Miracle-dz/UniFAR-FTUs huggingface dataset:
Melatonin modulates neuroinflammation and oxidative stress in experimental diabetic neuropathy: effects on NF‐κB and Nrf2 cascades

Abstract: Melatonin exhibits an array of biological activities, including antioxidant and anti‐inflammatory actions. Diabetic neuropathy is one of the complications of diabetes with a prevalence rate of 50–60%. We have previously reported the protective effect of melatonin in experimental diabetic neuropathy. In this study, we investigated the role of nuclear factor‐kappa B (NF‐κB) and nuclear erythroid 2‐related factor 2 (Nrf2) in melatonin‐mediated protection against streptozotocin‐induced diabetic neuropathy. Melatonin at doses of 3 and 10 mg/kg was administered daily in seventh and eighth week after diabetes induction. Motor nerve conduction velocity and nerve blood flow were improved in melatonin‐treated animals. Melatonin also reduced the elevated expression of NF‐κB, IκB‐α, and phosphorylated IκB‐α. Further, melatonin treatment also reduced the elevated levels of proinflammatory cytokines (TNF‐α and IL‐6), iNOS and COX‐2 in sciatic nerves of animals. The capacity of melatonin to modulate Nrf2 pathway was associated with increased heme oxygenase‐1 (HO‐1) expression, which strengthens antioxidant defense. This fact was also established by decreased DNA fragmentation (because inhibition of excessive oxidant‐induced DNA damage) in the sciatic nerve of melatonin‐treated animals. The results of this study suggest that melatonin modulates neuroinflammation by decreasing NF‐κB activation cascade and oxidative stress by increasing Nrf2 expression, which might be responsible at least in part, for its neuroprotective effect in diabetic neuropathy.
Genomic DNA recombination with cell‐penetrating peptide‐tagged cre protein in mouse skeletal and cardiac muscle

The Cre‐loxP recombination system has been used to promote DNA recombination both in vitro and in vivo. For in vivo delivery, Cre expression is commonly achieved through the use of tissue/cell type‐specific promoters, viral infection, or drug inducible transcription and protein translocation to promote targeted DNA excision. The development of cell permeable (or penetrating) peptide tagged proteins has facilitated the delivery of Cre recombinase protein into cells in culture, organotypic slide culture, or in living animals. In this report, we generated bacterially expressed, his‐tagged Cre protein with either a cardiac targeting peptide or an antennapedia peptide at the C‐terminus and demonstrated efficient uptake and recombination in both cell culture and mice. To facilitate delivery to cardiac and skeletal muscle, we mixed proteins with pluronic F‐127 hydrogel and delivered Cre protein into reporter Rosa26mTmG mouse skeletal muscle or Rosa26LacZ cardiac muscle via ultrasound guided injection. Activation of reporter gene expression indicated that these Cre proteins were enzymatically active. Recombination events were detected only in the vicinity of injection areas. In conclusion, we have developed a method to deliver enzymatically active Cre protein locally to skeletal muscle and cardiac muscle that may be adapted for use with other proteins. genesis 52:695–701, 2014. © 2014 Wiley Periodicals, Inc.
What counts as success? punctuated patterns of use in a persistent chat environment

This paper presents a case study of a globally distributed work group's use of an online environment called "Loops. " Loops is a web-based persistent chat system whose aim is to support collaboration amongst corporate work groups. We describe the ways in which the group turned the system's features to its own ends, and the unusual usage rhythm that corresponded with the team's varying needs for communication as it moved through its work cycle. We conclude with a discussion of design implications, and a suggestion that "community" may not always be the best way to think about groups' use of online systems.
Comparison of a single infusion of zoledronic acid with risedronate for Paget's disease.

BACKGROUND The advent of bisphosphonates advanced therapy for Paget's disease, but more effective and convenient agents are needed to increase adherence. Zoledronic acid, a bisphosphonate administered as a single intravenous infusion, might meet these needs. METHODS In two identical, randomized, double-blind, actively controlled trials of 6 months' duration, we compared one 15-minute infusion of 5 mg of zoledronic acid with 60 days of oral risedronate (30 mg per day). The primary efficacy end point was the rate of therapeutic response at six months, defined as a normalization of alkaline phosphatase levels or a reduction of at least 75 percent in the total alkaline phosphatase excess. The results of the studies were pooled. RESULTS At six months, 96.0 percent of patients receiving zoledronic acid had a therapeutic response (169 of 176), as compared with 74.3 percent of patients receiving risedronate (127 of 171, P<0.001). Alkaline phosphatase levels normalized in 88.6 percent of patients in the zoledronic acid group and 57.9 percent of patients in the risedronate group (P<0.001). Zoledronic acid was associated with a shorter median time to a first therapeutic response (64 vs. 89 days, P<0.001). Higher response rates in the zoledronic acid group were consistent across all demographic, disease-severity, and treatment-history subgroups and with changes in other bone-turnover markers. The physical-component summary score of the Medical Outcomes Study 36-item Short-Form General Health Survey, a measure of the quality of life, increased significantly from baseline at both three and six months in the zoledronic acid group and differed significantly from those in the risedronate group at three months. Pain scores improved in both groups. During post-trial follow-up (median, 190 days), 21 of 82 patients in the risedronate group had a loss of therapeutic response, as compared with 1 of 113 patients in the zoledronic acid group (P<0.001). CONCLUSIONS A single infusion of zoledronic acid produces more rapid, more complete, and more sustained responses in Paget's disease than does daily treatment with risedronate.
Prevalence and viral load of 51 genital human papillomavirus types and three subtypes

Of the 120 known human papillomaviruses (HPV), 51 HPV types infect the genital mucosa. Very little is known about the prevalence and viral load of the majority of these low‐risk (Lr‐) HPV types in screening populations. We determined the prevalence of 51 HPV types and three subtypes in 999 consecutive BD‐SurePath™ liquid‐based cervical cytology samples collected during routine gynecological health checks from Belgian women. This series of screening samples was enriched with ASC‐US (n = 100), low‐grade squamous intraepithelial lesion LSIL (n = 100) and high‐grade squamous intraepithelial lesion (HSIL) (n = 97) and analyzed by BSGP5+/6+‐PCR/MPG assay for 51 HPV types and three subtypes. In consecutive screening samples, any of the 54 genital HPV (sub)types was found in 37.1%; Hr‐HPV types were detected more frequently (26.8%) than the 31 Lr‐HPV types (16.4%) and the six possibly high‐risk types (6.6%). High viral load infections were present in 17.0% of the screening population. Among the women with cytological abnormalities, the prevalence of high viral loads of Hr‐HPV types increased from negative for intraepithelial lesion or malignancy (NIL/M) over ASC‐US, LSIL to HSIL (5.3, 47.1, 84.2 and 91.8%, respectively). The prevalence of possibly Hr and Lr‐HPV types increased from NIL/M to LSIL but declined to HSIL. From NIL/M to HSIL, Hr‐HPV infections showed an increasing frequency of high viral loads compared to total DNA positivity, but the increase between LSIL and HSIL was small. Type‐specific analyses revealed substantial differences between individual HPV types in these groups. Our study provides quantitative data for the whole spectrum of genital HPV in a Belgian screening population and in a representative set of women with cervical abnormalities.
Inflammation and Atherosclerosis: Novel Insights Into Plaque Formation and Destabilization

Background and Purpose— The simplistic view of atherosclerosis as a disorder of pathological lipid deposition has been redefined by the more complex concept of an ongoing inflammatory response. Summary of Review— Apolipoprotein E and low-density lipoprotein (LDL)-receptor-deficient mice develop accelerated atherosclerosis allowing in-depth pathophysiological investigations. Atherosclerotic plaques in these mice contain large numbers of T cells and macrophages. Crossbreading apolipoprotein E-deficient mice with T-cell-deficient mice and mice with impaired macrophage function (osteopetrotic op/op mice) disclosed the important impact of immune cells on atherosclerotic lesion development. In contrast to the detrimental role of T cells and macrophages, B cells appear to be atheroprotective. These basic experimental findings have partly been confirmed in studies of the human carotid artery system. Inflammation is not only instrumental in the development of human atheromatous plaques, but, importantly, plays a crucial role in the destabilization of internal carotid artery plaques, thus converting chronic atherosclerosis into an acute thrombo-embolic disorder. Humoral factors involved in internal carotid artery destabilization include cytokines, cyclooxygenase-2, matrix metalloproteinases, and tissue factor. Antibodies to oxidized LDL can reflect disease activity on one hand, but can also confer atheroprotection. Novel MRI techniques may aid in the in vivo assessment of acute plaque inflammation in humans. Conclusions— The impact of inflammation on the development of atherosclerotic plaques and their destabilization opens new avenues for treatment. The effects of statins, acetylsalicyclic acid and angiotensin-converting enzyme inhibitors on stroke prevention may partly be attributable to their profound anti-inflammatory actions. Vaccination against modified LDL and heat shock proteins halt plaque progression in experimental atherosclerosis. Their potential for prevention of human atherosclerosis is currently under investigation.
Lysosomal biogenesis and function is critical for necrotic cell death in Caenorhabditis elegans

Necrotic cell death is defined by distinctive morphological characteristics that are displayed by dying cells (Walker, N.I., B.V. Harmon, G.C. Gobe, and J.F. Kerr. 1988. Methods Achiev. Exp. Pathol. 13:18–54). The cellular events that transpire during necrosis to generate these necrotic traits are poorly understood. Recent studies in the nematode Caenorhabditis elegans show that cytoplasmic acidification develops during necrosis and is required for cell death (Syntichaki, P., C. Samara, and N. Tavernarakis. 2005. Curr. Biol. 15:1249–1254). However, the origin of cytoplasmic acidification remains elusive. We show that the alkalization of endosomal and lysosomal compartments ameliorates necrotic cell death triggered by diverse stimuli. In addition, mutations in genes that result in altered lysosomal biogenesis and function markedly affect neuronal necrosis. We used a genetically encoded fluorescent marker to follow lysosome fate during neurodegeneration in vivo. Strikingly, we found that lysosomes fuse and localize exclusively around a swollen nucleus. In the advanced stages of cell death, the nucleus condenses and migrates toward the periphery of the cell, whereas green fluorescent protein–labeled lysosomal membranes fade, indicating lysosomal rupture. Our findings demonstrate a prominent role for lysosomes in cellular destruction during necrotic cell death, which is likely conserved in metazoans.
Atypia of undetermined significance on thyroid fine needle aspiration: surgical outcome and risk factors for malignancy

Purpose This study was performed to analyze the surgical pathology results of the "atypia of undetermined significance" (AUS) category from thyroid fine needle aspiration (FNA) and to describe the characteristics to distinguish a malignant from a benign nodule. Methods A retrospective analysis was done on 116 patients who underwent thyroid surgery from December 2008 to December 2012, following a diagnosis of AUS from preoperative thyroid FNA. We investigated the age, gender, size and site of the nodules, ultrasonographic criteria, cytological features, the number of atypia results after repeated FNAs, surgical method, and final pathologic results. Results Sixty-five out of 116 patients underwent total thyroidectomy and the rest had partial thyroidectomy. The final pathologic results were 41 malignancies (35.3%) and 75 benign diseases (64.7%). AUS was divided into group 1: 'cannot rule out malignancy' or group 2: 'cannot rule out follicular neoplasm'. After surgery, group 1 revealed papillary thyroid cancer in most cases and group 2 revealed follicular adenoma in most cases. Age over 40 years, ultrasonographic findings suggestive of malignancy, more than 2 results of atypia from repeated FNAs and nodules less than 2 centimeters were risk factors for malignancy on univariate analysis. Multivariate analysis showed that ultrasonographic findings suggestive of malignancy was a significant risk factor for malignancy. Conclusion For proper evaluation of the risk for malignancy in thyroid AUS patients, the ultrasonographic criteria should be considered along with other clinicopathological findings such as age, nodule size, number of atypia, cytologic features.
Fluid Limits for Many-Server Systems with Reneging Under a Priority Policy

A multiclass many-server system is considered, in which customers are served according to a nonpreemptive priority policy and may renege while waiting to enter service. The service and reneging time distributions satisfy mild conditions. Building on an approach developed by Kaspi and Ramanan, the law-of-large-numbers many-server asymptotics are characterized as the unique solution to a set of differential equations in a measure space, regarded as fluid model equations. In stationarity, convergence to the explicitly solved invariant state of the fluid-model equations is established. An immediate consequence of the results in the case of exponential reneging is the asymptotic optimality of an index policy, called the c(mu) / (theta) rule, for the problem of minimizing linear queue-length and reneging costs. A certain Skorohod map plays an important role in obtaining both uniqueness of solutions to the fluid-model equations and convergence.
Langerhans cell histiocytosis of bone in children: a long-term retrospective study

Langerhans cell histiocytosis is rare and frequently involves the bone. We retrospectively reviewed the orthopaedic aspects (symptoms, localizations, treatments) and the long-term outcome [disease status, overall survival (OS), event-free survival (EFS)] of 121 patients (June 1968–December 2009). The main symptom was local pain. The orthopaedic treatment was mainly conservative. The most frequent localization was osseous monofocal (62% of monosystemic diseases). Monosystemic and osseous monofocal localizations, treatment after 1991 (OS, P=0.007; EFS, P=0.03) and age older than 2 years (OS, P=0.003; EFS, P=0.001) were prognostic factors that were positively associated with survival. Oncologic treatment has improved over time, translating into better survival. A biopsy is often mandatory.
Adaptive Path-Following Control for an Unmanned Surface Vessel Using an Identified Dynamic Model

This paper proposes a path-following control method for an unmanned surface vessel (USV) based on an identified dynamic model. To handle the USV dynamic model effectively, a three degree-of-freedom model is employed instead of a full nonlinear dynamic model and linearized at specific equilibrium condition. The linearized model is identified with real data from several experiments by utilizing a particle swarm optimization method. Then, based on the identified model, an adaptive control algorithm is proposed to follow several waypoints and velocity command. The proposed control method utilizes virtual control input, dynamic surface control method, and adaptive terms to handle matched and unmatched uncertainties simultaneously. The overall closed-loop stability is analyzed by introducing deadzone errors composed of tracking error and saturation function. Finally, some experiment with a remodeled commercial fishing boat are conducted and analyzed to validate the performance of the proposed methods.
Dyspnea and the Affective Response During Exercise Training in Obstructive Pulmonary Disease

BackgroundDyspnea (SOB), dyspnea-related anxiety (DA), and exercise performance have been shown to improve after exercise training in patients with Chronic Obstructive Pulmonary Disease (COPD). However, there are no published descriptions of the changes in dyspnea intensity or dyspnea-related anxiety during or across the exercise training sessions. ObjectivesTo describe and compare the differences in the patterns of change in SOB, DA, and exercise performance during 12 exercise training sessions with and without nurse coaching. MethodsForty-five dyspnea-limited patients with COPD were randomly assigned to nurse-monitored (ME) or nurse-coached exercise (CE). SOB and DA were rated on a 200 mm VAS every 2 minutes during each of 12 treadmill training sessions. ResultsWarm-up, peak, cool-down, mean SOB, and peak SOB/stage remained constant over the exercise sessions, with increasing exercise performance for both groups over the 12 sessions (p < .001). There was a significant difference in the pattern of mean SOB over time between the ME and CE group (p < . 05). Mean, peak DA, and peak DA/stage showed a rapid decrease within the first 4 sessions (p < . 05) with no significant differences between the groups. Warm-up and cool-down DA remained constant. There were large intra-and inter-subject variations in the rating of dyspnea and dyspnea-related anxiety within and across sessions. ConclusionsAs theoretically proposed, both groups significantly decreased their DA over the training sessions. This decrease was early in the sessions and was not accompanied by a decrease in the SOB. In contrast, subjects maintained a nearly constant mean and peak SOB with increasing exercise performance, suggesting that people may have a dyspnea threshold above which they are unable to tolerate greater dyspnea. Description of the changes in dyspnea and the affective response during training need to be expanded, while studying the type and timing of strategies to enhance the improvement in dyspnea and dyspnea-related anxiety.
INTRARENAL COMPLEMENT FIXATION BY CYTOTOXIC ANTIBODIES

The reactivity of histocompatibility antigens with serum antibodies and complement was studied in a short term model of allotransplantation. Lewis and DA rat kidneys were perfused with cytotoxic antisera and tissue sections analyzed for adsorption of fluorescent antibodies against γ-globulin and complement (β1C protein). Both, the presumed cytotoxic antibody and C were localized at similar sites in the endothelial lining and in the walls of the arterial vessels and of the larger veins. The pattern of immune globulin deposition was distinct from that observed in glomerulonephritis. It may thus become helpful in the differential diagnosis between graft rejection and glomerulonephritis. At the sites of the deposits, the endothelial cells appeared enlarged and their nuclei protruded into the lumen. The findings are in line with the hypothesis that an antibody-mediated local activation of serum complement may be involved in the destruction of allografted tissue.
Fatty Acid-Induced Injury in Developing Piglet Intestine: Effect of Degree of Saturation and Carbon Chain Length

ABSTRACT: Luminal perfusion with the long-chain fatty acid (LCFA) oleate in concentrations similar to that found in premature infant formula produces a dose- and age-dependent mucosal injury in developing intestine. To investigate whether this lipid-induced phenomenon is a function of the degree of saturation and/or chain length of the fatty acid, 51Cr-EDTA plasma-to-lumen clearance was measured in jejunum and ileum of 1-d-, 3-d-, 2-wk-, and 1-mo-old piglets after perfusion with 5-mM solutions of different medium-chain saturated fatty acids and saturated and un-saturated LCFA. Mono- and polyunsaturated LCFA produced significant increases in jejunal permeability. In general, this effect was greater in piglets ≤2 wk old compared with 1-mo-old animals, but no differences were observed among the unsaturated LCFA within an age group. In contrast, the alterations in mucosal permeability induced by medium-chain fatty acids were overall more attenuated than those induced by LCFA. Our results suggest that developing intestine is vulnerable to the injurious effect of dietary fatty acids and that the lipid-induced changes in mucosal permeability appear to be a function of the fatty acid chain length. The degree of saturation of the fatty acid does not alter its cytotoxic effects.
Sustainable Development and the Sustainability of Competitive Advantage: A Dynamic and Sustainable View of the Firm

Does the need for sustainable development hinder businesses’ ability to create value? Is a firm’s competitiveness negatively affected by considering that need? After quickly reviewing the main literature contributions on the relationship between business and society, and drawing from resource-based view of the firm and sustainable development literature, this paper presents a proposal for a dynamic and sustainable view of the firm. It shows how considering the changes introduced into the competitive landscape by sustainable development influences the way in which companies develop their resources, capabilities and activities, fostering the persistence of competitive advantages based on knowledge and innovation.
Address Auto-configuration in MANET with multiple gateways: Analysis and measurement

A mobile node who wants to access the Internet must be firstly configured a global IP address. An address autoconfiguration scheme used for assigning IP address to the mobile nodes in the MANET is proposed in this paper. The proposed scheme works correctly and does not have the limitations of earlier solutions. This scheme enables the mobile node to configure a MANET-local address and then configure a global address. Then, we evaluate the performance of the solution through theoretical analysis and simulation experiments. Through the theoretical analysis and simulation experiments, it shows that our approach has lower latency and reasonable communication overhead. Finally, we conclude with a discussion of the related future work. Keywords-auto-configuration; address assignment; MANET; multiple gateways; global connectivity
French version of the Brief Infant-Toddler Social and Emotional Assessment questionnaire-BITSEA.

OBJECTIVE The aim of the present study was to examine the psychometric properties of the French version of the Brief Infant-Toddler Social and Emotional Assessment (BITSEA). METHODS The sample consisted of 589 low-risk infants aged 12-36 months and their parents. Parents completed the BITSEA, the Child Behavior Checklist 1½-5 (CBCL - 18 months to 5 years version), and the Parenting Stress Index - Short Form (PSI-SF). RESULTS Multitrait-multimethod and confirmatory factor analyses revealed adequate psychometric properties for the French version of the BITSEA. Scores on the BITSEA Problem scale were positively correlated to all CBCL and PSI-SF subscales, whereas negative correlations were found between BITSEA Competence scale and CBCL and PSI-SF subscales. The BITSEA Problem score significantly increased with level of parental worry, examined through a single-item question that is part of the BITSEA. CONCLUSION Findings support the validity of the French version of the BITSEA. However, additional work on the clinical validity of the BITSEA, including with at-risk children, is warranted.