bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clara cell protein in bronchoalveolar lavage fluid: a predictor of ventilator-associated pneumonia?
Authors: Vanspauwen Marijke J , Linssen Catharina FM , Bruggeman Cathrien A , Jacobs Jan A , Drent Marjolein , Bergmans Dennis CJJ , van Mook Walther NKA 
Published: February 2011

Abstract
Introduction
Clara cell protein 10 (CC-10) has been associated with inflammatory and infectious pulmonary diseases. This study evaluates CC-10 concentrations in bronchoalveolar lavage (BAL) fluid as a potential marker of ventilator-associated pneumonia (VAP).

Methods
Between January 2003 and December 2007, BAL fluid samples obtained from critically ill patients at the intensive care unit of the Maastricht University Medical Centre clinically suspected of having VAP were included. Patients were divided into two groups: (1) microbiologically confirmed VAP (the VAP group) and (2) microbiologically unconfirmed VAP (the non-VAP group). The concentration of CC-10 was measured by means of a commercially available enzyme-linked immunosorbent assay kit, and retrospective analysis was performed. Areas under the curve of receiver operating characteristic curves were calculated for CC-10 concentrations.

Results
A total of 196 patients (122 men, 74 women) were included. A total of 79 (40%) of 196 cases of suspected VAP were microbiologically confirmed. The median CC-10 concentration in the VAP group was 3,019 ng/mL (range, 282 to 65,546 ng/mL) versus 2,504 ng/mL (range, 62 to 30,240 ng/mL) in the non-VAP group (P = 0.03). There was no significant difference in CC-10 concentrations between patients treated with or without corticosteroids (P = 0.26) or antibiotic therapy (P = 0.9). The CC-10 concentration did not differ significantly between patients with Gram-positive versus Gram-negative bacteria that caused the VAP (P = 0.06). However, CC-10 concentrations did differ significantly between the late-onset VAP group and the non-VAP group.

Conclusions
The CC-10 concentration in BAL fluid yielded low diagnostic accuracy in confirming the presence of VAP.
High levels of circulating leukocyte microparticles are associated with better outcome in acute respiratory distress syndrome
Authors: Guervilly Christophe , Lacroix Romaric , Forel Jean-Marie , Roch Antoine , Camoin-Jau Laurence , Papazian Laurent , Dignat-George Françoise 
Published: February 2011

Abstract
Introduction
The current study has addressed the presence and the cellular origin of microparticles (MP) isolated from bronchoalveolar lavage (BAL) fluid and from blood samples from patients with acute respiratory distress syndrome (ARDS). Their prognostic interest was also investigated.

Methods
Fifty-two patients were included within the first 24 hours of ARDS. They were compared to spontaneous breathing (SB) and ventilated control (VC) groups. Bronchoalveolar lavage (BAL) and blood samples were obtained on Day 1 and Day 3 in an ARDS group. Leukocyte microparticles (LeuMP), neutrophil microparticles (NeuMP), endothelial microparticles (EMP), and platelet microparticles (PMP) were measured in arterial blood and in BAL samples by flow cytometry. Mortality from all causes was recorded at Day 28.

Results
All MP subpopulations were detected in BAL. However, only LeuMP and NeuMP were elevated in ARDS patients compared to the SB group (P = 0.002 for both). Among ARDS patients, higher levels of LeuMP were detected in blood (Day 1) and in BAL (Day 3) in survivors as compared with the non survivors. Circulating LeuMP >60 elements/microliter detectable on Day 1 of ARDS, was associated with a higher survival rate (odds ratio, 5.26; 95% confidence interval, 1.10 to 24.99; P = 0.037).

Conclusions
The identification of the cellular origin of microparticles at the onset of ARDS has identified LeuMP as a biomarker of prognostic significance. The higher levels of LeuMP in survivors could be associated with a protective role of this MP subpopulation. This hypothesis needs further investigations.
Characterization of the radioresponse of human apical papilla-derived cells
Authors: Abe Shigehiro , Hamada Keiichi , Yamaguchi Satoshi , Amagasa Teruo , Miura Masahiko 
Published: February 2011

Abstract
Background
The purpose of this study was to characterize the radiobiological properties of stem/progenitor cells derived from apical papilla-derived cells (APDCs) compared to bulk APDCs.

Methods
APDCs were isolated from freshly extracted human third molars with immature apices. Multipotent spheres, which are thought to contain an enriched population of stem/progenitor cells, were formed from the APDCs, using a neurosphere culture technique. After γ-irradiation, papillary sphere-forming cells (PSFCs) and bulk APDCs were subjected to radiosensitivity and hard tissue-forming assays.

Results
Compared to bulk APDCs, the PSFCs exhibited a radioresistant phenotype and a higher capacity for DNA double strand break repair. Irradiation induced a significant increase in a senescence-like phenotype in both cell types. Neither type of cells exhibited a significant induction of apoptotic changes after 8 Gy of irradiation. Ability to form hard tissue in vivo was significantly decreased in PSFCs, but not in APDCs following 4 Gy of irradiation.

Conclusions
We demonstrated for the first time that stem/progenitor cells derived from APDCs exhibit a radioresistant phenotype; however, the hard tissue forming ability in vivo, but not bulk APDCs, was significantly reduced after irradiation.
Fetal derived embryonic-like stem cells improve healing in a large animal flexor tendonitis model
Authors: Watts Ashlee E , Yeager Amy E , Kopyov Oleg V , Nixon Alan J 
Published: February 2011

Abstract
Introduction
Tendon injury is a common problem in athletes, with poor tissue regeneration and a high rate of re-injury. Stem cell therapy is an attractive treatment modality as it may induce tissue regeneration rather than tissue repair. Currently, there are no reports on the use of pluripotent cells in a large animal tendon model in vivo. We report the use of intra-lesional injection of male, fetal derived embryonic-like stem cells (fdESC) that express Oct-4, Nanog, SSEA4, Tra 1-60, Tra 1-81 and telomerase.

Methods
Tendon injury was induced using a collagenase gel-physical defect model in the mid-metacarpal region of the superficial digital flexor tendon (SDFT) of eight female adult Thoroughbred or Thoroughbred cross horses. Tendon lesions were treated one week later with intra-lesional injection of male derived fdESCs in media or media alone. Therapy was blinded and randomized. Serial ultrasound examinations were performed and final analysis at eight weeks included magnetic resonance imaging (MRI), biochemical assays (total DNA, glycosaminoglycan, collagen), gene expression (TNC, TNMD, SCX, COL1A1, COL3A1, COMP, DCN, MMP1, MMP3, MMP13, 18S) and histology. Differences between groups were assessed with Wilcoxon's rank sum test.

Results
Cell survival was demonstrated via the presence of the SRY gene in fdESC treated, but not control treated, female SDFT at the end of the trial. There were no differences in tendon matrix specific gene expression or total proteoglycan, collagen or DNA of tendon lesions between groups. Tissue architecture, tendon size, tendon lesion size, and tendon linear fiber pattern were significantly improved on histologic sections and ultrasound in the fdESC treated tendons.

Conclusions
Such profound structural effects lend further support to the notion that pluripotent stem cells can effect musculoskeletal regeneration, rather than repair, even without in vitro lineage specific differentiation. Further investigation into the safety of pluripotent cellular therapy as well as the mechanisms by which repair was improved seem warranted.
Phase II Study of Vorinostat for Treatment of Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma
Authors: Kirschbaum Mark , Frankel Paul , Popplewell Leslie , Zain Jasmine , Delioukina Maria , Pullarkat Vinod , Matsuoka Deron , Pulone Bernadette , Rotter Arnold J. , Espinoza-Delgado Igor , Nademanee Auayporn , Forman Stephen J. , Gandara David , Newman Edward 
Published: February 2011

Purpose We performed a phase II study of oral vorinostat, a histone and protein deacetylase inhibitor, to examine its efficacy and tolerability in patients with relapsed/refractory indolent lymphoma. Patients and Methods In this open label phase II study (NCT00253630), patients with relapsed/refractory follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL), with ≤ 4 prior therapies were eligible. Oral vorinostat was administered at a dose of 200 mg twice daily on days 1 through 14 of a 21-day cycle until progression or unacceptable toxicity. The primary end point was objective response rate (ORR), with secondary end points of progression-free survival (PFS), time to progression, duration of response, safety, and tolerability. Results All 35 eligible patients were evaluable for response. The median number of vorinostat cycles received was nine. ORR was 29% (five complete responses [CR] and five partial responses [PR]). For 17 patients with FL, ORR was 47% (four CR, four PR). There were two of nine responders with MZL (one CR, one PR), and no formal responders among the nine patients with MCL, although one patient maintained stable disease for 26 months. Median PFS was 15.6 months for patients with FL, 5.9 months for MCL, and 18.8 months for MZL. The drug was well-tolerated over long periods of treatment, with the most common grade 3 adverse events being thrombocytopenia, anemia, leucopenia, and fatigue. Conclusion Oral vorinostat is a promising agent in FL and MZL, with an acceptable safety profile. Further studies in combination with other active agents in this setting are warranted.
DHEA Suppresses Longitudinal Bone Growth by Acting Directly at Growth Plate through Estrogen Receptors
Authors: Sun Hongzhi , Zang Weijin , Zhou Bo , Xu Lin , Wu Shufang 
Published: February 2011

AbstractDehydroepiandrosterone (DHEA) is produced by the adrenal cortex and is the most abundant steroid in humans. Although in some physiological and pathological conditions the increased secretion of DHEA and its sulfated form is associated with accelerated growth rate and skeletal maturation, it is unclear whether DHEA can affect longitudinal bone growth and skeletal maturation by acting directly at the growth plate. In our study, DHEA suppressed metatarsal growth, growth plate chondrocyte proliferation, and hypertrophy/differentiation. In addition, DHEA increased the number of apoptotic chondrocytes in the growth plate. In cultured chondrocytes, DHEA reduced chondrocyte proliferation and induced apoptosis. The DHEA-induced inhibition of metatarsal growth and growth plate chondrocyte proliferation and hypertrophy/differentiation was nullified by culturing metatarsals with DHEA in the presence of ICI 182,780, an inhibitor of estrogen receptor, but not in the presence of Casodex, an inhibitor of androgen receptor. Lastly, nuclear factor-κB DNA binding activity was inhibited by the addition of DHEA in the medium of cultured chondrocyte. Our findings indicate that DHEA suppressed bone growth by acting directly at growth plate through estrogen receptor. Such growth inhibition is mediated by decreased chondrocyte proliferation and hypertrophy/differentiation and by increased chondrocyte apoptosis.
Increase of Anteroventral Periventricular Kisspeptin Neurons and Generation of E2-Induced LH-Surge System in Male Rats Exposed Perinatally to Environmental Dose of Bisphenol-A
Authors: Bai Yinyang , Chang Fei , Zhou Rong , Jin Peng-Peng , Matsumoto Hirokazu , Sokabe Masahiro , Chen Ling 
Published: February 2011

Abstract
Perinatal exposure to environmental levels of bisphenol-A (BPA) impairs sexually dimorphic behaviors in rodents. Kisspeptin neurons in anteroventral periventricular nucleus (AVPV), which plays an important role in the activation of GnRH neurons and the initiation of LH-surge, have been suggested to be sexual dimorphism in rats. This study focused on exploring the influence of a perinatal exposure to an environmental dose of BPA on the development and maturation of male AVPV kisspeptin neurons and hypothalamus-pituitary-gonadal axis. Female rats were injected sc with 2 μg BPA/kg·d from gestation d 10 through lactation d 7. Anatomical and functional changes in AVPV kisspeptin neurons and hypothalamus-pituitary-gonadal axis were examined in prepubertal, pubertal, and adult male rats exposed perinatally to BPA (BPA-rats). Here, we show that in postnatal d (PND)30/50/90 BPA-rats, the number of AVPV kisspeptin-immunoreactive cells was persistently increased in comparison with age-matched control male rats. The number of GnRH-immunoreactive cells in PND30 BPA-rats declined approximately 40% compared with control male rats, whereas that in PND50/90 BPA-rats was increased in a G protein-coupled receptor 54-dependent manner. Estradiol could induce a stable LH-surge in PND90 BPA-rats and control female rats, which was sensitive to the G protein-coupled receptor 54 inhibitor. In PND30/50 BPA-rats, plasma level of LH was higher, but the level of testosterone was lower than control male rats. These findings provide evidence that perinatal exposure to an environmental dose of BPA causes a sustained increase in AVPV kisspeptin neurons in male rats, leading to the generation of estradiol-induced LH-surge system.
Absence of Melatonin Induces Night-Time Hepatic Insulin Resistance and Increased Gluconeogenesis Due to Stimulation of Nocturnal Unfolded Protein Response
Authors: Nogueira Tatiane C. , Lellis-Santos Camilo , Jesus Daniel S. , Taneda Marco , Rodrigues Sandra C. , Amaral Fernanda G. , Lopes Ana Maria S. , Cipolla-Neto José , Bordin Silvana , Anhê Gabriel F. 
Published: February 2011

Abstract
It is known that the circadian rhythm in hepatic phosphoenolpyruvate carboxykinase expression (a limiting catalytic step of gluconeogenesis) and hepatic glucose production is maintained by both daily oscillation in autonomic inputs to the liver and night feeding behavior. However, increased glycemia and reduced melatonin (Mel) levels have been recently shown to coexist in diabetic patients at the end of the night period. In parallel, pinealectomy (PINX) is known to cause glucose intolerance with increased basal glycemia exclusively at the end of the night. The mechanisms that underlie this metabolic feature are not completely understood. Here, we demonstrate that PINX rats show night-time hepatic insulin resistance characterized by reduced insulin-stimulated RAC-α serine/threonine-protein kinase phosphorylation and increased phosphoenolpyruvate carboxykinase expression. In addition, PINX rats display increased conversion of pyruvate into glucose at the end of the night. The regulatory mechanism suggests the participation of unfolded protein response (UPR), because PINX induces night-time increase in activating transcription factor 6 expression and prompts a circadian fashion of immunoglobulin heavy chain-binding protein, activating transcription factor 4, and CCAAT/enhancer-binding protein-homologous protein expression with Zenith values at the dark period. PINX also caused a night-time increase in Tribble 3 and regulatory-associated protein of mammalian target of rapamycin; both were reduced in liver of PINX rats treated with Mel. Treatment of PINX rats with 4-phenyl butyric acid, an inhibitor of UPR, restored night-time hepatic insulin sensitivity and abrogated gluconeogenesis in PINX rats. Altogether, the present data show that a circadian oscillation of UPR occurs in the liver due to the absence of Mel. The nocturnal UPR activation is related with night-time hepatic insulin resistance and increased gluconeogenesis in PINX rats.
Essential Roles of Androgen Signaling in Wolffian Duct Stabilization and Epididymal Cell Differentiation
Authors: Murashima Aki , Miyagawa Shinichi , Ogino Yukiko , Nishida-Fukuda Hisayo , Araki Kimi , Matsumoto Takahiro , Kaneko Takehito , Yoshinaga Kazuya , Yamamura Ken-ichi , Kurita Takeshi , Kato Shigeaki , Moon Anne M. , Yamada Gen 
Published: February 2011

AbstractThe epididymis is a male accessory organ and functions for sperm maturation and storage under the control of androgen. The development of the epididymis is also androgen dependent. The Wolffian duct (WD), anlagen of the epididymis, is formed in both male and female embryos; however, it is stabilized only in male embryos by testicular androgen. Androgen drives subsequent differentiation of the WD into the epididymis. Although the essential roles of androgen in WD masculinization and epididymal function have been established, little is known about cellular events regulated precisely by androgen signaling during these processes. It is also unclear whether androgen signaling, especially in the epithelia, has further function for epididymal epithelial cell differentiation. In this study we examined the cellular death and proliferation controlled by androgen signaling via the androgen receptor (AR) in WD stabilization. Analyses using AR knockout mice revealed that androgen signaling inhibits epithelial cell death in this process. Analysis of AP2α-Cre;ARflox/Y mice, in which AR function is deleted in the WD epithelium, revealed that epithelial AR is not required for the WD stabilization but is required for epithelial cell differentiation in the epididymis. Specifically, loss of epithelial AR significantly reduced expression of p63 that is essential for differentiation of basal cells in the epididymal epithelium. We also interrogated the possibility of regulation of the p63 gene (Trp63) by AR in vitro and found that p63 is a likely direct target of AR regulation.
Evidence of a central pattern generator regulating spermathecal muscle activity inLocusta migratoriaand its coordination with oviposition
Authors: da Silva Rosa , Lange Angela B. 
Published: February 2011

SUMMARYElectrophysiological recordings were conducted to determine the control of spermathecal contractions during oviposition of interrupted egg-laying locusts, Locusta migratoria. Following transection of the central nervous system below the metathoracic ganglion, rhythmic patterned bursting was detected by extracellular recordings of the nerve N2B2 that innervates the muscles of the spermatheca. Subsequent transections at more posterior regions of the ventral nerve cord revealed more robust rhythmic bursting in N2B2. This rhythmic bursting pattern was found to be coordinated with bursting in the ventral opener nerve (N2B1) that innervates the ventral opener muscle. This muscle controls the ventral ovipositor valves. Electromyographic recordings from the spermathecal muscle and ventral opener muscle confirmed a rhythmic bursting pattern resulting in an increase in muscle activity. Taken together, the results indicate that there is probably a central pattern generator (CPG), which is regulated by descending inhibition, that controls the spermathecal muscle activity. This CPG appears to be located within the VIIth and VIIIth abdominal ganglia, and was found to integrate with the CPG that regulates oviposition digging in locusts. These results provide further insight into the intricate coordination and control of reproductive tissues underlying reproductive behaviours in locusts.
Implementation of computerized add-on testing for hospitalized patients in a large academic medical center
Authors: Kim Ji Yeon , Kamis Irina K. , Singh Balaji , Batra Shalini , Dixon Roberta H. , Dighe Anand S. 
Published: February 2011

Abstract

Background: Physician requests for additional testing on an existing laboratory specimen (add-ons) are resource intensive and generally require a phone call to the laboratory. Verbal orders such as these have been noted to be associated with errors in accuracy. The aim of this study was to compare a novel computerized system for add-on requests to the prior verbal system.

Method: We compare the computerized add-on request system to the verbal system with respect to order completeness and workflow.

Results: We demonstrate that the computerized add-on system resulted in the complete in-laboratory documentation of the add-on request 100% of the time, compared to 58% with the verbal add-on system. In addition, we show that documentation of a verbal add-on request in the electronic medical record (EMR) occurred for 4% of requests, while in the computerized system EMR documentation occurred 100% of the time. We further demonstrate that the computerized add-on request process was well accepted by providers and did not significantly change the test mix of the add-on requests.

Conclusions: In computerized physician order entry (CPOE) implementations, add-on order functionality should be considered so these orders are documented in the EMR.
Long-term effects of radiotherapy on cardiovascular risk factors in acromegaly
Authors: Ronchi Cristina L , Verrua Elisa , Ferrante Emanuele , Bender Gwendolyn , Sala Elisa , Lania Andrea G , Fassnacht Martin , Beck-Peccoz Paolo , Allolio Bruno , Spada Anna , Arosio Maura 
Published: February 2011

ObjectiveRadiation therapy (RT) is a useful adjuvant tool for acromegalic patients not cured by surgery and/or not responding to pharmacotherapy. However, its specific effects on cardio- and cerebrovascular morbidity are still on debate.DesignRetrospective analysis of 42 acromegalic patients cured after conventional radiotherapy (CRT, n=31) or radiosurgery by gamma-knife (GKRS, n=11) followed for a median period of 16.5 years (range: 2–40). Totally, 56 patients cured by surgery alone, with similar GH/IGF1 levels and duration of disease remission, served as control group.MethodsChanges in cardiovascular risk factors, such as body mass index, glucose metabolism, insulin resistance, blood pressure, and lipid profile (pre-defined primary end point) and occurrence of new major cardio- and cerebrovascular events (secondary end point) during follow-up.ResultsThe number of obese, hypertensive, and dyslipidemic subjects increased over time only in patients cured with RT. In contrast, the glucose response to the oral glucose tolerance test and the percentage of subjects with glucose alterations improved only in controls. As expected, the percentage of patients with pituitary failure was deeply higher among RT patients than among controls (86 vs 30%, P<0.0005). Despite these findings, a similar number of RT patients and controls developed major cardio- or cerebrovascular events (4/42 vs 3/56, P: NS). No differences were found between CRT and GKRS subgroups.ConclusionsPrevious RT seems to be associated with a worse metabolic profile in acromegalic patients studied after a long-term follow-up. Nevertheless, a direct link between RT and cardiovascular events remains to be proven.
Maximally Efficient Modeling of DNA Sequence Motifs at All Levels of Complexity
Authors: Stormo Gary D 
Published: February 2011

Abstract
Identification of transcription factor binding sites is necessary for deciphering gene regulatory networks. Several new methods provide extensive data about the specificity of transcription factors but most methods for analyzing these data to obtain specificity models are limited in scope by, for example, assuming additive interactions or are inefficient in their exploration of more complex models. This article describes an approach—encoding of DNA sequences as the vertices of a regular simplex—that allows simultaneous direct comparison of simple and complex models, with higher-order parameters fit to the residuals of lower-order models. In addition to providing an efficient assessment of all model parameters, this approach can yield valuable insight into the mechanism of binding by highlighting features that are critical to accurate models.