bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emerging roles of RB family: New defense mechanisms against tumor progression
Authors: Indovina Paola , Marcelli Eleonora , Casini Nadia , Rizzo Valeria , Giordano Antonio 
Published: August 2012

AbstractThe retinoblastoma (RB) family of proteins, including RB1/p105, retinoblastoma‐like 1 (RBL1/p107), and retinoblastoma‐like 2 (RBL2/p130), is principally known for its central role on cell cycle regulation. The inactivation of RB proteins confers a growth advantage and underlies multiple types of tumors. Recently, it has been shown that RB proteins have other important roles, such as preservation of chromosomal stability, induction and maintenance of senescence and regulation of apoptosis, cellular differentiation, and angiogenesis. RB proteins are involved in many cellular pathways and act as transcriptional regulators able to bind several transcription factors, thus antagonizing or potentiating their functions. Furthermore, RB proteins might control the expression of specific target genes by recruiting chromatin remodeling enzymes. Although many efforts have been made to dissect the different functions of RB proteins, it remains still unclear which are necessary for cancer suppression and the role they play at distinct steps of carcinogenesis. Moreover, RB proteins can behave differently in various cell types or cell states. Elucidating the intricate RB protein network in regulating cell fate might provide the knowledge necessary to explain their potent tumor suppressor activity and to design novel therapeutic strategies. J. Cell. Physiol. 228: 525–535, 2013. © 2012 Wiley Periodicals, Inc.
Retinoic acid derived from the fetal ovary initiates meiosis in mouse germ cells
Authors: Mu Xinyi , Wen Jing , Guo Meng , Wang Jianwei , Li Ge , Wang Zhengpin , Wang Yijing , Teng Zhen , Cui Yan , Xia Guoliang 
Published: August 2012

AbstractMeiotic initiation of germ cells at 13.5 dpc (days post‐coitus) indicates female sex determination in mice. Recent studies reveal that mesonephroi‐derived retinoic acid (RA) is the key signal for induction of meiosis. However, whether the mesonephroi is dispensable for meiosis is unclear and the role of the ovary in this meiotic process remains to be clarified. This study provides data that RA derived from fetal ovaries is sufficient to induce germ cell meiosis in a fetal ovary culture system. When fetal ovaries were collected from 11.5 to 13.5 dpc fetuses, isolated and cultured in vitro, germ cells enter meiosis in the absence of mesonephroi. To exclude RA sourcing from mesonephroi, 11.5 dpc urogenital ridges (UGRs; mesonephroi and ovary complexes) were treated with diethylaminobenzaldehyde (DEAB) to block retinaldehyde dehydrogenase (RALDH) activity in the mesonephros and the ovary. Meiosis occurred when DEAB was withdrawn and the mesonephros was removed 2 days later. Furthermore, RALDH1, rather than RALDH2, serves as the major RA synthetase in UGRs from 12.5 to 15.5 dpc. DEAB treatment to the ovary alone was able to block germ cell meiotic entry. We also found that exogenously supplied RA dose‐dependently reduced germ cell numbers in ovaries by accelerating the entry into meiosis. These results suggest that ovary‐derived RA is responsible for meiosis initiation. J. Cell. Physiol. 228: 627–639, 2013. © 2012 Wiley Periodicals, Inc.
Carotid circumferential wall stress homeostasis in early remodeling: Theoretical approach and clinical application
Authors: Bokov Plamen , Chironi Gilles , Orobinskaia Ludmila , Flaud Patrice , Simon Alain 
Published: August 2012

AbstractPurpose.To assess the influence of cardiovascular risk factors on arterial wall growth and the remodeling process.Methods.In a theoretical part, we used a well‐established relationship linking the rate of thickening of the arterial wall to the circumferential wall stress (CWS) increase. In a clinical part, we measured the intima‐media thickness (IMT) in 166 subjects with increased cardiovascular risk score but no treatment for hypertension or hypercholesterolemia, no diabetes, and no cardiovascular disease. Far wall IMT and lumen diameter were measured along the right carotid artery by high‐resolution ultrasonography and computerized image analysis.Results.A decreasing linear relationship between IMT and CWS was deduced from the theoretical model, implying that an increase in CWS would result in an IMT increase, and that the higher the IMT‐CWS slope, the higher the thickening response. Subjects with advanced age, renal insufficiency, high 10‐year Framingham risk, carotid atherosclerosis, and advanced atherosclerosis at other sites had sharper IMT‐CWS slope (p < 0.05), in agreement with the homeostasis of CWS hypothesis.Conclusions.The IMT increase responding to a CWS increase was greater in high‐risk patients. © 2012 Wiley Periodicals, Inc. J Clin Ultrasound 40:486–494, 2012
Poloxamer synperonic F108 improves cellular transduction with lentiviral vectors
Authors: Höfig Ines , Atkinson Michael J. , Mall Sabine , Krackhardt Angela M. , Thirion Christian , Anastasov Nataša 
Published: August 2012

AbstractBackgroundAlthough lentiviral transduction methods are widely used, their broader application is dependent upon the optimization of lentiviral transduction efficiency for a broad range of cell types. In the present study, we focus on the evaluation of two chemical classes with respect to their ability to increase lentiviral transduction without cytotoxicity.MethodsWe compared the activity of adjuvants that are already used for lentivirus delivery with that of novel adjuvants selected on the basis of their chemical and physical characteristics.ResultsThe novel poloxamer synperonic F108 demonstrated superior characteristics for enhancing lentiviral transduction over the best‐in‐class polybrene‐assisted transduction. The results revealed that poloxamer synperonic F108 exhibited the dual benefits of low toxicity and a high efficiency of lentiviral gene delivery into a range of different primary cell cultures. In the presence of poloxamer synperonic F108, cells showed an increased propidium dye influx indicating a re‐organization of membrane microstructures accompanying lentivirus uptake. The administration of a mixture of poloxamer synperonic F108 with polybrene further enhanced lentiviral transduction rates.ConclusionsThe results obtained in the present study indicate that a contribution to efficiency is made by each adjuvant, with polybrene acting as a charge protector and poloxamer synperonic F108 as a membrane modulator. Therefore, poloxamer synperonic F108, either alone or in combination, can lead to the optimization of large‐scale lentiviral transduction approaches. Copyright © 2012 John Wiley & Sons, Ltd.
Effects of sclerostin antibody on healing of a non‐critical size femoral bone defect
Authors: Jawad Muhammad U. , Fritton Kate E. , Ma Ting , Ren Pei‐Gen , Goodman Stuart B. , Ke Hua Z. , Babij Philip , Genovese Mark C. 
Published: August 2012

AbstractSclerostin is a glycoprotein secreted by osteocytes and inhibits osteoblastogenesis via inhibition of Wnt signaling. We hypothesized that sclerostin antibody (Scl‐AbIII) would accelerate the healing of a murine femoral non‐critical size bone defect model. A unilateral and unicortical 0.8 mm‐sized drill hole was made in the proximal femoral shaft of adult female nude mice. One group of mice received subcutaneous injections of Scl‐AbIII and a second group received vehicle only. Reporter MC3T3 osteoprogenitor cells were injected via the tail vein 3 days after surgery to monitor systemic trafficking of exogenous osteoprogenitors. Bioluminescence imaging (BLI), microcomputed tomography (microCT), micropositron emission tomography (microPET) and histological analysis were used to compare the bone healing responses to Scl‐AbIII treatment. Bone mineral density (BMD) significantly increased at the defect site after week 1, and was significantly higher in the treatment compared with the control group at all time points. This finding was also confirmed on histological analysis by increased deposition of new woven bone. MicroPET scanning showed a trend for greater activity in the control group at day 21 compared with the Scl‐AbIII group, indicating early bone maturation following treatment with Scl‐AbIII. Whereas the BLI signals derived from the injected osteoprogenitor cells showed no differences between vehicle and Scl‐AbIII treated groups, systemic migration of MC3T3 cells to the bone defect was clearly identified in both groups using immunohistochemistry. Systemic administration of Scl‐AbIII resulted in earlier healing and maturation of a non‐critical size bone defect. These findings underscore the potential use of Scl‐AbIII for treatment of complicated fractures, non‐unions, and other clinical scenarios. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:155–163, 2012
Assessment of loading history of compartments in the knee using bone SPECT/CT: A study combining alignment and 99mTc‐HDP tracer uptake/distribution patterns
Authors: Hirschmann Michael T. , Schön Stephan , Afifi Faik K. , Amsler Felix , Rasch Helmut , Friederich Niklaus F. , Arnold Markus P. 
Published: August 2012

AbstractThis study investigates if the mechanical/anatomical alignment influences the intensity values as well as the distribution pattern of SPECT/CT tracer uptake. Eighty‐five knees (mean age 48 ± 16) undergoing 99mTc‐HDP‐SPECT/CT due to pain were prospectively included. SPECT/CTs were analyzed using a previously validated localization method. The maximum intensities in each femoral, tibial, and patellar joint compartment (medial, lateral, central, superior, and inferior) were noted using a color‐coded grading scale (0–10). The Kellgren–Lawrence osteoarthritis score (KL) was assessed on standardized radiographs. Long leg radiographs were used to assess the mechanical/anatomical leg alignment, which was classified as varus, valgus, or neutral. The alignment and KL was correlated with the intensity of tracer uptake in each area of interest (p < 0.05). The intensity of SPECT/CT tracer uptake in the medial and lateral knee compartment significantly correlated with varus or valgus alignment of the knee. A higher degree of osteoarthritis was significantly related to higher tracer uptake in the corresponding joint compartments. SPECT/CT reflects the specific loading pattern of the knee with regard to its alignment. It is also related to the degree of osteoarthritis. Hence, SPECT/CT should be considered for follow‐up of patients after realignment treatments, osteotomies, deloader devices, or insoles. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 268–274, 2013
Efficacy of disinfecting solutions in removing biofilms from polyvinyl chloride tracheostomy tubes
Authors: Silva Rodrigo C. , Carver Ryan A. , Ojano‐Dirain Carolyn P. , Antonelli Patrick J. 
Published: August 2012

AbstractObjectives/Hypothesis:Bacterial biofilms are prevalent in pediatric tracheostomy tubes (TTs) and are not completely cleared by standard cleaning with gauze and household detergents. We aimed to examine the effectiveness of different disinfecting solutions to remove Staphylococcus aureus (SA) and Pseudomonas aerginosa (PA) biofilms from TTs.Study Design:Prospective, controlled, in vitro microbiologic study.Methods:Uniform coupons obtained from polyvinyl chloride (PVC) pediatric TTs were briefly exposed to human plasma. The samples were incubated in growth media with either PA or SA for 7 days, and total bacterial growth was monitored by media turbidity. Five sets of 18 coupons each were exposed for 5 minutes to one of five different solutions: 2% aqueous chlorhexidine gluconate solution, 0.3% aqueous sodium hypochlorite, Polident denture cleanser, 3% hydrogen peroxide, or preservative‐free phosphate‐buffered saline (PBS) as a negative control. Biofilm presence was measured with bacterial counts, and surface integrity was assessed with scanning electron microscopy (SEM).Results:All treatments significantly reduced mean SA counts (P = <.001). Sodium hypochlorite and chlorhexidine were more effective than peroxide and Polident. Chlorhexidine, sodium hypochlorite, and peroxide reduced PA counts (P = .001, .001, and .002, respectively), but Polident tabs had no significant effect. SEM revealed preserved TT surface integrity after exposure to all solutions.Conclusions:Disinfection with sodium hypochlorite or chlorhexidine solutions significantly reduces SA and PA biofilms on PVC TTs. Standard home care of reusable pediatric TTs may be improved by use of these readily available solutions. Laryngoscope, 2013
Direct femtosecond laser surface nano/microstructuring and its applications
Authors: Vorobyev Anatoliy Y. , Guo Chunlei 
Published: August 2012

AbstractThis paper reviews a new field of direct femtosecond laser surface nano/microstructuring and its applications. Over the past few years, direct femtosecond laser surface processing has distinguished itself from other conventional laser ablation methods and become one of the best ways to create surface structures at nano‐ and micro‐scales on metals and semiconductors due to its flexibility, simplicity, and controllability in creating various types of nano/microstructures that are suitable for a wide range of applications. Significant advancements were made recently in applying this technique to altering optical properties of metals and semiconductors. As a result, highly absorptive metals and semiconductors were created, dubbed as the “black metals” and “black silicon”. Furthermore, various colors other than black have been created through structural coloring on metals. Direct femtosecond laser processing is also capable of producing novel materials with wetting properties ranging from superhydrophilic to superhydrophobic. In the extreme case, superwicking materials were created that can make liquids run vertically uphill against the gravity over an extended surface area. Though impressive scientific achievements have been made so far, direct femtosecond laser processing is still a young research field and many exciting findings are expected to emerge on its horizon.
Mathematical Modeling of Temperature Rising Elution Fractionation (TREF) of Polyethylene and Ethylene/1‐Olefin Copolymers
Authors: Siriwongsarn Ekaphol , Anantawaraskul Siripon , Chokputtanawuttilerd Nuttawat , Alghyamah Abdulaziz A. , Soares João B. P. 
Published: August 2012

AbstractTemperature rising elution fractionation (TREF) is a characterization technique widely used to estimate chemical composition distribution (CCD) of semicrystalline copolymers. Although several mathematical models have been previously proposed to elucidate the TREF fractionation mechanism, all previous TREF models assume equilibrium fractionation; thus, they cannot describe important kinetics effects observed in TREF experiments. In this work, a new TREF model is developed incorporating crystallization and dissolution kinetic models during the fractionation process. The proposed model describes the effects of molecular weight, comonomer content, cooling rate, heating rate, and solvent flow rate on experimental TREF profiles for both polyethylene and ethylene/1‐olefin copolymers very well.
Which prior knowledge? Quantification of in vivo brain 13C MR spectra following 13C glucose infusion using AMARES
Authors: Lanz Bernard , Duarte João M. N. , Kunz Nicolas , Mlynárik Vladimir , Gruetter Rolf , Cudalbu Cristina 
Published: August 2012

AbstractThe recent developments in high magnetic field 13C magnetic resonance spectroscopy with improved localization and shimming techniques have led to important gains in sensitivity and spectral resolution of 13C in vivo spectra in the rodent brain, enabling the separation of several 13C isotopomers of glutamate and glutamine. In this context, the assumptions used in spectral quantification might have a significant impact on the determination of the 13C concentrations and the related metabolic fluxes. In this study, the time domain spectral quantification algorithm AMARES (advanced method for accurate, robust and efficient spectral fitting) was applied to 13C magnetic resonance spectroscopy spectra acquired in the rat brain at 9.4 T, following infusion of [1,6‐13C2] glucose. Using both Monte Carlo simulations and in vivo data, the goal of this work was: (1) to validate the quantification of in vivo 13C isotopomers using AMARES; (2) to assess the impact of the prior knowledge on the quantification of in vivo 13C isotopomers using AMARES; (3) to compare AMARES and LCModel (linear combination of model spectra) for the quantification of in vivo 13C spectra. AMARES led to accurate and reliable 13C spectral quantification similar to those obtained using LCModel, when the frequency shifts, J‐coupling constants and phase patterns of the different 13C isotopomers were included as prior knowledge in the analysis. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.
Importance of voriconazole therapeutic drug monitoring in pediatric cancer patients with invasive aspergillosis
Authors: Choi Soo‐Han , Lee Soo‐Youn , Hwang Ji‐Young , Lee Soo Hyun , Yoo Keon Hee , Sung Ki Woong , Koo Hong Hoe , Kim Yae‐Jean 
Published: August 2012

AbstractBackgroundVoriconazole is the drug of choice for invasive aspergillosis (IA) and drug levels are influenced by interactions with other drugs and genetic predisposition. We performed a retrospective analysis of voriconazole drug levels and investigated the adequacy of drug levels in pediatric cancer patients and hematopoietic cell transplant (HCT) recipients with IA.ProcedureTrough serum concentrations of voriconazole in patients younger than 19 years during a 30‐month period were analyzed. The therapeutic range was determined as 1–6 µg/ml.ResultsA total of 193 voriconazole measurements at steady‐state [86 on intravenous (IV) and 107 on oral (PO) doses] were obtained from 27 patients (median age 12.2 years). On the first monitoring, 19 patients (70.4%) achieved the therapeutic range. However, only 10 patients (37.0%) achieved the therapeutic range on second monitoring. Sixty‐four percent of the total measurements were within the therapeutic range: 66.3% of IV and 61.7% of PO. A significant correlation between oral doses and trough levels of voriconazole was observed in patients ≤6 years old (Spearman's rank correlation coefficient = 0.4819, P = 0.027). Patients aged ≤6 years needed a significantly higher median dose of PO voriconazole to maintain therapeutic trough levels compared to older patient groups (8.9 vs. 4.2 mg/kg/dose, P < 0.001). Voriconazole level <1 µg/ml was more frequently observed in patients with treatment failure at week 6 of voriconazole therapy (failure vs. success, 42.1% vs. 19.7%; P = 0.012).ConclusionsSerum concentrations of voriconazole in children were variable, depending on the patient's age and route of administration. Continuous and careful drug level monitoring should be performed. Pediatr Blood Cancer 2013; 60: 82–87. © 2012 Wiley Periodicals, Inc.
Phase I dose‐escalation trial of clofarabine followed by escalating doses of fractionated cyclophosphamide in children with relapsed or refractory acute leukemias
Authors: Abd Elmoneim Abeer , Gore Lia , Ricklis Rebecca M. , Boklan Jessica , Cooper Todd , Narendran Aru , Rolla Katherine , Scott Tammy , Arceci Robert J. 
Published: August 2012

AbstractBackgroundBy inhibiting DNA repair, clofarabine (CLO) may augment cyclophosphamide (CY)‐induced DNA damage and apoptosis. We performed a Phase I study for refractory and/or relapsed (R/R) leukemia in children to determine maximum‐tolerated dose (MTD) of time‐sequential CLO followed by CY.ProcedureThirteen patients with (R/R) ALL (n = 8) and AML (N = 5), median age 9 years (range: 2–12 years), were treated with escalating doses of CLO on days 1, 2, 3 and 8, 9, 10 and CY 200 mg/m2/day on days 0 and 1 then 400 mg/m2/day on days 2, 3, 8, 9, and 10. Ten patients were treated at dose level 1 (DL1) (CLO 20 mg/m2/day) and three patients at DL2 (CLO 30 mg/m2/day). The average number of prior chemotherapies was 8.9. DNA damage testing was performed before treatment on day 0, and 2 hours after CY on day 0, before sequential CLO, CY treatment on day 1, and 2 hours after CLO followed by CY on day 1.ResultsTwo patients at DL2 had dose‐limiting toxicities (DLTs) that included hypotension with cardio‐respiratory failure (1) and hepato‐renal failure (1). Complete remission (CR) was achieved in 2/11 (18.2%) and partial remission (PR) in 2/11 (18.2%) for an overall response (OR) of 36.4%. The use of CLO before CY augmented CY‐induced DNA damage in leukemic blasts compared to CY alone.ConclusionIn pediatric patients with R/R leukemia, 20 mg/m2/day is the MTD for CLO in timed sequential combination with CY. Increased DNA damage with the use of this combination suggests a mechanism for the sequential timing of these two chemotherapeutic agents. Pediatr Blood Cancer 2012; 59: 1252–1258. © 2012 Wiley Periodicals, Inc.
Neuroendocrine tumors of the appendix in children and adolescents
Authors: Boxberger Nicole , Redlich Antje , Böger Christine , Leuschner Ivo , von Schweinitz Dietrich , Dralle Henning , Vorwerk Peter 
Published: August 2012

AbstractBackgroundNeuroendocrine tumors (NET) of the appendix in children and adolescents are rare and mostly detected postoperatively by a histopathological examination. Since the malignant potential of these tumors remains unclear, therapeutic recommendations are not evidence based. The Society of Pediatric Oncology and Hematology (GPOH) has prospectively registered and followed children with appendical NET since 1997 (GPOH‐MET trial). The objective of this study was to critically evaluate the therapeutic recommendations for appendical NET in children.ProcedureClinical data of 237 children with appendical NET were prospectively analyzed.ResultsThe mean age at presentation was 13.0 years, while the mean follow‐up time was 2.9 (0.0–12.8) years. The majority of tumors (70.9%) were located at the apex, and were smaller than or equal to 10 mm (72.7%). Tumor size was directly correlated with age. A second operation or primary lymph node sampling was done in 25.3% (N = 60) of the patients, and infiltration of the lymph nodes by tumor cells was found in nine of these patients (15%). All 237 patients are alive without tumor symptoms.ConclusionsROC analysis and subsequent calculations identified a tumor size of >15 mm as the optimal cut‐off point for the prediction of metastatic spread into the lymph system, with a sensitivity of 77.8% and a specificity of 66.7%. Therefore, secondary right hemicolectomy in completely removed appendical NET is recommended only in tumors >15 mm in size. For incompletely removed tumors ≤15 mm a local follow‐up resection with lymph node sampling is recommended. Pediatr Blood Cancer 2013; 60: 65–70. © 2012 Wiley Periodicals, Inc.