Miracle-dz/UniFAR-FTUs huggingface dataset:
Lupus anticoagulant and history of thrombosis are not associated with persistent endothelial cell activation in systemic lupus erythematosus

Antiphospholipid antibodies (aPL), especially lupus anticoagulant (LAC), characterize systemic lupus erythematosus (SLE) patients at increased risk for arterial and venous thromboembolic complications. It has been reported that purified human anti‐phospholipid antibodies cause endothelial cell activation in in vitro experiments. In order to investigate whether increased endothelial cell activation is associated with thromboembolic events in SLE patients with LAC, we measured plasma levels of thrombomodulin (TM), von Willebrand factor (vWf), sP‐selectin, vascular cell adhesion molecule‐1 (sVCAM‐1) and ED1‐fibronectin in a study of 76 patients with SLE. Patients were subdivided on the basis of: no history of thrombosis and LAC‐negative (n = 22) or LAC‐positive (n = 17); positive history of thrombosis and LAC‐negative (n = 16) or LAC‐positive (n = 21). The median SLE disease activity index (SLEDAI) was 4. Although concentrations of sTM, vWf, sP‐selectin and sVCAM‐1 were significantly elevated in SLE compared with values in healthy controls, they did not differ between the four groups, between patients with or without history of thrombosis, and between patients with or without LAC. Presence of anticardiolipin antibodies could not explain these negative findings. Adjustment of the concentrations for significantly associated variables, such as age, hypertension, smoking, immunosuppressive treatment and concentrations of creatinine, cholesterol and homocysteine, did not change the main results of the study. Only sTM was significantly lower in patients with both LAC and thrombosis than in patients without both these features after adjustment for serum creatinine concentrations. In conclusion, we did not find an association between endothelial cell activation and presence of LAC or history of thrombosis in SLE.
Feasibility and short‐term efficacy of percutaneous mitral annular reduction for the therapy of functional mitral regurgitation in patients with heart failure

Background: While functional mitral regurgitation (MR) commonly accompanies heart failure and contributes to heart failure progression, mitral repair in the setting of HF is not routinely practiced because of the attendant significant morbidity and mortality. This limitation has fostered the development of percutaneous devices to reduce MR, and our group has recently reported the short‐ and long‐term effectiveness of a percutaneous mitral annuloplasty device placed in the coronary sinus (Percutaneous Mitral Annuloplasty Device (PMAD), Cardiac Dimensions®, Inc., Kirkland, WA) in reducing MR in experimental animal models of heart failure with associated MR. In this article, we report results of a “first‐in‐human” study of temporary placement of the PMAD device. The aim of this study was to demonstrate the feasibility and safety of temporary deployment of this device in patients with functional MR in association with heart failure. Methods: Five patients undergoing scheduled coronary angiography with heart failure and functional MR (mean age 52 ± 9 [SD] years) were recruited, and four had anatomy suitable for deployment of the device. Transthoracic echocardiography and coronary angiography were performed before and after temporary placement and tensioning of the PMAD via the right internal jugular vein. Results: Temporary deployment of the device resulted in a significant reduction in the septal‐lateral mitral annular dimension from 35.5 ± 4.7 to 32.2 ± 4.6 mm (P = 0.02), with evidence of a reduction in the MR color Doppler area from 98.3 ± 43.6 to 83.3 ± 35.1 mm2 (P = 0.09). There were no complications. Conclusions: This first‐in‐human study of a novel device for percutaneous treatment of functional MR has shown that temporary placement of this device in the coronary sinus/great cardiac vein of patients with heart failure and MR is feasible and safe. Evidence of temporary reduction in MR and a reduction in mitral annular area indicate promise for device effectiveness in chronic implantation. © 2006 Wiley‐Liss, Inc.
Assessment of Optic Nerve Head Drusen Using Enhanced Depth Imaging and Swept Source Optical Coherence Tomography

Background: Optic nerve head drusen (ONHD) are calcific deposits buried or at the surface of the optic disc. Although ONHD may be associated with progressive visual field defects, the mechanism of drusen-related field loss is poorly understood. Methods for detecting and imaging disc drusen include B-scan ultrasonography, fundus autofluorescence, and optical coherence tomography (OCT). These modalities are useful for drusen detection but are limited by low resolution or poor penetration of deep structures. This review was designed to assess the potential role of new OCT technologies in imaging ONHD. Evidence Acquisition: Critical appraisal of published literature and comparison of new imaging devices to established technology. Results: The new imaging modalities of enhanced depth imaging optical coherence tomography (EDI-OCT) and swept source optical coherence tomography (SS-OCT) are able to provide unprecedented in vivo detail of ONHD. Using these devices it is now possible to quantify optic disc drusen dimensions and assess integrity of neighboring retinal structures, including the retinal nerve fiber layer. Conclusions: EDI-OCT and SS-OCT have the potential to allow better detection of longitudinal changes in drusen and neural retina and improve our understanding of drusen-related visual field loss.
Influenza type A virus: an outstandingly protean pathogen and a potent modular weapon

A remarkable debate recently arose on a global scale, about bioethics, biohazard, bioweaponry and bioterrorism issues related to scientific research concerning the induced transition of the highly lethal H5N1 avian flu virus from a non-pandemic to a tentatively pandemic strain, which might fall into malevolent hands. Appreciable ecogenetic complexity marks the main attributes of influenza type A viruses, namely infectivity, virulence, antigenicity, transmissibility, host range, endemicity, and epidemicity. They all shape, conjunctively, the outstanding protean nature of this pathogen, hence the modularity of the latter as a potent weapon. The present analysis inquires into those attributes, so as to profile and gauge threat, usability, impact and coping, particularly that the dimension of genetic engineering of this virus largely amplifies its potential. Within that context, various human interventions and misuses, including human experimental infections, undesirable vaccinations, as well as unauthorized and unskillful operations, led to bad corollaries and are also discussed in the present study. Altogether, a variety of interrelated properties underlying the complicatedness of and menaces posed by influenza A virus as a grave medical challenge, a dually explorable pathogen, and a modular biological warfare agent, are thereby illuminated, alongside with their scientific, strategic and practical implications.
Recovery of gut-associated lymphoid tissue and upper respiratory tract immunity after parenteral nutrition.

OBJECTIVE The authors characterize the recovery of parenteral nutrition-induced changes in gut-associated lymphoid tissue (GALT) and upper respiratory tract immunity with enteral nutrition and provide further information defining the effects of enteral feeding on mucosal immunity. SUMMARY BACKGROUND DATA The small intestine plays a prominent role in development and maintenance of mucosal immunity, both intestinal and extraintestinal, primarily through immunoglobulin A (IgA)-mediated mechanisms. Prior research has shown that mice fed total parenteral nutrition (TPN) have reduced GALT T and B cells, the cells responsible for IgA production, as well as impaired upper respiratory tract immunity to viral challenge of previously immunized animals. The recovery of TPN-induced changes in GALT and upper respiratory tract immunity after enteral refeeding is studied. METHODS Male institute of Cancer Research mice received 5 days of TPN followed by 0 to 4 days of chow. Small intestinal GALT was characterized by flow cytometry. In a second experiment, animals were immunized intranasally with moused-adapted influenza virus. Three weeks later, one group received a 5-day course of TPN followed by enteral refeeding for 5 days. A second group received TPN alone. Both groups were challenged with intranasal virus and killed 40 hours postchallenge to determine viral shedding from the upper respiratory tract. RESULTS Animals fed TPN only had significantly fewer GALT lymphocytes compared with those chow-fed control subjects. Peyer's patch counts increased after a single day of refeeding, returning to normal levels by 48 hours. Lamina propria counts remained significantly depressed after 24 hours of refeeding, but also returned to normal after 48 hours of refeeding. The T-cell and B-cell populations mimicked total cell patterns. Lamina propria CD4+/CD8+ ratio returned to normal only after 72 hours of refeeding. None of the 9 animals refed enterally for 5 days were positive for viral shedding, compared with 8 of 12 matched TPN-fed animals. CONCLUSIONS Enteral refeeding after TPN is associated with rapid repletion of GALT cellularity, initially within Peyer's patches and subsequently within the lamina propria. Refeeding corrects the impairment of IgA-mediated upper respiratory tract antiviral immunity occurring with TPN administration. This work further enhances the authors' knowledge of the underlying immunologic differences influenced by routes of nutrition.
Gene × Environment interaction and resilience: Effects of child maltreatment and serotonin, corticotropin releasing hormone, dopamine, and oxytocin genes

Abstract In this investigation, gene–environment interaction effects in predicting resilience in adaptive functioning among maltreated and nonmaltreated low-income children (N = 595) were examined. A multicomponent index of resilient functioning was derived and levels of resilient functioning were identified. Variants in four genes (serotonin transporter linked polymorphic region, corticotropin releasing hormone receptor 1, dopamine receptor D4–521C/T, and oxytocin receptor) were investigated. In a series of analyses of covariance, child maltreatment demonstrated a strong negative main effect on children's resilient functioning, whereas no main effects for any of the genotypes of the respective genes were found. However, gene–environment interactions involving genotypes of each of the respective genes and maltreatment status were obtained. For each respective gene, among children with a specific genotype, the relative advantage in resilient functioning of nonmaltreated compared to maltreated children was stronger than was the case for nonmaltreated and maltreated children with other genotypes of the respective gene. Across the four genes, a composite of the genotypes that more strongly differentiated resilient functioning between nonmaltreated and maltreated children provided further evidence of genetic variations influencing resilient functioning in nonmaltreated children, whereas genetic variation had a negligible effect on promoting resilience among maltreated children. Additional effects were observed for children based on the number of subtypes of maltreatment children experienced, as well as for abuse and neglect subgroups. Finally, maltreated and nonmaltreated children with high levels of resilience differed in their average number of differentiating genotypes. These results suggest that differential resilient outcomes are based on the interaction between genes and developmental experiences.
AttackDive: Diving Deep into the Cloud Ecosystem to Explore Attack Surfaces

A multitude of issues affect the broader adoption of Cloud computing, with security arguably being amongst the most significant. To address security concerns, the process of threat analysis is advocated to assess potential attacks that can undermine the security goals. However, conducting threat analysis for the Cloud is a non-trivial task given the plethora of attack surfaces entailed in the multiple layers of the operational stack and the resource/customer interfaces. Consequently, contemporary Cloud threat analyses approaches primarily focus on specific services/layers without analyzing the malicious behaviors over the complete multi-layered Cloud ecosystem. Hence, the need is of a comprehensive Cloud threat analysis approach that can (a) analyze the spectrum of malicious behaviors stemming from the vulnerable service interactions across the multi-level operational stack, and (b) correspondingly enumerate the attack surface exploitability by varied types of attackers. We achieve such a holistic Cloud threat analysis via a novel multi-level modeling of Cloud operations to obtain a comprehensive behavioral profile of its underlying services. Our proposed approach, using Petri Nets, targets the identification of core operational states to enumerate the normal sequence of Cloud operations along with the triggers that provide the state transitions. The obtained states transition enumerate comprehensive multi-level state space baseline of "normal" sequences and also constitutes to identify multi-level vulnerabilities not recognizable by the traditional single-level threat analysis.
[Prostaglandin analogues and central corneal thickness].

UNLABELLED Prostaglandin analogs reduce intraocular pressure (IOP) by activation of matrixmetalloproteinase enzymes (MMP) and increasing uveoscleral outflow. MMP's were found in cornea and their activation could change the central corneal thickness (CCT). PURPOSE To compare the effects of different prostaglandin analogues on central corneal thickness (CCT). METHODS Clinical, observational, prospectively and randomised study during 3 month on 26 patients (52 eyes) newly diagnosed with primary open angle glaucoma or ocular hypertension. The patients were distributed in two groups concerning topical treatment: - group I: 15 patients treat with travoprost 0,004%; - group II: 11 patients treat with latanoprost 0,005%. The treatment was administrated daily at 9:00 pm, one drop. The CCT was measured for each patient for 3 times by ultrasound pachimetry: at the beginning of the study, at one month and three months. The groups were homogeneous concerning age and sex distribution. Exclusion criteria were: any topical eye drug usage, history of corneal disease or intraocular surgery. The statistic analyse was realised with Mann-Whitman test. RESULTS The mean central corneal thickness for the two groups was similar: 521,27+/-28,54 microm for group I and 522,18+/-27,52 microm for group II. A statistically significant CCT reduction was observed in both groups: 516,88+/-28,61 microm at one month and 515,04+/-27,59 microm at three month for group I; respectively 518,41+/-27,36 microm at one month and 517,98+/-27,86 microm at three month for group II. CONCLUSIONS The results of this study show that both classes of prostaglandin analogs reduce the mean CCT, the effect being equivalent for the both studied groups.
Manganese‐enhanced magnetic resonance imaging (MEMRI) of brain activity and applications to early detection of brain ischemia

Divalent manganese ion (Mn2+) has been reported to be a useful contrast agent for functional MRI, through a technique named activity‐induced manganese‐dependent MRI (AIM). In AIM, signal enhancement is related to functional increases in calcium influx, and therefore AIM is, thus far, the only MRI method able to map brain activation in vivo independently of the surrogate hemodynamic changes used in functional MRI. Because of its high signal‐to‐noise ratio (SNR) and high sensitivity, AIM allows the use of multi‐slice or three‐dimensional MRI techniques to map functional activity at high spatial resolution. In the present review, we define AIM as a functional MRI tool based on the administration of divalent ionized manganese through an open or disrupted blood–brain barrier (BBB). The adequacy and efficacy of AIM in detecting neural activation is described in light of supporting experiments on inhibition of calcium channels, FOS expression, and on direct comparison to BOLD‐ and perfusion‐based functional MRI. Two main applications of AIM, mapping brain activation in rat somatosensory cortex, as well stroke research based on the well‐established middle cerebral artery occlusion model, are described in detail. Methodological problems associated with a strong dependence on anesthetic conditions, potential corruption due to disruption of the BBB, and unspecific increase of the baseline signal due to acoustical noise are discussed. Finally, recommended preparation methods and experimental protocols for AIM are introduced. Copyright © 2004 John Wiley & Sons, Ltd.
Speaking rate of adventitiously deaf male cochlear implant candidates.

No objective group data on speaking rate or speaking duration have been reported on the speech of adventitiously profoundly hearing-impaired adults. Results of the present study showed that speaking rate, i.e., number of syllables per second, was significantly slower and speaking duration was significantly longer for 25 adventitiously profoundly hearing-impaired adult male cochlear implant candidates than for 10 normal-hearing control subjects. The factors of length of time since onset of profound hearing loss and hearing aid use did not significantly affect speaking rate. Based on these objective data, a rationale and method are presented for aural rehabilitation of the profoundly hearing-impaired who exhibit speaking rate abnormalities.
Epigenetic silencing of CDX2 is a feature of squamous esophageal cancer

CDX2, a mammalian homologue of the homeobox gene ‘caudal,’ is expressed in gut epithelia and plays an important role in establishing the intestinal phenotype during development. Mice heterozygously disrupted for CDX2 develop disorganized polypoid hamartomas with glandular epithelium and stratified squamous metaplasia resembling foregut mucosa. Since no genetic disruptions of CDX2 have been reported to explain loss of gene function, we examined whether epigenetic mechanisms altered CDX2 expression. Eleven of 17 squamous esophageal cancer cell lines lacked expression of CDX2 that was restored following treatment with 5‐aza‐2′‐deoxycytidine, while all colorectal cancer cell lines expressed CDX2. Loss of expression was associated with DNA methylation in the 5′ region of CDX2 determined by methylation specific PCR and bisulfite sequencing. Methylation of CDX2 was rare in primary colorectal (1 of 44 tumors, 2%) and esophageal adenocarcinoma neoplasms (2 of 43 tumors, 5%), but was common in esophageal squamous carcinoma (24 of 45 tumors, 49%). No CDX2 methylation was found in normal tissues. Using semi‐quantitative RT‐PCR, expression of CDX2 was found in low level in normal esophagus, at higher levels in primary adenocarcinoma of the esophagus, but not in primary squamous cancers of the esophagus. Restoration of CDX2 in silenced cell lines resulted in expression of the CDX2 target gene MUC2, a gene important in glandular differentiation. Our results suggest that the inactivation of CDX2 in esophageal cancer associated with DNA methylation may be an important determinant of the squamous or non‐adenomatous phenotype. © 2007 Wiley‐Liss, Inc.
The effect of Edmonston-Zagreb and Schwarz measles vaccines on immune response in infants.

The effects of measles immunization on immune responses in infants and the roles of vaccine strain and age of immunization are not known. Eighty-eight children were immunized at 6 or 9 months of age with the Edmonston-Zagreb (EZ) or Schwarz (SW6, SW9) strain of measles vaccine. Children were studied before and 2 weeks and 3 months after immunization. Seroconversion was similar, but geometric mean neutralizing titers at 3 months differed by vaccine group: SW9, 1367 mIU/mL; SW6, 982; and EZ, 303 (P = .003). Mitogen-induced lymphoproliferation was decreased at 2 weeks in the SW9 group and at 3 months in all groups and was negatively correlated with measles antibody level at 3 months (r = -.387, P = .003). CD8 T cells, soluble CD8, neopterin, and beta2-microglobulin were increased at 2 weeks in the SW9 group, and soluble CD8 and beta2-microglobulin remained elevated at 3 months. Therefore, measles immunization resulted in suppression of lymphoproliferation, which was most evident in infants with the highest antibody responses and most immune activation.
Hypoxia mediates mitochondrial biogenesis in hepatocellular carcinoma to promote tumor growth through HMGB1 and TLR9 interaction

The ability of cancer cells to survive and grow under hypoxic conditions has been known for decades, but the mechanisms remain poorly understood. Under certain conditions, cancer cells undergo changes in their bioenergetic profile to favor mitochondrial respiration by activating the peroxisome proliferator–activated receptor gamma coactivator 1 alpha (PGC‐1α) and up‐regulating mitochondrial biogenesis. In this study, we hypothesized that augmented mitochondrial biogenesis plays a critical role for cancer cells to survive hypoxia. Consistent with this hypothesis, both hypoxic human hepatocellular carcinoma (HCC) tumors and HCC cell lines subjected to hypoxia increase mitochondrial biogenesis. Silencing of PGC‐1α in hypoxic HCC cell lines halts their proliferation. Mechanistic investigations in vitro indicated that intracellular high mobility group box 1 (HMGB1) protein, a nuclear protein overexpressed in HCC, is essential for the process. Silencing of HMGB1 in hypoxic HCC cell lines resulted in a significant decrease in PGC‐1α activation and mitochondrial biogenesis. Without HMGB1, hypoxic HCC cells had significantly reduced adenosine triphosphate production, decreased cellular proliferation, and increased apoptosis. In a diethylnitrosamine‐induced murine model of HCC, genetic blocking of HMGB1 in hypoxic tumors resulted in a significant decrease in tumor growth. Tumors lacking HMGB1 had a significant reduction in mitochondrial biogenesis and a significant increase in mitochondrial dysfunction. Further in vitro mechanistic experiments indicated that during hypoxia HMGB1 translocates from the nucleus to the cytoplasm and binds to cytoplasmic Toll‐like receptor‐9. This binding leads to activation of p38 and subsequent phosphorylation of PGC‐1α, with resultant up‐regulation of mitochondrial biogenesis. Conclusion: Taken together, our findings suggest that during hypoxia HMGB1 up‐regulates mitochondrial biogenesis in HCC cancer cells, promoting tumor survival and proliferation. (Hepatology 2017;66:182–197).
Glaucoma and Keratoprosthesis Surgery: Role of Adjunctive Cyclophotocoagulation

PurposeTo evaluate the efficacy and safety of diode laser transscleral cyclophotocoagulation (DLTSC) to control intraocular pressure (IOP) in keratoprosthesis patients with uncontrolled glaucoma. Patients and MethodsBetween 1993 and 2007, 18 eyes of 18 patients underwent DLTSC, either before (n=3), during (n=1), or after (n=14) keratoprosthesis surgery. Keratoprosthesis type I was used in 72%. All but one of these patients received an Ahmed Glaucoma Valve, either with or after the keratoprosthesis placement. Best-corrected visual acuity, IOP (assessed by digital palpation), number of medications, and complications were recorded preoperatively, at day 7, at 1, 3, and 6 months then every 6 months postoperatively. ResultsMean follow-up was 26.6±19.6 months (mean±SD) and mean age was 50.1±15.6 years. Glaucoma was identified in 11 eyes before keratoprosthesis surgery and in 7 eyes after. Mean postoperative IOP was significantly reduced at 6, 12, 24, 36, and 48 months after DLTSC. DLTSC was repeated in 6 eyes. At final visit, mean best-corrected visual acuity was not decreased and there were no statistically significant differences in the number of glaucoma medications. Two patients had complications after DLTSC: a conjunctival dehiscence and a fungal endophthalmitis. ConclusionsDLTSC has beneficial long-term effects in the control of IOP and can be considered in the management of keratoprosthesis patients with refractory glaucoma.