Passenger domains of conserved autotransporter proteins could contribute to protective immune responses that develop following infection with ETEC, and these antigens consequently represent potential targets to explore in vaccine development.
Evolutionary Approaches to Off-Line Routing in Backbone Communications Networks

O -line routing in backbone communications networks is an important combinatorial optimisation problem. It has three main uses: rst, o -line routing provides reference benchmark results for dynamic (on-line) routing strategies. Second, and more interestingly, o -line routing is becoming more and more investigated and employed in its own right as a way of quickly nding signi cantly improved routings for live networks which can then be imposed on the network to o er a net improvement in quality of service. Third, it can be used in networks where bandwidth may be booked in advance. In this paper we introduce and investigate a number of heuristic techniques applicable to the routing problem for use in stochastic, iterative search. Results are presented which indicate that these heuristics signi cantly improve the search for solutions, particularly when on-line performance is considered. We also investigate how computation time can be further reduced by the use of delta-evaluation of solutions. Previously, simulated annealing has had a signi cant advantage over genetic algorithms on problems where delta-evaluation is possible because the technique is not usually applicable in genetic algorithms employing standard crossover operators. However, we introduce a specialised crossover operator which enables a genetic algorithm to exploit delta-evaluation e ectively on this problem. We compare the performance of the genetic algorithm employing the new crossover operator with a mutation-only genetic algorithm and nd the performance of the former to be signi cantly better. Nonetheless, results indicate that when our heuristics are used in a simulated annealer and initialisation is performed in a certain way, it outperforms our genetic algorithm on a range of problems of di erent sizes and di culties. This nding leads us to investigate a local search approach to a multiobjective formulation of the routing problem. To this end, a new local search multiobjective optimiser is described, and its performance on the routing problem is compared with that of a multiobjective EA based on the Niched Pareto GA. The ndings from these experiments indicate important roles for both local search and population-based search methods when addressing the multiobjective form of this problem.
Lack of an Antibacterial Response Defect in Drosophila Toll-9 Mutant

Toll and Toll-like receptors represent families of receptors involved in mediating innate immunity response in insects and mammals. Although Drosophila proteome contains multiple Toll paralogs, Toll-1 is, so far, the only receptor to which an immune role has been attributed. In contrast, every single mammalian TLR is a key membrane receptor upstream of the vertebrate immune signaling cascades. The prevailing view is that TLR-mediated immunity is ancient. Structural analysis reveals that Drosophila Toll-9 is the most closely related to vertebrate TLRs and utilizes similar signaling components as Toll-1. This suggests that Toll-9 could be an ancestor of TLR-like receptors and could have immune function. Consistently, it has been reported that over-expression of Toll-9 in immune tissues is sufficient to induce the expression of some antimicrobial peptides in flies. These results have led to the idea that Toll-9 could be a constitutively active receptor that maintain significant levels of antimicrobial molecules and therefore provide constant basal protection against micro-organisms. To test theses hypotheses, we generated and analyzed phenotypes associated with a complete loss-of-function allele of Toll-9. Our results suggest that Toll-9 is neither required to maintain a basal anti-microbial response nor to mount an efficient immune response to bacterial infection.
On the Sum of Laplacian Eigenvalues of Graphs

Let k be a natural number and let G be a graph with at least k vertices. A.E. Brouwer conjectured that the sum of the k largest Laplacian eigenvalues of G is at most e(G) (k choose 2), where e(G) is the number of edges of G. We prove this conjecture for k = 2. We also show that if G is a tree, then the sum of the k largest Laplacian eigenvalues of G is at most e(G) 2k-1.
The frequency and severity of placental findings in women with preeclampsia are gestational age dependent.

OBJECTIVE The purpose of this study was to evaluate placental lesions found in women with preeclampsia compared with normotensive control subjects and to determine whether the presence of these lesions are related to gestational age at delivery. STUDY DESIGN Placental disease of women with preeclampsia at 24 to 42 weeks of gestation was compared with the placental disease of normotensive gestational age-matched control subjects. The placental lesions that were studied specifically included decidual arteriolopathy, thrombi in the fetal circulation, central infarction, intervillous thrombi, and hypermaturity of villi. Data analysis involved the chi(2) test, the Student t test, and logistic regression; odds ratios and CIs were estimated. RESULTS Placentas from women with preeclampsia (n=158) and normotensive control subjects (n=156) were evaluated. Among women with preeclampsia, 67% had severe disease. Placental lesions were studied according to gestational age at delivery: <28, 28 to 32, 33 to 36, and >or=37 weeks of gestation. Of the placental lesions that were studied, decidual arteriolopathy (odds ratio, 23.8, 95% CI 10.0-57.0), hypermaturity of villi (odds ratio, 12.4; 95% CI 5.3-29.2), intervillous thrombi (odds ratio, 1.95;95% CI 1.0-3.7), central infarction (odds ratio, 5.9; 95% CI 3.1-11.1), and thrombi in the fetal circulation (odds ratio, 2.8; 95% CI 1.2-6.6) were found to have significantly higher rates in the preeclamptic group. In contrast, the rate of chorioamnionitis was significantly lower in the preeclamptic group (odds ratio, 0.2; 95% CI 0.1-0.4). The rates of abruptio placentae and meconium staining were not different between the two groups. Within the preeclamptic group, the rates of decidual arteriolopathy (P<.0001), central infarction (P=.0001), and hypermaturity of villi (P<.0001) were higher the earlier the gestational age at delivery. CONCLUSION Placentas in women with preeclampsia have increased amounts of disease. The rate is increased with lower gestational ages at the time of delivery for women with preeclampsia.