Miracle-dz/UniFAR-FTUs huggingface dataset:
Resolvin E1 (RX-10001) Reduces Corneal Epithelial Barrier Disruption and Protects Against Goblet Cell Loss in a Murine Model of Dry Eye

Purpose: Resolvin E1 (RvE1; RX-10001) belongs to a new class of endogenous immunoregulating mediators, originally identified as a metabolite of the omega-3 polyunsaturated fatty acid, eicosapentaenoic acid. Based on its proven efficacy in models of chronic inflammation, this study investigated the efficacy of resolvin E1 in a murine model of dry eye. Methods: C57/B6 mice, aged 6 to 8 weeks, were treated with systemic scopolamine and exposed to air draft and low humidity for 16 hours/day for 5 days and allocated to the following groups: unexposed controls, disease controls, treatment with vehicle or RvE1 delivered topically as its methyl ester prodrug, RX-10005, to enhance corneal surface penetration. Treatment was initiated at the time of desiccating stress induction. Treatment efficacy was assessed by corneal permeability using Oregon Green Dextran and by conjunctival goblet cell density using periodic acid–Schiff reagent. Results: RvE1 reduced the increase in corneal staining by 80% compared with untreated disease controls. Goblet cell density was reduced by 20% in disease controls but fully maintained in the group receiving RvE1. Conclusions: RvE1, delivered as its methyl ester prodrug, improved the outcome measures of corneal staining and goblet cell density in this murine model of dry eye, indicating the potential utility of endogenous resolvins and resolvin analogues in the treatment of dry eye.
Effect of angiogenesis inhibitors on oestrogen-mediated endometrial endothelial cell proliferation in the ovariectomized mouse.

It has been suggested that endometrial angiogenesis in response to the sex steroids oestrogen and progesterone is mediated at a local level via compounds such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF), acting through their respective tyrosine kinase receptors. The aim of the present study was to use SUGEN tyrosine kinase receptor angiogenic inhibitor compounds SU5416, SU5402, SU11652 and SU11685, to determine whether VEGF, FGF or PDGF play a role in mediating endometrial endothelial cell proliferation after administration of oestrogen and progesterone. Endometrial endothelial cell proliferation was induced in adult ovariectomized mice by either oestrogen alone for 24 h (E1), or a regimen using oestrogen alone, then progesterone with low dose oestrogen, followed by progesterone with high-dose oestrogen (PE) over a total of 7 days. Each angiogenesis inhibitor compound was injected daily for 4 days (100 mg kg(-1) day(-1), s.c. ) before endometrial tissue collection at either the E1 or PE stage. This study also evaluated the effect of VEGF antiserum (0.2 ml, i.p.) on endothelial cell proliferation at the E1 stage. All four angiogenic inhibitor compounds significantly reduced endothelial cell proliferation activity at the E1 and PE stages. The greatest reduction in the endothelial cell proliferative index was at the E1 stage in the group treated with the VEGF receptor inhibitor SU5416 (2.5 +/- 0.7% versus 27.9 +/- 1.1%, P < 0.001), with a reduction of similar magnitude in the group treated with anti-VEGF antibody. At the PE stage, all four inhibitors significantly reduced endothelial cell proliferation to a similar extent, indicating that VEGF, FGF and PDGF are all involved. These results demonstrate that endometrial angiogenesis after acute oestrogen treatment is primarily mediated by VEGF, but that under the influence of combined oestrogen and progesterone, FGF and PDGF are also probably involved.
Winning the battle against ST-segment-elevation myocardial infarction: continued progress, but still a long way to go.

This editorial refers to ‘Reperfusion strategy in Europe: temporal trends in performance measures for reperfusion therapy in ST-elevation myocardial infarction’[†][1], by F. Schiele et al . , on page 2614 With the Euro Heart Survey Acute Coronary Syndromes III (EHS ACS III) results presented in this issue of the Journal , Schiele et al. 1 are the bearers of good news. In their detailed analysis of the data gathered from 6481 patients admitted within 12 h of the onset of an ST-segment-elevation myocardial infarction (STEMI), the proportion of patients receiving reperfusion therapy increased from 77% in 2006 to 81% in 2008, while time delays from admission to reperfusion decreased [from 60 to 45 min for primary percutaneous coronary intervention (PCI), and from 20 to 15 min for intravenous fibrinolysis]. Concomitantly, in-hospital mortality decreased from 8.1% to 6.6%, a remarkable 19% relative decrease in just 2 years. These findings are important, as they show that improvement in the management of patients admitted for STEMI is still possible and they should be an incentive for continued efforts for all institutions and networks taking care of STEMI patients. The main strength of the study is that it was carried out in 138 highly motivated institutions across 21 European Society of Cardiology (ESC) member countries, which included patients according to a similar methodology for a period of 2 years, thereby making temporal comparisons possible with only limited risk of bias. In addition, the investigators used the Cardiology Audit and Registration Data Standards (CARDS) to collect the data according to common definitions,2 thereby ascertaining that the items recorded had exactly the same meaning in the different participating centres. The results presented can therefore be considered most reliable. But satisfying … [1]: #fn-2
Quality of life in chronically mentally ill patients in day treatment

Synopsis A structured assessment instrument, the Quality of Life Interview, was used to explain the quality of life of seventy patients with chronic psychiatric illness attending a day treatment programme. The interview was found to have acceptable psychometric properties. Factors that best predicted the quality of life of these patients included the number of re-admissions in the last year, frequency of family contacts, satisfaction with social life, psychiatric health and adult education. The theoretical implications and potential clinical benefits of these findings for chronic psychiatric patients are discussed.
Potential role of platelets in endothelial damage observed during treatment with cisplatin, gemcitabine, and the angiogenesis inhibitor SU5416.

PURPOSE An increased incidence of thromboembolic events was observed during treatment with cisplatin-gemcitabine plus SU5416 (CG+SU5416), a tyrosine kinase inhibitor targeting the vascular endothelial growth factor (VEGF) receptor-1 and -2. Nine thromboembolic events occurred in eight of 19 patients. We performed an analysis of parameters of the coagulation cascade and vessel wall activation. MATERIALS AND METHODS Markers for thrombin generation and endothelial cell activation were measured in three patients treated with CG+SU5416, two of whom developed a thromboembolic event. The results were compared with measurements in six patients treated with CG alone, and in 17 patients treated with SU5416 alone. RESULTS During cycles 1 and 2 of treatment with CG+SU5416, a significant cycle-dependent activation of both the coagulation cascade and endothelial cells occurred, whereas platelet counts decreased. Change in platelet number had a significant negative predictive effect on soluble (s)-E-selectin levels. Significant activation of the coagulation cascade only was observed in the patients treated with CG alone, whereas in patients treated with SU5416 alone, significant endothelial cell activation was observed. CONCLUSION We hypothesize that endothelial cells deprived of VEGF after exposure to SU5416 became activated and more susceptible to damage during treatment with CG+SU5416, which was aggravated by a transient decrease in platelets, which are, among other things, carriers of VEGF. These results suggests that VEGF, in addition to being a permeability, proliferation, and migration factor, also is a maintenance and protection factor for endothelial cells, and that platelets may have a role in maintaining vascular integrity.
Emodin inhibits vascular endothelial growth factor‐A‐induced angiogenesis by blocking receptor‐2 (KDR/Flk‐1) phosphorylation

Emodin (1,3,8‐trihydroxy‐6‐methylanthraquinone), an active component in the root and rhizome of Rheum palmatum, is a tyrosine kinase inhibitor with a number of biological activities, including antitumor effects. Here, we examine the effects of emodin on vascular endothelial growth factor (VEGF)‐A‐induced angiogenesis, both in vitro and in vivo. In vitro, emodin dose‐dependently inhibits proliferation, migration into the denuded area, invasion through a layer of Matrigel and tube formation of human umbilical vein endothelial cells (HUVECs) stimulated with VEGF‐A. Emodin also inhibits basic fibroblast growth factor‐induced proliferation and migration of HUVECs and VEGF‐A‐induced tube formation of human dermal microvascular endothelial cells. Specifically, emodin induces the cell cycle arrest of HUVECs in the G0/G1 phase by suppressing cyclin D1 and E expression and retinoblastoma protein phosphorylation, and suppresses Matrigel invasion by inhibiting the basal secretion of matrix metalloproteinase‐2 and VEGF‐A‐stimulated urokinase plasminogen activator receptor expression. Additionally, emodin effectively inhibits phosphorylation of VEGF‐A receptor‐2 (KDR/Flk‐1) and downstream effector molecules, including focal adhesion kinase, extracellular signal‐regulated kinase 1/2, p38 mitogen‐activated protein kinase, Akt and endothelial nitric oxide synthase. In vivo, emodin strongly suppresses neovessel formation in the chorioallantoic membrane of chick and VEGF‐A‐induced angiogenesis of the Matrigel plug in mice. Our data collectively demonstrate that emodin effectively inhibits VEGF‐A‐induced angiogenesis in vitro and in vivo. Moreover, inhibition of phosphorylation of KDR/Flk‐1 and downstream effector molecules is a possible underlying mechanism of the anti‐angiogenic activity of emodin. Based on these data, we propose that an interaction of emodin with KDR/Flk‐1 may be involved in the inhibitory function of emodin toward VEGF‐A‐induced angiogenesis in vitro and responsible for its potent anti‐angiogenic in vivo. © 2006 Wiley‐Liss, Inc.
Postsynaptic expression of an epidermal growth factor receptor regulates cholinergic synapse formation between identified molluscan neurons

Epidermal growth factor (EGF) family members are conserved in both vertebrates and invertebrates. Recent studies suggest that EGF ligands in invertebrates may have neurotrophic actions that possibly compensate for the apparent absence of neurotrophins in these species. In this study, we have cloned an EGF receptor from the mollusk Lymnaea stagnalis (L‐EGFR), and shown that L‐EGFR is the receptor for a previously identified EGF‐like peptide in Lymnaea, named Lymnaea EGF (L‐EGF). Knock‐down of L‐EGFR expression prevented L‐EGF‐induced excitatory synapse formation between identified cholinergic neuron visceral dorsal 4 (VD4) and its postsynaptic partner left pedal dorsal 1 (LPeD1). Moreover, knock‐down of L‐EGFR also prevented synapse formation induced by Lymnaea brain conditioned medium, suggesting that L‐EGF is the most important, if not the only, brain‐derived factor that promotes excitatory cholinergic synapse formation in Lymnaea. Thus, our data establish canonical EGF/EGFR signaling as an important synaptotrophic mechanism in invertebrates.
Mutants highlight the modular control of butterfly eyespot patterns

SUMMARY The eyespots on butterfly wings are thought to be serially homologous pattern elements. Yet eyespots differ greatly in number, shape, color, and size, within and among species. To what extent do these serially homologues have separate developmental identities, upon which selection acts to create diversity? We examined x‐ray–induced mutations for the eyespots of the nymphalid butterfly Bicyclus anynana that highlight the modular control of these serially homologous wing pattern elements. These mutations reduce or eliminate individual eyespots, or groups of eyespots, with no further effect on the wing color pattern. The collection of mutants highlights a greater potential developmental repertoire than that observed across the genus Bicyclus. We studied in detail one such mutation, of codominant effect, that causes the elimination of two adjacent eyespots on the ventral hindwing. By analyzing the expression of genes known to be involved in eyespot formation, we found an alteration in the differentiation of the “organizing” cells at the eyespot's center. No such cells differentiate in the wing subdivisions lacking the two eyespots in the mutants. We propose several developmental models, based on wing compartmentalization in Drosophila, that provide the first framework for thinking about the molecular evolution of butterfly wing pattern modularity.
The Importance of Expectations in Economic Development

What factors and processes influence the wealth of nations? This is the central question addressed by North, Wallis, and Weingast (NWW) (2009) in their framework for "interpreting recorded human history. " This essay emphasizes that the implications of NWW's analysis provide the foundations for a realistic reassessment of the constraints facing the development community in their efforts to assist "natural states. " The main theme of this paper is the role that expectations play in development. Expectations play a key role in development efforts because they frame the activities of the development community, as well as the perceptions of indigenous politicians and citizens living in the natural state. The failure of many development efforts is due to a lack of appreciation for the important role played by expectations.
Trends in body size across an environmental gradient: A differential response in scavenging and non-scavenging demersal deep-sea fish

Body size trends across environmental gradients are widely reported but poorly understood. Here, we investigate contrasting relationships between size (body mass) and depth in the scavenging and predatory demersal ichthyofauna (800–4800 m) of the North-east Atlantic. The mean size of scavenging fish, identified as those regularly attracted to baited cameras, increased significantly with depth, while in non-scavengers there was a significant decline in size. The increase in scavenger size is a consequence of both intra and inter-specific effects. The observation of opposing relationships, in different functional groups, across the same environmental gradient indicates ecological rather than physiological causes. Simple energetic models indicate that the dissimilarity can be explained by different patterns of food distribution. While food availability declines with depth for both groups, the food is likely to be in large, randomly distributed packages for scavengers and as smaller but more evenly distributed items for predators. Larger size in scavengers permits higher swimming speeds, greater endurance as a consequence of larger energy reserves and lower mass specific metabolic rate, factors that are critical to survival on sporadic food items.
Pulsed Electromagnetic Fields Accelerate Normal and Diabetic Wound Healing by Increasing Endogenous FGF-2 Release

Background: Chronic wounds, particularly in diabetics, result in significant morbidity and mortality and have a profound economic impact. The authors demonstrate that pulsed electromagnetic fields significantly improve both diabetic and normal wound healing in 66 mice through up-regulation of fibroblast growth factor (FGF)-2 and are able to prevent tissue necrosis in diabetic tissue after an ischemic insult. Methods: Db/db and C57BL6 mice were wounded and exposed to pulsed electromagnetic fields. Gross closure, cell proliferation, and vascularity were assessed. Cultured medium from human umbilical vein endothelial cells exposed to pulsed electromagnetic fields was analyzed for FGF-2 and applied topically to wounds. Skin flaps were created on streptozocin-induced diabetic mice and exposed to pulsed electromagnetic fields. Percentage necrosis, oxygen tension, and vascularity were determined. Results: Pulsed electromagnetic fields accelerated wound closure in diabetic and normal mice. Cell proliferation and CD31 density were significantly increased in pulsed electromagnetic field–treated groups. Cultured medium from human umbilical vein endothelial cells in pulsed electromagnetic fields exhibited a three-fold increase in FGF-2, which facilitated healing when applied to wounds. Skin on diabetic mice exposed to pulsed electromagnetic fields did not exhibit tissue necrosis and demonstrated oxygen tensions and vascularity comparable to those in normal animals. Conclusions: This study demonstrates that pulsed electromagnetic fields are able to accelerate wound healing under diabetic and normal conditions by up-regulation of FGF-2–mediated angiogenesis. They also prevented tissue necrosis in response to a standardized ischemic insult, suggesting that noninvasive angiogenic stimulation by pulsed electromagnetic fields may be useful to prevent ulcer formation, necrosis, and amputation in diabetic patients.
Addressing Challenges in the Management of Paediatric Intussusceptions in the District Hospital

Intussusception is the leading cause of intestinal obstruction in children and its management can be challenging especially in centres with inadequate resources where this problem becomes more daunting. Nineteen cases of intussusception in the paediatric age group which were managed by medical officers in a district Hospital in Ghana are discussed. The outcomes of cases treated by open surgery, and those managed by pneumatic reduction were studied. We highlight the use of an improvised set up used in achieving pneumatic reduction thereby obviating operative reduction.
Scholarly Use of the Web: What Are the Key Inducers of Links to Journal Web Sites

Web links have been studied by information scientists for at least six years but it is only in the past two that clear evidence has emerged to show that counts of links to scholarly Web spaces (universities and departments) can correlate significantly with research measures, giving some credence to their use for the investigation of scholarly communication. This paper reports on a study to investigate the factors that influence the creation of links to journal Web sites. An empirical approach is used: collecting data and testing for significant patterns. The specific questions addressed are whether site age and site content are inducers of links to a journal's Web site as measured by the ratio of link counts to Journal Impact Factors, two variables previously discovered to be related. A new methodology for data collection is also introduced that uses the Internet Archive to obtain an earliest known creation date for Web sites. The results show that both site age and site content are significant factors for the disciplines studied: library and information science, and law. Comparisons between the two fields also show disciplinary differences in Web site characteristics. Scholars and publishers should be particularly aware that richer content on a journal's Web site tends to generate links and thus the traffic to the site.
Differential modulation of a 40 kDa catecholamine regulated protein in the core and shell subcompartments of the nucleus accumbens following chronic quinpirole and haloperidol administration in the rat

Past reports have shown dopamine (DA) D2/D3 receptor agonist quinpirole (QNP) and the DA D2 receptor antagonist, haloperidol (HAL) display a significant increase in expression of catecholamine regulated protein (CRP40) in the nucleus accumbens (NAcc) and the striatum, respectively. The present study investigated the in vivo effects of QNP and HAL on CRP40 protein levels within the core and shell subcompartments of the NAcc. As significant homology exists between CRP40 and Hsp70/Hsc70, parallel studies with inducible Hsp70 and constitutive Hsc70 were conducted to establish the specificity with respect to QNP on Hsp70 and CRP40. Results demonstrated that CRP40 protein was significantly expressed in the shell relative to the core region of NAcc following chronic QNP (+16.28% ± 0.42%, P < 0.05) and CRP40 protein was significantly expressed in the core vs. the shell following chronic HAL (+36.02% ± 0.75%, P < 0.05). There was no significant change in Hsp70 protein levels following chronic QNP or HAL administration. The results demonstrated selective modulation of CRP40 within NAcc by QNP and HAL treatment, without affecting Hsp70. Synapse 61:835–842, 2007. © 2007 Wiley‐Liss, Inc.
Increased Circulating Levels of Lipopolysaccharide Binding Protein in Children with Escherichia coli O157:H7 Hemorrhagic Colitis and Hemolytic Uremic Syndrome

We report double-determinant sandwich enzyme-linked immunosorbent assay measurements ([4][1]) of lipopolysaccharide (LPS) binding protein (LBP) in children with uncomplicated Escherichia coli O157:H7 hemorrhagic colitis (HC) and those with O157:H7-associated hemolytic uremic syndrome (HUS).
Liver size: Waning by day, Waxing by Night

1) Wree A, Broderick L, Canbay A, Hoffman HM, Feldstein AE. From NAFLD to NASH to cirrhosis—new insights into disease mechanisms. Nat Rev Gastroenterol Hepatol 2013;10:627-636. 2) Ye D, Li FY, Lam KS, Li H, Jia W, Wang Y, et al. Toll-like receptor-4 mediates obesity-induced non-alcoholic steatohepatitis through activation of X-box binding protein-1 in mice. Gut 2012; 61:1058-1067. 3) Ciechanover A. Intracellular protein degradation: from a vague idea thru the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting. Cell Death Differ 2005; 12:1178-1190. 4) Rojas-Rivera D, Hetz C. TMBIM protein family: ancestral regulators of cell death. Oncogene 2015;34:269-280. 5) Zhao GN, Zhang P, Gong J, Zhang XJ, Wang PX, Yin M, et al. Tmbim1 is a multivesicular body regulator that protects against non-alcoholic fatty liver disease in mice and monkeys by targeting the lysosomal degradation of Tlr4. Nat Med 2017;23:742-752. 6) Guo J, Friedman SL. Toll-like receptor 4 signaling in liver injury and hepatic fibrogenesis. Fibrogenesis Tissue Repair 2010;3:21. 7) Lazic M, Eguchi A, Berk MP, Povero D, Papouchado B, Mulya A, et al. Differential regulation of inflammation and apoptosis in Fas-resistant hepatocyte-specific Bid-deficient mice. J Hepatol 2014;61:107-115. 8) Wang PX, Ji YX, Zhang XJ, Zhao LP, Yan ZZ, Zhang P, et al. Targeting CASP8 and FADD-like apoptosis regulator ameliorates nonalcoholic steatohepatitis in mice and nonhuman primates. Nat Med 2017;23:439-449.
Effects of Thermomechanical Densification and Heat Treatment on Density and Brinell Hardness of Scots Pine (Pinus sylvestris L.) and Eastern Beech (Fagus orientalis L.)

The effects of thermomechanical densification (TMD) and heat treatment on density and Brinell hardness of Scots pine (Pinus sylvestris L.) and Eastern beech (Fagus orientalis L.) woods were investigated. Samples were densified using a specially designed hydraulic press with target compression ratios of 20 and 40%, and at 110 °C and 150 °C. Then, the heat treatment was applied to the samples at three different temperatures. To determine whether the changes occurred because of technological properties, tests of Brinell hardness and air-dry density were conducted. Increases of 42 and 35% were obtained for the density of Scots pine and beech samples, respectively. After the densification process, increases in radial and tangential hardness values were obtained. Decreases were observed in the density and hardness values of the samples because of the increase in temperature during heat treatment. After heat treatment, there were 4 and 5% decreases in the respective densities of Scots pine and beech, and decreases in their radial and tangential hardness values.