Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation and Prognostic Relevance of Symmetric Dimethylarginine Serum Concentrations in Critical Illness and Sepsis

In systemic inflammation and sepsis, endothelial activation and microvascular dysfunction are characteristic features that promote multiorgan failure. As symmetric dimethylarginine (SDMA) impacts vascular tension and integrity via modulating nitric oxide (NO) pathways, we investigated circulating SDMA in critical illness and sepsis. 247 critically ill patients (160 with sepsis, 87 without sepsis) were studied prospectively upon admission to the medical intensive care unit (ICU) and on day 7, in comparison to 84 healthy controls. SDMA serum levels were significantly elevated in critically ill patients at admission to ICU compared to controls and remained stably elevated during the first week of ICU treatment. The highest SDMA levels were found in patients with sepsis. SDMA levels closely correlated with disease severity scores, biomarkers of inflammation, and organ failure (renal, hepatic, and circulatory). We identified SDMA serum concentrations at admission as an independent prognostic biomarker in critically ill patients not only for short-term mortality at the ICU but also for unfavourable long-term survival. Thus, the significant increase of circulating SDMA in critically ill patients indicates a potential pathogenic involvement in endothelial dysfunction during sepsis and may be useful for mortality risk stratification at the ICU.
Microsatellite Instability in Pediatric and Adult High‐grade Gliomas

About 15% of sporadic gastrointestinal and endometrial tumors show the microsatellite instability (MSI) phenotype because of loss of DNA mismatch repair (MMR) function. The incidence of MSI in tumors of the central nervous system still remains controversial. Previous studies reported a particular high frequency of MSI (∼25%) in young patients suffering from high‐grade gliomas. Based on these data and the fact that in different tumor entities MMR deficiency defines a subgroup of tumors with distinct pathogenesis and particular clinicopathological features that may have impact on prognosis and therapy, we screened 624 gliomas from 71 young and 553 adult patients for MMR deficiency by MSI analysis using three highly sensitive diagnostic markers. Alterations of MMR protein expression was examined by immunohistochemistry. A malignant glioma from an adult patient displayed MSI and concomitant loss of nuclear MSH2 and MSH6 protein expression (0.16%; 1/619). No evidence for MSI or loss of MMR protein expression was observed in 71 gliomas from young patients (0%; 0/71) including 41 high‐grade astrocytic tumors. Overall, we observed a much lower incidence of MSI among high‐grade pediatric gliomas than initially reported and suggest that MMR deficiency does not play a major role in the pathogenesis of glial neoplasms.
Transcranial magnetic stimulation of visual area V5 in migraine

ObjectiveTo examine visual cortical excitability in persons with migraine using transcranial magnetic stimulation (TMS) over an extrastriate area of the brain, area V5. BackgroundPrevious studies found that persons with migraine have a lower phosphene threshold than healthy control subjects with TMS delivered over the primary visual cortical area V1. The result suggests that the occipital cortex in migraineurs between migraine attacks is hyperexcitable. However, it is not known whether interictal cortical hyperexcitability is also present in areas of the association visual cortex. MethodTo investigate this, single-pulse TMS was delivered over visual area V5, the motion cortex, to 16 persons with migraine and visual aura, nine migraineurs without visual aura, and 16 healthy control subjects. TMS was delivered at intensities ranging from 30 to 100% of maximum stimulator output or until the participant reported seeing phosphenes (visual illusions characterized by flashes of light). Thresholds to phosphenes were obtained for each participant using a staircase procedure. ResultSignificantly lower phosphene thresholds for TMS delivered over V5 were found in migraineurs as compared with control subjects. Qualitatively, the migraineurs’ experience of phosphenes were more vivid, florid, and sustained compared with that of control subjects. ConclusionResults of this study indicate that hyperexcitability of the visual cortex in migraine goes beyond visual area V1 and demonstrates for the first time a significant difference in threshold for excitability of visual area V5 in persons with migraine.
Brain Edema Predicts Outcome After Nonlacunar Ischemic Stroke

Background and Purpose— In malignant infarction, brain edema leads to secondary neurological deterioration and poor outcome. We sought to determine whether swelling is associated with outcome in smaller volume strokes. Methods— Two research cohorts of acute stroke subjects with serial brain MRI were analyzed. The categorical presence of swelling and infarct growth was assessed on diffusion-weighted imaging (DWI) by comparing baseline and follow-up scans. The increase in stroke volume (&Dgr;DWI) was then subdivided into swelling and infarct growth volumes using region-of-interest analysis. The relationship of these imaging markers with outcome was evaluated in univariable and multivariable regression. Results— The presence of swelling independently predicted worse outcome after adjustment for age, National Institutes of Health Stroke Scale, admission glucose, and baseline DWI volume (odds ratio, 4.55; 95% confidence interval, 1.21–18.9; P<0.02). Volumetric analysis confirmed that &Dgr;DWI was associated with outcome (odds ratio, 4.29; 95% confidence interval, 2.00–11.5; P<0.001). After partitioning &Dgr;DWI into swelling and infarct growth volumetrically, swelling remained an independent predictor of poor outcome (odds ratio, 1.09; 95% confidence interval, 1.03–1.17; P<0.005). Larger infarct growth was also associated with poor outcome (odds ratio, 7.05; 95% confidence interval, 1.04–143; P<0.045), although small infarct growth was not. The severity of cytotoxic injury measured on apparent diffusion coefficient maps was associated with swelling, whereas the perfusion deficit volume was associated with infarct growth. Conclusions— Swelling and infarct growth each contribute to total stroke lesion growth in the days after stroke. Swelling is an independent predictor of poor outcome, with a brain swelling volume of ≥11 mL identified as the threshold with greatest sensitivity and specificity for predicting poor outcome.
Early proteinuria response: a valid real-life situation predictor of long-term lupus renal outcome in an ethnically diverse group with severe biopsy-proven nephritis?

Objective Two recent important lupus nephritis trials reported that proteinuria was a good predictor of renal outcome in Caucasians, but data on real-life situation, other races and severe nephritis are lacking to substantiate this finding as a simple test to guide clinical practice. The aim of this study was to validate proteinuria as a predictor of long-term renal outcome in real-life situation in a racially diverse group of patients with severe nephritis. Methods Proteinuria, serum creatinine (SCr) and urine red blood cells were assessed at baseline and after 3, 6 and 12 months, as early predictors of long-term renal outcome (SCr <1.5 mg/dL at 7 years), in 94 patients with biopsy-proven lupus nephritis. The parameter performance and cut-off values were computed by receiver operating characteristic curves. Kaplan-Meier curves were used to validate the parameter. Results A proteinuria <0.8 g/24 hours at 12 months was the best single predictor of long-term renal outcome (sensitivity 90%, specificity 78%, positive predictive value 67%, negative predictive value (NPV) 94% and area under the curve 0.86; p<0.001). Addition of other variables to proteinuria such as SCr and haematuria at 12 months did not improve its performance. The proteinuria cut-off value of 0.8 g/24 hours at 12 months was a good predictor of 7-year renal survival (years free of dialysis) for patients with pure membranous (p=0.005) and proliferative nephritis (p=0.043), as well as black (p=0.002) and white race (p=0.001), anti-dsDNA positive (p=0.001) and anti-dsDNA negative (p=0.04) and male (p=0.028) and female (p=0.003) patients. Conclusion We provided novel evidence that, in a real-life situation, proteinuria at 12 months of follow-up was the single best predictor of renal outcome at 7 years for an ethnically diverse group of patients with severe nephritis and a valid parameter for distinct histological classes, races, genders and anti-dsDNA profiles. The remarkably high NPV obtained reinforces its recommendation as the ideal predictor for clinical practice, since it is of low cost, easy to interpret, non-invasive and widely available.
WebCore: Architectural support for mobile Web browsing

The Web browser is undoubtedly the single most important application in the mobile ecosystem. An average user spends 72 minutes each day using the mobile Web browser. Web browser internal engines (e.g., WebKit) are also growing in importance because they provide a common substrate for developing various mobile Web applications. In a user-driven, interactive, and latency-sensitive environment, the browser's performance is crucial. However, the battery-constrained nature of mobile devices limits the performance that we can deliver for mobile Web browsing. As traditional general-purpose techniques to improve performance and energy efficiency fall short, we must employ domain-specific knowledge while still maintaining general-purpose flexibility. In this paper, we first perform design-space exploration to identify appropriate general-purpose architectures that uniquely fit the characteristics of a popular Web browsing engine. Despite our best effort, we discover sources of energy inefficiency in these customized general-purpose architectures. To mitigate these inefficiencies, we propose, synthesize, and evaluate two new domain-specific specializations, called the Style Resolution Unit and the Browser Engine Cache. Our optimizations boost energy efficiency and at the same time improve mobile Web browsing performance. As emerging mobile workloads increasingly rely more on Web browser technologies, the type of optimizations we propose will become important in the future and are likely to have lasting widespread impact.
A U-Shaped Dose–Response Relationship between X Radiation and Sex-Linked Recessive Lethal Mutation in Male Germ Cells of Drosophila

Abstract We reported previously that low-dose X irradiation of DNA repair-proficient immature sperm of wild-type Drosophila melanogaster at a low dose rate (50 mGy/min) resulted in a mutation frequency that was lower than that in the sham-irradiated group. Therefore, a U-shaped dose–response relationship was suggested. Here we show that the dose–response curve is actually U-shaped by carrying out a large-scale sex-linked recessive lethal assay using Drosophila. No reduction of the mutation frequency was observed in a strain mutant for the nucleotide excision repair gene mei-9a (Drosophila homologue of human XPF). Introduction of a chromosome fragment containing mei-9+ into the mei-9a mutant strain restored the reduction of the mutation frequency in the low-dose-irradiated group. These results showed that DNA repair was responsible for the U-shaped dose–response relationship in Drosophila.
Efficacy of Zolpidem for Dystonia: A Study Among Different Subtypes

Although there are some newly developed options to treat dystonia, its medical treatment is not always satisfactory. Zolpidem, an imidazopyridine agonist with a high affinity on benzodiazepine subtype receptor BZ1 (ω1), was found to improve clinical symptoms of dystonia in a limited number of case reports. To investigate what subtype of dystonia is responsive to the therapy, we conducted an open label study to assess the efficacy of zolpidem (5–20 mg) in 34 patients suffering from miscellaneous types of dystonia using the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS). Patients were entered into the study if they had been refractory to other medications as evaluated by BFMDRS (no change in the previous two successive visits). After zolpidem therapy, the scores in the patients as a whole were decreased from 7.2 ± 7.9 to 5.5 ± 5.0 (P = 0.042). Patients with generalized dystonia, Meige syndrome/blepharospasm, and hand dystonia improved in the scale by 27.8, 17.8, and 31.0%, respectively, whereas no improvement was found in cervical dystonia patients. Overall response rate among patients were comparable to that of trihexyphenidyl. Zolpidem may be a therapeutic option for generalized dystonia, Meige syndrome, and hand dystonia including musician’s. Drowsiness was the dose-limiting factor.
Ecoimmunity in Darwin's Finches: Invasive Parasites Trigger Acquired Immunity in the Medium Ground Finch (Geospiza fortis)

Background Invasive parasites are a major threat to island populations of animals. Darwin's finches of the Galápagos Islands are under attack by introduced pox virus (Poxvirus avium) and nest flies (Philornis downsi). We developed assays for parasite-specific antibody responses in Darwin's finches (Geospiza fortis), to test for relationships between adaptive immune responses to novel parasites and spatial-temporal variation in the occurrence of parasite pressure among G. fortis populations. Methodology/Principal Findings We developed enzyme-linked immunosorbent assays (ELISAs) for the presence of antibodies in the serum of Darwin's finches specific to pox virus or Philornis proteins. We compared antibody levels between bird populations with and without evidence of pox infection (visible lesions), and among birds sampled before nesting (prior to nest-fly exposure) versus during nesting (with fly exposure). Birds from the Pox-positive population had higher levels of pox-binding antibodies. Philornis-binding antibody levels were higher in birds sampled during nesting. Female birds, which occupy the nest, had higher Philornis-binding antibody levels than males. The study was limited by an inability to confirm pox exposure independent of obvious lesions. However, the lasting effects of pox infection (e.g., scarring and lost digits) were expected to be reliable indicators of prior pox infection. Conclusions/Significance This is the first demonstration, to our knowledge, of parasite-specific antibody responses to multiple classes of parasites in a wild population of birds. Darwin's finches initiated acquired immune responses to novel parasites. Our study has vital implications for invasion biology and ecological immunology. The adaptive immune response of Darwin's finches may help combat the negative effects of parasitism. Alternatively, the physiological cost of mounting such a response could outweigh any benefits, accelerating population decline. Tests of the fitness implications of parasite-specific immune responses in Darwin's finches are urgently needed.
Developing hierarchical Bayesian safety performance functions using real-time weather and traffic data

Safety Performance Function (SPF) is essential in traffic safety analysis, and it is useful to unveil hazardous factors related to the crash occurrence. Recently, Bayesian inference technology has drawn many researchers’ interest as an alternative. Among those frequently used models, Hierarchical Bayesian (HB) models are the most popular ones. One reason that HB models are frequently used is that the data structures for crash frequency studies are originally hierarchical (e.g. segment level, seasonal level, and corridor level). Besides, HB models are powerful enough to solve the over-dispersion issue which usually exists in traffic safety data. In this study, four types of HB models are compared (Poisson-gamma model, Random effects Poisson-gamma model, Correlated Random effects Poisson-lognormal model, Uncorrelated Random effects Poisson-lognormal model) with the basic Poisson model. The study focuses on a 15-mile mountainous freeway on I-70 in Colorado. Crash occurrences are aggregated at the homogenous segmentation level and the whole segment was split into 120 homogenous segments. Moreover, real-time traffic data prior to each crash were archived by 30 Remote Traffic Microwave Sensors (RTMS) and real-time weather information are provided by 6 weather stations along the studied roadway. For the model evaluation methods, Deviance Information Criterion (DIC), which recognized as Bayesian generalization of AIC (Akaike information criterion, and standard errors of the estimated coefficients for the independent variables was selected as the evaluation measure to select the best model(s). Comparisons across the models indicate that the Correlated Random effect Poisson model is superior with the smallest DIC values and the least standard errors. Model results indicate that hazardous factors related to the crash occurrence on the roadway segment should be studied by season. For example, the average temperature variable has a distinct coefficient sign for the snow and dry seasons. Moreover, two different sets of parameters have been concluded. Finally, conclusions have shed some lights on designing Active Traffic Management (ATM) strategies: for the dry season, the management strategy should focus on speed control and harmonize, while for the snow season special attentions are needed for the adverse weather conditions.
A review of the specificity of exercises designed for conditioning the lumbar extensors

Objective To review the specificity of exercises designed to condition the lumbar extensor musculature (ie, lumbar erector spinae and multifidus). Methods A review of studies examining effects of exercises designed to condition the lumbar extensors was conducted. Included were studies that examined the acute activation and chronic adaptation of the lumbar extensor musculature in response to benches and roman chair trunk extensions, free weights exercises (ie, deadlifts, squats, good-mornings, etc), floor and stability ball exercise (ie, trunk extensions, bridging, four-point kneeling, etc) and resistance machines (ie, those with and without pelvic restraints). Results Evidence suggests that the reviewed exercises designed to condition the lumbar extensors all may result in significant activation of this musculature during their performance. However, examination of training studies shows that for benches and roman chair trunk extensions, free weights exercises, floor and stability ball exercise and resistance machines without appropriate pelvic restraints, evidence suggests that they may be less effective for inducing chronic adaptations in the lumbar extensors as a result of their performance. Contrastingly, resistance machines that employ appropriate pelvic restraint to isolate lumbar extension are better evidenced to confer specific adaptations to the lumbar extensors. Conclusions Numerous exercise approaches have been designed with the intention of conditioning the lumbar extensors. Those examined appear to activate the lumbar extensors; however, the specificity of many of these exercises for producing chronic adaptations may be questionable, potentially due to the compound nature of them allowing involvement of other musculature such as the hip extensors. Many of the reviewed exercises offer potential to condition the lumbar extensors, however, isolation of lumbar extension through appropriate pelvic restraint appears important for optimising specific adaptations in the lumbar extensors.
Time lapse structure‐from‐motion photogrammetry for continuous geomorphic monitoring

Recent advances are made in earth surface reconstruction with high spatial resolution due to SfM photogrammetry. High flexibility of data acquisition and high potential of process automation allows for a significant increase of the temporal resolution, as well, which is especially interesting to assess geomorphic changes. Two case studies are presented where 4D reconstruction is performed to study soil surface changes at 15 seconds intervals: (a) a thunderstorm event is captured at field scale and (b) a rainfall simulation is observed at plot scale. A workflow is introduced for automatic data acquisition and processing including the following approach: data collection, camera calibration and subsequent image correction, template matching to automatically identify ground control points in each image to account for camera movements, 3D reconstruction of each acquisition interval, and finally applying temporal filtering to the resulting surface change models to correct random noise and to increase the reliability of the measurement of signals of change with low intensity. Results reveal surface change detection with cm‐ to mm‐accuracy. Significant soil changes are measured during the events. Ripple and pool sequences become obvious in both case studies. Additionally, roughness changes and hydrostatic effects are apparent along the temporal domain at the plot scale. 4D monitoring with time‐lapse SfM photogrammetry enables new insights into geomorphic processes due to a significant increase of temporal resolution. Copyright © 2017 John Wiley & Sons, Ltd.
The CXCR3(+)CD56Bright Phenotype Characterizes a Distinct NK Cell Subset with Anti-Fibrotic Potential That Shows Dys-Regulated Activity in Hepatitis C

Background In mouse models, natural killer (NK) cells have been shown to exert anti-fibrotic activity via killing of activated hepatic stellate cells (HSC). Chemokines and chemokine receptors critically modulate hepatic recruitment of NK cells. In hepatitis C, the chemokine receptor CXCR3 and its ligands have been shown to be associated with stage of fibrosis suggesting a role of these chemokines in HCV associated liver damage by yet incompletely understood mechanisms. Here, we analyzed phenotype and function of CXCR3 expressing NK cells in chronic hepatitis C. Methods Circulating NK cells from HCV-infected patients (n = 57) and healthy controls (n = 27) were analyzed with respect to CXCR3 and co-expression of different maturation markers. Degranulation and interferon-γ secretion of CXCR3(+) and CXCR3(−) NK cell subsets were studied after co-incubation with primary human hepatic stellate cells (HSC). In addition, intra-hepatic frequency of CXCR3(+) NK cells was correlated with stage of liver fibrosis (n = 15). Results We show that distinct NK cell subsets can be distinguished based on CXCR3 surface expression. In healthy controls CXCR3(+)CD56Bright NK cells displayed strongest activity against HSC. Chronic hepatitis C was associated with a significantly increased frequency of CXCR3(+)CD56Bright NK cells which showed impaired degranulation and impaired IFN-γ secretion in response to HSC. Of note, we observed intra-hepatic accumulation of this NK cell subset in advanced stages of liver fibrosis. Conclusion We show that distinct NK cell subsets can be distinguished based on CXCR3 surface expression. Intra-hepatic accumulation of the functionally impaired CXCR3(+)CD56Bright NK cell subset might be involved in HCV-induced liver fibrosis.