bluuebunny/crossref_metadata_2025_split huggingface dataset:
CaMKII γ, a critical regulator of CML stem/progenitor cells, is a target of the natural product berbamine
Authors: Gu Ying , Chen Ting , Meng Zhipeng , Gan Yichao , Xu Xiaohua , Lou Guiyu , Li Hongzhi , Gan Xiaoxian , Zhou Hong , Tang Jinfen , Xu Genbo , Huang Liansheng , Zhang Xiaohong , Fang Yongming , Wang Kai , Zheng Shu , Huang Wendong , Xu Rongzhen 
Published: October 2012

Abstract
Bcr-Abl tyrosine kinase inhibitors (TKIs) have been a remarkable success for the treatment of Ph+ chronic myeloid leukemia (CML). However, a significant proportion of patients treated with TKIs develop resistance because of leukemia stem cells (LSCs) and T315I mutant Bcr-Abl. Here we describe the unknown activity of the natural product berbamine that efficiently eradicates LSCs and T315I mutant Bcr-Abl clones. Unexpectedly, we identify CaMKII γ as a specific and critical target of berbamine for its antileukemia activity. Berbamine specifically binds to the ATP-binding pocket of CaMKII γ, inhibits its phosphorylation and triggers apoptosis of leukemia cells. More importantly, CaMKII γ is highly activated in LSCs but not in normal hematopoietic stem cells and coactivates LSC-related β-catenin and Stat3 signaling networks. The identification of CaMKII γ as a specific target of berbamine and as a critical molecular switch regulating multiple LSC-related signaling pathways can explain the unique antileukemia activity of berbamine. These findings also suggest that berbamine may be the first ATP-competitive inhibitor of CaMKII γ, and potentially, can serve as a new type of molecular targeted agent through inhibition of the CaMKII γ activity for treatment of leukemia.
Prospective serial evaluation of 2-hydroxyglutarate, during treatment of newly diagnosed acute myeloid leukemia, to assess disease activity and therapeutic response
Authors: Fathi Amir T. , Sadrzadeh Hossein , Borger Darrell R. , Ballen Karen K. , Amrein Philip C. , Attar Eyal C. , Foster Julia , Burke Meghan , Lopez Hector U. , Matulis Christina R. , Edmonds Katherine M. , Iafrate A. John , Straley Kimberly S. , Yen Katharine E. , Agresta Samuel , Schenkein David P. , Hill Cedric , Emadi Ashkan , Neuberg Donna S. , Stone Richard M. , Chen Yi-Bin 
Published: October 2012

Abstract
Mutations of genes encoding isocitrate dehydrogenase (IDH1 and IDH2) have been recently described in acute myeloid leukemia (AML). Serum and myeloblast samples from patients with IDH-mutant AML contain high levels of the metabolite 2-hydroxyglutarate (2-HG), a product of the altered IDH protein. In this prospective study, we sought to determine whether 2-HG can potentially serve as a noninvasive biomarker of disease burden through serial measurements in patients receiving conventional therapy for newly diagnosed AML. Our data demonstrate that serum, urine, marrow aspirate, and myeloblast 2-HG levels are significantly higher in IDH-mutant patients, with a correlation between baseline serum and urine 2-HG levels. Serum and urine 2-HG, along with IDH1/2-mutant allele burden in marrow, decreased with response to treatment. 2-HG decrease was more rapid with induction chemotherapy compared with DNA-methyltransferase inhibitor therapy. Our data suggest that serum or urine 2-HG may serve as noninvasive biomarkers of disease activity for IDH-mutant AML.
How air pollution influences clinical management of respiratory diseases. A case-crossover study in Milan
Authors: Santus Pierachille , Russo Antonio , Madonini Enzo , Allegra Luigi , Blasi Francesco , Centanni Stefano , Miadonna Antonio , Schiraldi Gianfranco , Amaducci Sandro 
Published: October 2012

Abstract

Background
Environmental pollution is a known risk factor for multiple diseases and furthermore increases rate of hospitalisations. We investigated the correlation between emergency room admissions (ERAs) of the general population for respiratory diseases and the environmental pollutant levels in Milan, a metropolis in northern Italy.

Methods
We collected data from 45770 ERAs for respiratory diseases. A time-stratified case-crossover design was used to investigate the association between air pollution levels and ERAs for acute respiratory conditions. The effects of air pollutants were investigated at lag 0 to lag 5, lag 0–2 and lag 3–5 in both single and multi-pollutant models, adjusted for daily weather variables.

Results
An increase in ozone (O3) levels at lag 3–5 was associated with a 78% increase in the number of ERAs for asthma, especially during the warm season. Exposure to carbon monoxide (CO) proved to be a risk factor for pneumonia at lag 0–2 and in the warm season increased the risk of ERA by 66%. A significant association was found between ERAs for COPD exacerbation and levels of sulphur dioxide (SO2), CO, nitrate dioxide (NO2), and particulate matter (PM10 and PM2.5). The multipollutant model that includes all pollutants showed a significant association between CO (26%) and ERA for upper respiratory tract diseases at lag 0–2. For chronic obstructive pulmonary disease (COPD) exacerbations, only CO (OR 1.19) showed a significant association.

Conclusions
Exposure to environmental pollution, even at typical low levels, can increase the risk of ERA for acute respiratory diseases and exacerbation of obstructive lung diseases in the general population.
Wnt5a promotes ewing sarcoma cell migration through upregulating CXCR4 expression
Authors: Jin Zhe , Zhao Chenghai , Han Xiaorui , Han Yaxin 
Published: October 2012

Abstract

Background
As one of the malignant tumors most often affecting children and young adults, Ewing sarcoma (ES) is characterized by early metastasis contributing to unfavorable prognosis. However, the molecular mechanisms responsible for ES metastasis remain poorly understood. In this study, we aimed to explore whether Wnt5a, a putative pro-metastatic factor, plays a role in ES metastasis.

Methods
Expression of Wnt5a and CXCR4 was determined by real-time PCR or Western blot in 15 ES specimens and 4 ES cell lines, A-673, RD-ES, SK-N-MC and SK-ES-1. Expression of Wnt antagonists, SFRP1, SFRP2 and SFRP5, and some components in noncanonical Wnt pathway (p-JNK, p-cJUN and p-PKC) was also analyzed in this study. Methylation status of SFRP1, SFRP2 and SFRP5 was detected by Methylation-specific PCR (MSP). Wnt5a shRNA and pcDNA3.1 SFRP5 vector were used to abrogate Wnt5a expression and overexpress SFRP5 in ES cells, respectively.

Results
Wnt5a expression was positively correlated with CXCR4 expression in ES specimens. Levels of both Wnt5a mRNA and CXCR4 mRNA were significantly higher in specimens from ES patients with metastasis at diagnosis compared with specimens from those without metastasis. Recombinant Wnt5a enhanced CXCR4 expression in ES cells, which was accompanied by increased ES cell migration, whereas Wnt5a shRNA has opposite effects. SFRP5 was methylated and silenced in ES cells, and both recombinant SFRP5 and pcDNA3.1 SFRP5 vector suppressed CXCR4 expression as well as ES cell migration. Wnt5a shRNA and recombinant SFRP5 inhibited phosphorylation of JNK and cJUN, and JNK inhibitor also reduced CXCR4 expression and cell migration in ES cells.

Conclusions
Wnt5a increases ES cell migration via upregulating CXCR4 expression in the absence of Wnt antagonist SFRP5, suggesting that Wnt5a overexpression and SFRP5 deficiency may jointly promote ES metastasis.
A novel tool for assessing and summarizing the built environment
Authors: Kroeger Gretchen L , Messer Lynne , Edwards Sharon E , Miranda Marie Lynn 
Published: October 2012

Abstract

Background
A growing corpus of research focuses on assessing the quality of the local built environment and also examining the relationship between the built environment and health outcomes and indicators in communities. However, there is a lack of research presenting a highly resolved, systematic, and comprehensive spatial approach to assessing the built environment over a large geographic extent. In this paper, we contribute to the built environment literature by describing a tool used to assess the residential built environment at the tax parcel-level, as well as a methodology for summarizing the data into meaningful indices for linkages with health data.

Methods
A database containing residential built environment variables was constructed using the existing body of literature, as well as input from local community partners. During the summer of 2008, a team of trained assessors conducted an on-foot, curb-side assessment of approximately 17,000 tax parcels in Durham, North Carolina, evaluating the built environment on over 80 variables using handheld Global Positioning System (GPS) devices. The exercise was repeated again in the summer of 2011 over a larger geographic area that included roughly 30,700 tax parcels; summary data presented here are from the 2008 assessment.

Results
Built environment data were combined with Durham crime data and tax assessor data in order to construct seven built environment indices. These indices were aggregated to US Census blocks, as well as to primary adjacency communities (PACs) and secondary adjacency communities (SACs) which better described the larger neighborhood context experienced by local residents. Results were disseminated to community members, public health professionals, and government officials.

Conclusions
The assessment tool described is both easily-replicable and comprehensive in design. Furthermore, our construction of PACs and SACs introduces a novel concept to approximate varying scales of community and describe the built environment at those scales. Our collaboration with community partners at all stages of the tool development, data collection, and dissemination of results provides a model for engaging the community in an active research program.
Item and response-category functioning of the Persian version of the KIDSCREEN-27: Rasch partial credit model
Authors: Jafari Peyman , Bagheri Zahra , Safe Mozhgan 
Published: October 2012

Abstract

Background
The purpose of the study was to determine whether the Persian version of the KIDSCREEN-27 has the optimal number of response category to measure health-related quality of life (HRQoL) in children and adolescents. Moreover, we aimed to determine if all the items contributed adequately to their own domain.

Findings
The Persian version of the KIDSCREEN-27 was completed by 1083 school children and 1070 of their parents. The Rasch partial credit model (PCM) was used to investigate item statistics and ordering of response categories. The PCM showed that no item was misfitting. The PCM also revealed that, successive response categories for all items were located in the expected order except for category 1 in self- and proxy-reports.

Conclusions
Although Rasch analysis confirms that all the items belong to their own underlying construct, response categories should be reorganized and evaluated in further studies, especially in children with chronic conditions.
Immunohistochemical consistency between primary tumors and lymph node metastases of gastric neuroendocrine carcinoma
Authors: Uchiyama Chieko , Tamura Shigeyuki , Nakatsuka Shinichi , Takeno Atsushi , Miki Hirofumi , Kanemura Takashi , Nakahira Shin , Suzuki Rei , Nakata Ken , Takeda Yutaka , Kato Takeshi 
Published: October 2012

Abstract

Background
Gastric neuroendocrine carcinoma (G-NEC) is a rare, highly malignant tumor that exhibits aggressive growth leading to vascular invasion, distant metastasis and extremely poor prognosis. We studied the clinicopathological findings of seven patients at our institute to better under this disease.

Methods
Seven cases of G-NEC were identified among 1,027 cases of gastric carcinoma that underwent gastrectomy at Kansai Rousai Hospital between 2002 and 2010. We studied the pathological and immunohistochemical features of gastric neuroendocrine carcinomas at both the primary site and metastatic lymph nodes.

Results
The mean patient age was 73 years (range 63 to 86 years). There were no females in this series. The final staging was Stage I in one case, Stage II in two, Stage III in two and Stage IV in two. A total of 31 metastatic lymph nodes were found in these patients. This study revealed that the ratio of neuroendocrine cells was similar between the primary and metastatic sites, which tended to show the same expression patterns of neuroendocrine markers.

Conclusions
Metastatic lymph nodes showed heterogeneous immunohistochemical expression patterns similar to the primary sites. G-NEC is far advanced at diagnosis and rapidly reaches the lymph nodes retaining its heterogeneity, carrying a worse prognosis than common gastric cancer.

Mini abstract
G-NEC grows rapidly and metastasizes to the lymph nodes, retaining its pathological and immunohistochemical heterogeneity even at the metastatic sites.
Molecular response of Escherichia coli adhering onto nanoscale topography
Authors: Rizzello Loris , Galeone Antonio , Vecchio Giuseppe , Brunetti Virgilio , Sabella Stefania , Pompa Pier Paolo 
Published: October 2012

Abstract
Bacterial adhesion onto abiotic surfaces is an important issue in biology and medicine since understanding the bases of such interaction represents a crucial aspect in the design of safe implant devices with intrinsic antibacterial characteristics. In this framework, we investigated the effects of nanostructured metal substrates on Escherichia coli adhesion and adaptation in order to understand the bio-molecular dynamics ruling the interactions at the interface. In particular, we show how highly controlled nanostructured gold substrates impact the bacterial behavior in terms of morphological changes and lead to modifications in the expression profile of several genes, which are crucially involved in the stress response and fimbrial synthesis. These results mainly demonstrate that E. coli cells are able to sense even slight changes in surface nanotopography and to actively respond by activating stress-related pathways. At the same time, our findings highlight the possibility of designing nanoengineered substrates able to trigger specific bio-molecular effects, thus opening the perspective of smartly tuning bacterial behavior by biomaterial design.
Clinical course of chronic hepatitis B patients who were off-treated after lamivudine treatment: analysis of 138 consecutive patients
Authors: Jin Young-Joo , Kim Kang Mo , Yoo Dong-jun , Shim Ju Hyun , Lee Han Chu , Chung Young-Hwa , Lee Yung Sang , Suh Dong Jin 
Published: October 2012

AbstractBackground/aimsLittle is known about the long-term outcome of chronic hepatitis B (CHB) patients who discontinued antiviral therapy. We intended to analyze the long-term outcome of CHB patients who discontinued lamivudine therapy and to evaluate predictors for post-treatment outcome.Material/methodsFrom 2007 to 2008, 138 lamivudine off-treated CHB patients with alanine aminotransferase normalization were consecutively enrolled. Post-treatment virologic relapse, biochemical breakthrough, hepatitis flare, and retreatment results were retrospectively analyzed.ResultsAmong 138 patients, 102 were initially HBeAg-positive at the start of lamivudine treatment. Virologic relapse, biochemical breakthrough, and hepatitis flare were observed in 45.2, 52.9, and 12.7% of HBeAg-positive and 29.4, 30.6, and 8.3% of HBeAg-negative patients during the median follow-up of 28 and 30 months, respectively. The cumulative virologic relapse and biochemical breakthrough rates were significantly lower in patients with HBV DNA <50 copies/mL than 50-104copies/mL at lamivudine cessation. Hepatitis flare was observed in 4.8 and 11.8% of HBeAg-positive and HBeAg-negative patients with HBV DNA <50copies/mL, respectively. Thirty-eight among 138 patients received retreatment and most of them achieved biochemical (37/38) and virologic response (35/38) within 1 year of retreatment. Undetectable serum HBV DNA (<50 copies/mL) and young age at lamivudine cessation were inversely associated with virologic relapse. Undetectable HBV DNA at cessation, female, and initial HBeAg-negative were inversely associated with biochemical breakthrough.ConclusionsPost-treatment virologic relapse and biochemical breakthrough incidence were low in patients who achieved undetectable viral titer at lamivudine cessation. Retreatment after biochemical breakthrough or virologic relapse was safe and effective. Intermittent antiviral therapy might be cautiously considered in appropriately selected CHB patients.
In defense of adolescents: They really do use braces for the hours prescribed, if good help is provided. Results from a prospective everyday clinic cohort using thermobrace
Authors: Donzelli Sabrina , Zaina Fabio , Negrini Stefano 
Published: October 2012

Abstract

Background
The effectiveness of bracing relies on the quality of the brace, compliance of the patient, and some disease factors. Patients and parents tend to overestimate adherence, so an objective assessment of compliance has been developed through the use of heat sensors. In 2010 we started the everyday clinical use of a temperature sensor, and the aim of this study is to present our initial results.

Methods
Population: A prospective cohort of 68 scoliosis patients that finished at least 4 months of brace treatment on March 31, 2011: 48 at their first evaluation (79% females, age 14.2±2.4) and 20 already in treatment.
Treatment: Bracing (SPoRT concept); physiotherapic specific exercises (SEAS School); team approach according to the SOSORT Bracing Management Guidelines.
Methods. A heat sensor, “Thermobrace” (TB), has been validated and applied to the brace. The real (measured by TB) and referred (reported by the patient) compliances were calculated.
Statistics. The distribution was not normal, hence median and 95% interval confidence (IC95) and non-parametric tests had to be used.

Results
Average TB use: 5.5±1.5 months. Brace prescription was 23 hours/day (h/d) (IC95 18–23), with a referred compliance of 100% (IC95 70.7-100%) and a real one of 91.7% (IC95 56.6-101.7%), corresponding to 20 h/d (IC95 11–23). The more the brace was prescribed, the more compliant the patient was (94.8% in 23 h/d vs. 73.2% in 18 h/d, P < 0.05). Sixty percent of the patients had at least 90% compliance, and 45% remained within 1 hour of what had been prescribed. Non-wearing days were 0 (IC95 0–12.95), and involved 29% of patients.

Conclusion
This is the first study using a TB in a setting of respect for the SOSORT criteria for bracing, and it states that it is possible to achieve a very good compliance, even with a full time prescription, and better than what was previously reported (80% maximum). We hypothesize that the treating team (SOSORT criteria) plays a major role in our results. This study suggests that compliance is neither due to the type of treatment only nor to the patient alone. According to our experience, TB offers valuable insights and do not undermine the relationship with the patients.
An epidemiological and clinical analysis of craniomaxillofacial fibrous dysplasia in a Chinese population
Authors: Cheng Jie , Wang Yanling , Yu Hongbo , Wang Dongmiao , Ye Jinhai , Jiang Hongbin , Wu Yunong , Shen Guofang 
Published: October 2012

Abstract

Background
Craniomaxillofacial fibrous dysplasia (FD) is a benign bone lesion characterized by facial disfigurement and functional impairment. The aim of this study was to characterize the epidemiological and clinical features of craniomaxillofacial FD by presenting data from a representative Chinese population during a 15-year period (1994–2009).

Method
The craniomaxillofacial disease registries of two Chinese tertiary referral hospitals (Shanghai Ninth People’s Hospital and Stomatological hospital of Jiangsu Province) were searched and reviewed to collect relevant information for patients with craniomaxillofacial FD between Jan.1994 and Dec.2009. All included cases were further analyzed with regard to associated epidemiological and clinicopathological variables.

Results
A total number of 266 cases with definitive diagnosis were identified with 219 primary cases and 47 recurrent cases. There were 111 males and 155 females with a male to female ratio of 0.716:1. They were clinically categorized into three groups: monostotic (71.1%), polysotic (27.4%) and Albright syndrome (1.5%). Maxilla alone or with adjacent bones was the most common affected site. The serum alkaline phosphatase (ALP) in patients was much higher than that in healthy control, whereas comparable between primary patients and recurrent ones. Three patients (3/266, 1.1%) with polysotic lesions underwent spontaneous malignant transformation into osteosarcoma. The majority of patients underwent conservative surgery, while the others received radical resection with or without reconstruction.

Conclusions
Craniomaxillofacial FD is a rare bony disorder with defined epidemiological and clinicopathological features in Chinese population. Further investigations are warranted to establish the optimized timing, treatment strategy and prognostic prediction for this clinical entity.
MicroRNAs and Toll-like Receptor/Interleukin-1 Receptor Signaling
Authors: Virtue Anthony , Wang Hong , Yang Xiao-feng 
Published: October 2012

AbstractThe discovery of miRNAs has revolutionized the way we examine the genome, RNA products, and the regulation of transcription and translation. Their ability to modulate protein expression through mRNA degradation and translation repression resulted in avid scientific interest in miRNAs over the past decade. This research has led to findings that indicate miRNAs can regulate an array of cellular functions such as cellular apoptosis, proliferation, differentiation, and metabolism. Specifically, the capability of miRNAs to finely-tune gene expression naturally lends itself to immune system regulation which requires precise control for proper activity. In fact, abnormal miRNAs expression is often seen with inflammatory disorders like rheumatoid arthritis, systemic lupus erthematosus, experimental autoimmune encephalomyelitis, and inflammatory cancers. As a result, research investigating miRNAs modulation of immune cell proliferation, differentiation, and cellular signaling has yielded fruitful results. Specifically, in this review, we will examine the impact of miRNAs on toll-like receptor (TLRs) and interleukin-1β (IL-1β) signaling, which are integral in the proper functioning of the innate immune system. These signaling pathways share several key downstream signaling adaptors and therefore produce similar downstream effects such as the production of pro-inflammatory cytokines, chemokines, and interferons. This review will examine in depth the specific interactions of miRNAs with receptors, adaptor molecules, and regulator molecules within these cellular pathways. In addition, we will discuss the modulation of miRNAs’ expression by TLR and IL-1R signaling through positive and negative feedback loops.
Humeral head osteonecrosis in an adolescent amateur swimming athlete: a case report
Authors: Zuo Jianlin , Sano Hirotaka , Yamamoto Nobuyuki , Sakoma Yoshimasa , Shinozaki Nobuhisa , Itoigawa Yoshiaki , Omi Rei , Itoi Eiji 
Published: October 2012

Abstract
Osteonecrosis of the humeral head in an adolescent without clear pathogenesis has not been reported in the literature. In this case report, we present such a case of humeral head osteonecrosis in a 15-year-old adolescent. The lesion was located at the subchondral area of the medial part of the humeral head with characteristic appearances on MRI. The shoulder was immobilized in a sling until the pain disappeared, and the patient was told to refrain any kind of sport activities. Bone remodeling was noted five months after the first visit, and it took 2 years for the lesion to be totally healed.