bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antitrypanosomal Activity of Fexinidazole Metabolites, Potential New Drug Candidates for Chagas Disease
Authors: Bahia Maria T. , Nascimento Alvaro F. S. , Mazzeti Ana Lia , Marques Luiz F. , Gonçalves Karolina R. , Mota Ludmilla W. R. , Diniz Lívia de F. , Caldas Ivo S. , Talvani André , Shackleford David M. , Koltun Maria , Saunders Jessica , White Karen L. , Scandale Ivan , Charman Susan A. , Chatelain Eric 
Published: May 2014

ABSTRACT

This study was designed to verify the
in vivo
efficacy of sulfoxide and sulfone fexinidazole metabolites following oral administration in a murine model of Chagas disease. Female Swiss mice infected with the Y strain of
Trypanosoma cruzi
were treated orally once per day with each metabolite at doses of 10 to 100 mg/kg of body weight for a period of 20 days. Parasitemia was monitored throughout, and cures were detected by parasitological and PCR assays. The results were compared with those achieved with benznidazole treatment at the same doses. Fexinidazole metabolites were effective in reducing the numbers of circulating parasites and protecting mice against death, compared with untreated mice, but without providing cures at daily doses of 10 and 25 mg/kg. Both metabolites were effective in curing mice at 50 mg/kg/day (30% to 40%) and 100 mg/kg/day (100%). In the benznidazole-treated group, parasitological cure was detected only in animals treated with the higher dose of 100 mg/kg/day (80%). Single-dose pharmacokinetic parameters for each metabolite were obtained from a parallel group of uninfected mice and were used to estimate the profiles following repeated doses. Pharmacokinetic data suggested that biological efficacy most likely resides with the sulfone metabolite (or subsequent reactive metabolites formed following reduction of the nitro group) following administration of either the sulfoxide or the sulfone and that prolonged plasma exposure over the 24-h dosing window is required to achieve high cure rates. Fexinidazole metabolites were effective in treating
T. cruzi
in a mouse model of acute infection, with cure rates superior to those achieved with either fexinidazole itself or benznidazole.
Five-Year Longitudinal Assessment (2008 to 2012) of E-101 Solution Activity against Clinical Target and Antimicrobial-Resistant Pathogens
Authors: Denys Gerald A. , Pillar Chris M. , Sahm Daniel F. , O'Hanley Peter , Stephens Jackson T. 
Published: May 2014

ABSTRACT
This study summarizes the topical E-101 solution susceptibility testing results for 760 Gram-positive and Gram-negative target pathogens collected from 75 U.S. sites between 2008 and 2012 and 103 ESKAPE pathogens. E-101 solution maintained potent activity against all bacterial species studied for each year tested, with MICs ranging from <0.008 to 0.25 μg porcine myeloperoxidase (pMPO)/ml. These results confirm that E-101 solution retains its potent broad-spectrum activity against U.S. clinical isolates and organisms with challenging resistance phenotypes.
Deficiency of Double-Strand DNA Break Repair Does Not Impair Mycobacterium tuberculosis Virulence in Multiple Animal Models of Infection
Authors: Heaton Brook E. , Barkan Daniel , Bongiorno Paola , Karakousis Petros C. , Glickman Michael S. 
Published: May 2014

ABSTRACT

Mycobacterium tuberculosis
persistence within its human host requires mechanisms to resist the effector molecules of host immunity, which exert their bactericidal effects through damaging pathogen proteins, membranes, and DNA. Substantial evidence indicates that bacterial pathogens, including
M. tuberculosis
, require DNA repair systems to repair the DNA damage inflicted by the host during infection, but the role of double-strand DNA break (DSB) repair systems is unclear. Double-strand DNA breaks are the most cytotoxic form of DNA damage and must be repaired for chromosome replication to proceed.
M. tuberculosis
elaborates three genetically distinct DSB repair systems: homologous recombination (HR), nonhomologous end joining (NHEJ), and single-strand annealing (SSA). NHEJ, which repairs DSBs in quiescent cells, may be particularly relevant to
M. tuberculosis
latency. However, very little information is available about the phenotype of DSB repair-deficient
M. tuberculosis
in animal models of infection. Here we tested
M. tuberculosis
strains lacking NHEJ (a Δ
ku
Δ
ligD
strain), HR (a Δ
recA
strain), or both (a Δ
recA
Δ
ku
strain) in C57BL/6J mice, C3HeB/FeJ mice, guinea pigs, and a mouse hollow-fiber model of infection. We found no difference in bacterial load, histopathology, or host mortality between wild-type and DSB repair mutant strains in any model of infection. These results suggest that the animal models tested do not inflict DSBs on the mycobacterial chromosome, that other repair pathways can compensate for the loss of NHEJ and HR, or that DSB repair is not required for
M. tuberculosis
pathogenesis.
Identification of Lysine Residues in the Borrelia burgdorferi DbpA Adhesin Required for Murine Infection
Authors: Fortune Danielle E. , Lin Yi-Pin , Deka Ranjit K. , Groshong Ashley M. , Moore Brendan P. , Hagman Kayla E. , Leong John M. , Tomchick Diana R. , Blevins Jon S. 
Published: May 2014

ABSTRACT

Decorin-binding protein A (DbpA) of
Borrelia burgdorferi
mediates bacterial adhesion to heparin and dermatan sulfate associated with decorin. Lysines K82, K163, and K170 of DbpA are known to be important for
in vitro
interaction with decorin, and the DbpA structure, initially solved by nuclear magnetic resonance (NMR) spectroscopy, suggests these lysine residues colocalize in a pocket near the C terminus of the protein. In the current study, we solved the structure of DbpA from
B. burgdorferi
strain 297 using X-ray crystallography and confirmed the existing NMR structural data.
In vitro
binding experiments confirmed that recombinant DbpA proteins with mutations in K82, K163, or K170 did not bind decorin, which was due to an inability to interact with dermatan sulfate. Most importantly, we determined that the
in vitro
binding defect observed upon mutation of K82, K163, or K170 in DbpA also led to a defect during infection. The infectivity of
B. burgdorferi
expressing individual
dbpA
lysine point mutants was assessed in mice challenged via needle inoculation. Murine infection studies showed that strains expressing
dbpA
with mutations in K82, K163, and K170 were significantly attenuated and could not be cultured from any tissue. Proper expression and cellular localization of the mutated DbpA proteins were examined, and NMR spectroscopy determined that the mutant DbpA proteins were structurally similar to wild-type DbpA. Taken together, these data showed that lysines K82, K163, and K170 potentiate the binding of DbpA to dermatan sulfate and that an interaction(s) mediated by these lysines is essential for
B. burgdorferi
murine infection.
Postgraduate anaesthesiology education: protocol for a scoping review
Authors: Ringsted Charlotte , Bance Sheena , Murgaski Laura Leigh , Herold Jodi , Glover Takahashi Susan 
Published: May 2014

IntroductionThe link between education and clinical practice is vital, yet the current state of research suggests there is a substantial gap between medical education research and practice. This too is the case in the domain of anaesthesiology education research, as much of the research focuses on simulation studies, and a narrow range of research methods. The aim of this study is to comprehensively review the existing literature in postgraduate anaesthesiology education research in order to identify key research priorities. The findings from this review will be used to establish a base for developing a strategic research programme in anaesthesia education and practice.Methods and analysisWe will employ the scoping review methodology outlined by Arksey and O'Malley (2005) to comprehensively search the literature pertaining to postgraduate anaesthesiology education. We will search relevant electronic databases (eg, MEDLINE, EMBASE) and grey literature. After conducting calibration exercises, two authors will independently apply inclusion criteria to all titles and abstracts and perform full-text review of all eligible articles. Data to be extracted will include basic information about the study (eg, location, design) as well as detailed information regarding the context of the research and type of education examined. Our results will be used to develop a framework of themes that outline the research currently being conducted and identify gaps in research.Ethics and disseminationThis review is the first step in a strategic research plan in postgraduate anaesthesiology education. We plan to disseminate this research through publications, presentations and meetings with relevant stakeholders. Ethical approval was not sought for this scoping review.
Differences in case-mix can influence the comparison of standardised mortality ratios even with optimal risk adjustment: an analysis of data from paediatric intensive care
Authors: Manktelow Bradley N , Evans T Alun , Draper Elizabeth S 
Published: May 2014

Background and objectiveThe publication of clinical outcomes for consultant surgeons in 10 specialties within the NHS has, along with national clinical audits, highlighted the importance of measuring and reporting outcomes with the aim of monitoring quality of care. Such information is vital to be able to identify good and poor practice and to inform patient choice. The need to adequately adjust outcomes for differences in case-mix has long been recognised as being necessary to provide ‘like-for-like’ comparisons between providers. However, directly comparing values of the standardised mortality ratio (SMR) between different healthcare providers can be misleading even when the risk-adjustment perfectly quantifies the risk of a poor outcome in the reference population. An example is shown from paediatric intensive care.MethodsUsing observed case-mix differences for 33 paediatric intensive care units (PICUs) in the UK and Ireland for 2009–2011, SMRs were calculated under four different scenarios where, in each scenario, all of the PICUs were performing identically for each patient type. Each scenario represented a clinically plausible difference in outcome from the reference population.ResultsDespite the fact that the outcome for any patient was the same no matter which PICU they were to be admitted to, differences between the units were seen when compared using the SMR: scenario 1, 1.07–1.21; scenario 2, 1.00–1.14; scenario 3, 1.04–1.13; scenario 4, 1.00–1.09.ConclusionsEven if two healthcare providers are performing equally for each type of patient, if their patient populations differ in case-mix their SMRs will not necessarily take the same value. Clinical teams and commissioners must always keep in mind this weakness of the SMR when making decisions.
Phase change memory in enterprise storage systems
Authors: Kim Hyojun , Seshadri Sangeetha , Dickey Clement L. , Chiu Lawrence 
Published: May 2014

Storage devices based on Phase Change Memory (PCM) devices are beginning to generate considerable attention in both industry and academic communities. But whether the technology in its current state will be a commercially and technically viable alternative to entrenched technologies such as flash-based SSDs still remains unanswered. To address this it is important to consider PCM SSD devices not just from a device standpoint, but also from a holistic perspective.
This paper presents the results of our performance measurement study of a recent all-PCM SSD prototype. The average latency for 4 KB random read is 6.7 ?s, which is about 16x faster than a comparable eMLC flash SSD. The distribution of I/O response times is also much narrower than the flash SSD for both reads and writes. Based on real-world workload traces, we model a hypothetical storage device which consists of flash, HDD, and PCM to identify the combinations of device types that offer the best performance within cost constraints. Our results show that - even at current price points - PCM storage devices show promise as a new component in multi-tiered enterprise storage systems.
Schurm-Power Convexity of a Class of Multiplicatively Convex Functions and Applications
Authors: Wang Wen , Yang Shiguo 
Published: May 2014

We investigate the conditions under which the symmetric functionsFn,k(x,r)=∏1≤i1<i2<⋯<ik≤n ‍f(∑j=1k‍xijr)1/r,  k=1,2,…,n,are Schurm-power convex forx∈R++nandr>0. As a consequence, we prove that these functions are Schur geometrically convex and Schur harmonically convex, which generalizes some known results. By applying the theory of majorization, several inequalities involving thepth power mean and the arithmetic, the geometric, or the harmonic means are presented.
Reinforcement of Dental Methacrylate with Glass Fiber after Heated Silane Application
Authors: Fonseca Rodrigo Borges , Paula Marcella Silva de , Favarão Isabella Negro , Kasuya Amanda Vessoni Barbosa , Almeida Letícia Nunes de , Mendes Gustavo Adolfo Martins , Carlo Hugo Lemes 
Published: May 2014

This study evaluated the influence of silane heat treatment and glass fiber fabrication type, industrially treated (I) or pure (P), on flexural and compressive strength of methacrylate resin bars (BISGMA/TEGDMA, 50/50%). Six groups(n=10)were created: I-sil: I/silanated; P-sil: P-silanated; I-sil/heat: I/silanated heated to 100°; P-sil/heat: P/silanated heated to 100°; (I: I/not silanated; and P: P/not silanated. Specimens were prepared for flexural strength(10×2×1 mm)and for compressive strength9.5×5.5×3 mm) and tested at 0.5 mm/min. Statistical analysis demonstrated the following for flexural strength(P< 0.05 ): I-sil:155.89±45.27BC; P-sil:155.89±45.27BC; I-sil/heat:130.20±22.11C; P-sil/heat:169.86±50.29AB; I:131.87±15.86C. For compressive strength, the following are demonstrated: I-sil:1367.25±188.77ab; P-sil:867.61±102.76d; I-sil/heat:1162.98±222.07c; P-sil/heat:1499.35±339.06a; and I:1245.78±211.16bc. Due to the impossibility of incorporating the stipulated amount of fiber, P group was excluded. Glass fiber treatment with heated silane enhanced flexural and compressive strength of a reinforced dental methacrylate.
S100A1 in Human Heart Failure
Authors: Bennett Mosi K. , Sweet Wendy E. , Baicker-McKee Sara , Looney Elizabeth , Karohl Kristen , Mountis Maria , Tang W.H. Wilson , Starling Randall C. , Moravec Christine S. 
Published: May 2014

Background—
We hypothesized that S100A1 is regulated during human hypertrophy and heart failure and that it may be implicated in remodeling after left ventricular assist device. S100A1 is decreased in animal and human heart failure, and restoration produces functional recovery in animal models and in failing human myocytes. With the potential for gene therapy, it is important to carefully explore human cardiac S100A1 regulation and its role in remodeling.

Methods and Results—

We measured S100A1, the sarcoplasmic endoplasmic reticulum Ca
2+
ATPase, phospholamban, and ryanodine receptor proteins, as well as β-adrenergic receptor density in nonfailing, hypertrophied (left ventricular hypertrophy), failing, and failing left ventricular assist device–supported hearts. We determined functional consequences of protein alterations in isolated contracting muscles from the same hearts. S100A1, sarcoplasmic endoplasmic reticulum Ca
2+
ATPase and phospholamban were normal in left ventricular hypertrophy, but decreased in failing hearts, while ryanodine receptor was unchanged in either group. Baseline muscle contraction was not altered in left ventricular hypertrophy or failing hearts. β-Adrenergic receptor and inotropic response were decreased in failing hearts. In failing left ventricular assist device–supported hearts, S100A1 and sarcoplasmic endoplasmic reticulum Ca
2+
ATPase showed no recovery, while phospholamban, β-adrenergic receptor, and the inotropic response fully recovered.

Conclusions—

S100A1 and sarcoplasmic endoplasmic reticulum Ca
2+
ATPase, both key Ca
2+
-regulatory proteins, are decreased in human heart failure, and these changes are not reversed after left ventricular assist device. The clinical significance of these findings for cardiac recovery remains to be addressed.
An Online Spaced-Education Game Among Clinicians Improves Their Patients’ Time to Blood Pressure Control
Authors: Kerfoot B. Price , Turchin Alexander , Breydo Eugene , Gagnon David , Conlin Paul R. 
Published: May 2014

Background—
Many patients with high blood pressure (BP) do not have antihypertensive medications appropriately intensified at clinician visits. We investigated whether an online spaced-education (SE) game among primary care clinicians can decrease time to BP target among their hypertensive patients.

Methods and Results—

A 2-arm randomized trial was conducted over 52 weeks among primary care clinicians at 8 hospitals. Educational content consisted of 32 validated multiple-choice questions with explanations on hypertension management. Providers were randomized into 2 groups: SE clinicians were enrolled in the game, whereas control clinicians received identical educational content in an online posting. SE game clinicians were e-mailed 1 question every 3 days. Adaptive game mechanics resent questions in 12 or 24 days if answered incorrectly or correctly, respectively. Clinicians retired questions by answering each correctly twice consecutively. Posting of relative performance among peers fostered competition. Primary outcome measure was time to BP target (<140/90 mm Hg). One hundred eleven clinicians enrolled. The SE game was completed by 87% of clinicians (48/55), whereas 84% of control clinicians (47/56) read the online posting. In multivariable analysis of 17 866 hypertensive periods among 14 336 patients, the hazard ratio for time to BP target in the SE game cohort was 1.043 (95% confidence interval, 1.007–1.081;
P
=0.018). The number of hypertensive episodes needed to treat to normalize one additional patient’s BP was 67.8. The number of clinicians needed to teach to achieve this was 0.43.

Conclusions—
An online SE game among clinicians generated a modest but significant reduction in the time to BP target among their hypertensive patients.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00904007.
Unacknowledged Pioneer: Gender, Nation, and Class in the Short Stories of Samīrah ʿAzzām
Authors: Farag Joseph R. 
Published: May 2014

Abstract
This paper charts the articulation of feminist, gender, and nationalist concerns in the writings of Samīrah ʿAzzām (1927-1967). It situates ʿAzzām’s oeuvre within the Palestinian literary canon, arguing through a series of close readings of her short stories that, though overlooked, ʿAzzām’s writings are in fact seminal. Writing in the wake of the Nakbah, ʿAzzām was among the first to articulate many of the tropes and motifs that would become central to Palestinian literary production. While her overriding concern was with class critique, ʿAzzām’s writing simultaneously prefigures later Palestinian feminist literary social critiques.
Bankers and Politics: The Network of Shi‘i Moneychangers in Eighth-Ninth Century Kufa and their Role in the Shi‘i Community
Authors: Asatryan Mushegh 
Published: May 2014

Abstract
The article studies the network of moneychangers in the Shi‘i community of Kufa during the eighth-ninth centuries. It argues that apart from exchanging currencies, some of these moneychangers acted as financial agents for the imams, collecting funds from their following, receiving donations on their behalf, and with the collected money regulating the internal affairs of the Kufan Shi‘i community. By looking at the history of the Shi‘i community and, still broader, of the region as a whole, the article seeks to explain why the group of moneychangers became important among the Kufan Shi‘is, especially during Ja‘far al-Sadeq’s time and later, while being virtually insignificant at earlier periods. The article combines a quantitative study of biographical dictionaries with evidence found in literary accounts.
Illicit Acts and Sacred Space: Everyday Crime in the Shrine City of Mashhad, 1913-1914
Authors: Vejdani Farzin 
Published: May 2014

Abstract
This article explores the connection between individuals, spaces, and daily crime in the shrine city of Mashhad during 1913-4. It challenges the prevailing emphasis on the city’s sacred status by highlighting the frequency and nature of illicit activities often involving urban non-elites. Using the Mashhad police newspaper Ettelā‘āt-e Yawmiya, it reconstructs conflicts between masters and apprentices, soldiers and civilians, tribes and settled populations, artisans, and family members. The article pays attention to the spatial distribution of crime in public and private spaces throughout the city. Finally, it considers the spectrum of crimes falling within the purview of the police including theft, raids, violence, debauchery, drunkenness, public disorder, and gambling.
The Shajara-ye Turk as an Important Source on the History of Relations between Khiva and Its Neighbors
Authors: Allaeva Nigora 
Published: May 2014

Abstract
This article examines the relations between Khiva and its neighbors, specifically the Safavids and the Shaybanids, in the sixteenth and first half of the seventeenth century. It draws substantially on the Shajara-ye Turk, which has hitherto not been analysed in order to illustrate the relations between Khiva and other regional powers in its immediate reach. Using a comparative approach, we argue that, contrary to the prevailing notion of isolation found in the secondary literature, Khiva maintained manifold ties with its neighbors and was well embedded within the framework of regional states. Contrary to the arguments in the secondary literature, the article concludes that the Sunni-Shi‘i conflict had a more political rather than religious character, and did not create any impediment between dynasties of different religious backgrounds.
Translation, Authority and Exegesis in Modern Iranian Sufism: Two Iranian Sufi Masters in Dialogue
Authors: Cancian Alessandro 
Published: May 2014

Abstract
This paper is a reflection on the treatise, Qor’ān-e majid va se dāstān-e asrār-āmiz-e ‘erfāni (“The noble Koran and three arcane mystical stories”), composed by the Iranian Sufi master Hājj Soltān-Hoseyn Tābanda Gonābādi “Rezā-‘Ali Shāh” (d. 1992). The “three arcane mystical stories” in this treatise are the pericopes presented in the Surat al-Kahf (i.e., those of the seven sleepers, Moses and al-Khezr, and Zu’l-qarneyn), and the work itself is what I call an “augmented translation” into Persian of the relevant passages of Soltān-‘Ali Shāh’s (1835-1909) tafsir, the Bayān al-saāda fi maqāmāt al-‘ebāda.The augmented translation carried out by Rezā-‘Ali Shāh is interesting not only because of its doctrinal content (and, in this respect, probably only to a limited extent), but also because it provides an example of how religious authority is articulated in contemporary Iran. The way it was done, the language that was used, the conscious introduction of new material all show how a modern 20th-century Iranian spiritual master struggled to transform the language of tradition while respecting the very authority from which his religious status stemmed.
Paradoxical Influence of the Islamicized School Education in Iran since the 1980s on Performance
Authors: Matti Nathalie 
Published: May 2014

Abstract
After the 1979 revolution, the education system in Iran was reformed. In order to create a “new individual integrated in the Islamic society” (Paivandi, 14), at the beginning of the 1980s, the Iranian regime put the issue of learning at the center of the construction of a new society with a strong Islamic identity.
The implications of the reformed school in the aesthetic field, and in particular in actresses’ performances, created very tight meshes, linking together the active and the passive learning of the Iranian population. Nevertheless, it is possible to understand its complexity through the observation and analysis of actresses’ performances in the theater and cinema, considering it as a laboratory of life that gives us access to the realm of the senses.