bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of a small-molecule type II inhibitor of wild-type and gatekeeper mutants of BCR-ABL, PDGFRα, Kit, and Src kinases: novel type II inhibitor of gatekeeper mutants
Authors: Weisberg Ellen , Choi Hwan Geun , Ray Arghya , Barrett Rosemary , Zhang Jianming , Sim Taebo , Zhou Wenjun , Seeliger Markus , Cameron Michael , Azam Mohammed , Fletcher Jonathan A. , Debiec-Rychter Maria , Mayeda Mark , Moreno Daisy , Kung Andrew L. , Janne Pasi Antero , Khosravi-Far Roya , Melo Junia V. , Manley Paul W. , Adamia Sophia , Wu Catherine , Gray Nathanael , Griffin James D. 
Published: March 2010

Abstract
Many clinically validated kinases, such as BCR-ABL, c-Kit, PDGFR, and EGFR, become resistant to adenosine triphosphate-competitive inhibitors through mutation of the so-called gatekeeper amino acid from a threonine to a large hydrophobic amino acid, such as an isoleucine or methionine. We have developed a new class of adenosine triphosphate competitive inhibitors, exemplified by HG-7-85-01, which is capable of inhibiting T315I- BCR-ABL (clinically observed in chronic myeloid leukemia), T670I-c-Kit (clinically observed in gastrointestinal stromal tumors), and T674I/M-PDGFRα (clinically observed in hypereosinophilic syndrome). HG-7-85-01 is unique among all currently reported kinase inhibitors in having the ability to accommodate either a gatekeeper threonine, present in the wild-type forms of these kinases, or a large hydrophobic amino acid without becoming a promiscuous kinase inhibitor. The distinctive ability of HG-7-85-01 to simultaneously inhibit both wild-type and mutant forms of several kinases of clinical relevance is an important step in the development of the next generation of tyrosine kinase inhibitors.
Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma: a population-based study
Authors: Kristinsson Sigurdur Y. , Pfeiffer Ruth M. , Björkholm Magnus , Goldin Lynn R. , Schulman Sam , Blimark Cecilie , Mellqvist Ulf-Henrik , Wahlin Anders , Turesson Ingemar , Landgren Ola 
Published: March 2010

AbstractPatients with multiple myeloma (MM) have an increased risk of venous thrombosis. Interestingly, excess risk of venous thromboembolism has been observed among patients with monoclonal gammopathy of undetermined significance (MGUS). Using population-based data from Sweden, we assessed the risks of venous and arterial thrombosis in 18 627 MM and 5326 MGUS patients diagnosed from 1958 to 2006, compared with 70 991 and 20 161 matched controls, respectively. At 1, 5, and 10 years after MM diagnosis, there was an increased risk of venous thrombosis: hazard ratios (95% confidence intervals) were 7.5 (6.4-8.9), 4.6 (4.1-5.1), and 4.1 (3.8-4.5), respectively. The corresponding results for arterial thrombosis were 1.9 (1.8-2.1), 1.5 (1.4-1.6), and 1.5 (1.4-1.5). At 1, 5, and 10 years after MGUS diagnosis, hazard ratios were 3.4 (2.5-4.6), 2.1 (1.7-2.5), and 2.1 (1.8-2.4) for venous thrombosis. The corresponding risks for arterial thrombosis were 1.7 (1.5-1.9), 1.3 (1.2-1.4), and 1.3 (1.3-1.4). IgG/IgA (but not IgM) MGUS patients had increased risks for venous and arterial thrombosis. Risks for thrombosis did not vary by M-protein concentration (> 10.0 g/L or < 10.0 g/L) at diagnosis. MGUS patients with (vs without) thrombosis had no excess risk of MM or Waldenström macroglobulinemia. Our findings are of relevance for future studies and for improvement of thrombosis prophylaxis strategies.
Phase 1/2 and extension study of velaglucerase alfa replacement therapy in adults with type 1 Gaucher disease: 48-month experience
Authors: Zimran Ari , Altarescu Gheona , Philips Mici , Attias Drorit , Jmoudiak Marina , Deeb Maher , Wang Nan , Bhirangi Kiran , Cohn Gabriel M. , Elstein Deborah 
Published: March 2010

Abstract
Enzyme replacement therapy is the standard of care for symptomatic Gaucher disease. Velaglucerase alfa is a human β-glucocerebrosidase produced in a well-characterized human cell line. A 9-month phase 1/2 open-label, single-center trial and ongoing extension study were conducted to evaluate safety and efficacy of velaglucerase alfa. Twelve symptomatic adult type 1 Gaucher patients (intact spleens) received velaglucerase alfa (60 U/kg per infusion) during phase 1/2. An extension study was offered to patients completing the trial; step-wise dose reduction (to 30 U/kg per infusion) was instituted. Eleven patients completed phase 1/2; 10 entered the extension; 9 patients reached 39 months of extension. No drug-related serious adverse events or withdrawals, and no antibodies were observed. Home therapy was successfully implemented during the extension. Statistically significant improvements (P < .004) were noted in mean percentage change from baseline to 9 months and baseline to 48 months for hemoglobin (+19.2%, +21.7%, respectively), platelet counts (+67.6%, +157.8%, respectively), normalized liver volume (−18.2%, −42.8%, respectively), and normalized spleen volume (−49.5%, −79.3%, respectively). These significant clinical changes and safety profile led to phase 3 trials and highlight the potential of velaglucerase alfa as alternative therapy for type 1 Gaucher disease. The extension trial is registered at http://www.clinicaltrials.gov as NCT00391625.
Genetic evidence supports linguistic affinity of Mlabri - a hunter-gatherer group in Thailand
Authors: Xu Shuhua , Kangwanpong Daoroong , Seielstad Mark , Srikummool Metawee , Kampuansai Jatupol , Jin Li ,   The HUGO Pan-Asian SNP Consortium*
Published: March 2010

AbstractBackgroundThe Mlabri are a group of nomadic hunter-gatherers inhabiting the rural highlands of Thailand. Little is known about the origins of the Mlabri and linguistic evidence suggests that the present-day Mlabri language most likely arose from Tin, a Khmuic language in the Austro-Asiatic language family. This study aims to examine whether the genetic affinity of the Mlabri is consistent with this linguistic relationship, and to further explore the origins of this enigmatic population.ResultsWe conducted a genome-wide analysis of genetic variation using more than fifty thousand single nucleotide polymorphisms (SNPs) typed in thirteen population samples from Thailand, including the Mlabri, Htin and neighboring populations of the Northern Highlands, speaking Austro-Asiatic, Tai-Kadai and Hmong-Mien languages. The Mlabri population showed higher LD and lower haplotype diversity when compared with its neighboring populations. Both model-free and Bayesian model-based clustering analyses indicated a close genetic relationship between the Mlabri and the Htin, a group speaking a Tin language.ConclusionOur results strongly suggested that the Mlabri share more recent common ancestry with the Htin. We thus provided, to our knowledge, the first genetic evidence that supports the linguistic affinity of Mlabri, and this association between linguistic and genetic classifications could reflect the same past population processes.
Examination of equine glandular stomach lesions for bacteria, including Helicobacter spp by fluorescence in situ hybridisation
Authors: Husted Louise , Jensen Tim K , Olsen Susanne N , Mølbak Lars 
Published: March 2010

AbstractBackgroundThe equine glandular stomach is commonly affected by erosion and ulceration. The aim of this study was to assess whether bacteria, including Helicobacter, could be involved in the aetiology of gastric glandular lesions seen in horses.ResultsStomach lesions, as well as normal appearing mucosa were obtained from horses slaughtered for human consumption. All samples were tested for urease activity using the Pyloritek®assay, while mucosal bacterial content was evaluated using FluorescenceIn SituHybridisation. In selected sub samples, bacteria characterisation was pursued further by cloning and sequencing. Mucosal lesions were found in 36/63 stomachs and included hyperplastic rugae, polypoid structures and focal erosions. None of the samples were tested positive for urease activity or for FISH using the Helicobacter genus specific probe. In samples of lesions, as well as normal samples, clones with 99% similarities toLactobacillus salivariusandSarcina ventriculiwere found.Escherichialike bacterium clones and Enterococcus clones were demonstrated in one focal erosion. Based on a phylogenetic tree these clones had 100% similarity toEscherichia fergusonii and Enterococcus faecium. The Enterococcus were found colonising the mucosal surface, whileE. fergusoniiorganisms were also demonstrated intraepithelial.ConclusionGastric Helicobacter spp. could not be verified as being involved in lesions of the glandular stomach of the horse. SinceE. fergusoniihas been described as an emerging pathogen in both humans and animals, the finding of this bacterium in gastric erosion warrants further clarification to whether gastric infection with this type bacterium is important for horses.
Transmission ratio distortion results in asymmetric introgression in Louisiana Iris
Authors: Tang Shunxue , Okashah Rebecca A , Knapp Steven J , Arnold Michael L , Martin Noland H 
Published: March 2010

AbstractBackgroundLinkage maps are useful tools for examining both the genetic architecture of quantitative traits and the evolution of reproductive incompatibilities. We describe the generation of two genetic maps using reciprocal interspecific backcross 1 (BC1) mapping populations from crosses betweenIris brevicaulisandIris fulva. These maps were constructed using expressed sequence tag (EST)- derived codominant microsatellite markers. Such a codominant marker system allowed for the ability to link the two reciprocal maps, and compare patterns of transmission ratio distortion observed between the two.ResultsLinkage mapping resulted in markers that coalesced into 21 linkage groups for each of the reciprocal backcross maps, presumably corresponding to the 21 haploid chromosomes ofI. brevicaulisandI. fulva. The composite map was 1190.0-cM long, spanned 81% of theI. brevicaulisandI. fulvagenomes, and had a mean density of 4.5 cM per locus. Transmission ratio distortion (TRD) was observed in 138 (48.5%) loci distributed in 19 of the 21 LGs in BCIB, BCIF, or both BC1mapping populations. Of the distorted markers identified,I.fulvaalleles were detected at consistently higher-than-expected frequencies in both mapping populations.ConclusionsThe observation thatI. fulvaalleles are overrepresented in both mapping populations suggests thatI.fulvaalleles are favored to introgress intoI.brevicaulisgenetic backgrounds, whileI.brevicaulisalleles would tend to be prevented from introgressing intoI.fulva. These data are consistent with the previously observed patterns of introgression in natural hybrid zones, whereI.fulvaalleles have been consistently shown to introgress across species boundaries.
Identification of a deep intronic mutation in the COL6A2 gene by a novel custom oligonucleotide CGH array designed to explore allelic and genetic heterogeneity in collagen VI-related myopathies
Authors: Bovolenta Matteo , Neri Marcella , Martoni Elena , Urciuolo Anna , Sabatelli Patrizia , Fabris Marina , Grumati Paolo , Mercuri Eugenio , Bertini Enrico , Merlini Luciano , Bonaldo Paolo , Ferlini Alessandra , Gualandi Francesca 
Published: March 2010

Abstract

Background
Molecular characterization of collagen-VI related myopathies currently relies on standard sequencing, which yields a detection rate approximating 75-79% in Ullrich congenital muscular dystrophy (UCMD) and 60-65% in Bethlem myopathy (BM) patients as PCR-based techniques tend to miss gross genomic rearrangements as well as copy number variations (CNVs) in both the coding sequence and intronic regions.

Methods
We have designed a custom oligonucleotide CGH array in order to investigate the presence of CNVs in the coding and non-coding regions of COL6A1, A2, A3, A5 and A6 genes and a group of genes functionally related to collagen VI. A cohort of 12 patients with UCMD/BM negative at sequencing analysis and 2 subjects carrying a single COL6 mutation whose clinical phenotype was not explicable by inheritance were selected and the occurrence of allelic and genetic heterogeneity explored.

Results
A deletion within intron 1A of the COL6A2 gene, occurring in compound heterozygosity with a small deletion in exon 28, previously detected by routine sequencing, was identified in a BM patient. RNA studies showed monoallelic transcription of the COL6A2 gene, thus elucidating the functional effect of the intronic deletion. No pathogenic mutations were identified in the remaining analyzed patients, either within COL6A genes, or in genes functionally related to collagen VI.

Conclusions
Our custom CGH array may represent a useful complementary diagnostic tool, especially in recessive forms of the disease, when only one mutant allele is detected by standard sequencing. The intronic deletion we identified represents the first example of a pure intronic mutation in COL6A genes.
Factors associated with health-seeking behavior among migrant workers in Beijing, China
Authors: Peng Yingchun , Chang Wenhu , Zhou Haiqing , Hu Hongpu , Liang Wannian 
Published: March 2010

Abstract

Background
Migrant workers are a unique phenomenon in the process of China's economic transformation. The household registration system classifies them as temporary residents in cities, putting them in a vulnerable state with an unfair share of urban infrastructure and social public welfare. The amount of pressure inflicted by migrant workers in Beijing, as one of the major migration destinations, is currently at a threshold. This study was designed to assess the factors associated with health-seeking behavior and to explore feasible solutions to the obstacles migrant workers in China faced with when accessing health-care.

Methods
A sample of 2,478 migrant workers in Beijing was chosen by the multi-stage stratified cluster sampling method. A structured questionnaire survey was conducted via face-to-face interviews between investigators and subjects. The multilevel methodology (MLM) was used to demonstrate the independent effects of the explanatory variables on health seeking behavior in migrant workers.

Results
The medical visitation rate of migrant workers within the past two weeks was 4.8%, which only accounted for 36.4% of those who were ill. Nearly one-third of the migrant workers chose self-medication (33.3%) or no measures (30.3%) while ill within the past two weeks. 19.7% of the sick migrants who should have been hospitalized failed to receive medical treatment within the past year. According to self-reported reasons, the high cost of health service was a significant obstacle to health-care access for 40.5% of the migrant workers who became sick. However, 94.0% of the migrant workers didn't have any insurance coverage in Beijing. The multilevel model analysis indicates that health-seeking behavior among migrants is significantly associated with their insurance coverage. Meanwhile, such factors as household monthly income per capita and working hours per day also affect the medical visitation rate of the migrant workers in Beijing.

Conclusion
This study assesses the influence of socio-demographic characteristics on the migrant workers' decision to seek health care services when they fall ill, and it also indicates that the current health service system discourages migrant workers from seeking appropriate care of good quality. Relevant policies of public medical insurance and assistance program should be vigorously implemented for providing affordable health care services to the migrants. Feasible measures need to be taken to reduce the health risks associated with current hygiene practices and equity should be assured in access to health care services among migrant workers.
Production of recombinant proteins in E. coli by the heat inducible expression system based on the phage lambda pL and/or pR promoters
Authors: Valdez-Cruz Norma A , Caspeta Luis , Pérez Néstor O , Ramírez Octavio T , Trujillo-Roldán Mauricio A 
Published: March 2010

Abstract
The temperature inducible expression system, based on the pL and/or pR phage lambda promoters regulated by the thermolabile cI857 repressor has been widely use to produce recombinant proteins in prokariotic cells. In this expression system, induction of heterologous protein is achieved by increasing the culture temperature, generally above 37°C. Concomitant to the overexpression of heterologous protein, the increase in temperature also causes a variety of complex stress responses. Many studies have reported the use of such temperature inducible expression system, however only few discuss the simultaneous stress effects caused by recombinant protein production and the up-shift in temperature. Understanding the integral effect of such responses should be useful to develop improved strategies for high yield protein production and recovery. Here, we describe the current status of the heat inducible expression system based on the pL and/or pR λ phage promoters, focusing on recent developments on expression vehicles, the stress responses at the molecular and physiological level that occur after heat induction, and bioprocessing factors that affect protein overexpression, including culture operation variables and induction strategies.
Quality of life measurement in women with cervical cancer: implications for Chinese cervical cancer survivors
Authors: Zeng Ying Chun , Ching Shirley SY , Loke Alice Y 
Published: March 2010

Abstract

Background
Women with cervical cancer now have relatively good 5-year survival rates. Better survival rates have driven the paradigm in cancer care from a medical illness model to a wellness model, which is concerned with the quality of women's lives as well as the length of survival. Thus, the assessment of quality of life among cervical cancer survivors is increasingly paramount for healthcare professionals. The purposes of this review were to describe existing validated quality of life instruments used in cervical cancer survivors, and to reveal the implications of quality of life measurement for Chinese cervical cancer survivors.

Methods
A literature search of five electronic databases was conducted using the terms cervical/cervix cancer, quality of life, survivors, survivorship, measurement, and instruments. Articles published in either English or Chinese from January 2000 to June 2009 were searched. Only those adopting an established quality of life instrument for use in cervical cancer survivors were included.

Results
A total of 11 validated multidimensional quality of life instruments were identified from 41 articles. These instruments could be classified into four categories: generic, cancer-specific, cancer site-specific and cancer survivor-specific instruments. With internal consistency varying from 0.68-0.99, the test-retest reliability ranged from 0.60-0.95 based on the test of the Pearson coefficient. One or more types of validity supported the construct validity. Although all these instruments met the minimum requirements of reliability and validity, the original versions of these instruments were mainly in English.

Conclusion
Selection of an instrument should consider the purpose of investigation, take its psychometric properties into account, and consider the instrument's origin and comprehensiveness. As quality of life can be affected by culture, studies assessing the quality of life of cervical cancer survivors in China or other non-English speaking countries should choose or develop instruments relevant to their own cultural context. There is a need to develop a comprehensive quality of life instrument for Chinese cervical cancer survivors across the whole survivorship, including immediately after diagnosis and for short- (less than 5 years) and long-term (more than 5 years) survivorship.
A case report of acute dermatitis that developed during an experiment examining the bromination of 3-hexylthiophene
Authors: Sato Mikiya , Yoshiki Hajime , Horie Masaki , Yano Eiji 
Published: March 2010

Abstract
Occupational cases with allergic reaction to fragrance substances, which refer to various chemicals providing aroma characteristics, are arising with its recent usage diversification from pharmaceutical, perfume industry to aromatic remedies. However, chemicals responsible for fragrance allergy have hardly been identified because its component is complex and its sensitization is not frequent. This report will present a case of acute allergic dermatitis that is likely induced by 3-hexylthiophene, one of aromatic compounds often contained in fragrance substances. The case, who was a 27-year male researcher engaged in organic chemical synthesis for six years, was exposed to 3-hexylthiophene and its product (2-bromo-3-hexylthiophene) through an experiment in May 2004 and itching, swelling and eczema immediately developed from face to back. This case of sensitization to 3-hexylthiophene suggests that it be a possible allergen for fragrance allergy.
Exophytic benign mixed epithelial stromal tumour of the kidney: case report of a rare tumour entity
Authors: Richter Michael , Meyer Werner , Küster Jens , Middel Peter 
Published: March 2010

Abstract

Background
Mixed epithelial and stromal tumour (MEST) represents a recently described benign composite neoplasm of the kidney, which predominantly affects perimenopausal females. Most tumours are benign, although rare malignant cases have been observed.

Case report
A 47-year-old postmenopausal female presented to the urologist with flank pain. A CT scan of the abdomen showed a 30-mm-in-diameter uniform mass adjacent to the pelvis of the left kidney. Surgical exploration showed a tumour arising from the lower anterior hilus of the left kidney. The tumour could be excised by preserving the kidney. By intraoperative frozen section the tumour showed characteristic features of MEST with epithelial-covered cysts embedded in an "ovarian-like" stroma. Additional immunohistochemistry investigations showed expression for hormone receptors by the stromal component of the tumour.

Discussion
MEST typically presents in perimenopausal women as a primarily cystic mass. Commonly, the tumour arises from the renal parenchyma or pelvis. The tumour is composed of an admixture of cystic and sometimes more solid areas. The stromal cells typically demonstrate an ovarian-type stroma showing expression for the estrogen and progesterone receptors.

Conclusion
MEST represents a distinctive benign tumour entity of the kidney, which affects perimenopausal woman. The tumour should be distinguished from other cystic renal neoplasms. By imaging studies it is difficult to distinguish between a benign or malignant nature of the tumour. Thus, intraoperative frozen section is necessary for conservative surgery, since the overall prognosis is favourable and renal function can be preserved in most cases.