Miracle-dz/UniFAR-FTUs huggingface dataset:
The Putative Catalytic Bases Have, at Most, an Accessory Role in the Mechanism of Arginine Kinase*

Arginine kinase is a member of the phosphagen kinase family that includes creatine kinase and likely shares a common reaction mechanism in catalyzing the buffering of cellular ATP energy levels. Abstraction of a proton from the substrate guanidinium by a catalytic base has long been thought to be an early mechanistic step. The structure of arginine kinase as a transition state analog complex (Zhou, G., Somasundaram, T., Blanc, E., Parthasarathy, G., Ellington, W. R., and Chapman, M. S. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 8449–8454) showed that Glu-225 and Glu-314 were the only potential catalytic residues contacting the phosphorylated nitrogen. In the present study, these residues were changed to Asp, Gln, and Val or Ala in several single and multisite mutant enzymes. These mutations had little impact on the substrate binding constants. The effect upon activity varied with reductions in kcat between 3000-fold and less than 2-fold. The retention of significant activity in some mutants contrasts with published studies of homologues and suggests that acid-base catalysis by these residues may enhance the rate but is not absolutely essential. Crystal structures of mutant enzymes E314D at 1.9 Å and E225Q at 2.8 Å resolution showed that the precise alignment of substrates is subtly distorted. Thus, pre-ordering of substrates might be just as important as acid-base chemistry, electrostatics, or other potential effects in the modest impact of these residues upon catalysis.
BURN INJURY : REVIEW OF PATHOPHYSIOLOGY AND THERAPEUTIC MODALITIES IN MAJOR BURNS REVUE

The number of burn injury victims in the United States is estimated to be 1.2 million per year, with an annual incidence of 2 million fire accidents reported.1 Among these injuries, 75% are considered mild, treated on an outpatient basis,2,3 while on average 50,000 burn patients require admission to a hospital or major burn center.4 Despite a considerable decrease in the incidence of burns in the developed world, they remain one of the commonest forms of injury, accounting for a significant proportion of trauma cases in hospital emergencies worldwide, and they continue to cause devastating morbidity and mortality.5,6 The distressing consequences of burns have been recognized by the medical community, and significant amounts of resources and research have been dedicated to successfully improving these dismal statistics. Recent reports revealed a 50% decline in burn-related deaths and hospital admissions in the USA over the last 20 years. This is attributable to the effective prevention strategies that have been introduced to the practice, limiting burn-associated morbidities as well as reducing the number and severity of burns.7,8,9,10
Patterns of Drug Use Among Drug Misusers in Sweden. Gender Differences

The goal of the article is to provide information about polydrug abuse and drug misuse patterns in Sweden among women and men. The data has been taken from a 1998 national survey of “Heavy”/severe drug misuse in Sweden, project “MAX-98” (). The drug misusers were reported by various government agencies, including health services, social services, police, and correctional treatment facilities on a special form. One of the significant gender differences that emerged was that a greater percent of the women in the survey used and injected amphetamines, injected opiates, and used tranquilizers/sedatives, while a greater percent of the men smoked cannabis, smoked heroin, and misused alcohol. Furthermore, the most common combinations for both genders was amphetamines + cannabis, followed by amphetamines + heroin + cannabis. Alcohol played a large role for the narcotics users. Heroin as a primary drug has grown in the age groups under 35. The trends document that the use of ecstasy as well as chemical CNS-stimulating/hallucinogenic drugs has grown, that polydrug use has increased compared with earlier surveys, and that the methods of ingestion have changed. It is therefore more precise today to speak of different types of polydrug users than about users of exclusively one drug.
Targeting TNF-α for the treatment of inflammatory bowel disease

Introduction: The advent of tumor necrosis factor (TNF) antagonists represented a radical change in the management of inflammatory bowel disease (IBD). Both in short- and long-term, anti-TNF therapy has been shown to reduce symptoms, heal mucosal ulcers, reduce hospitalizations and surgeries and spare corticosteroids. Areas covered: A literature search to August 2013 was performed to identify the most relevant reports on the use of TNF antagonists in IBD. First, the authors focused on the mechanism of action of TNF antagonists. Second, they evaluated different indications, contraindications, the optimal time to start and the role of combining TNF antagonists with immunomodulators. Third, they explored the importance of mucosal healing, followed by the controversial topic on when TNF antagonists should be stopped. This is followed by the subjects of treatment failure, immunogenicity and therapeutic drug monitoring. Last, they analyzed safety issues including exposure to TNF antagonists during pregnancy. Expert opinion: TNF antagonists have become indispensable in the management of IBD. Efforts to focus on treatment of inflammatory signs only and on optimization of treatment with therapeutic drug monitoring are underway. The advent of several new compounds and “biosimilars” will further challenge the position of TNF antagonists in the treatment algorithm of IBD.
Thymoma: A population-based study of the management and outcomes for the province of British Columbia.

7023 Background: The optimal approach to the management of thymoma and thymic carcinomas is unclear, particularly for advanced stage disease. Our primary study aim was to analyze treatment practices and outcomes in a population-based cohort of thymoma patients. METHODS All patients (pts) with a pathological diagnosis of thymoma or thymic carcinoma and referred to the British Columbia Cancer Agency (BCCA) between 1994 and 2009 were reviewed. Kaplan-Meier curves and Cox proportional hazard models were used to correlate histology, stage, and treatment with outcomes. Pathology review using WHO classification is currently underway. RESULTS 190 pts were identified of which 171 (90%) were referred to BCCA and eligible for analyses. Median was 60 years; 50% of pts were male. 26% had paraneoplastic phenomena; including 21% with myasthenia gravis.Pts with thymic carcinoma (n=23) and thymoma (n=148) had 5-year overall survival (OS) rates of 38% and 81%, respectively. Survival by stage is detailed in the table. Pts with stage I disease were treated primarily with surgery. Selected stage II pts received adjuvant radiation therapy, which conferred a significant improvement in progression free survival (98 vs. 62 months, p<0.01), but no OS benefit. There were practice variations in management of pts with advanced stage disease (n=71). A multimodality approach that included surgery, radiation, and chemotherapy correlated with better outcomes. Tri-modality treatment for thymoma achieved a 5-year OS of 85%; however, pts with advanced thymic carcinoma had poor outcomes despite aggressive treatment. In multivariate analyses histology (thymoma vs. thymic carcinoma) and surgery were significant predictors of OS. CONCLUSIONS This study is the first population-based series to detail treatment and outcomes for thymoma. Outcomes compare favorably to series from single institutions. Pts with locally advanced disease for whom initial surgical resectibility is uncertain should be triaged to a multidisciplinary team for consideration of multimodality treatment. [Table: see text].
Someone in Your Contact List: Cued Recall-Based Textual Passwords

Textual passwords remain the most commonly employed user authentication mechanism, and potentially will continue to be so for years to come. Despite the well-known security and usability issues concerning textual passwords, none of the numerous proposed authentication alternatives appear to have achieved a sufficient level of adoption to dominate in the foreseeable future. Password hints, consisting of a user generated text saved at the account setup stage, are employed in several authentication systems to help users to recall forgotten passwords. However, users are often unable to create hints that jog the memory without revealing too much information regarding the passwords themselves. We propose a rethink of password hints by introducing SỲNTHIMA, a novel cued recall-based textual password method that reveals no information regarding the password, requires no modifications to authentication servers, and requires no additional setup or registration steps. SỲNTHIMA makes use of users’ contact lists, so that mapped password hints extracted from a user’s contacts are automatically generated while the user is typing the password. We create formal models for relevant aspects of the password hint mechanism, define its threat model, and analyze the security and usability of SỲNTHIMA. We also present the results of an in-lab user study of SỲNTHIMA on 30 participants to evaluate its effectiveness and usability. The results demonstrate that SỲNTHIMA minimizes the number of incorrect login attempts and improves long-term password recall, with acceptable login times and positive user feedback. We summarize the lessons learned from the user study, with the hope of provoking further insights regarding the design of effective cued recall-based textual password schemes.
Protecting the brain during neurosurgical procedures: strategies that can work

Purpose of review The quest for neuroprotection strategies during periods of neuronal vulnerability persists despite decades of basic and clinical research. This review will focus on the latest developments in the area of clinical brain protection with the major emphasis on strategies that can be beneficial during neurosurgical procedures. Recent findings Brain protection in neurosurgical patients may be achieved by nonpharmacological and pharmacological strategies. Pharmacological neuroprotection including anaesthetic administration have not been recently shown to be successful. Alternatively, nonpharmacological strategies including maintenance of cerebral perfusion by adequate control of mean arterial pressure (≥80 mmHg), liberal normoglycaemia (7.8–10 mmol/l), adequate haemoglobin levels (preoperative ≥120 g/l and intraoperative ≥90 g/l) and induction of hypertension (20–40% of preoperative values) in certain neurosurgical situations can be beneficial as neuroprotectants during neurosurgery. Mild hypothermia (32–35°C) failed to achieve neuroprotective effects in several situations of brain injury. Summary The findings of this review suggest that the anaesthesiologist is compelled to use nonpharmacological strategies sometimes based on empiric evidence to protect the brain during neurosurgical procedures. These strategies are simple, have high benefit/risk ratios and are inexpensive. Rigorous controlled clinical studies are needed to investigate the neuroprotective efficacy of these commonly used nonpharmacological methods.
Price Response to Factor Index Additions and Deletions

Abnormal price reaction around S&P 500 index changes has been considered as strong evidence that long term demand for stocks is downward sloping. This notion, however, has recently lost popularity due to the evidence that new additions are accompanied with a contemporaneous change in future earnings expectations. In this study we show that factor index rebalancing is a true information free event. The cumulative abnormal return from announcement to effective day is 1.07% for new additions and -0.91% for new deletions and around two-thirds of this effect is permanent. We find a direct relationship between the magnitude of abnormal returns and the abnormal volume coming from index funds. The documented effect results in a direct loss to index fund investors of 16.5 bps per annum.
Social Presence and Interaction in Learning Environments: The Effect on Student Success

With the increased use of social media there is a growing interest in using social interaction and social presence in education. Despite this phenomenon, no appropriate methodology was found on effective integrating of both concepts into online learning. In this study, we propose integrating two different kinds of learning tools to provide social interaction and social presence in Personal Learning Environments. We have evaluated the proposed concept in a classroom setting, using a specific social interaction tool and a specific social presence tool. The findings revealed that although the use of the social interaction tool was positively associated with students' academic success, the perceived ease of using the social presence tool was negatively related to students' success.
Safety and Efficacy of an Experimental Reovirus Vaccine for In Ovo Administration

Abstract SUMMARY. A commercial reovirus vaccine alone or experimental reovirus vaccine plus antibody complex were inoculated into 18-day-old specific pathogen free (SPF) broiler embryos at 0.1 of the recommended chick dose. The following groups were used: group 1A was not vaccinated or challenged; group 1B was not vaccinated, but was challenged with virulent reovirus; group 2 received the vaccine complexed with 1/4 dilution of antiserum; group 3 received the vaccine with 1/8 dilution of antiserum; group 4 received the vaccine with 1/16 dilution of antiserum, and group 5 received vaccine alone. At 1, 3, 6, 9, and 12 days of age, serum was collected and antibody against avian reovirus was analyzed by enzyme-linked immunosorbent assay (ELISA). At the same times, spleens were collected and vaccine virus detected by inoculating chicken embryo fibroblasts (CEFs) and examining for cytopathic effect. At 15 days of age, chickens in groups 2–5 were challenged with reovirus. At 22 days of age, birds were euthanatized and weighed. Efficacy of the vaccines was based on safety, percent protection, and antibody response. In ovo vaccination with the commercial or experimental vaccines did not adversely affect hatchability of SPF chickens. The vaccine complexed with antibody resulted in significantly less posthatch mortality (3.7%) when compared to mortality of chickens that received vaccine alone (17%). Both vaccine virus recovery and antibody response were delayed at least 3 days in birds receiving the experimental vaccines. In ovo administration of reovirus antibody complex vaccines provided at least 70% protection. The experimental reovirus–antibody complex vaccines were safe and efficacious when given in ovo to SPF broiler embryos.
Opinions of University Music Teachers on the Musical Competencies Necessary for Primary Education Teachers

This paper describes the research conducted in the Republic of Croatia during the 2012/13 academic year. We have gathered opinions from experts, i.e. teaching methods teachers from seven faculties of teacher education, regarding the music teaching competencies necessary for primary education teachers teaching music in the first several grades of elementary school. We used the Delphi method in our research, i.e. in our sample survey among teaching methods teachers. The teachers also evaluated the competencies of their students and some elements of teacher education studies course syllabi and programmes. The sample survey among the teachers was implemented via email. The goal of the research was to determine if the programmes of the music courses at the teacher education studies are appropriate for the development of the competencies necessary for students of music education. Teaching methods teachers emphasized the need for more practical training, primarily regarding playing instruments and singing, and they pointed out that the course Teaching Methods in Music is the most important course for the training of future music teachers. Aside from that, they believe that more classes should be devoted to music courses, i.e. they propose to reorganise the contents of the courses by increasing the amount of practical classes and reducing the amount of theory classes. They also believe that it is necessary to introduce testing of musical ability at entrance exams for admission into the teacher education studies.
Galactomannan detection in computerized tomography‐based broncho‐alveolar lavage fluid and serum in haematological patients at risk for invasive pulmonary aspergillosis

Summary. We determined the value of galactomannan (GM) detection in computerized tomography (CT)‐based broncho‐alveolar lavage (BAL) fluid and serum for the diagnosis of invasive pulmonary aspergillosis (IPA) in haemato‐oncological patients with neutropenia. CT of the thorax and BAL were performed systematically at predefined clinical indications. GM was determined by sandwich enzyme‐linked immunosorbent assay; the clinicians were unaware of the results. Of 160 patients, 17 patients (10·6%) presented with proven, probable or suspected IPA. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of GM detection in CT‐based BAL fluid were all 100%. For GM detection in serially sampled serum, the sensitivity was 47%, the specificity 93%, the PPV 73% and the NPV 82%. A non‐blinded follow‐up study was performed to validate these results. In this study, 22 of 198 patients (11·1%) presented with IPA, and the sensitivity, specificity, PPV and NPV of GM detection in CT‐based BAL fluid were 85%, 100%, 100% and 88% respectively. None of BAL fluids obtained after antifungal treatment of 3 d or more were positive. These results indicate that, when CT is used systematically and at an early stage, GM detection in CT‐based BAL fluid has a high PPV for diagnosing IPA early in untreated patients.
The North/South Ireland Food Consumption Survey: the dietary fibre intake of Irish adults

Abstract Objective Mean daily intakes of dietary fibre (DF, Southgate) and non-starch polysaccharide (NSP, Englyst) are estimated in a representative sample of adults aged 18-64 years in Ireland. The contribution of food groups to DF and NSP intake is reported and fibre intakes are compared with dietary recommendations and with intakes in some European countries. Design Food consumption was estimated using 7-day food diaries for a representative sample (n = 1379; 662 men, 717 women) of 18–64 year old adults in the Republic of Ireland and Northern Ireland selected from the electoral register. DF and NSP intakes were estimated from tables of food composition. Results The mean daily intake of DF in the total sample was 20.2 g (standard deviation (SD) 7.8) [23-2 g (SD 8.5) in men, 17.4 g (SD 5.9) in women] or 2.24 g MJ−1 (SD 0.7) [2.16 g MJ−1 (SD 0.7) in men, 2.33 g MJ−1 (SD 0.7) in women]. Mean daily intake of NSP was 14.8 g (SD 6.2) [16.7 g (SD 6.8) in men, 13.0 g (SD 5.0) in women] or 1.65 g MJ−1 (SD 0.6) [1.56 g MJ−1 (SD 0.6) in men, 1.74 g MJ−1 (SD 0.6) in women]. The main food groups that contributed to mean daily intake of DF (NSP) in the sample were breads 31% (23%), potatoes 19% (23%), and vegetables 17% (19%). Absolute intakes of DF and NSP were higher (P < 0.001) in men than women; however, women overall consumed more (P < 0.001) fibre-dense diets than men. Women aged 18-35 years consumed less (P < 0.01) DF and NSP (g) than women aged 36-64 years. Both men and women aged 18–35 years consumed less (P < 0.01) fibre-dense diets than men and women aged 36–64 years. The NSP intake was below the nutritional goal of 18 g day−1 in 77% of adults and below the minimum of the recommended range (12 g day−1) in 37% of the total sample. Compliance (i.e. the maximum number of individuals whose collective mean daily intake corresponded to the population goal) with the (UK) population goal for an average intake of 18 g day−1 NSP was achieved by a greater proportion of the population (63%) than compliance with the (German) dietary fibre recommendation of 30 g day−1 (27%) or the (Nordic) recommendation of 3 g MJ−1 day−1 (33%). Conclusion DF (NSP) intakes were lower than dietary recommendations in a substantial proportion of the population. This is likely to contribute to impaired bowel function and constipation, which in turn may contribute to increased risk of chronic gastrointestinal disease.
Effective Implementation Strategies and Tactics for Leading Change on Maternity Units

Change implementation within organizations is a complex and dynamic process that is not always successful. Tailoring the implementation strategies and tactics to address the identified barriers to change is one method that has been shown to be effective. Examples of 3 broad types of interrelated strategies used by frontline leaders when implementing quality improvement (QI) projects are (1) discourse (communication), (2) education (formal and informal), and (3) data (audit). Examples of common barriers to implementation are leaders' and clinicians' knowledge, attitudes, and practices, the QI topic characteristics, and the implementation climate. External pressures from national organizations such as the National Quality Forum, the Leapfrog Group, and The Joint Commission likely facilitate change. Knowledgeable, tenacious, and creative frontline physician and nurse leaders may have the greatest impact on QI implementation effectiveness because they are the individuals who decide how the strategies and tactics will be tailored.
The Inducible Costimulator Plays the Major Costimulatory Role in Humoral Immune Responses in the Absence of CD28 1

CD28 plays crucial costimulatory roles in T cell proliferation, cytokine production, and germinal center response. Mice that are deficient in the inducible costimulator (ICOS) also have defects in cytokine production and germinal center response. Because the full induction of ICOS in activated T cells depends on CD28 signal, the T cell costimulatory capacity of ICOS in the absence of CD28 has remained unclear. We have clarified this issue by comparing humoral immune responses in wild-type, CD28 knockout (CD28 KO), and CD28-ICOS double-knockout (DKO) mice. DKO mice had profound defects in Ab responses against environmental Ags, T-dependent protein Ags, and vesicular stomatitis virus that extended far beyond those observed in CD28 KO mice. However, DKO mice mounted normal Ab responses against a T-independent Ag, indicating that B cell function itself was normal. Restimulated CD4+ DKO T cells that had been primed in vivo showed decreased proliferation and reduced IL-4 and IL-10 production compared with restimulated CD4+ T cells from CD28 KO mice. Thus, in the absence of CD28, ICOS assumes the major T cell costimulatory role for humoral immune responses. Importantly, CD28-mediated ICOS up-regulation is not essential for ICOS function in vivo.