bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rac2-MRC-cIII–generated ROS cause genomic instability in chronic myeloid leukemia stem cells and primitive progenitors
Authors: Nieborowska-Skorska Margaret , Kopinski Piotr K. , Ray Regina , Hoser Grazyna , Ngaba Danielle , Flis Sylwia , Cramer Kimberly , Reddy Mamatha M. , Koptyra Mateusz , Penserga Tyrone , Glodkowska-Mrowka Eliza , Bolton Elisabeth , Holyoake Tessa L. , Eaves Connie J. , Cerny-Reiterer Sabine , Valent Peter , Hochhaus Andreas , Hughes Timothy P. , van der Kuip Heiko , Sattler Martin , Wiktor-Jedrzejczak Wieslaw , Richardson Christine , Dorrance Adrienne , Stoklosa Tomasz , Williams David A. , Skorski Tomasz 
Published: March 2012

Abstract
Chronic myeloid leukemia in chronic phase (CML-CP) is induced by BCR-ABL1 oncogenic tyrosine kinase. Tyrosine kinase inhibitors eliminate the bulk of CML-CP cells, but fail to eradicate leukemia stem cells (LSCs) and leukemia progenitor cells (LPCs) displaying innate and acquired resistance, respectively. These cells may accumulate genomic instability, leading to disease relapse and/or malignant progression to a fatal blast phase. In the present study, we show that Rac2 GTPase alters mitochondrial membrane potential and electron flow through the mitochondrial respiratory chain complex III (MRC-cIII), thereby generating high levels of reactive oxygen species (ROS) in CML-CP LSCs and primitive LPCs. MRC-cIII–generated ROS promote oxidative DNA damage to trigger genomic instability, resulting in an accumulation of chromosomal aberrations and tyrosine kinase inhibitor–resistant BCR-ABL1 mutants. JAK2(V617F) and FLT3(ITD)–positive polycythemia vera cells and acute myeloid leukemia cells also produce ROS via MRC-cIII. In the present study, inhibition of Rac2 by genetic deletion or a small-molecule inhibitor and down-regulation of mitochondrial ROS by disruption of MRC-cIII, expression of mitochondria-targeted catalase, or addition of ROS-scavenging mitochondria-targeted peptide aptamer reduced genomic instability. We postulate that the Rac2-MRC-cIII pathway triggers ROS-mediated genomic instability in LSCs and primitive LPCs, which could be targeted to prevent the relapse and malignant progression of CML.
An institutional perspective on the impact of recent antibiotic exposure on length of stay and hospital costs for patients with gram-negative sepsis
Authors: Micek Scott , Johnson Michael T , Reichley Richard , Kollef Marin H 
Published: March 2012

Abstract

Background
Prior antibiotic exposure has been associated with the emergence of antibiotic resistance in subsequent bacterial infections, whose outcomes are typically worse than similar infections with more antibiotic susceptible infections. The influence of prior antibiotic exposure on hospital length of stay (LOS) and costs in patients with severe sepsis or septic shock attributed to Gram-negative bacteremia has not been previously examined.

Methods
A retrospective cohort study of hospitalized patients (January 2002-December 2007) was performed at Barnes-Jewish Hospital, a 1200-bed urban teaching hospital. Patients with Gram-negative bacteremia complicated by severe sepsis or septic shock had data abstraction from computerized medical records. We examined a consecutive cohort of 754 subjects (mean age 59.3 ± 16.3 yrs, mean APACHE II 23.7 ± 6.7).

Results

Escherichia coli (30.8%), Klebsiella pneumoniae (23.2%), and Pseudomonas aeruginosa (17.6%) were the most common organisms isolated from blood cultures. 310 patients (41.1%) had exposure to antimicrobial agents in the previous 90 days. Patients with recent antibiotic exposure had greater inappropriate initial antimicrobial therapy (45.4% v. 21.2%; p < 0.001) and hospital mortality (51.3% v. 34.0%; p < 0.001) compared to patients without recent antibiotic exposure. The unadjusted median LOS (25th percentile, 75th percentile) following sepsis onset in patients with prior antimicrobial exposure was 13.0 days (5.0 days, 24.0 days) compared to 8.0 days (5.0 days, 14.0 days) in those without prior antimicrobial exposure (p < 0.001). In a Cox model controlling for multiple confounders, prior antibiotic exposure independently correlated with remaining hospitalized (Adjusted hazard ratio: 1.473, 95% CI: 1.297-1.672, p < 0.001). Adjusting for potential confounders indicated that prior antibiotic exposure independently increased median attributable LOS by 5.0 days. Similarly, total hospital costs following sepsis onset was significantly greater among patients with prior antimicrobial exposure (median values: $94,737 v. $21,329; p < 0.001).

Conclusions
Recent antibiotic exposure is associated with increased LOS and hospital costs in Gram-negative bacteremia complicated by severe sepsis or septic shock. Clinicians and hospital administrators should consider the potential impact of recent antibiotic exposure when formulating empiric treatment decisions for patients with serious infections attributed to Gram-negative bacteria.
Addition of bevacizumab to first-line chemotherapy in advanced colorectal cancer: a systematic review and meta-analysis, with emphasis on chemotherapy subgroups
Authors: Macedo Ligia Traldi , da Costa Lima Andre Bacellar , Sasse Andre Deeke 
Published: March 2012

Abstract

Background
Bevacizumab has an important role in first-line treatment of metastatic colorectal cancer. However, clinical trials studying its effect have involved distinct chemotherapy regimens with divergent results. The aim of this meta-analysis is to gather current data and evaluate not only the efficacy of bevacizumab, but also the impact of divergent backbone regimens.

Methods
A wide search of randomized clinical trials using bevacizumab in first-line metastatic colorectal cancer was performed in Embase, MEDLINE, LILACS and Cochrane databases. Meeting presentations and abstracts were also investigated. The resulting data were examined and included in the meta-analysis according to the type of regimen.

Results
Six trials, totaling 3060 patients, were analyzed. There was an advantage to using bevacizumab for overall survival (OS) and progression-free survival (PFS) (HR = 0.84; CI: 0.77-0.91; P < 0.00001 and HR = 0.72; CI: 0.66-0.78; P < 0.00001, respectively). However, heterogeneity of results was very high for both outcomes, and subgroup analyses supported the OS advantage with bevacizumab restricted to irinotecan-based regimens. Infusional fluorouracil subsets involved a minor proportion, and did not demonstrate statistical benefit in PFS or OS. Regarding toxicity, higher rates of grades 3-4 hypertension, bleeding, thromboembolic events and proteinuria were uniformly observed with bevacizumab, leading to increased treatment interruptions (HR = 1.47; P = 0.0004).

Conclusions
Bevacizumab has efficacy in first-line treatment of advanced colorectal cancer, but the current data are insufficient to support efficacy in all regimens, especially infusional fluorouracil regimens, like FOLFIRI and FOLFOX.
Patient-reported physical activity questionnaires: A systematic review of content and format
Authors: Williams Kate , Frei Anja , Vetsch Anders , Dobbels Fabienne , Puhan Milo A , Rüdell Katja 
Published: March 2012

AbstractBackgroundMany patients with chronic illness are limited in their physical activities. This systematic review evaluates the content and format of patient-reported outcome (PRO) questionnaires that measure physical activity in elderly and chronically ill populations.MethodsQuestionnaires were identified by a systematic literature search of electronic databases (Medline, Embase, PsychINFO & CINAHL), hand searches (reference sections and PROQOLID database) and expert input. A qualitative analysis was conducted to assess the content and format of the questionnaires and a Venn diagram was produced to illustrate this. Each stage of the review process was conducted by at least two independent reviewers.Results104 questionnaires fulfilled our criteria. From these, 182 physical activity domains and 1965 items were extracted. Initial qualitative analysis of the domains found 11 categories. Further synthesis of the domains found 4 broad categories: 'physical activity related to general activities and mobility', 'physical activity related to activities of daily living', 'physical activity related to work, social or leisure time activities', and '(disease-specific) symptoms related to physical activity'. The Venn diagram showed that no questionnaires covered all 4 categories and that the '(disease-specific) symptoms related to physical activity' category was often not combined with the other categories.ConclusionsA large number of questionnaires with a broad range of physical activity content were identified. Although the content could be broadly organised, there was no consensus on the content and format of physical activity PRO questionnaires in elderly and chronically ill populations. Nevertheless, this systematic review will help investigators to select a physical activity PRO questionnaire that best serves their research question and context.
From "best practice" to "next practice": the effectiveness of school-based health promotion in improving healthy eating and physical activity and preventing childhood obesity
Authors: Fung Christina , Kuhle Stefan , Lu Connie , Purcell Megan , Schwartz Marg , Storey Kate , Veugelers Paul J 
Published: March 2012

Abstract

Background
In 2005, we reported on the success of Comprehensive School Health (CSH) in improving diets, activity levels, and body weights. The successful program was recognized as a "best practice" and has inspired the development of the Alberta Project Promoting active Living and healthy Eating (APPLE) Schools. The project includes 10 schools, most of which are located in socioeconomically disadvantaged areas. The present study examines the effectiveness of a CSH program adopted from a "best practice" example in another setting by evaluating temporal changes in diets, activity levels and body weight.

Methods
In 2008 and 2010, we surveyed grade 5 students from approximately 150 randomly selected schools from the Canadian province of Alberta and students from 10 APPLE Schools. Students completed the Harvard Youth/Adolescent Food Frequency Questionnaire, questions on physical activity, and had their height and weight measured. Multilevel regression methods were used to analyze changes in diets, activity levels, and body weight between 2008 and 2010.

Results
In 2010 relative to 2008, students attending APPLE Schools were eating more fruits and vegetables, consuming fewer calories, were more physically active and were less likely obese. These changes contrasted changes observed among students elsewhere in the province.

Conclusions
These findings provide evidence on the effectiveness of CSH in improving health behaviors. They show that an example of "best practice" may lead to success in another setting. Herewith the study provides the evidence that investments for broader program implementation based on "best practice" are justified.
Comparison of worm development and host immune responses in natural hosts of schistosoma japonicum, yellow cattle and water buffalo
Authors: Yang Jianmei , Fu Zhiqiang , Feng Xingang , Shi Yaojun , Yuan Chunxiu , Liu Jinming , Hong Yang , Li Hao , Lu Ke , Lin Jiaojiao 
Published: March 2012

AbstractBackgroundYellow cattle and water buffalo are two of the most important natural hosts forSchistosoma japonicumin China. Previous observation has revealed that yellow cattle are more suited to the development ofS. japonicumthan water buffalo. Understanding more about the molecular mechanisms involved in worm development, as well as the pathological and immunological differences between yellow cattle and water buffalo post infection withS japonicumwill provide useful information for the vaccine design and its delivery procedure.ResultsThe worm length (p< 0.01), worm recovery rate (p< 0.01) and the percentage of paired worms (p< 0.01) were significantly greater in yellow cattle than those in water buffalo. There were many white egg granulomas in the livers of yellow cattle, but fewer were observed in water buffalo at 7 weeks post infection. The livers of infected yellow cattle contained significantly increased accumulation of inflammatory cells, and the schistosome eggs were surrounded with large amounts of eosinophil infiltration. In contrast, no hepatocyte swelling or lymphocyte infiltration, and fewer white blood cells, was observed in water buffalo. The percentage of CD4+T cells was higher in yellow cattle, while the percentage of CD8+T cells was higher in water buffalo from pre-infection to 7 w post infection. The CD4/CD8 ratios were decreased in both species after challenge with schistosomes. Comparing with water buffalo, the IFN-γ level was higher and decreased significantly, while the IL-4 level was lower and increased gradually in yellow cattle from pre-infection to 7 w post infection.ConclusionsIn this study, we confirmed that yellow cattle were more suited to the development ofS. japonicumthan water buffalo, and more serious pathological damage was observed in infected yellow cattle. Immunological analysis suggested that CD4+T cells might be an integral component of the immune response and might associate with worm development in yellow cattle. A shift from Th1 to Th2 type polarized immunity was only shown clearly in schistosome-infected yellow cattle, but no shift in water buffalo. The results provide valuable information for increased understanding of host-schistosome interactions, and for control of schistosomiasis.
Automatic single-trial discrimination of mental arithmetic, mental singing and the no-control state from prefrontal activity: toward a three-state NIRS-BCI
Authors: Power Sarah D , Kushki Azadeh , Chau Tom 
Published: March 2012

Abstract

Background
Near-infrared spectroscopy (NIRS) is an optical imaging technology that has recently been investigated for use in a safe, non-invasive brain-computer interface (BCI) for individuals with severe motor impairments. To date, most NIRS-BCI studies have attempted to discriminate two mental states (e.g., a mental task and rest), which could potentially lead to a two-choice BCI system. In this study, we attempted to automatically differentiate three mental states - specifically, intentional activity due to 1) a mental arithmetic (MA) task and 2) a mental singing (MS) task, and 3) an unconstrained, "no-control (NC)" state - to investigate the feasibility of a three-choice system-paced NIRS-BCI.

Results
Deploying a dual-wavelength frequency domain near-infrared spectrometer, we interrogated nine sites around the frontopolar locations while 7 able-bodied adults performed mental arithmetic and mental singing to answer multiple-choice questions within a system-paced paradigm. With a linear classifier trained on a ten-dimensional feature set, an overall classification accuracy of 56.2% was achieved for the MA vs. MS vs. NC classification problem and all individual participant accuracies significantly exceeded chance (i.e., 33%). However, as anticipated based on results of previous work, the three-class discrimination was unsuccessful for three participants due to the ineffectiveness of the mental singing task. Excluding these three participants increases the accuracy rate to 62.5%. Even without training, three of the remaining four participants achieved accuracies approaching 70%, the value often cited as being necessary for effective BCI communication.

Conclusions
These results are encouraging and demonstrate the potential of a three-state system-paced NIRS-BCI with two intentional control states corresponding to mental arithmetic and mental singing.
Web-Based Tailored Education Program for Disease-Free Cancer Survivors With Cancer-Related Fatigue: A Randomized Controlled Trial
Authors: Yun Young Ho , Lee Keun Seok , Kim Young-Woo , Park Sang Yoon , Lee Eun Sook , Noh Dong-Young , Kim Sung , Oh Jae Hwan , Jung So Youn , Chung Ki-Wook , Lee You Jin , Jeong Seung-Yong , Park Kyu Joo , Shim Young Mog , Zo Jae Ill , Park Ji Won , Kim Young Ae , Shon En Jung , Park Sohee 
Published: March 2012

Purpose To determine whether an Internet-based tailored education program is effective for disease-free cancer survivors with cancer-related fatigue (CRF). Patients and Methods We randomly assigned patients who had completed primary cancer treatment within the past 24 months in any of four Korean hospitals and had reported moderate to severe fatigue for at least 1 week to participate in a 12-week, Internet-based, individually tailored CRF education program or to receive routine care. We based the program on the CRF guidelines of the National Comprehensive Cancer Network (NCCN) and incorporated the transtheoretic model (TTM). At baseline and 12 weeks, we used the Brief Fatigue Inventory (BFI) and Fatigue Severity Scale (FSS) as primary outcomes and the Hospital Anxiety and Depression Scale (HADS) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) for secondary outcomes. Results We recruited 273 participants and randomly assigned 136 to the intervention group. Compared with the control group, the intervention group had an improvement in fatigue as shown by a significantly greater decrease in BFI global score (−0.66 points; 95% CI −1.04 to −0.27) and FSS total score (−0.49; 95% CI, −0.78 to −0.21). In secondary outcomes, the intervention group experienced a significantly greater decrease in HADS anxiety score (−0.90; 95% CI, −1.51 to −0.29) as well as global quality of life (5.22; 95% CI, 0.93 to 9.50) and several functioning scores of the EORTC QLQ-C30. Conclusion An Internet-based education program based on NCCN guidelines and TTM may help patients manage CRF.
Palliative Sedation in End-of-Life Care and Survival: A Systematic Review
Authors: Maltoni Marco , Scarpi Emanuela , Rosati Marta , Derni Stefania , Fabbri Laura , Martini Francesca , Amadori Dino , Nanni Oriana 
Published: March 2012

Purpose Palliative sedation is a clinical procedure aimed at relieving refractory symptoms in patients with advanced cancer. It has been suggested that sedative drugs may shorten life, but few studies exist comparing the survival of sedated and nonsedated patients. We present a systematic review of literature on the clinical practice of palliative sedation to assess the effect, if any, on survival. Methods A systematic review of literature published between January 1980 and December 2010 was performed using MEDLINE and EMBASE databases. Search terms included palliative sedation, terminal sedation, refractory symptoms, cancer, neoplasm, palliative care, terminally ill, end-of-life care, and survival. A manual search of the bibliographies of electronically identified articles was also performed. Results Eleven published articles were identified describing 1,807 consecutive patients in 10 retrospective or prospective nonrandomized studies, 621 (34.4%) of whom were sedated. One case-control study was excluded from prevalence analysis. The most frequent reason for sedation was delirium in the terminal stages of illness (median, 57.1%; range, 13.8% to 91.3%). Benzodiazepines were the most common drug category prescribed. Comparing survival of sedated and nonsedated patients, the sedation approach was not shown to be associated with worse survival. Conclusion Even if there is no direct evidence from randomized clinical trials, palliative sedation, when appropriately indicated and correctly used to relieve unbearable suffering, does not seem to have any detrimental effect on survival of patients with terminal cancer. In this setting, palliative sedation is a medical intervention that must be considered as part of a continuum of palliative care.
Improved Survival for Children and Adolescents With Acute Lymphoblastic Leukemia Between 1990 and 2005: A Report From the Children's Oncology Group
Authors: Hunger Stephen P. , Lu Xiaomin , Devidas Meenakshi , Camitta Bruce M. , Gaynon Paul S. , Winick Naomi J. , Reaman Gregory H. , Carroll William L. 
Published: March 2012

PurposeTo examine population-based improvements in survival and the impact of clinical covariates on outcome among children and adolescents with acute lymphoblastic leukemia (ALL) enrolled onto Children's Oncology Group (COG) clinical trials between 1990 and 2005.Patients and MethodsIn total, 21,626 persons age 0 to 22 years were enrolled onto COG ALL clinical trials from 1990 to 2005, representing 55.8% of ALL cases estimated to occur among US persons younger than age 20 years during this period. This period was divided into three eras (1990-1994, 1995-1999, and 2000-2005) that included similar patient numbers to examine changes in 5- and 10-year survival over time and the relationship of those changes in survival to clinical covariates, with additional analyses of cause of death.ResultsFive-year survival rates increased from 83.7% in 1990-1994 to 90.4% in 2000-2005 (P < .001). Survival improved significantly in all subgroups (except for infants age ≤ 1 year), including males and females; those age 1 to 9 years, 10+ years, or 15+ years; in whites, blacks, and other races; in Hispanics, non-Hispanics, and patients of unknown ethnicity; in those with B-cell or T-cell immunophenotype; and in those with National Cancer Institute (NCI) standard- or high-risk clinical features. Survival rates for infants changed little, but death following relapse/disease progression decreased and death related to toxicity increased.ConclusionThis study documents ongoing survival improvements for children and adolescents with ALL. Thirty-six percent of deaths occurred among children with NCI standard-risk features emphasizing that efforts to further improve survival must be directed at both high-risk subsets and at those children predicted to have an excellent chance for cure.
Preoperative Identification of a Low-Risk Group for Lymph Node Metastasis in Endometrial Cancer: A Korean Gynecologic Oncology Group Study
Authors: Kang Sokbom , Kang Woo Dae , Chung Hyun Hoon , Jeong Dae Hoon , Seo Sang-Soo , Lee Jong-Min , Lee Jae-Kwan , Kim Jae Weon , Kim Seok-Mo , Park Sang-Yoon , Kim Ki Tae 
Published: March 2012

Purpose The aim of this study was to develop a preoperative risk prediction model for lymph node metastasis in patients with endometrial cancer and to identify a low-risk group before surgery. Patients and Methods The medical records of 360 patients with endometrial cancer who underwent surgical staging were collected from four institutions and were retrospectively reviewed. By using serum CA-125 levels, preoperative biopsy data, and magnetic resonance imaging (MRI) data, a multivariate logistic model was created. Patients whose predicted probability was less than 4% were defined as low risk. The developed model was externally validated in 180 patients from two independent institutions. Results Serum CA-125 levels and three MRI parameters (deep myometrial invasion, lymph node enlargement, and extension beyond uterine corpus) were found to be independent risk factors for nodal metastasis. The model classified 53% of patients as part of a low-risk group, and the false negative rate was 1.7%. In the validation cohort, the model classified 43% of patients as low-risk, and the false negative rate was 1.4%. The model showed good discrimination (area under the receiver operator characteristic curve = 0.85) and was calibrated well. The negative likelihood ratio of our low-risk criteria was 0.11 (95% CI, 0.04 to 0.29), which was equivalent to the false-negative rate of 1.3% (95% CI, 0.5% to 3.3%) at the assumed prevalence of nodal metastasis of 10%. Conclusion Using serum CA-125 and MRI as criteria resulted in the accurate identification of a low-risk group for lymph node metastasis among patients with endometrial cancer.