bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-adjusted recipient pretransplantation telomere length and treatment-related mortality after hematopoietic stem cell transplantation
Authors: Peffault de Latour Régis , Calado Rodrigo T. , Busson Marc , Abrams Jeffrey , Adoui Nadir , Robin Marie , Larghero Jérôme , Dhedin Nathalie , Xhaard Alienor , Clave Emmanuel , Charron Dominique , Toubert Antoine , Loiseau Pascale , Socié Gérard , Young Neal S. 
Published: September 2012

Abstract
Telomere attrition induces cell senescence and apoptosis. We hypothesized that age-adjusted pretransplantation telomere length might predict treatment-related mortality (TRM) after hematopoietic stem cell transplantation (HSCT). Between 2000 and 2005, 178 consecutive patients underwent HSCT from HLA-identical sibling donors after myeloablative conditioning regimens, mainly for hematologic malignancies (n = 153). Blood lymphocytes' telomere length was measured by real-time quantitative PCR before HSCT. Age-adjusted pretransplantation telomere lengths were analyzed for correlation with clinical outcomes. After age adjustment, patients' telomere-length distribution was similar among all 4 quartiles except for disease stage. There was no correlation between telomere length and engraftment, GVHD, or relapse. The overall survival was 62% at 5 years (95% confidence interval [CI], 54-70). After a median follow-up of 51 months (range, 1-121 months), 43 patients died because of TRM. The TRM rate inversely correlated with telomere length. TRM in patients in the first (lowest telomere length) quartile was significantly higher than in patients with longer telomeres (P = .017). In multivariate analysis, recipients' age (hazard ratio, 1.1; 95% CI, .0-1.1; P = .0001) and age-adjusted telomere length (hazard ratio, 0.4; 95% CI; 0.2-0.8; P = .01) were independently associated with TRM. In conclusion, age-adjusted recipients' telomere length is an independent biologic marker of TRM after HSCT.
Regulation of plasmacytoid dendritic cell responses by PIR-B
Authors: Mitsuhashi Yoshiya , Nakamura Akira , Endo Shota , Takeda Kazuya , Yabe-Wada Toshiki , Nukiwa Toshihiro , Takai Toshiyuki 
Published: September 2012

Abstract
Plasmacytoid dendritic cells (PDCs) produce type I interferons (IFNs) in response to viral nucleic acids to exert antiviral immunity. However, PDCs are related to the progress and severity of autoimmune diseases, such as systemic lupus erythematosus, because they respond to host DNA. Therefore, the regulation of PDC activation is critical for maintaining adequate immune responses. Here we show that an inhibitory major histocompatibility complex class I receptor, paired immunoglobulin-like receptor B (PIR-B), suppressed Fms-like tyrosine kinase 3 ligand-induced PDC differentiation in BM cells, as well as Toll-like receptor 9-mediated IFN-α production by PDCs, through the dephosphorylation of STAT1/STAT2. In particular, PIR-B inhibited IFN-α–mediated STAT phosphorylation, suggesting that PIR-B negatively regulates the positive feedback mechanism of IFN-α secretion triggered by Toll-like receptor 9. These results demonstrate a novel regulatory role for PIR-B in PDCs.
Oestradiol ameliorates monocrotaline pulmonary hypertensionviaNO, prostacyclin and endothelin-1 pathways
Authors: Yuan Ping , Wu Wen-Hui , Gao Lan , Zheng Ze-Qi , Liu Dong , Mei Han-Ying , Zhang Zhuo-Li , Jing Zhi-Cheng 
Published: August 2012

Pulmonary hypertension continues to be a serious clinical problem with high mortality. As oestrogen is a potential vasodilator of the pulmonary circulation, this study examined the mechanisms by which 17β-oestradiol improves monocrotaline (MCT)-induced pulmonary hypertension.Female Sprague–Dawley rats underwent bilateral ovariectomy or sham operations. The rats received MCT (50 mg·kg−1) and were treated with 17β-oestradiol (1 mg·kg−1per day) for either 5 weeks or only from week 4 to week 5. Plasma 17β-oestradiol concentrations were decreased in sham-operated, MCT-treated rats when compared with sham-operated rats (17.7±4.7versus50.3±15.4 pg·mL−1; p=0.029). The 17β-oestradiol anabolic enzyme cytochrome P450 (CYP)-19 was decreased by MCT treatment, while the catabolic enzymes CYP-1A1 and -1B1 were increased. Ovariectomised and MCT-treated rats had more severe pulmonary hypertension. 17β-oestradiol suppressed pulmonary arterial smooth muscle cell proliferation and macrophage infiltration, and enhanced apoptosis by increasing nitric oxide (NO) and prostacyclin (prostaglandin (PG)I2) levels and reducing endothelin (ET)-1 levels. Phosphoinositide-3-kinase (PI3K) and Akt phosphorylations were markedly increased, but were inhibited by 17β-oestradiol treatment in rats with pulmonary hypertension.Oestrogen deficiency may aggravate development of pulmonary hypertension. 17β-oestradiol improved pulmonary hypertensionviaactivation of the PI3K/Akt pathway to regulate NO, PGI2and ET-1 expression.
TheTL,NO/TL,COratio in pulmonary function test interpretation
Authors: Hughes J. Michael B. , van der Lee Ivo 
Published: August 2012

The transfer factor of the lung for nitric oxide (TL,NO) is a new test for pulmonary gas exchange. The procedure is similar to the already well-established transfer factor of the lung for carbon monoxide (TL,CO). Physiologically,TL,NOpredominantly measures the diffusion pathway from the alveoli to capillary plasma. In the Roughton–Forster equation,TL,NOacts as a surrogate for the membrane diffusing capacity (DM). The red blood cell resistance to carbon monoxide uptake accounts for ∼50% of the total resistance from gas to blood, but it is much less for nitric oxide.TL,NOandTL,COcan be measured simultaneously with the single breath technique, andDMand pulmonary capillary blood volume (Vc) can be estimated.TL,NO, unlikeTL,CO, is independent of oxygen tension and haematocrit. TheTL,NO/TL,COratio is weighted towards theDM/Vcratio and to α; where α is the ratio of physical diffusivities of NO to CO (α=1.97). TheTL,NO/TL,COratio is increased in heavy smokers, with and without computed tomography evidence of emphysema, and reduced in the voluntary restriction of lung expansion; it is expected to be reduced in chronic heart failure. TheTL,NO/TL,COratio is a new index of gas exchange that may, more than derivations from them ofDMandVcwith their in-built assumptions, give additional insights into pulmonary pathology.
Impact of obesity on outcomes for patients hospitalised with pneumonia
Authors: King Phoebe , Mortensen Eric M. , Bollinger Mary , Restrepo Marcos I. , Copeland Laurel A. , Pugh Mary Jo V. , Nakashima Brandy , Anzueto Antonio , Hitchcock Noël Polly 
Published: August 2012

Obesity is an increasing problem in the USA, and research into the association between obesity and pneumonia has yielded conflicting results.Using Department of Veterans Affairs administrative data from fiscal years 2002–2006, we examined a cohort of patients hospitalised with a discharge diagnosis of pneumonia. Body mass index was categorised as underweight (<18.5 kg·m−2), normal (18.5–24.9 kg·m−2, reference group), overweight (25–29.9 kg·m−2), obese (30–39.9 kg·m−2) and morbidly obese (≥40 kg·m−2). Our primary analyses were multi level regression models with the outcomes of 90-day mortality, intensive care unit (ICU) admission, need for mechanical ventilation and vasopressor utilisation.The cohort comprised 18 746 subjects: 3% were underweight, 30% were normal, 36% were overweight, 27% were obese and 4% were morbidly obese. In the regression models, after adjusting for potential confounders, morbid obesity was not associated with mortality (OR 0.96, 95% CI 0.72–1.28), but obesity was associated with decreased mortality (OR 0.86, 95% CI 0.74–0.99). Neither obesity nor morbid obesity was associated with ICU admission, use of mechanical ventilation or vasopressor utilisation. Underweight patients had increased 90-day mortality (OR 1.40, 95% CI 1.14–1.73).Although obesity is a growing health epidemic, it appears to have little impact on clinical outcomes and may reduce mortality for veterans hospitalised with pneumonia.
Transcripts with in silico predicted RNA structure are enriched everywhere in the mouse brain
Authors: Seemann Stefan E , Sunkin Susan M , Hawrylycz Michael J , Ruzzo Walter L , Gorodkin Jan 
Published: September 2012

Abstract

Background
Post-transcriptional control of gene expression is mostly conducted by specific elements in untranslated regions (UTRs) of mRNAs, in collaboration with specific binding proteins and RNAs. In several well characterized cases, these RNA elements are known to form stable secondary structures. RNA secondary structures also may have major functional implications for long noncoding RNAs (lncRNAs). Recent transcriptional data has indicated the importance of lncRNAs in brain development and function. However, no methodical efforts to investigate this have been undertaken. Here, we aim to systematically analyze the potential for RNA structure in brain-expressed transcripts.

Results
By comprehensive spatial expression analysis of the adult mouse in situ hybridization data of the Allen Mouse Brain Atlas, we show that transcripts (coding as well as non-coding) associated with in silico predicted structured probes are highly and significantly enriched in almost all analyzed brain regions. Functional implications of these RNA structures and their role in the brain are discussed in detail along with specific examples. We observe that mRNAs with a structure prediction in their UTRs are enriched for binding, transport and localization gene ontology categories. In addition, after manual examination we observe agreement between RNA binding protein interaction sites near the 3’ UTR structures and correlated expression patterns.

Conclusions
Our results show a potential use for RNA structures in expressed coding as well as noncoding transcripts in the adult mouse brain, and describe the role of structured RNAs in the context of intracellular signaling pathways and regulatory networks. Based on this data we hypothesize that RNA structure is widely involved in transcriptional and translational regulatory mechanisms in the brain and ultimately plays a role in brain function.
Simultaneous copy number gains of NUPR1 and ERBB2 predicting poor prognosis in early-stage breast cancer
Authors: Jung Seung-Hyun , Lee Ahwon , Yim Seon-Hee , Hu Hae-Jin , Choe Chungyoul , Chung Yeun-Jun 
Published: August 2012

Abstract

Background
The full extent of chromosomal alterations and their biological implications in early breast carcinogenesis has not been well examined. In this study, we aimed to identify chromosomal alterations associated with poor prognosis in early-stage breast cancers (EBC).

Methods
A total of 145 EBCs (stage I and II) were examined in this study. We analyzed copy number alterations in a discovery set of 48 EBCs using oligoarray-comparative genomic hybridization. In addition, the recurrently altered regions (RARs) associated with poor prognosis were validated using an independent set of 97 EBCs.

Results
A total of 23 RARs were defined in the discovery set. Six were commonly detected in both stage I and II groups (> 50%), suggesting their connection with early breast tumorigenesis. There were gains on 1q21.2-q21.3, 8q24.13, 8q24.13-21, 8q24.3, and 8q24.3 and a loss on 8p23.1-p22. Among the 23 RARs, copy number gains on 16p11.2 (NUPR1) and 17q12 (ERBB2) showed a significant association with poor survival (P = 0.0186 and P = 0.0186, respectively). The patients simultaneously positive for both gains had a significantly worse prognosis (P = 0.0001). In the independent replication, the patients who were double-positive for NUPR1-ERBB2 gains also had a significantly poorer prognosis on multivariate analysis (HR = 7.31, 95% CI 2.65-20.15, P = 0.0001).

Conclusions
The simultaneous gain of NUPR1 and ERBB2 can be a significant predictor of poor prognosis in EBC. Our study will help to elucidate the molecular mechanisms underlying early-stage breast cancer tumorigenesis. This study also highlights the potential for using combinations of copy number alterations as prognosis predictors for EBC.
An uncommon case of random fire-setting behavior associated with Todd paralysis: A case report
Authors: Kanehisa Masayuki , Morinaga Katsuhiko , Kohno Hisae , Maruyama Yoshihiro , Ninomiya Taiga , Ishitobi Yoshinobu , Tanaka Yoshihiro , Tsuru Jusen , Hanada Hiroaki , Yoshikawa Tomoya , Akiyoshi Jotaro 
Published: August 2012

Abstract

Background
The association between fire-setting behavior and psychiatric or medical disorders remains poorly understood. Although a link between fire-setting behavior and various organic brain disorders has been established, associations between fire setting and focal brain lesions have not yet been reported. Here, we describe the case of a 24-year-old first time arsonist who suffered Todd’s paralysis prior to the onset of a bizarre and random fire-setting behavior.

Case presentation
A case of a 24-year-old man with a sudden onset of a bizarre and random fire-setting behavior is reported. The man, who had been arrested on felony arson charges, complained of difficulties concentrating and of recent memory disturbances with leg weakness. A video-EEG recording demonstrated a close relationship between the focal motor impairment and a clear-cut epileptic ictal discharge involving the bilateral motor cortical areas. The SPECT result was statistically analyzed by comparing with standard SPECT images obtained from our institute (easy Z-score imaging system; eZIS). eZIS revealed hypoperfusion in cingulate cortex, basal ganglia and hyperperfusion in frontal cortex,. A neuropsychological test battery revealed lower than normal scores for executive function, attention, and memory, consistent with frontal lobe dysfunction.

Conclusion
The fire-setting behavior and Todd’s paralysis, together with an unremarkable performance on tests measuring executive function fifteen months prior, suggested a causal relationship between this organic brain lesion and the fire-setting behavior. The case describes a rare and as yet unreported association between random, impulse-driven fire-setting behavior and damage to the brain and suggests a disconnection of frontal lobe structures as a possible pathogenic mechanism.
Unmet need for induction of labor in Africa: secondary analysis from the 2004 - 2005 WHO Global Maternal and Perinatal Health Survey (A cross-sectional survey)
Authors: Bukola Fawole , Idi Nafiou , M’Mimunya Machoki , Jean-Jose Wolomby-Molondo , Kidza Mugerwa , Isilda Neves , Faouzi Amokrane , Archana Shah , Paulo Souza Joao , Matthews Mathai , Metin Gulmezoglu 
Published: August 2012

Abstract

Background
Induction of labor is being increasingly used to prevent adverse outcomes in the mother and the newborn.This study assessed the prevalence of induction of labor and determinants of its use in Africa.

Methods
We performed secondary analysis of the WHO Global Survey of Maternal and Newborn Health of 2004 and 2005. The African database was analyzed to determine the use of induction of labor at the country level and indications for induction of labor. The un-met needs for specific obstetric indications and at country level were assessed. Determinants of use of induction of labor were explored with multivariate regression analysis.

Results
A total of 83,437 deliveries were recorded in the 7 participating countries. Average rate of induction was 4.4% with a range of 1.4 – 6.8%. Pre-labor rupture of membranes was the commonest indication for induction of labor. Two groups of women were identified: 2,776 women with indications had induction of labor while 7,996 women although had indications but labor was not induced.
Induction of labor was associated with reduction of stillbirths and perinatal deaths [OR – 0.34; 95% CI (0.27 – 0.43)].
Unmet need for induction of labor ranged between 66.0% and 80.2% across countries. Determinants of having an induction of labor were place of residence, duration of schooling, type of health facility and level of antenatal care.

Conclusion
Utilization of induction of labor in health facilities in Africa is very low. Improvements in social and health infrastructure are required to reverse the high unmet need for induction of labor.
The effects of extraction of pulpally involved primary teeth on weight, height and BMI in underweight Filipino children. A cluster randomized clinical trial
Authors: Monse Bella , Duijster Denise , Sheiham Aubrey , Grijalva-Eternod Carlos S , van Palenstein Helderman Wim , Hobdell Martin H 
Published: August 2012

AbstractBackgroundSevere dental caries and the treatment thereof are reported to affect growth and well-being of young children. The objective of this study was to assess the effects of extraction of severely decayed pulpally involved primary teeth on weight and height in underweight preschool Filipino children.MethodsUnderweight preschool Filipino children with severe dental decay had their pulpally involved primary teeth extracted during a stepped wedge cluster randomized clinical trial. Day care centers were randomly divided into two groups; children from Group A day care centers received treatment as soon as practical, whereas children from Group B day care centers were treated four months after Group A. Clinical oral examinations using WHO criteria and the pufa-index were carried out. Anthropometric measurements were done on both groups immediately before treatment of Group A and at follow-up four months later. Height and weightz-scores were calculated using 2006 and 2007 WHO Growth Standards. Multilevel analysis was used to assess the effect of dental extractions on changes in anthropometric measurements after dental treatment.ResultsData on 164 children (85 in Group A and 79 in Group B), mean age 59.9 months, were analyzed. Both groups gained weight and height during the trial period. Children in Group A significantly increased their BMI (p < 0.001), and their weight-for-age (p < 0.01) and BMI-for-agez-scores (p < 0.001) after dental treatment, whereas untreated children in Group B did not. Children in Group A had significantly more weight gain (p < 0.01) compared to untreated children in Group B. However, children in Group A had an inverse change in height gain (p < 0.001). Adjustment for the time interval between the two visits had little effect on the results.ConclusionsThe extraction of severely decayed primary teeth resulted in significant weight gain in underweight Filipino children. Untreated dental decay should be considered an important co-factor affecting child growth and should be considered when planning for interventions to improve child growth.Trial registrationISRCTN90779069http://www.controlled-trials.com/isrctn/isrctn_loa
Obesity does not aggravate vitrification injury in mouse embryos: a prospective study
Authors: Ma Wenhong , Yang Xing , Liang Xiaoyan 
Published: August 2012

Abstract

Background
Obesity is associated with poor reproductive outcomes, but few reports have examined thawed embryo transfer in obese women. Many studies have shown that increased lipid accumulation aggravates vitrification injury in porcine and bovine embryos, but oocytes of these species have high lipid contents (63 ng and 161 ng, respectively). Almost nothing is known about lipids in human oocytes except that these cells are anecdotally known to be relatively lipid poor. In this regard, human oocytes are considered to be similar to those of the mouse, which contain approximately 4 ng total lipids/oocyte. To date, no available data show the impact of obesity on vitrification in mouse embryos. The aim of this study was to establish a murine model of maternal diet-induced obesity and to characterize the effect of obesity on vitrification by investigating the survival rate and embryo developmental competence after thawing.

Methods
Prospective comparisons were performed between six–eight-cell embryos from obese and normal-weight mice and between fresh and vitrified embryos. Female C57BL/6 mice were fed standard rodent chow (normal-weight group) or a high-fat diet (obese group) for 6 weeks. The mice were mated, zygotes were collected from oviducts and cultured for 3 days, and six–eight-cell embryos were then selected to assess lipid content in fresh embryos and to evaluate differences in apoptosis, survival, and development rates in response to vitrification.

Results
In fresh embryos from obese mice, the lipid content (0.044 vs 0.030, P<0.01) and apoptosis rate (15.1% vs.9.3%, P<0.05)were significantly higher, the survival rate (83.1% vs. 93.1%, P<0.01) on day 5 was significantly lower, and embryo development was notably delayed on days 3–5 compared with the normal-weight group. After vitrification, no significant difference was found between thawed embryos from obese and normal-weight mice in apoptosis, survival, and development rates on days 4 and 5. In both groups, pre- and post-vitrification embryo apoptosis, survival, and development rates were similar.

Conclusions
This study demonstrated that differences in survival and developmental rates between embryos from obese and normal-weight mice were eliminated after vitrification. Thus, maternal obesity does not aggravate vitrification injury, but obesity alone greatly impairs pre-implantation embryo survival and development.
Epigenetic dysregulation of secreted frizzled-related proteins in myeloproliferative neoplasms complements the JAK2V617F-mutation
Authors: Bennemann Karla , Galm Oliver , Wilop Stefan , Schubert Claudia , Brümmendorf Tim H , Jost Edgar 
Published: August 2012

Abstract

Background
Secreted frizzled-related proteins (SFRPs) are antagonists of the Wnt signaling pathway, which plays a central role in stem cell maintenance and differentiation of stem cells and hematopoietic progenitors. Epigenetic downregulation of SFRPs by promoter hypermethylation has been described to be involved in the pathogenesis of hematopoietic malignancies. There is an association between aberrant Wnt signaling and the established cancer stem cell concept. In contrast to BCR-ABL1-positive chronic myeloid leukemia CML, BCR-ABL1-negative myeloproliferative neoplasms (Ph-MPN) are characterized by the frequent occurrence of an autoactivating mutation in the JAK2 tyrosine kinase (JAK2V617F) or other mutations in the JAK-STAT pathway. However, pathogenetic mechanisms of JAK2 mutated or unmutated Ph-MPN remain not completely understood. We determined the promoter methylation status of SFRP-1, -2, -4, and -5 in 57 MPN patient samples by methylation-specific polymerase chain reaction (PCR) (MSP). JAK2V617F was assessed by allele-specific PCR.

Results
Aberrant methylation among primary MPN samples was 4% for SFRP-1, 25% for SFRP-2, 2% for SFRP-4, and 0% for SFRP-5. Hypermethylation of SFRP-2, which was the most frequently hypermethylated gene in our study, could not be correlated to any specific MPN subtype. However, we detected a significant correlation between SFRP-2 methylation and presence of a JAK2V617F mutation (P = 0.008). None of the 10 CML samples showed any SFRP-methylation.

Conclusions
Our data indicate that epigenetic dysregulation of the Wnt signaling pathway is a common event in MPN with aberrant methylation of at least one SFRP being detected in 25% of the primary patient samples and in 30% if only accounting for Ph-MPN. A significant correlation between SFRP-2 methylation and presence of JAK2V617F in our data supports the hypothesis that epigenetic dysregulation may be a complementary mechanism to genetic aberrations. Aberrant methylation of crucial stem cell maintenance genes seems to contribute to disease pathogenesis in Ph-MPN.