bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Wheat Milling on Low-hydration Bread Quality Developed by Sheeting Rolls
Authors: Gómez M. , Ruiz-París E. , Oliete B.
Published: May 2011

It is well known that milling influences the characteristics of flour and products made from it. This article analyzed the influence of milling on the quality of low-hydration bread. In general, milling influenced the quality of these products more than the type of wheat selected. Among the various mill streams, the last break and reduction streams produced lower quality bread and must be eliminated in milling. These streams had a higher protein and ash content, showing the presence of components of the outer layers of the grain. The flour was able to absorb more water, but had less extensibility in kneading and the dough generated was weaker due the poorer quality of its proteins and the influence of elements from the outer layers. Thus, bread made from these streams had smaller volume, had a firmer texture and had both darker crumb and crust. These differences, along with the effect of the kind of flour on the flavor and aroma of the bread, made it less acceptable than flour from the rest of the streams studied.
Effectiveness of Smoking Cessation and Reduction in Pregnancy Treatment (SCRIPT) Methods in Medicaid-Supported Prenatal Care
Authors: Windsor Richard , Woodby Lesa , Miller Thomas , Hardin Michael
Published: May 2011

This two-phase evaluation documented the delivery and effectiveness of evidence-based health education methods by regular staff to pregnant smokers. During Phase 1, a total of 436 Medicaid patients were screened and 416 (95%) gave consent: 334 nonsmokers and 102 smokers. This historical Comparison (C) group was assessed to document the “normal” pretrial smoking prevalence, patient nondisclosure (deception), and cessation rates at the first prenatal visit and during care. After this study, a formative evaluation of SCRIPT methods was conducted among 139 experimental group patients and 126 control group patients. During Phase 2, a total of 6,514 patients were screened over a 36-month period: 1,736 (27%) were smokers and 1,340 (77%) gave consent. After randomization, 247 became ineligible. The remaining 1,093 smokers received brief routine advice to quit. The experimental group ( n = 544) also received a Commit to Quit video, A Pregnant Woman’s Guide to Quit Smoking, and counseling. Self-reports and saliva were collected at baseline, ≥60 days, and ≤90 days postpartum for cotinine analyses to document cessation and significant reduction (SR) rates. The Phase 1 formative evaluation documented a 24% nondisclosure rate at the onset of care. It also confirmed a significantly higher experimental (17.3%) versus control group (8.8%) cessation rate and experimental versus control group SR rates of 22% and 16%. During Phase 2, unplanned policy changes, and delivery of experimental group counseling procedures to 15% to 20% of control group patients, resulted in a final experimental group cessation rate of 12% and a control group rate of 10%. The experimental group SR rate of 18%, however, was significantly higher than the control group SR rate of 13%. Effectiveness varied by the stability of clinic infrastructure, and degree of fidelity of staff performance of assessment and intervention procedures. The methods and results of this study will assist future health education programs for pregnant smokers to plan and conduct process and impact evaluations in prenatal care.
A Family and Community Focused Lifestyle Program Prevents Weight Regain in Pacific Islanders
Authors: Kaholokula Joseph Keawe‘aimoku , Mau Marjorie K. , Efird Jimmy T. , Leake Anne , West Margaret , Palakiko Donna-Marie , Yoshimura Sheryl R. , Kekauoha B. Puni , Rose Charles , Gomes Henry
Published: May 2011

Preventing weight regain after the loss of excess weight is challenging for people, especially for ethnic minorities in the United States. A 6-month weight loss maintenance intervention designed for Pacific Islanders, called the PILI Lifestyle Program (PLP), was compared with a 6-month standard behavioral weight loss maintenance program (SBP) in a pilot randomized controlled trial using a community-based participatory research approach. Adult Pacific Islanders ( N = 144) were randomly assigned to either PLP ( n = 72) or SBP ( n = 72) after completing a 3-month weight loss program. Successful weight maintenance was defined as participants’ postintervention weight change remaining ≤3% of their preintervention mean weight. Both PLP and SBP participants achieved significant weight loss maintenance ( p ≤ .05). Among participants who completed at least half of the prescribed sessions, PLP participants were 5.1-fold (95% confidence interval = 1.06, 24; p = .02) more likely to have maintained their initial weight loss than SBP participants. The pilot PLP shows promise as a lifestyle intervention to address the obesity disparities of Pacific Islanders and thus warrants further investigation.
Sex Educators and Self-Efficacy
Authors: Jensen Robin E.
Published: May 2011

Enactive mastery experiences have been identified as the most influential source of self-efficacy beliefs. Yet little is known about enactive mastery experiences, including how such experiences manifest in naturally occurring situations (as opposed to simulated situations). This study draws from semistructured interviews ( N = 50) with sex educators working in public secondary schools throughout Indiana to explicate distinct categories of enactive mastery experiences. Three types of enactive mastery experiences—growth, interactive, and endorsed—emerged from the data and are delineated. This formative taxonomy provides detailed targets for those working to foster individuals’ perceived self-efficacy in a variety of contexts, including the health education classroom.
A study on the influence of cylinder liner distortion on piston ring kinetic characteristic and lubricating oil consumption
Authors: Shu G , Dong L , Liang X
Published: May 2011

This article studies the influence of cylinder liner distortion on piston ring kinetic characteristic and oil consumption on a single cylinder natural aspirated direct injection-diesel four-stroke engine. The distance between the groove and the piston ring is tested with the consideration of different cylinder liner distortions at different speeds when the oil thrown into the combustion chamber is also collected and measured during the operation with the application of the motoring test method. A conclusion can be drawn that oil thrown into the combustion chamber increases with the cylinder liner distortion getting more complex. The reason is that the sealing function of the ring is weakened with bad adherence of the ring to the cylinder liner when the distance between cylinder liner and piston ring increases.
Synergistic effect of diisopropyl phosphite and ashless organic ammonium phosphate salt additives on tribological properties of AISI 52100 steel/Al2O3 ceramics
Authors: Jiang S Y , Xie H J
Published: May 2011

The friction-reducing and antiwear effects of the 500SN base oil containing diisopropyl phosphite (T451) and ashless organic ammonium phosphate salt (KT139) on AISI 52100 steel/Al2O3 ceramic were investigated with a ball-on-disc tribometer at a light load of 200 N and a high load of 400 N. The results indicate that the 500SN base oil containing T451 and KT139 appears with a synergistic effect on AISI 52100 steel/Al2O3 ceramic. Under a single additive, increasing percentage of T451 or KT139 can decrease the friction coefficient and the wear rate of the pair monotonously. However, under the compound system, the tribological behaviour of the pair is strongly dependent of the concentrations of additives. Within the experimental data, the most effective compositions for the loads 200 and 400 N are 2 wt%T451 + 2 wt%KT139 and 1 wt%T451 + 3 wt%KT139, respectively. The scanning electron microscopic images showed that plowed grooves, spalling, and corrosion are the dominant wear modes for the pair. The energy dispersive spectroscopy analysis shows that a protective tribochemical film containing both S and P forms on the steel ball worn surface. Nevertheless, the atom concentrations of P and S are too low to be referred for further analysis of the tribochemical reaction mechanism.
Wear characteristics of polyamide nanocomposite spur gears
Authors: Gurunathan C , Kirupasankar S , Gnanamoorthy R
Published: May 2011

Polymer nanocomposites have received considerable research attention in the past decade due to its remarkable improvement in tensile, fatigue, and tribological characteristics. This article reports the wear characteristics of pristine polyamide 6 and polyamide 6 nanocomposite (PA6NC) spur gears. The nanocomposite was made by melt intercalation method and injection moulded into gears. Molecular level interaction of nano-size reinforcement enhances the mechanical properties of polymer nanocomposite. The performance of gears at different torque levels were studied using a power absorption type gear test rig. The gear tooth surface temperature affects the wear rate and service life. The enhanced mechanical properties of PA6NC results in reduced frictional and hysteresis heat generation associated with less wear and increased life.
Feasibility of utilizing response surface methodology for predicting wear of steels
Authors: Selçuk B
Published: May 2011

In this study, statistical models were developed in terms of contact load, sliding time, hardness, and r/min using the response surface method (RSM). In RSM, central composite design (CCD) was selected for wear tests. In wear tests, responses are the measurements of the weight loss from specimens. Specimens were machined from AISI 4140 and AISI 1040 steels. The wear model was estimated by the least-squares method for each steel after conducting tests in terms of CCD. When they were analysed, the agreement between the predicted and actual wear resistance values was observed within −8 per cent. Then, model adequacy tests were made by performing several new wear tests. Moreover, the models were applied to new tests which consist of different materials and wear factors for the feasibility. In conclusion, predictive wear models using RSM can be applicable for a certain wear system in order to estimate its wear rate.
An experimental study of the influence of loading direction on the thermohydrodynamic behaviour of twin axial groove journal bearing
Authors: Solghar A Arab , Brito F P , Claro J C P , Nassab S A Gandjalikhan
Published: May 2011

An experimental assessment of the influence of angle between the groove axis and the load line on the thermohydrodynamic behaviour of twin groove hydrodynamic journal bearings has been undertaken. At nine different loading direction angles, the oil–bush interface temperature profiles, oil outlet temperature, maximum bush temperature, total flow rate, and oil flow rate through each groove were measured for variable applied load and oil supply pressure while the feeding temperature was kept constant (40°C). To the authors’ knowledge, this is the first study of the influence of loading direction on the performance of journal bearing with two axial grooves in which the flow rate were measured in each groove for different working conditions under laminar regime. It was found that the variation of loading direction has a strong effect on the bearing performance. Under some running conditions, negative lubricant flow rate (hot oil reflux) at one groove was detected. This seldom-reported phenomenon was found to affect the bearing performance dramatically. Increasing supply pressure yielded a temperature decrease, especially for high loads, and sometimes prevented the occurrence of hot oil reflux.
Latitudinal prevalence gradient of multiple sclerosis in Latin America
Authors: Risco J , Maldonado H , Luna L , Osada J , Ruiz P , Juarez A , Vizcarra D
Published: May 2011

Background: Multiple sclerosis (MS) has a unique geographical distribution that reflects both genetic and environmental factors. Many studies have shown a positive correlation between MS frequency and latitude across both large and small geographical regions. However, scarce data have been published on the epidemiology of MS in Latin America and no study has evaluated latitudinal variation.

Objective: To evaluate the effect of latitude on MS prevalence in Latin America.

Methods: We conducted a systematic review of MS prevalence during January 2011. Prevalence rates were collected from eligible publications. The effect of latitude on prevalence was analyzed using linear regression.

Results: A total of ten studies were eligible for analysis, corresponding to six countries, spanning from Panama to Argentina. The crude prevalence of MS ranged from 0.75 to 21.5 per 100,000. We found a strong and significant association between prevalence and latitude ( r2 0.8; p < 0.001) and determined an increase in prevalence of 0.33 per 100,000 per degree latitude.

Conclusion: Our findings suggest a latitudinal prevalence gradient of MS in Latin American countries between Panama and Argentina.
Non-conventional practices and immune functioning among individuals receiving conventional care for HIV
Authors: Nightingale Vienna R. , Sher Tamara G. , Thilges Sarah , Niel Kristin , Rolfsen Norma , Hansen Nathan B.
Published: May 2011

Objective: to examine the relationships among non-conventional practices, adherence and immune functioning in individuals with HIV. Methods: 92 participants completed an interview on non-conventional practices (complementary and alternative medicines (CAM), psychosocial therapies, and religious practice). They also completed the Psychiatric Symptom Index and the AIDS Clinical Trials Group Adherence Follow-up Questionnaire. Medical chart reviews determined CD4 count and viral load. Results: Hierarchical logistic regressions revealed religious practice was associated with adherence and CAM was associated with viral load. Conclusion: Participation in non-conventional practices in HIV populations may lead to positive health and health behaviors. Clinical implications are discussed.
Risk prediction of incident coronary heart disease in the Netherlands: re-estimation and improvement of the SCORE risk function
Authors: Merry Audrey HH , Boer Jolanda MA , Schouten Leo J , Ambergen Ton , Steyerberg Ewout W , Feskens Edith JM , Verschuren WM Monique , Gorgels Anton PM , van den Brandt Piet A
Published: May 2011

Aims: To re-estimate the SCORE risk function using individual data on risk factors and coronary heart disease (CHD) incidence from the Dutch Cardiovascular Registry Maastricht (CAREMA) population-based cohort study; to evaluate changes that may improve risk prediction after re-estimation; and to compare the performance of the resulting CAREMA risk function with that of existing risk scores.

Methods and results: The cohort consisted of 21,148 participants, born in 1927–1977 and randomly sampled from the Maastricht region in 1987–1997. After follow-up (median 10.9 years), 783 incident CHD cases occurred. Model performance was assessed by discrimination and calibration. The additional value of including other risk factors or current risk factors in a different manner was evaluated using the net reclassification index (NRI). The c statistic of the re-estimated SCORE model was 0.799 (95% CI 0.782–0.816). Separating the total/high-density lipoprotein (HDL) cholesterol ratio into total and HDL cholesterol levels did not improve the c statistic ( p = 0.22), but reclassified 6.0% of the participants into a more appropriate risk category ( p < 0.001) compared with the re-estimated model. The resulting CAREMA function reclassified 28% of the participants into a more appropriate risk category than the Framingham score. Compared with the SCORE functions for high- and low-risk regions, the NRIs were 28% and 35%, respectively, which can largely be explained by the difference in outcome definition (CHD incidence vs. CHD mortality).

Conclusion: In this Dutch population, a re-estimated SCORE function with total and HDL cholesterol levels instead of the cholesterol ratio can be used for the risk prediction of CHD incidence.
Factors influencing maternal attachment of first-time Jordanian mothers
Authors: Gharaibeh Muntaha K. , Hamlan Adlah M.
Published: May 2011

The purposes of this study were to identify differences in maternal attachment according to maternal characteristics (socio-demographic, perinatal and self-efficacy variables) and identify factors influencing maternal attachment of first-time Jordanian mothers. A cross-sectional correlational design was used in this study. A convenience sample of 220 first-time Jordanian mothers was recruited during a period of three months in the summer of 2008. Participants completed a socio-demographic and perinatal data sheet, the Parental Self-efficacy scale and the Perceived Maternal Attachment Inventory. ‘Pleasure of proximity’ was the maternal attachment dimension that received the highest mean score, and the highest mean score on the maternal self-efficacy (MSE) measure was reported for the ‘situational belief’ subscale. A significant positive correlation was found between maternal attachment and maternal self-efficacy ( r = 0.54, p < 0.001). Factors influencing maternal attachment were maternal self-efficacy, perception of marital relationship and pregnancy and delivery experience, which together explained 33% of the variance in maternal attachment ( R2 = 0.33). Maternal self-efficacy, a good marital relationship and difficulties during pregnancy and delivery are important factors that influence maternal attachment of first-time Jordanian mothers. Health care providers from Jordan and other parts of the world need to acknowledge these factors when dealing with the health and social well-being of mothers and their infants.
Instrumentation in endourology
Authors: Khanna Rakesh , Monga Manoj
Published: May 2011

Success with endourological procedures requires expertise and instrumentation. This review focuses on the instrumentation required for ureteroscopy and percutaneous nephrolithotomy, and provides a critical assessment of in vitro and clinical studies that have evaluated the comparative effectiveness of these medical devices.
Is It Time for “Baby-Friendly” Pediatric Hospitals?
Authors: Carney Ginger , Bruce Debbie
Published: May 2011

Because pediatric hospitals provide care for infants and children, a baby-friendly environment must be in place to help support both the initiation and continuation of breastfeeding. Many opportunities exist for the pediatric practitioner and other staff members to assist mothers of pediatric patients to achieve and continue successful breastfeeding. Pediatric hospitals must ensure an environment that protects breastfeeding for established breastfeeding dyads, and also take steps to assist in the initiation of the breastfeeding relationship when the infant presents in the newborn period. Without support from the entire healthcare team that cares for women and children, the 2020 US goals for breastfeeding cannot be attained. Many have outlined ways in which this mission can be carried out in pediatric facilities, and these ideas are utilized in suggesting a plan for use in pediatric environments modeled after the “10 Steps to Successful Breastfeeding,” as outlined in the Baby-Friendly Hospital Initiative by UNICEF/WHO.
Is Fellowship Training Necessary for Neurohospitalists?
Authors: Barrett Kevin M. , Fowler Mariecken V.
Published: May 2011

Neurohospitalists are an emerging subspecialty group in neurology. 1 A recent survey of neurohospitalists found 75% of respondents had completed general neurology residency plus additional fellowship training (54% vascular neurology, 13% neurocritical care, and 33% other). 2 A limited number of neurohospitalist fellowship positions 3 , 4 are offered in the United States, however, a standardized curriculum or subspecialty certification examination does not currently exist. Given the recent dialogue surrounding the utility of neurohospitalist fellowship training, the purpose of this article is to provide 2 contrasting perspectives on the perceived need for neurohospitalist fellowship training.
PTPN2 negatively regulates oncogenic JAK1 in T-cell acute lymphoblastic leukemia
Authors: Kleppe Maria , Soulier Jean , Asnafi Vahid , Mentens Nicole , Hornakova Tekla , Knoops Laurent , Constantinescu Stefan , Sigaux François , Meijerink Jules P. , Vandenberghe Peter , Tartaglia Marco , Foa Robin , Macintyre Elizabeth , Haferlach Torsten , Cools Jan
Published: May 2011

We have recently reported inactivation of the tyrosine phosphatase PTPN2 (also known as TC-PTP) through deletion of the entire gene locus in ∼ 6% of T-cell acute lymphoblastic leukemia (T-ALL) cases. T-ALL is an aggressive disease of the thymocytes characterized by the stepwise accumulation of chromosomal abnormalities and gene mutations. In the present study, we confirmed the strong association of the PTPN2 deletion with TLX1 and NUP214-ABL1 expression. In addition, we found cooperation between PTPN2 deletion and activating JAK1 gene mutations. Activating mutations in JAK1 kinase occur in ∼ 10% of human T-ALL cases, and aberrant kinase activity has been shown to confer proliferation and survival advantages. Our results reveal that some JAK1 mutation–positive T-ALLs harbor deletions of the tyrosine phosphatase PTPN2, a known negative regulator of the JAK/STAT pathway. We provide evidence that down-regulation of Ptpn2 sensitizes lymphoid cells to JAK1-mediated transformation and reduces their sensitivity to JAK inhibition.
The RacGAP ArhGAP15 is a master negative regulator of neutrophil functions
Authors: Costa Carlotta , Germena Giulia , Martin-Conte Erica L. , Molineris Ivan , Bosco Eleonora , Marengo Stefano , Azzolino Ornella , Altruda Fiorella , Ranieri V. Marco , Hirsch Emilio
Published: May 2011

In phagocytes, GTPases of the Rac family control crucial antimicrobial functions. The RacGAP ArhGAP15 negatively modulates Rac activity in leukocytes, but its in vivo role in innate immunity remains largely unknown. Here we show that neutrophils and macrophages derived from mice lacking ArhGAP15 presented higher Rac activity but distinct phenotypes. In macrophages, the loss of ArhGAP15 induced increased cellular elongation and membrane protrusions but did not modify chemotactic responses. Conversely, the lack of ArhGAP15 in neutrophils affected critical Rac-dependent antimicrobial functions, specifically causing enhanced chemotactic responses, straighter directional migration, amplified reactive oxygen species production, increased phagocytosis, and improved bacterial killing. In vivo, in a model of severe abdominal sepsis, these effects contributed to increase neutrophil recruitment to the site of infection, thereby limiting bacterial growth, controlling infection spread, reducing systemic inflammation, and ultimately improving survival in ArhGAP15-null mice. Altogether, these results demonstrate the relevance of ArhGAP15 in the selective regulation of multiple neutrophil functions, suggesting that ArhGAP15 targeting might be beneficial in specific pathologic settings like severe sepsis.
Modulation of microRNA expression in human T-cell development: targeting of NOTCH3 by miR-150
Authors: Ghisi Margherita , Corradin Alberto , Basso Katia , Frasson Chiara , Serafin Valentina , Mukherjee Subhamoy , Mussolin Lara , Ruggero Katia , Bonanno Laura , Guffanti Alessandro , De Bellis Gianluca , Gerosa Gino , Stellin Giovanni , D'Agostino Donna M. , Basso Giuseppe , Bronte Vincenzo , Indraccolo Stefano , Amadori Alberto , Zanovello Paola
Published: May 2011

Ontogenesis of T cells in the thymus is a complex process whose molecular control is poorly understood. The present study investigated microRNAs involved in human thymocyte differentiation by comparing the microRNA expression profiles of thymocytes at the double-positive, single-positive CD4+ and single-positive CD8+ maturation stages. Microarray analysis showed that each thymocyte population displays a distinct microRNA expression profile that reflects their developmental relationships. Moreover, analysis of small-RNA libraries generated from human unsorted and double-positive thymocytes and from mature peripheral CD4+ and CD8+ T lymphocytes, together with the microarray data, indicated a trend toward up-regulation of microRNA expression during T-cell maturation after the double-positive stage and revealed a group of microRNAs regulated during normal T-cell development, including miR-150, which is strongly up-regulated as maturation progresses. We showed that miR-150 targets NOTCH3, a member of the Notch receptor family that plays important roles both in T-cell differentiation and leukemogenesis. Forced expression of miR-150 reduces NOTCH3 levels in T-cell lines and has adverse effects on their proliferation and survival. Overall, these findings suggest that control of the Notch pathway through miR-150 may have an important impact on T-cell development and physiology.
Anti-inflammatory protein TSG-6 secreted by activated MSCs attenuates zymosan-induced mouse peritonitis by decreasing TLR2/NF-κB signaling in resident macrophages
Authors: Choi Hosoon , Lee Ryang Hwa , Bazhanov Nikolay , Oh Joo Youn , Prockop Darwin J.
Published: May 2011

Human mesenchymal stem/progenitor cells (hMSCs) repair tissues and modulate immune systems but the mechanisms are not fully understood. We demonstrated that hMSCs are activated by inflammatory signals to secrete the anti-inflammatory protein, TNF-α–stimulated gene 6 protein (TSG-6) and thereby create a negative feedback loop that reduces inflammation in zymosan-induced peritonitis. The results demonstrate for the first time that TSG-6 interacts through the CD44 receptor on resident macrophages to decrease zymosan/TLR2-mediated nuclear translocation of the NF-κB. The negative feedback loop created by MSCs through TSG-6 attenuates the inflammatory cascade that is initiated by resident macrophages and then amplified by mesothelial cells and probably other cells of the peritoneum. Because inflammation underlies many pathologic processes, including immune responses, the results may explain the beneficial effects of MSCs and TSG-6 in several disease models.
Prognostic significance of additional cytogenetic aberrations in 733 de novo pediatric 11q23/MLL-rearranged AML patients: results of an international study
Authors: Coenen Eva A. , Raimondi Susana C. , Harbott Jochen , Zimmermann Martin , Alonzo Todd A. , Auvrignon Anne , Beverloo H. Berna , Chang Myron , Creutzig Ursula , Dworzak Michael N. , Forestier Erik , Gibson Brenda , Hasle Henrik , Harrison Christine J. , Heerema Nyla A. , Kaspers Gertjan J. L. , Leszl Anna , Litvinko Nathalia , Lo Nigro Luca , Morimoto Akira , Perot Christine , Reinhardt Dirk , Rubnitz Jeffrey E. , Smith Franklin O. , Stary Jan , Stasevich Irina , Strehl Sabine , Taga Takashi , Tomizawa Daisuke , Webb David , Zemanova Zuzana , Pieters Rob , Zwaan C. Michel , van den Heuvel-Eibrink Marry M.
Published: May 2011

We previously demonstrated that outcome of pediatric 11q23/MLL-rearranged AML depends on the translocation partner (TP). In this multicenter international study on 733 children with 11q23/MLL-rearranged AML, we further analyzed which additional cytogenetic aberrations (ACA) had prognostic significance. ACAs occurred in 344 (47%) of 733 and were associated with unfavorable outcome (5-year overall survival [OS] 47% vs 62%, P < .001). Trisomy 8, the most frequent specific ACA (n = 130/344, 38%), independently predicted favorable outcome within the ACAs group (OS 61% vs 39%, P = .003; Cox model for OS hazard ratio (HR) 0.54, P = .03), on the basis of reduced relapse rate (26% vs 49%, P < .001). Trisomy 19 (n = 37/344, 11%) independently predicted poor prognosis in ACAs cases, which was partly caused by refractory disease (remission rate 74% vs 89%, P = .04; OS 24% vs 50%, P < .001; HR 1.77, P = .01). Structural ACAs had independent adverse prognostic value for event-free survival (HR 1.36, P = .01). Complex karyotype, defined as ≥ 3 abnormalities, was present in 26% (n = 192/733) and showed worse outcome than those without complex karyotype (OS 45% vs 59%, P = .003) in univariate analysis only. In conclusion, like TP, specific ACAs have independent prognostic significance in pediatric 11q23/MLL-rearranged AML, and the mechanism underlying these prognostic differences should be studied.
Disruption of MyD88 signaling suppresses hemophagocytic lymphohistiocytosis in mice
Authors: Krebs Philippe , Crozat Karine , Popkin Daniel , Oldstone Michael B. , Beutler Bruce
Published: May 2011

Hemophagocytic lymphohistiocytosis (HLH) is a rare inflammatory disorder with a poor prognosis for affected individuals. To find a means of suppressing the clinical phenotype, we investigated the cellular and molecular mechanisms leading to HLH in Unc13djinx/jinx mice, in which cytolytic function of NK and CD8+ T cells is impaired. Unc13djinx/jinx mutants infected with lymphochoriomeningitis virus (LCMV) present typical clinical features of HLH, including splenomegaly, elevated serum IFNγ, and anemia. Proteins mediating cell-cell contact, cytokine signaling or Toll-like receptor (TLR) signaling were analyzed. We show that neither the integrin CD18, which is involved in adhesion between antigen-presenting cells and effector T cells, nor tumor necrosis factor (TNF) made nonredundant contributions to the disease phenotype. Disruption of IFNγ signaling reduced immune cell activation in Unc13djinx/jinx mice, but also resulted in uncontrolled viral proliferation and exaggerated release of inflammatory cytokines. Abrogating the function of myeloid differentiation primary response gene 88 (MyD88) in Unc13djinx/jinx mice suppressed immune cell activation and controlled cytokine production in an IL-1 receptor 1 (IL-1R1)–independent way. Our findings implicate MyD88 as the key initiator of myeloid and lymphoid proliferation in HLH, and suggest that blockade of this signaling molecule may reduce immunopathology in patients.
A phase 2 study of lenalidomide monotherapy in patients with deletion 5q acute myeloid leukemia: Southwest Oncology Group Study S0605
Authors: Sekeres Mikkael A. , Gundacker Holly , Lancet Jeffrey , Advani Anjali , Petersdorf Stephen , Liesveld Jane , Mulford Deborah , Norwood Tom , Willman Cheryl L. , Appelbaum Frederick R. , List Alan F.
Published: May 2011

Older acute myeloid leukemia (AML) patients with a chromosome 5q deletion have poor outcomes with conventional chemotherapy. This phase 2 study explored the safety and efficacy of single-agent lenalidomide in previously untreated older AML patients with del(5q) who declined standard chemotherapy. Patients were treated with lenalidomide 50 mg daily for 28 days as induction therapy and 10 mg daily for 21 days of a 28-day cycle as maintenance until disease progression or unacceptable toxicity. Among 37 evaluable patients, the median age was 74 years (range, 60-94), 21 (57%) were female, 19 (51%) had prior myelodysplastic syndrome, and 30 (81%) had pretreatment cytogenetic studies evaluated centrally. Six had isolated del(5q), 1 had del(5q) and +8, 23 had complex cytogenetics, and 7 others had del(5q) identified locally. Fourteen patients (38%) completed induction therapy: 7 patients died during induction therapy, 8 had disease progression, 7 had nonfatal adverse events, and 1 entered hospice. Eight patients started maintenance therapy. Five patients (14%) achieved a partial or complete response, 2 with isolated del(5q) and 3 with complex cytogenetics. Relapse-free survival was 5 months (range, 0-19). Median overall survival was 2 months for the entire population. In conclusion, lenalidomide as a single agent has modest activity in older del(5q) AML patients. Southwest Oncology Group Study S0605 is registered at www.clinicaltrials.gov as NCT00352365.
HIV-associated Hodgkin lymphoma during the first months on combination antiretroviral therapy
Authors: Lanoy Emilie , Rosenberg Philip S. , Fily Fabien , Lascaux Anne-Sophie , Martinez Valerie , Partisani Maria , Poizot-Martin Isabelle , Rouveix Elisabeth , Engels Eric A. , Costagliola Dominique , Goedert James J.
Published: May 2011

Hodgkin lymphoma (HL) incidence with HIV infection may have increased with the introduction of combination antiretroviral therapy (cART), suggesting that immune reconstitution may contribute to some cases. We evaluated HL risk with cART during the first months of treatment. With 187 HL cases among 64 368 HIV patients in France, relative rates (RRs) and 95% confidence intervals (CIs) of HL were estimated using Poisson models for duration of cART, CD4 count, and HIV load, with and without adjustment for demographic/clinical covariates. HL risk was unrelated to cART use overall, but it was related to time intervals after cART initiation (P = .006). Risk was especially and significantly elevated in months 1-3 on cART (RR 2.95, CI 1.64-5.31), lower in months 4-6 (RR 1.63), and null with longer use (RR 1.00). CD4 count was strongly associated with HL risk (P < 10−6), with the highest HL incidence at 50-99 CD4 cells/mm3. With adjustment for CD4 count and covariates, HL risk was elevated, but not significantly (RR 1.42), in months 1-3 on cART. HIV load had no added effect. HL risk increased significantly soon after cART initiation, which was largely explained by the CD4 count. Further studies of HIV-associated HL are needed.
Ex vivo characterization and isolation of rare memory B cells with antigen tetramers
Authors: Franz Bettina , May Kenneth F. , Dranoff Glenn , Wucherpfennig Kai
Published: May 2011

Studying human antigen-specific memory B cells has been challenging because of low frequencies in peripheral blood, slow proliferation, and lack of antibody secretion. Therefore, most studies have relied on conversion of memory B cells into antibody-secreting cells by in vitro culture. To facilitate direct ex vivo isolation, we generated fluorescent antigen tetramers for characterization of memory B cells by using tetanus toxoid as a model antigen. Brightly labeled memory B cells were identified even 4 years after last immunization, despite low frequencies ranging from 0.01% to 0.11% of class-switched memory B cells. A direct comparison of monomeric to tetrameric antigen labeling demonstrated that a substantial fraction of the B-cell repertoire can be missed when monomeric antigens are used. The specificity of the method was confirmed by antibody reconstruction from single-cell sorted tetramer+ B cells with single-cell RT-PCR of the B-cell receptor. All antibodies bound to tetanus antigen with high affinity, ranging from 0.23 to 2.2 nM. Furthermore, sequence analysis identified related memory B cell and plasmablast clones isolated more than a year apart. Therefore, antigen tetramers enable specific and sensitive ex vivo characterization of rare memory B cells as well as the production of fully human antibodies.
Assessing affymetrix GeneChip microarray quality
Authors: McCall Matthew N , Murakami Peter N , Lukk Margus , Huber Wolfgang , Irizarry Rafael A
Published: May 2011

Background

Microarray technology has become a widely used tool in the biological sciences. Over the past decade, the number of users has grown exponentially, and with the number of applications and secondary data analyses rapidly increasing, we expect this rate to continue. Various initiatives such as the External RNA Control Consortium (ERCC) and the MicroArray Quality Control (MAQC) project have explored ways to provide standards for the technology. For microarrays to become generally accepted as a reliable technology, statistical methods for assessing quality will be an indispensable component; however, there remains a lack of consensus in both defining and measuring microarray quality.

Results

We begin by providing a precise definition of microarray quality and reviewing existing Affymetrix GeneChip quality metrics in light of this definition. We show that the best-performing metrics require multiple arrays to be assessed simultaneously. While such multi-array quality metrics are adequate for bench science, as microarrays begin to be used in clinical settings, single-array quality metrics will be indispensable. To this end, we define a single-array version of one of the best multi-array quality metrics and show that this metric performs as well as the best multi-array metrics. We then use this new quality metric to assess the quality of microarry data available via the Gene Expression Omnibus (GEO) using more than 22,000 Affymetrix HGU133a and HGU133plus2 arrays from 809 studies.

Conclusions

We find that approximately 10 percent of these publicly available arrays are of poor quality. Moreover, the quality of microarray measurements varies greatly from hybridization to hybridization, study to study, and lab to lab, with some experiments producing unusable data. Many of the concepts described here are applicable to other high-throughput technologies.
Eukaryotic Protein Kinases (ePKs) of the Helminth Parasite Schistosoma mansoni
Authors: Andrade Luiza F , Nahum Laila A , Avelar Lívia GA , Silva Larissa L , Zerlotini Adhemar , Ruiz Jerônimo C , Oliveira Guilherme
Published: May 2011

Background

Schistosomiasis remains an important parasitic disease and a major economic problem in many countries. The Schistosoma mansoni genome and predicted proteome sequences were recently published providing the opportunity to identify new drug candidates. Eukaryotic protein kinases (ePKs) play a central role in mediating signal transduction through complex networks and are considered druggable targets from the medical and chemical viewpoints. Our work aimed at analyzing the S. mansoni predicted proteome in order to identify and classify all ePKs of this parasite through combined computational approaches. Functional annotation was performed mainly to yield insights into the parasite signaling processes relevant to its complex lifestyle and to select some ePKs as potential drug targets.

Results

We have identified 252 ePKs, which corresponds to 1.9% of the S. mansoni predicted proteome, through sequence similarity searches using HMMs (Hidden Markov Models). Amino acid sequences corresponding to the conserved catalytic domain of ePKs were aligned by MAFFT and further used in distance-based phylogenetic analysis as implemented in PHYLIP. Our analysis also included the ePK homologs from six other eukaryotes. The results show that S. mansoni has proteins in all ePK groups. Most of them are clearly clustered with known ePKs in other eukaryotes according to the phylogenetic analysis. None of the ePKs are exclusively found in S. mansoni or belong to an expanded family in this parasite. Only 16 S. mansoni ePKs were experimentally studied, 12 proteins are predicted to be catalytically inactive and approximately 2% of the parasite ePKs remain unclassified. Some proteins were mentioned as good target for drug development since they have a predicted essential function for the parasite.

Conclusions

Our approach has improved the functional annotation of 40% of S. mansoni ePKs through combined similarity and phylogenetic-based approaches. As we continue this work, we will highlight the biochemical and physiological adaptations of S. mansoni in response to diverse environments during the parasite development, vector interaction, and host infection.
A quantitative real-time RT-PCR assay for mature C. albicans biofilms
Authors: Xie Zhihong , Thompson Angela , Kashleva Helena , Dongari-Bagtzoglou Anna
Published: May 2011

Background

Fungal biofilms are more resistant to anti-fungal drugs than organisms in planktonic form. Traditionally, susceptibility of biofilms to anti-fungal agents has been measured using the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxyanilide (XTT) assay, which measures the ability of metabolically active cells to convert tetrazolium dyes into colored formazan derivatives. However, this assay has limitations when applied to high C. albicans cell densities because substrate concentration and solubility are limiting factors in the reaction. Because mature biofilms are composed of high cell density populations we sought to develop a quantitative real-time RT-PCR assay (qRT-PCR) that could accurately assess mature biofilm changes in response to a wide variety of anti-fungal agents, including host immune cells.

Results

The XTT and qRT-PCR assays were in good agreement when biofilm changes were measured in planktonic cultures or in early biofilms which contain lower cell densities. However, the real-time qRT-PCR assay could also accurately quantify small-medium size changes in mature biofilms caused by mechanical biomass reduction, antifungal drugs or immune effector cells, that were not accurately quantifiable with the XTT assay.

Conclusions

We conclude that the qRT-PCR assay is more accurate than the XTT assay when measuring small-medium size effects of anti-fungal agents against mature biofilms. This assay is also more appropriate when mature biofilm susceptibility to anti-fungal agents is tested on complex biological surfaces, such as organotypic cultures.
The four Zn fingers of MBNL1 provide a flexible platform for recognition of its RNA binding elements
Authors: Cass Danielle , Hotchko Rachel , Barber Paul , Jones Kimberly , Gates Devika P , Berglund J Andrew
Published: May 2011

Background

Muscleblind-like 1 (MBNL1) is an alternative splicing factor containing four CCCH Zinc fingers (ZnFs). The sequestration of MBNL1 by expanded CUG and CCUG repeats is a major component in causing myotonic dystrophy. In addition to binding the structured expanded CUG and CCUG repeats; previous results suggested that MBNL1 binds single-stranded RNAs containing GC dinucleotides.

Results

We performed a systematic analysis of MBNL1 binding to single-stranded RNAs. These studies revealed that a single GC dinucleotide in poly-uridine is sufficient for MBNL1 binding and that a second GC dinucleotide confers higher affinity MBNL1 binding. However additional GC dinucleotides do not enhance RNA binding. We also showed that the RNA sequences adjacent to the GC dinucleotides play an important role in MBNL1 binding with the following preference: uridines >cytidines >adenosines >guanosines. For high affinity binding by MBNL1, the distance between the two GC dinucleotides can vary from 1 to 17 nucleotides.

Conclusions

These results suggest that MBNL1 is highly flexible and able to adopt different conformations to recognize RNAs with varying sequence configurations. Although MBNL1 contains four ZnFs, only two ZnF - GC dinucleotide interactions are necessary for high affinity binding.
Comparison of hemodynamic, biochemical and hematological parameters of healthy pregnant women in the third trimester of pregnancy and the active labor phase
Authors: Rodríguez-Dennen Fernando , Martínez-Ocaña Joel , Kawa-Karasik Simón , Villanueva-Egan Luis , Reyes-Paredes Norberto , Flisser Ana , Olivo-Díaz Angélica
Published: May 2011

Background

Pregnancy is accompanied by several hemodynamic, biochemical and hematological changes which revert to normal values after labor. The mean values of these parameters have been reported for developed countries, but not for Mexican women. Furthermore, labor constitutes a stress situation, in which these factors may be altered. It is known that serologic increase of heat shock protein (Hsp) 70 is associated with abnormal pregnancies, presenting very low level in normal pregnant women. Nevertheless, there are no studies where these measurements are compared in healthy pregnant women at their third trimester of pregnancy (3TP) and the active labor phase (ActLP).

Methods

Seventy five healthy Mexican pregnant women were included. Hemodynamic, biochemical and hematological parameters were obtained in all cases, and serum Hsp70 levels were measured in a sample of 15 women at 3TP and at ActLP.

Results

Significant differences were found in most analysis performed and in Hsp70 concentration at 3TP as compared to ActLP, however all were within normal range in both conditions, supporting that only in pathological pregnancies Hsp70 is drastically increased.

Conclusion

Results obtained indicate that 3TP and ActLP have clinical similarities in normal pregnancies, therefore if abnormalities are found during 3TP, precautions should be taken before ActLP.
Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival of gastric cancer with peritoneal carcinomatosis: evidence from an experimental study
Authors: Tang Li , Mei Lie-Jun , Yang Xiao-Jun , Huang Chao-Qun , Zhou Yun-Feng , Yonemura Yutaka , Li Yan
Published: May 2011

Background

Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) has been considered as a promising treatment modality for gastric cancer with peritoneal carcinomatosis (PC). However, there have also been many debates regarding the efficacy and safety of this new approach. Results from experimental animal model study could help provide reliable information. This study was to investigate the safety and efficacy of CRS + HIPEC to treat gastric cancer with PC in a rabbit model.

Methods

VX2 tumor cells were injected into the gastric submucosa of 42 male New Zealand rabbits using a laparotomic implantation technique, to construct rabbit model of gastric cancer with PC. The rabbits were randomized into control group (n = 14), CRS alone group (n = 14) and CRS + HIPEC group (n = 14). The control group was observed for natural course of disease progression. Treatments were started on day 9 after tumor cells inoculation, including maximal removal of tumor nodules in CRS alone group, and maximal CRS plus heperthermic intraperitoneal chemoperfusion with docetaxel (10 mg/rabbit) and carboplatin (40 mg/rabbit) at 42.0 ± 0.5°C for 30 min in CRS + HIPEC group. The primary endpoint was overall survival (OS). The secondary endpoints were body weight, biochemistry, major organ functions and serious adverse events (SAE).

Results

Rabbit model of gastric cancer with PC was successfully established in all animals. The clinicopathological features of the model were similar to human gastric PC. The median OS was 24.0 d (95% confidence interval 21.8 - 26.2 d ) in the control group, 25.0 d (95% CI 21.3 - 28.7 d ) in CRS group, and 40.0 d (95% CI 34.6 - 45.4 d ) in CRS + HIPEC group (P = 0.00, log rank test). Compared with CRS only or control group, CRS + HIPEC could extend the OS by at least 15 d (60%). At the baseline, on the day of surgery and on day 8 after surgery, the peripheral blood cells counts, liver and kidney functions, and biochemistry parameters were all comparable. SAE occurred in 0 animal in control group, 2 animals in CRS alone group including 1 animal death due to anesthesia overdose and another death due to postoperative hemorrhage, and 3 animals in CRS + HIPEC group including 1 animal death due to anesthesia overdose, and 2 animal deaths due to diarrhea 23 and 27 d after operation.

Conclusions

In this rabbit model of gastric cancer with PC, CRS alone could not bring benefit while CRS + HIPEC with docetaxel and carboplatin could significantly prolong the survival with acceptable safety.