Miracle-dz/UniFAR-FTUs huggingface dataset:
Endovascular Treatment versus Best Medical Treatment in Patients with Acute Ischemic Stroke: A Meta-Analysis of Randomized Controlled Trials

BACKGROUND AND PURPOSE: Endovascular treatment has emerged as a minimally invasive technique for patients with acute ischemic stroke to achieve recanalization. Our aim was to determine the effects of endovascular treatment on clinical and safety outcomes compared with best medical treatment. MATERIALS AND METHODS: Fifteen randomized trials that compared endovascular treatment with best medical treatment in patients with acute ischemic stroke met the inclusion criteria. We calculated pooled odds ratios and 95% CIs by using random-effects models. The primary end point was a favorable outcome defined by a modified Rankin Scale score of 0 (no symptoms), 1 (no significant disability), or 2 (slight disability) at 90 days postrandomization. RESULTS: Of the 2980 subjects randomized, the proportion of subjects who achieved a favorable outcome was significantly greater among those randomized to endovascular treatment compared with best medical treatment (2949 subjects analyzed; odds ratio, 1.82; 95% CI, 1.38–2.40; P < .001). Excellent outcome (modified Rankin Scale score of 0 or 1) was also significantly greater among those randomized to endovascular treatment (2791 subjects analyzed; odds ratio, 1.77; 95% CI, 1.29–2.43, P < .001). Risk of symptomatic intracranial hemorrhage was similar between endovascular treatment and best medical treatment (2906 subjects analyzed; odds ratio, 1.19; 95% CI, 0.84–1.68; P = .34). CONCLUSIONS: Compared with best medical treatment, the odds of achieving a favorable outcome or excellent outcome at 3 months postrandomization are approximately 80% higher with endovascular treatment among patients with acute ischemic stroke.
Dichotomy between factors inducing the immunosuppressive enzyme IL‐4‐induced gene 1 (IL4I1) in B lymphocytes and mononuclear phagocytes

MΦ and DC are key elements in the control of tissue homeostasis and response to insult. In this work, we demonstrate that MΦ and DC are the major producers of the phenylalanine catabolizing enzyme IL‐4‐induced gene 1 (IL4I1) under inflammatory conditions. IL4I1 was first described in B cells, which indeed can produce IL4I1 in vitro, although at much lower levels. In vivo, IL4I1 is highly expressed by MΦ and DC of Th1 granulomas (sarcoidosis, tuberculosis) but poorly detected in Th2 granulomas (schistosomiasis). In vitro, expression of the enzyme is induced in mononuclear phagocytes by various pro‐inflammatory stimuli through the activation of the transcription factors NF‐κB and/or STAT1. B cells also express IL4I1 in response to NF‐κB‐activating stimuli such as CD40L; however, in contrast to myeloid cells, B cells are insensitive to IFN‐γ but respond to stimulation of the IL‐4/STAT6 axis. As we show that the expression of IL4I1 by a monocytic cell line inhibits T‐cell proliferation and production of IFN‐γ and inflammatory cytokines, we propose that IL4I1 participates in the downregulation of Th1 inflammation in vivo.
All Competition Is Not Alike: Neural Mechanisms for Resolving Underdetermined and Prepotent Competition

People must constantly select among potential thoughts and actions in the face of competition from (a) multiple task-relevant options (underdetermined competition) and (b) strongly dominant options that are not appropriate in the current context (prepotent competition). These types of competition are ubiquitous during language production. In this work, we investigate the neural mechanisms that allow individuals to effectively manage these cognitive control demands and to quickly choose words with few errors. Using fMRI, we directly contrast underdetermined and prepotent competition within the same task (verb generation) for the first time, allowing localization of the neural substrates supporting the resolution of these two types of competition. Using a neural network model, we investigate the possible mechanisms by which these brain regions support selection. Together, our findings demonstrate that all competition is not alike: resolving prepotent competition and resolving underdetermined competition rely on partly dissociable neural substrates and mechanisms. Specifically, activation of left ventrolateral pFC is specific to resolving underdetermined competition between multiple appropriate responses, most likely via competitive lateral inhibition. In contrast, activation of left dorsolateral pFC is sensitive to both underdetermined competition and prepotent competition from response options that are inappropriate in the current context. This region likely provides top–down support for task-relevant responses, which enables them to out-compete prepotent responses in the selection process that occurs in left ventrolateral pFC.
Modification of penicillin-binding protein 5 associated with high-level ampicillin resistance in Enterococcus faecium

High-level ampicillin resistance in Enterococcus faecium has been shown to be associated with the synthesis of a modified penicillin-binding protein 5 (PBP 5) which had apparently lost its penicillin-binding capability (R. Fontana, M. Aldegheri, M. Ligozzi, H. Lopez, A. Sucari, and G. Satta. Antimicrob. Agents Chemother. 38:1980-1983, 1994). The pbp5 gene of the highly resistant strain E. faecium 9439 was cloned and sequenced. The deduced amino acid sequence showed 77 and 54% homologies with the PBPs 5 of Enterococcus hirae and Enterococcus faecalis, respectively. A gene fragment coding for the C-terminal part of PBP 5 containing the penicillin-binding domain was also cloned from several E. faecium strains with different levels of ampicillin resistance. Sequence comparison revealed a few point mutations, some of which resulted in amino acid substitutions between SDN and KTG motifs in PBPs 5 of highly resistant strains. One of these converted a polar residue (the T residue at position 562 or 574) of PBP 5 produced by susceptible and moderately resistant strains into a nonpolar one (A or I). This alteration could be responsible for the altered phenotype of PBP 5 in highly resistant strains.
Thrombus versus Wall Biological Activities in Experimental Aortic Aneurysms

Background/Aim: The intraluminal thrombus (ILT) is considered to participate in abdominal aortic aneurysm (AAA) evolution. To assess whether this role proceeds via ILT influence on biological activity of the AAA wall, we studied the relationships between the levels of some relevant proteases and microparticles (MP) released by ILT versus wall in rat experimental AAAs. Methods and Results: Two weeks after elastase perfusion, ILT and AAA wall were incubated in cell culture medium and studies were performed on conditioned media. As shown by gelatin zymography, ILT released higher amounts of MMP9 than the wall, whereas the level of MMP2 activation (active/pro) was similar. Levels of elastase and urokinase plasminogen activator, plasmin and MPs, determined, respectively, by casein zymography, substrate hydrolysis and flow cytometry, were higher in ILT than in wall. Aneurysm diameter positively correlated with wall MMP9 levels, MMP2 activation, plasmin activity and MP release. Moreover, wall and ILT levels of pro- and active forms of MMP2, elastase and plasmin were positively correlated. Wall levels of MMP2 activation and plasmin activity also correlated with ILT weight. Conclusion: The present data suggest that, in this experimental model, ILT may contribute to AAA evolution via its influence on the level of aneurysmal wall protease activity.
Asking territories: the constituency orientation of Italian and French members of the European Parliament

In this article, we explore how electoral systems influence attitudes and behavior of elected representatives. Focusing on constituency representation, we consider how variation in electoral systems may shape forms of political representation. An analysis of written parliamentary questions (PQs) is an important instrument to look at the role of parliamentarians even where, as in the European Parliament, political parties enforce discipline in roll-call voting. This kind of investigation offers the opportunity to partially resolve empirical and theoretical problems related to other methods of research. Unlike voting and speeches, PQs face fewer constrains from party leaders. This article analyses the constituency focus of members of European Parliament from France and Italy. These countries differ with regard to two main dimensions of electoral systems: ballot structure and district magnitude. The study is conducted through a content analysis of 5343 written PQs during the sixth term (2004–09). The results suggest that, despite the lack of strong electoral connection, electoral institutions shape the legislative behavior of the Italian and French parliamentarians providing incentives to cultivate personal reputation and constituency-orientation.
Overhead Bryant’s Traction Does Not Improve the Success of Closed Reduction or Limit AVN in Developmental Dysplasia of the Hip

Background: Preoperative Bryant’s overhead traction before closed reduction (CR) in developmental dysplasia of the hip (DDH) remains controversial and its success in increasing CR rates and reducing avascular necrosis (AVN) rates has not been specifically reported in a large cohort. Methods: IRB-approved retrospective study of patients (below 3 y)who were treated with attempted CR for idiopathic DDH from 1980 to 2009. Successful CR was defined as a hip that remained reduced and did not require repeat CR or open reduction. Patients were grouped by age, hip instability [Ortolani positive (reducible) vs. fixed dislocation], and Tonnis classification and rates of successful CR were compared between groups with P<0.05. Results: A total of 342 hips were included with a mean age of 0.9 years (0.2 to 2.8 y) and a mean follow-up of 10.4 years (2.0 to 27.7 y). There were 269 hips with fixed dislocations and 73 Ortolani-positive hips. Traction was used in 276 hips. There was no difference in traction utilization in the 3 age groups (below 1, below 1.5, and below 2 y) for either Ortolani-positive hips (P=0.947) or fixed dislocations (P=0.943). There was no difference in achieving a successful CR comparing traction (60.9%) and no-traction groups (60.6%) (P=1.00). For Ortolani-positive hips, traction did not improve the incidence of a successful CR for any age group: below 1 year: P=0.19; below 1.5 years: P=0.23; and below 2 years: P=0.25. Similarly, fixed dislocation patients had no benefit from traction: below 1 year: P=0.76; below 1.5 years: P=0.82; and below 2 years: P=0.85. Tonnis classification did predict success of CR but had no influence on traction success. There was no difference in the rate of AVN between the traction (18%) and no-traction (8%) groups for all patients (P=0.15). Conclusions: In this retrospective series, preoperative Bryant’s traction does not improve the rate of a successful CR for patients with DDH and has no protective effect on the development of AVN of the femoral head. These results suggest that Bryant’s overhead traction may not be warranted for patients below 3 years of age with DDH. Level of Evidence: Level III.
Switching patients with lamivudine resistant chronic hepatitis B virus from tenofovir to adefovir results in less potent HBV‐DNA suppression

Summary. The nucleotide analogues, tenofovir disoproxil fumarate and adefovir dipivoxil, inhibit viral replication and are both effective against the hepatitis B virus (HBV). In our department, tenofovir was prescribed in addition to lamivudine for the treatment of lamivudine resistant chronic hepatitis B. After registration of adefovir, 10 patients were switched to adefovir monotherapy. We studied changes in HBV‐DNA and alanine aminotransferase (ALT) in these patients. The median treatment duration with tenofovir was 78 weeks resulting in a median viral load reduction of 5.4 (range 6.8–2.3) log10 copies/mL compared to baseline (P = 0.005). Two patients had an increase >1 log10 copies/mL during tenofovir treatment. After the switch to adefovir, six out of 10 patients had an HBV‐DNA >4 log10 copies/mL and the median HBV‐DNA increased from 2.8 to 4.5 log10 copies/mL (P = 0.017). The factors associated with relapse were HBV‐DNA PCR positivity at the time of switch and genotype B or D. ALT levels at the beginning of tenofovir treatment also might be a factor. Retreatment with tenofovir (n = 3) resulted in a rapid decline in HBV‐DNA. Tenofovir is a potent antiviral drug. Switching to adefovir resulted in viral relapse in 60% of patients and retreatment with tenofovir resulted again in viral decline, which suggests that tenofovir is a more potent antiviral agent.
Correlates of Job Satisfaction and Their Implications for Work Redesign: A Focus on the Australian Telecommunications Industry

The relative impacts of demography, job/task characteristics; structural aspects; computerization; and perceived work-group performance on job satisfaction were examined, using data from 1300 employees from the Australian telecommunications industry. In support of previous research, the results revealed that job satisfaction was strongly influenced by the extent of task variety and the degree of participation in decisions. The results also indicated that satisfaction increases when greater certainty about future directions/outcomes of the organization is experienced and when job incumbents perceive positive work-group performance. Further analysis divulged significant differences between managerial and non-managerial employees in this regard. The differences illuminated some of the contemporary issues and challenges that organizations engaged in work redesign endeavours may need to address. These issues and challenges are highlighted and discussed.
MicroRNAs in early diabetic retinopathy in streptozotocin-induced diabetic rats.

PURPOSE Diabetic retinopathy (DR) is one of the leading causes of blindness. However, the roles of microRNAs (miRNAs) in DR are still unknown. The aims of this study were to identify miRNAs involved in early DR and to characterize their roles in the pathogenesis of DR. METHODS miRNA-expression profiling was performed in the retina and retinal endothelial cells (RECs) of streptozotocin (STZ)-induced diabetic rats 3 months after the onset of diabetes and miRNAs differentially expressed in diabetic rats were identified and compared with controls. Subsequently, functional annotation analysis was conducted to identify miRNA signatures of pathologic pathways of DR. In addition, in vitro functional assays were used to dissect interactions of miR-146 and NF-κB activation in a conditionally immortalized retinal capillary endothelial cell line, Tr-iBRB. RESULTS Approximately 350 and 220 miRNAs were detected in the retinas and RECs, respectively, in both control and diabetic rats. At least 86 and 120 miRNAs were differentially expressed (P < 0.01) in the retinas and RECs of diabetic rats and controls, respectively. Upregulation of NF-κB-, VEGF-, and p53-responsive miRNAs constituted key miRNA signatures, reflecting ongoing pathologic changes of early DR. In addition, it was demonstrated that the negative feedback regulation of miR-146 on NF-κB activation may function in Tr-iBRB endothelial cells, suggesting that miR-146 is a potential therapeutic target for the treatment of DR through its inhibition on NF-κB activation in RECs. CONCLUSIONS miRNAs are involved in the pathogenesis of DR through the modulation of multiple pathogenetic pathways and may be novel therapeutic targets for the treatment of DR.
Unique potential of 4-1BB agonist antibody to promote durable regression of HPV+ tumors when combined with an E6/E7 peptide vaccine

Significance Nearly all cervical, anal, vulvar, and penile cancer and up to half of oropharyngeal cancers are driven by the E6 and E7 oncoproteins of human papilloma virus (HPV). Therapeutic vaccination against these HPV proteins can slow disease progression in animal models and in patients, but is rarely curative. We demonstrate that coadministration of agonist antibodies targeting the T-cell costimulatory receptor 4-1BB and an intranasal HPV E6/E7 peptide vaccine promoted durable regression in 100% of animals bearing HPV+ TC-1 tumors established in the female reproductive tract. The efficacy of 4-1BB in this system was unique among immune checkpoint antibodies and provides a paradigm for enhancement of therapeutic cancer vaccines with costimulatory agonist antibodies. Antibody modulation of T-cell coinhibitory (e.g., CTLA-4) or costimulatory (e.g., 4-1BB) receptors promotes clinical responses to a variety of cancers. Therapeutic cancer vaccination, in contrast, has produced limited clinical benefit and no curative therapies. The E6 and E7 oncoproteins of human papilloma virus (HPV) drive the majority of genital cancers, and many oropharyngeal tumors. We discovered 15–19 amino acid peptides from HPV-16 E6/E7 for which induction of T-cell immunity correlates with disease-free survival in patients treated for high-grade cervical neoplasia. We report here that intranasal vaccination with these peptides and the adjuvant alpha-galactosylceramide elicits systemic and mucosal T-cell responses leading to reduced HPV+ TC-1 tumor growth and prolonged survival in mice. We hypothesized that the inability of these T cells to fully reject established tumors resulted from suppression in the tumor microenvironment which could be ameliorated through checkpoint modulation. Combining this E6/E7 peptide vaccine with checkpoint blockade produced only modest benefit; however, coadministration with a 4-1BB agonist antibody promoted durable regression of established genital TC-1 tumors. Relative to other therapies tested, this combination of vaccine and α4-1BB promoted the highest CD8+ versus regulatory FoxP3+ T-cell ratios, elicited 2- to 5-fold higher infiltration by E7-specific CTL, and evoked higher densities of highly cytotoxic TcEO (T cytotoxic Eomesodermin) CD8 (>70-fold) and ThEO (T helper Eomesodermin) CD4 (>17-fold) T cells. These findings have immediate clinical relevance both in terms of the direct clinical utility of the vaccine studied and in illustrating the potential of 4-1BB antibody to convert therapeutic E6/E7 vaccines already in clinical trials into curative therapies.
Automated generation of diverse and challenging scenarios for test and evaluation of autonomous vehicles

We propose a novel method for generating test scenarios for a black box autonomous system that demonstrate critical transitions in its performance modes. In complex environments it is possible for an autonomous system to fail at its assigned mission even if it complies with requirements for all subsystems and throws no faults. This is particularly true when the autonomous system may have to choose between multiple exclusive objectives. The standard approach of testing robustness through fault detection is directly stimulating the system and detecting violations of the system requirements. Our approach differs by instead running the autonomous system through full missions in a simulated environment and measuring performance based on high-level mission criteria. The result is a method of searching for challenging scenarios for an autonomous system under test that exercise a variety of performance modes. We utilize adaptive sampling to intelligently search the state space for test scenarios which exist on the boundary between distinct performance modes. Additionally, using unsupervised clustering techniques we can group scenarios by their performance modes and sort them by those which are most effective at diagnosing changes in the autonomous system's behavior.
Absence of detectable measles virus genome sequence in inflammatory bowel disease tissues and peripheral blood lymphocytes

A highly sensitive measles‐specific RT‐PCR‐nested PCR system was established, which consistently amplified measles virus genome sequence from control samples containing as little as 5.5 × 10−3 pfu per reaction. This method failed to detect the presence of measles virus in 93 colonoscopic biopsies and 31 peripheral blood lymphocyte preparations, examined and obtained from patients with inflammatory bowel disease (IBD) and noninflammatory controls. All patients had detectable levels of serum neutralization antibody against measles virus. Each biopsy was estimated to have about one million cells, based on the amplification of the beta actin gene. The assay was calibrated by use of a known number of lymphocytes. The method applied was able to amplify measles virus RNA from a nucleic acid mixture equivalent to 18 cells derived from subacute sclerosing panencephalitis (SSPE) brain material. The level of measles RNA present, if any, in the biopsies is therefore at least 50,000‐fold less than in SSPE. J. Med. Virol. 55:243–249, 1998. © 1998 Wiley‐Liss, Inc.
First Symptoms – Frontotemporal Dementia versus Alzheimer’s Disease

Frontotemporal dementia (FTD) is often misdiagnosed as Alzheimer’s disease (AD). We hypothesized that the first symptoms associated with FTD would be different from those seen in AD and that the first symptoms in FTD would reflect loss of function in the frontal region with the greatest degree of degeneration. The objective of the study was to compare the earliest symptoms in patients with FTD and AD, and to delineate the symptoms that were associated with right, left or bilateral frontotemporal degeneration in FTD. The first symptoms in 52 FTD and 101 AD patients were determined in retrospect. Based on functional imaging studies, the FTD patients were divided into those with predominantly bilateral (n = 15), left-sided (n = 19) and right-sided (n = 18) patterns of atrophy. The results showed that disinhibition, social awkwardness, passivity and loss of executive function were more common in FTD, while memory loss was more common in AD. Disinhibition was greatest in the asymmetric right-sided group, language dysfunction was commonest in the asymmetric left-sided group and loss of executive function was most frequent in the bilateral group. In summary, different first symptoms appeared in FTD and AD, which may help distinguish between the diseases. The anatomic site for FTD largely determined the kind of first symptoms.
Morphological and functional effects of altered cysteine string protein at the Drosophila larval neuromuscular junction

The synaptic vesicle‐associated cysteine string protein (CSP) is critical for neurotransmitter release at the neuromuscular junction (NMJ) of Drosophila, where the ∼4% of mutant flies lacking CSP that survive to adulthood exhibit spastic jumping and shaking, temperature‐sensitive paralysis, and premature death. Previously, it has been shown that CSP is also required for nerve terminal growth and the prevention of neurodegeneration in Drosophila and mice. At larval csp null mutant NMJs of Drosophila, intracellular recordings from the muscle showed that evoked release is significantly reduced at room temperature. However, it remained unclear whether the reduction in evoked release might be due to a loss of synaptic boutons, loss of synapses, and alterations in trafficking of vesicles to synapses. To resolve these issues, we have examined synaptic structure and function of csp null mutant NMJs at the level of single boutons. csp null mutations proportionally reduce the number of synaptic boutons of both motor neurons (1s and 1b) innervating larval muscles 6 and 7, while the number of synapses per bouton remains normal. However, focal recordings from individual synaptic boutons show that nerve‐evoked neurotransmitter release is also impaired in both 1s and 1b boutons. Further, our ultrastructural analyses show that the reduction in evoked release at low stimulation frequencies is not due to a loss of synapses or to alterations in docked vesicles at synapses. Together, these data suggest that CSP promotes synaptic growth and evoked neurotransmitter release by mechanistically independent signaling pathways. Synapse 61:1–16, 2007. © 2006 Wiley‐Liss, Inc.