bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pain in patients with myotonic dystrophy type 2: A postal survey in finland
Authors: Suokas Kimmo I. , Haanpää Maija , Kautiainen Hannu , Udd Bjarne , Hietaharju Aki J. 
Published: July 2011

AbstractIntroduction:Widespread musculoskeletal pain is a well‐known symptom of myotonic dystrophy type 2 (DM2), but so far it has been addressed in only a few studies.Methods:A postal survey for all traceable DM2 patients (n = 132) was conducted. A specific questionnaire, and severity and interference subscales of the Brief Pain Inventory, quality of life (RAND‐36), and modified Beck Depression Inventory were completed.Results:The response rate was 70%. The mean age of respondents was 53 years, 59% of whom were women. Current pain was reported by 54%. Lifetime prevalence of pain was 76%. The mean intensity of pain at its highest in the last week was 5.9, and 2.3 at its lowest (on a numerical rating scale of 0–10). Quality of life was lower in DM2 patients who reported pain. In 18%, the depression score was noticeably different.Conclusions:Pain of moderate severity and unpleasant muscular symptoms are common in DM2. DM2 should be taken into consideration in the differential diagnosis of musculoskeletal pain. Muscle Nerve 45: 70–74, 2012
NMDA receptors at the endplate of rat skeletal muscles: Precise postsynaptic localization
Authors: Malomouzh Artem I. , Nurullin Leniz F. , Arkhipova Svetlana S. , Nikolsky Evgeny E. 
Published: July 2011

AbstractIn this study we demonstrate expression of the N‐methyl‐D‐aspartate receptor NR1 subunit in the rat neuromuscular junction of skeletal muscles of different functional types (extensor digitorum longus, soleus, and diaphragm muscles) using fluorescence immunocytochemistry. Electron microscopic immunocytochemistry has shown that the NR1 subunit is localized solely on the sarcolemma in the depths of the postsynaptic folds. These findings suggest participation of the glutamatergic signaling system in functioning of the adult mammalian neuromuscular junction. Muscle Nerve, 2011
Frequency, Risk‐Factors and Survival of Children With Atypical Teratoid Rhabdoid Tumors (AT/RT) of the CNS Diagnosed between 1988 and 2004, and Registered to the German HIT Database
Authors: von Hoff Katja , Hinkes Bernward , Dannenmann‐Stern Elke , von Bueren André O. , Warmuth‐Metz Monika , Soerensen Niels , Emser Angela , Zwiener Isabella , Schlegel Paul G. , Kuehl Joachim , Frühwald Michael C. , Kortmann Rolf D. , Pietsch Torsten , Rutkowski Stefan 
Published: July 2011

AbstractPurposeTo analyze the frequency, prognostic factors, and outcome of children with atypical teratoid/rhabdoid tumors (AT/RT), a rare and highly malignant embryonal brain tumor.Materials and MethodsClinical data of patients diagnosed between 1988 and 2004 with AT/RT who were registered to the German HIT trial center, were correlated with outcome. Patient numbers for AT/RT were compared to numbers for primitive neuroectodermal tumors and medulloblastomas (PNET/MB) registered to the population‐based HIT trials.ResultsWe identified 56 patients with the centrally confirmed histopathological diagnosis of AT/RT with a median age of 1.2 years (range, 0.1–14.0 years). The AT/RT:PNET/MB ratio was 1:12.2 for all children, and 1:1.5 for children younger than 1 year at diagnosis. Three‐year overall survival (OS) and event‐free survival (EFS) for all patients were 22% and 13%, respectively. Eight patients (14%) are considered long‐term event‐free survivors (follow‐up 1.4–10.6 years). By univariable analyses, younger age, metastatic disease, infratentorial location, and less than complete remission at the end of chemotherapy were identified as negative influencing factors for OS. By multivariable analyses, younger age (OS, EFS) and metastatic disease (OS) were identified as independent risk factors.ConclusionThe incidence of AT/RT in children below 1 year is higher than previously reported. A subset of patients with favorable clinical risk factors profits from intensive multimodal treatment. Prospective clinical and biological studies are needed to further define prognostic factors and optimize therapy. Pediatr Blood Cancer 2011; 57: 978–985. © 2011 Wiley‐Liss, Inc.
Young adults with SCD in US children's hospitals: Are they different from adolescents?
Authors: Dickerson Amanda K. , Klima Jennifer , Rhodes Melissa M. , O'Brien Sarah H. 
Published: July 2011

AbstractBackgroundThe period of transition from pediatric to adult care is a vulnerable time for patients with sickle cell disease (SCD). The optimal time for transition is unknown and there is no standard of care regarding this timing in the United States.ProceduresWe collected administrative data from the Pediatric Health Information System for all SCD admissions from 2000 to 2009. We compared reasons for hospitalization and resulting charges in adolescents (13–17 years) and young adults (18–21 years).ResultsWe identified 25,371 admissions of adolescents (n = 18,299) and young adults (n = 7,072) with SCD. Median admissions per patient per year was higher in young adults (0.6) compared to adolescents (0.2, P < 0.001), but reasons for hospitalization were similar between the two age groups. Complications of adult SCD such as nephropathy and pulmonary hypertension were rare (<2.5% of discharges) but more frequent in older patients (P = 0.001). Although length of stay was similar between the two groups (median = 4 days), young adults tended to incur higher charges (median +$1,314, P < 0.001) and were less likely to utilize private insurance (P < 0.001). Deaths (0.2% of admissions) were rare and similar across age groups (P = 0.7).ConclusionIn a national sample of US children's hospitals, adolescents (13–17 years) and young adults (18–21 years) with SCD had similar reasons for hospitalization and low mortality. Further studies are needed to investigate whether extending the age of transition to ≥21 years as a national standard may decrease morbidity and mortality, improve health‐related quality of life, or increase readiness for transition in patients with SCD. Pediatr Blood Cancer 2012; 58: 741–745. © 2011 Wiley Periodicals, Inc.
Treatment of relapsed acute lymphoblastic leukemia: Approaches used by pediatric oncologists and bone marrow transplant physicians
Authors: Burke Michael J. , Lindgen Bruce , Verneris Michael R. 
Published: July 2011

AbstractBackgroundManagement of relapsed B‐precursor acute lymphoblastic leukemia (ALL) is challenging and varied. We hypothesized that treatment approaches differ between pediatric oncologists and bone marrow transplant (BMT) physicians.ProcedureA survey addressing management of relapsed ALL was sent to pediatric oncologists (n = 883) and BMT (n = 86) physicians across North America.ResultsA number of similarities in treatment approaches were identified including: choice of chemotherapy for re‐induction/consolidation, preference for unrelated donors (URDs) in very early marrow relapse and the choice to not use URD donors in late marrow relapse. However, differences between the two disciplines were noted. For patients who relapsed 18–36 months from diagnosis, the majority of oncologists (53.7%) would retreat with chemotherapy while a majority BMT physicians (70.3%) recommended URD transplant (P < 0.001). Oncologists were also less likely to use minimal residual disease (MRD) in relapse assessment compared to BMT physicians (52% vs. 67.2%; P = 0.028) and more oncologists believed MRD testing was experimental and/or not proven in relapsed ALL (27.1% vs. 12.3%; P = 0.011).ConclusionsThis study highlights management differences in children with ALL between pediatric oncologists and BMT physicians, identifying opportunities for collaborative clinical trials. Pediatr Blood Cancer 2012; 58: 840–845. © 2011 Wiley Periodicals, Inc.
Anti‐tumor activity of the HSP90 inhibitor SNX‐2112 in pediatric cancer cell lines
Authors: Chinn Danielle C. , Holland William S. , Yoon Janet M. , Zwerdling Theodore , Mack Philip C. 
Published: July 2011

AbstractBackgroundHSP90 plays a central role in stabilizing client proteins involved in malignant processes. SNX‐2112 is an orally administered potent HSP90 inhibitor that has demonstrated pre‐clinical anti‐tumor activity in adult malignancies. As many childhood tumors depend upon HSP90 client proteins, we sought to test the pre‐clinical efficacy of SNX‐2112 in a panel of pediatric cancer cell lines both as a single‐agent and in combination with cisplatin (CP).ProcedureEight cell lines (from osteosarcoma, neuroblastoma, hepatoblastoma, and lymphoma) were studied. Short‐ and long‐term effects of SNX‐2112 were assessed by MTT and clonogenic assays. Cell cycling was measured using flow cytometry. Status of HSC70, HSP72, AKT1, C‐Raf, and PARP was assessed by immunoblotting. Efficacy of SNX‐2112 in combination with CP was assessed using median‐effect analysis.ResultsCell lines studied demonstrated sensitivity to SNX‐2112 with IC50 values ranging from 10–100 nM. Low dose treatments (12 nM) resulted in a cytostatic response with a minimal increase in sub‐G1 content. A higher dose (70 nM) exhibited a more prolonged inhibition and larger sub‐G1 accumulation. Observed levels of AKT1 and C‐Raf were markedly reduced over time along with an increase in PARP cleavage. In concurrently administered combination treatments, SNX‐2112 and CP synergistically inhibited cell growth.ConclusionsSNX‐2112 showed marked single‐agent activity in pediatric cancer cell lines with downstream effects on HSP90 client proteins. The combination of SNX‐2112 and CP showed synergistic activity in two cell lines tested. Further studies of HSP90 inhibitors such as SNX‐2112 as a single agent or in combination with chemotherapy are warranted in pediatric cancer. Pediatr Blood Cancer 2012; 58: 885–890. © 2011 Wiley Periodicals, Inc.
Hearing loss among survivors of childhood brain tumors treated with an irradiation‐sparing approach
Authors: Orgel Etan , Jain Shveta , Ji Lingyun , Pollick Liora , Si Stephanie , Finlay Jonathan , Freyer David R. 
Published: July 2011

AbstractBackgroundIntensive, irradiation‐sparing chemotherapy regimens for malignant brain tumors have improved survival and neurocognitive outcomes in very young children. Platinum compounds are pivotal to this approach's success but are associated with hearing loss that markedly reduces quality of life for survivors. The purpose of this study was to determine the prevalence and severity of ototoxicity associated with Head Start and similar irradiation‐sparing regimens.ProcedureA retrospective cohort study was conducted of children treated for malignant brain tumors at Children's Hospital Los Angeles using irradiation‐sparing regimens. Patient and treatment characteristics were ascertained. Primary outcomes were post‐treatment hearing status, need for hearing aids, and hearing threshold change.ResultsTwenty‐nine patients were evaluable. The most common diagnosis was medulloblastoma (n = 14). The median age at diagnosis was 2.0 years (range, 0.2–9.2). Median time from diagnosis to most recent hearing assessment was 1.1 years (mean 2.4; range, 0.2–17.5). Cumulative cisplatin and carboplatin dose was 281 ± 88 mg/m2 and 1,205 ± 277 mg/m2, respectively. All patients had aminoglycoside exposure. Following treatment, 18 patients (62.1%) had abnormal hearing and 11 (37.9%) required hearing aids. At 4,000 Hz, statistically significant hearing loss was documented in the range of 30–40 dB.ConclusionsWhile eliminating cranial irradiation has dramatically improved survival and neurocognitive and neuroendocrine outcomes in this population, clinically significant hearing loss is now the leading late effect due to the necessity of platinum‐based chemotherapy. Our results document the need for audiometric monitoring and developing otoprotective strategies in this vulnerable population. Pediatr Blood Cancer 2012; 58: 953–958. © 2011 Wiley Periodicals, Inc.
Using MS‐MLPA as an efficient screening tool for detecting 9p21 abnormalities in pediatric acute lymphoblastic leukemia
Authors: Gardiner R. Brett , Morash Barbara A. , Riddell Christie , Wang Hao , Fernandez Conrad V. , Yhap Margaret , Berman Jason N. 
Published: July 2011

AbstractBackgroundCharacterization of recurrent genetic lesions in childhood acute lymphoblastic leukemia (ALL) has enabled therapeutic stratification with improved outcomes. The tumor suppressor genes, CDKN2A and CDKN2B, encoding p16INK4a, p14ARF, and p15INK4b have been localized to 9p21. Abnormalities of 9p21 have been reported in 10–30% of childhood ALL using conventional cytogenetics and fluorescence in situ hybridization (FISH). The incidence of 9p21 using more sensitive techniques, such as methylation specific multiplex ligation‐dependent probe amplification (MS‐MLPA), remains uncertain, and thus also the prognostic significance.ProcedureWe investigated the incidence and prognostic importance of 9p21 abnormalities in pediatric ALL patients using MS‐MLPA and compared these results to FISH.ResultsIn total, MS‐MLPA or FISH detected aberrations (both dosage and methylation abnormalities) at 9p21 in a remarkable 32/48 (67%) patients in contrast to a much lower rate of only 8% of patients identified to have deletions by standard G banding cytogenetics. MS‐MLPA identified five deletions not found by FISH. Aberrant methylation at CDKN2B was found in 19 (46%) patients. 9p21 abnormalities were associated with National Cancer Institute (NCI) high‐risk criteria (P = 0.04) and were present in all five patients with T‐cell disease. Four pre‐B‐cell ALL patients relapsed, three of whom had prior 9p21 abnormalities.ConclusionsMS‐MLPA had a higher detection rate for 9p21 abnormalities than previously reported for other techniques. Given the ease of processing, minimal equipment and low cost of MS‐MLPA, our results suggest that previous reports may have underestimated the true frequency of 9p21 abnormalities and their potential impact upon ALL outcome. Pediatr Blood Cancer 2012; 58: 852–859. © 2011 Wiley Periodicals, Inc.
Creating a human brain proteome atlas – 14th HUPO BPP workshop September 20–21, 2010, Sydney, Australia
Authors: Gröttrup Bernd , Marcus Katrin , Grinberg Lea T. , Lee Sang K. , Meyer Helmut E. , Park Young M. 
Published: July 2011

AbstractThe HUPO Brain Proteome Project (HUPO BPP) held its 14th workshop during the HUPO 9th Annual World Congress in Sydney, Australia. The principal aim of this project is to discover prognostic and diagnostic biomarkers associated with neurodegenerative diseases and brain aging, with the ultimate objective of obtaining a better understanding of these conditions and creating roads for the development of novel diagnostic techniques and effective treatments. The attendees came together to discuss progress in the human clinical neuroproteomics and to define the needs and guidelines required for more advanced proteomics approaches.
Structure of a novel thermostable GH51 α‐L‐arabinofuranosidase from Thermotoga petrophila RKU‐1
Authors: Souza Tatiana A.C.B. , Santos Camila R. , Souza Angelica R. , Oldiges Daiane P. , Ruller Roberto , Prade Rolf A. , Squina Fabio M. , Murakami Mario T. 
Published: July 2011

Abstractα‐L‐arabinofuranosidases (EC 3.2.1.55) participate in the degradation of a variety of L‐arabinose‐containing polysaccharides and interact synergistically with other hemicellulases in the production of oligosaccharides and bioconversion of lignocellulosic biomass into biofuels. In this work, the structure of a novel thermostable family 51 (GH51) α‐L‐arabinofuranosidase from Thermotoga petrophila RKU‐1 (TpAraF) was determined at 3.1 Å resolution. The TpAraF tertiary structure consists of an (α/β)‐barrel catalytic core associated with a C‐terminal β‐sandwich domain, which is stabilized by hydrophobic contacts. In contrast to other structurally characterized GH51 AraFs, the accessory domain of TpAraF is intimately linked to the active site by a long β‐hairpin motif, which modifies the catalytic cavity in shape and volume. Sequence and structural analyses indicate that this motif is unique to Thermotoga AraFs. Small angle X‐ray scattering investigation showed that TpAraF assembles as a hexamer in solution and is preserved at the optimum catalytic temperature, 65°C, suggesting functional significance. Crystal packing analysis shows that the biological hexamer encompasses a dimer of trimers and the multiple oligomeric interfaces are predominantly fashioned by polar and electrostatic contacts.
Inhibitory effects of antagonists of growth hormone releasing hormone on experimental prostate cancers are associated with upregulation of wild‐type p53 and decrease in p21 and mutant p53 proteins
Authors: Stangelberger Anton , Schally Andrew V. , Rick Ferenc G. , Varga Jozsef L. , Baker Benjamin , Zarandi Marta , Halmos Gabor 
Published: July 2011

AbstractBACKGROUNDThe tumor suppressor gene p53 is implicated in cell cycle control and apoptosis. Antagonists of growth hormone‐releasing hormone (GHRH) have been shown to inhibit human experimental prostate cancers.METHODSWe investigated the involvement of p53 apoptotic pathways in this effect. Nude mice bearing xenografted PC‐3, DU‐145, and MDA‐PCa‐2b human prostate cancer lines were treated with a new potent GHRH antagonist MZ‐J‐7‐138. To determine whether tumor inhibition by MZ‐J‐7‐138 involves apoptotic mechanisms such as p53 and p21, we evaluated by Western Blot the expression of mutant mt‐p53 in PC‐3 and DU‐145 and of wild type (wt‐p53) in MDA‐PCa‐2b prostate cancers as well as p21.RESULTSMZ‐J‐7‐138 significantly inhibited the growth of PC‐3, DU‐145, and MDA‐PCa‐2b xenografts in nude mice. Androgen deprivation with the LHRH antagonist Cetrorelix enhanced the anti‐proliferative effect of GHRH antagonist MZ‐J‐7‐138 on MDA‐PCa‐2b tumors. The expression of mutant (mt‐p53) and p21 protein in PC‐3 and DU‐145 tumors was significantly decreased by treatment with MZ‐J‐7‐138, whereas wild type wt‐p53 expression in MDA‐PCA‐2b tumors was up regulated by treatment with Cetrorelix. All three models investigated expressed specific, high affinity GHRH receptors.CONCLUSIONSOur findings indicate that the anti‐proliferative effects of GHRH antagonist MZ‐J‐7‐138 and LHRH antagonist Cetrorelix on prostate cancers involve p53 and p21 signaling. Prostate 72:555–565, 2012. © 2011 Wiley Periodicals, Inc.
PDEF in Prostate Cancer
Authors: Sood Ashwani K. , Kim Hyung , Geradts Joseph 
Published: July 2011

AbstractProstate‐derived Ets factor (PDEF) is a relatively recently described member of the Ets family of transcription factors. It differs from other family members in its restricted and epithelial‐specific expression in normal tissues and its unique DNA‐binding motif that together may impart interesting specificity to its function. This communication reviews our current understanding of the expression characteristics of PDEF in normal prostate and in prostate cancer. Also, the biochemical and genetic evidence relating to the role of this transcription factor in prostate cancer is reviewed. Most evidence is consistent with an oncogenic role for PDEF in prostate cancer. Specific observations about the loss of PDEF expression in prostate tumors and its apparent role as a prostate tumor suppressor are also discussed. PDEF is one of the few transcription factors with potential to have a significant impact on the management of prostate cancer. A better understanding of its biology and its role in prostate cancer is urgently needed. Prostate 72:592–596, 2012. © 2011 Wiley Periodicals, Inc.
Predictive Performance of prostate cancer risk in Chinese men using 33 reported prostate cancer risk‐associated SNPs
Authors: Zheng Jie , Liu Fang , Lin Xiaoling , Wang Xiang , Ding Qiang , Jiang Haowen , Chen Hongyan , Lu Daru , Jin Guangfu , Hsing Ann W. , Shao Qiang , Qi Jun , Ye Yu , Wang Zhong , Gao Xin , Wang Guozeng , Chu Lisa W. , OuYang Jun , Huang Yichen , Chen Yanbo , Gao Yutang , Shi Rong , Wu Qijun , Wang Meilin , Zhang Zhengdong , Hu Yanlin , Sun Jielin , Zheng S. Lilly , Gao Xu , Xu Chuanliang , Mo Zengnan , Sun Yinghao , Xu Jianfeng 
Published: July 2011

AbstractBACKGROUNDGenome‐wide association studies (GWAS) have identified more than 30 single nucleotide polymorphisms (SNPs) that were reproducibly associated with prostate cancer (PCa) risk in populations of European descent. In aggregate, these variants have shown potential to predict risk for PCa in European men. However, their utility for PCa risk prediction in Chinese men is unknown.METHODSWe selected 33 PCa risk‐related SNPs that were originally identified in populations of European descent. Genetic scores were estimated for subjects in a Chinese case–control study (1,108 cases and 1,525 controls) based on these SNPs. To assess the performance of the genetic score on its ability to predict risk for PCa, we calculated area under the curve (AUC) of the receiver operating characteristic (ROC) in combination with 10‐fold cross‐validation.RESULTSThe genetic score was significantly higher for cases than controls (P = 5.91 × 10−20), and was significantly associated with risk of PCa in a dose‐dependent manner (P for trend: 4.78 × 10−18). The AUC of the genetic score was 0.604 for risk prediction of PCa in Chinese men. When ORs derived from this Chinese study population were used to calculate genetic score, the AUCs were 0.631 for all 33 SNPs and 0.617 when using only the 11 significant SNPs.CONCLUSIONOur results indicate that genetic variants related to PCa risk may be useful for risk prediction in Chinese men. Prospective studies are warranted to further evaluate these findings. Prostate 72:577–583, 2012. © 2011 Wiley Periodicals, Inc.
Pathway specific gene expression profiling reveals oxidative stress genes potentially regulated by transcription co‐activator LEDGF/p75 in prostate cancer cells
Authors: Basu Anamika , Drame Awa , Muñoz Ruben , Gijsbers Rik , Debyser Zeger , De Leon Marino , Casiano Carlos A. 
Published: July 2011

AbstractBACKGROUNDLens epithelium‐derived growth factor p75 (LEDGF/p75) is a stress survival transcription co‐activator and autoantigen that is overexpressed in tumors, including prostate cancer (PCa). This oncoprotein promotes resistance to cell death induced by oxidative stress and chemotherapy by mechanisms that remain unclear. To get insights into these mechanisms we identified candidate target stress genes of LEDGF/p75 using pathway‐specific gene expression profiling in PCa cells.METHODSA “Human oxidative stress and antioxidant defense” qPCR array was used to identify genes exhibiting significant expression changes in response to knockdown or overexpression of LEDGF/p75 in PC‐3 cells. Validation of array results was performed by additional qPCR and immunoblotting.RESULTSCytoglobin (CYGB), Phosphoinositide‐binding protein PIP3‐E/IPCEF‐1, superoxidase dismutase 3 (SOD3), thyroid peroxidase (TPO), and albumin (ALB) exhibited significant transcript down‐ and up‐regulation in response to LEDGF/p75 knockdown and overexpression, respectively. CYGB gene was selected for further validation based on its emerging role as a stress oncoprotein in human malignancies. In light of previous reports indicating that LEDGF/p75 regulates peroxiredoxin 6 (PRDX6), and that PRDXs exhibit differential expression in PCa, we also examined the relationship between these proteins in PCa cells. Our validation data revealed that changes in LEDGF/p75 transcript and protein expression in PCa cells closely paralleled those of CYGB, but not those of the PRDXs.CONCLUSIONSOur study identifies CYGB and other genes as stress genes potentially regulated by LEDGF/p75 in PCa cells, and provides a rationale for investigating their role in PCa and in promoting resistance to chemotherapy‐ and oxidative stress‐induced cell death. Prostate 72:597–611, 2012. © 2011 Wiley Periodicals, Inc.