Miracle-dz/UniFAR-FTUs huggingface dataset:
Nitrate/Nitrite as Critical Mediators to Limit Oxidative Injury and Inflammation.

SIGNIFICANCE Nitric oxide (NO) is a critical signaling molecule marked by complex chemistry and varied biological responses depending on the context of the redox environment. In the setting of inflammation, NO can not only contribute to tissue injury and be causative of oxidative damage but can also signal as an adaptive molecule to limit inflammatory signaling in multiple cell types and tissues. RECENT ADVANCES An advance in our understanding of NO biology was the recognition of the nitrate-nitrite-NO axis, whereby nitrate (predominantly from dietary sources) could be converted to nitrite and nitrite could be reduced to NO. CRITICAL ISSUES Intriguingly, the recognition of multiple enzymes that serve as nitrite reductases in the setting of hypoxia or ischemia established the concept of nitrite as a circulating endocrine reservoir of NO, with the selective release of NO at sites that were primed for this reaction. This review highlights the anti-inflammatory roles of nitrite in numerous clinical conditions, including ischemia/reperfusion, transplant, cardiac arrest, and vascular injury, and in gastrointestinal inflammation. FUTURE DIRECTIONS These preclinical and clinical investigations set up further clinical trials and studies that elucidate the endogenous role this pathway plays in protection against inflammatory signaling.
Fluorescence microtopography of oxidative stress in lung ischemia-reperfusion.

BACKGROUND Generation of oxidizing radicals in lung ischemia-reperfusion (I/R) was evaluated with the oxidation-dependent fluorogen 2'-7' dichlorofluorescin diacetate (DCF-DA). EXPERIMENTAL DESIGN Isolated, artificial media perfused, oxygen ventilated rat lungs were subjected to 1 hour of ischemia followed by 1 hour of reperfusion. DCF-DA (5 microM) present in 40 ml of recirculating perfusate served as a source of subsequent intracellular fluorogen. Fluorescence was measured in lung homogenate, and in histologic sections of lung tissue using a confocal laser scanning microscope. Control experiments were 2 hours of continuous perfusion, and 1 hour of perfusion with 1 mM tertiary butyl hydroperoxide as oxidative challenge. Dye distribution was evaluated with the oxidation-independent fluorogen analog 5'- (and 6') carboxy 2'-7' dichlorofluorescin diacetate. Dependence of oxidant generation on the presence of oxygen was studied by substituting oxygen with nitrogen in the ventilation gas. RESULTS Perfusion with 5'-(and 6') carboxy 2'-7' dichlorofluorescein diacetate resulted in even distribution of fluorescence, indicating uptake and esterolytic conversion of this dye by all cell types. Perfusion with an exogenous oxidant, tertiary butyl hydroperoxide, plus DCF-DA resulted in a marked generalized increase in fluorescence indicating the presence of the peroxidases necessary to produce the fluorogen from the precursor. Lung I/R, in the presence of oxygen in the ventilation gas, also resulted in marked increase in DCF-DA-associated fluorescence, indicating generation of oxidants. Tissue distribution of fluorescence was nonhomogenous; significant increases were associated with the arteries, veins and bronchial epithelium and at the alveolar level. Of the alveolar cells, the greatest increase in fluorescence was noted in cuboidal epithelium, capillary endothelium, and macrophages. One class of bronchial cells (tentatively identified as goblet cells) took up the dye but showed no fluorescence change with I/R. Ventilation with nitrogen (plus 5% CO2) virtually abolished the I/R-induced fluorescence increase. Preperfusion with catalase before I/R markedly attenuated the increase in fluorescence, indicating the diffusion of hydrogen peroxide from its sites of production. CONCLUSIONS The results indicate generation of oxidizing species in lungs as a result of I/R, and show predominant localization of oxidants in endothelial, type II, Clara, and ciliated cells and in macrophages.
A Predicted Secondary Structural Domain within the Internal Ribosome Entry Site of Echovirus 12 Mediates a Cell-Type-Specific Block to Viral Replication

ABSTRACT The enterovirus 5′ nontranslated region (NTR) contains an internal ribosome entry site (IRES), which facilitates translation initiation of the viral open reading frame in a 5′ (m7GpppN) cap-independent manner, and cis-acting signals for positive-strand RNA replication. For several enteroviruses, the 5′ NTR has been shown to determine the virulence phenotype. We have constructed a chimera consisting of the putative IRES element from the Travis strain of echovirus 12 (ECV12), a wild-type, relatively nonvirulent human enterovirus, exchanged with the homologous region of a full-length infectious clone of coxsackievirus B3 (CBV3). The resulting chimera, known as ECV12(5′NTR)CBV3, replicates similarly to CBV3 in human and simian cell lines yet, unlike CBV3, is completely restricted for growth on two primary murine cell lines at 37°C. By utilizing a reverse-genetics approach, the growth restriction phenotype was localized to the predicted stem-loop II within the IRES of ECV12. In addition, a revertant of ECV12(5′NTR)CBV3 was isolated which possessed three transition mutations and had restored capability for replication in the utilized murine cell lines. Assays for cardiovirulence indicated that the ECV12 IRES is responsible for a noncardiovirulent phenotype in a murine model for acute myocarditis. The results indicate that the 5′ NTRs of ECV12 and CBV3 exhibit variable intracellular requirements for function and serve as secondary determinants of tissue or species tropism.
German Kava Ban Lifted by Court: The Alleged Hepatotoxicity of Kava (Piper methysticum) as a Case of Ill-Defined Herbal Drug Identity, Lacking Quality Control, and Misguided Regulatory Politics

Abstract Kava, the rhizome and roots of Piper methysticum, are one of the most important social pillars of Melanesian societies. They have been used for more than 1000 years in social gatherings for the preparation of beverages with relaxing effects. During the colonial period, extract preparations found their way into Western medicinal systems, with experience especially concerning the treatment of situational anxiety dating back more than 100 years. It therefore came as a surprise when the safety of kava was suddenly questioned based on the observation of a series of case reports of liver toxicity in 1999 and 2000. These case reports ultimately led to a ban of kava products in Europe – a ban that has been contested because of the poor evidence of risks related to kava. Only recently, two German administrative courts decided that the decision of the regulatory authority to ban kava as a measure to ensure consumer safety was inappropriate and even associated with an increased risk due to the higher risk inherent to the therapeutic alternatives. This ruling can be considered as final for at least the German market, as no further appeal has been pursued by the regulatory authorities. However, in order to prevent further misunderstandings, especially in other markets, the current situation calls for a comprehensive presentation of the cardinal facts and misconceptions concerning kava and related drug quality issues.
Correlated Errors: Why a Monotone Relationship between Forecast Precision and Trading Profitability May Not Hold

This paper argues that the relation between financial analysts’ earnings forecast accuracy and their recommendation profitability has to be augmented by the extent of commonality in their forecast errors. We show that while accuracy is positively related to expected performance, the correlation in forecasting errors has a negative impact. This implies that a monotonic relationship between ex ante identifiable forecast accuracy and ex post recommendation profitability does not need to hold. Thus, agents may be better off by making comparatively large but less correlated errors, than by making precise but highly correlated forecasts.
FDG‐PET and magnetoencephalography in presurgical workup of children with localization‐related nonlesional epilepsy

2‐[18F]Fluoro‐2‐deoxy‐d‐glucose positron emission tomography (FDG‐PET) and magnetoencephalography (MEG) may assist in identifying the epileptogenic zone in children with nonlesional localization‐related epilepsy. The aim of this study was to evaluate sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FDG‐PET, MEG, FDG‐PET + MEG, and FDG‐PET/MEG in children with nonlesional localization‐related epilepsy.
Towards optimal user involvement in innovation processes: A panel-centered Living Lab-approach

Living Labs as seen as a rather new research area with only a limited amount of supporting theories for understanding this concept. The absence of supporting theories, or rather the lack of agreement regarding the supporting theories has induced on the one hand a proliferation of papers and articles on Living Labs and on the other hand a wide variety of approaches and projects carried out under the Living Labs-umbrella. In short, on a theoretical as well as on a practical level, a further narrowing and specifying of the Living Lab-concept remains a task in progress. Within this research paper, we will show that the Living Lab-approach is in many ways a logical extension of some of the principles of the Open Innovation-concept. In order to aid to the concrete conceptualization of Living Labs, we will give an overview of history of the Living Lab-concept with a focus on characteristics and applications. This allows us to make a meta-analysis of discerning elements that, according to the most recent literature, should or should not be present in best practice Living Labs-research. Based on this meta-analysis and on the literature review, we will construct a modified consensus-definition of the Living Lab-concept as it is currently understood, described and practiced. By adding the `panel-centered' characteristic, we also add a Living Lab-characteristic that remained overlooked in most literature on Living Labs that however bears a large potential in terms of sustainability and added value of Living Labs.
Fetal MBL2 haplotypes combined with viral exposure are associated with adverse pregnancy outcomes

Objective. To investigate the roles of inherited polymorphisms in the MBL2 gene and exposure to viral infection in the development of a range of adverse pregnancy outcomes, including birthweight <10th percentile (small-for-gestational age, SGA), antepartum hemorrhage (APH), pregnancy-induced hypertensive disorders (PIHD), and preterm birth (PTB). Methods. This was a case–control study using DNA from newborn screening cards of 717 cases (babies with at least one of the adverse pregnancy outcomes listed above) and 609 controls, to screen for six polymorphisms within the MBL2 gene. These combine to create haplotypes with high (HYPA), intermediate (LYQA, LYPA), low (LXPA), and defective (HYPD, LYQC, LYPB) circulating MBL2 levels. Results. Significant associations were found between variant MBL2 haplotypes and SGA (LYPA <32 weeks OR 5.37, 95% CI 1.50–17.27), antepartum hemorrhage (LYPA <37 weeks OR 2.29, 95% CI 1.25–4.18), and PIHD (LYQC <32 weeks (OR 17.89, 95% CI 2.20–139.57). Evidence of exposure to infection increased the effect of these associations, (SGA OR 17.00, 95% CI 1.03–252.48; APH OR 5.67, 95% CI 1.73–18.84; PIHD OR 23.80, 95% CI 1.08–1414.76), while no evidence of exposure to infection demonstrated no associations. PTB was significantly associated with the defective HYPD haplotype with evidence of exposure to infection (OR 6.14, 95% CI 1.21–29.89). Conclusions. This research suggests that the combination of fetal MBL2 haplotypes and exposure to in utero viral infection increases the risk of adverse pregnancy outcomes, including PTB, antepartum hemorrhage, small-for-gestational age and PIHD.
Barrett's esophagus: Prevalence and its relationship with dyspeptic symptoms

Background and Aim: Barrett's metaplasia is a premalign condition which plays a pivotal role in the development of esophageal adenocarcinoma. It is considered a complication of chronic gastroesophageal reflux disease. Although esophageal adenocarcinoma is an uncommon cancer, its incidence is rapidly increasing. The aims of the present study were to determine the prevalence of Barrett's metaplasia in outpatients referred for gastroscopy for upper gastrointestinal symptoms, and to clarify the relationship between Barrett's metaplasia and upper gastrointestinal symptoms.
Antiviral effect of hepatitis B virus S / C gene loci antisense locked nucleic acid on transgenic mice in vivo

We investigated the effects of hepatitis B virus (HBV) S/C double gene loci antisense locked nucleic acid on replication and expression of HBV in hepatitis transgenic mice. HBV mice (N = 30) were randomly divided into five groups of six mice: 5% glucose solution control, empty liposome control, single-target S, single-target C, and dual-target SC groups. An antisense locked nucleic acid fragment was injected into the mice. Serum HBsAg, serum HBV DNA, HBV C-mRNA expression in liver tissue, HbsAg and HbcAg expression in hepatocytes, serum albumin, alanine transaminase (ALT), urea nitrogen, and creatinine were detected. Liver and kidney sections were examined for the effects of antisense locked nucleic acid. The expression of HBsAg was markedly inhibited; the inhibition rates of the S, C, and SC target groups were 36.63, 31.50, and 54.87%, respectively; the replication of HBV DNA was also inhibited: 23.97, 21.13, and 35.83%, respectively. After injection at 1, 3, and 5 days, the corresponding rates for HBsAg inhibition were 14.40, 25.61, and 31.33%, and for HBV DNA inhibition they were 11.04, 19.24, and 24.13%. Compared with the control group, the differences in serum albumin, ALT, urea nitrogen, 10088 Y.B. Deng et al. ©FUNPEC-RP www.funpecrp. com.br Genetics and Molecular Research 14 (3): 10087-10095 (2015) and creatinine in each group were not statistically significant, and the number of HbsAgand HBcAg-positive cells in the mouse liver was significantly reduced. The liver and kidney tissues were normal. The gene therapy had significant inhibitory effects on the replication and expression of HBV in transgenic mice, and double-gene targeting was better than single-gene targeting.
Acupuncture treatment of severe knee osteoarthrosis. A long‐term study

Purpose: Acupuncture treatment of patients waiting for arthroplasty surgery. Methods: 29 patients with a total of 42 osteoarthritic knees were randomized to two groups. Group A was treated while Group B served as a no‐treatment control group. After 9 weeks Group B was treated too. Analgesic consumption, pain and objective measurements were registered. All objective measures were done by investigators who were “blinded” as to Group A & B. In the second part of the study 17 patients (26 knees) continued with treatments once a month. Registration of analgesic consumption, pain and objective measurements continued. Total study period 49 weeks. Results: Comparing Group A to B there was a significant reduction in pain, analgesic consumption and in most objective measures. In Group A + B combined there was an 80% subjective improvement, and a significantly increased knee range movement – an increase mainly in the worst knees. Results were significantly better in those who had not been ill for a long time. In the second part of the study, it was shown that it was possible to maintain the improvements. Conclusions: Acupuncture can ease the discomfort while waiting for an operation and perhaps even serve as an alternative to surgery. Seven patients have responded so well that at present they do not want an operation. (USD 9000 saved per operation).
Rumen microbes and microbial protein synthesis in Thai native beef cattle fed with feed blocks supplemented with a urea–calcium sulphate mixture

The influence of slow-release urea ( urea–calcium sulphate mixture; U–CaS) in feed blocks on rumen micro-organisms, predominant cellulolytic bacteria, microbial protein synthesis and ecology was studied in Thai native beef cattle. Four animals with an initial body weight of 100 ± 3.0 kg were randomly assigned to a 4 × 4 Latin square design with four dietary treatments (U–CaS in iso-nitrogen feed blocks at 0, 120, 150 and 180 g/kg dry matter (DM), respectively; U–CaS replaced urea). After 21 days of experimental feeding, rumen fluid was collected at 0 and 4 h after feeding. The mean intake of feed blocks and other feedstuffs offered (rice straw and concentrates) amounted to 0.3, 2.3 and 0.6 kg DM/day, respectively. Inclusion of U–CaS did not altered pH and temperature in the rumen. However, ruminal NH3–N concentration decreased quadratically (p < 0.05) in response to U–CaS inclusion, with the lowest value at 180 g U–CaS per kg feed block. With inclusion of U–CaS, the populations of rumen bacteria increased quadratically (p < 0.05) and counts of fungal zoospores were linearly enhanced (p < 0.05), being highest at 180 g U–CaS per kg feed block. Supplementation of U–CaS increased the concentration of total bacteria linearly (p < 0.05) and of Fibrobacter succinogenes quadratically (p < 0.05), whereas Ruminococcus flavefaciens and Ruminococcus albus were not affected by dietary treatments. Microbial crude protein yield and efficiency of microbial nitrogen (N) synthesis were linearly increased with different levels of U–CaS addition. Furthermore, current data clearly indicate that inclusion of U–CaS in feed blocks can affect micro-organism diversity and major cellulolytic bacteria.
Plasticity and intracortical inhibition in dystonia--methodological reconsiderations.

Sir, I read with interest the article ‘Abnormal sensorimotor plasticity in organic but not psychogenic dystonia’ by Quartarone et al. published in Brain (2009; 132: 2871–7). Dystonia is a challenging condition for clinicians and neuroscientists alike. The presented symptoms are often bizarre and a diagnostic tool that reliably distinguishes between organic and psychogenic origin is highly desirable. In their manuscript, the authors describe that ‘plasticity’, which they refer to as long-term potentiation-like plasticity that can be induced by the paired-associative stimulation (PAS) protocol (Stefan et al. , 2000), is ‘abnormally high’ only in patients with organic dystonia, while short-interval intracortical inhibition, a parameter of GABA-ergic intracortical inhibition (Mueller-Dahlhaus et al. , 2008), is equally ‘abnormal’ in psychogenic and organic dystonia. They conclude that ‘abnormal plasticity is a hallmark of organic dystonia; furthermore it is not a consequence of reduced inhibition since the latter is seen in psychogenic patients who have normal plasticity’. This conclusion is appealing since it not only offers a diagnostic tool for organic dystonia but also a simple solution to the intensively researched and still not well understood pathophysiology of this movement disorder. Transcranial magnetic stimulation is now an easily accessible and intensively used research tool in human basic and clinical neuroscience. With increasing insights into the mechanisms and effects of transcranial magnetic stimulation, even well established protocols such as short-interval intracortical inhibition or PAS are scrutinized again and further refined in order to make our research findings more reliable and valid. With this in mind, the findings and conclusions proposed in the current paper by Quartarone et al. (2009) require and might benefit from some methodological and conceptual re-considerations. There is no doubt that transcranial magnetic stimulation protocols, particularly PAS (Stefan et al. , 2000), have contributed significantly to our understanding of plasticity of the …
Risk models with capital injections

One of the main issues in ruin theory is that existing formulae for continuous time models can only be applied to some special claim size distributions and the analytical expressions for other claim size distributions do not exist. This thesis addresses this issue by considering discrete time models as approximations to continuous time models, including the classical risk model, the Markov-modulated risk model and the classical risk model with dividends. It also shows that how these models are affected by the introduction of capital injections. In Chapters 3 and 4 we construct a Gerber-Shiu function and use this to analyse the classical risk model with capital injections both analytically and probabilistically. Quantities such as the ultimate ruin probability and the joint density of the time of ruin and the number of claims until ruin are obtained by the inversion of the Laplace transform of our Gerber-Shiu function. In Chapter 5 we develop a discrete time model to approximate the probability of ruin in infinite and finite time under the classical risk model with capital injections, and show that capital injections can lead to a reduction in the probability of ruin even when claim amounts follow a heavy-tailed distribution. In Chapter 6 we extend our numerical algorithm from Chapter 5 to approximate the ultimate probability of ruin under a two-state Markov-modulated risk model with and without capital injections, and the density of the time of ruin under the same model with more than two states. The final chapter investigates dividend strategies with capital injections. We examine the effect of capital injections on the barrier and threshold strategies and consider a reinsurance arrangement that covers any fall below a positive pre-determined surplus level, so that the insurance company may operate indefinitely. To my dearest mum and the memory of my beloved father “We cannot change the wind, but set sail differently” –Aristotle
Tissue-Specific Cross-Reactivity of Connexin32 Antibodies: Problems and Solutions Unique to the Central Nervous System

Abstract Gap junction proteins are a highly homologous family of 21 connexins. Here, the authors describe a tissue-specific technical artifact complicating analysis of connexin32 protein expression in the central nervous system. The authors show that in brain, but not liver, eight commonly employed antibodies exhibit a higher affinity for a cross-reactive protein that masks the detection of connexin32. Cross-reactivity is evident in Western blot analyses when proteins are subjected to reducing/denaturing conditions but not immunoprecipitation or immunofluorescent applications. Through bioinformatic analyses, tested by sucrose gradient fractionation and immunoblotting of lysates from connexin null-mutant mice, the authors show that the cross-reactive protein is not found in the same cellular compartments as connexin32 and is likely not a member of the connexin family. These findings are presented with the intent of helping to reduce the amount of time laboratories currently expend in validating changes in connexin32 expression in the central nervous system.