Miracle-dz/UniFAR-FTUs huggingface dataset:
Improving Door-to-needle Times in the Treatment of Acute Ischemic Stroke Across a Canadian Province: Methodology

Background: Alteplase is a proven medical treatment for acute ischemic stroke; however, the effectiveness of this treatment is highly time dependent. Therefore, it is imperative that hospitals treat acute ischemic stroke patients as quickly as possible. The measure, door-to-needle time, is the time from hospital arrival to when alteplase administration begins. Objective: The goal in the Canadian province of Alberta was to reduce the door-to-needle time to a median of 30 minutes and to increase the percent of patients treated within 60 minutes to 90%. Overview of Methodology: A modified version of Institute for Healthcare Improvement Breakthrough Series Collaborative was used. All stroke centers self-enrolled into the collaborative after initial contact, and sites created interdisciplinary teams to participate in the Collaborative. Leadership and faculty were highly experienced in quality improvement and acute stroke. There were 3 daylong face-to-face learning sessions that were attended by enrolled teams, which included presentation about the evidence, site presentations to promote cross-site learning, and time to plan changes with their teams. The sites were also supported by site visits, webinars, and data feedback.
Electrocardiographic and Seasonal Patterns Allow Accurate Differentiation of Tako-Tsubo Cardiomyopathy from Acute Anterior Myocardial Infarction: Results of a Multicenter Study and Systematic Overview of Available Studies

Background. Though several studies about prevalence, etiology, clinical characteristics, preceding events, clinical management, and outcome of Tako-Tsubo cardiomyopathy (TTC) exist, the current knowledge of TTC remains limited. Objective. In 2006, TTC was classified among the acquired forms of cardiomyopathy. On the basis of pathophysiological implications, we analyzed whether the presence of ST-segment elevation in lead -aVR (i.e., ST-segment depression in aVR) and the simultaneous absence of ST-segment elevation in lead V1 allow a reliable differentiation of TTC from acute anterior ST-segment elevation myocardial infarction (STEMI). A further investigative feature is the seasonal variation of TTC. Since acute cardiovascular events exhibit definite chronobiological patterns, various small studies have tried to evaluate whether this is also the case for TTC. Because results are conflicting, we also conducted a multicenter study and analyzed the findings in context with a systematic overview of available studies. Methods. We compared the ECG patterns of 115 patients with TTC, who were admitted to five large acute cardiac care centers associated with university hospitals in Southwestern Germany between January 2001 and June 2011, with those of 100 patients with acute anterior ST-segment elevation myocardial infarction (STEMI) treated in one of these centers. In addition, we performed a computer-assisted MEDLINE search of the literature from January 2000 to September 2011 and analyzed the chronobiological patterns of available TTC cases, including our TTC cohort. Results. Testing the predefined diagnostic criteria was superior to any other electrocardiographic finding and differentiated TTC from anterior STEMI with a sensitivity of 73%, a specificity of 84%, a positive predictive value of 63%, and a negative predictive value of 89%. Beyond that, the onset of TTC showed a clear variation as a function of season and month. While events occurred most frequently during summer (38.4%, p < 0.01), the event rate was the lowest in autumn (16.4%) and winter (21.9%). Chronobiological analyses on a monthly basis identified a significant annual rhythmic pattern in TTC, which peaked in August (11.9%; p < 0.01) and had its nadir in November (6.3%). Conclusions. Our data illustrate that the ST-segment changes in leads aVR and V1 represent a simple and accurate ECG criterion to differentiate TTC from anterior STEMI in patients who are admitted within 12 h of symptom onset. Similarly, the results of our seasonal analysis indicate a distinct chronobiological variation in TTC occurrence. TTC, thereby, differs from major acute cardiovascular diseases, especially acute myocardial infarction (AMI), which is characterized by winter peaks and troughs in summer. If these results are confirmed in large independent cohorts, they may yield diagnostic implications, changing the regular invasive AMI management in TTC patients.
Revision of road traffic law in Japan and mental health stigma

A revised road traffic law took effect in Japan in 2014, involving an obligatory disease condition declaration form when acquiring or renewing a driver's license, and imposing a penalty for making false statements about serious symptoms due to specific illnesses (e.g., epilepsy, schizophrenia, and mood disorder). Objections were raised regarding this legal revision, claiming that it could worsen the stigma associated with mental illness. However, the relationship between the law and mental illness-related stigma has not been investigated. This article is protected by copyright. All rights reserved.
The Role of Redundant Information in Cultural Transmission and Cultural Stabilization

Redundant copying has been proposed as a manner to achieve the high-fidelity necessary to pass on and preserve complex traits in human cultural transmission. There are at least 2 ways to define redundant copying. One refers to the possibility of copying repeatedly the same trait over time, and another to the ability to exploit multiple layers of information pointing to the same trait during a single copying event. Using an individual-based model, we explore how redundant copying (defined as in the latter way) helps to achieve successful transmission. The authors show that increasing redundant copying increases the likelihood of accurately transmitting a behavior more than either augmenting the number of copying occasions across time or boosting the general accuracy of social learning. They also investigate how different cost functions, deriving, for example, from the need to invest more energy in cognitive processing, impact the evolution of redundant copying. The authors show that populations converge either to high-fitness/high-costs states (with high redundant copying and complex culturally transmitted behaviors; resembling human culture) or to low-fitness/low-costs states (with low redundant copying and simple transmitted behaviors; resembling social learning forms typical of nonhuman animals). This outcome may help to explain why cumulative culture is rare in the animal kingdom.
Cardiovascular, Bleeding, and Mortality Risks in Elderly Medicare Patients Treated With Dabigatran or Warfarin for Nonvalvular Atrial Fibrillation

Background— The comparative safety of dabigatran versus warfarin for treatment of nonvalvular atrial fibrillation in general practice settings has not been established. Methods and Results— We formed new-user cohorts of propensity score–matched elderly patients enrolled in Medicare who initiated dabigatran or warfarin for treatment of nonvalvular atrial fibrillation between October 2010 and December 2012. Among 134 414 patients with 37 587 person-years of follow-up, there were 2715 primary outcome events. The hazard ratios (95% confidence intervals) comparing dabigatran with warfarin (reference) were as follows: ischemic stroke, 0.80 (0.67–0.96); intracranial hemorrhage, 0.34 (0.26–0.46); major gastrointestinal bleeding, 1.28 (1.14–1.44); acute myocardial infarction, 0.92 (0.78–1.08); and death, 0.86 (0.77–0.96). In the subgroup treated with dabigatran 75 mg twice daily, there was no difference in risk compared with warfarin for any outcome except intracranial hemorrhage, in which case dabigatran risk was reduced. Most patients treated with dabigatran 75 mg twice daily appeared not to have severe renal impairment, the intended population for this dose. In the dabigatran 150-mg twice daily subgroup, the magnitude of effect for each outcome was greater than in the combined-dose analysis. Conclusions— In general practice settings, dabigatran was associated with reduced risk of ischemic stroke, intracranial hemorrhage, and death and increased risk of major gastrointestinal hemorrhage compared with warfarin in elderly patients with nonvalvular atrial fibrillation. These associations were most pronounced in patients treated with dabigatran 150 mg twice daily, whereas the association of 75 mg twice daily with study outcomes was indistinguishable from warfarin except for a lower risk of intracranial hemorrhage with dabigatran.
Very-low-dose twice-daily aspirin maintains platelet inhibition and improves haemostasis during dual-antiplatelet therapy for acute coronary syndrome

Abstract Higher aspirin doses may be inferior in ticagrelor-treated acute coronary syndrome (ACS) patients and reducing bleeding risk whilst maintaining antithrombotic benefits could improve outcomes. We characterized the pharmacodynamics of a novel dual-antiplatelet-therapy regimen consisting of very-low-dose twice-daily (BD) aspirin with standard-dose ticagrelor. A total of 20 ticagrelor-treated ACS patients entered a randomized crossover to take aspirin 20 mg BD (12-hourly) during one 14-day period and 75 mg once-daily (OD) in the other. After 14 days of treatment, serum thromboxane (TX)B2 and light-transmittance aggregometry were assessed pre- and 2 h post-morning-dose, bleeding time was measured post-dose, and TXA2 and prostacyclin stable metabolites were measured in urine collected 2 h post-morning-dose. Data are expressed as mean ± SD. After 14 days treatment, serum TXB2 levels were significantly greater 2 h post-dosing with aspirin 20 mg BD vs. 75 mg OD (3.0 ± 3.6 ng/mL vs. 0.8 ± 1.9 ng/mL; p = 0.018) whereas pre-dosing levels were not significantly different (3.5 ± 4.1 ng/mL vs. 2.5 ± 3.1 ng/mL, p = 0.23). 1-mmol/L arachidonic acid-induced platelet aggregation was similarly inhibited by both regimens pre-dose (8.5 ± 14.3% vs. 5.1 ± 3.6%, p = 0.24) and post-dose (8.7 ± 14.2% vs. 6.6 ± 5.3%; p = 0.41). Post-dose bleeding time was shorter with 20 mg BD (680 ± 306 s vs. 834 ± 386 s, p = 0.02). Urinary prostacyclin and TX metabolite excretion were not significantly different. In conclusion, compared to aspirin 75 mg OD, aspirin 20 mg BD provided consistent inhibition of platelet TXA2 release and aggregation, and improved post-dose hemostasis, in ticagrelor-treated ACS patients. Further studies are warranted to assess whether this regimen improves the balance of clinical efficacy and safety.
Small‐molecule inhibition of prostaglandin E receptor 2 impairs cyclooxygenase‐associated malignant glioma growth

An up‐regulation of COX‐2 in malignant gliomas causes excessive synthesis of PGE2, which is thought to facilitate brain tumour growth and invasion. However, which downstream PGE2 receptor subtype (i.e., EP1–EP4) directly contributes to COX activity‐promoted glioma growth remains largely unknown.
The impact of dietary linseed oil and pomegranate peel extract on broiler growth, carcass traits, serum lipid profile, and meat fatty acid, phenol, and flavonoid contents

Objective The current study aimed to replace soybean oil in broiler diets with linseed oil, which is rich in omega-3 fatty acid supplemented with pomegranate peel extract (PPE) and measured its effect on broiler performance, carcass traits, lipid profile, as well as fatty acids composition, phenols and flavonoids content of broiler muscles and immunity of broiler chicks. Methods A total of 300 1-day-old Cobb chicks were randomly allotted into six experimental groups, T1 fed on basal diet with soybean oil without any additives, T2 fed on basal diet with soybean oil with addition of 0.5 g/kg diet PPE, T3 fed on fed on basal diet with soybean oil with addition of 1 g/kg diet PPE, T4 fed on basal diet with linseed oil without any additives, T5 fed on basal diet with linseed oil with addition of 0.5 g/kg diet PPE and T6 fed on basal diet with linseed oil with addition of 1 g/kg diet PPE. The PPE supplementation with 0.05% improved final body weight with either soybean oil ration or linseed oil ration. Results The PPE improved carcass dressing percentage in comparison with the control groups. Body fat levels decreased with increasing PPE levels, especially with a linseed oil diet. Replacing soybean oil with linseed oil decreased the total cholesterol and triacylglycerol levels in broiler serum. The PPE supplementation decreased serum total cholesterol levels and increased high-density lipoprotein cholesterol levels. The content of the breast muscle alpha linolenic acid improved after replacement of soybean oil with linseed oil in broiler diets. PPE supplementation increased the phenol and flavonoid content in broiler meat and increased lysozyme activity. Conclusion Replacing soybean oil with linseed oil in broiler diets with the addition of PPE enriched muscle meat with omega-3 fatty acids and antioxidants and improved broiler immunity and their serum lipid profile.
Self versus Nonself Discrimination by the Soluble Complement Regulators Factor H and FHL-1

The plasma proteins Factor H (FH) and its alternate splice variant FH-like protein 1 (FHL-1) are the major regulators of the complement alternative pathway. The indiscriminate nature of alternative pathway activation necessitates the regulators to be host selective, but the underlying principles of selectivity remained largely elusive. By analyzing human FH and FHL-1 for protection of different host and foreign cells (rabbit and yeast), we uncovered a 2-fold discriminatory mechanism of FH in favor of self: relative to FHL-1, FH exhibits a regulatory benefit on self but importantly, also, a regulatory penalty on nonself surfaces, yielding a selectivity factor of ∼2.4 for sialylated host surfaces. We further show that FHL-1 possesses higher regulatory activity than known but is relatively unselective. The reason for this unexpected high activity of FHL-1 is the observation that the complement regulatory site in FH exceeds the established first four domains. Affinity for C3b, cofactor and decay-accelerating activities, and serum assays demonstrate that the regulatory site extends domains 1–4 and includes domains 5–7. But unlike FH, FHL-1 exhibits a fast plasma clearance in mice, occurs sparsely in human plasma (at one fortieth of the FH concentration), and resists deregulation by FH-related proteins. These physiological differences and its late phylogenetic occurrence argue that FHL-1 is crucial for local rather than systemic compartments. In conclusion, we demonstrate a 2-fold discriminatory power of FH to promote selectivity for self over foreign and show that FHL-1 is more active than known but specialized for regulation on local tissues.
Binaural advantages in using a cochlear implant for adults with profound unilateral hearing loss

Abstract Background: Recent studies of cochlear implants (CIs) in profound unilateral hearing loss (UHL) patients have demonstrated a restoration of some binaural hearing. Aims/Objectives: The objective was to evaluate three possible advantages of binaural hearing in CIs adult users with UHL including single-side deafness (SSD) and asymmetric hearing loss (AHL) subgroups. Material and methods: A prospective study was conducted that included 70 sequentially implanted patients. Subgroups of these subjects included 64 with a postlingual onset of a profound hearing loss on the implanted side and 6 with a prelingual onset of that loss. Three binaural effects – redundancy, head shadow, and squelch – were evaluated. Results: Significant differences between the ‘CI on’ and ‘CI off’ conditions were found for all three binaural effects for the study group as a whole and for the postlingual subgroup. However, results for the subjects in the prelingual subgroup did not demonstrate any of the binaural advantages. Conclusion and significance: Patients with a postlingual onset of a profound hearing loss in one ear and normal hearing or only a moderate loss in the other ear are able to make the effective use of a CI in the profound-loss ear in conjunction with acoustic stimulation of the other ear.
Partner Conflict and Support as Moderators of Alcohol Use on Alcohol Problems and Marital Satisfaction in Young Adult Marital Dyads

BACKGROUND This cross-sectional study used data from 483 young adult marital dyads to evaluate conflict-with-partner and support-from-partner as moderators of alcohol use on 2 outcomes: alcohol problems and marital satisfaction. A path analytic modeling approach was used to test stress-exacerbating and stress-buffering hypotheses, and to accommodate the interdependent nature of the dyadic data. METHODS This cross-sectional sample was selected from an adolescent-to-young adult longitudinal study in which spouses were recruited into the study during a later young adult assessment when the sample was, on average, 32.5 years old. Individual interviews using computerized technology were conducted with participants. RESULTS Findings for the outcome of alcohol problems indicated stress exacerbation in that higher conflict by each partner in interaction with higher alcohol use was associated with more alcohol problems for wives. Husbands' and wives' alcohol problems were lower when higher partner support buffered the association between alcohol use and alcohol problems. For the outcome of marital satisfaction, higher support-from-partner buffered the association between alcohol use and marital satisfaction. Finally, the combination of alcohol use and conflict-with-partner had more adverse implications for women's alcohol problems relative to men's alcohol problems. CONCLUSIONS These findings highlight that interactions between interpersonal dimensions of romantic relationships and alcohol use by both partners contribute to our understanding of their associations with alcohol problems and marital satisfaction within the marital relationship. Furthermore, there was some sex specificity in that some interactions were more prominently associated with alcohol problems for wives than husbands.
Latent structure and factorial invariance of a neuropsychological test battery for the study of preclinical Alzheimer's disease.

OBJECTIVE To examine the latent structure of a test battery currently being used in a longitudinal study of asymptomatic middle-aged adults with a parental history of Alzheimer's disease (AD) and test the invariance of the factor solution across subgroups defined by selected demographic variables and known genetic risk factors for AD. METHOD An exploratory factor analysis (EFA) and a sequence of confirmatory factor analyses (CFA) were conducted on 24 neuropsychological measures selected to provide a comprehensive estimate of cognitive abilities most likely to be affected in preclinical AD. Once the underlying latent model was defined and the structural validity established through model comparisons, a multigroup confirmatory factor analysis model was used to test for factorial invariance across groups. RESULTS The EFA solution revealed a factor structure consisting of five constructs: verbal ability, visuospatial ability, speed & executive function, working memory, and verbal learning & memory. The CFA models provided support for the hypothesized 5-factor structure. Results indicated factorial invariance of the model across all groups examined. CONCLUSIONS Collectively, the results suggested a relatively strong psychometric basis for using the factor structure in clinical samples that match the characteristics of this cohort. This confirmed an invariant factor structure should prove useful in research aimed to detect the earliest cognitive signature of preclinical AD in similar middle aged cohorts.
Response to Immune Checkpoint Inhibition in Two Patients with Alveolar Soft-Part Sarcoma

Two patients with ASPS responded to immune checkpoint inhibition. Genomic analysis of a larger group of patients demonstrated molecular mismatch repair deficiency signatures in 71% of patients. Immune checkpoint blockade may be a useful therapy for ASPS. Alveolar soft-part sarcoma (ASPS) is a morphologically distinctive mesenchymal tumor characterized by a canonical ASPL–TFE3 fusion product. In the metastatic setting, standard cytotoxic chemotherapies are typically ineffective. Studies have suggested modest clinical response to multitargeted receptor tyrosine kinase inhibitors. Here, we report sustained partial responses in two patients with immune checkpoint inhibition treated with either durvalumab (anti–PD-L1) alone or in combination with tremelimumab (anti–CTLA-4), which appeared unrelated to tumor immune infiltrates or mutational burden. Genomic analysis of these patients, and other cases of ASPS, demonstrated molecular mismatch-repair deficiency signatures. These findings suggest that immune checkpoint blockade may be a useful therapeutic strategy for ASPS. Cancer Immunol Res; 6(9); 1001–7. ©2018 AACR.
Acute spinal cord injury in rats should target activated autophagy.

OBJECT Autophagy is a cellular mechanism of maintaining balance between protein synthesis and degradation; the latter can be induced by starvation and neurodegenerative disease. Spinal cord injury (SCI) induces necrosis and apoptosis. Autophagic flux has not yet been defined, especially the potential role of autophagy in relation to apoptosis in different tissue cells. The object of this study was to investigate the occurrence of autophagic flux and the potential role of autophagy and apoptosis post-SCI in rats. METHODS Following creation of SCI in rats, activation of autophagic flux was detected at the protein (LC3, beclin1, and p62) and mRNA (beclin1) levels and on electron microscopy images. Distribution of LC3, colocalization of activated caspase-3, and changes in expression levels of bcl-2 and Bax were assessed to investigate the potential role of autophagy and apoptosis. Sprague-Dawley rats were used, and T9-10 hemitransection was performed. Expression levels of LC3, beclin1, p62, bcl-2, and Bax were assessed by Western blot analysis, and beclin1 mRNA levels were assessed by reverse transcription-polymerase chain reaction. Distribution of LC3 and colocalization of activated caspase-3 were analyzed by immunohistochemistry. Autophagosome formation was investigated by electron microscopy. RESULTS The authors found a dramatic elevation in LC3 and beclin1 levels near the scar region. Using double staining, they observed that upregulation of LC3 started at 4 hours in neurons and at 3 days in astrocytes after SCI. Confocal images indicated that the percentage of neurons with apoptosis was reduced, while the percentage of astrocytes with apoptosis was high at 4 hours, 8 hours, and 1 day post-SCI but decreased sharply at 3 days. Electron microscopy images provided evidence of autophagosome formation. Elimination of p62 indicated occurrence of autophagic flux. Expression levels of bcl-2 and Bax were increased and decreased, respectively, near the injury site. CONCLUSIONS The results of this research demonstrated that autophagic flux is activated after SCI. Potentially, inhibition of apoptosis could be a target to promote neural recovery.