bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clonal Evolution in Aplastic Anemia
Authors: Afable Manuel G. , Tiu Ramon V. , Maciejewski Jaroslaw P. 
Published: December 2011

AbstractCurrent immunosuppressive treatment (IST) induces remissions in 50%-70% of patients with aplastic anemia (AA) and result in excellent long-term survival. In recent years, the survival of refractory patients has also improved. Apart from relapse and refractoriness to IST, evolution of clonal diseases, including paroxysmal nocturnal hemoglobinuria and myelodysplastic syndrome (MDS), are the most serious long-term complications and constitute a strong argument for definitive therapy with BM transplantation if possible. Consequently, the detection of diagnostic chromosomal abnormalities (mostly monosomy 7) is of great clinical importance. Newer whole-genome scanning technologies such as single nucleotide polymorphism (SNP) array–based karyotyping may be a helpful diagnostic test for the detection of chromosomal defects in AA due to its precision/resolution and lack of reliance on cell division.
Nurture versus Nature: The Microenvironment in Chronic Lymphocytic Leukemia
Authors: Burger Jan A. 
Published: December 2011

AbstractIntrinsic factors such as genetic lesions, anti-apoptotic proteins, and aberrant signaling networks within leukemia cells have long been the main focus of chronic lymphocytic leukemia (CLL) research. However, over the past decade, it became increasingly clear that external signals from the leukemia microenvironment make pivotal contributions to disease progression in CLL and other B-cell malignancies. Consequently, increasing emphasis is now placed on exploring and targeting the CLL microenvironment. This review highlights critical cellular and molecular pathways of CLL-microenvironment cross-talk. In vitro and in vivo models for studying the CLL microenvironment are discussed, along with their use in searching for therapeutic targets and in drug testing. Clinically, CXCR4 antagonists and small-molecule antagonists of B cell receptor (BCR)-associated kinases (spleen tyrosine kinase [Syk], Bruton's tyrosine kinase [Btk], and PI3Kδ) are the most advanced drugs for targeting specific interactions between CLL cells and the miocroenvironment. Preclinical and first clinical evidence suggests that high-risk CLL patients can particularly benefit from these alternative agents. These findings indicate that interplay between leukemia-inherent and environmental factors, nature and nurture determines disease progression in CLL.
Progress in Hodgkin lymphoma: a population-based study on patients diagnosed in Sweden from 1973-2009
Authors: Sjöberg Jan , Halthur Cat , Kristinsson Sigurdur Y. , Landgren Ola , Axdorph Nygell Ulla , Dickman Paul W. , Björkholm Magnus 
Published: December 2011

Abstract
In recent decades, attention has focused on reducing long-term, treatment-related morbidity and mortality in Hodgkin lymphoma (HL). In the present study, we looked for trends in relative survival for all patients diagnosed with HL in Sweden from 1973-2009 (N = 6949; 3985 men and 2964 women; median age, 45 years) and followed up for death until the end of 2010. Patients were categorized into 6 age groups and 5 calendar periods (1973-1979, 1980-1986, 1987-1994, 1994-2000, and 2001-2009). Relative survival improved in all age groups, with the greatest improvement in patients 51-65 years of age (P < .0005). A plateau in relative survival was observed in patients below 65 years of age during the last calendar period, suggesting a reduced long-term, treatment-related mortality. The 10-year relative survival for patients diagnosed in 2000-2009 was 0.95, 0.96, 0.93, 0.80, and 0.44 for the age groups 0-18, 19-35, 36-50, 51-65, and 66-80, respectively. Therefore, despite progress, age at diagnosis remains an important prognostic factor (P < .0005). Advances in therapy for patients with limited and advanced-stage HL have contributed to an increasing cure rate. In addition, our findings support that long-term mortality of HL therapy has decreased. Elderly HL patients still do poorly, and targeted treatment options associated with fewer side effects will advance the clinical HL field.
KIT with D816 mutations cooperates with CBFB-MYH11 for leukemogenesis in mice
Authors: Zhao Ling , Melenhorst Jan J. , Alemu Lemlem , Kirby Martha , Anderson Stacie , Kench Maggie , Hoogstraten-Miller Shelley , Brinster Lauren , Kamikubo Yasuhiko , Gilliland D. Gary , Liu P. Paul 
Published: December 2011

Abstract
KIT mutations are the most common secondary mutations in inv(16) acute myeloid leukemia (AML) patients and are associated with poor prognosis. It is therefore important to verify that KIT mutations cooperate with CBFB-MYH11, the fusion gene generated by inv(16), for leukemogenesis. Here, we transduced wild-type and conditional Cbfb-MYH11 knockin (KI) mouse bone marrow (BM) cells with KIT D816V/Y mutations. KIT transduction caused massive BM Lin− cell death and fewer colonies in culture that were less severe in the KI cells. D816Y KIT but not wild-type KIT enhanced proliferation in Lin− cells and led to more mixed lineage colonies from transduced KI BM cells. Importantly, 60% and 80% of mice transplanted with KI BM cells expressing D816V or D816Y KIT, respectively, died from leukemia within 9 months, whereas no control mice died. Results from limiting dilution transplantations indicate higher frequencies of leukemia-initiating cells in the leukemia expressing mutated KIT. Signaling pathway analysis revealed that p44/42 MAPK and Stat3, but not AKT and Stat5, were strongly phosphorylated in the leukemia cells. Finally, leukemia cells carrying KIT D816 mutations were sensitive to the kinase inhibitor PKC412. Our data provide clear evidence for cooperation between mutated KIT and CBFB-MYH11 during leukemogenesis.
Global gene expression profiling in mouse plasma cell tumor precursor and bystander cells reveals potential intervention targets for plasma cell neoplasia
Authors: LeGrand Jason , Park Eun Sung , Wang Hongyang , Gupta Shalu , Owens James D. , Nelson Patrick J. , DuBois Wendy , Bair Thomas , Janz Siegfried , Mushinski J. Frederic 
Published: December 2011

AbstractTumor progression usually proceeds through several sequential stages, any of which could be targets for interrupting the progression process if one understood these steps at the molecular level. We extracted nascent plasma cell tumor (PCT) cells from within inflammatory oil granulomas (OG) isolated from IP pristane-injected BALB/c.iMycEμ mice at 5 different time points during tumor progression. We used laser capture microdissection to collect incipient PCT cells and analyzed their global gene expression on Affymetrix Mouse Genome 430A microarrays. Two independent studies were performed with different sets of mice. Analysis of the expression data used ANOVA and Bayesian estimation of temporal regulation. Genetic pathway analysis was performed using MetaCore (GeneGo) and IPA (Ingenuity). The gene expression profiles of PCT samples and those of undissected OG samples from adjacent sections showed that different genes and pathways were mobilized in the tumor cells during tumor progression, compared with their stroma. Our analysis implicated several genetic pathways in PCT progression, including biphasic (up- and then down-regulation) of the Spp1/osteopontin-dependent network and up-regulation of mRNA translation/protein synthesis. The latter led to a biologic validation study that showed that the AMPK-activating diabetes drug, metformin, was a potent specific PCT inhibitor in vitro.
Acid-sensing ion channel 3 mediates peripheral anti-hyperalgesia effects of acupuncture in mice inflammatory pain
Authors: Chen Wei-Hsin , Hsieh Ching-Liang , Huang Chun-Ping , Lin Tzu-Jou , Tzen Jason TC , Ho Tin-Yun , Lin Yi-Wen 
Published: December 2011

Abstract

Background
Peripheral tissue inflammation initiates hyperalgesia accompanied by tissue acidosis, nociceptor activation, and inflammation mediators. Recent studies have suggested a significantly increased expression of acid-sensing ion channel 3 (ASIC3) in both carrageenan- and complete Freund's adjuvant (CFA)-induced inflammation. This study tested the hypothesis that acupuncture is curative for mechanical hyperalgesia induced by peripheral inflammation.

Methods
Here we used mechanical stimuli to assess behavioral responses in paw and muscle inflammation induced by carrageenan or CFA. We also used immunohistochemistry staining and western blot methodology to evaluate the expression of ASIC3 in dorsal root ganglion (DRG) neurons.

Results
In comparison with the control, the inflammation group showed significant mechanical hyperalgesia with both intraplantar carrageenan and CFA-induced inflammation. Interestingly, both carrageenan- and CFA-induced hyperalgesia were accompanied by ASIC3 up-regulation in DRG neurons. Furthermore, electroacupuncture (EA) at the ST36 rescued mechanical hyperalgesia through down-regulation of ASIC3 overexpression in both carrageenan- and CFA-induced inflammation.

Conclusions
In addition, electrical stimulation at the ST36 acupoint can relieve mechanical hyperalgesia by attenuating ASIC3 overexpression.
The small heat shock proteins from Acidithiobacillus ferrooxidans: gene expression, phylogenetic analysis, and structural modeling
Authors: Ribeiro Daniela A , Del Bem Luiz EV , Vicentini Renato , Ferraz Lúcio FC , Murakami Mario T , Ottoboni Laura MM 
Published: December 2011

Abstract

Background

Acidithiobacillus ferrooxidans is an acidophilic, chemolithoautotrophic bacterium that has been successfully used in metal bioleaching. In this study, an analysis of the A. ferrooxidans ATCC 23270 genome revealed the presence of three sHSP genes, Afe_1009, Afe_1437 and Afe_2172, that encode proteins from the HSP20 family, a class of intracellular multimers that is especially important in extremophile microorganisms.

Results
The expression of the sHSP genes was investigated in A. ferrooxidans cells submitted to a heat shock at 40°C for 15, 30 and 60 minutes. After 60 minutes, the gene on locus Afe_1437 was about 20-fold more highly expressed than the gene on locus Afe_2172. Bioinformatic and phylogenetic analyses showed that the sHSPs from A. ferrooxidans are possible non-paralogous proteins, and are regulated by the σ32 factor, a common transcription factor of heat shock proteins. Structural studies using homology molecular modeling indicated that the proteins encoded by Afe_1009 and Afe_1437 have a conserved α-crystallin domain and share similar structural features with the sHSP from Methanococcus jannaschii, suggesting that their biological assembly involves 24 molecules and resembles a hollow spherical shell.

Conclusion
We conclude that the sHSPs encoded by the Afe_1437 and Afe_1009 genes are more likely to act as molecular chaperones in the A. ferrooxidans heat shock response. In addition, the three sHSPs from A. ferrooxidans are not recent paralogs, and the Afe_1437 and Afe_1009 genes could be inherited horizontally by A. ferrooxidans.
Differential expression of cysteine desulfurases in soybean
Authors: Heis Marta D , Ditmer Elisabeth M , de Oliveira Luisa A , Frazzon Ana Paula G , Margis Rogério , Frazzon Jeverson 
Published: December 2011

Abstract

Background
Iron-sulfur [Fe-S] clusters are prosthetic groups required to sustain fundamental life processes including electron transfer, metabolic reactions, sensing, signaling, gene regulation and stabilization of protein structures. In plants, the biogenesis of Fe-S protein is compartmentalized and adapted to specific needs of the cell. Many environmental factors affect plant development and limit productivity and geographical distribution. The impact of these limiting factors is particularly relevant for major crops, such as soybean, which has worldwide economic importance.

Results
Here we analyze the transcriptional profile of the soybean cysteine desulfurases NFS1, NFS2 and ISD11 genes, involved in the biogenesis of [Fe-S] clusters, by quantitative RT-PCR. NFS1, ISD11 and NFS2 encoding two mitochondrial and one plastid located proteins, respectively, are duplicated and showed distinct transcript levels considering tissue and stress response. NFS1 and ISD11 are highly expressed in roots, whereas NFS2 showed no differential expression in tissues. Cold-treated plants showed a decrease in NFS2 and ISD11 transcript levels in roots, and an increased expression of NFS1 and ISD11 genes in leaves. Plants treated with salicylic acid exhibited increased NFS1 transcript levels in roots but lower levels in leaves. In silico analysis of promoter regions indicated the presence of different cis-elements in cysteine desulfurase genes, in good agreement with differential expression of each locus. Our data also showed that increasing of transcript levels of mitochondrial genes, NFS1/ISD11, are associated with higher activities of aldehyde oxidase and xanthine dehydrogenase, two cytosolic Fe-S proteins.

Conclusions
Our results suggest a relationship between gene expression pattern, biochemical effects, and transcription factor binding sites in promoter regions of cysteine desulfurase genes. Moreover, data show proportionality between NFS1 and ISD11 genes expression.
The HOPE fixation technique - a promising alternative to common prostate cancer biobanking approaches
Authors: Braun Martin , Menon Roopika , Nikolov Pavel , Kirsten Robert , Petersen Karen , Schilling David , Schott Christina , Gündisch Sibylle , Fend Falko , Becker Karl-Friedrich , Perner Sven 
Published: December 2011

Abstract

Background
The availability of well-annotated prostate tissue samples through biobanks is key for research. Whereas fresh-frozen tissue is well suited for a broad spectrum of molecular analyses, its storage and handling is complex and cost-intensive. Formalin-fixed paraffin-embedded specimens (FFPE) are easy to handle and economic to store, but their applicability for molecular methods is restricted. The recently introduced Hepes-glutamic acid-buffer mediated Organic solvent Protection Effect (HOPE) is a promising alternative, which might have the potential to unite the benefits of FFPE and fresh-frozen specimen. Aim of the study was to compare HOPE-fixed, FFPE and fresh-frozen bio-specimens for their accessibility for diagnostic and research purposes.

Methods
10 prostate cancer samples were each preserved with HOPE, formalin, and liquid nitrogen and studied with in-situ and molecular methods. Samples were H&E stained, and assessed by immunohistochemistry (i.e. PSA, GOLPH2, p63) and FISH (i.e. ERG rearrangement). We assessed DNA integrity by PCR, using control genes ranging from 100 to 600 bp amplicon size. RNA integrity was assessed through qRT-PCR on three housekeeping genes (TBP, GAPDH, β-actin). Protein expression was analysed by performing western blot analysis using GOLPH2 and PSA antibodies.

Results
Of the HOPE samples, morphologic quality of H&E sections, immunohistochemical staining, and the FISH assay was at least equal to FFPE tissue, and significantly better than the fresh-frozen specimens. DNA, RNA, and protein analysis of HOPE samples provided similar results as compared to fresh-frozen specimens. As expected, FFPE-samples were inferior for most of the molecular analyses.

Conclusions
This is the first study, comparatively assessing the suitability of these fixation methods for diagnostic and research utilization. Overall, HOPE-fixed bio-specimens combine the benefits of FFPE- and fresh-frozen samples. Results of this study have the potential to expand on contemporary prostate tissue biobanking approaches and can serve as a model for other organs and tumors.
General and specific components of depression and anxiety in an adolescent population
Authors: Brodbeck Jeannette , Abbott Rosemary A , Goodyer Ian M , Croudace Tim J 
Published: December 2011

Abstract

Background
Depressive and anxiety symptoms often co-occur resulting in a debate about common and distinct features of depression and anxiety.

Methods
An exploratory factor analysis (EFA) and a bifactor modelling approach were used to separate a general distress continuum from more specific sub-domains of depression and anxiety in an adolescent community sample (n = 1159, age 14). The Mood and Feelings Questionnaire and the Revised Children's Manifest Anxiety Scale were used.

Results
A three-factor confirmatory factor analysis is reported which identified a) mood and social-cognitive symptoms of depression, b) worrying symptoms, and c) somatic and information-processing symptoms as distinct yet closely related constructs. Subsequent bifactor modelling supported a general distress factor which accounted for the communality of the depression and anxiety items. Specific factors for hopelessness-suicidal thoughts and restlessness-fatigue indicated distinct psychopathological constructs which account for unique information over and above the general distress factor. The general distress factor and the hopelessness-suicidal factor were more severe in females but the restlessness-fatigue factor worse in males. Measurement precision of the general distress factor was higher and spanned a wider range of the population than any of the three first-order factors.

Conclusions
The general distress factor provides the most reliable target for epidemiological analysis but specific factors may help to refine valid phenotype dimensions for aetiological research and assist in prognostic modelling of future psychiatric episodes.
Very high vitamin D supplementation rates among infants aged 2 months in Vancouver and Richmond, British Columbia, Canada
Authors: Crocker Barbara , Green Tim J , Barr Susan I , Beckingham Bridgid , Bhagat Radhika , Dabrowska Beata , Douthwaite Rachel , Evanson Carmen , Friesen Russell , Hydamaka Kathy , Li Wangyang , Simmons Kelly , Tse Lillian 
Published: December 2011

Abstract

Background
Vitamin D deficiency during infancy may lead to rickets and possibly other poor health outcomes. The World Health Organization recommends exclusive breastfeeding for the first 6 months. Breast milk is the best food for infants but does not contain adequate vitamin D. Health Canada recommends all breastfed infants receive a daily vitamin D supplement of 400 IU; however, there appears to be limited current Canadian data as to whether parents or caregivers are following this advice. The aim of this study was to determine the rates of vitamin D supplementation among 2-month old infants in Vancouver and Richmond, British Columbia, Canada.

Methods
Mothers of all healthy infants born between April and May 2010 were approached to participate. Telephone surveys were conducted with 577 mothers (response rate 56%) when their infants turned 2 months.

Results
Over half of the infants received only breast milk in the week prior to the survey. One third received a mixture of breast milk and infant formula and 10% received only formula. About 80% of the infants were supplemented with vitamin D at 2 months. Infants who received only breast milk were most likely to be supplemented with vitamin D (91%). Over 60% of the infants had a total vitamin D intake of 300- < 500 IU/d from supplements and formula and only 5% did not receive any vitamin D. Most parents were advised to give vitamin D supplement by health professionals, such as public health nurses, midwives, and doctors.

Conclusions
About 90% of the infants received breast milk at 2 months of age. The vitamin D supplementation rate was 80%. Future studies are needed to monitor breastfeeding duration and vitamin D supplementation rates as infants get older.
Predictors and outcome of surgical repair of obstetric fistula at a regional referral hospital, Mbarara, western Uganda
Authors: Kayondo Musa , Wasswa Ssalongo , Kabakyenga Jerome , Mukiibi Nozmo , Senkungu Jude , Stenson Amy , Mukasa Peter 
Published: December 2011

Abstract

Background
Obstetric fistula although virtually eliminated in high income countries, still remains a prevalent and debilitating condition in many parts of the developing world. It occurs in areas where access to care at childbirth is limited, or of poor quality and where few hospitals offer the necessary corrective surgery.

Methods
This was a prospective observational study where all women who attended Mbarara Regional Referral Hospital in western Uganda with obstetric fistula during the study period were assessed pre-operatively for social demographics, fistula characteristics, classification and outcomes after surgery. Assessment for fistula closure and stress incontinence after surgery was done using a dye test before discharge

Results
Of the 77 women who were recruited in this study, 60 (77.9%) had successful closure of their fistulae. Unsuccessful fistula closure was significantly associated with large fistula size (Odds Ratio 6 95% Confidential interval 1.46-24.63), circumferential fistulae (Odds ratio 9.33 95% Confidential interval 2.23-39.12) and moderate to severe vaginal scarring (Odds ratio 12.24 95% Confidential interval 1.52-98.30). Vaginal scarring was the only factor independently associated with unsuccessful fistula repair (Odds ratio 10 95% confidential interval 1.12-100.57). Residual stress incontinence after successful fistula closure was associated with type IIb fistulae (Odds ratio 5.56 95% Confidential interval 1.34-23.02), circumferential fistulae (Odds ratio 10.5 95% Confidential interval 1.39-79.13) and previous unsuccessful fistula repair (Odds ratio 4.8 95% Confidential interval 1.27-18.11). Independent predictors for residual stress incontinence after successful fistula closure were urethral involvement (Odds Ratio 4.024 95% Confidential interval 2.77-5.83) and previous unsuccessful fistula repair (Odds ratio 38.69 95% Confidential interval 2.13-703.88).

Conclusions
This study demonstrated that large fistula size, circumferential fistulae and marked vaginal scarring are predictors for unsuccessful fistula repair while predictors for residual stress incontinence after successful fistula closure were urethral involvement, circumferential fistulae and previous unsuccessful fistula repair.
Choroidal metastases in testicular choriocarcinoma, successful treatment with chemo- and radiotherapy: a case report
Authors: Guber Ivo , Zografos Leonidas , Schalenbourg Ann 
Published: December 2011

Abstract

Background
Choriocarcinoma is a very rare cause of ocular metastasis. Only 18 male patients have been reported on, 4 of whom survived, but with significant loss of vision.

Case presentation
A 26-year-old Caucasian man, suffering from testicular choriocarcinoma with pulmonary, cerebral, renal, hepatic and osseous metastases, underwent left radical orchiectomy. While being treated with chemotherapy, he presented with loss of vision in the left eye. Ophthalmoscopy revealed bilateral non-pigmented, hemorrhagic choroidal tumours, compatible with secondary lesions. Continued chemotherapy and stereotactic radiotherapy of the skull and spine lead to full remission with excellent vision, after more than 4 years of follow up.

Conclusion
Testicular choriocarcinoma is an exceptional cause of choroidal metastasis, potentially asymptomatic and with specific clinical features. Radiotherapy can complement radical orchiectomy and chemotherapy, to achieve full remission and maintain good vision.