bluuebunny/crossref_metadata_2025_split huggingface dataset:
Donor cycle and donor segmentation: new tools for improving blood donor management
Authors: Veldhuizen I. , Folléa G. , de Kort W. 
Published: February 2013

Background and ObjectivesAn adequate donor population is of key importance for the entire blood transfusion chain. For good donor management, a detailed overview of the donor database is therefore imperative. This study offers a new description of the donor cycle related to the donor management process. It also presents the outcomes of a European Project, Donor Management IN Europe (DOMAINE), regarding the segmentation of the donor population into donor types.Materials and MethodsBlood establishments (BEs) from 18 European countries, the Thalassaemia International Federation and a representative from the South‐Eastern Europe Health Network joined forces in DOMAINE. A questionnaire assessed blood donor management practices and the composition of the donor population using the newly proposed DOMAINE donor segmentation. 48 BEs in 34 European countries were invited to participate.ResultsThe response rate was high (88%). However, only 14 BEs could deliver data on the composition of their donor population. The data showed large variations and major imbalances in the donor population. In 79% of the countries, inactive donors formed the dominant donor type. Only in 21%, regular donors were the largest subgroup, and in 29%, the proportion of first‐time donors was higher than the proportion of regular donors.ConclusionGood donor management depends on a thorough insight into the flow of donors through their donor career. Segmentation of the donor database is an essential tool to understand the influx and efflux of donors. The DOMAINE donor segmentation helps BEs in understanding their donor database and to adapt their donor recruitment and retention practices accordingly. Ways to use this new tool are proposed.
On the Iwasawa theory of the Lubin–Tate moduli space
Authors: Kohlhaase Jan 
Published: February 2013

AbstractWe study the affine formal algebra$R$of the Lubin–Tate deformation space as a module over two different rings. One is the completed group ring of the automorphism group$\Gamma $of the formal module of the deformation problem, the other one is the spherical Hecke algebra of a general linear group. In the most basic case of height two and ground field$\mathbb {Q}_p$, our structure results include a flatness assertion for$R$over the spherical Hecke algebra and allow us to compute the continuous (co)homology of$\Gamma $with coefficients in $R$.
Calcium dynamics during NMDA‐induced membrane potential oscillations in lamprey spinal neurons – contribution of L‐type calcium channels (CaV1.3)
Authors: Wang Di , Grillner Sten , Wallén Peter 
Published: February 2013

Key points
Intrinsic NMDA‐induced oscillations of membrane potential are important for the operation of the spinal locomotor network in the lamprey, and involve a cyclic influx of calcium.
The spatial and temporal calcium dynamics during oscillations were investigated, using calcium imaging combined with intracellular recordings.
Calcium fluctuations were observed in both soma and dendrites, timed to the membrane potential oscillations, with the peak in distal dendritic locations typically occurring earlier than in the soma.
The L‐type calcium channel antagonist nimodipine prolonged the plateau phase of membrane potential oscillations, whereas the agonist Bay K 8644 shortened the plateau. Bay K 8644 also increased the amplitude of calcium fluctuations, particularly in distal dendrites. On the contrary, nimodipine decreased calcium fluctuation amplitudes.
Low‐voltage‐activated L‐type (CaV1.3‐like) calcium channels at distal dendrites are activated during membrane potential oscillations. The resulting calcium influx contributes to the activation of calcium‐activated potassium channels and thereby the control of the plateau duration during oscillations.
Abstract  NMDA receptor‐dependent, intrinsic membrane potential oscillations are an important element in the operation of the lamprey locomotor network. They involve a cyclic influx of calcium, leading to an activation of calcium‐activated potassium (KCa) channels that in turn contributes to the termination of the depolarized plateau and membrane repolarization. In this study, we have investigated the calcium dynamics in different regions of lamprey spinal neurons during membrane potential oscillations, using confocal calcium imaging in combination with intracellular recordings. Calcium fluctuations were observed in both soma and dendrites, timed to the oscillations. The calcium level increased sharply at the onset of membrane depolarization, to reach its maximum by the end of the plateau. The calcium peak in distal dendrites typically occurred earlier than in the soma during the oscillatory cycle. The L‐type calcium channel blocker nimodipine increased the duration of the depolarized plateau phase in most cells tested, whereas the agonist Bay K 8644 decreased plateau duration. Bay K 8644 increased the amplitude of calcium fluctuations, particularly in distal dendrites, whereas nimodipine caused a decrease, suggesting that L‐type low‐voltage‐activated calcium channels are mainly localized in these regions. Our results thus indicate that dendritic CaV1.3‐like calcium channels are activated during NMDA‐mediated membrane potential oscillations. This calcium influx activates KCa channels involved in plateau termination.
Half radiofrequency pulse excitation with a dedicated prescan to correct eddy current effect and gradient delay
Authors: Abe Takayuki 
Published: February 2013

Purpose:To improve the slice profile of the half radiofrequency (RF) pulse excitation and image quality of ultrashort echo time (UTE) imaging by compensating for an eddy current effect.Methods:The dedicated prescan has been developed to measure the phase accumulation due to eddy currents induced by the slice‐selective gradient. The prescan measures two one‐dimensional excitation k‐space profiles, which can be acquired with a readout gradient in the slice‐selection direction by changing the polarity of the slice‐selective gradient. The time shifts due to the phase accumulation in the excitation k‐space were calculated. The time shift compensated for the start time of the slice‐selective gradient. The total prescan time was 6–15 s. The slice profile and the UTE image with the half RF pulse excitation were acquired to evaluate the slice selectivity and the image quality.Results:Improved slice selectivity was obtained. The simple method proposed in this paper can eliminate eddy current effect. Good UTE images were obtained.Conclusions:The slice profile of the half RF pulse excitation and the image quality of UTE images have been improved by using a dedicated prescan. This method has a possibility that can improve the image quality of a clinical UTE imaging.
Rapid Emergence of Echinocandin Resistance during Candida kefyr Fungemia Treatment with Caspofungin
Authors: Fekkar A. , Meyer I. , Brossas J. Y. , Dannaoui E. , Palous M. , Uzunov M. , Nguyen S. , Leblond V. , Mazier D. , Datry A. 
Published: February 2013

ABSTRACT

Echinocandin drugs are widely used for the treatment of candidemia. Resistance is considered rare, and only a few cases of breakthrough candidiasis in patients receiving echinocandin have been reported worldwide. We report here for the first time a
Candida kefyr
isolate that acquired echinocandin resistance very rapidly after the initiation of caspofungin treatment for candidemia. We characterized the
FKS
gene mutation responsible for the resistance via the comparison of isolates sampled before and during treatment.
Azithromycin To Prevent Bronchopulmonary Dysplasia in Ureaplasma-Infected Preterm Infants: Pharmacokinetics, Safety, Microbial Response, and Clinical Outcomes with a 20-Milligram-per-Kilogram Single Intravenous Dose
Authors: Viscardi Rose M. , Othman Ahmed A. , Hassan Hazem E. , Eddington Natalie D. , Abebe Elias , Terrin Michael L. , Kaufman David A. , Waites Ken B. 
Published: February 2013

ABSTRACTUreaplasmarespiratory tract colonization is associated with bronchopulmonary dysplasia (BPD) in preterm infants. Previously, we demonstrated that a single intravenous (i.v.) dose of azithromycin (10 mg/kg of body weight) is safe but inadequate to eradicateUreaplasmaspp. in preterm infants. We performed a nonrandomized, single-arm open-label study of the pharmacokinetics (PK) and safety of intravenous 20-mg/kg single-dose azithromycin in 13 mechanically ventilated neonates with a gestational age between 24 weeks 0 days and 28 weeks 6 days. Pharmacokinetic data from 25 neonates (12 dosed with 10 mg/kg i.v. and 13 dosed with 20 mg/kg i.v.) were analyzed using a population modeling approach. Using a two-compartment model with allometric scaling of parameters on body weight (WT), the population PK parameter estimates were as follows: clearance, 0.21 liter/h × WT(kg)0.75[WT(kg)0.75indicates that clearance was allometrically scaled on body weight (in kilograms) with a fixed exponent of 0.75]; intercompartmental clearance, 2.1 liters/h × WT(kg)0.75; central volume of distribution (V), 1.97 liters × WT (kg); and peripheralV, 17.9 liters × WT (kg). There was no evidence of departure from dose proportionality in azithromycin exposure over the tested dose range. The calculated area under the concentration-time curve over 24 h in the steady state divided by the MIC90(AUC24/MIC90) for the single dose of azithromycin (20 mg/kg) was 7.5 h. Simulations suggest that 20 mg/kg for 3 days will maintain azithromycin concentrations of >MIC50of 1 μg/ml for this group ofUreaplasmaisolates for ≥96 h after the first dose. Azithromycin was well tolerated with no drug-related adverse events. One of seven (14%)Ureaplasma-positive subjects and three of six (50%)Ureaplasma-negative subjects developed physiologic BPD.Ureaplasmawas eradicated in all treatedUreaplasma-positive subjects. Simulations suggest that a multiple-dose regimen may be efficacious for microbial clearance, but the effect on BPD remains to be determined.
Staphylococcus aureus SasA Is Responsible for Binding to the Salivary Agglutinin gp340, Derived from Human Saliva
Authors: Kukita Kenji , Kawada-Matsuo Miki , Oho Takahiko , Nagatomo Mami , Oogai Yuichi , Hashimoto Masahito , Suda Yasuo , Tanaka Takuo , Komatsuzawa Hitoshi 
Published: February 2013

ABSTRACT

Staphylococcus aureus
is a major human pathogen that can colonize the nasal cavity, skin, intestine, and oral cavity as a commensal bacterium. gp340, also known as DMBT1 (deleted in malignant brain tumors 1), is associated with epithelial differentiation and innate immunity. In the oral cavity, gp340 induces salivary aggregation with several oral bacteria and promotes bacterial adhesion to tissues such as the teeth and mucosa.
S. aureus
is often isolated from the oral cavity, but the mechanism underlying its persistence in the oral cavity remains unclear. In this study, we investigated the interaction between
S. aureus
and gp340 and found that
S. aureus
interacts with saliva- and gp340-coated resin. We then identified the
S. aureus
factor(s) responsible for binding to gp340. The cell surface protein SasA, which is rich in basic amino acids (BR domain) at the N terminus, was responsible for binding to gp340. Inactivation of the
sasA
gene resulted in a significant decrease in
S. aureus
binding to gp340-coated resin. Also, recombinant SasA protein (rSasA) showed binding affinity to gp340, which was inhibited by the addition of
N
-acetylneuraminic acid. Surface plasmon resonance analysis showed that rSasA significantly bound to the NeuAcα(2-3)Galβ(1-4)GlcNAc structure. These results indicate that SasA is responsible for binding to gp340 via the
N
-acetylneuraminic acid moiety.
Porphyromonas gingivalis Infection-Associated Periodontal Bone Resorption Is Dependent on Receptor Activator of NF-κB Ligand
Authors: Han Xiaozhe , Lin Xiaoping , Yu Xiaoqian , Lin Jiang , Kawai Toshihisa , LaRosa Karen B. , Taubman Martin A. 
Published: February 2013

ABSTRACT

Porphyromonas gingivalis
is one of the oral microorganisms associated with human chronic periodontitis. The purpose of this study is to determine the role of the receptor activator of nuclear factor-κB ligand (RANKL) in
P. gingivalis
infection-associated periodontal bone resorption. Inbred female Rowett rats were infected orally on four consecutive days (days 0 to 3) with 1 × 10
9
P. gingivalis
bacteria (strain ATCC 33277). Separate groups of rats also received an injection of anti-RANKL antibody, osteoprotegerin fusion protein (OPG-Fc), or a control fusion protein (L6-Fc) into gingival papillae in addition to
P. gingivalis
infection. Robust serum IgG and salivary IgA antibody (
P
< 0.01) and T cell proliferation (
P
< 0.05) responses to
P. gingivalis
were detected at day 7 and peaked at day 28 in
P. gingivalis
-infected rats. Both the concentration of soluble RANKL (sRANKL) in rat gingival tissues (
P
< 0.01) and periodontal bone resorption (
P
< 0.05) were significantly elevated at day 28 in the
P. gingivalis
-infected group compared to levels in the uninfected group. Correspondingly, RANKL-expressing T and B cells in rat gingival tissues were significantly increased at day 28 in the
P. gingivalis
-infected group compared to the levels in the uninfected group (
P
< 0.01). Injection of anti-RANKL antibody (
P
< 0.05) or OPG-Fc (
P
< 0.01), but not L6-Fc, into rat gingival papillae after
P. gingivalis
infection resulted in significantly reduced periodontal bone resorption. This study suggests that
P. gingivalis
infection-associated periodontal bone resorption is RANKL dependent and is accompanied by increased local infiltration of RANKL-expressing T and B cells.
Role of Toll-Like Receptor 9 Signaling in Experimental Leishmania braziliensis Infection
Authors: Weinkopff Tiffany , Mariotto Anita , Simon Gregoire , Hauyon-La Torre Yazmin , Auderset Floriane , Schuster Steffen , Zangger Haroun , Fasel Nicolas , Barral Aldina , Tacchini-Cottier Fabienne 
Published: February 2013

ABSTRACTInfection withLeishmania braziliensiscauses cutaneous or mucocutaneous leismaniasis in humans. Toll-like receptor 9 (TLR9) expression has been found in granulomas of lesions inL. braziliensis-infected individuals.L. braziliensisinoculation in mice induces very small lesions that are self-healing, whereas deficiency in the TLR adaptor molecule, MyD88, renders mice susceptible to infection. The TLR involved has not been identified, prompting us to investigate if TLR9 triggering by the parasite contributes to the strong resistance to infection observed inL. braziliensis-inoculated mice. The parasites activated wild-type (WT) dendritic cells (DCs)in vitrobut not DCs derived from TLR9−/−mice. TLR9−/−mice inoculated withL. braziliensisexhibited a transient susceptibility characterized by increased lesion size and parasite burden compared to those of WT mice. Surprisingly, elevated levels of gamma interferon (IFN-γ) were measured at the site of infection and in draining lymph node T cells of TLR9−/−mice at the peak of susceptibility, suggesting that unlike observationsin vitro, the parasite could induce DC activation leading to the development of Th1 cells in the absence of TLR9 expression. Taken together, these data show that TLR9 signaling is important for the early control of lesion development and parasite burden but is dispensable for the differentiation of Th1 cells secreting IFN-γ, and the high levels of this cytokine are not sufficient to control early parasite replication followingL. braziliensisinfection.
A Double Mutant Heat-Labile Toxin from Escherichia coli, LT(R192G/L211A), Is an Effective Mucosal Adjuvant for Vaccination against Helicobacter pylori Infection
Authors: Sjökvist Ottsjö Louise , Flach Carl-Fredrik , Clements John , Holmgren Jan , Raghavan Sukanya 
Published: February 2013

ABSTRACT

Helicobacter pylori
infection in the stomach is a common cause of peptic ulcer disease and is a strong risk factor for the development of gastric adenocarcinoma, yet no effective vaccine against
H. pylori
infection is available to date. In mice, mucosal vaccination with
H. pylori
antigens when given together with cholera toxin (CT) adjuvant, but not without adjuvant, can induce protective immune responses against
H. pylori
infection. However, the toxicity of CT precludes its use as a mucosal adjuvant in humans. We evaluated a recently developed, essentially nontoxic double mutant
Escherichia coli
heat-labile toxin, LT(R192G/L211A) (dmLT), as a mucosal adjuvant in an experimental
H. pylori
vaccine and compared it to CT in promoting immune responses and protection against
H. pylori
infection in mice. Immunization via the sublingual or intragastric route with
H. pylori
lysate antigens and dmLT resulted in a significant decrease in bacterial load after challenge compared to that in unimmunized infection controls and to the same extent as when using CT as an adjuvant. Cellular immune responses in the sublingually immunized mice known to correlate with protection were also fully comparable when using dmLT and CT as adjuvants, resulting in enhanced
in vitro
proliferative and cytokine responses from spleen and mesenteric lymph node cells to
H. pylori
antigens. Our results suggest that dmLT is an attractive adjuvant for inclusion in a mucosal vaccine against
H. pylori
infection.
Endocrine Fibroblast Growth Factor FGF19 Promotes Prostate Cancer Progression
Authors: Feng Shu , Dakhova Olga , Creighton Chad J. , Ittmann Michael 
Published: February 2013

Abstract
Prostate cancer is the most common visceral malignancy and the second leading cause of cancer deaths in US men. There is broad evidence that fibroblast growth factor (FGF) receptors are important in prostate cancer initiation and progression, but the contribution of particular FGFs in this disease is not fully understood. The FGF family members FGF19, FGF21, and FGF23 comprise a distinct subfamily that circulate in serum and act in an endocrine manner. These endocrine FGFs require α-Klotho (KL) and/or β-Klotho (KLB), two related single-pass transmembrane proteins restricted in their tissue distribution, to act as coreceptors along with classic FGF receptors (FGFR) to mediate potent biologic activity. Here we show that FGF19 is expressed in primary and metastatic prostate cancer tissues, where it functions as an autocrine growth factor. Exogenous FGF19 promoted the growth, invasion, adhesion, and colony formation of prostate cancer cells at low ligand concentrations. FGF19 silencing in prostate cancer cells expressing autocrine FGF19 decreased invasion and proliferation in vitro and tumor growth in vivo. Consistent with these observations, KL and/or KLB were expressed in prostate cancer cells in vitro and in vivo, raising the possibility that additional endocrine FGFs may also exert biologic effects in prostate cancer. Our findings support the concept that therapies targeting FGFR signaling may have efficacy in prostate cancer and highlight FGF19 as a relevant endocrine FGF in this setting. Cancer Res; 73(8); 2551–62. ©2013 AACR.
Tumor-Specific Isoform Switch of the Fibroblast Growth Factor Receptor 2 Underlies the Mesenchymal and Malignant Phenotypes of Clear Cell Renal Cell Carcinomas
Authors: Zhao Qi , Caballero Otavia L. , Davis Ian D. , Jonasch Eric , Tamboli Pheroze , Yung W.K. Alfred , Weinstein John N. ,   Kenna Shaw for the TCGA research network, Strausberg Robert L. , Yao Jun 
Published: February 2013

Abstract
Purpose: We aim to identify tumor-specific alternative splicing events having potential applications in the early detection, diagnosis, prognosis, and therapy for cancers.
Experimental Design: We analyzed RNA-seq data on 470 clear cell renal cell carcinomas (ccRCC) and 68 kidney tissues to identify tumor-specific alternative splicing events. We further focused on the fibroblast growth factor receptor 2 (FGFR2) isoform switch and characterized ccRCCs expressing different FGFR2 isoforms by integrated analyses using genomic data from multiple platforms and tumor types.
Results: We identified 113 top candidate alternatively spliced genes in ccRCC. Prominently, the FGFR2 gene transcript switched from the normal IIIb isoform (“epithelial”) to IIIc isoform (“mesenchymal”) in nearly 90% of ccRCCs. This switch is kidney specific as it was rarely observed in other cancers. The FGFR2-IIIb ccRCCs show a transcriptome and methylome resembling those from normal kidney, whereas FGFR2-IIIc ccRCCs possess elevated hypoxic and mesenchymal expression signatures. Clinically, FGFR2-IIIb ccRCCs are smaller in size, of lower tumor grade, and associated with longer patient survival. Gene set enrichment and DNA copy number analyses indicated that FGFR2-IIIb ccRCCs are closely associated with renal oncocytomas and chromophobe RCCs (chRCC). A reexamination of tumor histology by pathologists identified FGFR2-IIIb tumors as chRCCs and clear cell papillary RCCs (ccpRCC).
Conclusions: FGFR2 IIIb RCCs represent misdiagnosed ccRCC cases, suggesting FGFR2 isoform testing can be used in the diagnosis of RCC subtypes. The finding of a prevalent isoform switch of FGFR2 in a tissue-specific manner holds promise for the future development of FGFR2-IIIc as a distinct early detection biomarker and therapeutic target for ccRCC. Clin Cancer Res; 19(9); 2460–72. ©2013 AACR.
Towards a Spirituality of Public Leadership: Engaging Dietrich Bonhoeffer
Authors: Nullens Patrick 
Published: February 2013

Abstract
This article is a reflective answer to the growing interest in the ‘spirituality’ of a leader found both among active leaders and in the field of Leadership Studies. The term ‘spirituality’ is so complex, however, it requires a more thorough theological reflection than (secular) Leadership Studies can offer, especially considering the more specific matter of how a Christian leader embodies his/her spirituality in his/her leadership. This article discusses four components of leadership: the leader’s sense of reality, the sense of a higher calling, the sense of belonging and the sense of morality. Further, the thought of Dietrich Bonhoeffer provides each of these components with not only a Christian but an explicitly Christocentric content.
Investigation of enhancing effect of nano-montmorillonite on fire-retardant added low-density polyethylene–ethylene vinyl acetate hybrid system
Authors: Bee Soo-Tueen , Hassan A , Ratnam CT , Tee Tiam-Ting , Sin Lee Tin 
Published: February 2013

In this study, nano-montmorillonite (NMMT) was incorporated in alumina trihydrate (ATH) added low-density polyethylene–ethylene vinyl acetate (LDPE-EVA) for enhancing the mechanical and electrical properties of the hybrid blends. The Young’s modulus of 50 phr ATH added LDPE-EVA (LE) blends has improved significantly, when the NMMT loading level increased from 5 to 15 phr. This is because the intercalation of NMMT particles reduces the cavities while enhancing the interfacial adhesion between the particle surface and LE matrix as observed via morphology analysis. The good interfacial adhesion could effectively transfer the stress from polymer matrix to filler’s particles during straining and improved the mechanical properties. On the other hand, the volume resistivity of 5 phr added LE blends was gradually decreased as the loading level of ATH has increased from 50 to 150 phr. The surface and volume resistivity of LE blends exhibited that high polarity of ATH and NMMT molecules could increase the mobility of charges in passages through polymer matrix and surface. Thus, the incorporation of ATH and NMMT could reduce the electrical resistance of LE blends. In addition, the increasing of ATH loading level also improved fire resistivity of LE blends as indicated by the promising limiting oxygen index. This is because the endothermic reaction of ATH during combustion process could reduce the temperature of polymer blends while releasing water vapour and the formation of alumina char. Furthermore, the increasing of NMMT loading level in ATH-added LE blends was found to slightly increase the fire retardancy. This is due to the addition of NMMT that could promote the dripping characteristics and charring effect during combustion and subsequently improve the fire retardancy of ATH added LE blends.