bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unintentional injury among low-income 5-year-olds with chronic health conditions
Authors: Schwebel David C , Brezausek Carl M 
Published: February 2011

Background: Growing numbers of children suffer from chronic health conditions, and initial evidence suggests chronic illness may be associated with increased child injury risk. We examined injury risk among 5-year-olds with and without chronic health conditions. Methods: Data from a diverse US sample of 7954 low-income 5-year-olds participating in the National Head Start/Public School Early Childhood Transition Demonstration Study were analysed. Mothers reported demographics, presence/absence of eight chronic health conditions, and whether children had experienced injuries requiring professional medical attention in the past year. Primary analyses used ordinal logistic regression. Results: Asthma, bronchitis, recurrent ear infections, hay fever/allergies and speech problems associated with increased injury risk (OR range = 1.20—1.49 in bivariate ordinal logistic regression, ps < 0.01). Children with cerebral palsy had reduced injury risk (OR = 0.37, 95% CI = 0.15—0.91, p < 0.05). Most findings held after including demographic covariates in multivariate models. Conclusion: Because a range of chronic health conditions associated with increased injury risk, the causal mechanism behind relations between chronic illness and injury risk may not be disease-specific. Instead, factors related to having chronic medical conditions—not any particular condition—might contribute. Possible mediators include impaired family functioning, impaired peer relations, and familiarity with the health system/health-seeking behaviours.
In vitro generation of HSC-like cells from murine ESCs/iPSCs by enforced expression of LIM-homeobox transcription factor Lhx2
Authors: Kitajima Kenji , Minehata Ken-ichi , Sakimura Kenji , Nakano Toru , Hara Takahiko 
Published: February 2011

AbstractIdentification of genes involved in in vitro differentiation induction of embryonic stem cells (ESCs) into hematopoietic stem cells (HSCs) has been challenged during last decade. To date, a homeobox transcription factor Hoxb4 has been only demonstrated to possess such an effect in mice. Here, we show that HSC-like cells were efficiently induced from mouse ESCs by enforced expression of Lhx2, a LIM-homeobox transcription factor. Transduction of Lhx2 into ESC-derived mesodermal cells resulted in robust differentiation of c-Kit+/Sca-1+/Lineage− (KSL) cells in vitro. The KSL cell induction frequency was superior to the case of Hoxb4. Furthermore, transplantation of Lhx2-transduced hematopoietic cells into lethally irradiated mice resulted in multilineage repopulation of hematopoietic cells over 4 months. Transduction of Lhx2 into induced pluripotent stem cells (iPSCs) was also effective in generating KSL cells in vitro, as well as HSC-like activities in vivo. These results demonstrate that ectopic expression of Lhx2 confers an in vivo engrafting capacity to ESC/iPSC-derived hematopoietic cells and in vivo behavior of iPSC-derived hematopoietic cells is almost identical to that of ESC-derived cells.
Prdm16 is a physiologic regulator of hematopoietic stem cells
Authors: Aguilo Francesca , Avagyan Serine , Labar Amy , Sevilla Ana , Lee Dung-Fang , Kumar Parameet , Lemischka Ihor R. , Zhou Betty Y. , Snoeck Hans-Willem 
Published: February 2011

AbstractFetal liver and adult bone marrow hematopoietic stem cells (HSCs) renew or differentiate into committed progenitors to generate all blood cells. PRDM16 is involved in human leukemic translocations and is expressed highly in some karyotypically normal acute myeloblastic leukemias. As many genes involved in leukemogenic fusions play a role in normal hematopoiesis, we analyzed the role of Prdm16 in the biology of HSCs using Prdm16-deficient mice. We show here that, within the hematopoietic system, Prdm16 is expressed very selectively in the earliest stem and progenitor compartments, and, consistent with this expression pattern, is critical for the establishment and maintenance of the HSC pool during development and after transplantation. Prdm16 deletion enhances apoptosis and cycling of HSCs. Expression analysis revealed that Prdm16 regulates a remarkable number of genes that, based on knockout models, both enhance and suppress HSC function, and affect quiescence, cell cycling, renewal, differentiation, and apoptosis to various extents. These data suggest that Prdm16 may be a critical node in a network that contains negative and positive feedback loops and integrates HSC renewal, quiescence, apoptosis, and differentiation.
Evaluation of the profibrinolytic properties of an anti-TAFI monoclonal antibody in a mouse thromboembolism model
Authors: Vercauteren Ellen , Emmerechts Jan , Peeters Miet , Hoylaerts Marc F. , Declerck Paul J. , Gils Ann 
Published: February 2011

Abstract
The enhancement of fibrinolysis constitutes a promising approach to treat thrombotic diseases. Activated thrombin activatable fibrinolysis inhibitor (TAFIa) attenuates fibrinolysis and is an attractive target to develop profibrinolytic drugs. TAFI can be activated by thrombin, thrombin/thrombomodulin, or plasmin, but the in vivo physiologic TAFI activator(s) are unknown. Here, we generated and characterized MA-TCK26D6, a monoclonal antibody raised against human TAFI, and examined its profibrinolytic properties in vitro and in vivo. In vitro, MA-TCK26D6 showed a strong profibrinolytic effect caused by inhibition of the plasmin-mediated TAFI activation. In vivo, MA-TCK26D6 significantly decreased fibrin deposition in the lungs of thromboembolism-induced mice. Moreover, in the presence of MA-TCK26D6, plasmin-α2-antiplasmin complexes in plasma of thromboembolism-induced mice were significantly increased compared with a control antibody, indicative of an acceleration of fibrinolysis through MA-TCK26D6. In this study, we show that plasmin is an important TAFI activator that hampers in vitro clot lysis. Furthermore, this is the first report on an anti-TAFI monoclonal antibody that demonstrates a strong profibrinolytic effect in a mouse thromboembolism model.
Family psychoeducation for major depression: randomised
controlled trial
Authors: Shimazu Kae , Shimodera Shinji , Mino Yoshio , Nishida Atsushi , Kamimura Naoto , Sawada Ken , Fujita Hirokazu , Furukawa Toshi A. , Inoue Shimpei 
Published: February 2011

BackgroundThe value of family psychoeducation for schizophrenia has been well
established, and indications for its use have recently expanded to
include bipolar affective disorder. However, no study to date has
adequately examined its use in depression.AimsTo examine family psychoeducation in the maintenance treatment of
depression and to investigate the influence of the family's expressed
emotion (EE) on its effectiveness.MethodOf 103 patients diagnosed with major depression and their primary family
members, 57 pairs provided written informed consent. The pairs were
randomly allocated to the intervention (n = 25) or
control (n = 32). One family in the intervention group
and two in the control group withdrew their consent after randomisation.
The intervention group underwent four psychoeducation sessions consisting
of didactic lectures about depression and group problem-solving focusing
on how to cope in high-EE situations. Patients did not attend these
sessions. Patients in both the intervention and control groups received
treatment as usual. The families' EE levels were evaluated through
Five-Minute Speech Samples. The primary outcome was relapse.ResultsTime to relapse was statistically significantly longer in the
psychoeducation group than in the control group (Kaplan–Meier survival
analysis, P = 0.002). The relapse rates up to the
9-month follow-up were 8% and 50% respectively (risk ratio 0.17, 95% CI
0.04–0.66; number needed to treat 2.4, 95% CI 1.6–4.9). In Cox
proportional hazard analysis, baseline EE did not moderate the
effectiveness of the intervention.ConclusionsFamily psychoeducation is effective in the prevention of relapse in adult
patients with major depression.
Prevalence of autoimmune thyroid dysfunction in postpartum psychosis
Authors: Bergink Veerle , Kushner Steven A. , Pop Victor , Kuijpens Hans , Lambregtse-van den Berg Mijke P. , Drexhage Roos C. , Wiersinga Wilmar , Nolen Willem A. , Drexhage Hemmo A. 
Published: February 2011

BackgroundPostpartum psychosis is a life-threatening psychiatric emergency, which often occurs without significant premorbid symptoms. Although many studies have postulated an involvement of the immune and endocrine systems in the onset of postpartum psychosis, the specific aetiological factors have remained unknown.AimsTo examine the hypothesis that autoimmune thyroid dysfunction may be associated with the onset of postpartum psychosis.MethodThirty-one consecutive primiparous women with no prior psychiatric history were referred to our in-patient unit for postpartum psychosis. The control group (n = 117) comprised primiparous women with consecutive deliveries at a community practice. Blood samples were obtained from all participants at 4 weeks and 9 months postpartum. Thyroperoxidase antibody levels were quantified as immunological measures of autoimmune thyroid disease (AITD). Thyroid-stimulating hormone and free thyroxine levels were measured to assess clinical thyroid dysfunction.ResultsAt 4 weeks postpartum and prior to the initiation of mood stabiliser therapy, 19% of women with postpartum psychosis had AITD compared with only 5% in the control group. Women with both postpartum psychosis and AITD had a dramatically higher risk of progression to clinical thyroid dysfunction (67%) than control participants with AITD (20%).ConclusionsWomen with postpartum psychosis are at higher risk not only of AITD but also of clinical thyroid failure. These data implicate thyroid function as an important clinical outcome in patients with postpartum psychosis. Further, AITD represents a potentially strong aetiological factor for the development of postpartum psychosis. Therefore, screening for thyroperoxidase antibodies is warranted in patients with postpartum psychosis.
RUNX1 Mutations in Acute Myeloid Leukemia: Results From a Comprehensive Genetic and Clinical Analysis From the AML Study Group
Authors: Gaidzik Verena I. , Bullinger Lars , Schlenk Richard F. , Zimmermann Andreas S. , Röck Jürgen , Paschka Peter , Corbacioglu Andrea , Krauter Jürgen , Schlegelberger Brigitte , Ganser Arnold , Späth Daniela , Kündgen Andrea , Schmidt-Wolf Ingo G.H. , Götze Katharina , Nachbaur David , Pfreundschuh Michael , Horst Heinz A. , Döhner Hartmut , Döhner Konstanze 
Published: February 2011

Purpose To evaluate frequency, biologic features, and clinical relevance of RUNX1 mutations in acute myeloid leukemia (AML). Patients and Methods Diagnostic samples from 945 patients (age 18 to 60 years) were analyzed for RUNX1 mutations. In a subset of cases (n = 269), microarray gene expression analysis was performed. Results Fifty-nine RUNX1 mutations were identified in 53 (5.6%) of 945 cases, predominantly in exons 3 (n = 11), 4 (n = 10), and 8 (n = 23). RUNX1 mutations clustered in the intermediate-risk cytogenetic group (46 of 640, 7.2%; cytogenetically normal, 34 of 538, 6.3%), whereas they were less frequent in adverse-risk cytogenetics (five of 109, 4.6%) and absent in core-binding-factor AML (0 of 77) and acute promyelocytic leukemia (0 of 61). RUNX1 mutations were associated with MLL-partial tandem duplications (P = .0007) and IDH1/IDH2 mutations (P = .03), inversely correlated with NPM1 (P < .0001), and in trend with CEBPA (P = .10) mutations. RUNX1 mutations were characterized by a distinct gene expression pattern; this RUNX1 mutation-derived signature was not exclusive for the mutation, but also included mostly adverse-risk AML [eg, 7q-, -7, inv(3), or t(3;3)]. RUNX1 mutations predicted for resistance to chemotherapy (rates of refractory disease 30% and 19%, P = .047, for RUNX1-mutated and wild-type patients, respectively), as well as inferior event-free survival (EFS; P < .0001), relapse-free survival (RFS, P = .022), and overall survival (P = .051). In multivariable analysis, RUNX1 mutations were an independent prognostic marker for shorter EFS (P = .007). Explorative subgroup analysis revealed that allogeneic hematopoietic stem-cell transplantation had a favorable impact on RFS in RUNX1-mutated patients (P < .0001). Conclusion AML with RUNX1 mutations are characterized by distinct genetic properties and are associated with resistance to therapy and inferior outcome.
Randomized, Double-Blind Study of Denosumab Versus Zoledronic Acid in the Treatment of Bone Metastases in Patients With Advanced Cancer (Excluding Breast and Prostate Cancer) or Multiple Myeloma
Authors: Henry David H. , Costa Luis , Goldwasser Francois , Hirsh Vera , Hungria Vania , Prausova Jana , Scagliotti Giorgio Vittorio , Sleeboom Harm , Spencer Andrew , Vadhan-Raj Saroj , von Moos Roger , Willenbacher Wolfgang , Woll Penella J. , Wang Jianming , Jiang Qi , Jun Susie , Dansey Roger , Yeh Howard 
Published: February 2011

Purpose This study compared denosumab, a fully human monoclonal anti-receptor activator of nuclear factor kappa-B ligand antibody, with zoledronic acid (ZA) for delaying or preventing skeletal-related events (SRE) in patients with advanced cancer and bone metastases (excluding breast and prostate) or myeloma. Patients and Methods Eligible patients were randomly assigned in a double-blind, double-dummy design to receive monthly subcutaneous denosumab 120 mg (n = 886) or intravenous ZA 4 mg (dose adjusted for renal impairment; n = 890). Daily supplemental calcium and vitamin D were strongly recommended. The primary end point was time to first on-study SRE (pathologic fracture, radiation or surgery to bone, or spinal cord compression). Results Denosumab was noninferior to ZA in delaying time to first on-study SRE (hazard ratio, 0.84; 95% CI, 0.71 to 0.98; P = .0007). Although directionally favorable, denosumab was not statistically superior to ZA in delaying time to first on-study SRE (P = .03 unadjusted; P = .06 adjusted for multiplicity) or time to first-and-subsequent (multiple) SRE (rate ratio, 0.90; 95% CI, 0.77 to 1.04; P = .14). Overall survival and disease progression were similar between groups. Hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred at similarly low rates in both groups. Acute-phase reactions after the first dose occurred more frequently with ZA, as did renal adverse events and elevations in serum creatinine based on National Cancer Institute Common Toxicity Criteria for Adverse Events grading. Conclusion Denosumab was noninferior (trending to superiority) to ZA in preventing or delaying first on-study SRE in patients with advanced cancer metastatic to bone or myeloma. Denosumab represents a potential novel treatment option with the convenience of subcutaneous administration and no requirement for renal monitoring or dose adjustment.
DNA Methylation Array Analysis Identifies Profiles of Blood-Derived DNA Methylation Associated With Bladder Cancer
Authors: Marsit Carmen J. , Koestler Devin C. , Christensen Brock C. , Karagas Margaret R. , Houseman E. Andres , Kelsey Karl T. 
Published: February 2011

Purpose Epigenetic alterations in tissues targeted for cancer play a causal role in carcinogenesis. Changes in DNA methylation in nontarget tissues, specifically peripheral blood, can also affect risk of malignant disease. We sought to identify specific profiles of DNA methylation in peripheral blood that are associated with bladder cancer risk and therefore serve as an epigenetic marker of disease susceptibility. Methods We performed genome-wide DNA methylation profiling on participants involved in a population-based incident case-control study of bladder cancer. Results In a training set of 112 cases and 118 controls, we identified a panel of 9 CpG loci whose profile of DNA methylation was significantly associated with bladder cancer in a masked, independent testing series of 111 cases and 119 controls (P < .0001). Membership in three of the most methylated classes was associated with a 5.2-fold increased risk of bladder cancer (95% CI, 2.8 to 9.7), and a model that included the methylation classification, participant age, sex, smoking status, and family history of bladder cancer was a significant predictor of bladder cancer (area under the curve, 0.76; 95% CI, 0.70 to 0.82). CpG loci associated with bladder cancer and aging had neighboring sequences enriched for transcription-factor binding sites related to immune modulation and forkhead family members. Conclusion These results indicate that profiles of epigenetic states in blood are associated with risk of bladder cancer and signal the potential utility of epigenetic profiles in peripheral blood as novel markers of susceptibility to this and other malignancies.
Prognostic and Clinicopathologic Associations of Oncogenic BRAF in Metastatic Melanoma
Authors: Long Georgina V. , Menzies Alexander M. , Nagrial Adnan M. , Haydu Lauren E. , Hamilton Anne L. , Mann Graham J. , Hughes T. Michael , Thompson John F. , Scolyer Richard A. , Kefford Richard F. 
Published: February 2011

Purpose To assess the frequency and type of oncogenic BRAF mutations in metastatic melanoma and correlate BRAF status with clinicopathologic features and outcome. Patients and Methods Consecutive BRAF-tested Australian patients with metastatic melanoma (n = 197) were observed prospectively. A comprehensive range of clinicopathologic variables were correlated with BRAF mutation status, and a survival analysis was conducted. Results Forty-eight percent of patients had a BRAF mutation; 70 patients (74%) had V600E, 19 (20%) had V600K, and six (6%) had other genotypes. Other than age at diagnosis of distant metastasis (median age, 56 v 63 years for BRAF-mutant v BRAF wild-type patients, respectively; P < .001), there was no significant difference in clinical features of patients with metastatic melanoma by mutation status. Features of the antecedent primary melanoma significantly associated with a BRAF mutation (P < .05) were histopathologic subtype, presence of mitoses, single or occult primary melanoma, truncal location, and age at diagnosis of primary tumor ≤ 50 years. The interval from diagnosis of first-ever melanoma to distant metastasis was not significantly different between BRAF-mutant and BRAF wild-type patients; however, the median survival of patients with newly diagnosed metastatic melanoma was 5.7 months for BRAF-mutant patients not treated with a BRAF inhibitor, 8.5 months for BRAF wild-type patients, and not reached for BRAF-mutant patients treated with a BRAF inhibitor. Conclusion V600K mutations comprised 20% of BRAF mutations. Characteristics of the antecedent primary melanoma and age at diagnosis differed in BRAF-mutant and BRAF wild-type patients. The presence of mutant BRAF had no impact on the disease-free interval from diagnosis of first-ever melanoma to first distant metastasis; however, it may have impacted survival thereafter.
Can Patient-Reported Outcome Measures Identify Cancer Patients' Most Bothersome Issues?
Authors: Snyder Claire F. , Blackford Amanda L. , Aaronson Neil K. , Detmar Symone B. , Carducci Michael A. , Brundage Michael D. , Wu Albert W. 
Published: February 2011

Purpose Patient-reported outcome (PRO) questionnaires are being investigated for their ability to aid in individual patient management. We evaluated whether PROs can identify patients' most bothersome quality-of-life issues and compared approaches for interpreting PRO scores. Methods This secondary data analysis included 130 patients with cancer (mean age, 57 years; 71% female) receiving outpatient palliative chemotherapy. Patients completed a PRO (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire [QLQ-C30]) at up to three consecutive visits and reported one or two of their most bothersome function and symptom issues from categories based on QLQ-C30 domains. We compared two approaches for interpreting PRO scores and identified which way better identified patients' most bothersome issues: worst scores in absolute terms or worst change from the previous time point. Results For patients reporting one bothersome issue, absolute scores identified it correctly 91% of the time for both function and symptoms versus change scores' accuracy of 40% for function and 26% for symptoms. For patients reporting two bothersome issues, absolute scores identified at least one correctly 98% of the time for both function and symptoms versus change scores' 63% for function and 62% for symptoms. Absolute scores identified both issues correctly 42% of the time for function and 66% of the time for symptoms versus change scores' performance of 23% for both function and symptoms. Conclusion Absolute scores identify patients' most bothersome quality-of-life issues better than change scores. These results support the use of PROs in clinical practice and suggest that clinicians may want to focus on the worst absolute scores when examining PRO score reports.
Use of Gabapentin for the Management of Natural or Surgical Menopausal Hot Flashes
Authors: Hayes Laura P , Carroll Dana G , Kelley Kristi W 
Published: February 2011

Objective: To review the literature examining the use of gabapentin for treatment of hot flashes during natural or surgically Induced menopause. Data Sources: A literature search was conducted via PubMed, MEDLINE, and International Pharmaceutical Abstracts (1948-November 2010) using the search terms gabapentin, hot flashes, and menopause. Literature was limited to English-language, human studies. Additional material was identified by reviewing reference citations of the articles retrieved. Study Selection and Data Extraction: Studies with data describing gabapentin for hot flash management during natural or surgically induced menopause were included. Any studies including women with a history of breast cancer were excluded. Four studies met the inclusion criteria. Data Synthesis: Gabapentin significantly decreased hot flash frequency and hot flash composite scores by 45-71% from baseline in the 4 trials included in this review. In 2 of the trials, gabapentin was comparable to hormone replacement therapy (71 % vs 72%, respectively, p = 0.63) in decreasing hot flash composite scores at the end of 12 weeks and in decreasing hot flash frequency at the end of 8 weeks (58.9% vs 70.1 %, p > 0.05). In all trials, the most common adverse effects with gabapentin were somnolence/drowsiness, unsteadiness, and dizziness. These adverse effects were most pronounced during the first 1-2 weeks of therapy, but resolved and were similar to those reported with placebo by week 4. These trials were short (<12 weeks) and had small sample sizes; however, their results appear to show that gabapentin is safe and effective for short-term treatment of hot flashes in women who have entered menopause either naturally or surgically. Conclusions: Gabapentin 600-2400 mg/day in divided doses may be a viable option for treating hot flashes in menopausal women who do not want to use hormone replacement therapy.