Miracle-dz/UniFAR-FTUs huggingface dataset:
CGX1037 is a novel PKC isoform delta selective inhibitor in platelets

Abstract Platelets upon activation change their shape, aggregate and secrete alpha and dense granule contents among which ADP acts as a feedback activator. Different Protein Kinase C (PKC) isoforms have specific non-redundant roles in mediating platelet responses including secretion and thrombus formation. Murine platelets lacking specific PKC isoforms have been used to evaluate the isoform specific functions. Novel PKC isoform δ has been shown to play an important role in some pathological processes. Lack of specific inhibitors for PKCδ has restricted analysis of its role in various cells. The current study was carried out to evaluate a novel small molecule PKCδ inhibitor, CGX1037 in platelets. Platelet aggregation, dense granule secretion and western blotting experiments were performed to evaluate CGX1037. In human platelets, CGX1037 inhibited PAR4-mediated phosphorylation on PKD2, a PKCδ-specific substrate. Pre-treatment of human or murine platelets with CGX1037 inhibited PAR4-mediated dense granule secretion whereas it potentiated GPVI-mediated dense granule secretion similar to the responses observed in murine platelets lacking PKCδ· Furthermore, pre-treatment of platelets from PKCδ−/− mice with CGX1037 had no significant additive effect on platelet responses suggesting the specificity of CGX1037. Hence, we show that CGX1037 is a selective small molecule inhibitor of PKCδ in platelets.
Methylenedioxymethamphetamine (MDMA, ‘Ecstasy’): a stressor on the immune system

Drug abuse is a global problem of considerable concern to health. One such health concern stems from the fact that many drugs of abuse have immunosuppressive actions and consequently have the potential to increase susceptibility to infectious disease. This article is focused on the impact of the amphetamine derivative, methylenedioxymethamphetamine (MDMA; ‘Ecstasy’) on immunity. Research conducted over the last 5 years, in both laboratory animals and humans, has demonstrated that MDMA has immunosuppressive actions. Specifically, MDMA suppresses neutrophil phagocytosis, suppresses production of the pro‐inflammatory cytokines tumour necrosis factor‐α (TNF‐α) and interleukin (IL)‐1β, and increases production of the endogenous immunosuppressive cytokine (IL‐10), thereby promoting an immunosuppressive cytokine phenotype. MDMA also suppresses circulating lymphocyte numbers, with CD4+ T cells being particularly affected, and alters T‐cell function as indicated by reduced mitogen‐stimulated T‐cell proliferation, and a skewing of T‐cell cytokine production in a T helper 2 (Th2) direction. For the most part, the aforementioned effects of MDMA are not the result of a direct action of the drug on immune cells, but rather caused by the release of endogenous immunomodulatory substances. Consequently, the physiological mechanisms that are thought to underlie the immunosuppressive effects of MDMA will be discussed. As many of the physiological changes elicited by MDMA closely resemble those induced by acute stress, it is suggested that exposure to MDMA could be regarded as a ‘chemical stressor’ on the immune system. Finally, the potential of MDMA‐induced immunosuppression to translate into significant health risks for abusers of the drug will be discussed.
Childhood predictors of adult medically unexplained hospitalisations

Background It has been suggested that adults with medically unexplained physical symptoms experienced greater ill-health then others (either in themselves or their families) during childhood. Aims To test these hypotheses. Method We used data from the Medical Research Council (MRC) National Survey of Health and Development, a population-based cohort study established in 1946 (n=5362). Subjects were followed from birth in 1946 until 1989 (age 43 years). As outcome, we used operationally defined medically unexplained hospital admissions at age 15–43 years. Exposure variables included childhood illness, and illness in parents during the childhood of the subjects. Results The risk set (n=4603) comprised individuals still in the Survey at age 15. Ninety-five unexplained hospital admissions were identified. Subjects whose mothers reported below-average health in the father were at increased risk of subsequent unexplained admissions. Below average reported health in the mother was not associated with this increased risk. Defined physical diseases in childhood were not associated, but persistent abdominal pain at age 7–15 years was. Conclusions Unexplained hospital admissions are associated with certain childhood experiences of illness, but defined physical illness in childhood is not a risk factor.
Does the identification of simple features require serial processing?

Several recent studies have shown performance decrements with increasing display size when background texture elements are present in a same-different feature discrimination task--a result that challenges the traditional notion that the identities of simple visual features are processed in parallel, preattentively. Four experiments are reported that explore the implications of these results. Experiment 1 replicates the recent studies but limits the generalizability of the results to small target numbers. Experiments 2 and 3 show that the observed performance decrements are not due to a serial or even limited-capacity, parallel process. Experiment 4 suggests that decision factors idiosyncratic to the use of texture elements in a same-different task are responsible for the effect. It is concluded that the identification of simple visual features proceeds in parallel, with unlimited capacity (i.e., preattentively).
Endovascular and surgical treatment of unruptured cerebral aneurysms: Comparison of risks

Unruptured cerebral aneurysms are commonly treated by surgical clipping, but endovascular coil embolization is increasingly employed as an alternative. In a blinded review of unruptured aneurysms treated at our institution since 1990, we identified patients whose aneurysms were judged to be treatable by both neurosurgeons and neurointerventional radiologists. A change in Rankin Scale score of 2 or more from hospital admission to discharge, indicating a new moderate disability or worse, was predefined as the primary outcome measure. Long‐term follow‐up was obtained by mailed questionnaire and telephone interview. Length of stay and hospital charges were totaled for all hospitalizations, including follow‐up. Sixty‐eight patients treated surgically and 62 patients treated with endovascular coil embolization were considered candidates for either procedure on blinded review, and overall anticipated procedure risk was rated as identical. A larger proportion of patients in the surgical group developed a change in Rankin Scale score of 2 or more (25% of surgical patients vs 8% of endovascular patients). Total length of stay was longer (mean days: 7.7 for surgical patients vs 5.0 for endovascular patients) and hospital charges were greater (mean, $38,000 for surgical patients vs $33,400 for endovascular patients) for the surgical patients. At follow‐up, an average of 3.9 years after the procedure, surgical patients were more likely to report persistent new symptoms or disability since treatment (34% of surgical patients vs 8% of endovascular patients) and a longer period for recovery to normal (50% returning to normal in 1 year for surgery and in 27 days for coil embolization). Coil embolization of unruptured cerebral aneurysms seems to be associated with significantly fewer complications than surgical clipping. More long‐term data on aneurysm rupture rates are required to confirm efficacy. Ann Neurol 2000;48:11–19
A perceived reliability-based customer satisfaction model in self-service technology

ABSTRACT Technical reliability of self-service technologies (SSTs) has been found to be a strong determinant of satisfaction with tech-enabled services. Yet, the interpretation of the factors affecting reliability and its subsequent influences on customer satisfaction (CS) with SSTs is inadequate. The purpose of this investigation has, therefore, been to demarcate a model to fulfill the gap with an empirical examination, and accordingly a model was developed and tested by applying a global structural equation model. The model results of banking SST users specify how the reliability of SSTs is perceived by the users. The findings have reported that the best predictor of perceived reliability (PRe) is perceived security followed by perceived control. Surprisingly, no significant impact of perceived ease of use was found on PRe. The research also attempted to shed light on the influence of PRe on perceived risk, technology trust, and CS in the light of technology-enabled self-service.
Radiographic resolution of community-acquired pneumonia.

Clinicians are frequently faced with patients in whom the radiographic resolution of community-acquired pneumonia seems delayed. Previous studies of radiographic resolution of the disease have yielded conflicting results. We prospectively assessed the radiographic resolution of pneumonia in 81 non-immuno-compromised patients, presenting to the emergency room and ambulatory clinics of a large university hospital, who met clinical and radiographic criteria for pneumonia. Serial chest radiographs were obtained every 2 wk for an initial period of 8 wk, and then every 4 wk until 24 wk had passed, or until all radiographic abnormalities had cleared. Forty-one of the 81 patients (50.6%) demonstrated complete clearance after 2 wk. Fifty of the 75 patients (66.7%) followed to 4 wk demonstrated complete clearance. The rate of clearance was inversely correlated with age (p < 0.001) and involvement of single versus multiple lobes (p < 0.0001) (log-rank test). Clearance was faster in those patients treated as outpatients (3.8 wk versus 9.1 wk, p = 0.03) and in patients who were nonsmokers (4.5 wk versus 8.4 wk, p = 0.05) (log-rank test). Multivariate regression analysis demonstrated that only age (relative risk for clearance, +0.79 per decade) and single versus multiple lobes involved (relative risk for clearance, 0.55 for more than one lobe) had independent predictive value (Cox proportional hazards regression model). The radiographic resolution of pneumonia occurs more rapidly in younger patients and in those with only a single lobe involved. (ABSTRACT TRUNCATED AT 250 WORDS)
An efficient particle filter-based potential game method for distributed sensor network management

This paper addresses information-based sensor selection that determines a set of measurement points maximizing the mutual information between the measurements and the target states. The problem is formulated as a potential game in which each player computes a local utility function defined by the conditional mutual information. A new approximation method is proposed for computing the conditional mutual information when the target states are represented using a particle filter to handle a non-linear system with non-Gaussian noise. This method approximates the conditional entropy of an agent conditioned on other agents sensing decision by sampling the other agents measurements from a particle filter. This computational method makes it possible to apply the potential game approach to non-linear/non-Gaussian problems with a large number of the measurements. We performed simulations for localization and tracking of a target with mobile/deployed sensor networks.
Clinical impact of negative‐pressure wound therapy: A 1,126‐patient observational prospective study

Negative‐pressure wound therapy (NPWT) was developed in the early 1990s and reported in 1997 by Argenta and Morykwas. Ignored at first, this technique progressively came to be considered as an outstanding advancement in reconstructive surgery. Several randomized controlled studies produced evidence for the effect of NPWT on promotion of granulation tissue formation and prevention of tissue damage and amputation. However, no important longitudinal study has yet produced clinical and economic data on the consequences of integrating NPWT into practice in multiple institutions.
Effect of time since exposure to Chlamydia trachomatis on chlamydia antibody detection in women: a cross-sectional study

Objectives To investigate what factors influence the detection of Chlamydia trachomatis antibody following genital tract infection. Methods One hundred and sixty-four women with a previous history of C trachomatis infection contributed to an earlier report on the performance of chlamydia antibody ELISA assays. We undertook further analysis to explore how chlamydia antibody assay sensitivity changes with time since infection. Results Chlamydia antibody was detected in more women soon after the last detection of chlamydia at the lower genital tract than at later times. This holds true for all tests, but the Anilabsystems IgG EIA, Medac pELISA plus ELISA and the Savyon SeroCT-IgG ELISA were less sensitive than the pgp3 ELISA and the Anilabsystems microimmunofluorescence (MIF) assay at all time points except during current infection. Fall in seropositivity in women generally occurred in the early weeks and months following the last episode of chlamydia infection. There was no clear pattern of further reduction in seropositivity after 6 months. Multiple previous episodes were associated with increased seropositivity in the pgp3 assay (two or more vs one, OR 19, p<0.001) and other tests, but the effect was significantly smaller for the Anilabs, Medac and SeroCT MOMP peptide ELISAs, but not for the MIF assay. Conclusions Chlamydia antibody detection decreases with time since infection and this is most apparent in the first 6 months. In women who have had more than one infection, antibody remained detectable longer for all tests, but this was more marked for the pgp3 ELISA and MIF assay.
Clinical outcomes after stereotactic radiosurgery for idiopathic trigeminal neuralgia.

OBJECT Stereotactic radiosurgery is an increasingly used and the least invasive surgical option for patients with trigeminal neuralgia. In this study, the authors investigate the clinical outcomes in patients treated with this procedure. METHODS Independently acquired data from 220 patients with idiopathic trigeminal neuralgia who underwent gamma knife radiosurgery were reviewed. The median age was 70 years (range 26-92 years). Most patients had typical features of trigeminal neuralgia, although 16 (7.3%) described additional atypical features. One hundred thirty-five patients (61.4%) had previously undergone surgery and 80 (36.4%) had some degree of sensory disturbance related to the earlier surgery. Patients were followed for a maximum of 6.5 years (median 2 years). Complete or partial relief was achieved in 85.6% of patients at 1 year. Complete pain relief was achieved in 64.9% of patients at 6 months, 70.3% at 1 year, and 75.4% at 33 months. Patients with an atypical pain component had a lower rate of pain relief (p = 0.025). Because of recurrences, only 55.8% of patients had complete or partial pain relief at 5 years. The absence of preoperative sensory disturbance (p = 0.02) or previous surgery (p = 0.01) correlated with an increased proportion of patients who experienced complete or partial pain relief over time. Thirty patients (13.6%) reported pain recurrence 2 to 58 months after initial relief (median 15.4 months). Only 17 patients (10.2% at 2 years) developed new or increased subjective facial paresthesia or numbness, including one who developed deafferentation pain. CONCLUSIONS Radiosurgery for idiopathic trigeminal neuralgia was safe and effective, and it provided benefit to a patient population with a high frequency of prior surgical intervention.
The effect of casting combined with stretching on passive ankle dorsiflexion in adults with traumatic head injuries.

BACKGROUND AND PURPOSE Ankle plantar-flexion contractures are a common problem following traumatic head injury. Although serial casting is used to correct and prevent ankle plantar-flexion contractures, treatment efficacy has not been evaluated using an experimental design. The aim of this research was to establish the effect of a regimen of casting combined with stretching on passive ankle dorsiflexion motion. SUBJECTS Nine people who had sustained traumatic closed head injuries and had limited dorsiflexion motion participated in the study. METHODS A crossover design was used in the study. Subjects were assigned to both experimental and control groups. Torque-controlled measurements of passive ankle dorsiflexion motion were obtained for all subjects before and after 1 week of casting combined with stretching, as well as before and after a 1-week control period. The order of the experimental and control conditions was randomized. RESULTS Passive ankle dorsiflexion increased by a mean of 13.5 degrees (SD = 9.3) during the experimental condition, as compared with a mean decrease of 1.9 degrees (SD = 10.2) during the control condition. The difference between the experimental and control conditions was statistically significant. CONCLUSION AND DISCUSSION These findings suggest that casting combined with stretching is an effective method of correcting ankle plantar-flexion contractures in patients with traumatic head injuries.
A Complex Comprising Phosphatidylinositol 4-Kinase IIIβ, ACBD3, and Aichi Virus Proteins Enhances Phosphatidylinositol 4-Phosphate Synthesis and Is Critical for Formation of the Viral Replication Complex

ABSTRACT Phosphatidylinositol 4-kinase IIIβ (PI4KB) is a host factor required for the replication of certain picornavirus genomes. We previously showed that nonstructural proteins 2B, 2BC, 2C, 3A, and 3AB of Aichi virus (AiV), a picornavirus, interact with the Golgi protein, acyl-coenzyme A binding domain containing 3 (ACBD3), which interacts with PI4KB. These five viral proteins, ACBD3, PI4KB, and the PI4KB product phosphatidylinositol 4-phosphate (PI4P) colocalize to the AiV RNA replication sites (J. Sasaki et al., EMBO J. 31:754–766, 2012). We here examined the roles of these viral and cellular molecules in the formation of AiV replication complexes. Immunofluorescence microscopy revealed that treatment of AiV polyprotein-expressing cells with a small interfering RNA targeting ACBD3 abolished colocalization of the viral 2B, 2C, and 3A proteins with PI4KB. A PI4KB-specific inhibitor also prevented their colocalization. Virus RNA replication increased the level of cellular PI4P without affecting that of PI4KB, and individual expression of 2B, 2BC, 2C, 3A, or 3AB stimulated PI4P generation. These results suggest that the viral protein/ACBD3/PI4KB complex plays an important role in forming the functional replication complex by enhancing PI4P synthesis. Of the viral proteins, 3A and 3AB were shown to stimulate the in vitro kinase activity of PI4KB through forming a 3A or 3AB/ACBD3/PI4KB complex, whereas the ACBD3-mediated PI4KB activation by 2B and 2C remains to be demonstrated. IMPORTANCE The phosphatidylinositol 4-kinase PI4KB is a host factor required for the replication of certain picornavirus genomes. Aichi virus, a picornavirus belonging to the genus Kobuvirus, forms a complex comprising one of the viral nonstructural proteins 2B, 2BC, 2C, 3A, and 3AB, the Golgi protein ACBD3, and PI4KB to synthesize PI4P at the sites for viral RNA replication. However, the roles of this protein complex in forming the replication complex are unknown. This study showed that virus RNA replication and individual viral proteins enhance the level of cellular PI4P, and suggested that the viral protein/ACBD3/PI4KB complex plays an important role in forming a functional replication complex. Thus, the present study provides a new example of modulation of cellular lipid metabolism by viruses to support the replication of their genomes.
Effect of vehicle characteristics on safety, fuel use and emissions

During the last years, the number of fatalities per million inhabitants in Portugal has always been higher than the average in the European Union. Therefore, at national level, there is a need for a more effective understanding of crash data and vehicles effects on crash severity. This research examined the effects of vehicle characteristics on severity risk, fuel use and emissions. The main goal of this research was to develop models for crash severity prediction in single vehicle-crashes and two-vehicle collisions. Furthermore, this research aimed at developing an integrated analysis to evaluate vehicle’s safety, fuel efficiency and emission performances. Crash data were collected from the Portuguese Police Republican National Guard records for the Porto metropolitan area, for the period 2006-2010. A total of 1,374 crashes were collected, 500 singlevehicle crashes and 874 two-vehicle collisions. For the safety analysis, logistic regressions were used. For single-vehicle crashes, the effect of vehicle characteristics to predict the probability of a serious injury and/or killed in vehicle occupants (designed as binary target) was explored. For two-vehicle collisions, additional binary targets were designed: one target to predict the probability of a serious injury and/or killed in vehicle V1) and another target to predict the probability of a serious injury and/or killed in vehicle V2). To overcome the challenge imposed by sample size and high imbalanced data (only 5.1% were severe crashes), research methodology was developed based on a resampling strategy and 10 stratified random samples were used for validation. During the modeling stage, the effect of vehicle characteristics, such as weight, engine size, wheelbase and age of vehicle were analyzed. For the vehicle’s fuel efficiency and emissions analysis, pollutants were estimated using CORINAIR methodology. Following, emissions data were fit into linear regression models. Finally, an integrated analysis indicator (entitled “SEG”) that provides rating classification for the evaluation of vehicle’s safety, fuel efficiency and emission performances, was developed. Regarding these results, for single-vehicle crashes, injury severity prediction model identified age of the vehicle and engine size as statistically significant, at 5% level. Model performance accuracy rate was 58.0% (S.D. 3.1). For twovehicle collisions, when predicting injury severity in vehicle V1, the engine size of the opponent vehicle (vehicle V2) increased the risk for the occupants of the subject vehicle (vehicle V1), at 10% level. Injury severity prediction model for vehicle V1 revealed a good performance with a mean prediction accuracy rate of 61.2% (S.D. 2.4). When predicting injury severity for the other vehicle involved (vehicle V2), the engine size of the opponent vehicle (vehicle V1) increased the risk for the occupants of vehicle V2, at 5% level. Injury severity prediction model for vehicle V2 achieved a mean prediction accuracy rate of 40.5% (S.D. 2.1).
Dmd of bacteriophage T4 functions as an antitoxin against Escherichia coli LsoA and RnlA toxins

Enterohaemorrhagic Escherichia coli O157:H7 harbours a cryptic plasmid, pOSAK1, that carries only three ORFs: mobA (involved in plasmid mobilization), ORF1 and ORF2. Predicted proteins encoded by these two ORFs were found to share a weak homology with RnlA and RnlB, respectively, a toxin–antitoxin system encoded on the E. coli K‐12 chromosome. Here, we report that lsoA (ORF1) encodes a toxin and lsoB (ORF2) an antitoxin. In spite of the homologies, RnlB and LsoB functioned as antitoxins against only their cognate toxins and not interchangeably with each other. Interestingly, T4 phage Dmd suppressed the toxicities of both RnlA and LsoA by direct interaction, the first example of a phage with an antitoxin against multiple toxins.