bluuebunny/crossref_metadata_2025 huggingface dataset:
Silymarin inhibits melanoma cell growth both in vitro and in vivo by targeting cell cycle regulators, angiogenic biomarkers and induction of apoptosis
Authors: Vaid Mudit , Singh Tripti , Prasad Ram , Katiyar Santosh K.
Published: August 2014

Cutaneous malignant melanoma is the leading cause of death from skin diseases and is often associated with activating mutations of the proto‐oncogene BRAF. To develop more effective strategies for the prevention or treatment of melanoma, we have examined the inhibitory effects of silymarin, a flavanoid from Silybum marianum, on melanoma cells. Using A375 (BRAF‐mutated) and Hs294t (non BRAF‐mutated but highly metastatic) human melanoma cell lines, we found that in vitro treatment with silymarin resulted in a dose‐dependent: (i) reduction in cell viability; (ii) enhancement of either Go/G1 (A375) or G2‐M (Hs294t) phase cell cycle arrest with corresponding alterations in cyclins and cyclin‐dependent kinases; and (iii) induction of apoptosis. The silymarin‐induced apoptosis of human melanoma cells was associated with a reduction in the levels of anti‐apoptotic proteins (Bcl‐2 and Bcl‐xl), an increase in the levels of pro‐apoptotic protein (Bax), and activation of caspases. Further, oral administration of silymarin (500 mg/kg body weight/2× a week) significantly inhibited (60%, P < 0.01) the growth of BRAF‐mutated A375 melanoma tumor xenografts, and this was associated with: (i) inhibition of cell proliferation; (ii) induction of apoptosis of tumor cells; (iii) alterations in cell cycle regulatory proteins; and (iv) reduced expression of tumor angiogenic biomarkers in tumor xenograft tissues. These results indicate that silymarin may have a chemotherapeutic effect on human melanoma cell growth and warrant its further evaluation. © 2014 Wiley Periodicals, Inc.
Simultaneous acquisition of cerebral blood volume‐, blood flow‐, and blood oxygenation‐weighted MRI signals at ultra‐high magnetic field
Authors: Krieger Steffen N. , Huber Laurentius , Poser Benedikt A. , Turner Robert , Egan Gary F.
Published: September 2014

Purpose

Yang et al. proposed an MRI technique for the simultaneous acquisition of cerebral blood volume (CBV), cerebral blood flow (CBF), and blood oxygenation level‐dependent (BOLD)‐weighted MRI signals (9). The purpose of this study was to develop modified version of the Yang sequence, which utilizes the advantages of 7 Tesla, leading to a robust and reliable MRI sequence.

Methods

The inversion recovery‐based MR pulse sequence introduced here involves slice‐saturation slab‐inversion vascular space occupancy (SI‐SS‐VASO) MRI, double echo planar imaging readouts for arterial spin labeling, and VASO in order to correct for BOLD contamination, and a separate BOLD acquisition to minimize inversion effects on the BOLD signal. A standard visual stimulus block design was used to evaluate the spatial and temporal characteristics of CBV‐, CBF‐, and BOLD‐weighted images.

Results

The high signal‐to‐noise ratio and spatial resolution of this method leads to robust activation maps. This technique enables the investigation of the differential spatial specificity and temporal characteristics of the different modalities.

Conclusion

The pulse sequence could be a powerful tool for studies of neurovascular coupling, hemodynamic response, or calibrated BOLD. Magn Reson Med 74:513–517, 2015. © 2014 Wiley Periodicals, Inc.
Liminality as a Conceptual Frame for Understanding the Family Caregiving Rite of Passage: An Integrative Review
Authors: Gibbons Susanne W. , Ross Alyson , Bevans Margaret
Published: August 2014

Family caregiving is a significant rite of passage experienced by family caregivers of individuals with protracted illness or injury. In an integrative review of 26 studies, we characterized family caregiving from the sociocultural perspective of liminality and explored associated psychosocial implications. Analysis of published evidence on this dynamic and formative transition produced a range of themes. While role ambiguity resolved for most, for others, uncertainty and suffering continued. The process of becoming a caregiver was transformative and can be viewed as a rebirth that is largely socially and culturally driven. The transition to family caregiving model produced by this review provides a holistic perspective on this phenomenon and draws attention to aspects of the experience previously underappreciated. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
Pyrene‐Capped CdSe@ZnS Nanoparticles as Sensitive Flexible Oxygen Sensors in Non‐Aqueous Media
Authors: González-Carrero Soranyel , de la Guardia Miguel , Galian Raquel E. , Pérez-Prieto Julia
Published: September 2014

A flexible, highly sensitive sensor of oxygen in non‐aqueous solvents is described. It consists of CdSe/ZnS nanoparticles decorated with a considerable number of pyrene units, thus making the formation of the pyrene excimer possible. The emission of the pyrene excimer and that of the nanoparticle are suitably separated from each other and also from the excitation wavelength. This sensor can be applied as a ratiometric oxygen sensor by using the linear response of the pyrene excimer lifetime combined with the linear response of the nanoparticle excited state lifetime. This nanohybrid has been assayed in seven media with different dielectric constants and viscosities over the whole oxygen concentration range. In addition, the sensor versatility provides an easy way for monitoring oxygen diffusion through systems.
Altered α‐defensin 5 expression in cervical squamocolumnar junction: implication in the formation of a viral/tumour‐permissive microenvironment
Authors: Hubert Pascale , Herman Ludivine , Roncarati Patrick , Maillard Catherine , Renoux Virginie , Demoulin Stéphanie , Erpicum Charlotte , Foidart Jean‐Michel , Boniver Jacques , Noël Agnès , Delvenne Philippe , Herfs Michael
Published: September 2014

Human papillomavirus (HPV) infection, particularly type 16, is causally associated with cancer of the uterine cervix, which mainly develops at the squamocolumnar (SC) junction. The progression of cervical HPV infections into (pre)neoplastic lesions suggests that viral antigens are not adequately recognized by innate immunity or presented to the adaptive immune system. Members of the defensin family have recently been found to inhibit viral and bacterial pathogens, to stimulate the migration of immune cells and to play a role in anticancer responses. In the present study, we focused on the poorly characterized human α‐defensin 5 (HD‐5) and its possible role in these processes. We showed that HD‐5 was able to prevent HPV virion entry into cervical keratinocytes and to influence adaptive immunity. Indeed, this peptide specifically induced the chemoattraction and proliferation of both activated T lymphocytes and immature dendritic cells in a CCR2/CCR6‐dependent manner and stimulated the infiltration of these professional antigen‐presenting cells in a (pre)neoplastic epithelium transplanted in vivo in immunodeficient mice. No chemotactic effect was observed with plasmacytoid dendritic cells, macrophages or natural killer cells. Proliferative and angiogenic effects of HD‐5 were also assessed in vitro and in vivo. However there was a striking regional disparity in expression of HD‐5, being prominent in ectocervical, vaginal and vulvar neoplasia, while absent, or nearly so, in the cervical SC junction. Taken together, these results suggest one possible explanation for why the SC junction is uniquely vulnerable to both high‐risk HPV infection (via reduced HD‐5 expression and viral entry) and progression of neoplasia (via altered cell‐mediated immune responses and altered microenvironment). Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd
Corticosteroid administration is associated with improved outcome of patients presenting high inflammatory cytokine levels during septic shock
Authors: Xu Xiao‐Jun , Tang Yong‐Min , Song Hua , Yang Shi‐Long , Xu Wei‐Qun , Shi Shu‐Wen
Published: August 2014

Background

This study aimed to investigate the corticosteroid effects on pediatric hematology/oncology patients with septic shock.

Procedure

We performed a retrospective study by examining data from a prospective observational study in pediatric hematology/oncology patients with septic shock. We compared the clinical features and the outcomes of the patients treated with and without corticosteroid.

Results

One hundred episodes of septic shock were recorded in this study. The 28‐day mortality of this cohort was 14.0%. Sixty‐eight episodes of shock were treated with corticosteroids while 32 were not. The demographic features and disease severity were comparable between patients with and without corticosteroid treatment. Corticosteroid therapy was associated with improved shock reversal rate (92.6% vs. 78.1%, P = 0.049) and decreased 28‐day mortality rate (8.8 ± 3.4% vs. 25.0 ± 7.7%, P = 0.032) in univariate analysis. For patients who received vasopressor support, corticosteroid therapy was associated with shortened duration of vasopressor infusion in univariate analysis as well (median: 44 hour vs. 92 hour, P = 0.035). In multivariate analysis, corticosteroid therapy did not show significant impact on the outcome for the whole cohort (HR = 0.36, P = 0.079), but it decreased the 28‐day mortality of patients presenting high inflammatory cytokine levels (HR = 0.29, 95% CI, 0.09–0.95, P = 0.040). Corticosteroid administration did not increase the superinfection rate (24.2% vs. 8.3%, P = 0.134) and did not result in superinfection‐related death in this cohort.

Conclusions

Corticosteroid administration is associated with improved outcome in pediatric hematology/oncology patients presenting high inflammatory cytokine levels during septic shock. Pediatr Blood Cancer 2014;61:2243–2248. © 2014 Wiley Periodicals, Inc.
Proposed strategy for the use of high‐dose chemotherapy with stem cell rescue and intrathecal topotecan without whole‐brain irradiation for infantile classic medulloblastoma
Authors: Yamada Ai , Moritake Hiroshi , Kamimura Sachiyo , Yamashita Shinji , Takeshima Hideo , Nunoi Hiroyuki
Published: August 2014

We describe a 6‐month‐old infant with classic medulloblastoma. Gross total resection of the left cerebellar tumor was performed; however, relapse occurred during the administration of intrathecal and intravenous methotrexate‐based chemotherapy. After undergoing resection, high‐dose chemotherapy was administered consisting of topotecan, melphalan, and cyclophosphamide with autologous peripheral stem cell rescue followed by local irradiation and intrathecal topotecan, which resulted in a complete response for more than two years. The administration of high‐dose chemotherapy followed by intrathecal topotecan as maintenance therapy is an effective strategy, without losses in the cognitive function, for avoiding the use of whole‐brain irradiation for infantile classic medulloblastoma. Pediatr Blood Cancer 2014;61:2316–2318. © 2014 Wiley Periodicals, Inc.
Clear cell sarcoma of the kidney: Patients' characteristics and improved outcome in developing countries
Authors: Zekri Wael , Alfaar Ahmad Samir , Yehia Dina , Elshafie Maged M. , Zaghloul Mohamed Saad , El‐Kinaai Naglaa , Taha Hala , Refaat Amal , Younes Alaa A.
Published: August 2014

Background

Clear cell sarcoma of the kidney (CCSK) is a rare and aggressive tumor accounting for 5% of pediatric renal tumors with an incidence of 20 patients per year in the USA. It is bone metastasizing with poor prognosis. Our aim was to show characteristics of patients in relation to improved outcome in one of the developing countries.

Procedure

We included all patients diagnosed as CCSK in the period between July 2007 and March 2012 at Children's Cancer Hospital, Egypt. Patients' demographics, clinical presentation, pathology, and management were reviewed. Follow up was continued until April 2013.

Results

Twenty‐five patients were identified in the defined time interval, accounting for 7% all renal tumors diagnosed at the hospital. Mean age was 36 months. Abdominal swelling and hematuria were the most common presentations. Stages I, II, III, IV, and V represented 9 (36%), 3 (12%), 8 (32%), 3 (12%), and 2 (8%), respectively. Twenty‐four patients had radical nephrectomy either upfront or after neo‐adjuvant chemotherapy. Surgery was followed by adjuvant chemotherapy. Abdominal radiotherapy was given for local stages II and III. Twenty‐two patients reached complete remission, while one patient had stationary disease and two patients died due to progression and relapse. Overall survival was 88.5% and event‐free survival was 87.8% at 45 months.

Conclusion

Although previous studies indicate poor prognosis of CCSK, our experience shows that those patients can be treated using extensive chemotherapy combined with proper local control. Pediatr Blood Cancer 2014;61:2185–2190. © 2014 Wiley Periodicals, Inc.
Family life events in the first year of acute lymphoblastic leukemia therapy: A children's oncology group report
Authors: Lau Samantha , Lu Xiaomin , Balsamo Lyn , Devidas Meenakshi , Winick Naomi , Hunger Stephen P. , Carroll William , Stork Linda , Maloney Kelly , Kadan‐Lottick Nina
Published: August 2014

Background

Despite higher cure rates, childhood acute lymphoblastic leukemia (ALL) may continue to result in considerable family strain. We sought to (i) measure incidence of divorce, reduced career opportunities, changes to work hours, home relocation, and changes to family planning at one year after ALL diagnosis; and (ii) Identify family and patient factors associated with these events.

Procedure

We conducted a prospective cohort study of 159 children with average risk‐ALL enrolled and treated on COG protocol AALL0331 at 31 selected sites. Eligibility criteria included age ≥2 years and English or Spanish comprehension. Parents completed surveys at three time points during the first 12 months of therapy.

Results

Parents were at significantly increased risk of loss of employment (46% vs. 9.1%, P ≤ 0.001) than peers nationally. 13% divorced/separated, 27% relocated homes, 22% decided not to have more children, 51% declined occupational opportunities, and 68% decreased work hours. In adjusted analyses, relocation correlated with less maternal education (OR: 4.27 [95% CI: 1.43–12.82]). Declining parental opportunities associated with family income <$50,000 (OR: 4.25 [95% CI: 1.50–12.02]) and child <5 years old (OR: 4.21 [95% CI: 1.73–10.25]). Deciding not to have more children correlated with smaller family size 2–3 versus 4–5 (OR: 3.62 [95% CI: 1.10–11.96]).

Conclusion

Families experience a high incidence of major life changes in the first year of ALL treatment. Understanding these burdens helps health care providers to provide appropriate anticipatory guidance and support. No unifying factor was associated with the different family events. Ongoing follow‐up is planned to measure long‐term outcomes. Pediatr Blood Cancer 2014;61:2277–2284. © 2014 Wiley Periodicals, Inc.
Design of a drug‐drug interaction study of vincristine with azole antifungals in pediatric cancer patients using clinical trial simulation
Authors: van Hasselt J. G. Coen , van Eijkelenburg Natasha K. A. , Beijnen Jos H. , Schellens Jan H.M. , Huitema Alwin D. R.
Published: August 2014

Background

The aim of the current work was to perform a clinical trial simulation (CTS) analysis to optimize a drug‐drug interaction (DDI) study of vincristine in children who also received azole antifungals, taking into account challenges of conducting clinical trials in this population, and, to provide a motivating example of the application of CTS in the design of pediatric oncology clinical trials.

Procedure

A pharmacokinetic (PK) model for vincristine in children was used to simulate concentration‐time profiles. A continuous model for body surface area versus age was defined based on pediatric growth curves. Informative sampling time windows were derived using D‐optimal design. The CTS framework was used to different magnitudes of clearance inhibition (10%, 25%, or 40%), sample size (30–500), the impact of missing samples or sampling occasions, and the age distribution, on the power to detect a significant inhibition effect, and in addition, the relative estimation error (REE) of the interaction effect.

Results

A minimum group specific sample size of 38 patients with a total sample size of 150 patients was required to detect a clearance inhibition effect of 40% with 80% power, while in the case of a lower effect of clearance inhibition, a substantially larger sample size was required. However, for the majority of re‐estimated drug effects, the inhibition effect could be estimated precisely (REE < 25%) in even smaller sample sizes and with lower effect sizes.

Conclusion

This work demonstrated the utility of CTS for the evaluation of PK clinical trial designs in the pediatric oncology population. Pediatr Blood Cancer 2014;61:2223–2229. © 2014 Wiley Periodicals, Inc.
Nothing but NET: A review of norepinephrine transporter expression and efficacy of 131I‐mIBG therapy
Authors: Streby Keri A. , Shah Nilay , Ranalli Mark A. , Kunkler Anne , Cripe Timothy P.
Published: August 2014

Neuroblastoma is unique amongst common pediatric cancers for its expression of the norepinephrine transporter (NET), enabling tumor‐selective imaging and therapy with radioactive analogues of norepinephrine. The majority of neuroblastoma tumors are avid for 123I‐metaiodobenzaguanidine (mIBG) on imaging, yet the therapeutic response to 131I‐mIBG is only 30% in clinical trials, and off‐target effects cause short‐ and long‐term morbidity. We review the contemporary understanding of the tumor‐selective uptake, retention, and efflux of meta‐iodobenzylguanidine (mIBG) and strategies currently in development for improving its efficacy. Combination treatment strategies aimed at enhancing NET are likely necessary to reach the full potential of 131I‐mIBG therapy. Pediatr Blood Cancer 2015;62:5–11 © 2014 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals, Inc.
Subclinical cardiotoxicity in childhood cancer survivors exposed to very low dose anthracycline therapy
Authors: Leger Kasey , Slone Tamra , Lemler Matthew , Leonard David , Cochran Cindy , Bowman W. Paul , Bashore Lisa , Winick Naomi
Published: August 2014

Background

Subclinical cardiotoxicity occurs in childhood cancer survivors following moderate and high anthracycline doses. However, less is known about the subclinical changes in left ventricular (LV) structure that occur after very low anthracycline doses of ≤100 mg/m2. This study was designed to assess LV function and key structural parameters following very low doses of anthracycline.

Procedure

Conventional 2‐dimensional echocardiograms with Doppler were obtained in 91 survivors of childhood cancer exposed to ≤100 mg/m2,an average of 9.8 years from diagnosis. LV structural measurements were converted into Z‐scores. The Z‐score distributions were compared to those of the normal population. Diastolic and systolic function were quantified.

Results

The cohort demonstrated a decreased posterior wall thickness (mean Z‐score −1.01) and mildly decreased LV end diastolic (mean Z‐score −0.85) and systolic (mean Z‐score −0.84) dimensions compared to the normal population (P < 0.001). Further, 28% of patients (n = 25) had abnormal LV posterior wall thickness, ≥2 standard deviations below the mean (Z‐score ≤ −2). There were no patients with diastolic dysfunction or symptomatic systolic dysfunction, however four patients demonstrated abnormal SF ≤ 28%.

Conclusions

A significant proportion of patients exposed to very low doses of anthracycline demonstrate subclinical abnormalities in LV structure, despite the absence of radiation or other risk factors. While we cannot say whether these structural changes will result in clinically significant cardiac disease, the reported progressive nature of these findings raises concern that there may truly be no safe dose of anthracycline. Pediatr Blood Cancer 2015;62:123–127. © 2014 Wiley Periodicals, Inc.
Population based surveillance in sickle cell disease: Methods, findings and implications from the California registry and surveillance system in hemoglobinopathies project (RuSH)
Authors: Paulukonis Susan T. , Harris William T. , Coates Thomas D. , Neumayr Lynne , Treadwell Marsha , Vichinsky Elliott , Feuchtbaum Lisa B.
Published: August 2014

Background

There are no population‐based surveillance systems to determine prevalence, impact or outcomes in sickle cell disease (SCD). Estimates of the SCD population in California range broadly from 4,500 to 7,000, and little is known about their health status, health care utilization or health outcomes. A surveillance strategy was implemented using diverse data sources to develop a multi‐dimensional, state‐based surveillance system for SCD that includes adults and children and describes utilization, treatment and outcomes.

Procedure

Data from California newborn screening, inpatient and emergency room records, Medi‐Cal/Medicaid claims and two SCD special care centers were collected for 2004–2008. A multi‐step, iterative linkage process was used to link and de‐duplicate these data sources, and case definitions were used to categorize cases.

Results

After linking and de‐duplicating, there were 1,975 confirmed cases of SCD, 3,159 probable cases as well as 8,024 possible cases. Among individual data sources, newborn screening and data from clinics contributed the greatest number of unique cases to the total. Select analyses of utilization and treatments for the population are described.

Conclusions

Using linked existing data sources, an estimate of the statewide count of the SCD population is possible. The approach can be used to create an in‐depth health status profile of the affected population by aggregating utilization, treatment, and outcomes data including mortality and morbidity information. This effort sets the stage for development of an on‐going, state‐based surveillance system. Pediatr Blood Cancer 2014;61:2271–2276. © 2014 Wiley Periodicals, Inc.
Ewing‐like sarcomas with BCOR‐CCNB3 fusion transcript: A clinical, radiological and pathological retrospective study from the Société Française des Cancers de L'Enfant
Authors: Cohen‐Gogo Sarah , Cellier Cécile , Coindre Jean‐Michel , Mosseri Véronique , Pierron Gaëlle , Guillemet Cécile , Italiano Antoine , Brugières Laurence , Orbach Daniel , Laurence Valérie , Delattre Olivier , Michon Jean
Published: August 2014

Background

This retrospective multicenter study assessed the clinical, radiological and pathological presentation, treatment and outcome of 26 patients with Ewing‐like sarcoma harboring BCOR‐CCNB3 gene fusion transcript. Tumor samples had been collected between 1994 and April 2012.

Procedure

Eligibility criteria included assessment of a BCOR‐CCNB3 transcript‐positive tumor after molecular analysis and availability of minimal clinical and pathological data. Radiological data were also retrieved when possible. Data were analyzed by descriptive statistics and methods for survival analysis.

Results

Median age at diagnosis was 13.1 years (5.9 to 25.6 years). Most patients (24/26) had localized tumors. All tumors but five were localized to bone. CCNB3 immunochemistry showed strong nuclear staining on all samples. No specific radiological features were found. Most patients received chemotherapy (15 according to protocols designed for Ewing tumors), before and/or after local treatment (surgery and/or radiotherapy, with 46.2% receiving both). Local and metastatic relapses were of poor prognosis. Induction chemotherapy and treatment according to an Ewing protocol might influence survival for patients with localized tumors. Sixteen patients are alive in complete remission with a median follow‐up of 86 months. Five year overall survival and disease‐free survival were respectively 76.5% (95% CI, 58%–95%) and 67.9% (95% CI, 48%–88%).

Conclusions

BCOR‐CCNB3 transcript‐positive Ewing‐like sarcoma diagnosis should be discussed for a transcript‐negative small round cell sarcoma in a child, adolescent or young adult patient. Diagnosis needs to be stated through CCNB3 immunochemistry or transcript identification. The exquisite chemosensitivity of these tumors should encourage the use of polychemotherapy for appropriate care, associated with best local tumor control. Pediatr Blood Cancer 2014;61:2191–2198. © 2014 Wiley Periodicals, Inc.
CALR mutation screening in pediatric primary myelofibrosis
Authors: An Wenbin , Wan Yang , Guo Ye , Chen Xiaojuan , Ren Yuanyuan , Zhang Jingliao , Chang Lixian , Wei Wei , Zhang Peihong , Zhu Xiaofan
Published: August 2014

Background

Primary myelofibrosis (PMF) is quite rare in children. Mutations of JAK2V617F or MPLW515K/L were absent in pediatric patients with PMF according to previous studies. Recently, mutations in calreticulin (CALR) were described in adult patients with JAK2/MPL‐unmutated PMF. Our study aimed to analyze the clinical and genetic features of Chinese pediatric patients with PMF.

Procedures

We retrospectively investigated 14 pediatric patients diagnosed as PMF according to WHO 2008 criteria. Direct sequencing was performed for the existence of genetic alterations in JAK2, MPL, TET2, CBL, ASXL1, IDH1, IDH2, SRSF2, EZH2, DNMT3A and CALR.

Results

In our cohort, all patients had anemia, three patients (21%) had splenomegaly, six patients (43%) had micromegakaryocytes at time of diagnosis. No patient had spontaneous remission and six patients (43%) transformed to acute myelocytic leukemia. In nine patients with evaluable cytogenetic information, three subjects (33%) had abnormal karyotypes. The median survival from time of diagnosis was 28 months. Seven patients (50%) had type 2 mutations of CALR. No patient had mutations in the other candidate genes. There was no statistical differences in age, gender, hemoglobin, WBC, neutrophil and platelet counts, percentage of circulating blast, overall survival and leukemia transformation between patients with and without CALR mutation.

Conclusion

Our study documented that Chinese pediatric patients with PMF in our cohort had its own clinical characteristics and poor outcome. CALR mutations were detected in 50% of our pediatric patients with PMF. Based on our study, CALR mutations screening could be used as molecular marker for diagnosis of pediatric patients with PMF. Pediatr Blood Cancer 2014;61:2256–2262. © 2014 Wiley Periodicals, Inc.
Utility of bone marrow aspiration and biopsy in initial staging of Ewing sarcoma
Authors: Kopp Lisa M. , Hu Chengcheng , Rozo Beatriz , White‐Collins Andrea , Huh Winston W. , Yarborough Angela , Herzog Cynthia E. , Hingorani Pooja
Published: August 2014

Background

The current standard of care for initial staging of pediatric Ewing sarcoma (EWS) patients is to obtain a bilateral bone marrow aspiration and biopsy (BMAB). The incidence of bone marrow (BM) disease in patients deemed non‐metastatic by conventional and metabolic imaging and the concordance of BM positivity with other clinical characteristics are not well established.

Procedure

This study is a multi‐institutional retrospective review of newly diagnosed EWS patients less than 40 years of age with initial staging that included imaging and BMAB.

Results

A total of 116 patients were eligible with 85 patients considered non‐metastatic and 31 considered metastatic by imaging. None of the 85 patients with non‐metastatic disease were BMAB positive (0%; 95% CI: 0–4.2%); 13 of the 31 patients with metastases were BMAB positive (41.9%; 95% CI: 24.5–60.9%). Primary tumor size was significantly higher in patients with metastases (P = 0.017). Bone metastasis by imaging had high correlation with BMAB positivity (P = 0.0002). In addition, the number of bony metastatic sites was significantly higher in patients with a positive BMAB as compared to those with a negative BMAB (median 3.5 and 0.0, respectively; P < 0.001).

Conclusions

BMAB may not be required for initial staging of pediatric and young adult EWS patients deemed non‐metastatic by imaging. In patients with metastatic disease, there is a high correlation of BM involvement with multiple bone metastases. Pediatr Blood Cancer 2015;62:12–15. © 2014 Wiley Periodicals, Inc.
Capacity building and stroke risk assessment in Nigerian children with sickle cell anaemia
Authors: Soyebi Kofo , Adeyemo Titilope , Ojewunmi Oyesola , James Funmi , Adefalujo Kunle , Akinyanju Olu
Published: August 2014

Background

Transcranial Doppler ultrasonography (TCD) measures blood flow velocities in the large cerebral vessels and thus, detects the risk of stroke. This report describes a capacity building program which enabled the use of TCD for detecting stroke risk and also describes the pattern of non‐imaging TCD examinations seen in Nigerian children with sickle cell anaemia (SCA).

Procedure

Ten university graduates were trained on the use of TCD in a 5‐day capacity building workshop after which, the three best candidates were employed to provide a 5‐day a week TCD screening service in Lagos. Data from TCD examination collected between March 2011 and September 2013 were analysed and reported.

Result

Between March 2011 and September 2013, 2,331 children with SCA aged 2–16 years had TCD studies. TCD's findings were classified as normal (standard risk) in 70.4%, conditional in 19% and abnormal (high risk) in 9.3%. The majority of children (76.9%) in the high risk category were aged 2–8 years. TCD study was inadequate for risk categorisation in 1.3% of the patients.

Conclusion

Effective capacity building of middle level manpower is feasible and can provide a credible TCD screening service to communities with a high demand and a shortage of trained professionals. The pattern of TCD abnormalities seen in Africa are comparable to those obtained in several previous worldwide reports. Pediatr Blood Cancer 2014;61:2263–2266. © 2014 Wiley Periodicals, Inc.
Relapsed perinatal neuroblastoma after expectant observation
Authors: Salloum Ralph , Garrison Aaron , von Allmen Daniel , Sheridan Rachel , Towbin Alexander J. , Adams Denise , Weiss Brian
Published: August 2014

The Children's Oncology Group (COG) study ANBL00P2 showed that expectant observation of patients younger than six months of age with perinatal neuroblastoma presenting as a small adrenal mass yields excellent overall survival and spares surgical resection to the majority of patients. We report a 5‐year‐old female who was initially diagnosed with a perinatal neuroblastoma. The patient was observed on COG study ANBL00P2. By nine months of age she had no ultrasonographic or biochemical evidence of disease. She presented four years later with abdominal pain and was found to have high‐risk stage 4 MYCN amplified neuroblastoma. Pediatr Blood Cancer 2015;62:160–162. © 2014 Wiley Periodicals, Inc.
Successful treatment of intraocular post‐transplant lymphoproliferative disorder with intravenous rituximab
Authors: Iu Lawrence P. , Yeung Jane C. , Loong Florence , Chiang Alan K.
Published: August 2014

We reported a rare case of intraocular post‐transplant lymphoproliferative disorder (PTLD) arising in a 3‐year‐old liver transplant recipient who had a prior history of systemic PTLD. The first PTLD entered remission after treatment with intravenous rituximab and withdrawal of immunosuppressants. One year after remission, she presented with granulomatous uveitis and iris nodules in the right eye. Iris biopsy confirmed recurrence of intraocular PTLD, which resolved completely after a second course of intravenous rituximab. Pediatr Blood Cancer 2015;62:169–172. © 2014 Wiley Periodicals, Inc.
Comparison of Soxhlet, Accelerated Solvent and Supercritical Fluid Extraction Techniques for Volatile (GC–MS and GC/FID) and Phenolic Compounds (HPLC–ESI/MS/MS) from Lamiaceae Species
Authors: Rodríguez‐Solana Raquel , Salgado José Manuel , Domínguez José Manuel , Cortés‐Diéguez Sandra
Published: September 2014

Introduction

Plants from the Lamiaceae family have been known traditionally for their beneficial health‐promoting properties, attributed to their anti‐inflammatory, anaesthetic and anti‐microbial effects.

Objective

The purposes of this study was to characterise the essential oils from four Lamiaceae plants by applying different extraction techniques.

Methods

Accelerated solvent (ASE), Soxhlet and supercritical fluid (SFE) extraction methods were compared for their efficiency in obtaining the essential oils from plants. The volatile compounds were identified by GC–MS and the main chemotype was quantified by GC with flame ionisation detection (FID). Phenolic compounds were identified and quantified by HPLC and electrospray ionisation (ESI) with MS/MS.

Results

The essential oils Mentha piperita (ct. menthol/menthone), Rosmarinus officinalis L. (ct. eucalyptol/camphor) and Origanum vulgare (ct. carvacrol/thymol), whereas Thymus vulgaris L. was found to be a pure chemotype (ct. thymol). All three extracts also contained six phenolic compounds. The highest extraction yields were achieved by the Soxhlet and ASE techniques, with M. piperita and R. officinalis L. producing the highest concentrations of rosmarinic and carnosic acids. Finally, it was observed that M. piperita and O. vulgare produced the highest total phenolic content, whereas R. officinalis L. and T. vulgaris L. produced the highest anti‐oxidant activity.

Conclusion

The ASE and Soxhlet extraction techniques presented the highest yields of volatile and phenolic compounds, showing their suitability to characterise the chemical profile of aromatic plants. Copyright © 2014 John Wiley & Sons, Ltd.
PERFECTIONISM, PERSPECTIVE TAKING, AND SOCIAL CONNECTION IN ADOLESCENTS
Authors: Gilman Rich , Rice Kenneth G. , Carboni Inga
Published: September 2014

Although studies examining multidimensional perfectionism among adolescents have increased over the past two decades, most continue to focus on psychological outcomes such as anxiety or depression. The purpose of this study was to examine two social outcomes that may differ among perfectionistic subtypes: social perspective taking (i.e., the ability to judge a situation from the perspective of another person) and social agency (i.e., the motivation to connect with others). Latent profile analysis was used to classify more than 700 high school adolescents into adaptive perfectionists (high standards, low self‐criticism), maladaptive perfectionists (high standards, high self‐criticism), and nonperfectionists (comparatively low standards). Results revealed significant mean score differences with respect to social perspective taking, with higher scores among both adaptive and maladaptive perfectionists than nonperfectionists. No mean score differences were found with respect to social agency. Implications of these findings, as well suggestions for future research, conclude the article.
Burning Characteristics of Consolidated Gun Propellants
Authors: Li Yuxiang , Yang Weitao , Ying Sanjiu
Published: September 2014

To improve the combustion behaviors of conventional consolidated propellants, consolidated propellants were prepared using porous propellant grains as fast‐burning filler. The porous propellant grains were prepared by supercritical fluid foaming process and exhibited the high burning rate. The multi‐perforated structure of the consolidated propellants was designed and adopted to obtain high burning progressivity. To investigate the burning characteristics of the consolidated propellants, closed vessel and quenched combustion experiments were carried out. The results show that deconsolidation of the consolidated propellants does not occur, and that the consolidated propellants exhibit high burning rates and high burning progressivities. Besides, the results show that the consolidated propellants burn steadily even at low (−40 °C) and high temperatures (50 °C).
The pluripotency factor Nanog is directly upregulated by the Androgen Receptor in prostate cancer cells
Authors: Kregel Steven , Szmulewitz Russell Z. , Griend Donald J. Vander
Published: August 2014

BACKGROUND

The Androgen Receptor (AR) is a nuclear hormone receptor that functions as a critical oncogene in all stages of prostate cancer progression, including progression to castration‐resistance following androgen‐deprivation therapy. Thus, identifying and targeting critical AR‐regulated genes is one potential method to block castration‐resistant cancer proliferation. Of particular importance are transcription factors that regulate stem cell pluripotency; many of these genes are emerging as critical oncogenes in numerous tumor cell types. Of these, Nanog has been previously shown to increase the self‐renewal and stem‐like properties of prostate cancer cells. Thus, we hypothesized that Nanog is a candidate AR target gene that may impart castration‐resistance.

METHODS

We modulated AR signaling in LNCaP prostate cancer cells and assayed for Nanog expression. Direct AR binding to the NANOG promoter was tested using AR Chromatin Immunoprecipation (ChIP) and analyses of publically available AR ChIP‐sequencing data‐sets. Nanog over‐expressing cells were analyzed for cell growth and cytotoxicity in response to the AR antagonist enzalutamide and the microtubule stabilizing agent docetaxel.

RESULTS

AR signaling upregulates Nanog mRNA and protein. AR binds directly to the NANOG promoter, and was not identified within 75 kb of the NANOGP8 pseudogene, suggesting the NANOG gene locus was preferentially activated. Nanog overexpression in LNCaP cells increases overall growth, but does not increase resistance to enzalutamide or docetaxel.

CONCLUSIONS

Nanog is a novel oncogenic AR target gene in prostate cancer cells, and stable expression of Nanog increases proliferation and growth of prostate cancer cells, but not resistance to enzalutamide or docetaxel. Prostate 74:1530–1543, 2014. © 2014 Wiley Periodicals, Inc.
weather@home—development and validation of a very large ensemble modelling system for probabilistic event attribution
Authors: Massey N. , Jones R. , Otto F. E. L. , Aina T. , Wilson S. , Murphy J. M. , Hassell D. , Yamazaki Y. H. , Allen M. R.
Published: September 2014

Demonstrating the effect that climate change is having on regional weather is a subject which occupies climate scientists, government policy makers and the media. After an extreme weather event occurs, the question is often posed, ‘Was the event caused by anthropogenic climate change?’ Recently, a new branch of climate science (known as attribution) has sought to quantify how much the risk of extreme events occurring has increased or decreased due to climate change. One method of attribution uses very large ensembles of climate models computed via volunteer distributed computing. A recent advancement is the ability to run both a global climate model and a higher resolution regional climate model on a volunteer's home computer. Such a set‐up allows the simulation of weather on a scale that is of most use to studies of the attribution of extreme events. This article introduces a global climate model that has been developed to simulate the climatology of all major land regions with reasonable accuracy. This then provides the boundary conditions to a regional climate model (which uses the same formulation but at higher resolution) to ensure that it can produce realistic climate and weather over any region of choice. The development process is documented and a comparison to previous coupled climate models and atmosphere‐only climate models is made. The system (known as weather@home) by which the global model is coupled to a regional climate model and run on volunteers' home computers is then detailed. Finally, a validation of the whole system is performed, with a particular emphasis on how accurately the distributions of daily mean temperature and daily mean precipitation are modelled in a particular application over Europe. This builds confidence in the applicability of the weather@home system for event attribution studies.
Assessment of glutamine synthetase activity by [13N]ammonia uptake in living rat brain
Authors: Momosaki Sotaro , Ito Miwa , Tonomura Misato , Abe Kohji
Published: September 2014

Glutamine synthetase (GS) plays an important role in glutamate neurotransmission or neurological disorder in the brain. [13N]Ammonia blood flow tracer has been reported to be metabolically trapped in the brain via the glutamate‐glutamine pathway. The present study investigated the effect of an inhibitor of GS on [13N]ammonia uptake in order to clarify the feasibility of measuring GS activity in the living brain. l‐Methionine sulfoximine (MSO), a selective GS inhibitor was microinjected into the ipsilateral striatum in rats. [13N]Ammonia uptake was quantified by autoradiography method as well as small animal positron emission tomography (PET) scans. The GS activity of the brain homogenate was assayed from the γ‐glutamyl transferase reaction. Autoradiograms showed a decrease of [13N]ammonia radioactivity on the MSO‐injected side compared with the saline‐injected side of the striatum. This reduction could be detected with a small animal PET scanner. MSO had no effect on cerebral blood flow measured by uptake of [15O]H2O. The reduction of [13N]ammonia uptake was closely related to the results of GS activity assay. These results indicated that [13N]ammonia may enable measurement of GS activity in the living brain. Synapse 69:26–32, 2015. © 2014 Wiley Periodicals, Inc.
Synthetic virology: engineering viruses for gene delivery
Authors: Guenther Caitlin M. , Kuypers Brianna E. , Lam Michael T. , Robinson Tawana M. , Zhao Julia , Suh Junghae
Published: September 2014

The success of gene therapy relies heavily on the performance of vectors that can effectively deliver transgenes to desired cell populations. As viruses have evolved to deliver genetic material into cells, a prolific area of research has emerged over the last several decades to leverage the innate properties of viruses as well as to engineer new features into them. Specifically, the field of synthetic virology aims to capitalize on knowledge accrued from fundamental virology research in order to design functionally enhanced gene delivery vectors. The enhanced viral vectors, or ‘bionic’ viruses, feature engineered components, or ‘parts’, that are natural (intrinsic to viruses or from other organisms) and synthetic (such as man‐made polymers or inorganic nanoparticles). Various design strategies—rational, combinatorial, and pseudo‐rational—have been pursued to create the hybrid viruses. The gene delivery vectors of the future will likely criss‐cross the boundaries between natural and synthetic domains to harness the unique strengths afforded by the various functional parts that can be grafted onto virus capsids. Such research endeavors will further expand and enable enhanced control over the functional capacity of these nanoscale devices for biomedicine. WIREs Nanomed Nanobiotechnol 2014, 6:548–558. doi: 10.1002/wnan.1287

This article is categorized under:

Biology-Inspired Nanomaterials > Protein and Virus-Based Structures
Frey’s Pancreaticojejunostomy in Tropical Pancreatitis: Assessment of Quality of Life. A Prospective Study
Authors: Pothula Rajendra Vamsi Krishna , Sivanpillay Mahadevan Sivaraj , Parvathareddy Sivacharan Reddy , Nara Bharat Kumar , Gorlagunta Ramachandra Mallikarjuna , Tripuraneni Venkata Aditya Chowdary , Bathalapalli Jagan Mohan Reddy , Gudi Vara Prasada Rao , Sampath Thirunavukkarasu
Published: September 2014

Introduction

Tropical pancreatitis is a form of chronic pancreatitis originally described in the tropics. Prospective studies in Western countries have shown improved quality of life (QOL) following surgery in alcoholic chronic pancreatitis. In studies on Frey’s pancreaticojejunostomy for tropical pancreatitis, improvement in pain was considered the endpoint, and there is a paucity of data in the literature with regard to QOL with tropical pancreatitis following surgery.

Objective

Our objective was to prospectively analyze the outcome of Frey’s pancreaticojejunostomy in tropical pancreatitis and health‐related QOL following surgery by administering the Short Form 36‐item health survey (SF‐36).

Materials and methods

A total of 25 patients underwent Frey’s pancreaticojejunostomy between 2010 and 2012 and were included in the study; data were collected prospectively. The visual analog scale (VAS) for pain and the SF‐36 form were used to record health‐related QOL preoperatively, and at 3 and 12 months post‐surgery, comparing the same with the general population.

Results

Patients with tropical pancreatitis experience poor QOL (26.71 ± 15.95) compared with the general population (84.54 ± 12.42). Post‐operative QOL scores (78.54 ± 15.84) were better than the pre‐operative scores (26.71 ± 15.95) at 12‐month post‐surgery follow‐up. The VAS score for pain improved at 12 months post‐surgery (1.58 ± 1.41 vs. 8.21 ± 1.64). Two of the three patients (12.5 %) who had diabetes were free from anti‐diabetes medication at 12 months post‐surgery. Steatorrhea was seen in five patients (20.8 %) before surgery and increased to eight (33.3 %) at 12 months post‐surgery. Mean body weight increased from 45.75 kg pre‐operatively to 49.25 kg at 12 months post‐operatively.

Conclusions

Frey’s pancreaticojejunostomy effectively reduces pain in tropical pancreatitis, with significant improvement in health‐related QOL, which is comparable with the general population in most aspects.
Surgical Options after a Failed Neurectomy in Anterior Cutaneous Nerve Entrapment Syndrome
Authors: van Assen T. , Boelens O. B. , van Eerten P. V. , Scheltinga M. R. , Roumen R. M.
Published: September 2014

Background

Injection treatment followed by an anterior neurectomy in patients insufficiently responding to an injection regimen is successful long term in three‐quarters of patients with anterior cutaneous nerve entrapment syndrome (ACNES). The efficacy of secondary surgery, including re‐exploration or a posterior neurectomy in patients reporting recurrent pain after initially successful surgery or following an immediately failed anterior neurectomy is unknown.

Methods

A database of ACNES patients receiving surgery between 2004 and 2012 in the SolviMáx institution was analysed. Adult patients with residual pain after an anterior neurectomy (failures) or with recurrent pain after initially successful surgery (recurrences) were selected. Following a re‐exploration or a posterior neurectomy, pain was scored using a pain intensity numeric rating scale (PI‐NRS 0–10) and a six‐point verbal category rating scale (VRS). Success was defined as a ≥50 % PI‐NRS reduction and/or ≥2 point VRS reduction.

Results

ACNES patients undergoing an anterior neurectomy (n = 181) were analysed during the 8‐year study period. At follow‐up, 51 patients reported unacceptable pain levels following an anterior neurectomy, whereas 20 developed recurrent abdominal wall pain. Of these 71 unsuccessful patients, 41 underwent secondary surgery, including a re‐exploration (n = 10), or a posterior neurectomy (n = 31). After a 25‐month median follow‐up, secondary surgical treatment regimens proved successful in 66 % (27/41). Patients with recurrent pain did better (14/15) than patients who were immediate failures after the anterior neurectomy (13/26, p = 0.01).

Conclusions

Secondary surgery including re‐explorations and posterior neurectomies are successful in two‐thirds of ACNES patients with persistent pain or recurrence of pain after an anterior neurectomy.