Miracle-dz/UniFAR-FTUs huggingface dataset:
Synergistic Effects of Celecoxib and Bupropion in a Model of Chronic Inflammation-Related Depression in Mice

This study was aimed to characterize the depression-like behaviour in the classical model of chronic inflammation induced by Complete Freund’s Adjuvant (CFA). Male Swiss mice received an intraplantar (i.pl.) injection of CFA (50 µl/paw) or vehicle. Behavioural and inflammatory responses were measured at different time-points (1 to 4 weeks), and different pharmacological tools were tested. The brain levels of IL-1β and BDNF, or COX-2 expression were also determined. CFA elicited a time-dependent edema formation and mechanical allodynia, which was accompanied by a significant increase in the immobility time in the tail suspension (TST) or forced-swimming (FST) depression tests. Repeated administration of the antidepressants imipramine (10 mg/kg), fluoxetine (20 mg/kg) and bupropion (30 mg/kg) significantly reversed depression-like behaviour induced by CFA. Predictably, the anti-inflammatory drugs dexamethasone (0.5 mg/kg), indomethacin (10 mg/kg) and celecoxib (30 mg/kg) markedly reduced CFA-induced edema. The oral treatment with the analgesic drugs dipyrone (30 and 300 mg/kg) or pregabalin (30 mg/kg) significantly reversed the mechanical allodyinia induced by CFA. Otherwise, either dipyrone or pregabalin (both 30 mg/kg) did not significantly affect the paw edema or the depressive-like behaviour induced by CFA, whereas the oral treatment with dipyrone (300 mg/kg) was able to reduce the immobility time in TST. Noteworthy, CFA-induced edema was reduced by bupropion (30 mg/kg), and depression behaviour was prevented by celecoxib (30 mg/kg). The co-treatment with bupropion and celecoxib (3 mg/kg each) significantly inhibited both inflammation and depression elicited by CFA. The same combined treatment reduced the brain levels of IL-1β, as well as COX-2 immunopositivity, whilst it failed to affect the reduction of BDNF levels. We provide novel evidence on the relationship between chronic inflammation and depression, suggesting that combination of antidepressant and anti-inflammatory agents bupropion and celecoxib might represent an attractive therapeutic strategy for depression.
Number of Sperms Required for Fertilization

MUCH has been done in recent years to determine the number of sperms which must be introduced by artificial insemination to maintain a normal rate of fertilization. There are, however, markedly divergent views as to the number of sperms normally present in the immediate vicinity of the eggs at fertilization. Such direct evidence as exists suggests very small numbers. Thus Hammond1 reports finding remarkably few in smears prepared from the fallopian tube of rabbits killed 10 hr. after coitus. Hammond and Walton2 examined the ovarian capsules of ferrets at 3–36 hr. after coitus, and counted 1,600 sperms in one ferret and 0–75 sperms in six others. The number of sperms in the tubes of rats were observed by Blandau and Money3 to increase during the hour after coitus to a maximum of about 200.
Compositional Zoning of the BishopTuff WES HILDRETH 1 * AND COLIN

V53A-0623. Wark, D. A. , Hildreth,W. , Spear, F. S. , Cherniak, D. J. & Watson, E. B. (2007). Pre-eruption recharge of the Bishop magma system. Geology 35, 235^238. Weinberg, R. F. (1997). The disruption of a diorite magma pool by intruding granite: the Sobu body, Ladakh batholith, Indian Himalayas. Journal of Geology 105, 87^98. Weinberg, R. F. & Leitch, A. M. (1998). Mingling in mafic magma chambers replenished by light felsic inputs: fluid dynamical experiments. Earth and Planetary Science Letters 157, 41^56. Weinberg, R. F. , Sial, A. N. & Pessoa, R. R. (2001). Magma flow within the Tavares pluton, northeastern Brazil: compositional and thermal convection. Geological Society of America Bulletin 113, 508^520. Wiebe, R. A. (1987). Rupture and inflation of a basic magma chamber by silicic liquid. Nature 326, 69^71. Wiebe, R. A. (1993). The Pleasant Bay layered gabbro^diorite, coastal Maine: ponding and crystallization of basaltic injections into a silicic magma chamber. Journal of Petrology 34, 461^489. Wiebe, R. A. (1996). Mafic^silicic layered intrusions: the role of basaltic injections on magmatic processes and the evolution of silicic magma chambers.Transactions of the Royal Society of Edinburgh (Earth Sciences) 87, 233^242. Wiebe, R. A. & Collins,W. J. (1998). Depositional features and stratigraphic sections in granitic plutons: implications for the emplacement and crystallization of granitic magma. Journal of Structural Geology 20, 1273^1289. Wilson, C. J. N. & Hildreth, W. (1997). The Bishop Tuff: new insights from eruptive stratigraphy. Journal of Geology 105, 407^439. Wilson, C. J. N. & Hildreth, W. (1998). Hybrid fall deposits in the Bishop Tuff, California: a novel pyroclastic depositional mechanism. Geology 26, 7^10. Wilson, C. J. N. & Hildreth, W. (2003). Assembling an ignimbrite: mechanical and thermal building blocks in the Bishop Tuff, California. Journal of Geology 111, 653^670. Wilson, C. J. N. , Blake, S. , Charlier, B. L. A. & Sutton, A. N. (2006). The 26! 5 ka Oruanui eruption,Taupo volcano, New Zealand: development, characteristics and evacuation of a large rhyolitic magma body. Journal of Petrology 47, 35^69. Winick, J. A. , McIntosh, W. C. & Dunbar, N. W. (2001). Melt-inclusion-hosted excess Ar in quartz crystals of the Bishop and Bandelier magma systems. Geology 29, 275^278. Wolf, M. B. & Wyllie, P. J. (1994). Dehydration-melting of amphibolite at 10 kbar: the effects of temperature and time. Contributions to Mineralogy and Petrology 115, 369^383. Wolff, J. A. & Ramos, F. C. (2003). Pb isotope variations among Bandelier Tuff feldspars: no evidence for a long-lived silicic magma chamber. Geology 31, 533^536. Wolff, J. A. , Ramos, F. C. & Davidson, J. P. (1999). Sr isotope disequilibrium during differentiation of the Bandelier Tuff, New Mexico: constraints on the crystallization of a large rhyolitic magma chamber. Geology 27, 495^498. Zhang, Y. , Xu, Z. & Behrens, H. (2000). Hydrous species geospeedometer in rhyolite: improved calibration and application. Geochimica et Cosmochimica Acta 64, 3347^3355. HILDRETH & WILSON ZONING OF THE BISHOP TUFF
Impact of quantitative invasive diagnostic techniques in the management and outcome of mechanically ventilated patients with suspected pneumonia

ObjectiveTo assess how data obtained by invasive diagnostic techniques may affect management and outcome of patients with suspected ventilator-associated pneumonia (VAP), in comparison with noninvasive qualitative techniques. DesignProspective study. SettingAn 18-bed medical and surgical intensive care unit. PatientsA total of 91 patients suspected of having VAP were randomized into two groups. In group A (n = 45), quantitative cultures obtained by either bronchoscopic or nonbronchoscopic techniques were performed, whereas in group B (n = 43), patients were treated based on clinical judgment and nonquantitative tracheal aspirates cultures. Three patients were excluded because of the absence of follow-up. ResultsIn patients with positive cultures, therapeutic changes were made in 20 patients. In four patients (three from group A and one from group B, p = NS), initial empirical antibiotic treatment was modified because the isolated microorganisms were not susceptible (all of them had late-onset pneumonia). The isolated organisms responsible for antibiotic modifications were methicillin-resistant Staphylococcus aureus (three patients) and Pseudomonas aeruginosa (one patient). In three patients, the antimicrobial therapy was considered inappropriate because the isolated microorganisms were multiresistant and treated with only one effective antibiotic. In 13 patients (ten from group A and three from group B, p < .05), treatment was changed to select a narrower spectrum antibiotic. No therapeutic modifications were made in patients with negative cultures based on the results of quantitative cultures.The overall mortality was 22.2% in group A and 20.9% in group B. There were no differences in intensive care unit stay or days of mechanical ventilation (23.67 ± 3.15 vs. 22.42 ± 3.01 and 19.99 ± 2.88 vs. 19.24 ± 3.04, respectively). ConclusionsIn our study population, the routine use of quantitative invasive diagnostic tools is not justified in the setting of ventilated patients clinically suspected of having nosocomial pneumonia.
Unusual case of hemangioblastoma of the cerebellopontine angle

Background: Hemangioblastomas are the most common primary tumor of the posterior fossa. There are few cases of hemangioblastoma of the cerebellopontine angle (CPA). When present in this location, hemangioblastoma presents a diagnostic challenge as its imaging findings closely resemble those of vestibular schwannoma (VS), which is much more common in the CPA. Case Description: We report the case of a 42-year-old man presenting with vertigo and diplopia found to have a CPA tumor with imaging resembling VS. He underwent retrosigmoidal resection of his tumor, which was found to be a hemangioblastoma. Conclusion: Hemangioblastoma, though rare in the CPA, should be considered in the differential diagnosis of CPA tumors.
Weakly Supervised Foreground Segmentation Based on Superpixel Grouping

Image segmentation is of great significance to a variety of tasks in image processing and computer vision. Since fully unsupervised image segmentation is usually very hard in most cases, a task-oriented interactive segmentation approach becomes a popular solution. This paper proposes a weakly supervised image segmentation algorithm to extract foreground from a complex background relying only on a roughly predefined bounding-box. The algorithm integrates the Watershed algorithm and Mean-shift clustering algorithm to obtain reliable initial foreground and background labels for simple linear iterative clustering (SLIC) superpixels. Then, a synthetic superpixel grouping mechanism is proposed to group the remainder SLIC superpixels into foreground or background until the whole superpixels are completely grouped. The proposed algorithm reliefs the interactive information from users while maintaining the segmentation precision. Extensive experiments are performed, and the results indicate that the proposed algorithm can reliably segment the image foreground from the complex background with only a weakly supervision.
Transcriptional Dynamics During Human Adipogenesis and Its Link to Adipose Morphology and Distribution

White adipose tissue (WAT) can develop into several phenotypes with different pathophysiological impact on type 2 diabetes. To better understand the adipogenic process, the transcriptional events that occur during in vitro differentiation of human adipocytes were investigated and the findings linked to WAT phenotypes. Single-molecule transcriptional profiling provided a detailed map of the expressional changes of genes, enhancers, and long noncoding RNAs, where different types of transcripts share common dynamics during differentiation. Common signatures include early downregulated, transient, and late induced transcripts, all of which are linked to distinct developmental processes during adipogenesis. Enhancers expressed during adipogenesis overlap significantly with genetic variants associated with WAT distribution. Transiently expressed and late induced genes are associated with hypertrophic WAT (few but large fat cells), a phenotype closely linked to insulin resistance and type 2 diabetes. Transcription factors that are expressed early or transiently affect differentiation and adipocyte function and are controlled by several well-known upstream regulators such as glucocorticosteroids, insulin, cAMP, and thyroid hormones. Taken together, our results suggest a complex but highly coordinated regulation of adipogenesis.
Shear bond strength of universal adhesive systems to a bioactive dentin substitute (Biodentine®) at different time intervals

Aim: The aim of this study was to compare the shear bond strength (SBS) of various adhesive systems to a bioactive dentin substitute Biodentine® with different time intervals. Methods: Three hundred and fifty cylindrical acrylic blocks with a hole (4 mm diameter and 2 mm height) were prepared. The holes were filled with Biodentine®, and the specimens were allocated into 5 main groups according to waiting times (group 1, 12 min; group 2, 24 h; group 3, 48 h; group 4, 72 h; and group 5, 96 h). All specimens were stored at 37 °C with 100% humidity during the waiting time. Then each group was divided into 7 subgroups of 10 units each: subgroup 1, Prime&Bond NTTM; subgroup 2, Single Bond Universal (self-etch mode); subgroup 3, Single Bond Universal (etch and rinse mode); subgroup 4, All-Bond UniversalTM (self-etch mode); subgroup 5, All-Bond UniversalTM (etch and rinse mode); subgroup 6, G-aenial Universal BondTM (self-etch mode); and subgroup 7, G-aenial Universal BondTM (etch-and-rinse mode). After the application of adhesive systems, compomer Dyract XP Bond® was applied over Biodentine® SBSs were measured using a universal testing machine. After the SBS test, the fractured surfaces were examined under a stereomicroscope at 25× magnification, and the data were analyzed with Kruskal-Wallis and Mann-Whitney U (with Bonferroni correction) tests. Results: Biodentine® exhibits lower shear bond strength values in the 12 min groups. No significant differences were observed between self-etch or etch-and-rinse bonding modes. Conclusion: A 24-h waiting period after the mixing of Biodentine® could be useful to obtain higher SBS measurements. Also, similar SBS values were observed for the universal adhesives regardless of application mode.
CB1 and CB2 cannabinoid receptors differentially regulate the production of reactive oxygen species by macrophages.

AIMS We investigated the mechanism by which cannabinoid receptors-1 (CB1) and -2 (CB2) modulate inflammatory activities of macrophages. METHODS AND RESULTS Real-time polymerase chain reaction showed the predominant CB2 expression in freshly isolated human monocytes. PMA, a potent inducer of differentiation, upregulated CB1 and increased CB1:CB2 transcript ratio from 1:17.5 to 1:3 in 5 days of culture. Immunohistochemistry showed that CB1 protein was colocalized in CD68- and CD36-positive macrophages in human atheroma. Through selective expression of CB1 or CB2 to thioglycollate-elicited peritoneal macrophages, we proved that CB1 and CB2 mediate opposing influences on the production of reactive oxygen species (ROS). Flow cytometry showed that cannabinoid-induced ROS production by macrophages was CB1-dependent. Immunoblotting assays confirmed that macrophage CB1, not CB2, induced phosphorylation of p38-mitogen-activated protein kinase, which modulated ROS production and the subsequent synthesis of tumour necrosis factor-alpha and monocyte chemoattractant protein-1. Pull-down assays showed that the Ras family small G protein, Rap1 was activated by CB2. Dominant-negative Rap1 profoundly enhanced CB1-dependent ROS production by macrophages, suggesting CB2 Rap1-dependently inhibits CB1-stimulated ROS production. CONCLUSION CB1 promotes pro-inflammatory responses of macrophages through ROS production, which is negatively regulated by CB2 through Rap1 activation. Blocking CB1 together with selective activation of CB2 may suppress pro-inflammatory responses of macrophages.
Low Connectivity between Mediterranean Marine Protected Areas: A Biophysical Modeling Approach for the Dusky Grouper Epinephelus marginatus

Marine protected areas (MPAs) are major tools to protect biodiversity and sustain fisheries. For species with a sedentary adult phase and a dispersive larval phase, the effectiveness of MPA networks for population persistence depends on connectivity through larval dispersal. However, connectivity patterns between MPAs remain largely unknown at large spatial scales. Here, we used a biophysical model to evaluate connectivity between MPAs in the Mediterranean Sea, a region of extremely rich biodiversity that is currently protected by a system of approximately a hundred MPAs. The model was parameterized according to the dispersal capacity of the dusky grouper Epinephelus marginatus, an archetypal conservation-dependent species, with high economic importance and emblematic in the Mediterranean. Using various connectivity metrics and graph theory, we showed that Mediterranean MPAs are far from constituting a true, well-connected network. On average, each MPA was directly connected to four others and MPAs were clustered into several groups. Two MPAs (one in the Balearic Islands and one in Sardinia) emerged as crucial nodes for ensuring multi-generational connectivity. The high heterogeneity of MPA distribution, with low density in the South-Eastern Mediterranean, coupled with a mean dispersal distance of 120 km, leaves about 20% of the continental shelf without any larval supply. This low connectivity, here demonstrated for a major Mediterranean species, poses new challenges for the creation of a future Mediterranean network of well-connected MPAs providing recruitment to the whole continental shelf. This issue is even more critical given that the expected reduction of pelagic larval duration following sea temperature rise will likely decrease connectivity even more.
Heart Rate and its Variability Assessed by Spectral Analysis in Elderly Subjects with Orthostatic Hypotension: A Case-Control Study

Background The prevalence of orthostatic hypotension (OH) increases with age and is associated with changes in autonomic regulation of blood pressure (BP) and heart rate (HR). Objective to assess HR and HR variability (HRV) in elderly subjects with OH and determine OH predictors. Methods a total of 105 patients aged ≥ 60 years, 39 with OH (case group) and 66 without OH (control group) (age-matched) were studied. Patients underwent clinical assessment, electrocardiogram, biochemistry tests and Holter monitoring for spectral analysis of HRV (Fourier transform) in the supine and orthostatism positions to identify low frequency (LF) and high frequency (HF) components, as well as the LF/HF ratio. Results median age was 73.0 years, 64 patients were women. In all participants, there was a reduction in HF (133.0 versus 76.0 ms2, p = 0.001) and increase in LF/HF (1.6 vs 2.1; p < 0.001) and no change in LF (233.0 versus 218.0 ms2, p = 0.080). Between-group comparisons revealed significant differences in the median values of HR in the supine position (62.0 vs. 69.0 bpm, p = 0.001) and LF in the supine position (157.0 in case group vs. 275.0 ms2 in the control group, p = 0.014). Spearman’s correlation coefficient of 0.27 was found between the groups. Multivariate analysis revealed that HR in the supine position was an independent variable for OH (p = 0.001- 95%CI = -0.022 and -0.006). Using the operating characteristic curve, the best cutoff point was 61 bpm, with a sensitivity of 77.3% and specificity of 51.3%, positive predictive value of 61.3%, and negative predictive value 69.3%. Odds ratio was 3.23 for OH in patients with a HR lower than 61 bpm. Conclusions lower LF and HR in the supine position were found in patients with OH, regardless of age and gender. The independent predictor for OH was HR in the supine position, with an odds ratio of 3.23 for values lower than 61 bpm.
BET Bromodomain Inhibition of MYC-Amplified Medulloblastoma

Purpose: MYC-amplified medulloblastomas are highly lethal tumors. Bromodomain and extraterminal (BET) bromodomain inhibition has recently been shown to suppress MYC-associated transcriptional activity in other cancers. The compound JQ1 inhibits BET bromodomain-containing proteins, including BRD4. Here, we investigate BET bromodomain targeting for the treatment of MYC-amplified medulloblastoma. Experimental Design: We evaluated the effects of genetic and pharmacologic inhibition of BET bromodomains on proliferation, cell cycle, and apoptosis in established and newly generated patient- and genetically engineered mouse model (GEMM)-derived medulloblastoma cell lines and xenografts that harbored amplifications of MYC or MYCN. We also assessed the effect of JQ1 on MYC expression and global MYC-associated transcriptional activity. We assessed the in vivo efficacy of JQ1 in orthotopic xenografts established in immunocompromised mice. Results: Treatment of MYC-amplified medulloblastoma cells with JQ1 decreased cell viability associated with arrest at G1 and apoptosis. We observed downregulation of MYC expression and confirmed the inhibition of MYC-associated transcriptional targets. The exogenous expression of MYC from a retroviral promoter reduced the effect of JQ1 on cell viability, suggesting that attenuated levels of MYC contribute to the functional effects of JQ1. JQ1 significantly prolonged the survival of orthotopic xenograft models of MYC-amplified medulloblastoma (P < 0.001). Xenografts harvested from mice after five doses of JQ1 had reduced the expression of MYC mRNA and a reduced proliferative index. Conclusion: JQ1 suppresses MYC expression and MYC-associated transcriptional activity in medulloblastomas, resulting in an overall decrease in medulloblastoma cell viability. These preclinical findings highlight the promise of BET bromodomain inhibitors as novel agents for MYC-amplified medulloblastoma. Clin Cancer Res; 20(4); 912–25. ©2013 AACR.
Major influence of a ‘smoke and mirrors’ effect caused by wave reflection on early diastolic coronary arterial wave intensity

Coronary wave intensity analysis (WIA) is an emerging technique for assessing upstream and downstream influences on myocardial perfusion. It is thought that a dominant backward decompression wave (BDWdia) is generated by a distal suction effect, while early‐diastolic forward decompression (FDWdia) and compression (FCWdia) waves originate in the aorta. We show that wave reflection also makes a substantial contribution to FDWdia, FCWdia and BDWdia, as quantified by a novel method. In 18 sheep, wave reflection accounted for ∼70% of BDWdia, whereas distal suction dominated in a computer model representing a hypertensive human. Non‐linear addition/subtraction of mechanistically distinct waves (e.g. wave reflection and distal suction) obfuscates the true contribution of upstream and downstream forces on measured waves (the ‘smoke and mirrors’ effect). The mechanisms underlying coronary WIA are more complex than previously thought and the impact of wave reflection should be considered when interpreting clinical and experimental data.