Miracle-dz/UniFAR-FTUs huggingface dataset:
Asymmetric Dimethylarginine Produces Vascular Lesions in Endothelial Nitric Oxide Synthase–Deficient Mice: Involvement of Renin-Angiotensin System and Oxidative Stress

Objective—Asymmetric dimethylarginine (ADMA) is widely believed to be an endogenous nitric oxide synthase (eNOS) inhibitor. However, in this study, we examined our hypothesis that the long-term vascular effects of ADMA are not mediated by inhibition of endothelial NO synthesis. Methods and Results—ADMA was infused in wild-type and eNOS-knockout (KO) mice by osmotic minipump for 4 weeks. In wild-type mice, long-term treatment with ADMA caused significant coronary microvascular lesions. Importantly, in eNOS-KO mice, treatment with ADMA also caused an extent of coronary microvascular lesions that was comparable to that in wild-type mice. These vascular effects of ADMA were not prevented by supplementation of l-arginine, and vascular NO production was not reduced by ADMA treatment. Treatment with ADMA caused upregulation of angiotensin-converting enzyme (ACE) and an increase in superoxide production that were comparable in both strains and that were abolished by simultaneous treatment with temocapril (ACE inhibitor) or olmesartan (AT1 receptor antagonist), which simultaneously suppressed vascular lesion formation. Conclusions—These results provide the first direct evidence that the long-term vascular effects of ADMA are not solely mediated by simple inhibition of endothelial NO synthesis. Direct upregulation of ACE and increased oxidative stress through AT1 receptor appear to be involved in the long-term vascular effects of ADMA in vivo.
Cerebral hemodynamics in patients with cirrhosis.

BACKGROUND/AIMS Cirrhosis causes a decrease in cerebral blood flow because of a hyperdynamic circulatory state. We aimed to study the cerebral hemodynamic parameters in patients with decompensated cirrhosis and their relationship to the Child-Pugh and Model for End-Stage Liver Disease (MELD) scores. MATERIALS AND METHODS We used transcranial Doppler to investigate the cerebral hemodynamic parameters, namely the mean flow velocity of the middle cerebral artery, pulsatility index (PI), and resistive index (RI), in 50 patients who had decompensated cirrhosis and in a control group of 50 healthy people. We also investigated their relationship to the Child-Pugh and MELD scores. RESULTS Patients with cirrhosis had a lower mean flow velocity than those in the control group. Further, patients with cirrhosis had higher PI and RI values. There was a positive correlation between PI and the Child-Pugh score. In addition, there was a positive correlation among PI, RI, and the MELD score. The RI values of patients with ascites were higher than those of patients without ascites. CONCLUSION Cerebral autoregulation might be impaired in patients with cirrhosis. Cerebral resistance proportionally increases to disease severity. There was a positive correlation among PI, RI, and MELD scores, which means that transcranial Doppler might be useful not only in the follow-up of the severity of the disease but also in determining the survival of these patients.
Does the Use of Honorific Appellations in Audit Reports Connote Higher Financial Misstatement Risk? Evidence from China

Purpose - From the sociolinguistic perspective, the purpose of this paper is to examine whether the honorific and actual-name appellations that Chinese auditors use to address clients in audit reports connote differential financial misstatement risk. Specifically, the authors hypothesize that auditors’ use of honorifics signals their inferior social status relative to their clients, thereby leading to compromised auditor independence, lower audit quality, and higher financial misstatement risk. Design/methodology/approach - The authors use a sample of manually coded appellation data from audit reports of Chinese public firms between 2003 and 2012 to conduct the research. Findings - The authors find significantly greater financial misstatements, both in terms of likelihoods and magnitudes, for companies addressed by honorifics than for those addressed by actual names. Moreover, compared to auditors’ consistent honorific usage, discretionary honorific usage has a stronger positive association with misstatements. The authors further show that the positive association between honorific usage and client misstatement risk weakens when the audit firm is a Top 10 accounting firms in China, is an industry specialist, is formed as a partnership, or resides in a more concentrated audit market. Originality/value - This study contributes to the sociolinguistics literature in accounting and provides evidence supporting the reform proposed by the International Auditing and Assurance Standards Board to enhance the usefulness of audit reporting.
The effect of mental alerting on peripheral vestibular nystagmus during spontaneous, gaze (30° left, 30° right) and body positional (left & right lateral lying) testing using electronystagmography (ENG)

The performance of mental alerting during caloric testing has always been considered important, however its use/benefit during electronystagmography (ENG)/videonystagmography (VNG) testing has been questioned. The aim of this study was to investigate the effect of mental alerting tasks on peripheral type vestibular nystagmus recorded during ENG. Thirty patients with significant spontaneous/gaze or positional nystagmus (slow phase velocity ≥ 6°/s) were recruited from consecutive referrals for vestibular assessment. Nystagmus was recorded by ENG both in the presence and absence of mental alerting for each patient. Investigation of nystagmus by analysis of variance (ANOVA) revealed significantly larger nystagmus (higher value SPV) with mental alerting than with no alerting (p<0.001), and for some patients nystagmus traces were reduced to a flat line (no nystagmus) with no alerting. The study demonstrates the importance of mental alerting in helping overcome central suppression of nystagmus and highlights its importance to help identify peripheral type nystagmus during ENG.
SUPPRESSION MEDIATED BY ANERGIC CD4+ T CELLS REQUIRES STIMULATION BY MHC-PEPTIDE COMPLEXES AND CAN BE INDUCED IN THE PRESENCE OF COSTIMULATION1

Background. In this study, we have investigated the mechanisms involved in both the induction of suppressive anergy, the stability of the anergy induced, and the possible mechanisms by which the response of immunocompetent CD4+ T cells are suppressed. Methods. We used immobilized anti-CD3 monoclonal antibody (mAb) to induce anergy in T helper (Th) 1 and Th0 cells reactive with MHC class II molecule H2 I-Ab. Results. We observed that suppressive anergy was induced independently of costimulation in Th0 but not Th1 cells. Although the anergic and suppressive states of Th0 cells were stable in the presence of exogenous interleukin-2, this was not the case for Th1 cells. No evidence for linked epitope suppression was observed for any of the I-Ab reactive cells investigated. Neither anergy nor suppression was observed in Th0 cells upon restimulation with anti-CD3 in the presence of syngeneic antigen-presenting cells (APCs). However, anergy but not suppression was observed in co-cultures restimulated with anti–T-cell antigen receptor (TCR) mAbs/syngeneic APCs and suppression could be restored by the addition of I-Ab+ APCs. Conclusions. Overall, these data suggested that the MHC-peptide complex recognized by the Th0 cells was required for suppression of the response of immunocompetent cells. We propose that suppression is mediated either by down-modulation of the MHC-peptide complex recognized by the anergic T cells or that a molecule specific to the MHC-peptide/TCR interaction facilitates negative regulation by APC:T or T:T interactions.
Predicting individual feed requirements of cattle fed in groups.

A published model designed to predict individual feed required for the observed shrunk BW and ADG of growing cattle when fed in groups was modified and evaluated to improve its accuracy. This model is needed to accurately bill feed and compute cost of gain in marketing programs based on individual animal management. Because of its importance in predicting energy required for growth, a database of 401 steers was used to develop an equation to predict percentage of empty-body fat (EBF) from carcass measurements (12th rib fat thickness, hot carcass weight, USDA quality grade, and longissimus muscle area), which accounted for 61% of the variation in EBF with no bias (P > 0.1). When tested with an independent data set of 951 steers, the equation accounted for 51% of the variation with 1% proportional bias. The large variation in the carcass measurements at a particular EBF observed in this study indicates further improvement is limited by the inability of carcass measurements to account for variation in fat distribution in the various carcass components. Because of its importance in setting the target end point, a database of 1,355 steers and heifers was used to determine the relationship between EBF and USDA quality grade. These data indicate growing and finishing cattle reach Select and low-Choice quality grades at an EBF of 26.15 +/- 0.19 and 28.61 +/- 0.20%, respectively (P < 0.05). A data set of 228 steers from different breeds from two serial slaughter studies indicated 14.26 +/- 1.52 kg of empty BW change are required to increase EBF one percentage unit for cattle fed high-energy diets; this adjustment is needed to adjust final shrunk BW to the target EBF end point. The model to predict DM required with modifications developed in this study was evaluated with data from 365 individually fed cattle and it accounted for 74% of the variation in observed DM consumed with no bias (P > 0.1). When the revised model was applied to a commercial feedlot data set containing 12,105 steers and heifers, the total observed DM consumed was predicted with a bias of less than 1%. The model presented in this study accounts for differences known to affect animal requirements (breed type, BW and ADG, and weight at the target EBF end point) and can be used to fairly allocate feed to individuals fed in a group under commercial feedlot conditions.
Hepatitis B virus suppresses toll‐like receptor–mediated innate immune responses in murine parenchymal and nonparenchymal liver cells

We have previously shown that Toll‐like receptor (TLR)‐activated murine nonparenchymal liver cells [(NPC); Kupffer cells (KC), liver sinusoidal endothelial cells (LSEC)] can suppress hepatitis B virus (HBV) replication. Therefore, the aim of this study was to investigate whether HBV has the ability to counteract the TLR‐mediated control of its replication. Freshly purified murine hepatocytes and NPCs obtained from C57BL6 mice were stimulated by TLR 1‐9 ligands in the presence or absence of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), HBV virions, or supernatants from HBV‐producing HBV‐Met cells, and HBV replication was suppressed by anti‐ hepatitis B virus X protein (HBx) small interfering RNA (siRNA) in HBV‐Met cells. Supernatants were collected and tested for antiviral cytokines by viral protection assay. HBV gene expression and replication was analyzed by southern blot. RNA and proteins were analyzed by quantitative reverse transcription polymerase chain reaction (RT‐PCR) or western blot and enzyme‐linked immunosorbent assay, respectively. Pretreatment of hepatocytes and NPCs with HBV‐Met cells supernatants, HBsAg, HBeAg, or HBV virions almost completely abrogated TLR‐induced antiviral activity, which correlated with suppression of interferon beta (IFN‐β) production and subsequent interferon‐stimulated gene induction as well as suppressed activation of interferon regulatory factor 3 (IRF‐3), nuclear factor kappa B (NF‐κB), and extracellular signal‐regulated kinase (ERK) 1/2. In HBV‐infected HBV‐Met cells, TLR stimulation did not induce antiviral cytokines in contrast to primary hepatocytes. TLR‐stimulated expression of proinflammatory cytokines [tumor necrosis factor alpha (TNF‐α), interleukin‐6 (IL‐6)], and activation of IRF‐3 was suppressed after up‐regulation of HBV replication in HBV‐Met cells. Accordingly, suppression of HBV replication by siRNA led to activation or expression of proinflammatory transcription factors and cytokines. Conclusion: Our data indicate that HBV can suppress the TLR‐induced antiviral activity of liver cells. This has major implications for the interaction between HBV and the immune system. (HEPATOLOGY 2009.)
Mat e Drinking and Esophageal Squamous Cell Carcinoma in South America : Pooled Results from Two Large Multicenter Case – Control Studies

Background: Mat e tea is a nonalcoholic infusion widely consumed in southern South America, and may increase risk of esophageal squamous cell carcinoma (ESCC) and other cancers due to polycyclic aromatic hydrocarbons (PAH) and/or thermal injury. Methods:Wepooled two case–control studies: a 1988 to 2005Uruguay study and a 1986 to 1992multinational study inArgentina, Brazil, Paraguay, andUruguay, including 1,400 cases and 3,229 controls.We computedORs and fitted a linear excess OR (EOR) model for cumulative mat e consumption in liters/day–year (LPDY). Results: The adjusted OR for ESCC with 95% confidence interval (CI) by ever compared with never use of mat ewas 1.60 (1.2–2.2). ORs increased linearlywith LPDY (test of nonlinearity; P1⁄4 0.69). The estimate of slope (EOR/LPDY) was 0.009 (0.005–0.014) and did not vary with daily intake, indicating mat e intensity did not influence the strength of association. EOR/LPDY estimates for consumption at warm, hot, and very hot beverage temperatures were 0.004 ( 0.002–0.013), 0.007 (0.003–0.013), and 0.016 (0.009–0.027), respectively, and differed significantly (P < 0.01). EOR/LPDY estimates were increased in younger (<65) individuals and never alcohol drinkers, but these evaluations were post hoc, and were homogeneous by sex. Conclusions: ORs for ESCC increased linearly with cumulative mat e consumption and were unrelated to intensity, so greater daily consumption for shorter duration or lesser daily consumption for longer duration resulted in comparable ORs. The strength of association increased with higher mat e temperatures. Impact: Increased understanding of cancer riskswithmat e consumption enhances the understanding of the public health consequences given its purported health benefits. Cancer Epidemiol Biomarkers Prev; 23(1); 1–10.
Interaction between Scene and Object Processing Revealed by Human fMRI and MEG Decoding

Scenes strongly facilitate object recognition, such as when we make out the shape of a distant boat on the water. Yet, although known to interact in perception, neuroimaging research has primarily provided evidence for separate scene- and object-selective cortical pathways. This raises the question of how these pathways interact to support context-based perception. Here we used a novel approach in human fMRI and MEG studies to reveal supra-additive scene-object interactions. Participants (men and women) viewed degraded objects that were hard to recognize when presented in isolation but easy to recognize within their original scene context, in which no other associated objects were present. fMRI decoding showed that the multivariate representation of the objects' category (animate/inanimate) in object-selective cortex was strongly enhanced by the presence of scene context, even though the scenes alone did not evoke category-selective response patterns. This effect in object-selective cortex was correlated with concurrent activity in scene-selective regions. MEG decoding results revealed that scene-based facilitation of object processing peaked at 320 ms after stimulus onset, 100 ms later than peak decoding of intact objects. Together, results suggest that expectations derived from scene information, processed in scene-selective cortex, feed back to shape object representations in visual cortex. These findings characterize, in space and time, functional interactions between scene- and object-processing pathways. SIGNIFICANCE STATEMENT Although scenes and objects are known to contextually interact in visual perception, the study of high-level vision has mostly focused on the dissociation between their selective neural pathways. The current findings are the first to reveal direct facilitation of object recognition and neural representation by scene background, even in the absence of contextually associated objects. Using a multivariate approach to both fMRI and MEG, we characterize the functional neuroanatomy and neural dynamics of such scene-based object facilitation. Finally, the correlation of this effect with scene-selective activity suggests that, although functionally distinct, scene and object processing pathways do interact at a perceptual level to fill in for insufficient visual detail.
Undoing segmentation? Latin American health care policy during the economic boom

For all the agreement regarding the segmented character of Latin America’s social policy, few studies define it clearly, let alone suggest exact ways to measure it. This article provides a more precise definition based on a threefold policy output made of coverage, generosity and equity. Empirically, the paper explores the cross-national variation in segmentation in health care within Latin America in 2000 and 2013, before and after Latin America´s economic boom. The article clusters countries, evaluate which ones improved their relative position during the 2000s, and determine the overall level of segmentation in the region. Findings are twofold. First, we identify three clusters: countries that respectively do particularly well and poorly across policy dimensions in 2000 and 2013, and a smaller set of countries that improved significantly, particularly regarding coverage and generosity. Secondly, despite cross-national differences, there are shared regional challenges – the risk of catastrophic expenditure being a case in point. Our analysis demonstrates the need to move beyond coverage as a policy goal and pay more attention to gaps in generosity in every country. We also call for better indicators to measure performance beyond coverage across countries and more studies that explain the similarities and differences between countries that improved considerably during the 2000s.
Modeling Social Pressures Toward Political Instability in the United Kingdom after 1960: A Demographic Structural Analysis

Author(s): Ortmans, Oscar; Mazzeo, Elisabetta; Meshcherina, Kira; Korotayev, Andrey | Abstract: In the current paper, we investigate the predictive ability of Goldstone’s demographic structural model. In particular we seek to apply Turchin’s version of it to modeling the social pressures for political instability in the UK. It is then demonstrated that Turchin’s analysis of ‘demographic structural’ pressures in the US presents similar conditions that developed under neoliberalism during the same time periods in both countries. It is also demonstrated that the modeling of social pressures toward political instability in the UK and the USA performed by Peter Turchin and us can throw some light on the factors and patterns of the global sociopolitical destabilization wave of the 2010s. Thus, Goldstone’s demographic structural model might have some predictive potential not only at the national level, but also global scale.
The Ambiguous Effects of Democracy on Bureaucratic Quality

Recent studies find that higher degrees of democracy are related to higher levels of bureaucratic quality. However, they only offer limited explanations for this pattern based on a unidimensional understanding of democracy. We argue that future uncertainties as perceived by the incumbent, the opposition, and voters are important for why bureaucratic reform takes place. Therefore, we expect no uniform effects of democracy but that the effect depends on the socioeconomic status of the median voter. Empirically, we examine the separate effects of three dimensions of democracy – competitive elections, legislative constraints on the executive, and suffrage. Based on a global sample of countries from 1790 to 2016 that adds historical depth and variation on bureaucratic quality and the dimensions of democracy, the results show that competitive elections and legislative constraints are connected with higher levels of bureaucratic quality. However, the third dimension of suffrage is not related to bureaucratic quality. Rather, the positive effects of competitive elections and legislative constraints seem to decrease in times of large suffrage extensions. (Less)
Profiling of apoptosis genes allows for clinical stratification of primary nodal diffuse large B‐cell lymphomas

Intrinsic resistance of lymphoma cells to apoptosis is a probable mechanism causing chemotherapy resistance and eventual fatal outcome in patients with diffuse large B cell lymphomas (DLBCL). We investigated whether microarray expression profiling of apoptosis related genes predicts clinical outcome in 46 patients with primary nodal DLBCL. Unsupervised cluster analysis using genes involved in apoptosis (n = 246) resulted in three separate DLBCL groups partly overlapping with germinal centre B‐lymphocytes versus activated B‐cells like phenotype. One group with poor clinical outcome was characterised by high expression levels of pro‐and anti‐apoptotic genes involved in the intrinsic apoptosis pathway. A second group, also with poor clinical outcome, was characterised by high levels of apoptosis inducing cytotoxic effector genes, possibly reflecting a cellular cytotoxic immune response. The third group showing a favourable outcome was characterised by low expression levels of genes characteristic for both other groups. Our results suggest that chemotherapy refractory DLBCL are characterised either by an intense cellular cytotoxic immune response or by constitutive activation of the intrinsic mediated apoptosis pathway with concomitant downstream inhibition of this apoptosis pathway. Consequently, strategies neutralising the function of apoptosis‐inhibiting proteins might be effective as alternative treatment modality in part of chemotherapy refractory DLBCL.
Structure/Function Studies of Ser/Thr and Tyr Protein Phosphorylation in Mycobacterium tuberculosis

Many bacterial species express ‘eukaryotic-like’ Ser/Thr or Tyr protein kinases and phosphatases that are candidate mediators of developmental changes and host/pathogen interactions. The biological functions of these systems are largely unknown. Recent genetic, biochemical and structural studies have begun to establish a framework for understanding the systems for Ser/Thr and Tyr protein phosphorylation in Mycobacterium tuberculosis (Mtb). Ser/Thr protein kinases (STPKs) appear to regulate diverse processes including cell division and molecular transport. Proposed protein substrates of the STPKs include putative regulatory proteins, as well as six proteins containing Forkhead-associated domains. Structures of domains of receptor STPKs and all three Mtb Ser/Thr or Tyr phosphatases afford an initial description of the principal modules that mediate bacterial STPK signaling. These studies revealed that universal mechanisms of regulation and substrate recognition govern the functions of prokaryotic and eukaryotic STPKs. Several structures also support novel mechanisms of regulation, including dimerization of STPKs, metal-ion binding to PstP and substrate mimicry in PtpB.