Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety and Tolerability of Desmoteplase Within 3 to 9 Hours After Symptoms Onset in Japanese Patients With Ischemic Stroke

Background and Purpose— This study investigated the safety and tolerability of desmoteplase administered within 3 to 9 hours after stroke symptoms onset in Japanese patients with acute ischemic stroke. Methods— Patients were randomized to treatment with either desmoteplase or placebo in a 2:1 ratio in 2 consecutive cohorts (70 &mgr;g/kg and then 90 &mgr;g/kg). Included patients had a baseline National Institutes of Health Stroke Scale score of 4 to 24 and occlusion or high-grade stenosis in the middle cerebral artery segment M1 or M2 on magnetic resonance angiography. The incidence of symptomatic intracranial hemorrhage (⩽72 hours) was defined as the primary end point. The occurrence of asymptomatic ICH, symptomatic cerebral edemas, and adverse events were other safety outcomes of special interest. Results— Symptomatic intracranial hemorrhage was observed within 72 hours in 2 patients treated with placebo and in 1 patient treated with 70 &mgr;g/kg desmoteplase. Any ICH (symptomatic or asymptomatic ICH) within 72 hours were observed in 7 (43.8%) patients treated with placebo, in 8 (50%) patients treated with 70 &mgr;g/kg desmoteplase, and in 9 (56.3%) patients treated with 90 &mgr;g/kg desmoteplase. Desmoteplase treatment with 70 or 90 &mgr;g/kg was not associated with an increased risk of symptomatic cerebral edema compared with placebo. There were no other serious safety concerns associated with desmoteplase. Conclusions— Desmoteplase in both 70 and 90 &mgr;g/kg doses had a favorable safety profile and was well tolerated in Japanese patients with acute ischemic stroke when administered 3 to 9 hours after stroke symptoms onset. Clinical Trial Registration— URL: http://www.clinicaltrials. gov. Unique identifier: NCT01104467.
In Vivo Microdialysis Coupled With On-line Electrochemical Detection for Continuous Monitoring Of Ascorbic Acid in Striatum During Exhaustive Exercise

In vivo microdialysis coupled with on-line electrochemical detection was used to continuous monitor the extracellular levels of ascorbic acid in striatum of rats during exhaustion exercise. 20 male rats were used. We found that there was a continuously increase in the concentration of extracellular ascorbic acid in rats striatum during exhaustion exercise. At the beginning of exercise there were no significant changes in the concentration of extracellular ascorbic acid. During the later period of the exercise there was a significant change in the concentrations of extracellular ascorbic acid (P<0.01) compared with that at rest. During the recovery period, the concentration of extracellular ascorbic acid begin to fall-off but still higher than that at rest (P<0.05). In vivo microdialysis coupled with on-line electrochemical detection for continuous monitoring the extracellular levels of ascorbic acid is a feasible method. The extracellular levels of ascorbic acid in striatum of rat show dynamic changes during exhaustive exercise. The reason for the increase of extracellular ascorbic acid maybe concerned with a large number of free radicals generated during exercise. Keywords-rat; exhaustive exercise; striatum; ascorbic acid; on-line monitor
Do They Tweet Differently? A Cross-Cultural Group Study of Twitter Use on Mobile Communication Devices

Culture is one of the classic and most widely studied topics in the field of technology. People of different cultural backgrounds interpret, consume, and disseminate technology differently. One conspicuous aspect of culture is communication. The expression, conversational patterns, and contextual nuances of different languages make communication a distinct cultural experience. Culture influences how communication functions between different people in different social contexts. It is also an underlying feature of encoded messages; a knowledge of the sender’s culture helps to discern his or her intention. Communication technology is also susceptible to the influence of culture. The mobile and social aspects of technology add another dimension to the communication process. Twitter, a leading social medium run on a mobile communication device, is a good example. This empirical study examines the use of Twitter in users with two distinctly different cultural ideologies: individualism (characteristic of the U.S.A.) and collectivism (common in Korea). Participants in both countries took part in a four-man group decision-making experiment. The groups were given decision tasks to complete within a timed period. The study yielded the following results: 1) the Korean participants tweeted significantly more often than the American participants; 2) the Korean participants initiated significantly more new tweets than the American participants; 3) the Korean participants sent significantly more friendly tweets than the American participants; 4) the American participants expressed disagreement significantly more often than the Korean participants; and 5) the Korean participants exhibited a significantly higher level of group cohesiveness than the American participants. These results shed light on the cultural applications of this new, emerging technology which is becoming essential to personal and business information sharing and communication of people of different cultures all over the world. Data analysis, discussion, and implications are provided.
RNA Interference Directed against the Transglutaminase Gene Triggers Dysbiosis of Gut Microbiota in Drosophila*

We recently reported that transglutaminase (TG) suppresses immune deficiency pathway-controlled antimicrobial peptides (IMD-AMPs), thereby conferring immune tolerance to gut microbes, and that RNAi of the TG gene in flies decreases the lifespan compared with non-TG-RNAi flies. Here, analysis of the bacterial composition of the Drosophila gut by next-generation sequencing revealed that gut microbiota comprising one dominant genus of Acetobacter in non-TG-RNAi flies was shifted to that comprising two dominant genera of Acetobacter and Providencia in TG-RNAi flies. Four bacterial strains, including Acetobacter persici SK1 and Acetobacter indonesiensis SK2, Lactobacillus pentosus SK3, and Providencia rettgeri SK4, were isolated from the midgut of TG-RNAi flies. SK1 exhibited the highest resistance to the IMD-AMPs Cecropin A1 and Diptericin among the isolated bacteria. In contrast, SK4 exhibited considerably lower resistance against Cecropin A1, whereas SK4 exhibited high resistance to hypochlorous acid. The resistance of strains SK1–4 against IMD-AMPs in in vitro assays could not explain the shift of the microbiota in the gut of TG-RNAi flies. The lifespan was reduced in gnotobiotic flies that ingested both SK4 and SK1, concomitant with the production of reactive oxygen species and apoptosis in the midgut, whereas the survival rate was not altered in gnotobiotic flies that mono-ingested either SK4 or SK1. Interestingly, significant amounts of reactive oxygen species were detected in the midgut of gnotobiotic flies that ingested SK4 and SK2, concomitant with no significant apoptosis in the midgut. In gnotobiotic flies that co-ingested SK4 and SK1, an additional unknown factor(s) may be required to cause midgut apoptosis.
Leukoaraiosis and lacunes are associated with poor clinical outcomes in ischemic stroke patients treated with intravenous thrombolysis

Background The effect of preexisting small vessel disease on outcomes of patients with ischemic stroke treated with i.v. thrombolysis is not fully understood. Aim We aim to investigate the effect of combined leukoaraiosis and lacunes as detected on unenhanced brain computer tomography at baseline on clinical outcomes after i.v. thrombolysis. Methods We analyzed data from the Canadian Alteplase for Stroke Effectiveness Study. Small vessel disease was assessed on baseline computer tomography rating for leukoaraiosis and lacunes. We dichotomized the burden of small vessel disease to “absent or moderate” and “severe. ” Clinical outcomes at 90 days included excellent outcome (mRS = 0–1), good outcome (mRS = 0–2), and the occurrence of symptomatic intracerebral hemorrhage. Sensitivity analysis was performed on two age groups (≤80 versus >80). We ran logistic regression adjusting for confounders to evaluate independent effect of small vessel disease on outcomes. Results There were 820 patients with available brain computer tomography with mean age (±SD) of 71.3 (±13.2), 455 (55.5%) were male. Of these, 123 (15%) patients had severe small vessel disease at baseline. Age group analysis revealed significant associations of small vessel disease only in patients aged ≤80. After adjustment for confounders, presence of severe small vessel disease reduced the chances of both excellent (OR = 0.42, 95% CI = 0.24–0.74) and good outcome (OR = 0.35, 95% CI = 0.21–0.58) and with an increased risk of symptomatic intracerebral hemorrhage (OR = 5.91; 95% CI = 2.40–14.57). Conclusion When considered together as radiological expressions of small vessel disease, presence and severity of severe leukoaraiosis and lacunes on baseline computer tomography scan are associated with poor clinical outcomes in patients treated with i.v. thrombolysis.
Antithrombotic outcome trials in acute coronary syndromes: seeking the optimal balance between safety and efficacy.

An intricate balance exists between the safety and efficacy of antithrombotic therapies in acute coronary syndrome (ACS). Safety is largely defined by bleeding risks. Many bleeding definitions are used in clinical trials, and conclusions may differ depending on the definition applied. Bleeding risks are typically dose related, making selection of the optimal dose (or preferably, doses) to advance from phase II to III testing a critical step in drug development.1 Efficacy is defined in terms of thrombotic event reduction and is commonly assessed using composite endpoints. However, composite endpoints create interpretive challenges within and across trials, particularly when endpoint definitions vary substantially. The trade-off between benefits (reduction in thrombotic events) and risks (increase in bleeding) is important to patients and clinicians; thus, it is imperative that data are presented clearly to facilitate informed decision making. Antithrombotic drug development for ACS is a challenging area of cardiovascular medicine, a topic discussed during the 7th and 8th Global Cardiovascular Clinical Trialists (CVCT) forums in December 2010 and 2011. This manuscript highlights key points from those discussions. Data from phase II trials are used to determine dose selection for phase III. However, it is not uncommon for phase II and III results to differ substantially ( Tables 1⇓–3 ). In the phase II studies of vorapaxar, prasugrel, and ticagrelor, there was no evidence of a statistically significant increase in bleeding when compared with standard therapy or placebo. However, in the larger phase III studies, an increased risk of bleeding not associated with coronary artery bypass graft (CABG) surgery was observed ( Tables 2 and 3 ). In the phase II studies of apixaban and rivaroxaban, dose-related increases in bleeding were observed leading to the selection of lower doses for phase III. Despite the dose reduction, bleeding was still higher with these drugs when …
Discovery of a Color-selected Quasar at z = 5.50

We present observations of RD J030117+002025, a quasar at z = 5.50 discovered from deep, multicolor, ground-based observations covering 74 arcmin2. This is the most distant quasar or active galaxy currently known. The object was targeted as an R-band dropout, with RAB > 26.3 (3 σ limit in a 3'' diameter region), IAB = 23.8, and zAB = 23.4. The Keck/Low-Resolution Imaging Spectrometer spectrum shows broad Lyα/N V λ1240 emission and sharp absorption decrements from the highly redshifted hydrogen forests. The fractional continuum depression due to the Lyα forest is DA = 0.90. RD J030117+002025 is the least luminous high-redshift quasar known (MB ≈ -22.7).
OsDIS1-mediated stress response pathway in rice

Ubiquitin-mediated protein degradation has been well demonstrated as a key regulatory mechanism in response to drought stress in Arabidopsis. However, the biological function of most E3 ligase genes in drought response is still unknown in rice. We recently showed that OsDIS1 (Oryza sativa drought-induced SINA protein 1), a SINA type E3 ligase, is involved in the drought-stress signal transduction in rice. OsDIS1 plays a negative role in drought stress tolerance through the transcriptional regulation of diverse stress-related genes and also possibly through the posttranslational regulation of its interacting protein OsNek6 in rice. Here we also show that OsDIS1 interacts with OsSKIPa, a drought and salt stress positive regulator in rice. Based on these results, we propose a working model for the function of OsDIS1 in regulating the stress signaling pathway in rice.
Neuroprotective effects of oestrogen against oxidative toxicity through activation of G‐protein‐coupled receptor 30 receptor

1. 17‐β‐oestradiol (E2) plays a critical role in neuroprotection through both genomic and non‐genomic mechanisms. The aim of the present study was to investigate the role of G‐protein‐coupled receptor 30 (GPR30), a new kind of oestrogen receptor, in the neuroprotection against oxidative insult.
Necessity, Possibility and Belief: A Study of Syllogistic Reasoning

The present study extended the investigation of the belief bias effect in syllogistic reasoning in two ways: (1) The effect was studied under instructions to decide whether conclusions were possible, as well as necessary, given the premises; and (2) the effect was studied for types of syllogism where people rarely endorse the conclusions as well as those (valid and fallacious) where endorsements are common. Three experiments are reported, which show first that there is a marked tendency to reject unbelievable conclusions relative to abstract or neutral controls on all kinds of syllogism and under both types of instruction. There was also significant evidence of positive belief bias (increased acceptance of believable conclusions) and of interactions between belief bias effects and logical form. The results are discussed with particular respect to accounts of belief bias offered by theorists in the mental-model tradition.
Design of ultra-thin composite deployable shell structures through machine learning

A data-driven computational framework is applied for the design of optimal ultra-thin Triangular Rollable and Collapsible (TRAC) carbon fiber booms. High-fidelity computational analyses of a large number of geometries are used to build a database. This database is then analyzed by machine learning to construct design charts that are shown to effectively guide the design of the ultra-thin deployable structure. The computational strategy discussed herein is general and can be applied to different problems in structural and materials design, with the potential of finding relevant designs within high-dimensional spaces.
Patterns of alcohol use and expectancies predict sexual risk taking among non-problem drinking women.

OBJECTIVE Although alcohol consumption and sexual risk taking are associated, not everyone who drinks alcohol engages in risky sexual behavior. The purposes of the present study were to identify patterns of alcohol use behaviors and alcohol expectancies among women who are non-problem drinkers and to examine how these patterns are associated with indices of sexual risk. METHOD Data from 758 non-problem drinking women who have sex with men and were not in committed relationships were analyzed using latent profile analysis to determine patterns of alcohol use and alcohol-related expectancies. RESULTS Of the four patterns observed, three classes had similar alcohol-related expectancies but differed with respect to drinking behavior (moderate drinking, regular heavy episodes, and frequent heavy episodes), and the fourth class consisted of moderate drinkers with low expectancies (low expectancies). Results revealed that those in the frequent heavy episodes class had the greatest number of sexual partners in the past year and drank the most alcohol before having sex compared with the other women. Both the regular and frequent heavy episodes classes reported greater likelihood of having unprotected sex in the future, more positive beliefs about casual sex, and greater subjective intoxication before having sex than women in the moderate drinking or low expectancies classes. Women in the low expectancies class reported less positive beliefs about condoms than those in the moderate drinking and regular heavy episodes classes. CONCLUSIONS Results suggest that different patterns of expectancies and drinking behaviors are associated with different indices of sexual risk taking and highlight the importance of individually tailored programs for prevention of sexually transmitted infections.
In situ detection of fragmented dna (tunel assay) fails to discriminate among apoptosis, necrosis, and autolytic cell death: A cautionary note

Detection of DNA fragments in situ using the terminal deoxyribonucleotidyl transferase (TDT)‐mediated dUTP‐digoxigenin nick end labeling (TUNEL) assay is increasingly applied to investigate active cell death (apoptosis). We studied the specificity of the assay in well‐defined models of apoptosis and necrosis as well as in postmortem autolysis in rat liver. During involution of liver hyperplasia, which follows stopping treatment with the hepatomitogens cyproterone acetate (CPA) or nafenopin (NAF), numerous apoptotic hepatocytes could be observed with TUNEL‐positive chromatin residues. A similar TUNEL‐positive reaction appeared in necrotic hepatocytes after a cytotoxic dose of carbon tetrachloride (CCl4) or N‐nitrosomorpholine (NNM). Also, in insufficiently fixed, autolytic livers TUNEL‐positive nuclei were observed. Thus, DNA fragmentation is common to different kinds of cell death; its detection in situ should not be considered a specific marker of apoptosis.
p53 in prostate cancer: frequent expressed transition mutations.

BACKGROUND Carcinoma of the prostate is the second most common cause of cancer deaths in men. Little is known about the pathogenesis of this disease and the molecular genetic events that contribute to its development. Molecular studies have begun to reveal biologic characteristics of this disease, notably, the loss of genetic material as determined by studies of restriction fragment length polymorphism, oncogene activation, and production and response to growth factors. PURPOSE Our goal was to characterize p53 gene mutations in human carcinoma of the prostate and to analyze base-pair changes within the coding regions of p53 mRNA (exons 4 through 11). METHODS Forty-four prostate tissue specimens and four metastatic lesions were obtained from 48 prostate carcinoma patients who had surgical resection. RNA was either immediately extracted or the specimens were snap-frozen in liquid N2 and stored at -70 degrees C until used. Total RNA was extracted from tumor specimens. Expression of p53 was analyzed by polymerase chain reaction (PCR) analysis of mRNA (RNA/PCR). Following confirmation of the RNA/PCR products by Southern blotting, quantitation of message levels was performed by laser densitometry. Absolute area integrations of the curves representing each tissue were then compared after adjustment for the housekeeping gene c-N-ras. Two overlapping regions (exons 4-6 and 6-11) were examined by a nonisotopic PCR single-strand conformation polymorphism (SSCP) analysis system. All specimens displaying SSCP abnormalities were sequenced in both directions to confirm the findings. RESULTS Of the 48 prostate specimens, three (6%) (two primary and one metastatic) displayed nearly undetectable expression of p53 mRNA (samples PS-70, L113, and PS-95) and 17 (35%) of 48 expressed mutant p53 mRNA encoding amino acid substitutions within exons 4-11 (14 of 17) and/or deletions within the p53 transcripts (three of 17). Overall, the frequency of p53 gene abnormalities that would result in altered protein expression was 20 (42%) of 48 in the tissue samples from prostate carcinoma patients. Nucleotide base-pair transitions of A-->G or T-->C were the most frequent. CONCLUSIONS p53 mutations are common in prostate cancer. The patterns of p53 gene mutations are dramatically different from data obtained on other cancers and indicate the possible involvement of a carcinogenic agent(s). IMPLICATIONS Further studies are required to determine the biologic role of p53 gene alterations in the development and progression of this disease and to determine whether p53 mutations can be useful as prognostic markers or for the selection of better treatments for prostate cancer patients.
An Investigation of TCP Congestion Window Validation over Satellite Paths

This paper examines an issue that arises when an Internet transport-layer connection using TCP is suspended (e.g. to mobile hand-off application dynamics or user preference) and later resumed. In particular, it examines whether congestion window validation (CWV) is an appropriate technique to prevent an application overwhelming the network path that it is using, and examines how widely CWV is implemented in current operating systems. This work is applicable to mobility between different types of networks, and when the network path properties can suddenly change - both of which can occur when IP mobility introduced into satellite systems. This change expected to reduce the impact of application-limited flows on other flows, by limiting the rate at which these applications can transmit following an idle, application-limited period or sudden change of networks.
Neuroblastoma: contemporary management

Neuroblastoma is the most frequently diagnosed extracranial solid tumour in childhood. While a subset of tumours show spontaneous regression or complete remission following conventional treatment, a substantial number remain resistant to intensive multimodal therapies. Survival rates approaching 40% place high-risk neuroblastoma as one of the greatest challenges in paediatric oncology. This contemporary review provides an update on the diagnosis, risk stratification and management for this enigmatic tumour. Neuroblastoma is the most common extracranial solid tumour in childhood and the most frequently diagnosed neoplasm during infancy.1 This malignant tumour consists of undifferentiated and/or differentiating cells originating from neural crest-derived sympathoadrenal precursors. Neuroblastoma is often described as “enigmatic” and “unpredictable” because of the broad spectrum of clinical behaviour ranging from life-threatening progression despite intensive treatment to complete spontaneous regression. Although outcome for certain subsets of patients has improved over the past few decades, children with high-risk disease continue to have less than 40% long-term survival.2 New therapeutic options are being sought through advances in basic science and translational clinical research. Neuroblastoma accounts for more than 7% of malignancies in patients younger than 15 years and around 15% of all paediatric oncology deaths.3 The incidence of neuroblastoma in predominantly Caucasian populations is 9–12 per million children.4 A family history of neuroblastoma has been reported in 1% to 2% of patients5 and follows an autosomal dominant pattern of inheritance. Supporting the Knudson two-mutation hypothesis, the median age at diagnosis for familial neuroblastoma cases is 9 months compared to 18 months in sporadic cases.3 Associations with Hirschsprung disease and congenital central hypoventilation syndrome6 with a shared PHOX2b mutation proposed to explain this link7 have been reported, as has neurofibromatosis type 1.8 At present, genetic predisposition to neuroblastoma appears to be heterogeneous and hence tumourigenesis is postulated …