bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene expression profiling of plasma cells at myeloma relapse from tandem transplantation trial Total Therapy 2 predicts subsequent survival
Authors: Nair Bijay , Shaughnessy John D. , Zhou Yiming , Astrid-Cartron Marie , Qu Pingping , van Rhee Frits , Anaissie Elias , Alsayed Yazan , Waheed Sarah , Hollmig Klaus , Szymonifka Jackie , Petty Nathan , Hoering Antje , Barlogie Bart 
Published: April 2009

AbstractWe report on prognostic implications for postrelapse survival (PRS) of a gene expression profiling (GEP)–defined risk score at relapse available in 120 myeloma patients previously enrolled in tandem transplantation trial Total Therapy 2. Among the 71 patients with additional GEP baseline information, 3-year PRS was 71% in 40 patients with low risk present both at baseline and relapse contrasting with only 17% in 28 patients with high risk at relapse, 12 of whom with baseline low-risk status fared better than the remainder (P = .08). On multivariate analysis of relapse parameters available in 104 patients, high risk conferred short PRS (hazard ratio = 4.00, P < .001, R2 = 33%), whereas relapse hyperdiploidy predicted long PRS (hazard ratio = 0.37, P = .022, cumulative R2 = 41%). In case the initial partial response lasted less than 2 years, relapse low-risk identified 26 patients with superior 3-year PRS of 61% versus 9% among 32 with relapse high-risk (P < .001). Based on its PRS predictive power, GEP analysis should be an integral part of new agent trials in search of better therapy for high-risk myeloma.
Compassionate use of sorafenib in FLT3-ITD–positive acute myeloid leukemia: sustained regression before and after allogeneic stem cell transplantation
Authors: Metzelder Stephan , Wang Ying , Wollmer Ellen , Wanzel Michael , Teichler Sabine , Chaturvedi Anuhar , Eilers Martin , Enghofer Erich , Neubauer Andreas , Burchert Andreas 
Published: April 2009

Abstract
Acute myeloid leukemia (AML) patients with internal tandem duplication (ITD) mutations in the Fms-like tyrosine-3 (FLT3) gene have a dismal prognosis. Here we report compassionate-use results with the multikinase and FLT3-ITD inhibitor sorafenib for the treatment of relapsed or refractory FLT3-ITD–positive AML. Sorafenib induced clinically meaningful and very rapid responses in all 6 patients treated either before (n = 2), after (n = 3), or both before and after (n = 1) allogeneic stem cell transplantation (allo-SCT). Sorafenib-induced remissions facilitated allo-SCT in 2 of the 3 refractory patients. Two of the 4 patients who were treated after allo-SCT survived 216 and 221 days, respectively, whereas the other 2 remain in ongoing complete molecular remission. Sorafenib response was associated with an inhibition of the antiapoptotic FLT3-ITD target Stat-5 in vivo. Together, sorafenib monotherapy before or after allo-SCT has remarkable clinical activity in poor risk FLT3-ITD–positive AML and deserves further evaluation in prospective clinical trials.
Exploring the functional interaction between POSH and ALIX and the relevance to HIV-1 release
Authors: Votteler Jörg , Iavnilovitch Elena , Fingrut Orit , Shemesh Vivian , Taglicht Daniel , Erez Omri , Sörgel Stefan , Walther Torsten , Bannert Norbert , Schubert Ulrich , Reiss Yuval 
Published: April 2009

Abstract

Background
The ALG2-interacting protein X (ALIX)/AIP1 is an adaptor protein with multiple functions in intracellular protein trafficking that plays a central role in the biogenesis of enveloped viruses. The ubiquitin E3-ligase POSH (plenty of SH3) augments HIV-1 egress by facilitating the transport of Gag to the cell membrane. Recently, it was reported, that POSH interacts with ALIX and thereby enhances ALIX mediated phenotypes in Drosophila.

Results
In this study we identified ALIX as a POSH ubiquitination substrate in human cells: POSH induces the ubiquitination of ALIX that is modified on several lysine residues in vivo and in vitro. This ubiquitination does not destabilize ALIX, suggesting a regulatory function. As it is well established that ALIX rescues virus release of L-domain mutant HIV-1, HIV-1ΔPTAP, we demonstrated that wild type POSH, but not an ubiquitination inactive RING finger mutant (POSHV14A), substantially enhances ALIX-mediated release of infectious virions derived from HIV-1ΔPTAP L-domain mutant (YPXnL-dependent HIV-1). In further agreement with the idea of a cooperative function of POSH and ALIX, mutating the YPXnL-ALIX binding site in Gag completely abrogated augmentation of virus release by overexpression of POSH. However, the effect of the POSH-mediated ubiquitination appears to be auxiliary, but not necessary, as silencing of POSH by RNAi does not disturb ALIX-augmentation of virus release.

Conclusion
Thus, the cumulative results identified ALIX as an ubiquitination substrate of POSH and indicate that POSH and ALIX cooperate to facilitate efficient virus release. However, while ALIX is obligatory for the release of YPXnL-dependent HIV-1, POSH, albeit rate-limiting, may be functionally interchangeable.
SNP HiTLink: a high-throughput linkage analysis system employing dense SNP data
Authors: Fukuda Yoko , Nakahara Yasuo , Date Hidetoshi , Takahashi Yuji , Goto Jun , Miyashita Akinori , Kuwano Ryozo , Adachi Hiroki , Nakamura Eiji , Tsuji Shoji 
Published: April 2009

Abstract

Background
During this recent decade, microarray-based single nucleotide polymorphism (SNP) data are becoming more widely used as markers for linkage analysis in the identification of loci for disease-associated genes. Although microarray-based SNP analyses have markedly reduced genotyping time and cost compared with microsatellite-based analyses, applying these enormous data to linkage analysis programs is a time-consuming step, thus, necessitating a high-throughput platform.

Results
We have developed SNP HiTLink (SNP
Hi gh T hroughput Link age analysis system). In this system, SNP chip data of the Affymetrix Mapping 100 k/500 k array set and Genome-Wide Human SNP array 5.0/6.0 can be directly imported and passed to parametric or model-free linkage analysis programs; MLINK, Superlink, Merlin and Allegro. Various marker-selecting functions are implemented to avoid the effect of typing-error data, markers in linkage equilibrium or to select informative data.

Conclusion
The results using the 100 k SNP dataset were comparable or even superior to those obtained from analyses using microsatellite markers in terms of LOD scores obtained. General personal computers are sufficient to execute the process, as runtime for whole-genome analysis was less than a few hours. This system can be widely applied to linkage analysis using microarray-based SNP data and with which one can expect high-throughput and reliable linkage analysis.
Transcriptional reprogramming of gene expression in bovine somatic cell chromatin transfer embryos
Authors: Rodriguez-Osorio Nelida , Wang Zhongde , Kasinathan Poothappillai , Page Grier P , Robl James M , Memili Erdogan 
Published: April 2009

Abstract

Background
Successful reprogramming of a somatic genome to produce a healthy clone by somatic cells nuclear transfer (SCNT) is a rare event and the mechanisms involved in this process are poorly defined. When serial or successive rounds of cloning are performed, blastocyst and full term development rates decline even further with the increasing rounds of cloning. Identifying the "cumulative errors" could reveal the epigenetic reprogramming blocks in animal cloning.

Results
Bovine clones from up to four generations of successive cloning were produced by chromatin transfer (CT). Using Affymetrix bovine microarrays we determined that the transcriptomes of blastocysts derived from the first and the fourth rounds of cloning (CT1 and CT4 respectively) have undergone an extensive reprogramming and were more similar to blastocysts derived from in vitro fertilization (IVF) than to the donor cells used for the first and the fourth rounds of chromatin transfer (DC1 and DC4 respectively). However a set of transcripts in the cloned embryos showed a misregulated pattern when compared to IVF embryos. Among the genes consistently upregulated in both CT groups compared to the IVF embryos were genes involved in regulation of cytoskeleton and cell shape. Among the genes consistently upregulated in IVF embryos compared to both CT groups were genes involved in chromatin remodelling and stress coping.

Conclusion
The present study provides a data set that could contribute in our understanding of epigenetic errors in somatic cell chromatin transfer. Identifying "cumulative errors" after serial cloning could reveal some of the epigenetic reprogramming blocks shedding light on the reprogramming process, important for both basic and applied research.
Evaluation of the effect of patient education on rates of falls in older hospital patients: Description of a randomised controlled trial
Authors: Hill Anne-Marie , Hill Keith , Brauer Sandra , Oliver David , Hoffmann Tammy , Beer Christopher , McPhail Steven , Haines Terry P 
Published: April 2009

AbstractBackgroundAccidental falls by older patients in hospital are one of the most commonly reported adverse events. Falls after discharge are also common. These falls have enormous physical, psychological and social consequences for older patients, including serious physical injury and reduced quality of life, and are also a source of substantial cost to health systems worldwide. There have been a limited number of randomised controlled trials, mainly using multifactorial interventions, aiming to prevent older people falling whilst inpatients. Trials to date have produced conflicting results and recent meta-analyses highlight that there is still insufficient evidence to clearly identify which interventions may reduce the rate of falls, and falls related injuries, in this population.Methods and designA prospective randomised controlled trial (n = 1206) is being conducted at two hospitals in Australia. Patients are eligible to be included in the trial if they are over 60 years of age and they, or their family or guardian, give written consent. Participants are randomised into three groups. The control group continues to receive usual care. Both intervention groups receive a specifically designed patient education intervention on minimising falls in addition to usual care. The education is delivered by Digital Video Disc (DVD) and written workbook and aims to promote falls prevention activities by participants. One of the intervention groups also receives follow up education training visits by a health professional. Blinded assessors conduct baseline and discharge assessments and follow up participants for 6 months after discharge. The primary outcome measure is falls by participants in hospital. Secondary outcome measures include falls at home after discharge, knowledge of falls prevention strategies and motivation to engage in falls prevention activities after discharge. All analyses will be based on intention to treat principle.DiscussionThis trial will examine the effect of a single intervention (specifically designed patient education) on rates of falls in older patients in hospital and after discharge. The results will provide robust recommendations for clinicians and researchers about the role of patient education in this population. The study has the potential to identify a new intervention that may reduce rates of falls in older hospital patients and could be readily duplicated and applied in a wide range of clinical settings.Trial RegistrationACTRN12608000015347
Dietary intake of folate, vitamin B6, and vitamin B12, genetic polymorphism of related enzymes, and risk of breast cancer: a case-control study in Brazilian women
Authors: Ma Enbo , Iwasaki Motoki , Junko Ishihara , Hamada Gerson Shigeaki , Nishimoto Ines Nobuko , Carvalho Solange Maria Torchia , Motola Juvenal , Laginha Fábio Martins , Tsugane Shoichiro 
Published: April 2009

AbstractBackgroundSeveral studies have determined that dietary intake of B vitamins may be associated with breast cancer risk as a result of interactions between5,10-methylenetetrahydrofolate reductase (MTHFR)andmethionine synthase(MTR) in the one-carbon metabolism pathway. However, the association between B vitamin intake and breast cancer risk in Brazilian women in particular has not yet been investigated.MethodsA case-control study was conducted in São Paulo, Brazil, with 458 age-matched pairs of Brazilian women. Energy-adjusted intakes of folate, vitamin B6, and vitamin B12were derived from a validated Food Frequency Questionnaire (FFQ). Genotyping was completed forMTHFRA1298C and C677T, andMTRA2756G polymorphisms. A logistical regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs).ResultsNeither dietary intake of folate, vitamin B6, or vitamin B12norMTHFRpolymorphisms were independently associated with breast cancer risk. Analysis stratified by menopausal status showed a significant association between placement in the highest tertile of folate intake and risk of breast cancer in premenopausal women (OR = 2.17, 95% CI: 1.23–3.83;Ptrend= 0.010). TheMTR2756GG genotype was associated with a higher risk of breast cancer than the 2756AA genotype (OR = 1.99, 95% CI = 1.01–3.92;Ptrend= 0.801), and statistically significant interactions with regard to risk were observed between theMTHFRA1298C polymorphism and folate (P = 0.024) or vitamin B6(P = 0.043), and between theMTHFRC677T polymorphism and folate (P = 0.043) or vitamin B12(P = 0.022).ConclusionMTHFRpolymorphisms and dietary intake of folate, vitamin B6, and vitamin B12had no overall association with breast cancer risk. However, increased risk was observed in total women with theMTR2756GG genotype and in premenopausal women with high folate intake. These findings, as well as significant interactions betweenMTHFRpolymorphisms and B vitamins, warrant further investigation.
Small local variations in B-form DNA lead to a large variety of global geometries which can accommodate most DNA-binding protein motifs
Authors: Marathe Arvind , Karandur Deepti , Bansal Manju 
Published: April 2009

Abstract

Background
An important question of biological relevance is the polymorphism of the double-helical DNA structure in its free form, and the changes that it undergoes upon protein-binding. We have analysed a database of free DNA crystal structures to assess the inherent variability of the free DNA structure and have compared it with a database of protein-bound DNA crystal structures to ascertain the protein-induced variations.

Results
Most of the dinucleotide steps in free DNA display high flexibility, assuming different conformations in a sequence-dependent fashion. With the exception of the AA/TT and GA/TC steps, which are 'A-phobic', and the GG/CC step, which is 'A-philic', the dinucleotide steps show no preference for A or B forms of DNA. Protein-bound DNA adopts the B-conformation most often. However, in certain cases, protein-binding causes the DNA backbone to take up energetically unfavourable conformations. At the gross structural level, several protein-bound DNA duplexes are observed to assume a curved conformation in the absence of any large distortions, indicating that a series of normal structural parameters at the dinucleotide and trinucleotide level, similar to the ones in free B-DNA, can give rise to curvature at the overall level.

Conclusion
The results illustrate that the free DNA molecule, even in the crystalline state, samples a large amount of conformational space, encompassing both the A and the B-forms, in the absence of any large ligands. A-form as well as some non-A, non-B, distorted geometries are observed for a small number of dinucleotide steps in DNA structures bound to the proteins belonging to a few specific families. However, for most of the bound DNA structures, across a wide variety of protein families, the average step parameters for various dinucleotide sequences as well as backbone torsion angles are observed to be quite close to the free 'B-like' DNA oligomer values, highlighting the flexibility and biological significance of this structural form.
Survey of doctors' opinions of the legalisation of physician assisted suicide
Authors: Lee William , Price Annabel , Rayner Lauren , Hotopf Matthew 
Published: April 2009

Abstract

Background
Assisted dying has wide support among the general population but there is evidence that those providing care for the dying may be less supportive. Senior doctors would be involved in implementing the proposed change in the law. We aimed to measure support for legalising physician assisted dying in a representative sample of senior doctors in England and Wales, and to assess any association between doctors' characteristics and level of support for a change in the law.

Methods
We conducted a postal survey of 1000 consultants and general practitioners randomly selected from a commercially available database. The main outcome of interest was level of agreement with any change in the law to allow physician assisted suicide.

Results
The corrected participation rate was 50%. We analysed 372 questionnaires. Respondents' views were divided: 39% were in favour of a change to the law to allow assisted suicide, 49% opposed a change and 12% neither agreed nor disagreed. Doctors who reported caring for the dying were less likely to support a change in the law. Religious belief was also associated with opposition. Gender, specialty and years in post had no significant effect.

Conclusion
More senior doctors in England and Wales oppose any step towards the legalisation of assisted dying than support this. Doctors who care for the dying were more opposed. This has implications for the ease of implementation of recently proposed legislation.
Evaluation of anti-IL-6 monoclonal antibody therapy using murine type II collagen-induced arthritis
Authors: Liang Bailin , Song Zheng , Wu Bin , Gardner Debra , Shealy David , Song Xiao-Yu , Wooley Paul H 
Published: April 2009

Abstract
Interleukin-6 is a multifunctional cytokine that is critical for T/B-cell differentiation and maturation, immunoglobulin secretion, acute-phase protein production, and macrophage/monocyte functions. Extensive research into the biology of IL-6 has implicated IL-6 in the pathophysiology and pathogenesis of RA. An anti-murine IL-6 mAb that neutralizes mouse IL-6 activities was tested in animal model of collagen-induced arthritis. Prophylactic treatment with anti-IL-6 mAb significantly reduced the incidence and severity of arthritis compared to control mAb treated mice. The mitogenic response of B and T cells isolated from the lymph nodes of anti-IL-6 treated mice was significantly reduced compared to cells isolated from control mAb treated mice. The overall histopathology score for paws from the anti-IL-6 treated mice was significantly reduced when compared to paws from mice treated with control mAb, including both inflammatory (synovitis and pannus) and erosive (erosions and architecture) parameters. Reduced loss of cartilage matrix components was also observed in the anti-IL-6 treated mice. Collectively, these data suggest that IL-6 plays a major role in the pathophysiology of rheumatoid arthritis, and thus support the potential benefit of anti-IL-6 mAb treatment in rheumatoid arthritis patients.
Synchronous infiltrating ductal carcinoma and primary extramedullary plasmacytoma of the breast
Authors: Cao Shui , Kang Hong-Gang , Liu Yan-Xue , Ren Xiu-Bao 
Published: April 2009

Abstract

Background
Extramedullary plasmacytomas are seldom solitary and usually progress to diffuse myelomatosis. Plasmacytomas of the breast are rare, especially when not associated multiple myeloma. Synchronous infiltrating ductal carcinoma and primary extramedullary plasmacytoma of the breast have not previously reported.

Case presentation
A 27-years-old woman with an untreated upper outer quadrant breast mass for 1-year was referred to our cancer hospital for surgical evaluation of increasing breast pain. Postoperatively, microscopic examination revealed an infiltrating ductal carcinoma complicated by an extramedullary plasmacytoma divided by fibrous tissue in one section. Following surgery, the patient received chemotherapy for the carcinoma and radiotherapy for the plasmacytoma.

Conclusion
In this case, careful histopathology examination was essential to make the correct diagnosis and therapy for these synchronous lesions. The patient finished chemotherapy and radiotherapy without significant adverse effects.
The roles of ASK family proteins in stress responses and diseases
Authors: Hattori Kazuki , Naguro Isao , Runchel Christopher , Ichijo Hidenori 
Published: April 2009

AbstractApoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein kinase kinase kinase family, which activates c-Jun N-terminal kinase and p38 in response to a diverse array of stresses such as oxidative stress, endoplasmic reticulum stress and calcium influx. In the past decade, various regulatory mechanisms of ASK1 have been elucidated, including its oxidative stress-dependent activation. Recently, it has emerged that ASK family proteins play key roles in cancer, cardiovascular diseases and neurodegenerative diseases. In this review, we summarize the recent findings on ASK family proteins and their implications in various diseases.
Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis
Authors: Riordan Neil H , Ichim Thomas E , Min Wei-Ping , Wang Hao , Solano Fabio , Lara Fabian , Alfaro Miguel , Rodriguez Jorge Paz , Harman Robert J , Patel Amit N , Murphy Michael P , Lee Roland R , Minev Boris 
Published: April 2009

Abstract
The stromal vascular fraction (SVF) of adipose tissue is known to contain mesenchymal stem cells (MSC), T regulatory cells, endothelial precursor cells, preadipocytes, as well as anti-inflammatory M2 macrophages. Safety of autologous adipose tissue implantation is supported by extensive use of this procedure in cosmetic surgery, as well as by ongoing studies using in vitro expanded adipose derived MSC. Equine and canine studies demonstrating anti-inflammatory and regenerative effects of non-expanded SVF cells have yielded promising results. Although non-expanded SVF cells have been used successfully in accelerating healing of Crohn's fistulas, to our knowledge clinical use of these cells for systemic immune modulation has not been reported. In this communication we discuss the rationale for use of autologous SVF in treatment of multiple sclerosis and describe our experiences with three patients. Based on this rationale and initial experiences, we propose controlled trials of autologous SVF in various inflammatory conditions.
The design and protocol of acupuncture for migraine prophylaxis: A multicenter randomized controlled trial
Authors: Zhang Yan , Wang Linpeng , Liu Huilin , Li Nan , Li Jingdao , Yi Jinghong 
Published: April 2009

AbstractBackgroundMany studies have already reported encouraging results in the prophylactic therapy of migraine by acupuncture, but there seems to be a lack of high quality randomized controlled trials from China. We design and perform a randomized controlled clinical trial to evaluate the efficacy of acupuncture compared with flunarizine in the prophylactic therapy of patients with migraine without aura in China.MethodsThis trial is a multicenter, prospective, randomized controlled clinical trial. The 140 migraine patients are randomly allocated to two different groups. The acupuncture groups (n = 70) is treated with acupuncture and placebo medicine; while the control group (n = 70) is treated with sham acupuncture and medicine (Flunarizine). Both Flunarizine and placebo are taken 10 mg once per night for the first 2 weeks and then 5 mg once per night for the next 2 weeks. Patients in both groups receive 12 sessions of verum/sham acupuncture in 4 weeks.DiscussionThe study design and the long term clinical practice of acupuncturists guarantee a high external validity for the results. The results of our trial will be helpful to supply the evidence on the efficacy of acupuncture for migraine prophylaxis in China.Trial RegistrationThe trial is registered at Controlled Clinical Trials: ISRCTN49839714.