bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Teratogenic Effect of Dofetilide during Rat Limb Development and Association with Drug‐Induced Bradycardia and Hypoxia in the Embryo
Authors: Ritchie Helen E. , Ababneh Deena H. , Oakes Diana J. , Power Carl A. , Webster William S. 
Published: March 2013

BACKGROUNDDofetilide is an antiarrhythmic drug that blocks the cardiac repolarizing current IKr ((IKr, rapid component of the delayed rectifying potassium current). Previous studies have shown that (a) IKr is essential for normal cardiac function of the embryonic heart and (b) dofetilide is teratogenic in rodents. This study was undertaken to examine the mechanism by which dofetilide causes limb defects on gestational day 13 (GD 13) in the rat.METHODSRats were treated with dofetilide (single oral dose, 5 mg/kg) on GD 13 and embryonic heart rates assessed by ultrasound (Vevo770, VisualSonics, Toronto, Ontario, Canada) 2 hr later. Fetuses were examined for malformations on GD 20. In a separate experiment, dofetilide treatment of GD 13 rats was followed 2, 4, 12, or 24 hr with iv dosing with the hypoxia marker, pimonidazole (60 mg/kg). Embryos were collected and heart rates were assessed in vitro and hypoxia in embryo limbs analyzed.RESULTSA teratogenic dose of dofetilide at a susceptible stage of development (GD 13) resulted in a period of bradycardia and arrhythmia of the embryonic heart and hypoxia in the developing limbs (GD 13) resulting in limb malformations (GD 20).CONCLUSIONSDrugs that induce periods of bradycardia and/or arrhythmia of the embryonic heart and cause the embryo to become hypoxic are potential human teratogens.
Diverse Effects of Macromolecular Crowding on the Sequential Glycan‐Processing Pathway Involved in Glycoprotein Quality Control
Authors: Matsushima Hikaru , Hirano Makoto , Ito Yukishige , Totani Kiichiro 
Published: March 2013

AbstractCompared with in vitro conditions, the intracellular environment is highly crowded with biomolecules; this has numerous effects on protein functions, including enzymatic activity. We examined the effects of macromolecular crowding on glycan processing of N‐glycoprotein in the endoplasmic reticulum as a model sequential metabolic pathway. Experiments with synthetic substrates of physiological glycan structure clearly showed that the first half of the pathway (glucose trimming) was accelerated, whereas the second (mannose trimming) was decelerated under molecular crowding conditions. Furthermore, calreticulin, a lectin‐like molecular chaperone, bound more strongly to a glycan‐processing intermediate under these conditions. This study demonstrates the diverse effects of molecular crowding on sequential enzymatic processing, and the importance of the effects of macromolecular crowding on in vitro assays for understanding sequential metabolic pathways.
Optical/Magnetic Multimodal Bioprobes Based on Lanthanide‐Doped Inorganic Nanocrystals
Authors: Tu Datao , Liu Yongsheng , Zhu Haomiao , Chen Xueyuan 
Published: March 2013

AbstractMultimodal bioprobes, which integrate the advantages of different diagnostic modes into one single particle, can overcome the current limitations of sensitivity and resolution in medical assays and significantly improve the outcome of existing therapeutics. Lanthanide‐doped inorganic multimodal bioprobes, which are emerging as a promising new class of optical/magnetic multimodal bioprobes, have been long sought‐after and have recently attracted revived interest owing to their distinct optical and magnetic properties. In this concept article, we introduce the controlled synthesis of lanthanide‐doped inorganic multimodal bioprobes, including core–shell structured and single‐phase nanoparticles, and demonstrate different design strategies for achieving dual‐modal functionalization of nanoprobes. In particular, we highlight the most recent advances in biodetection, bioimaging, targeted drug delivery, and therapy based on these nanoparticles.
Health‐related quality of life of patients with advanced breast cancer treated with everolimus plus exemestane versus placebo plus exemestane in the phase 3, randomized, controlled, BOLERO‐2 trial
Authors: Burris Howard A. , Lebrun Fabienne , Rugo Hope S. , Beck J. Thaddeus , Piccart Martine , Neven Patrick , Baselga Jose , Petrakova Katarina , Hortobagyi Gabriel N. , Komorowski Anna , Chouinard Edmond , Young Robyn , Gnant Michael , Pritchard Kathleen I. , Bennett Lee , Ricci Jean‐Francois , Bauly Hounayda , Taran Tetiana , Sahmoud Tarek , Noguchi Shinzaburo 
Published: March 2013

AbstractBACKGROUND:The randomized, controlled BOLERO‐2 (Breast Cancer Trials of Oral Everolimus) trial demonstrated significantly improved progression‐free survival with the use of everolimus plus exemestane (EVE + EXE) versus placebo plus exemestane (PBO + EXE) in patients with advanced breast cancer who developed disease progression after treatment with nonsteroidal aromatase inhibitors. This analysis investigated the treatment effects on health‐related quality of life (HRQOL).METHODS:Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire‐Core 30 (EORTC QLQ‐C30) questionnaire, HRQOL was assessed at baseline and every 6 weeks thereafter until disease progression and/or treatment discontinuation. The 30 items in 15 subscales of the QLQ‐C30 include global health status wherein higher scores (range, 0‐100) indicate better HRQOL. This analysis included a protocol‐specified time to definitive deterioration (TDD) analysis at a 5% decrease in HRQOL versus baseline, with no subsequent increase above this threshold. The authors report additional sensitivity analyses using 10‐point minimal important difference decreases in the global health status score versus baseline. Treatment arms were compared using the stratified log‐rank test and Cox proportional hazards model adjusted for trial stratum (visceral metastases, previous hormone sensitivity), age, sex, race, baseline global health status score and Eastern Cooperative Oncology Group performance status, prognostic risk factors, and treatment history.RESULTS:Baseline global health status scores were found to be similar between treatment groups (64.7 vs 65.3). The median TDD in HRQOL was 8.3 months with EVE + EXE versus 5.8 months with PBO + EXE (hazard ratio, 0.74; P = .0084). At the 10‐point minimal important difference, the median TDD with EVE + EXE was 11.7 months versus 8.4 months with PBO + EXE (hazard ratio, 0.80; P = .1017).CONCLUSIONS:In patients with advanced breast cancer who develop disease progression after treatment with nonsteroidal aromatase inhibitors, EVE + EXE was associated with a longer TDD in global HRQOL versus PBO + EXE. Cancer 2013. © 2013 American Cancer Society.
Elucidation of target muscle and detailed development of dorsal motor neurons in chick embryo spinal cord
Authors: Kobayashi Nobumi , Homma Shunsaku , Okada Tomoaki , Masuda Tomoyuki , Sato Noboru , Nishiyama Keiji , Sakuma Chie , Shimada Takako , Yaginuma Hiroyuki 
Published: March 2013

ABSTRACTThe avian cervical spinal cord includes motoneurons (MNs) that send their axons through the dorsal roots. They have been called dorsal motoneurons (dMNs) and assumed to correspond to MNs of the accessory nerve that innervate the cucullaris muscle (SAN‐MNs). However, their target muscles have not been elucidated to date. The present study sought to determine the targets and the specific combination of transcription factors expressed by dMNs and SAN‐MNs and to describe the detailed development of dMNs. Experiments with tracing techniques confirmed that axons of dMNs innervated the cucullaris muscle. Retrogradely labeled dMNs were distributed in the ventral horn of C3 and more caudal segments. In most cases, some dMNs were also observed in the C2 segment. It was also demonstrated that SAN‐MNs existed in the ventral horn of the C1–2 segments and the adjacent caudal hindbrain. Both SAN‐MNs and dMNs expressed Isl1 but did not express Isl2, MNR2, or Lhx3. Rather, these MNs expressed Phox2b, a marker for branchial motoneurons (brMNs), although the intensity of expression was weaker. Dorsal MNs and SAN‐MNs were derived from the Nkx2.2‐positive precursor domain and migrated dorsally. Dorsal MNs remain in the ventral domain of the neural tube, unlike brMNs in the brainstem. These results indicate that dMNs and SAN‐MNs belong to a common MN population innervating the cucullaris muscle and also suggest that they are similar to brMNs of the brainstem, although there are differences in Phox2b expression and in the final location of each population. J. Comp. Neurol. 521: 2987–3002, 2013. © 2013 Wiley Periodicals, Inc.
Socially regulated reproductive development: Analysis of GnRH‐1 and kisspeptin neuronal systems in cooperatively breeding naked mole‐rats (Heterocephalus glaber)
Authors: Zhou Shuzhi , Holmes Melissa M. , Forger Nancy G. , Goldman Bruce D. , Lovern Matthew B. , Caraty Alain , Kalló Imre , Faulkes Christopher G. , Coen Clive W. 
Published: March 2013

ABSTRACTIn naked mole‐rat (NMR) colonies, breeding is monopolized by the queen and her consorts. Subordinates experience gonadal development if separated from the queen. To elucidate the neuroendocrine factors underlying reproductive suppression/development in NMRs, we quantified plasma gonadal steroids and GnRH‐1‐ and kisspeptin‐immunoreactive (ir) neurons in subordinate adults and in those allowed to develop into breeders, with or without subsequent gonadectomy. In males and females, respectively, plasma testosterone and progesterone are higher in breeders than in subordinates. No such distinction occurs for plasma estradiol; its presence after gonadectomy and its positive correlation with adrenal estradiol suggest an adrenal source. Numbers of GnRH‐1‐ir cell bodies do not differ between gonad‐intact breeders and subordinates within or between the sexes. As in phylogenetically related guinea pigs, kisspeptin‐ir processes pervade the internal and external zones of the median eminence. Their distribution is consistent with actions on GnRH‐1 neurons at perikaryal and/or terminal levels. In previously investigated species, numbers of kisspeptin‐ir cell bodies vary from substantial to negligible according to sex and/or reproductive state. NMRs are exceptional: irrespective of sex, reproductive state, or presence of gonads, substantial numbers of kisspeptin‐ir cell bodies are detected in the rostral periventricular region of the third ventricle (RP3V) and in the anterior periventricular (PVa), arcuate, and dorsomedial hypothalamic nuclei. Nevertheless, the greater number in the RP3V/PVa of female breeders compared with female subordinates or male breeders suggests that emergence from a hypogonadotrophic state in females may involve kisspeptin‐related mechanisms similar to those underlying puberty or seasonal breeding in other species. J. Comp. Neurol. 521: 3003–3029, 2013. © 2013 Wiley Periodicals, Inc.
Seasonal changes in RFamide‐related peptide‐3 neurons in the hypothalamus of a seasonally breeding marsupial species, the brushtail possum (Trichosurus vulpecula)
Authors: Harbid Anan A. , McLeod Bernie J. , Caraty Alain , Anderson Greg M. 
Published: March 2013

ABSTRACTRFamide‐related peptide‐3 (RFRP‐3) neurons have been shown to inhibit gonadotropin‐releasing hormone (GnRH) neuronal activity and hence reproduction in birds and eutherian mammals. They have also been proposed to have a direct hypophysiotropic effect on pituitary gonadotropin release. We used a new RFRP‐3 antibody to characterize the cell body distribution and fiber projections of RFRP‐3 neurons in the adult female brushtail possum brain. RFRP‐3‐immunoreactive cell bodies were found scattered within the dorsomedial hypothalamus and the dorsomedial half of the ventromedial hypothalamus, while GnRH neurons were observed scattered rostrocaudally along the lateral septum, rostral to the medial septum. There was a significant 2‐fold increase in the RFRP‐3 cell body number during the nonbreeding season (summer) compared to the breeding season (winter). Immunoreactive RFRP‐3 fibers were distributed throughout the thalamus, preoptic area, and hypothalamus. Very few fibers were observed in the median eminence, especially in the external zone. Intraperitoneal injection of the retrograde tracer Fluoro‐Gold resulted in the labeling of 40% of hypophysiotropic tuberoinfundibular dopaminergic (tyrosine hydroxylase‐positive) neurons; however, <10% of zona incerta dopaminergic neurons (which are not hypophysiotropic) or RFRP‐3 neurons were labeled with this tracer. These observations suggest that RFRP‐3 exhibits a seasonal fluctuation in cell numbers, as seen in sheep and birds, which is consistent with an increased inhibitory tone during the nonbreeding season. The lack of RFRP‐3 fibers in the median eminence and of Fluoro‐Gold uptake from the periphery imply that the actions of this peptide occur primarily centrally rather than at the anterior pituitary gland. J. Comp. Neurol. 521: 3030–3041, 2013. © 2013 Wiley Periodicals, Inc.
Electrophilic Cyclization of N‐Alkynyl‐2‐(organochalcogen)imidazoles: An Alternative Access to Imidazo[2,1‐b]chalcogenazoles
Authors: Grimaldi Tamíris B. , Godoi Benhur , Roehrs Juliano A. , Sperança Adriane , Zeni Gilson 
Published: March 2013

AbstractWe present here a practical synthesis of multifunctional imidazo[2,1‐b]chalcogenazoles through electrophilic cyclization of N‐alkynyl‐2‐(organochalcogen)imidazoles. The cyclization reaction proceeded cleanly and smoothly under mild reaction conditions in the presence of air. The methodology was highly regioselective: In a competition between the chalcogen and oxygen atoms, only S‐, and Se‐heterocycles were obtained. The resulting imidazo[2,1‐b]chalcogenazoles proved to be versatile as precursors for the synthesis of more highly functionalized imidazoselenazoles through copper‐catalyzed cross‐coupling reactions with arene‐ and alkanethiols, leading to Ullmann‐type products in good yields.
Winner of the 2013 young investigator award for the society for biomaterials annual meeting and exposition, April 10–13, 2013, Boston, Massachusetts
Authors: Thibault Richard A. , Mikos Antonios G. , Kasper F. Kurtis 
Published: March 2013

AbstractDevitalization and demineralization processing of biodegradable polymer and extracellular matrix (ECM) hybrid constructs was explored for the effect on the retention of ECM components and construct osteogenicity. Hybrid constructs were generated by seeding osteogenically predifferentiated rat mesenchymal stem cells (MSCs) onto electrospun poly(ε‐caprolactone) fiber meshes and culturing in osteogenic medium for 12 or 16 days within a flow perfusion bioreactor to create an ECM coating. The resulting constructs were then either devitalized (using a freeze‐thaw or a detergent technique), devitalized and demineralized, or left untreated, and subsequently characterized for DNA, glycosaminoglycan, collagen, and calcium content. The osteogenicity of each construct was investigated by culturing MSCs on the hybrid constructs within a flow perfusion bioreactor for 4, 8, and 12 days in osteogenic medium. Histological staining demonstrated that devitalization via the freeze–thaw method retained the thickest coating of ECM components within the constructs. Demineralization and devitalization processing of ECM coated constructs resulted in a decrease in their osteogenicity. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Evaluation of the bulk platelet response and fibrinogen interaction to elastin‐like polypeptide coatings
Authors: Srokowski Elizabeth M. , Woodhouse Kimberly A. 
Published: March 2013

AbstractIn this work, we expand on our understanding of the thrombogenicity of coatings prepared with three different recombinant elastin‐like polypeptides (ELPs). The bulk platelet response of the ELP coatings was characterized following whole blood contact under physiological shear flow (300 s−1) using flow cytometry. Prolonged exposure to shear flow (1‐h) indicated that materials coated with the longer ELP coatings (ELP2 and ELP4) had less bulk platelet activation and microparticle formation than materials coated with the shorter ELP1. Quartz crystal microbalance with dissipation (QCM‐D) was used to monitor the binding of the platelet membrane receptor GPIIb/IIIa to ELP‐adsorbed fibrinogen (Fg) surfaces. Compared to the shorter ELPs, a lower amount of Fg adsorbed to the ELP4 coated material and ELP4 appeared to form a softer, more structurally flexible coating layer. When Fg was adsorbed to the ELP coated surface it demonstrated an altered binding for GPIIb/IIIa that was inhibited in the presence of an AGDV‐containing peptide but not an RGD‐containing peptide. Conversely, on the shorter ELP coatings, binding of GPIIb/IIIa to an adsorbed Fg layer was partially inhibited in the presence of an RGD‐containing peptide. These results indicate that both the quantity and conformational state of Fg varies when adsorbed to surfaces coated with ELPs of varying sequence length, which may be mediating their platelet response. Collectively, the findings reinforce the applicability of the ELPs as potential thromboresistant coatings, especially with the use of the longer polypeptide—ELP4. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 540–551, 2014.
Investigating surface topology and cyclic‐RGD peptide functionalization on vascular endothelialization
Authors: McNichols Colton , Wilkins Justin , Kubota Atsutoshi , Shiu Yan T. , Aouadi Samir M. , Kohli Punit 
Published: March 2013

AbstractThe advantages of endothelialization of a stent surface in comparison with the bare metal and drug‐eluting stents used today include reduced late‐stent restenosis and in‐stent thrombosis. In this article, we study the effect of surface topology and functionalization of tantalum (Ta) with cyclic‐(arginine‐glycine‐aspartic acid‐d‐phenylalanine‐lysine) (cRGDfK) on the attachment, spreading, and growth of vascular endothelial cells. Self‐assembled nanodimpling on Ta surfaces was performed using a one‐step electropolishing technique. Next, cRGDfK was covalently bonded onto the surface using silane chemistry. Our results suggest that nanotexturing alone was sufficient to enhance cell spreading, but the combination of a nanodimpled surfaces along with the cRGDfK peptide may produce a better endothelialization coating on the surface in terms of higher cell density, better cell spreading, and more cell–cell interactions, when compared to using cRGDfK peptide functionalization alone or nanotexturing alone. We believe that future research should look into how to implement both modifications (topographic and chemical modifications) to optimize the stent surface for endothelialization. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 532–539, 2014.
Sonographic predictors of ovarian malignancy
Authors: Barroilhet Lisa , Vitonis Allison , Shipp Thomas , Muto Michael , Benacerraf Beryl 
Published: March 2013

PurposeTo identify a combination of sonographic features that best predicts ovarian malignancy.MethodsSubjects included 249 women who had a transvaginal sonogram for a pelvic mass at Brigham and Women's Hospital between December 2005 and February 2010. Subjects underwent surgery for removal of the mass and pathologic diagnosis was available. Images were reviewed retrospectively by one sonologist blinded to diagnosis and clinical information. Twelve sonographic features were scored for each mass. The dataset was divided into training (n = 149) and testing (n = 100) sets. Within the training set, a stepwise logistic regression was used to weigh each variable and combination of features to identify those associated with malignancies. Using the results from the logistic regression analyses, we created a three‐level risk stratification that was applied to the sonograms of subjects in the testing set to assess its ability to distinguish benign lesions from invasive and borderline cancers.ResultsHigh risk lesions included all masses with internal vascularity. In our testing set, this feature was present in 9 out of 12 (75%) invasive cancers, 1 out of 6 (16.7%) borderline lesions, and 9 out of 82 (11%) benign masses. The intermediate risk level included lesions with a thick wall or thick septa without internal blood flow. This combination of features identified one additional invasive cancer and 5 out of 6 (83.3%) borderline tumors. Masses with low risk features had a 2/49 (4.0%) incidence of malignancy.ConclusionsIn the absence of high or intermediate risk sonographic features, the risk of malignancy is low. © 2013 Wiley Periodicals, Inc. J Clin Ultrasound, 41:269–274, 2013
Measurements of the lower uterine segment during gestation
Authors: Ginsberg Yuval , Goldstein Israel , Lowenstein Lior , Weiner Zeev 
Published: March 2013

AbstractPurpose:To establish normal values for the lower uterine segment (LUS) thickness and to recognize factors that may affect these values.Methods:In this cross‐sectional study, we measured the LUS thickness in women between 11 and 41 weeks gestation. Women with placental abnormalities and fetal anomalies were excluded. Fetal weight, location of placental implantation, and cervical length were estimated. The LUS was examined to identify the thinnest zone and evaluated using the transvaginal approach with an empty urinary bladder. Full LUS thickness was measured with a caliper at the inner surface of the posterior bladder wall and another caliper at the interface between the amniotic fluid and the decidua. The myometrium was measured with the first caliper at the interface between the amniotic fluid and the deciduas and the second between the bladder wall and the myometrium. Normal values for the LUS were established throughout gestation, and correlations between the LUS gestational age, fetal weight, previous cesarean section, and other parameters were examined.Results:Overall, 350 women were included in our study. Median parity was 1 (0–6) and the majority (62%, 218/350) of women have not had a previous cesarean section. The LUS thickness inversely correlated with gestational week (Pearson's r = −0.11, p < 0.03). When stratifying the linear regression model to women with and without a history of a previous cesarean section, it was demonstrated that gestational age was moderately correlated with LUS only in the second group of patients (Pearson's r = −0.16, p = 0.1 and Pearson's r = −0.47, p < 0.0001, respectively). During the post term period, patients who had had a previous cesarean section had significantly thinner LUS compared with patients who had not had a previous cesarean section (46 mm ± 20 versus 59 mm ± 20, p = 0.002, respectively). Neither parity nor the number of previous cesarean sections were found to correlate with the thickness of the LUS (p > 0.05). Multivariate linear regression (R2 = 0.215, F(2, 63) = 9.021, p < 0.001) demonstrated that both gestational week (β = −0.13, p < 0.04) and cesarean section (β = −0.01, p < 0.0001) were independent factors associated with the thickness of the LUS; for every 1 week increase in gestational week, there was a 1.3 mm decrease in the total thickness of the LUSConclusions:We have established reference ranges for LUS thickness throughout gestation. The LUS thickness decreases throughout gestation in singleton pregnancies and is significantly thinner in postterm period pregnant women with a previous cesarean section. © 2013 Wiley Periodicals, Inc., J Clin Ultrasound, 2013