bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors influencing enrollment of African Americans in the Look AHEAD trial
Authors: Mount David L , Davis Cralen , Kennedy Betty , Raatz Susan , Dotson Kathy , Gary-Webb Tiffany L , Thomas Sheikilya , Johnson Karen C , Espeland Mark A ,   and the Look AHEAD Research Group
Published: November 2011

Background Many factors have been identified that influence the recruitment of African Americans into clinical trials; however, the influence of eligibility criteria may not be widely appreciated. We used the experience from the Look AHEAD (Action for Health in Diabetes) trial screening process to examine the differential impact eligibility criteria had on the enrollment of African Americans compared to other volunteers. Methods Look AHEAD is a large randomized clinical trial to examine whether assignment to an intensive lifestyle intervention designed to produce and maintain weight loss reduces the long-term risk of major cardiovascular events in adults with type 2 diabetes. Differences in the screening, eligibility, and enrollment rates between African Americans and members of other racial/ethnic groups were examined to identify possible reasons. Results Look AHEAD screened 28,735 individuals for enrollment, including 6226 (21.7%) who were self-identified African Americans. Of these volunteers, 12.9% of the African Americans compared to 19.3% of all other screenees ultimately enrolled ( p < 0.001). African Americans no more often than others were lost to follow-up or refused to attend clinic visits to establish eligibility. Furthermore, the enrollment rates of individuals with histories of cardiovascular disease and diabetes therapy did not markedly differ between the ethnic groups. Higher prevalence of adverse levels of blood pressure, heart rate, HbA1c, and serum creatinine among African American screenees accounted for the greater proportions excluded (all p < 0.001). Conclusions Compared to non-African Americans, African American were more often ineligible for the Look AHEAD trial due to comorbid conditions. Monitoring trial eligibility criteria for differential impact, and modifying them when appropriate, may ensure greater enrollment yields.
Evaluation of bioactive sphingolipids in 4-HPR-resistant leukemia cells
Authors: Apraiz Aintzane , Idkowiak-Baldys Jolanta K , Boyano María Dolores , Pérez-Yarza Gorka , Hannun Yusuf A , Asumendi Aintzane 
Published: November 2011

Abstract

Background

N-(4-hydroxyphenyl)retinamide (4-HPR, fenretinide) is a synthetic retinoid with potent pro-apoptotic activity against several types of cancer, but little is known regarding mechanisms leading to chemoresistance. Ceramide and, more recently, other sphingolipid species (e.g., dihydroceramide and dihydrosphingosine) have been implicated in 4-HPR-mediated tumor cell death. Because sphingolipid metabolism has been reported to be altered in drug-resistant tumor cells, we studied the implication of sphingolipids in acquired resistance to 4-HPR based on an acute lymphoblastic leukemia model.

Methods
CCRF-CEM cell lines resistant to 4-HPR were obtained by gradual selection. Endogenous sphingolipid profiles and in situ enzymatic activities were determined by LC/MS, and resistance to 4-HPR or to alternative treatments was measured using the XTT viability assay and annexin V-FITC/propidium iodide labeling.

Results
No major crossresistance was observed against other antitumoral compounds (i.e. paclitaxel, cisplatin, doxorubicin hydrochloride) or agents (i.e. ultra violet C, hydrogen peroxide) also described as sphingolipid modulators. CCRF-CEM cell lines resistant to 4-HPR exhibited a distinctive endogenous sphingolipid profile that correlated with inhibition of dihydroceramide desaturase. Cells maintained acquired resistance to 4-HPR after the removal of 4-HPR though the sphingolipid profile returned to control levels. On the other hand, combined treatment with sphingosine kinase inhibitors (unnatural (dihydro)sphingosines ((dh)Sph)) and glucosylceramide synthase inhibitor (PPMP) in the presence or absence of 4-HPR increased cellular (dh)Sph (but not ceramide) levels and were highly toxic for both parental and resistant cells.

Conclusions
In the leukemia model, acquired resistance to 4-HPR is selective and persists in the absence of sphingolipid profile alteration. Therapeutically, the data demonstrate that alternative sphingolipid-modulating antitumoral strategies are suitable for both 4-HPR-resistant and sensitive leukemia cells. Thus, whereas sphingolipids may not be critical for maintaining resistance to 4-HPR, manipulation of cytotoxic sphingolipids should be considered a viable approach for overcoming resistance.
Mortality in an antiretroviral therapy programme in Jinja, south-east Uganda: a prospective cohort study
Authors: Amuron Barbara , Levin Jonathan , Birunghi Josephine , Namara Geoffrey , Coutinho Alex , Grosskurth Heiner , Jaffar Shabbar 
Published: November 2011

Abstract

Background
There have been few reports of long-term survival of HIV-infected patients on antiretroviral therapy (ART) in Africa managed under near normal health service conditions.

Methods
Participants starting ART between February 2005 and December 2006 in The AIDS Support (TASO) clinic in Jinja, Uganda, were enrolled into a cluster-randomised trial of home versus facility-based care and followed up to January 2009. The trial was integrated into normal service delivery with patients managed by TASO staff according to national guidelines. Rates of survival, virological failure, hospital admissions and CD4 count over time were similar between the two arms. Data for the present analysis were analysed using Cox regression analyses.

Results
1453 subjects were enrolled with baseline median count of 108 cells/μl. Over time, 119 (8%) withdrew and 34 (2%) were lost to follow-up. 197/1453 (14%) died. Mortality rates (95% CI) per 100 person-years were 11.8 (10.1, 13.8) deaths in the first year and 2.4 (1.8, 3.2) deaths thereafter. The one, two and three year survival probabilities (95% CI) were 0.89 (0.87 - 0.91), 0.86 (0.84 - 0.88) and 0.85 (0.83 - 0.87) respectively. Low baseline CD4 count, low body weight, advanced clinical condition (WHO stages III and IV), not being on cotrimoxazole prophylaxis and male gender were associated independently with increased mortality. Tuberculosis, cryptococcal meningitis and diarrhoeal disease were estimated to be major causes of death.

Conclusion
Practical and affordable interventions are needed to enable earlier initiation of ART and to reduce mortality risk among those who present late for treatment with advanced disease.
Survey of enterovirus infections from hand, foot and mouth disease outbreak in china, 2009
Authors: Yang Fan , Zhang Ting , Hu Yongfeng , Wang Xiaofang , Du Jiang , Li Yufen , Sun Shaoxia , Sun Xiuhua , Li Zhifang , Jin Qi 
Published: November 2011

Abstract

Background
In China, a rapid expansion of Hand, foot, and mouth disease (HFMD) outbreaks has occurred since 2004 and HFMD has become an important issue for China. However, people are still only concerned with human enterovirus 71(HEV-71) and coxsackie virus A16 (CV-A16). Much of what is known about the other enterovirus infections relies on fractional evidence and old epidemic data, with little knowledge concerning their distribution. To alert potential threatens of the other enteroviruses, our study genetically characterized specimens from different regions of China and yielded novel information concerning the circulating and phylogenetic characteristics of enteroviral strains from HFMD cases.

Findings
A total of 301 clinical throat swabs were randomly obtained from patients suffering from HFMD from the southern, northern and central regions of China during outbreaks in 2009. 266 of 301 (88.4%) HFMD cases were found positive for HEV and seven genotypes, HEV-71, CV-A16, -B5, -A4, -A6, -A10, and -A12, were detected.

Conclusions
The HFMD pathogen compositions in the different regions of China were significantly different. HFMD epidemics might persist for a long time in China due to the multiple pathogen compositions, the enteroviral characteristic of recombination and co-infection, the ever-increasing travel and migration and the deficiency of effective vaccine. Our study deserves the attention on HFMD control and vaccine development.
Expression and role of fibroblast activation protein-alpha in microinvasive breast carcinoma
Authors: Hua Xing , Yu Lina , Huang Xiaoxiao , Liao Zexiao , Xian Qi 
Published: November 2011

Abstract

Background
Diagnosis of ductal carcinoma in situ (DCIS) in breast cancer cases is challenging for pathologist due to a variety of in situ patterns and artefacts, which could be misinterpreted as stromal invasion. Microinvasion is detected by the presence of cytologically malignant cells outside the confines of the basement membrane and myoepithelium. When malignant cells invade the stroma, there is tissue remodeling induced by perturbed stromal-epithelial interactions. Carcinoma-associated fibroblasts (CAFs) are main cells in the microenvironment of the remodeled tumor-host interface. They are characterized by the expression of the specific fibroblast activation protein-alpha (FAP-α), and differ from that of normal fibroblasts exhibiting an immunophenotype of CD34. We hypothesized that staining for FAP-α may be helpful in determining whether DCIS has microinvasion.

Methods
349 excised breast specimens were immunostained for smooth muscle actin SMA, CD34, FAP-α, and Calponin. Study material was divided into 5 groups: group 1: normal mammary tissues of healthy women after plastic surgery; group 2: usual ductal hyperplasia (UDH); group 3: DCIS without microinvasion on H & E stain; group 4: DCIS with microinvasion on H & E stain (DCIS-MI), and group 5: invasive ductal carcinoma (IDC). A comparative evaluation of the four immunostains was conducted.

Results
Our results demonstrated that using FAP-α and Calponin adjunctively improved the sensitivity of pathological diagnosis of DCIS-MI by 11.29%, whereas the adjunctive use of FAP-α and Calponin improved the sensitivity of pathological diagnosis of DCIS by 13.6%.

Conclusions
This study provides the first evidence that immunostaining with FAP-α and Calponin can serve as a novel marker for pathologically diagnosing whether DCIS has microinvasion.
A survey of foot problems in community‐dwelling older Greek Australians
Authors: Kaoulla Patricia , Frescos Nicoletta , Menz Hylton B 
Published: November 2011

AbstractBackgroundFoot problems are common in older people and are associated with impaired mobility and quality of life. However, the characteristics of foot problems in older Australians for whom English is a second language have not been evaluated.MethodsOne hundred and four community‐dwelling people aged 64 to 90 years with disabling foot pain (according to the case definition of the Manchester Foot Pain and Disability Index, or MFPDI) were recruited from four Greek elderly citizens clubs in Melbourne, Australia. All participants completed a Greek language questionnaire consisting of general medical history, the Medical Outcomes Study Short‐Form 36 (SF‐36) questionnaire, the MFPDI, and specific questions relating to foot problems and podiatry service utilisation. In addition, all participants underwent a brief clinical foot assessment.ResultsThe MFPDI score ranged from 1 to 30 (median 14), out of a total possible score of 34. Women had significantly higher total MFPDI scores and MFPDI subscale scores. The MFPDI total score and subscale scores were significantly associated with most of the SF‐36 subscale scores. The most commonly reported foot problem was difficulty finding comfortable shoes (38%), and the most commonly observed foot problem was the presence of hyperkeratotic lesions (29%). Only 13% of participants were currently receiving podiatry treatment, and 40% stated that they required more help looking after their feet. Those who reported difficulty finding comfortable shoes were more likely to be female, and those who required more help looking after their feet were more likely to be living alone and have osteoarthritis in their knees or back.ConclusionsFoot problems appear to be common in older Greek Australians, have a greater impact on women, and are associated with reduced health‐related quality of life. These findings are broadly similar to previous studies in English‐speaking older people in Australia. However, only a small proportion of this sample was currently receiving podiatry treatment, and a substantial number stated that they required more help looking after their feet. To address this issue, steps need to be taken to increase awareness of podiatry services among older Greek Australians.
Survival following a vertical free fall from 300 feet: The crucial role of body position to impact surface
Authors: Weckbach Sebastian , Flierl Michael A , Blei Michael , Burlew Clay Cothren , Moore Ernest E , Stahel Philip F 
Published: November 2011

Abstract
We report the case of a 28-year old rock climber who survived an "unsurvivable" injury consisting of a vertical free fall from 300 feet onto a solid rock surface. The trauma mechanism and injury kinetics are analyzed, with a particular focus on the relevance of body positioning to ground surface at the time of impact. The role of early patient transfer to a level 1 trauma center, and "damage control" management protocols for avoiding delayed morbidity and mortality in this critically injured patient are discussed.
ARTEMIN synergizes with TWIST1 to promote metastasis and poor survival outcome in patients with ER negative mammary carcinoma
Authors: Banerjee Arindam , Wu Zheng-Sheng , Qian PengXu , Kang Jian , Pandey Vijay , Liu Dong-Xu , Zhu Tao , Lobie Peter E 
Published: November 2011

Abstract
Introduction
ARTEMIN (ARTN) is an estrogen regulated growth factor, the expression of which promotes resistance to antiestrogen therapies and predicts poorer survival outcome of patients with estrogen receptor (ER) positive mammary carcinoma (ER+MC) treated with tamoxifen. ARTN is also expressed in ER negative mammary carcinoma (ER-MC). Herein, we determined the role of ARTN in ER-MC and defined the mechanism of action producing poor patient prognosis.

Methods
We modulated the expression of ARTN in two ER- (mesenchymal/claudin-low) mammary carcinoma cell lines (BT549 and MDA-MB-231) by forced expression or small interfering RNA (siRNA) mediated depletion. The effects of modulation of ARTN expression were examined by various in vitro measures of oncogenicity, including the expression of TWIST1 messenger RNA (mRNA) and protein. In vitro results were correlated to xenograft studies in immunodeficient mice. Co-expression of ARTN and TWIST1 and their association to poor survival outcome were examined in a cohort of patients with ER-MC. Pathway analysis was performed by pharmacological inhibition of phosphorylation of AKT (pAKT-Ser 473) or modulation of TWIST1 expression.

Results
ARTN expression resulted in ER-MC cells with enhanced mesenchymal characteristics, including increased invasion and a gene expression profile consistent with enhanced mesenchymal phenotype. ARTN stimulated ER-MC cell anchorage independent and 3D matrigel growth, endothelial cell adhesion and transmigration of ER-MC cells through an endothelial cell barrier. Forced expression of ARTN produced a larger, locally invasive tumour mass with tumour emboli that produced distant metastasis. ARTN regulated TWIST1 expression in ER-MC cells and ARTN expression was significantly correlated to TWIST1 expression in a panel of mammary carcinoma cell lines and in a cohort of patients with ER-MC. Low expression of both ARTN and TWIST1 predicted 100% relapse free and overall survival in patients with ER-MC, whereas high expression of both ARTN and TWIST1 was associated with a poor survival outcome. ARTN stimulated an increase in TWIST1 expression via increased AKT activity. siRNA mediated depletion of TWIST1 abrogated ARTN stimulated cellular behaviour associated with metastasis, and forced expression of TWIST1 abrogated the functional effects of ARTN depletion.

Conclusions
ARTN and TWIST1 synergize to produce a worse outcome in ER-MC and combined inhibition of ARTN and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) may therefore provide a novel therapeutic strategy in this subtype of mammary carcinoma.
Development and Independent Validation of a Prognostic Assay for Stage II Colon Cancer Using Formalin-Fixed Paraffin-Embedded Tissue
Authors: Kennedy Richard D. , Bylesjo Max , Kerr Peter , Davison Timothy , Black Julie M. , Kay Elaine W. , Holt Robert J. , Proutski Vitali , Ahdesmaki Miika , Farztdinov Vadim , Goffard Nicolas , Hey Peter , McDyer Fionnuala , Mulligan Karl , Mussen Julie , O'Brien Eamonn , Oliver Gavin , Walker Steven M. , Mulligan Jude M. , Wilson Claire , Winter Andreas , O'Donoghue Diarmuid , Mulcahy Hugh , O'Sullivan Jacintha , Sheahan Kieran , Hyland John , Dhir Rajiv , Bathe Oliver F. , Winqvist Ola , Manne Upender , Shanmugam Chandrakumar , Ramaswamy Sridhar , Leon Eduardo J. , Smith William I. , McDermott Ultan , Wilson Richard H. , Longley Daniel , Marshall John , Cummins Robert , Sargent Daniel J. , Johnston Patrick G. , Harkin D. Paul 
Published: November 2011

Purpose Current prognostic factors are poor at identifying patients at risk of disease recurrence after surgery for stage II colon cancer. Here we describe a DNA microarray–based prognostic assay using clinically relevant formalin-fixed paraffin-embedded (FFPE) samples. Patients and Methods A gene signature was developed from a balanced set of 73 patients with recurrent disease (high risk) and 142 patients with no recurrence (low risk) within 5 years of surgery. Results The 634–probe set signature identified high-risk patients with a hazard ratio (HR) of 2.62 (P < .001) during cross validation of the training set. In an independent validation set of 144 samples, the signature identified high-risk patients with an HR of 2.53 (P < .001) for recurrence and an HR of 2.21 (P = .0084) for cancer-related death. Additionally, the signature was shown to perform independently from known prognostic factors (P < .001). Conclusion This gene signature represents a novel prognostic biomarker for patients with stage II colon cancer that can be applied to FFPE tumor samples.
Modellbasierte Regelung pneumatisch betriebener Herzunterstützungssysteme
Authors: Sievert Alexander , Drewelow Wolfgang , Lampe Bernhard P. , Arndt Andreas , Simanski Olaf 
Published: November 2011

Zusammenfassung
Dieser Beitrag stellt neue Ansätze für die Regelung eines extrakorporalen Herzunterstützungssystems vor. Die Grundlage ist eine kaskadierte Regelung von zwei Teilsystemen. Im ersten Teilsystem finden nichtlineare modellbasierte Regelungsansätze Anwendung. Im äußeren Regelkreis erfolgt die Regelung auf Basis einer Modellprädiktion der Regelgröße, da keine Messwerte zur Verfügung stehen. Die vorgestellte Regelung des Pumpvolumens adaptiert sich an zeitvariante, nicht direkt messbare Patientenparameter.
Paternal Depressive Symptoms and Child Behavioral or Emotional Problems in the United States
Authors: Weitzman Michael , Rosenthal David G. , Liu Ying-Hua 
Published: November 2011

BACKGROUND:
The negative effects of maternal mental health problems on child health are well documented. In contrast, there is a profound paucity of information about paternal mental health's association with child health.

OBJECTIVE:
To investigate the association of paternal mental health problems and depressive symptoms and children's emotional or behavioral problems.

METHODS:
We analyzed Medical Expenditure Panel Survey data, which included a representative sample of US children (N = 21 993) aged 5 to 17 years and their mothers and fathers. The main outcome measure was child emotional or behavioral problems assessed by using the Columbia Impairment Scale.

RESULTS:
Paternal depressive symptoms, as assessed using the Patient Health Questionnaire–2, and mental health problems, more generally, assessed by using the Short-Form 12 Scale, were independently associated with increased rates of child emotional or behavioral problems even after controlling for numerous potential confounders including maternal depressive symptoms and other mental health problems. The adjusted odds ratio (aOR) for emotional or behavioral problems among children of fathers with depressive symptoms was 1.72 (95% confidence interval [CI]: 1.33–2.23) and the aOR associated with abnormal paternal scores on the mental component scale of the Short-Form 12 was 1.33 (95% CI: 1.10–1.62) for those within 1 SD below average and 1.48 (95% CI: 1.20–1.84) for those &gt;1 SD below average.

CONCLUSIONS:
To the best of our knowledge, this is the first study to use a representative US sample to demonstrate that living with fathers with depressive symptoms and other mental health problems is independently associated with increased rates of emotional or behavioral problems of children.
Effect of Antihypotensive Treatment on Cerebral Oxygenation of Preterm Infants Without PDA
Authors: Bonestroo Hilde J. C. , Lemmers Petra M. A. , Baerts Wim , van Bel Frank 
Published: November 2011

BACKGROUND:
Preterm infants with hypotension (mean arterial blood pressure [MABP] &lt; gestational age [GA]) are treated with volume expansion and/or dopamine to ensure adequate cerebral perfusion/oxygenation. We used near-infrared spectroscopy to analyze the effects of volume expansion and dopamine on cerebral oxygenation in hypotensive preterm infants without patent ductus arteriosus (PDA).

PATIENTS AND METHODS:
Among 390 infants, 71 (GA &lt; 32 weeks) were hypotensive and eligible for inclusion. Thirty-three infants received volume expansion only (NaCl 0.9%; 20 mL/kg), and 38 received additional dopamine (5 μg/kg per minute). Nine and 11 infants initially treated with dopamine subsequently needed 7.5 and 10 μg/kg per minute, respectively. Seventy-one infants without hypotension were individually matched to serve as controls. MABP, regional cerebral oxygen saturation (rSco2), fractional tissue oxygen extraction (cFTOE), and arterial saturation (Sao2) were monitored 15 minutes before and 30 and 60 minutes after volume or dopamine and at comparable postnatal ages in controls.

RESULTS:
No changes in MABP, rSco2, or cFTOE were found 30 minutes after volume expansion. MABP increased 60 minutes after 5 μg/kg per minute dopamine (median [range]: 28 [19–32] vs 33 [23–46] mm Hg; P &lt; .001). There was a small increase and decrease, respectively, in rSco2 (63 [43–84] vs 66 [46–87]%; P &lt; .05) and cFTOE (0.33 [0.14–0.56] vs 0.31 [0.07–0.54]1/1; P &lt; .05). However, no differences were found at any time point between controls and infants treated with volume or additional dopamine (5, 7.5, and 10 μg/kg per minute) for rSco2 or cFTOE.

CONCLUSIONS:
Volume expansion and additional dopamine do not cause any significant change in rSco2 or cFTOE in hypotensive preterm infants without PDA. We speculate that very preterm infants with hypotension but without signs of a compromised cerebral oxygenation and systemic perfusion might not be in need of antihypotensive therapy.