bluuebunny/crossref_metadata_2025_split huggingface dataset:
Off-Label Drug Use in a Single-Center Pediatric Cardiac Intensive Care Unit
Authors: Maltz Lily A. , Klugman Darren , Spaeder Michael C. , Wessel David L. 
Published: July 2013

Background: The frequency of off-label drug use and its association with morbidity and mortality in the cardiac intensive care unit (CICU) has not been previously studied. Methods: Patients less than 18 years of age admitted to the CICU from June to August 2008 were retrospectively identified. Patient demographics were collected for 30 days or until CICU discharge. Off-label drug use was defined as the prescription of a medication that lacked a labeled indication based on patient’s age as reported in the Micromedex drug database and electronic Physician’s Desk Reference. Results: Eighty-two patients were admitted to the CICU during the study period. In all, 40 (46%) patients were male; the median age was 10.6 months. Common diagnoses were left-to-right shunt lesions (20.7%) and single-ventricle lesions (20.7%), with an overall mortality of 2.4%. Of all drugs prescribed, 36% were off-label. In all, 94% of the patients received ≥1 drug off-label. The median number of drugs prescribed off-label was four. Patients receiving more than four off-label medications were younger, had longer CICU lengths of stay (median 9.5 vs 2 days, P < .001), and increased ventilator days (median two vs one day, P < .001). Conclusions: Off-label drug use in the CICU is common. Frequency of use is likely higher in patients with a higher severity of illness. Further safety, efficacy, and pharmaceutical trials are warranted to optimize the use of these drugs to improve outcomes.
Virus-associated activation of innate immunity induces rapid disruption of Peyer’s patches in mice
Authors: Heidegger Simon , Anz David , Stephan Nicolas , Bohn Bernadette , Herbst Tina , Fendler Wolfgang Peter , Suhartha Nina , Sandholzer Nadja , Kobold Sebastian , Hotz Christian , Eisenächer Katharina , Radtke-Schuller Susanne , Endres Stefan , Bourquin Carole 
Published: July 2013

Key PointsSystemic virus infection leads to rapid disruption of the Peyer’s patches but not of peripheral lymph nodes. Virus-associated innate immune activation and type I IFN release blocks trafficking of B cells to Peyer’s patches.
Crystal structure of signal regulatory protein gamma (SIRPγ) in complex with an antibody Fab fragment
Authors: Nettleship Joanne E , Ren Jingshan , Scott David J , Rahman Nahid , Hatherley Deborah , Zhao Yuguang , Stuart David I , Barclay A Neil , Owens Raymond J 
Published: July 2013

Abstract

Background
Signal Regulatory Protein γ (SIRPγ) is a member of a closely related family of three cell surface receptors implicated in modulating immune/inflammatory responses. SIRPγ is expressed on T lymphocytes where it appears to be involved in the integrin-independent adhesion of lymphocytes to antigen-presenting cells. Here we describe the first full length structure of the extracellular region of human SIRPγ.

Results
We obtained crystals of SIRPγ by making a complex of the protein with the Fab fragment of the anti-SIRP antibody, OX117, which also binds to SIRPα and SIRPβ. We show that the epitope for FabOX117 is formed at the interface of the first and second domains of SIRPγ and comprises residues which are conserved between all three SIRPs. The FabOX117 binding site is distinct from the region in domain 1 which interacts with CD47, the physiological ligand for both SIRPγ and SIRPα but not SIRPβ. Comparison of the three domain structures of SIRPγ and SIRPα showed that these receptors can adopt different overall conformations due to the flexibility of the linker between the first two domains. SIRPγ in complex with FabOX117 forms a dimer in the crystal. Binding to the Fab fixes the position of domain 1 relative to domains 2/3 exposing a surface which favours formation of a homotypic dimer. However, the interaction appears to be relatively weak since only monomers of SIRPγ were observed in sedimentation velocity analytical ultracentrifugation of the protein alone. Studies of complex formation by equilibrium ultracentrifugation showed that only a 1:1 complex of SIRPγ: FabOX117 was formed with a dissociation constant in the low micromolar range (K
d = 1.2 +/− 0.3 μM).

Conclusion
The three-domain extracellular regions of SIRPs are structurally conserved but show conformational flexibility in the disposition of the amino terminal ligand-binding Ig domain relative to the two membrane proximal Ig domains. Binding of a cross-reactive anti-SIRP Fab fragment to SIRPγ stabilises a conformation that favours SIRP dimer formation in the crystal structure, though this interaction does not appear sufficiently stable to be observed in solution.
A commonly used rumen-protected conjugated linoleic acid supplement marginally affects fatty acid distribution of body tissues and gene expression of mammary gland in heifers during early lactation
Authors: Kramer Ronny , Wolf Simone , Petri Tobias , von Soosten Dirk , Dänicke Sven , Weber Eva-Maria , Zimmer Ralf , Rehage Juergen , Jahreis Gerhard 
Published: July 2013

Abstract

Background
Conjugated linoleic acids (CLA) in general, and in particular the trans- 10,cis- 12 (t 10,c 12-CLA) isomer are potent modulators of milk fat synthesis in dairy cows. Studies in rodents, such as mice, have revealed that t 10,c 12-CLA is responsible for hepatic lipodystrophy and decreased adipose tissue with subsequent changes in the fatty acid distribution. The present study aimed to investigate the fatty acid distribution of lipids in several body tissues compared to their distribution in milk fat in early lactating cows in response to CLA treatment. Effects in mammary gland are further analyzed at gene expression level.

Methods
Twenty-five Holstein heifers were fed a diet supplemented with (CLA groups) or without (CON groups) a rumen-protected CLA supplement that provided 6 g/d of c 9,t 11- and t 10,c 12-CLA. Five groups of randomly assigned cows were analyzed according to experimental design based on feeding and time of slaughter. Cows in the first group received no CLA supplement and were slaughtered one day postpartum (CON0). Milk samples were taken from the remaining cows in CON and CLA groups until slaughter at 42 (period 1) and 105 (period 2) days in milk (DIM). Immediately after slaughter, tissue samples from liver, retroperitoneal fat, mammary gland and M. longissimus (13th rib) were obtained and analyzed for fatty acid distribution. Relevant genes involved in lipid metabolism of the mammary gland were analyzed using a custom-made microarray platform.

Results
Both supplemented CLA isomers increased significantly in milk fat. Furthermore, preformed fatty acids increased at the expense of de novo- synthesized fatty acids. Total and single trans- octadecenoic acids (e.g., t 10-18:1 and t 11-18:1) also significantly increased. Fatty acid distribution of the mammary gland showed similar changes to those in milk fat, due mainly to residual milk but without affecting gene expression. Liver fatty acids were not altered except for trans- octadecenoic acids, which were increased. Adipose tissue and M. longissimus were only marginally affected by CLA supplementation.

Conclusions
Daily supplementation with CLA led to typical alterations usually observed in milk fat depression (reduction of de novo-synthesized fatty acids) but only marginally affected tissue lipids. Gene expression of the mammary gland was not influenced by CLA supplementation.
Can initial diagnostic PET-CT aid to localize tumor bed in breast cancer radiotherapy: feasibility study using deformable image registration
Authors: Cho Oyeon , Chun Mison , Oh Young Taek , Kim Mi Hwa , Park Hae Jin , Heo Jae Sung , Noh O Kyu 
Published: July 2013

Abstract

Background
Localization of the tumor bed of breast cancer is crucial for accurate planning of boost irradiation. Lumpectomy cavity and surgical clips provide localizing information about tumor bed. However, defining the tumor bed is often difficult because of presence of unclear lumpectomy cavity and lack of certain information such as absence of surgical clips. In the present study, we evaluated the feasibility of initial diagnostic PET-CT in localization of the tumor bed using deformable image registration (DIR).

Methods
We selected twenty-five patients who had an initial diagnostic PET-CT performed and underwent breast-conserving surgery with surgical clips in tumor bed. In every individual patient, two target volumes were separately delineated on planning CT; 1) target volume based on surgical clips with a margin of 1 cm (TVclip) and 2) tumor volume based on 90% of maximum SUV on PET-CT registered by DIR (TVPET). The percent of TVPET in TVclip (Vin) was calculated and distance between center points of two volumes (Dcenter) was also measured.

Results
Mean Dcenter between two volumes was 1.4 cm (range, 0.33 – 2.53). Mean Vin was 94.8% (range, 60.9-100) and 100% in 18 out of 25 patients. When compared to the center of TVclip, the center of TVPET tended to be located posteriorly (mean 0.3 cm, standard deviation 0.6), laterally (mean 0.3 cm, standard deviation 0.8) and inferiorly (mean 0.4 cm, standard deviation 0.9).

Conclusion
Initial diagnostic PET-CT can be one of the possible references to localize the tumor bed in breast cancer radiotherapy.
Preparation and Photovoltaic Application of Fullerene–Porphyrin Composite Micropowder
Authors: Kimura Kento , Oku Takeo , Akiyama Tsuyoshi 
Published: July 2013

Abstract
C60 fullerene and 5,10,15,20-tetrakis(4-aminophenyl)porphyrin (TAPP) composite micropowder was prepared by simply mixing C60 and TAPP in an organic solvent under ambient conditions. The composite micropowder contributed to photoelectric conversion, which was confirmed by a semi-wet-type photovoltaic application.
Unravelling the enigma of Perthes disease
Authors: Perry DC 
Published: July 2013

Perthes disease is an idiopathic avascular necrosis of a juvenile hip. Although 2010 marked a century since it was first described, the aetiology remains unknown. It is suggested that adverse socioeconomic circumstances may be a key precipitant. This work describes recent studies that explore the disease epidemiology. Descriptive studies include a case register from Merseyside, hospital discharge data from Scotland, analysis of the world’s largest community disease register (General Practice Research Database [GPRD]) and a systematic review of incidence. Analytical studies include a nested case-controlled study in the GPRD and a hospital case-controlled study. The studies demonstrated a striking north–south divide in the UK incidence of Perthes disease, similar to that seen in many adult diseases. There was a sustained fall in disease frequency in all studies, with a narrowing of the north–south divide. There was a strong association with area deprivation, independent of living in an urban environment. Internationally, equatorial regions were unaffected by disease and northern Europe had the highest incidence, which was primarily a function of race although latitude was an independent predictor. Individual characteristics associated with the disease were congenital anomalies of the genitourinary tract and a structural abnormality of arterial calibre. Despite a falling incidence, Perthes disease remains an important cause of child morbidity and exemplifies socioeconomic inequalities. A deprivation-related exposure, acting early in development, appears critical. The aetiological factor in Perthes disease remains elusive but it is likely that unravelling this enigma may unlock additional secrets pertaining to the developmental origins of this and other diseases.
Evaluation of the efficacy of a combination of diltiazem and periprostatic nerve block in pain control during transrectal ultrasonography-guided biopsy of the prostate
Authors: Jindal T , Mandal SN , Biswas G , Karmakar D 
Published: July 2013

Introduction The choice of analgesia during prostate biopsy remains controversial. The pain has dual origin: from the insertion of the probe as well as the biopsy itself. Periprostatic nerve block (PPNB) is currently the gold standard modality for decreasing pain of prostate biopsy but it does not alleviate the pain of probe insertion. A randomised controlled trial was performed to test the efficacy and safety of the combination of topical application of diltiazem gel and PPNB for pain control during transrectal ultrasonography guided prostate biopsy. Methods A total of 73 patients who were to undergo their first prostate biopsy were randomised to receive either 2ml of 2% topical diltiazem gel or a placebo 15 minutes before the biopsy. All the patients then had a PPNB using 1% lignocaine. A ten-point visual analogue scale was used to record the pain immediately after the insertion of the probe and during the biopsy. Any adverse effects were also recorded. Results There was no significant difference in the mean age and prostate volumes between the groups. There was a significantly lower mean pain score due to probe insertion in those patients who received topical diltiazem than in the placebo group (p<0.0001). There was no significant difference between the pain scores during the biopsy itself between the two groups. Conclusions Topical diltiazem significantly reduces the pain of probe insertion during prostate biopsy and can be used effectively as an adjuvant to PPNB.
Personalized Medicine in the Context of Comparative Effectiveness Research
Authors: Basu Anirban 
Published: July 2013

Abstract
The world of patient-centered outcomes research (PCOR) seems to bridge the previously disjointed worlds of comparative effectiveness research (CER) and personalized medicine (PM). Indeed, theoretical reasoning on how information on medical quality should inform decision making, both at the individual and the policy level, reveals that personalized information on the value of medical products is critical for improving decision making at all levels. However, challenges to generating, evaluating and translating evidence that might lead to personalization need to be critically assessed. In this paper, I discuss two different concepts of personalized medicine – passive personalization (PPM) and active personalization (APM) that are important to distinguish in order to invest efficiently in PCOR and develop objective evidence on the value of personalization that will aid in its translation. APM constitutes the process of actively seeking identifiers, which can be genotypical, phenotypical or even environmental, that can be used to differentiate between the marginal benefits of treatment across patients. In contrast, PPM involves a passive approach to personalization where, in the absence of explicit research to discover identifiers, patients and physicians “learn by doing” mostly due to the repeated use of similar products on similar patients. Benchmarking the current state of PPM sets the bar to which the expected value of any new APM agenda should be evaluated. Exploring processes that enable PPM in practice can help discover new APM agendas, such as those based on developing predictive algorithms based on clinical, phenotypical and preference data, which may be more efficient that trying to develop expensive genetic tests. It can also identify scenarios or subgroups of patients where genomic research would be most valuable since alternative prediction algorithms were difficult to develop in those settings. Two clinical scenarios are discussed where PPM was explored through novel econometric methods. Related discussions around exploring PPM processes, multi-dimensionality of outcomes, and a balanced agenda for future research on personalization follow.
Legendrian realization in convex Lefschetz fibrations and convex stabilizations
Authors: Akbulut Selman , Arikan Mehmet F. 
Published: July 2013

Abstract
We show that, up to a Liouville homotopy and a deformation of compact convex Lefschetz fibrations on W, any Lagrangian submanifold with trivial first de Rham cohomology group, embedded on a (symplectic) page of the (induced) convex open book on

∂
W

$\partial W$

, can be assumed to be Legendrian in

∂
W

$\partial W$

with the induced contact structure. This can be thought as the extension of Giroux's Legendrian realization (which holds for contact open books) for the case of convex open books. We also show that the convex stabilization of a compact convex Lefschetz fibration on W yields a compact convex Lefschetz fibration on a Liouville domain W' which is exact symplectomorphic to a positive expansion of W. In particular, with the induced structures

∂
W

$\partial W$

and

∂

W
'

$\partial W^{\prime }$

are contactomorphic.
Effects of selective hypothermia on blood-brain barrier integrity and tight junction protein expression levels after intracerebral hemorrhage in rats
Authors: Sun Hongwei , Tang Ying , Guan Xiqin , Li Lanfeng , Wang Desheng 
Published: July 2013

Abstract
Hypothermia has neuroprotective effects on global cerebral ischemic injuries. However, its efficacy after intracerebral hemorrhage (ICH) is inconclusive. In this study, bacterial collagenase was used to induce ICH stroke in male Wistar rats. We assessed the effects of normothermia and 4 h of local hypothermia (∼33.2°C) initiated 1, 6, or 12 h after collagenase infusion on hemorrhage volume and neurological outcomes. Following early cooling initiated after 1 h, blood-brain barrier (BBB) disruption and brain water content were tested. Furthermore, the expression levels of tight junction (TJ) proteins (claudin 5 and occludin) and the proinflammatory cytokines interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were determined using Western blotting, real-time quantitative PCR, and immunohistochemical staining at 1 and 3 d after ICH. Early local hypothermia tends to reduce hemorrhagic volume and neurological deficits, but the difference is not statistically significant compared with other groups. However, early hypothermia significantly reduces BBB disruption, edema formation, the expression levels of IL-1β and TNF-α, and the loss of TJ proteins. Together, these data suggest that local hypothermia is an effective treatment for edema formation and BBB disruption via the upregulation of TJ proteins and the suppression of TNF-α and IL-1β.
The amino acids surrounding the flavin 7a-methyl group determine the UVA spectral features of a LOV protein
Authors: Raffelberg Sarah , Gutt Alexander , Gärtner Wolfgang , Mandalari Carmen , Abbruzzetti Stefania , Viappiani Cristiano , Losi Aba 
Published: July 2013

Abstract
Flavin-binding light, oxygen, and voltage (LOV) domains are UVA/blue-light-sensing protein units that form a reversible flavin mononucleotide-cysteine adduct upon light induction. In their dark-adapted state, LOV domains exhibit the typical spectral features of fully oxidized riboflavin derivatives. A survey on the absorption spectra of various LOV domains revealed that the UVA spectral range is the most variable region (whereas the absorption band at 450 nm is virtually unchanged), showing essentially two distinct patterns found in plant phototropin LOV1 and LOV2 domains, respectively. In this work, we have identified a residue directly interacting with the isoalloxazine methyl group at C(7a) as the major UVA spectral tuner. In YtvA from Bacillus subtilis, this amino acid is threonine 30, and its mutation into apolar residues converts the LOV2-like spectrum of native YtvA into a LOV1-like pattern. Mutation T30A also accelerates the photocycle ca. 4-fold. Together with control mutations at different positions, our results experimentally confirm the previously calculated direction of the transition dipole moment for the UVA ππ* state and identify the mechanisms underlying spectral tuning in the LOV domains.
The Value of Community-Focused Interprofessional Care in Peru for Developing Cultural Competency in Health Professions Students
Authors: Allen Carol B. , Smart Denise A. , Odom-Maryon Tamara , Swain Deborah 
Published: July 2013

AbstractInternational immersion experiences for health-care students have increased over the past 10 years. Students and faculty expect these experiences to increase cultural competency; however, research on outcomes of these programs has lacked rigor. Over a 4-year period, groups of nursing and other health professions students spent 3 weeks in Peru providing primary care and health education. Students attended pre-departure seminars addressing personal travel health and safety, culture and health care in Peru, working with interpreters, and ethics of international health care. Student participants (N= 77) completed an instrument assessing self-perceived cultural competency before and after the experience. Results of pre- and post-immersion scores showed significant increases in perceived cultural competency and increased self-efficacy in cultural knowledge, skills, and attitudes for four groups of students. Implications and future directions are discussed and recommended.
Management of prelabour rupture of membranes (PROM) at term
Authors: Ismail Abdul Qader Tahir , Lahiri Soma 
Published: July 2013

Abstract
Over a 20-month period we identified several cases of neonatal pneumonia associated with prelabour rupture of membranes (PROM) at term. PROM complicates 8%–10% of all pregnancies, yet 60% of cases occur at term. Ascending infection is a contributing factor and the incidence of chorioamnionitis in these patients is relatively high, especially with prolonged membrane rupture. The signs and symptoms NICE recommends patients look out for are not always present as the majority of infections are subclinical, yet associated maternal and neonatal morbidity of chorioamnionitis is potentially devastating. A survey of maternity units in the West Midlands reveals significant variance in management of these cases. Given the lack of consensus and clear evidence on optimal management of PROM at term, we believe early detection of developing infections could be enhanced by using a combination of investigations (at presentation, 12 and 24 h), as well as current advice to self-monitor temperature and vaginal loss.
Correlation of the heater’s duty cycle and specific energy consumption, and reduction in energy consumption in the pultrusion process
Authors: Khan Wajid Ali , Methven Jim 
Published: July 2013

AbstractEfforts have been made to improve the line speed and consequently the economy of the pultrusion in last few years, but most of the reported work focuses on the kinematics of the curing reaction and different resin systems. Pultrusion is a fast cure process where heat is supplied through heaters to start and complete the curing process inside the die to get quality product at relatively high speeds. This work has extended the previous studies and quantifies for the first time the duty cycle of the heaters of a typical process to establish a relationship between the duty cycle and the specific energy consumption (SEC) of the process. It is shown experimentally and analytically that preheating the precursor would result in higher line speeds and shorter duty cycle, thus contributing to the reduction in SEC by up to 30%.