bluuebunny/crossref_metadata_2025 huggingface dataset:
ERBB3 is a marker of a ganglioneuroblastoma/ganglioneuroma-like expression profile in neuroblastic tumours
Authors: Wilzén Annica , Krona Cecilia , Sveinbjörnsson Baldur , Kristiansson Erik , Dalevi Daniel , Øra Ingrid , De Preter Katleen , Stallings Raymond L , Maris John , Versteeg Rogier , Nilsson Staffan , Kogner Per , Abel Frida
Published: July 2013

Background

Neuroblastoma (NB) tumours are commonly divided into three cytogenetic subgroups. However, by unsupervised principal components analysis of gene expression profiles we recently identified four distinct subgroups, r1-r4. In the current study we characterized these different subgroups in more detail, with a specific focus on the fourth divergent tumour subgroup (r4).

Methods

Expression microarray data from four international studies corresponding to 148 neuroblastic tumour cases were subject to division into four expression subgroups using a previously described 6-gene signature. Differentially expressed genes between groups were identified using Significance Analysis of Microarray (SAM). Next, gene expression network modelling was performed to map signalling pathways and cellular processes representing each subgroup. Findings were validated at the protein level by immunohistochemistry and immunoblot analyses.

Results

We identified several significantly up-regulated genes in the r4 subgroup of which the tyrosine kinase receptor ERBB3 was most prominent (fold change: 132–240). By gene set enrichment analysis (GSEA) the constructed gene network of ERBB3 (n = 38 network partners) was significantly enriched in the r4 subgroup in all four independent data sets. ERBB3 was also positively correlated to the ErbB family members EGFR and ERBB2 in all data sets, and a concurrent overexpression was seen in the r4 subgroup. Further studies of histopathology categories using a fifth data set of 110 neuroblastic tumours, showed a striking similarity between the expression profile of r4 to ganglioneuroblastoma (GNB) and ganglioneuroma (GN) tumours. In contrast, the NB histopathological subtype was dominated by mitotic regulating genes, characterizing unfavourable NB subgroups in particular. The high ErbB3 expression in GN tumour types was verified at the protein level, and showed mainly expression in the mature ganglion cells.

Conclusions

Conclusively, this study demonstrates the importance of performing unsupervised clustering and subtype discovery of data sets prior to analyses to avoid a mixture of tumour subtypes, which may otherwise give distorted results and lead to incorrect conclusions. The current study identifies ERBB3 as a clear-cut marker of a GNB/GN-like expression profile, and we suggest a 7-gene expression signature (including ERBB3) as a complement to histopathology analysis of neuroblastic tumours. Further studies of ErbB3 and other ErbB family members and their role in neuroblastic differentiation and pathogenesis are warranted.
Orthotopic transplantation of retinoblastoma cells into vitreous cavity of zebrafish for screening of anticancer drugs
Authors: Jo Dong Hyun , Son Dain , Na Yirang , Jang Manyoung , Choi Jae-Hoon , Kim Jin Hyoung , Yu Young Suk , Seok Seung Hyeok , Kim Jeong Hun
Published: July 2013

Background

With high throughput screening, novel therapeutic agents can be efficiently identified. Unfortunately, researchers only resort to in vitro cell viability assays for screening of anticancer drugs for retinoblastoma, the most common intraocular cancer in the childhood. Current available animal models of retinoblastoma require more than 2 weeks for tumour formation and the investigation of the efficacy of therapeutic agents. In this study, we established a novel orthotopic transplantation model of retinoblastoma in zebrafish as an in vivo animal model for screening of anticancer drugs.

Methods

We injected retinoblastoma cells into the vitreous cavity of zebrafish at 48 hours after fertilization. Eyeballs of zebrafish were scanned daily under the confocal laser microscope, and the tumor population was quantitatively analyzed by measuring the mean intensity of green fluorescent protein (GFP). Transplanted retinoblastoma cells were isolated to perform further analyses including Western blotting and reverse transcriptase-polymerase chain reaction to confirm that retinoblastoma cells maintained their characteristics as tumor cells even after transplantation and further isolation. To figure out the potential of this model for screening of anticancer drugs, zebrafish were cultured in Ringer’s solution containing carboplatin and melphalan after the injection of retinoblastoma cells.

Results

The degree of the tumor population was dependent on the number of retinoblastoma cells injected and maintained stably for at least 4 days. Transplanted retinoblastoma cells maintain their proliferative potential and characteristics as retinoblastoma cells after isolation. Interestingly, systemic application of carboplatin and melphalan demonstrated significant reduction in the tumor population, which could be quantitatively analyzed by the estimation of the mean intensity of GFP.

Conclusions

This orthotopic retinoblastoma model in zebrafish is expected to be utilized for the screening of anticancer drugs for the treatment of retinoblastoma.
Insulin enhances metabolic capacities of cancer cells by dual regulation of glycolytic enzyme pyruvate kinase M2
Authors: Iqbal Mohd Askandar , Siddiqui Farid Ahmad , Gupta Vibhor , Chattopadhyay Shilpi , Gopinath Prakasam , Kumar Bhupender , Manvati Siddharth , Chaman Noor , Bamezai Rameshwar NK
Published: July 2013

Background

Insulin is tightly associated with cancer progression; however, mechanistic insights into such observations are poorly understood. Recent studies show that metabolic transformation is critical to cancer cell proliferation. Here, we attempt to understand the role of insulin in promotion of cancer metabolism. To this end, the role of insulin in regulating glycolytic enzyme pyruvate kinase M2 (PKM2) was examined.

Results

We observed that insulin up-regulated PKM2 expression, through PI3K/mTOR mediated HIF1α induction, but significantly reduced PKM2 activity independent of this pathway. Drop in PKM2 activity was attributed to subunit dissociation leading to formation of low activity PKM2 oligomers, as assessed by density gradient centrifugation. However, tyrosine 105 phosphorylation of PKM2, known for inhibiting PKM2 activity, remained unaffected on insulin treatment. Interestingly, insulin-induced ROS was found responsible for PKM2 activity reduction. The observed changes in PKM2 status led to augmented cancer metabolism. Insulin-induced PKM2 up-regulation resulted in enhanced aerobic glycolysis as confirmed by PKM2 knockdown studies. Further, PKM2 activity reduction led to characteristic pooling of glycolytic intermediates and increased accumulation of NADPH; suggesting diversion of glucose flux towards macromolecular synthesis, necessary for cancer cell growth.

Conclusion

The study identifies new PKM2-mediated effects of insulin on cancer metabolism, thus, advancing the understanding of insulin’s role in cancer.
A real-time device-free localization system using correlated RSS measurements
Authors: Yang Zhiyong , Huang Kaide , Guo Xuemei , Wang Guoli
Published: July 2013

Device-free localization (DFL) with wireless sensor networks (WSN) is an emerging technology for target localization, which has received much attention in the area of Internet of Things. Received signal strength (RSS) measurements are the key to realize DFL and mainly affects the localization performance. Most existing approaches need to measure the RSS of all the wireless links in WSN, which take much time on measurement process and localization algorithm due to the large amounts of RSS data, thus they are inefficient, especially in the case of target tracking. In this paper, by making full use of the consecutiveness of motion, we present an efficient measurement strategy based on a small set of correlated wireless links. Furthermore, a lightweight compressed maximum matching select (CMMS) algorithm is proposed to localize target, which only needs a small-scale matrix-vector product operating for one estimation. The proposed approach can significantly reduce the number of RSS measurements and improve the real-time capability of the DFL system. Experimental results demonstrate the superior performance of the proposed method in the context of target localization and tracking.
Dual effects of noradrenaline on astroglial production of chemokines and pro-inflammatory mediators
Authors: Hinojosa Ara E , Caso Javier R , García-Bueno Borja , Leza Juan C , Madrigal José LM
Published: July 2013

Background

Noradrenaline (NA) is known to limit neuroinflammation. However, the previously described induction by NA of a chemokine involved in the progression of immune/inflammatory processes, such as chemokine (C-C motif) ligand 2 (CCL2)/monocyte chemotactic protein-1 (MCP-1), apparently contradicts NA anti-inflammatory actions. In the current study we analyzed NA regulation of astroglial chemokine (C-X3-C motif) ligand 1 (CX3CL1), also known as fractalkine, another chemokine to which both neuroprotective and neurodegenerative actions have been attributed. In addition, NA effects on other chemokines and pro-inflammatory mediators were also analyzed.

Methods

Primary astrocyte-enriched cultures were obtained from neonatal Wistar rats. These cells were incubated for different time durations with combinations of NA and lipopolysaccharide (LPS). The expression and synthesis of different proteins was measured by RT-PCR and enzyme-linked immunosorbent assay (ELISA) or enzyme immunoassays. Data were analyzed by one-way analysis of variance (ANOVA), followed by Newman-Keuls multiple comparison tests.

Results

The data presented here show that in control conditions, NA induces the production of CX3CL1 in rat cultured astrocytes, but in the presence of an inflammatory stimulus, such as LPS, NA has the opposite effect inhibiting CX3CL1 production. This inversion of NA effect was also observed for MCP-1. Based on the observation of this dual action, NA regulation of different chemokines and pro-inflammatory cytokines was also analyzed, observing that in most cases NA exerts an inhibitory effect in the presence of LPS. One characteristic exception was the induction of cyclooxygenase-2 (COX-2), where a summative effect was detected for both LPS and NA.

Conclusion

These data suggest that NA effects on astrocytes can adapt to the presence of an inflammatory agent reducing the production of certain cytokines, while in basal conditions NA may have the opposite effect and help to maintain moderate levels of these cytokines.
Mirror versus parallel bimanual reaching
Authors: Abdollahi Farnaz , Kenyon Robert V , Patton James L
Published: July 2013

Background

In spite of their importance to everyday function, tasks that require both hands to work together such as lifting and carrying large objects have not been well studied and the full potential of how new technology might facilitate recovery remains unknown.

Methods

To help identify the best modes for self-teleoperated bimanual training, we used an advanced haptic/graphic environment to compare several modes of practice. In a 2-by-2 study, we compared mirror vs. parallel reaching movements, and also compared veridical display to one that transforms the right hand’s cursor to the opposite side, reducing the area that the visual system has to monitor. Twenty healthy, right-handed subjects (5 in each group) practiced 200 movements. We hypothesized that parallel reaching movements would be the best performing, and attending to one visual area would reduce the task difficulty.

Results

The two-way comparison revealed that mirror movement times took an average 1.24 s longer to complete than parallel. Surprisingly, subjects’ movement times moving to one target (attending to one visual area) also took an average of 1.66 s longer than subjects moving to two targets. For both hands, there was also a significant interaction effect, revealing the lowest errors for parallel movements moving to two targets (p < 0.001). This was the only group that began and maintained low errors throughout training.

Conclusion

Combined with other evidence, these results suggest that the most intuitive reaching performance can be observed with parallel movements with a veridical display (moving to two separate targets). These results point to the expected levels of challenge for these bimanual training modes, which could be used to advise therapy choices in self-neurorehabilitation.
Evaluation and implementation of graded in vivo exposure for chronic low back pain in a German outpatient setting: a study protocol of a randomized controlled trial
Authors: Riecke Jenny , Holzapfel Sebastian , Rief Winfried , Glombiewski Julia Anna
Published: July 2013

Background

The purpose of the present study is to introduce an adapted protocol of in vivo exposure for fear avoidant back pain patients and its implementation in the German health care system without multidisciplinary teams. Case studies demonstrated promising effects but three preceding randomized controlled trials (RCTs) could not support the former results. More empirical support is necessary to further substantiate the effectiveness of in vivo exposure.

Methods

A total of 108 chronic low back pain patients are randomly assigned to one out of three conditions (A: exposure_long (15 sessions), B: exposure_short (10 sessions) or C: control condition cognitive behavioral therapy (15 sessions)). The inclusion criteria are: back pain ≥3 months and a sufficient level of fear-avoidance. An effect evaluation, a process evaluation and an economic evaluation are conducted. Primary outcomes are pain-related disability and pain intensity. Secondary outcomes are: emotional distress, fear avoidance, catastrophizing and costs. Data are collected at baseline, upon completion of the intervention, after 10 sessions, and at six months following completion of treatment. Besides the comparison of exposure in vivo and cognitive behavioral therapy (CBT), we additionally compare a short and a long version of exposure to analyze dose response effects.

Discussion

This is, to our knowledge, the first RCT comparing in vivo exposure to psychological treatment as usual in terms of cognitive behavioral therapy. Results will help to find out whether a tailored treatment for fear avoidant back pain patients is more effective than a general pain management treatment.

Trial registration

The trial has been registered to ClinicalTrial.gov. The trial registration number is NCT01484418
Usefulness and limitations of E-cadherin and β-catenin in the classification of breast carcinomas in situ with mixed pattern
Authors: Gomes Douglas S , Porto Simone S , Rocha Rafael M , Gobbi Helenice
Published: July 2013

Background

The distinction between lobular neoplasia of the breast and ductal carcinoma in situ has important therapeutic implications. In some cases, it is very difficult to determine whether the morphology of the lesion is ductal or lobular. The aim of this study was to evaluate the value of E-cadherin and β-catenin expression through the immunophenotypical characterization of carcinoma in situ with mixed pattern (CISM).

Methods

A total of 25 cases of CISM were analyzed considering cytology/mixed architecture (ductal and lobular), nuclear pleomorphism, loss of cell cohesion, and presence of comedonecrosis. The immunophenotype pattern was considered E-cadherin positive and β-catenin positive, or negative.

Results

Nineteen (76%) cases presented a mixed cytology and / or architectural pattern, two (8%) presented nuclear pleomorphism, two (8%) presented mixed cytology and nuclear pleomorphism, and two (8%) presented comedonecrosis and nuclear pleomorphism. A complete positivity for E-cadherin and β-catenin was observed in 11 cases (44%). In one case, the lesion was negative for both markers and showed nuclear pleomorphis. Thirteen lesions showed negative staining in areas of lobular cytology and positive staining in cells presenting the ductal pattern.

Conclusions

The expression of E-cadherin and β-catenin, combined with cytological and architectural analysis, may highlight different immunophenotypes and improve classification of CISM.

Virtual Slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1693384202970681
Ethnopharmacological survey of medicinal plants in Jeju Island, Korea
Authors: Song Mi-Jang , Kim Hyun , Heldenbrand Brian , Jeon Jongwook , Lee Sanghun
Published: July 2013

Background

This study aims to analyze and record orally transmitted knowledge of medicinal plants from the indigenous people living in Hallasan National Park of Korea.

Methods

Data was collected through the participatory rural appraisal method involving interviews, informal meetings, open and group discussions, and overt observations with semi-structured questionnaires.

Results

In this study, a total of 68 families, 141 genera, and 171 species of plants that showed 777 ways of usage were recorded. Looking into the distribution of the families, 14 species of Asteraceae occupied 11.1% of the total followed by 13 species of Rosaceae, 10 species of Rutaceae, and nine species of Apiaceae which occupied 5.0%, 7.1% and 3.0% of the whole, respectively. 32 kinds of plant-parts were used for 47 various medicinal purposes. Values for the informant consensus factor regarding the ailment categories were for birth related disorders (0.92), followed by respiratory system disorders (0.90), skin disease and disorders (0.89), genitourinary system disorders (0.87), physical pain (0.87), and other conditions. According to fidelity levels, 36 plant species resulted in fidelity levels of 100%.

Conclusion

Consequently, results of this study will legally utilize to provide preparatory measures against the Nagoya Protocol (2010) about benefit-sharing for traditional knowledge of genetic resources.
Differential effects of natural rewards and pain on vesicular glutamate transporter expression in the nucleus accumbens
Authors: Tukey David S , Lee Michelle , Xu Duo , Eberle Sarah E , Goffer Yossef , Manders Toby R , Ziff Edward B , Wang Jing
Published: July 2013

Background

Pain and natural rewards such as food elicit different behavioral effects. Both pain and rewards, however, have been shown to alter synaptic activities in the nucleus accumbens (NAc), a key component of the brain reward system. Mechanisms by which external stimuli regulate plasticity at NAc synapses are largely unexplored. Medium spiny neurons (MSNs) from the NAc receive excitatory glutamatergic inputs and modulatory dopaminergic and cholinergic inputs from a variety of cortical and subcortical structures. Glutamate inputs to the NAc arise primarily from prefrontal cortex, thalamus, amygdala, and hippocampus, and different glutamate projections provide distinct synaptic and ultimately behavioral functions. The family of vesicular glutamate transporters (VGLUTs 1–3) plays a key role in the uploading of glutamate into synaptic vesicles. VGLUT1-3 isoforms have distinct expression patterns in the brain, but the effects of external stimuli on their expression patterns have not been studied.

Results

In this study, we use a sucrose self-administration paradigm for natural rewards, and spared nerve injury (SNI) model for chronic pain. We examine the levels of VGLUTs (1–3) in synaptoneurosomes of the NAc in these two behavioral models. We find that chronic pain leads to a decrease of VGLUT1, likely reflecting decreased projections from the cortex. Pain also decreases VGLUT3 levels, likely representing a decrease in projections from GABAergic, serotonergic, and/or cholinergic interneurons. In contrast, chronic consumption of sucrose increases VGLUT3 in the NAc, possibly reflecting an increase from these interneuron projections.

Conclusion

Our study shows that natural rewards and pain have distinct effects on the VGLUT expression pattern in the NAc, indicating that glutamate inputs to the NAc are differentially modulated by rewards and pain.
The metabolic cost of lowering blood pressure with hydrochlorothiazide
Authors: Price Angela L , Lingvay Ildiko , Szczepaniak Edward W , Wiebel Jaime , Victor Ronald G , Szczepaniak Lidia S
Published: July 2013

Background

The landmark Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) placed a new spotlight on thiazide diuretics as the first-line therapy for hypertension. This is concerning as thiazide-diuretics may contribute to comorbidities associated with the current epidemic of obesity. Previous randomized clinical trials have linked thiazide diuretic treatment to insulin resistance, metabolic syndrome, and increased incidence of type 2 diabetes.

Methods

This proof of concept, longitudinal, randomized, double–blind study evaluated the effects of the angiotensin II receptor blocker Valsartan and the specific thiazide diuretic Hydrochlorothiazide (HCTZ) on hepatic triglyceride level (primary outcome), as well as triglyceride levels within other organs including the heart, skeletal muscle, and pancreas. Additionally, we evaluated whether myocardial function, insulin sensitivity, and insulin secretion were affected by these treatments.

Results

Hepatic TG levels increased by 57% post HCTZ treatment: ∆hTG HCTZ = 4.12% and remained unchanged post Valsartan treatment: ∆hTG V = 0.06%. The elevation of hepatic TG levels after HCTZ treatment was additionally accompanied by a reduction in insulin sensitivity: ∆SI HCTZ = -1.14. Treatment with Valsartan resulted in improved insulin sensitivity: ∆SI V = 1.24. Treatment-induced changes in hepatic TG levels and insulin sensitivity were statistically significant between groups (phTG = 0.0098 and pSI = 0.0345 respectively). Disposition index, DI, remained unchanged after HCTZ treatment: ∆DI HCTZ = -141 but it was increased by a factor of 2 after treatment with Valsartan: ∆DI V =1018). However, the change between groups was not statistically significant. Both therapies did not modify abdominal visceral and subcutaneous fat mass as well as myocardial structure and function. Additionally, myocardial, pancreatic, and skeletal muscle triglyceride deposits remained unchanged in both therapeutic arms.

Conclusions

Our findings are two-fold and relate to hepatic steatosis and insulin sensitivity. HCTZ treatment worsened hepatic steatosis measured as hepatic triglyceride content and reduced insulin sensitivity. Valsartan treatment did not affect hepatic triglyceride levels and improved insulin sensitivity. The results of this study reinforce the message that in patients at risk for type 2 diabetes it is particularly important to choose an antihypertensive regimen that lowers blood pressure without exacerbating patient’s metabolic profile.
A review of tuberculosis at the wildlife-livestock-human interface in Zambia
Authors: Malama Sydney , Muma John Bwalya , Godfroid Jacques
Published: July 2013

Zambia’s estimated incidence of all forms of human tuberculosis (TB) is 707/100,000. High prevalence of bovine tuberculosis (BTB) – infection with Mycobacterium bovis – in cattle and the Kafue lechwe antelopes (Kobus leche Kafuensis) has been reported in the Kafue basin. Consumption of unpasteurised milk and meat products from infected animals poses a risk of transmitting zoonotic tuberculosis to people living at the human-animal interface. Despite the reported high prevalence of BTB in both livestock and wildlife, information on the proportion of human patients infected with M. bovis is unknown in Zambia. This paper reviews the available information in English on human, livestock and wildlife TB in Zambia with the purpose of assessing the burden of animal infections with M. tuberculosis complex and its public health implications.
Empirical assessment of a RGB-D sensor on motion capture and action recognition for construction worker monitoring
Authors: Han SangUk , Achar Madhav , Lee SangHyun , Peña-Mora Feniosky
Published: July 2013

Background

For construction management, data collection is a critical process for gathering and measuring information for the evaluation and control of ongoing project performances. Taking into account that construction involves a significant amount of manual work, worker monitoring can play a key role in analyzing operations and improving productivity and safety. However, time-consuming tasks involved in field observation have brought up the issue of implementing worker observation in daily management practice.

Methods

In an effort to address the issue, this paper investigates the performances of a cost-effective and portable RGB-D sensor, based on recent research efforts extended from our previous study. The performance of an RGB-D sensor is evaluated in terms of (1) the 3D positions of the body parts tracked by the sensor, (2) the 3D rotation angles at joints, and (3) the impact of the RGB-D sensor’s accuracy on motion analysis. For the assessment, experimental studies were undertaken to collect motion capture datasets using an RGB-D sensor and a marker-based motion capture system, VICON, and to analyze errors as compared with the VICON used as the ground truth. As a test case, 25 trials of ascending and descending during ladder climbing were recorded simultaneously with both systems, and the resulting motion capture datasets (i.e., 3D skeleton models) were temporally and spatially synchronized for their comparison.

Results

Through the comparative assessment, we found a discrepancy of 10.7 cm in the tracked locations of body parts, and a difference of 16.2 degrees in rotation angles. However, motion detection results show that the inaccuracy of an RGB-D sensor does not have a considerable effect on action recognition in the experiment.

Conclusions

This paper thus provides insight into the accuracy of an RGB-D sensor on motion capture in various measures and directions of further research for the improvement of accuracy.
A visual energy performance assessment and decision support tool for dwellings
Authors: Mhalas Amit , Kassem Mohamad , Crosbie Tracey , Dawood Nashwan
Published: July 2013

Background

The target for carbon dioxide (CO2) emissions reduction in the UK is set at 20% by 2020 and 80% by 2050. The UK housing stock is one of the least energy efficient in Europe. The energy used in homes accounts for more than a quarter of energy use and carbon dioxide emissions in Great Britain. Therefore, it is imperative to improve the energy performance of the existing housing stock and fully exploit energy efficiency and renewable energy interventions. The UK has developed several policies and initiatives to improve the energy performance of the housing stock and there are a number of databases that hold information about the condition of the housing stock. However, existing approaches and tools do not allow decision makers to assess the environmental and economic effectiveness of CO2 reduction strategies at the neighbourhood level.

Methods

This research presents a methodology that integrates these energy databases with visualisation systems and multi-criteria decision analyses to enable the evaluation of the environmental and financial implications of various energy efficiency and renewable energy interventions at both building and neighbourhood levels. The methodology is prototyped in a proof-of-concept tool which is validated and tested in an empirical case study with local authorities and social housing providers.

Results

The validation study compared the energy performance of the dwellings estimated by the proposed methodology with the energy performance calculated from actual survey and confirmed that the results are consistent. The case study demonstrated that the methodology and the prototype can be reliably utilised to evaluate the environmental and financial implications of various energy efficiency and renewable energy interventions.

Conclusion

The findings illustrate that the tool is particularly useful for town planners, local authorities and social housing providers. They can make informed decisions about the implementation of energy policies and initiatives along with energy suppliers, building engineers and architects. The tool developed in the research and presented in this paper can contribute to meeting CO2 emission reduction targets.
Adipose-derived stem cells improved mouse ovary function after chemotherapy-induced ovary failure
Authors: Sun Min , Wang Shufang , Li Yi , Yu Ling , Gu Fang , Wang Changyong , Yao Yuanqing
Published: July 2013

Introduction

Young patients receiving chemotherapy occasionally face infertility and premature ovarian failure (POF). Numerous investigations reported that adipose-derived stem cells (ADSCs) transplantation could ameliorate the structure and function of injured tissues. The aim of this study was to explore the therapeutic efficacy of ADSC transplantation for chemotherapy-induced ovarian damage.

Methods

Female mice were injected intraperitoneally with 50 mg/kg cyclophosphamide (CTX). After 15 consecutive days of injection, ADSCs were transplanted either directly into bilateral ovaries or via intravenous injection, and the ovaries were excised after either 1 week or 1 month of treatment. The follicles were counted and categorized, and ovarian histologic sections were stained for TUNEL. Ovarian function was evaluated by monitoring ovulation. ADSC tracking, microarray analyses, and real-time polymerase chain reaction (PCR) were used to assess the inner mechanism of injury and repair.

Results

The ovarian function of mice exposed to CTX injection improved after ADSC transplantation. The population of follicles at different stages and ovulation significantly increased after the treatment. Immunofluorescence revealed reduced TUNEL staining. The tracking of ADSCs revealed that these cells did not directly differentiate into the follicle component. Microarray analyses indicated that changes in different groups of genes might affect follicle formation or ovulation.

Conclusions

ADSC transplantation improved ovarian function. Our results suggest a potential mechanism for ADSC therapy.
Subgroup-Specific Prognostic Implications of TP53 Mutation in Medulloblastoma
Authors: Zhukova Nataliya , Ramaswamy Vijay , Remke Marc , Pfaff Elke , Shih David J.H. , Martin Dianna C. , Castelo-Branco Pedro , Baskin Berivan , Ray Peter N. , Bouffet Eric , von Bueren André O. , Jones David T.W. , Northcott Paul A. , Kool Marcel , Sturm Dominik , Pugh Trevor J. , Pomeroy Scott L. , Cho Yoon-Jae , Pietsch Torsten , Gessi Marco , Rutkowski Stefan , Bognar Laszlo , Klekner Almos , Cho Byung-Kyu , Kim Seung-Ki , Wang Kyu-Chang , Eberhart Charles G. , Fevre-Montange Michelle , Fouladi Maryam , French Pim J. , Kros Max , Grajkowska Wieslawa A. , Gupta Nalin , Weiss William A. , Hauser Peter , Jabado Nada , Jouvet Anne , Jung Shin , Kumabe Toshihiro , Lach Boleslaw , Leonard Jeffrey R. , Rubin Joshua B. , Liau Linda M. , Massimi Luca , Pollack Ian F. , Shin Ra Young , Van Meir Erwin G. , Zitterbart Karel , Schüller Ulrich , Hill Rebecca M. , Lindsey Janet C. , Schwalbe Ed C. , Bailey Simon , Ellison David W. , Hawkins Cynthia , Malkin David , Clifford Steven C. , Korshunov Andrey , Pfister Stefan , Taylor Michael D. , Tabori Uri
Published: July 2013

Purpose

Reports detailing the prognostic impact of TP53 mutations in medulloblastoma offer conflicting conclusions. We resolve this issue through the inclusion of molecular subgroup profiles.

Patients and Methods

We determined subgroup affiliation, TP53 mutation status, and clinical outcome in a discovery cohort of 397 medulloblastomas. We subsequently validated our results on an independent cohort of 156 medulloblastomas.

Results

TP53 mutations are enriched in wingless (WNT; 16%) and sonic hedgehog (SHH; 21%) medulloblastomas and are virtually absent in subgroups 3 and 4 tumors (P < .001). Patients with SHH/TP53 mutant tumors are almost exclusively between ages 5 and 18 years, dramatically different from the general SHH distribution (P < .001). Children with SHH/TP53 mutant tumors harbor 56% germline TP53 mutations, which are not observed in children with WNT/TP53 mutant tumors. Five-year overall survival (OS; ± SE) was 41% ± 9% and 81% ± 5% for patients with SHH medulloblastomas with and without TP53 mutations, respectively (P < .001). Furthermore, TP53 mutations accounted for 72% of deaths in children older than 5 years with SHH medulloblastomas. In contrast, 5-year OS rates were 90% ± 9% and 97% ± 3% for patients with WNT tumors with and without TP53 mutations (P = .21). Multivariate analysis revealed that TP53 status was the most important risk factor for SHH medulloblastoma. Survival rates in the validation cohort mimicked the discovery results, revealing that poor survival of TP53 mutations is restricted to patients with SHH medulloblastomas (P = .012) and not WNT tumors.

Conclusion

Subgroup-specific analysis reconciles prior conflicting publications and confirms that TP53 mutations are enriched among SHH medulloblastomas, in which they portend poor outcome and account for a large proportion of treatment failures in these patients.
Use of Pharmacologic Interventions for Breast Cancer Risk Reduction: American Society of Clinical Oncology Clinical Practice Guideline
Authors: Visvanathan Kala , Hurley Patricia , Bantug Elissa , Brown Powel , Col Nananda F. , Cuzick Jack , Davidson Nancy E. , DeCensi Andrea , Fabian Carol , Ford Leslie , Garber Judy , Katapodi Maria , Kramer Barnett , Morrow Monica , Parker Barbara , Runowicz Carolyn , Vogel Victor G. , Wade James L. , Lippman Scott M.
Published: July 2013

Purpose

To update the 2009 American Society of Clinical Oncology guideline on pharmacologic interventions for breast cancer (BC) risk reduction.

Methods

A systematic review of randomized controlled trials and meta-analyses published from June 2007 through June 2012 was completed using MEDLINE and Cochrane Collaboration Library. Primary outcome of interest was BC incidence (invasive and noninvasive). Secondary outcomes included BC mortality, adverse events, and net health benefits. Guideline recommendations were revised based on an Update Committee's review of the literature.

Results

Nineteen articles met the selection criteria. Six chemoprevention agents were identified: tamoxifen, raloxifene, arzoxifene, lasofoxifene, exemestane, and anastrozole.

Recommendations

In women at increased risk of BC age ≥ 35 years, tamoxifen (20 mg per day for 5 years) should be discussed as an option to reduce the risk of estrogen receptor (ER) –positive BC. In postmenopausal women, raloxifene (60 mg per day for 5 years) and exemestane (25 mg per day for 5 years) should also be discussed as options for BC risk reduction. Those at increased BC risk are defined as individuals with a 5-year projected absolute risk of BC ≥ 1.66% (based on the National Cancer Institute BC Risk Assessment Tool or an equivalent measure) or women diagnosed with lobular carcinoma in situ. Use of other selective ER modulators or other aromatase inhibitors to lower BC risk is not recommended outside of a clinical trial. Health care providers are encouraged to discuss the option of chemoprevention among women at increased BC risk. The discussion should include the specific risks and benefits associated with each chemopreventive agent.
Challenges of Guarantee-Time Bias
Authors: Giobbie-Hurder Anita , Gelber Richard D. , Regan Meredith M.
Published: July 2013

The potential for guarantee-time bias (GTB), also known as immortal time bias, exists whenever an analysis that is timed from enrollment or random assignment, such as disease-free or overall survival, is compared across groups defined by a classifying event occurring sometime during follow-up. The types of events associated with GTB are varied and may include the occurrence of objective disease response, onset of toxicity, or seroconversion. However, comparative analyses using these types of events as predictors are different from analyses using baseline characteristics that are specified completely before the occurrence of any outcome event. Recognizing the potential for GTB is not always straightforward, and it can be challenging to know when GTB is influencing the results of an analysis. This article defines GTB, provides examples of GTB from several published articles, and discusses three analytic techniques that can be used to remove the bias: conditional landmark analysis, extended Cox model, and inverse probability weighting. The strengths and limitations of each technique are presented. As an example, we explore the effect of bisphosphonate use on disease-free survival (DFS) using data from the BIG (Breast International Group) 1-98 randomized clinical trial. An analysis using a naive approach showed substantial benefit for patients who received bisphosphonate therapy. In contrast, analyses using the three methods known to remove GTB showed no statistical evidence of a reduction in risk of a DFS event with bisphosphonate therapy.
Circulating Levels of IL-1B+IL-6 Cause ER Stress and Dysfunction in Islets From Prediabetic Male Mice
Authors: O'Neill Christina M. , Lu Christine , Corbin Kathryn L. , Sharma Poonam R. , Dula Stacey B. , Carter Jeffrey D. , Ramadan James W. , Xin Wenjun , Lee Jae K. , Nunemaker Craig S.
Published: July 2013

Elevated levels of circulating proinflammatory cytokines are associated with obesity and increased risk of type 2 diabetes, but the mechanism is unknown. We tested whether proinflammatory cytokines IL-1B+IL-6 at low picogram per milliliter concentrations (consistent with serum levels) could directly trigger pancreatic islet dysfunction. Overnight exposure to IL-1B+IL-6 in islets isolated from normal mice and humans disrupted glucose-stimulated intracellular calcium responses; cytokine-induced effects were more severe among islets from prediabetic db/db mice that otherwise showed no signs of dysfunction. IL-1B+IL-6 exposure reduced endoplasmic reticulum (ER) calcium storage, activated ER stress responses (Nos2, Bip, Atf4, and Ddit3 [CHOP]), impaired glucose-stimulated insulin secretion, and increased cell death only in islets from prediabetic db/db mice. Furthermore, we found increased serum levels of IL-1B and IL-6 in diabetes-prone mice at an age before hyperglycemia was exhibited, suggesting that low-grade systemic inflammation develops early in the disease process. In addition, we implanted normal outbred and inbred mice with subcutaneous osmotic mini-pumps containing IL-1B+IL-6 to mimic the serum increases found in prediabetic db/db mice. Both IL-1B and IL-6 were elevated in serum from cytokine-pump mice, but glucose tolerance and blood glucose levels did not differ from controls. However, when compared with controls, isolated islets from cytokine-pump mice showed deficiencies in calcium handling and insulin secretion that were similar to observations with islets exposed to cytokines in vitro. These findings provide proof of principle that low-grade systemic inflammation is present early in the development of type 2 diabetes and can trigger ER stress-mediated islet dysfunction that can lead to islet failure.
Asymmetric Syntheses of Pharmaceuticals Containing a Cyclopropane Moiety Using Catalytic Asymmetric Simmons–Smith Reactions of Allylalcohols: Syntheses of Optically Active Tranylcypromine and Milnacipran
Authors: Ishizuka Yuki , Fujimori Hirohisa , Noguchi Takuya , Kawasaki Masashi , Kishida Mari , Nagai Takuya , Imai Nobuyuki , Kirihara Masayuki
Published: July 2013

Asymmetric synthesis of tranylcypromine was achieved using an enantioselective Simmons–Smith cyclopropanation catalyzed by a simple disulfonamide derived from an α-amino acid. The optically active milnacipran was also synthesized by porcine pancreas lipase-catalyzed selective monoacylation of the C4-hydroxy group in (Z)-2-phenylbut-2-ene-1,4-diol and the enantioselective Simmons–Smith cyclopropanation as the key steps.
Hexaphenylethanes with an Ultralong C–C Bond: Expandability of the C–C Bond in Highly Strained Tetraarylpyracenes
Authors: Takeda Takashi , Uchimura Yasuto , Kawai Hidetoshi , Katoono Ryo , Fujiwara Kenshu , Suzuki Takanori
Published: July 2013

Over the past few decades, many studies have been conducted on ultralong C–C bonds (bond length greater than 1.7 Å). This highlight review discusses the molecular design of ultralong C–C bonds and their bonding properties, especially their “expandability.” In particular, the ultralong C–C bonds in tetraarylpyracene derivatives can change in length by adopting a slightly different conformation in the crystalline state. This expandability of ultralong C–C bonds could be due to the smaller decrease in bond energy at a longer interatomic distance (>1.7 Å). This interesting property can be applied to stimulus-responsive materials, as illustrated in the thermochromism of a bis(methylacridan)-substituted pyracene crystal, since the thermally induced change in bond-length modifies the HOMO–LUMO gap.
Detection of Melamine and Cyanuric Acid in Feed Ingredients by near Infrared Spectroscopy and Chemometrics
Authors: Abbas O. , Lecler B. , Dardenne P. , Baeten V.
Published: July 2013

This study investigated the detection of contamination of animal feed by melamine and its derivatives by rapid analytical methods. The main goal was to propose an effective tool to detect contaminantion by using multivariate calibration equations built on a large database of non-contaminated feed ingredients. Soybean meal, maize gluten and wheat gluten samples were contaminated by different percentages of melamine and cyanuric acid. The influence of these additives on near infrared (NIR) predicted values of crude protein was studied. The predicted values of protein, in terms of the adulteration percentage, were compared with those obtained by conventional methods (Kjeldahl and Dumas). The addition of the contaminant led to an increase in the protein value when measured by classical methods and to a decrease in the value when predicted by the NIR calibration models. Among the modifications in the spectral profile of affected feed was the intensity of the spectrum at about 2170 nm, characteristic of the absorption of proteins which might explain the reduction in NIR predicted protein values when contaminants were added. An important advantage of the approach is the simultaneous detection of several analytes, making it possible to detect melamine and cyanuric acid at the same time. Contaminated feed was analysed using the near infrared (NIR) general feed ingredient database. Calibration equations were developed and applied to the samples in this study to visualise their distribution with regard to the existing data set that does not contain contaminants. Contaminated samples presented global H ( GH) (Mahalanobis distance) values greater than three and were easily distinguished from the rest. Both the full spectrum and a selected spectral region between 2130 nm and 2230 nm, including wavelengths relevant for discrimination, were used to develop mathematical equations to predict the protein content and to detect contaminated samples.
A Haemodynamic Brain–Computer Interface Based on Real-Time Classification of near Infrared Spectroscopy Signals during Motor Imagery and Mental Arithmetic
Authors: Stangl Matthias , Bauernfeind Günther , Kurzmann Jürgen , Scherer Reinhold , Neuper Christa
Published: July 2013

Over the past decade, an increasing number of studies have investigated near infrared (NIR) spectroscopy for signal acquisition in brain–computer interface (BCI) systems. However, although a BCI relies on classifying brain signals in real-time, the majority of previous studies did not perform real-time NIR spectroscopy signal classification but derived knowledge about the feasibility of NIR spectroscopy for BCI purposes from offline analyses. The present study investigates whether NIR spectroscopy signals evoked by two different mental tasks (i.e. motor imagery and mental arithmetic) can be classified in real-time in order to control a NIR-BCI application. Furthermore, since this is the first study that attempts to distinguish between the haemodynamic responses to these two tasks, we aimed to investigate whether this task-combination is feasible for controlling a NIR-BCI. Twelve healthy participants were asked to control a moving ball on a computer screen by performing motor imagery and mental arithmetic tasks. The real-time classification of their task-specific NIR spectroscopy signals yielded accuracy rates ranging from 45% up to 93%. Offline analyses across all participants showed that both tasks evoked different haemodynamic responses in prefrontal and sensorimotor cortex areas. On the one hand, these results demonstrate the considerable potential of NIR spectroscopy for BCI signal acquisition and the feasibility of the applied mental tasks for NIR-BCI control. On the other hand, since the classification accuracy showed an unsatisfactory stability across measurement sessions, we conclude that further investigations and progress in methodological issues are needed and we discuss further steps that have to be taken until it is conceivable to implement a real-time capable NIR-BCI that works with sufficient accuracy across a large group of individuals.
Partial Least Square Discriminant Analysis of Mangosteen Pericarp Powder by near Infrared Spectroscopy
Authors: Peerapattana Jomjai , Shinzawa Hideyuki , Otsuka Kuniko , Hattori Yusuke , Otsuka Makoto
Published: July 2013

Partial least square discriminant analysis (PLS-DA) was applied to sort out the difference between mangosteen powder and fake samples measured by near infrared (NIR) spectroscopy. The main feature of the NIR diffuse reflectance spectra of the powder samples are overwhelmed by the baseline change due to the difference in the density and average particle size, making the discrimination difficult. The informative spectral feature was readily elucidated when the NIR spectra were subjected to the second derivative. The PLS-DA of the second derivative spectra revealed a substantial level of difference between the mangosteen powder and fake samples due to the resin and dietary fibre predominantly present in the mangosteen.
Discrimination of Pinus TaedaxP. Caribaea var. hondurensis between its Allele-Species and Hybrids using near Infrared Spectroscopy
Authors: Luan Qi-Fu , Li Yan-Jie , Jiang Jing-Min , Yue Hua-Feng , Diao Song-Feng
Published: July 2013

It is not easy to distinguish hybrid pines using their morphological characteristics. Traditional methods of identification, such as chemical analysis or molecular marker technology, are complicated, time-consuming and costly and are not very accurate. They are not, therefore, an ideal means of identification and the use of near-infrared technology, which is comparatively inexpensive and simple to use, is preferable. For the future development of Pinus taedax P. caribaea var. hondurensis (PTC) hybrid trials and breeding programmes, and to provide a more comprehensive understanding of their physiological and biochemical characteristics, it is necessary to identify PTC among the parents ( P. elliottii, P. taeda and P. caribaea var. hondurensis) and other possible hybrids ( P. elliottiix P. caribaea var. hondurensis) in order to be able to distinguish them from each other. In this study, partial least-squares discriminant analysis (PLS-DA) and linear discriminant analysis (LDA) regression modelling are used, The results are as follows: PLS-DA has a low accuracy rate, at 89.09%, but using the PLS-DA scores as the input data into the LDA resulted in LDA distinction models, with accuracy rates reaching 99%, allowing a reliable identification of pure species and hybrids. It is clear from the results that near infrared technology can be used to identify hybrid and purebreds in pine and that the accuracy rate is higher than that derived when using standard molecular techniques.