bluuebunny/crossref_metadata_2025_split huggingface dataset:
Boronophenylalanine, a boron delivery agent for boron neutron capture therapy, is transported by ATB0,+, LAT1 and LAT2
Authors: Wongthai Printip , Hagiwara Kohei , Miyoshi Yurika , Wiriyasermkul Pattama , Wei Ling , Ohgaki Ryuichi , Kato Itsuro , Hamase Kenji , Nagamori Shushi , Kanai Yoshikatsu 
Published: January 2015

The efficacy of boron neutron capture therapy relies on the selective delivery of boron carriers to malignant cells. p‐Boronophenylalanine (BPA), a boron delivery agent, has been proposed to be localized to cells through transporter‐mediated mechanisms. In this study, we screened aromatic amino acid transporters to identify BPA transporters. Human aromatic amino acid transporters were functionally expressed in Xenopus oocytes and examined for BPA uptake and kinetic parameters. The roles of the transporters in BPA uptake were characterized in cancer cell lines. For the quantitative assessment of BPA uptake, HPLC was used throughout the study. Among aromatic amino acid transporters, ATB0,+, LAT1 and LAT2 were found to transport BPA with Km values of 137.4 ± 11.7, 20.3 ± 0.8 and 88.3 ± 5.6 μM, respectively. Uptake experiments in cancer cell lines revealed that the LAT1 protein amount was the major determinant of BPA uptake at 100 μM, whereas the contribution of ATB0,+ became significant at 1000 μM, accounting for 20–25% of the total BPA uptake in MCF‐7 breast cancer cells. ATB0,+, LAT1 and LAT2 transport BPA at affinities comparable with their endogenous substrates, suggesting that they could mediate effective BPA uptake in vivo. The high and low affinities of LAT1 and ATB0,+, respectively, differentiate their roles in BPA uptake. ATB0,+, as well as LAT1, could contribute significantly to the tumor accumulation of BPA at clinical dose.
Balade Blanche: Putting New Museum Theory into Practice
Authors: Beaujot Ariel 
Published: January 2015

AbstractOver the past decade, museum administrators, curators, and staff have begun to recognize a subset of visitors that is starting to view their roles in museums differently. No longer is this new museum audience willing to accept curators’ authoritative narratives passively. Instead, this group of visitors seeks to share authority with curators. In response, some curators have employed strategies to encourage visitors to participate more fully in museums by asking them to contribute to exhibits more actively and by creating exhibits that allow visitors to immerse themselves into the stories that are being communicated. This article explores how Balade Blanche, a historical ghost tour that took place in France in 2010, took on some of the new demands of this “participatory visitor” and put them into practice by sharing curatorial authority and creating an immersive experience.
Creating Discursive Space for Intercultural Encounters: La Casa Encendida, Madrid
Authors: Moore Michelle 
Published: January 2015

AbstractAs increasingly heterogeneous museum audiences seek to participate actively in museum discourses, a new question arises: who is included in the conversation? This article extends that question to cultural‐spatial production, and seeks to illuminate key players’ roles in creating spaces that welcome marginalized groups in order to facilitate intercultural encounters. It argues that inclusive, discursive environments are as much a product of “scripting as design.” La Casa Encendida (The Incandescent House), a cultural center in Madrid, Spain, is used as a case study. It is examined in two stages: first, the ambitions and strategies of its makers and managers are explored; second, project outcomes are tested following the staging of Mundo Extreme (Extreme World), an exhibition that aimed to mediate between the hidden cultural worlds of artists with intellectual disabilities and wider arts scenes. This analysis highlights the contribution of cultural‐spatial production and occupation strategies to facilitating, revealing, and drawing into dialogue marginalized groups.
Effect of subcutaneous insulin detemir on glucose flux and lipolysis during hyperglycaemia in people with type 1 diabetes
Authors: Herring R. A. , Shojaee‐Moradie F. , Umpleby A. M. , Jones R. , Jackson N. , Russell‐Jones D. L. 
Published: January 2015

AimsTo investigate, using a novel non‐steady‐state protocol, the differential effects of subcutaneous (s.c.) detemir and NPH insulin on glucose flux and lipid metabolism after insulin withdrawal.MethodsAfter a period of insulin withdrawal resulting in whole‐blood glucose concentration of 7 mmol/l, 11 participants (five men, mean age 41.0 years, mean body mass index 25 kg/m2) with type 1 diabetes (mean glycated haemoglobin concentration 57 mmol/mol, mean diabetes duration 14 years) received 0.5 units per kg body weight s.c. insulin detemir or NPH insulin in random order. Stable isotopes of glucose and glycerol were infused intravenously throughout the study protocol.ResultsGlucose concentration decreased after insulin treatment as a result of suppression of endogenous glucose production, which occurred to a similar extent with both detemir and NPH insulin. The rate of glucose disappearance (Rd) was not increased significantly with either type of insulin. When the effect of detemir and NPH insulin on glucose flux at glucose concentrations between 9 and 6 mmol/l was examined, glucose rate of appearance (Ra) was similar with the two insulins; however, glucose Rd was greater with NPH insulin than with detemir at glucose concentrations of 8.0, 8.5, 7.0 and 6.0 mmol/l (p < 0.05) The percentage change in glycerol Ra, a measure of lipolysis, was greater in the NPH group than in the detemir group (p = 0.04).ConclusionsThe results of the study are consistent with the hypothesis that detemir has a lesser effect on the periphery, as evidenced by a lesser effect on peripheral glucose uptake at specific glucose concentrations.
Identification of a direct GABAergic pallidocortical pathway in rodents
Authors: Chen Michael C. , Ferrari Loris , Sacchet Matthew D. , Foland‐Ross Lara C. , Qiu Mei‐Hong , Gotlib Ian H. , Fuller Patrick M. , Arrigoni Elda , Lu Jun 
Published: January 2015

AbstractInteraction between the basal ganglia and the cortex plays a critical role in a range of behaviors. Output from the basal ganglia to the cortex is thought to be relayed through the thalamus, but an intriguing alternative is that the basal ganglia may directly project to and communicate with the cortex. We explored an efferent projection from the globus pallidus externa (GPe), a key hub in the basal ganglia system, to the cortex of rats and mice. Anterograde and retrograde tracing revealed projections to the frontal premotor cortex, especially the deep projecting layers, originating from GPe neurons that receive axonal inputs from the dorsal striatum. Cre‐dependent anterograde tracing in Vgat‐ires‐cre mice confirmed that the pallidocortical projection is GABAergic, and in vitro optogenetic stimulation in the cortex of these projections produced a fast inhibitory postsynaptic current in targeted cells that was abolished by bicuculline. The pallidocortical projections targeted GABAergic interneurons and, to a lesser extent, pyramidal neurons. This GABAergic pallidocortical pathway directly links the basal ganglia and cortex, and may play a key role in behavior and cognition in normal and disease states.
No abnormalities of intrinsic brain connectivity in the interictal phase of migraine with aura
Authors: Hougaard A. , Amin F. M. , Magon S. , Sprenger T. , Rostrup E. , Ashina M. 
Published: January 2015

Background and purposeFunctional neuroimaging studies have shown hyperresponsiveness of cortical areas to visual stimuli in migraine patients with aura outside of attacks. This may be a key feature in the initiation of aura episodes and possibly also migraine headache attacks. It is unknown if cortical dysfunction is present at rest, i.e. in the absence of any external stimuli. Functional magnetic resonance imaging is a powerful technique for evaluating resting state functional connectivity, i.e. coherence of brain activity across cerebral areas. The objective of this study was to investigate resting‐state functional brain connectivity in migraineurs with aura outside of attacks using functional magnetic resonance imaging.MethodsForty patients suffering from migraine with visual aura and 40 individually age and gender matched healthy controls with no history or family history of migraine were investigated. Following advanced denoising, the data were analyzed both in a hypothesis‐driven fashion, testing for abnormalities involving 27 different brain areas of potential relevance to migraine with aura including the cortical visual areas, the amygdala and peri‐aqueductal grey matter, and in a data‐driven exploratory fashion (dual regression) in order to reveal any possible between‐group differences of resting state networks. Age, gender, attack frequency and disease duration were included as nuisance variables.ResultsNo differences of functional connectivity were found between patients and controls.ConclusionsThe previously reported increased cortical hyperresponsivity in the interictal phase of migraine with aura is unlikely to be caused by abnormalities of intrinsic brain connectivity. The interictal migraine aura brain may be abnormally functioning only during exposure to external stimuli.
Hospital crossover increases utilization for people with epilepsy: A retrospective cohort study
Authors: Grinspan Zachary M. , Shapiro Jason S. , Abramson Erika L. , Jung Hye‐Young , Kaushal Rainu , Kern Lisa M. 
Published: January 2015

SummaryObjectives“Hospital crossover” occurs when people visit multiple hospitals for care, which may cause gaps in electronic health records. Although crossover is common among people with epilepsy, the effect on subsequent use of health services is unknown. Understanding this effect will help prioritize health care delivery innovations targeted for this population.MethodsWe collected de‐identified information from a health information exchange network describing 7,836 people with epilepsy who visited any of seven hospitals in New York, NY from 2009–2012. Data included demographics, comorbidities, and 2 years of visit information from ambulatory, inpatient, emergency department (ED), and radiology settings. We performed two complementary retrospective cohort analyses, in order to (1) illustrate the effect on a carefully selected subgroup, and (2) confirm the effect across the study population. First, we performed a matched cohort analysis on 410 pairs of individuals with and without hospital crossover in the baseline year. Second, we performed a propensity score odds weighted ordinal logistic regression analysis to estimate the effect across all 7,836 individuals. The outcomes were the use of six health services in the follow‐up year.ResultsIn the matched pair analysis, baseline hospital crossover increased the odds of more visits in the ED (odds ratio 1.42, 95% confidence interval [CI] 1.05–1.95) and radiology settings (1.7, 1.22–2.38). The regression analysis confirmed the ED and radiology findings, and also suggested that crossover led to more inpatient admissions (1.35, 1.11–1.63), head CTs (1.44, 1.04–2), and brain MRIs (2.32, 1.59–3.37).SignificanceBaseline hospital crossover is an independent marker for subsequent increased health service use in multiple settings among people with epilepsy. Health care delivery innovations targeted for people with epilepsy who engage in hospital crossover should prioritize (1) sharing radiology images and reports (to reduce unnecessary radiology use, particularly head CTs), and (2) improving coordination of care (to reduce unnecessary ED and inpatient use).
Assessment of aminoglycoside dosing and estimated glomerular filtration rate in determining gentamicin and tobramycin area under the curve and clearance
Authors: Lim A. K. H. , Mathanasenarajah G. , Larmour I. 
Published: January 2015

AbstractBackgroundAminoglycoside clearance depends on kidney function, but the Australian Therapeutic Guidelines for antibiotics (version 14, 2010) recommend initial dosing based on weight without consideration of kidney function. Other guidelines that modify dosing based on kidney function estimates often use the Cockroft–Gault equation, but the role of the estimated glomerular filtration rate equations for this purpose is unclear.AimTo determine the performance of current guideline dosing in achieving target area‐under‐the‐curve and examine the relative precision of the estimated glomerular filtration rate equations compared with traditional Cockroft–Gault creatinine clearance in predicting aminoglycoside clearance.MethodsWe analysed 496 aminoglycoside treatment episodes involving 1377 infusions in adult patients. Conformity with antibiotic guideline dosing was achieved if the discrepancy between prescribed and recommended dose was less than 15%. Aminoglycoside clearance was determined from linear regression using a one compartment model with the Aminoglycoside Levels and Daily Dose Indicator programme. We assessed the precision of the Cockroft–Gault, Modification of Diet in renal Disease Study and Chronic Kidney Disease–Epidemiology Collaboration (CKD–EPI) equations in predicting aminoglycoside clearance by correlation and linear regression.ResultsConformity with guideline dosing was not associated with achieving target area‐under‐the‐curve. The CKD‐EPI estimated glomerular filtration rate adjusted for body surface area showed the highest correlation (gentamicin, r = 0.66; tobramycin, r = 0.82) and best predictive model for aminoglycoside clearance.ConclusionCurrent guideline dosing may be suboptimal for achieving target area‐under‐the‐curve. The CKD‐EPI equation adjusted for patient body surface area best predicts aminoglycoside clearance, and could be evaluated as a covariate in determining initial aminoglycoside dosing.
Reversible lacrimal gland‐protective regulatory T‐cell dysfunction underlies male‐specific autoimmune dacryoadenitis in the non‐obese diabetic mouse model of Sjögren syndrome
Authors: Lieberman Scott M. , Kreiger Portia A. , Koretzky Gary A. 
Published: January 2015

SummaryCD4+ CD25+ Foxp3+ regulatory T (Treg) cells are required to maintain immunological tolerance; however, defects in specific organ‐protective Treg cell functions have not been demonstrated in organ‐specific autoimmunity. Non‐obese diabetic (NOD) mice spontaneously develop lacrimal and salivary gland autoimmunity and are a well‐characterized model of Sjögren syndrome. Lacrimal gland disease in NOD mice is male‐specific, but the role of Treg cells in this sex‐specificity is not known. This study aimed to determine if male‐specific autoimmune dacryoadenitis in the NOD mouse model of Sjögren syndrome is the result of lacrimal gland‐protective Treg cell dysfunction. An adoptive transfer model of Sjögren syndrome was developed by transferring cells from the lacrimal gland‐draining cervical lymph nodes of NOD mice to lymphocyte‐deficient NOD‐SCID mice. Transfer of bulk cervical lymph node cells modelled the male‐specific dacryoadenitis that spontaneously develops in NOD mice. Female to female transfers resulted in dacryoadenitis if the CD4+ CD25+ Treg‐enriched population was depleted before transfer; however, male to male transfers resulted in comparable dacryoadenitis regardless of the presence or absence of Treg cells within the donor cell population. Hormone manipulation studies suggested that this Treg cell dysfunction was mediated at least in part by androgens. Surprisingly, male Treg cells were capable of preventing the transfer of dacryoadenitis to female recipients. These data suggest that male‐specific factors promote reversible dysfunction of lacrimal gland‐protective Treg cells and, to our knowledge, form the first evidence for reversible organ‐protective Treg cell dysfunction in organ‐specific autoimmunity.
Improvement of overlapping nuclear track densitometry
Authors: GHERGHEREHCHI M. , KIM S. Y. , AFARIDEH H. , KIM Y. S. , CHAI J. S. 
Published: January 2015

SummaryDetection of tracks produced by α particles, protons or nuclear fission fragments in plastic detectors, viz., solid‐state nuclear track detectors, constitutes a very important tool in various areas. It is not easy for humans to count CR‐39 nuclear tracks manually, especially when the track density is very high. An automated computer program called KTTMS2, written in C++ and running with a user friendly interface, has been developed for recognition and parametric measurements of etched tracks in images captured from the surface of solid‐state nuclear track detectors. Well‐known edge detection methods were applied to estimate the precision and accuracy of nuclear track densitometry using the CR‐39 detector. Among the various routine edge detection methods, the Canny method was chosen because it was the most accurate technique. Because accuracy becomes more important as the track density increases, this allows more overlapping tracks to be detected. KTTMS2 (the proposed system) has an efficiency of 95% and can identify the noise as a background track (5%). Experimental results showed that the error percentage was reduced from 7.63% to 3.23% for high‐density tracks when the count was adjusted by the estimated overlapping tracks.
Erectile Dysfunction after Sickle Cell Disease–Associated Recurrent Ischemic Priapism: Profile and Risk Factors
Authors: Anele Uzoma A. , Burnett Arthur L. 
Published: January 2015

ABSTRACT

Introduction
Risk factors associated with erectile dysfunction (ED) that results from recurrent ischemic priapism (RIP) in sickle cell disease (SCD) are incompletely defined.

Aim
This study aims to determine and compare ED risk factors associated with SCD and non-SCD-related “minor” RIP, defined as having ≥2 episodes of ischemic priapism within the past 6 months, with the majority (&gt;75%) of episodes lasting &lt;5 hours.

Methods
We performed a retrospective study of RIP in SCD and non-SCD patients presenting from June 2004 to March 2014 using the International Index of Erectile Function (IIEF), IIEF-5, and priapism-specific questionnaires.

Main Outcome Measures
Prevalence rates and risk factor correlations for ED associated with RIP.

Results
The study was comprised of 59 patients (40 SCD [mean age 28.2 ± 8.9 years] and 19 non-SCD [15 idiopathic and four drug-related etiologies] [mean age 32.6 ± 11.7 years]). Nineteen of 40 (47.5%) SCD patients vs. four of 19 (21.1%) non-SCD patients (39% overall) had ED (IIEF &lt;26 or IIEF-5 &lt;22) (P = 0.052). SCD patients had a longer mean time-length with RIP than non-SCD patients (P = 0.004). Thirty of 40 (75%) SCD patients vs. 10 of 19 (52.6%) non-SCD patients (P = 0.14) had “very minor” RIP (episodes regularly lasting ≤2 hours). Twenty-eight of 40 (70%) SCD patients vs. 14 of 19 (73.7%) non-SCD patients had weekly or more frequent episodes (P = 1). Of all patients with very minor RIP, ED was found among 14 of 30 (46.7%) SCD patients vs. none of 10 (0%) non-SCD patients (P = 0.008). Using logistic regression analysis, the odds ratio for developing ED was 4.7 for SCD patients, when controlling for RIP variables (95% confidence interval: 1.1–21.0).

Conclusions
ED is associated with RIP, occurring in nearly 40% of affected individuals overall. SCD patients are more likely to experience ED in the setting of “very minor” RIP episodes and are five times more likely to develop ED compared with non-SCD patients.
Invasion history affects genetic structure in island rat populations
Authors: Theuerkauf J. , Kuehn R. , Gula R. , Sztencel‐Jabłonka A. , Jourdan H. , Taugamoa A. , Labrousse D. , Bogdanowicz W. 
Published: January 2015

AbstractInvasive species usually go through a period of reduced genetic variability due to a bottleneck. The genetic constitution of an invading population should therefore reflect the time since invasion and the number of introduction events. We studied genetic population structure of three rat species occurring sympatrically on the island of Futuna (46 km2), where they were introduced recently (Rattus rattus), 80–170 years ago (R. norvegicus) and about 3000 years ago (R. exulans). From 2007 to 2012, we trapped 3900 rats during a rodent regulation programme over 20 000 trap nights and took 565 rat tissue samples for genetic analyses. By examining genetic variation and spatial distribution of genetic resemblance, we evaluated the consequences of the time after introduction for genetic population structure. Observed heterozygosity, expected heterozygosity, number of alleles and allelic richness generally increased with increasing length of time a species was introduced to the island. The species with longer invasion history had also higher spatial admixture. However, in R. norvegicus, the observed heterozygosity was lower and inbreeding higher than expected by the invasion history. We relate this with the assumption that this species was introduced once or a few times and in low numbers, while R. exulans was intentionally introduced many times by Polynesian navigators and R. rattus had a high chance of being introduced on multiple occasions in recent times.
Maternal environment affects the genetic basis of seed dormancy in Arabidopsis thaliana
Authors: Postma Froukje M. , Ågren Jon 
Published: January 2015

AbstractThe genetic basis of seed dormancy, a key life history trait important for adaptive evolution in plant populations, has yet been studied only using seeds produced under controlled conditions in greenhouse environments. However, dormancy is strongly affected by maternal environmental conditions, and interactions between seed genotype and maternal environment have been reported. Consequently, the genetic basis of dormancy of seeds produced under natural field conditions remains unclear. We examined the effect of maternal environment on the genetic architecture of seed dormancy using a recombinant inbred line (RIL) population derived from a cross between two locally adapted populations of Arabidopsis thaliana from Italy and Sweden. We mapped quantitative trait loci (QTL) for dormancy of seeds produced in the greenhouse and at the native field sites of the parental genotypes. The Italian genotype produced seeds with stronger dormancy at fruit maturation than did the Swedish genotype in all three environments, and the maternal field environments induced higher dormancy levels compared to the greenhouse environment in both genotypes. Across the three maternal environments, a total of nine dormancy QTL were detected, three of which were only detected among seeds matured in the field, and six of which showed significant QTL × maternal environment interactions. One QTL had a large effect on dormancy across all three environments and colocalized with the candidate gene DOG1. Our results demonstrate the importance of studying the genetic basis of putatively adaptive traits under relevant conditions.