Miracle-dz/UniFAR-FTUs huggingface dataset:
Autonomic Dysfunction Predicts Clinical Outcomes After Acute Ischemic Stroke: A Prospective Observational Study

Background and Purpose— Central autonomic dysfunction increases stroke morbidity and mortality. We aimed to investigate whether poststroke autonomic dysfunction graded by Ewing battery can predict clinical outcome. Methods— In this prospective observational study, we assessed autonomic function of ischemic stroke patients within 7 days from symptom onset by Ewing battery. On the basis of the magnitude of autonomic dysfunction, we stratified patients into significant (definite, severe, or atypical) or minor (normal or early) autonomic function impairment groups and correlated the impairment with the 3-month modified Rankin Scale score (good outcome: modified Rankin Scale score 0≈2; poor outcome: modified Rankin Scale score 3≈6). Results— Among the 150 patients enrolled (mean age, 66.4±9.9 years; 70.7% males), minor autonomic dysfunction was identified in 36 patients (24.0%), and significant autonomic dysfunction was identified in 114 patients (76.0%) based on Ewing battery. In 3 months, a poor functional outcome was found in 32.5% of significant group patients compared with 13.9% in the minor group (P=0.031). Crude odds ratios of the magnitude of autonomic dysfunction and 3-month unfavorable functional outcome after acute ischemic stroke were 2.979 (95% confidence interval, 1.071–8.284; P=0.036). After adjusting for confounding variables with statistical significance between the 2 functional outcome subgroups identified in univariate analysis (including sex and National Institutes of Health Stroke Scale score on admission), the magnitude of autonomic dysfunction still independently predicted an unfavorable outcome, with an odds ratio of 3.263 (95% confidence interval, 1.141–9.335; P=0.027). Conclusions— Autonomic dysfunction gauged by Ewing battery predicts poor functional outcome after acute ischemic stroke.
A Review of Combination Antimicrobial Therapy for Enterococcus faecalis Bloodstream Infections and Infective Endocarditis

Enterococci, one of the most common causes of hospital-associated infections, are responsible for substantial morbidity and mortality. Enterococcus faecalis, the more common and virulent species, causes serious high-inoculum infections, namely infective endocarditis, that are associated with cardiac surgery and mortality rates that remained unchanged for the last 30 years. The best cures for these infections are observed with combination antibiotic therapy; however, optimal treatment has not been fully elucidated. It is the purpose of this review to highlight treatment options and their limitations, and provide direction for future investigative efforts to aid in the treatment of these severe infections. While ampicillin plus ceftriaxone has emerged as a preferred treatment option, mortality rates continue to be high, and from a safety standpoint, ceftriaxone, unlike other cephalosporins, promotes colonization with vancomycin resistant-enterococci due to high biliary concentrations. More research is needed to improve patient outcomes from this high-mortality disease.
Ablation of Cyclophilin D Results in an Activation of FAK, Akt, and ERK Pathways in the Mouse Heart

Cyclophilin D (CypD) is a mitochondrial chaperone that regulates the mitochondrial permeability transition pore. Metabolically, deletion of Ppif (the gene encoding CypD) in mice is associated with elevated levels of mitochondrial matrix Ca2+ that leads to increased glucose as relative to fatty acid oxidation. Here, we characterized the adaptive mechanisms involved in the regulation of glucose metabolism including the regulation of Akt and ERK kinases that we evaluated by Western blot analysis of Ppif−/− in comparison to wild type (WT) mouse hearts. CypD loss led to adaptive mechanisms in the heart resulting in an upregulation of focal adhesion kinase (phosphorylated at Tyr925) and increased phosphorylation of Akt at S473. The increased activity of this pathway (pAktS473 increased to 170% and 145% in Ppif−/− versus WT males and females, respectively) could be responsible for the observed metabolic switch towards glycolysis. Furthermore, the phosphorylation of ERK1/2 proteins was elevated following CypD ablation. In addition, we observed differences in protein expression and activity in male versus female hearts that were independent of CypD expression. This included an upregulation of pAktS473 (to 273% and 269% in Ppif−/− and WT females as compared to their corresponding males, respectively). Furthermore, decreased levels of endothelial nitric oxide synthase (eNOS) inhibitor asymmetric dimethylarginine were accompanied by an upregulation of eNOS in female mice. The higher extent of kinases phosphorylation may be responsible for the reported lowered tolerance of CypD animals to stress. Moreover, the higher nitric oxide production could be responsible for the cardioprotective properties observed only in female hearts. J. Cell. Biochem. 118: 2933–2940, 2017. © 2017 Wiley Periodicals, Inc.
A Demonstration of ‘Broken’ Visual Space

It has long been assumed that there is a distorted mapping between real and ‘perceived’ space, based on demonstrations of systematic errors in judgements of slant, curvature, direction and separation. Here, we have applied a direct test to the notion of a coherent visual space. In an immersive virtual environment, participants judged the relative distance of two squares displayed in separate intervals. On some trials, the virtual scene expanded by a factor of four between intervals although, in line with recent results, participants did not report any noticeable change in the scene. We found that there was no consistent depth ordering of objects that can explain the distance matches participants made in this environment (e.g. A>B>D yet also A<C<D) and hence no single one-to-one mapping between participants' perceived space and any real 3D environment. Instead, factors that affect pairwise comparisons of distances dictate participants' performance. These data contradict, more directly than previous experiments, the idea that the visual system builds and uses a coherent internal 3D representation of a scene.
Gaze‐evoked nystagmus induced by alcohol intoxication

The cerebellum is the core structure controlling gaze stability. Chronic cerebellar diseases and acute alcohol intoxication affect cerebellar function, inducing, among others, gaze instability as gaze‐evoked nystagmus. Gaze‐evoked nystagmus is characterized by increased centripetal eye‐drift. It is used as an important diagnostic sign for patients with cerebellar degeneration and to assess the ‘driving while intoxicated’ condition. We quantified the effect of alcohol on gaze‐holding using an approach allowing, for the first time, the comparison of deficits induced by alcohol intoxication and cerebellar degeneration. Our results showed that alcohol intoxication induces a two‐fold increase of centripetal eye‐drift. We establish analysis techniques for using controlled alcohol intake as a model to support the study of cerebellar deficits. The observed similarity between the effect of alcohol and the clinical signs observed in cerebellar patients suggests a possible pathomechanism for gaze‐holding deficits.
Seasonal Exposure to Drought and Air Warming Affects Soil Collembola and Mites

Global environmental changes affect not only the aboveground but also the belowground components of ecosystems. The effects of seasonal drought and air warming on the genus level richness of Collembola, and on the abundance and biomass of the community of Collembola and mites were studied in an acidic and a calcareous forest soil in a model oak-ecosystem experiment (the Querco experiment) at the Swiss Federal Research Institute WSL in Birmensdorf. The experiment included four climate treatments: control, drought with a 60% reduction in rainfall, air warming with a seasonal temperature increase of 1.4°C, and air warming + drought. Soil water content was greatly reduced by drought. Soil surface temperature was slightly increased by both the air warming and the drought treatment. Soil mesofauna samples were taken at the end of the first experimental year. Drought was found to increase the abundance of the microarthropod fauna, but reduce the biomass of the community. The percentage of small mites (body length 0.20 mm) increased, but the percentage of large mites (body length >0.40 mm) decreased under drought. Air warming had only minor effects on the fauna. All climate treatments significantly reduced the richness of Collembola and the biomass of Collembola and mites in acidic soil, but not in calcareous soil. Drought appeared to have a negative impact on soil microarthropod fauna, but the effects of climate change on soil fauna may vary with the soil type.
Hazardous Alcohol Consumption Is a Major Factor in Male Premature Mortality in a Typical Russian City: Prospective Cohort Study 2003–2009

Introduction Russia has experienced massive fluctuations in mortality at working ages over the past three decades. Routine data analyses suggest that these are largely driven by fluctuations in heavy alcohol drinking. However, individual-level evidence supporting alcohol having a major role in Russian mortality comes from only two case-control studies, which could be subject to serious biases due to their design. Methods and Findings A prospective study of mortality (2003–9) of 2000 men aged 25–54 years at recruitment was conducted in the city of Izhevsk, Russia. This cohort was free from key limitations inherent in the design of the two earlier case-control studies. Cox proportional hazards regression was used to estimate hazard ratios of all-cause mortality by alcohol drinking type as reported by a proxy informant. Hazardous drinkers were defined as those who either drank non-beverage alcohols or were reported to regularly have hangovers or other behaviours related to heavy drinking episodes. Over the follow-up period 113 men died. Compared to non-hazardous drinkers and abstainers, men who drank hazardously had appreciably higher mortality (HR = 3.4, 95% CI 2.2, 5.1) adjusted for age, smoking and education. The population attributable risk percent (PAR%) for hazardous drinking was 26% (95% CI 14,37). However, larger effects were seen in the first two years of follow-up, with a HR of 4.6 (2.5, 8.2) and a corresponding PAR% of 37% (17, 51). Interpretation This prospective cohort study strengthens the evidence that hazardous alcohol consumption has been a major determinant of mortality among working age men in a typical Russian city. As such the similar findings of the previous case-control studies cannot be explained as artefacts of limitations of their design. As Russia struggles to raise life expectancy, which even in 2009 was only 62 years among men, control of hazardous drinking must remain a top public health priority.
Numerical Model of an Argon Atmospheric Pressure RF Discharge

Radio-frequency discharges are known to operate in two different regimes. The alpha regime of low current density and the gamma regime with higher current density. Our recent simulation results suggest that the formation of filaments observed in an atmospheric pressure argon discharge under RF excitation could be triggered by the regime transition alphararrgamma. A unidimensional fluid model taking into account the external circuit shows that above 120 mA/cm2 , the differential conductivity of the discharge becomes negative with a rapid increase in density which can lead to the formation of filaments. As the transition to the gamma regime is due to secondary electrons, this threshold value depends on the secondary emission coefficient. In the gamma regime, the instantaneous cathode is sustained by secondary electron emission, which drastically changes the behavior of the discharge. In this paper, we present a numerical analysis of the transition between the two regimes and discuss how this could result in the filamentary mode observed in argon RF discharges.
Non-myeloablative allogeneic hematopoietic cell transplantation for relapsed or refractory Waldenström macroglobulinemia: evidence for a graft-versus-lymphoma effect

Irrespective of age, patients with aggressive Waldenstrom macroglobulinemia (WM) who have exhausted chemo-immunotherapy-based approaches may be candidates for allogeneic hematopoietic cell transplantation (HCT), a strategy that has been rarely attempted. [1][1]–[7][2] In Seattle, conditioning with
CMU OAQA at TREC 2017 LiveQA: A Neural Dual Entailment Approach for Question Paraphrase Identification

In this paper, we present CMU’s question answering system that was evaluated in the TREC 2017 LiveQA Challenge. Our overall approach this year is similar to the one used in 2015 and 2016. This system answers real-user submitted questions from Yahoo! Answers website and medical questions, which involves retrieving relevant web pages, extracting answer candidate texts, ranking and selecting ﬁnal answer text. The main improvement this year is the introduction of our new question paraphrase identiﬁcation module based on a neural dual entailment model. The model uses bidirectional recurrent neural network to encode the premise question into phrase vectors, and then align corresponding phrase vectors from the candidate question with the attention mechanism. The ﬁnal similarity score is produced based on aggregated phrase-wise comparisons of both entailment directions. In the TREC 2017 LiveQA evaluations, human assessors gave our system an average score of 1.139 on a three-point scale and the median score was 0.777 for all the systems evaluated. Overall, our approach received the highest average scores among automatic systems in main tasks of 2015, 2016 and 2017, and also the highest average score in the new medical subtask of 2017.
Use of Motor Abundance in Young and Older Adults during Dual-Task Treadmill Walking

Motor abundance allows individuals to perform any task reliably while being variable in movement's particulars. The study investigated age-related differences in this feature when young adults (YA) and older adults (OA) performed challenging tasks, namely treadmill walking alone and while performing a cognitive task. A goal function for treadmill walking was first defined, i.e., maintain constant speed at each step, which led to a goal equivalent manifold (GEM) containing all combinations of step time and step length that equally satisfied the function. Given the GEM, amounts of goal-equivalent and non-goal-equivalent variability were afterwards determined and used to define an index providing information about the set of effective motor solutions relative to the GEM. The set was limited in OA compared to YA in treadmill walking alone, indicating that OA made less flexible use of motor abundance than YA. However, this differentiation between YA and OA disappeared when concurrently performing the cognitive task. It is proposed that OA might have benefited from cognitive compensation.
Etiology of Valvular Heart Disease in the 21st Century

A metamorphosis in the etiology of valvular heart disease (VHD) has occurred over the last 6 decades. In this review, the factors contributing to this metamorphosis, the common causes of VHD today, the relationship of valvular calcification to atherosclerosis and the interrelationship of VHD with other systems/organs are presented.
PTPN22 contributes to exhaustion of T lymphocytes during chronic viral infection

Significance Some viruses, including lymphocytic choriomeningitis virus clone 13, shut down the ability of CD4 T lymphocytes to produce IL-2, a cytokine required for the survival and function of T lymphocytes. This shutdown contributes to exhaustion of CD4 and CD8 T lymphocytes and chronic viral infection of the host. The underlying mechanism responsible for the loss of cytokine production by CD4 T cells remains poorly understood. We demonstrate that the expression of a protein tyrosine phosphatase, PTPN22, contributes to chronic viral infection. PTPN22 increases the production of IFN-β following infection, resulting in increased expression of the cAMP response element modulator (CREM) in CD4 T lymphocytes. CREM prevents production of IL-2, thereby contributing to T-cell exhaustion and chronic viral infection. The protein encoded by the autoimmune-associated protein tyrosine phosphatase nonreceptor type 22 gene, PTPN22, has wide-ranging effects in immune cells including suppression of T-cell receptor signaling and promoting efficient production of type I interferons (IFN-I) by myeloid cells. Here we show that mice deficient in PTPN22 resist chronic viral infection with lymphocytic choriomeningitis virus clone 13 (LCMV cl13). The numbers and function of viral-specific CD4 T lymphocytes is greatly enhanced, whereas expression of the IFNβ-induced IL-2 repressor, cAMP-responsive element modulator (CREM) is reduced. Reduction of CREM expression in wild-type CD4 T lymphocytes prevents the loss of IL-2 production by CD4 T lymphocytes during infection with LCMV cl13. These findings implicate the IFNβ/CREM/IL-2 axis in regulating T-lymphocyte function during chronic viral infection.
The Relationship Between Sedatives, Sedative Strategy, and Healthcare-Associated Infection: A Systematic Review

BACKGROUND Healthcare-associated infections (HAIs) cause significant morbidity in critically ill patients. An underappreciated but potentially modifiable risk factor for infection is sedation strategy. Recent trials suggest that choice of sedative agent, depth of sedation, and sedative management can influence HAI risk in mechanically ventilated patients. OBJECTIVE To better characterize the relationships between sedation strategies and infection. METHODS Systematic literature review. RESULTS We found 500 articles and accepted 70 for review. The 3 most common sedatives for mechanically ventilated patients (benzodiazepines, propofol, and dexmedetomidine) have different pharmacologic and immunomodulatory effects that may impact infection risk. Clinical data are limited but retrospective observational series have found associations between sedative use and pneumonia whereas prospective studies of sedative interruptions have reported possible decreases in bloodstream infections, pneumonia, and ventilator-associated events. CONCLUSION Infection rates appear to be highest with benzodiazepines, intermediate with propofol, and lowest with dexmedetomidine. More data are needed but studies thus far suggest that a better understanding of sedation practices and infection risk may help hospital epidemiologists and critical care practitioners find new ways to mitigate infection risk in critically ill patients. Infect Control Hosp Epidemiol 2016;1–9
Role of Macrophages in the Altered Epithelial Function during a Type 2 Immune Response Induced by Enteric Nematode Infection

Parasitic enteric nematodes induce a type 2 immune response characterized by increased production of Th2 cytokines, IL-4 and IL-13, and recruitment of alternatively activated macrophages (M2) to the site of infection. Nematode infection is associated with changes in epithelial permeability and inhibition of sodium-linked glucose absorption, but the role of M2 in these effects is unknown. Clodronate-containing liposomes were administered prior to and during nematode infection to deplete macrophages and prevent the development of M2 in response to infection with Nippostrongylus brasiliensis. The inhibition of epithelial glucose absorption that is associated with nematode infection involved a macrophage-dependent reduction in SGLT1 activity, with no change in receptor expression, and a macrophage-independent down-regulation of GLUT2 expression. The reduced transport of glucose into the enterocyte is compensated partially by an up-regulation of the constitutive GLUT1 transporter consistent with stress-induced activation of HIF-1α. Thus, nematode infection results in a “lean” epithelial phenotype that features decreased SGLT1 activity, decreased expression of GLUT2 and an emergent dependence on GLUT1 for glucose uptake into the enterocyte. Macrophages do not play a role in enteric nematode infection-induced changes in epithelial barrier function. There is a greater contribution, however, of paracellular absorption of glucose to supply the energy demands of host resistance. These data provide further evidence of the ability of macrophages to alter glucose metabolism of neighboring cells.
High Mobility Group Box 1 Mediates Interferon‐γ‐Induced Phenotypic Modulation of Vascular Smooth Muscle Cells

The phenotypic modulation of VSMCs is a key cellular event driving neointimal formation and vascular remodeling. As a multifaceted cytokine of cell‐mediated immunity, IFN‐γ has been shown to play a critical role in the pathogenesis of vascular proliferative diseases. Although the important function of IFN‐γ on regulating VSMC activation is well established, the molecular mechanisms by which elicits VSMC responses are poorly defined. Recent studies have identified HMGB1 as a principal effector to mediate IFN‐γ‐dependent biological functions in multiple cell types. Moreover, SIRT1 has emerged as a critical regulator of cellular processes through deacetylating multiple substrates, including HMGB1. Thus, we examined the role of IFN‐γ on HMGB1 release, SIRT1 expression, and VSMC phenotypic modulation as well as the underlying molecular mechanisms. We show that IFN‐γ dose‐dependently induces HMGB1 cytoplasmic accumulation and its active release from VSMCs, resulting in enhanced HMGB1 in the medium. Conversely, IFN‐γ treatment led to a dramatic decrease in SIRT1 expression. Additionally, pretreatment with resveratrol, a selective SIRT1 activator, abrogated IFN‐γ‐induced HMGB1 translocation and its release. Moreover, IFN‐γ stimulates VSMC phenotypic modulation to an activated synthetic state characterized by the repression of SMC differentiation markers such as SM22α and calponin and the increase in cell motility. In contrast, blocking HMGB1 release or activity by resveratrol and HMGB1‐neutralizing antibody prevents IFN‐γ‐induced phenotypic modulation of VSMCs. Overall, this study provides the first evidence showing that HMGB1 plays a critical role in regulating VSMC phenotypic modulation, suggesting that HMGB1 may be a potential therapeutic target to prevent vascular occlusive diseases. J. Cell. Biochem. 118: 518–529, 2017. © 2016 Wiley Periodicals, Inc.