bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of JAK2V617F mutation status, allele burden, and clearance after allogeneic stem cell transplantation for myelofibrosis
Authors: Alchalby Haefaa , Badbaran Anita , Zabelina Tatjana , Kobbe Guido , Hahn Joachim , Wolff Daniel , Bornhäuser Martin , Thiede Christian , Baurmann Herrad , Bethge Wolfgang , Hildebrandt York , Bacher Ulrike , Fehse Boris , Zander Axel R. , Kröger Nicolaus 
Published: May 2010

Abstract
Allogeneic stem cell transplantation (ASCT) after reduced-intensity conditioning has become a reasonable treatment option for patients with advanced myelofibrosis. The role of characteristic molecular genetic abnormalities, such as JAK2V617F on outcome of ASCT, is not yet elucidated. In 139 of 162 myelofibrosis patients with known JAK2V617F mutation status who received ASCT after reduced-intensity conditioning, the impact of JAK2 genotype, JAK2V617F allele burden, and clearance of mutation after ASCT was evaluated. Overall survival was significantly reduced in multivariate analysis in patients harboring JAK2 wild-type (hazard ratio = 2.14, P = .01) compared with JAK2 mutated patients. No significant influence on outcome was noted for the mutated allele burden analyzed either as continuous variable or after dividing into quartiles. Achievement of JAK2V617F negativity after ASCT was significantly associated with a decreased incidence of relapse (hazard ratio = 0.22, P = .04). In a landmark analysis, patients who cleared JAK2 mutation level in peripheral blood 6 months after ASCT had a significant lower risk of relapse (5% vs 35%, P = .03). We conclude that JAK2V617F-mutated status, but not allele frequency, resulted in an improved survival and rapid clearance after allografting reduces the risk of relapse.
Impact of optimal follow-up of monoclonal gammopathy of undetermined significance on early diagnosis and prevention of myeloma-related complications
Authors: Bianchi Giada , Kyle Robert A. , Colby Colin L. , Larson Dirk R. , Kumar Shaji , Katzmann Jerry A. , Dispenzieri Angela , Therneau Terry M. , Cerhan James R. , Melton L. Joseph , Rajkumar S. Vincent 
Published: May 2010

Abstract
Monoclonal gammopathy of undetermined significance (MGUS) is associated with a long-term risk of progression to multiple myeloma (MM) or related malignancy. To prevent serious myeloma-related complications, lifelong annual follow-up has been recommended, but its value is unknown. We reviewed all patients from southeastern Minnesota seen at Mayo Clinic between 1973 and 2004 with MGUS who subsequently progressed to MM. Of 116 patients, 69% had optimal follow-up of MGUS. Among these, abnormalities on serial follow-up laboratory testing led to the diagnosis of MM in 16%, whereas MM was diagnosed only after serious MM-related complications in 45%. In the remaining, workup of less serious symptoms (25%), incidental finding during workup of unrelated medical conditions (11%), and unknown (3%) were the mechanisms leading to MM diagnosis. High-risk MGUS patients (≥ 1.5 g/dL and/or non-IgG MGUS) were more likely to be optimally followed (81% vs 64%), and be diagnosed with MM secondary to serial follow-up testing (21% vs 7%). This retrospective study suggests that routine annual follow-up of MGUS may not be required in low-risk MGUS. Future studies are needed to replicate and expand our findings and to determine the optimal frequency of monitoring in higher-risk MGUS patients.
Genome-wide expression links the electron transfer pathway of Shewanella oneidensis to chemotaxis
Authors: Tai Shang-Kai , Wu Guanl , Yuan Shinsheng , Li Ker-Chau 
Published: May 2010

Abstract

Background
By coupling the oxidation of organic substrates to a broad range of terminal electron acceptors (such as nitrate, metals and radionuclides), Shewanella oneidensis MR-1 has the ability to produce current in microbial fuel cells (MFCs). omcA, mtrA, omcB (also known as mtrC), mtrB, and gspF are some known genes of S. oneidensis MR-1 that participate in the process of electron transfer. How does the cell coordinate the expression of these genes? To shed light on this problem, we obtain the gene expression datasets of MR-1 that are recently public-accessible in Gene Expression Omnibus. We utilize the novel statistical method, liquid association (LA), to investigate the complex pattern of gene regulation.

Results
Through a web of information obtained by our data analysis, a network of transcriptional regulatory relationship between chemotaxis and electron transfer pathways is revealed, highlighting the important roles of the chemotaxis gene cheA-1, the magnesium transporter gene mgtE-1, and a triheme c-type cytochrome gene SO4572.

Conclusion
We found previously unknown relationship between chemotaxis and electron transfer using LA system. The study has the potential of helping researchers to overcome the intrinsic metabolic limitation of the microorganisms for improving power density output of an MFC.
Drain tube migration into the anastomotic site of an esophagojejunostomy for gastric small cell carcinoma: short report
Authors: Lai Peng-Sheng , Lo Chiao , Lin Long-Wei , Lee Po-Chu 
Published: May 2010

Abstract

Background
Intraluminal migration of a drain through an anastomotic site is a rare complication of gastric surgery.

Case Presentation
We herein report the intraluminal migration of a drain placed after a lower esophagectomy and total gastrectomy with Roux-en-Y anastomosis for gastric small cell carcinoma. Persistent drainage was noted 1 month after surgery, and radiographic studies were consistent with drain tube migration. Endoscopy revealed the drain had migrated into the esophagojejunostomy anastomotic site. The drain was removed from outside of abdominal wound while observing the anastomotic site endoscopically. The patient was treated with suction via a nasogastric tube drain for 5 days, and thereafter had an uneventful recovery.

Conclusions
Though drain tube migration is a rare occurrence, it should be considered in patients with persistent drainage who have undergone gastric surgery.
The sensitivity of real-time PCR amplification targeting invasive Salmonellaserovars in biological specimens
Authors: Nga Tran Vu Thieu , Karkey Abhilasha , Dongol Sabina , Thuy Hang Nguyen , Dunstan Sarah , Holt Kathryn , Tu Le Thi Phuong , Campbell James I , Chau Tran Thuy , Chau Nguyen Van Vinh , Arjyal Amit , Koirala Samir , Basnyat Buddha , Dolecek Christiane , Farrar Jeremy , Baker Stephen 
Published: May 2010

Abstract

Background
PCR amplification for the detection of pathogens in biological material is generally considered a rapid and informative diagnostic technique. Invasive Salmonella serovars, which cause enteric fever, can be commonly cultured from the blood of infected patients. Yet, the isolation of invasive Salmonella serovars from blood is protracted and potentially insensitive.

Methods
We developed and optimised a novel multiplex three colour real-time PCR assay to detect specific target sequences in the genomes of Salmonella serovars Typhi and Paratyphi A. We performed the assay on DNA extracted from blood and bone marrow samples from culture positive and negative enteric fever patients.

Results
The assay was validated and demonstrated a high level of specificity and reproducibility under experimental conditions. All bone marrow samples tested positive for Salmonella, however, the sensitivity on blood samples was limited. The assay demonstrated an overall specificity of 100% (75/75) and sensitivity of 53.9% (69/128) on all biological samples. We then tested the PCR detection limit by performing bacterial counts after inoculation into blood culture bottles.

Conclusions
Our findings corroborate previous clinical findings, whereby the bacterial load of S. Typhi in peripheral blood is low, often below detection by culture and, consequently, below detection by PCR. Whilst the assay may be utilised for environmental sampling or on differing biological samples, our data suggest that PCR performed directly on blood samples may be an unsuitable methodology and a potentially unachievable target for the routine diagnosis of enteric fever.
Is lymphadenectomy a prognostic marker in endometrioid adenocarcinoma of the human endometrium?
Authors: Bassarak Nina , Blankenstein Thomas , Brüning Ansgar , Dian Darius , Bergauer Florian , Friese Klaus , Mylonas Ioannis 
Published: May 2010

AbstractBackgroundDuring surgery for endometrial cancer, a pelvic lymphadenectomy with or without para-aortic lymphadenectomy is performed at least in patients with risk factors (stage I, grading 2 and/or histological subtypes with higher risk of lymphatic spread), and is hence recommended by the International Federation of Obstetrics and Gynecology (FIGO). Although lymph node metastases are important prognostic parameters, it has been contentious whether a pelvic lymph node dissection itself has a prognostic impact in the treatment of endometrial cancer, especially in endometrioid adenocarcinoma. Therefore, this study evaluated whether lymphadenectomy has a prognostic impact in patients with endometrioid adenocarcinoma.MethodsThe benefits of lymphadenectomy were examined in 214 patients with a histological diagnosis of endometrial adenocarcinoma. Tumour characteristics were analysed with respect to the surgical and pathological stage.ResultsOf the 214 patients with endometrial adenocarcinoma, 171 (79.9%) were classified as FIGO stage I, 15 (7.0%) FIGO stage II, 21 (9.8%) FIGO stage III and 7 (3.3%) FIGO stage IV. One hundred and thirty four (62.6%) of the patients had a histological grade 1 tumour, while 56 (26.2%) and 24 (11.2%) had a histological grade 2 or grade 3 tumour, respectively. Lymphadenectomy was performed in 151 (70.6%) patients. Only 11 (5.1%) patients showed metastatic disease in the lymph nodes. The performance of a lymphadenectomy resulted in significantly increased cause-specific and overall survival, while progression-free survival was not affected by this operative procedure.ConclusionsThe performance of an operative lymphadenectomy resulted in better survival of patients with endometrioid adenocarcinoma. This increase was significant for cause-specific and overall survival, while there was a tendency only towards increased progression-free survival. Therefore, even in endometrioid adenocarcinoma, a pelvic and/or para-aortic lymphadenectomy should be performed.
Quantitative evaluation of yeast's requirement for glycerol formation in very high ethanol performance fed-batch process
Authors: Pagliardini Julien , Hubmann Georg , Bideaux Carine , Alfenore Sandrine , Nevoigt Elke , Guillouet Stéphane E 
Published: May 2010

Abstract

Background
Glycerol is the major by-product accounting for up to 5% of the carbon in Saccharomyces cerevisiae ethanolic fermentation. Decreasing glycerol formation may redirect part of the carbon toward ethanol production. However, abolishment of glycerol formation strongly affects yeast's robustness towards different types of stress occurring in an industrial process. In order to assess whether glycerol production can be reduced to a certain extent without jeopardising growth and stress tolerance, the yeast's capacity to synthesize glycerol was adjusted by fine-tuning the activity of the rate-controlling enzyme glycerol 3-phosphate dehydrogenase (GPDH). Two engineered strains whose specific GPDH activity was significantly reduced by two different degrees were comprehensively characterized in a previously developed Very High Ethanol Performance (VHEP) fed-batch process.

Results
The prototrophic strain CEN.PK113-7D was chosen for decreasing glycerol formation capacity. The fine-tuned reduction of specific GPDH activity was achieved by replacing the native GPD1 promoter in the yeast genome by previously generated well-characterized TEF promoter mutant versions in a gpd2 Δ background. Two TEF promoter mutant versions were selected for this study, resulting in a residual GPDH activity of 55 and 6%, respectively. The corresponding strains were referred to here as TEFmut7 and TEFmut2. The genetic modifications were accompanied to a strong reduction in glycerol yield on glucose; the level of reduction compared to the wild-type was 61% in TEFmut7 and 88% in TEFmut2. The overall ethanol production yield on glucose was improved from 0.43 g g-1 in the wild type to 0.44 g g-1 measured in TEFmut7 and 0.45 g g-1 in TEFmut2. Although maximal growth rate in the engineered strains was reduced by 20 and 30%, for TEFmut7 and TEFmut2 respectively, strains' ethanol stress robustness was hardly affected; i.e. values for final ethanol concentration (117 ± 4 g L-1), growth-inhibiting ethanol concentration (87 ± 3 g L-1) and volumetric ethanol productivity (2.1 ± 0.15 g l-1 h-1) measured in wild-type remained virtually unchanged in the engineered strains.

Conclusions
This work demonstrates the power of fine-tuned pathway engineering, particularly when a compromise has to be found between high product yield on one hand and acceptable growth, productivity and stress resistance on the other hand. Under the conditions used in this study (VHEP fed-batch), the two strains with "fine-tuned" GPD1 expression in a gpd2 Δ background showed slightly better ethanol yield improvement than previously achieved with the single deletion strains gpd1 Δ or gpd2 Δ. Although glycerol reduction is known to be even higher in a gpd1 Δ gpd2 Δ double deletion strain, our strains could much better cope with process stress as reflected by better growth and viability.
Production and purification of staphylococcal nuclease in Lactococcus lactis using a new expression-secretion system and a pH-regulated mini-reactor
Authors: Trémillon Nicolas , Issaly Nicolas , Mozo Julien , Duvignau Thomas , Ginisty Hervé , Devic Eric , Poquet Isabelle 
Published: May 2010

Abstract

Background
Staphylococcal (or micrococcal) nuclease or thermonuclease (SNase or Nuc) is a naturally-secreted nucleic acid degrading enzyme that participates in Staphylococcus aureus spread in the infected host. Purified Nuc protein can be used as an exogenous reagent to clear cellular extracts and improve protein purification. Here, a recombinant form of Nuc was produced and secreted in a Gram-positive host, Lactococcus lactis, and purified from the culture medium.

Results
The gene segment corresponding to the S. aureus nuclease without its signal peptide was cloned in an expression-secretion vector. It was then fused to a lactococcal sequence encoding a signal peptide, and expressed under the control of a lactococcal promoter that is inducible by zinc starvation. An L. lactis subsp cremoris model strain (MG1363) transformed with the resulting plasmid was grown in either of two media (GM17v and CDM) that are free of animal compounds, allowing GMP (Good Manufacturing Practice) production. Induction conditions (concentration of the metal chelator EDTA and timing of addition) in small-scale pH-regulated fermentors were optimized using LacMF (Lactis Multi-Fermentor), a home-made parallel fermentation control system able to monitor 12 reactors simultaneously. Large amounts of recombinant Nuc (rNuc) were produced and secreted in both media, and rNuc was purified from GM17v medium in a single-step procedure.

Conclusions
In L. lactis, rNuc production and secretion were optimal after induction by 0.5 mM EDTA in small scale (200 mL) GM17v exponential phase cultures (at an OD600 of 2), leading to a maximal protein yield of 210 mg per L of culture medium. Purified rNuc was highly active, displaying a specific activity of 2000 U/mg.
The normal breast microenvironment of premenopausal women differentially influences the behavior of breast cancer cells in vitro and in vivo
Authors: Fleming Jodie M , Miller Tyler C , Quinones Mariam , Xiao Zhen , Xu Xia , Meyer Matthew J , Ginsburg Erika , Veenstra Timothy D , Vonderhaar Barbara K 
Published: May 2010

Abstract

Background
Breast cancer studies frequently focus on the role of the tumor microenvironment in the promotion of cancer; however, the influence of the normal breast microenvironment on cancer cells remains relatively unknown. To investigate the role of the normal breast microenvironment on breast cancer cell tumorigenicity, we examined whether extracellular matrix molecules (ECM) derived from premenopausal African-American (AA) or Caucasian-American (CAU) breast tissue would affect the tumorigenicity of cancer cells in vitro and in vivo. We chose these two populations because of the well documented predisposition of AA women to develop aggressive, highly metastatic breast cancer compared to CAU women.

Methods
The effects of primary breast fibroblasts on tumorigenicity were analyzed via real-time PCR arrays and mouse xenograft models. Whole breast ECM was isolated, analyzed via zymography, and its effects on breast cancer cell aggressiveness were tested in vitro via soft agar and invasion assays, and in vivo via xenograft models. Breast ECM and hormone metabolites were analyzed via mass spectrometry.

Results
Mouse mammary glands humanized with premenopausal CAU fibroblasts and injected with primary breast cancer cells developed significantly larger tumors compared to AA humanized glands. Examination of 164 ECM molecules and cytokines from CAU-derived fibroblasts demonstrated a differentially regulated set of ECM proteins and increased cytokine expression. Whole breast ECM was isolated; invasion and soft agar assays demonstrated that estrogen receptor (ER)-, progesterone receptor (PR)/PR- cells were significantly more aggressive when in contact with AA ECM, as were ER+/PR+ cells with CAU ECM. Using zymography, protease activity was comparatively upregulated in CAU ECM. In xenograft models, CAU ECM significantly increased the tumorigenicity of ER+/PR+ cells and enhanced metastases. Mass spectrometry analysis of ECM proteins showed that only 1,759 of approximately 8,000 identified were in common. In the AA dataset, proteins associated with breast cancer were primarily related to tumorigenesis/neoplasia, while CAU unique proteins were involved with growth/metastasis. Using a novel mass spectrometry method, 17 biologically active hormones were measured; estradiol, estriol and 2-methoxyestrone were significantly higher in CAU breast tissue.

Conclusions
This study details normal premenopausal breast tissue composition, delineates potential mechanisms for breast cancer development, and provides data for further investigation into the role of the microenvironment in cancer disparities.
Taking Action Together: A YMCA-based protocol to prevent Type-2 Diabetes in high-BMI inner-city African American children
Authors: Ritchie Lorrene D , Sharma Sushma , Ikeda Joanne P , Mitchell Rita A , Raman Aarthi , Green Barbara S , Hudes Mark L , Fleming Sharon E 
Published: May 2010

Abstract

Background
Associated with a tripling in obesity since 1970, type 2 diabetes mellitus (T2DM) in children has risen 9-10 fold. There is a critical need of protocols for trials to prevent T2DM in children.

Methods/Design
This protocol includes the theory, development, evaluation components and lessons learned from a novel YMCA-based T2DM prevention intervention designed specifically for high-BMI African American children from disadvantaged, inner-city neighborhoods of Oakland, California. The intervention was developed on the basis of: review of epidemiological and intervention studies of pediatric T2DM; a conceptual theory (social cognitive); a comprehensive examination of health promotion curricula designed for children; consultation with research, clinical experts and practitioners and; input from community partners. The intervention, Taking Action Together, included culturally sensitive and age-appropriate programming on: healthy eating; increasing physical activity and, improving self esteem.

Discussion
Evaluations completed to date suggest that Taking Action Together may be an effective intervention, and results warrant an expanded evaluation effort. This protocol could be used in other community settings to reduce the risk of children developing T2DM and related health consequences.

Trial registration
ClinicalTrials.gov NCT01039116.
National Betrayal: Language, Location, and Lesbianism in August Strindberg'sLe Plaidoyer D'un Fou
Authors: Stenport Anna Westerståhl 
Published: May 2010

Written in Denmark in French in 1887–88, Swedish author August Strindberg's novel A Madman's Defense (Le Plaidoyer d'un fou) was first published in an 1893 German translation and subsequently released in a manicured French version in 1895. The German version was taken to court on indecency charges in Vilhelmine Berlin, the French version became a scandal, and Strindberg never authorized the novel for publication in Sweden.Although A Madman's Defense helped cement Strindberg's reputation at home and abroad as a paranoid misogynist, it also provides a complementary trajectory for understanding the emergence of European transnational prose modernism. In its conception, publication, and reception, A Madman's Defense straddles both national and linguistic borders; its plot involves travel trajectories that link Sweden with the continent, and Stockholm with Paris. This novel tells a story of adultery, divorce, and lesbian desire, while tracing, through a first-person voice, the narrator's professed descent into madness. One thematic emphasis links transgressions of public and private with specific architectural manifestations. This article traces these architectural manifestations and argues that, as the narrator appears increasingly irrational, boundaries of nation, of public and private, and of gendered conventions disintegrate in ways that illustrate how literary setting becomes a vehicle of modernist literary experimentation. The article discusses specific locations through which this transformation is effected, including a bourgeois apartment, a railway station, a library, and a tourist boarding house. It also links Strindberg's writing about divorce and lesbian desire with nineteenth-century French literary texts, including those of the 1880s, and with Henrik Ibsen's plays and legacy in Paris during the 1880s and 1890s.
Newborn Screening of Lysosomal Storage Disorders
Authors: Marsden Deborah , Levy Harvey 
Published: May 2010

AbstractBackground: Newborn screening is a state-based public health program established as a means for the early detection and treatment of certain medical conditions to minimize developmental disability and mortality. The program was initiated more than 40 years ago to detect and prevent phenylketonuria. Recent technological advances have expanded the scope of newborn screening to include more than 30 inborn errors of metabolism. Consideration is now being given to inclusion of screening for lysosomal storage disorders (LSDs).Content: Some lysosomal storage disorders (LSDs) express early in infancy or childhood and are treatable. Initiation of treatment in presymptomatic patients or in syptomatic patients before important symptoms are present may improve the long-term outcome. Therefore, early diagnosis is critical. Based on the availability of therapy and development of a screening method, 6 of the more than 40 known LSDs are candidates for newborn screening in the US: Gaucher disease, Pompe disease, Fabry disease, Niemann-Pick disease, mucopolysaccharidosis I, and Krabbe disease. This report reviews the history of newborn screening, the technology that has allowed for expanded screening during the last decade, LSDs and their treatment, and the evolving methods that might allow additional expansion of newborn screening to include certain LSDs.Summary: Recent and evolving technological advances may be implemented for newborn screening for LSDs. This screening will identify presymptomatic newborns, allowing for early treatment and prevention or limitation of morbidity otherwise associated with these inherited rare diseases.