bluuebunny/crossref_metadata_2025_split huggingface dataset:
Forkhead Transcription Factor FOXO1 is a Direct Target of Progestin to Inhibit Endometrial Epithelial Cell Growth
Authors: Kyo Satoru , Sakaguchi Junko , Kiyono Tohru , Shimizu Yutaka , Maida Yoshiko , Mizumoto Yasunari , Mori Noriko , Nakamura Mitsuhiro , Takakura Masahiro , Miyake Kiyohiko , Sakamoto Masaru , Inoue Masaki 
Published: December 2010

Abstract
Purpose and experimental design: Despite the therapeutic utility of progestin in invasive and preinvasive endometrial neoplasias, the molecular mechanisms through which it exerts inhibitory effects on endometrial epithelial growth are largely unknown. The aim of the study was to clarify the molecular mechanisms of progestin action to endometrial epithelial cells using originally established in vitro and in vivo treatment models for immortalized and transformed endometrial epithelial cell lines that express progesterone receptor.
Results: In this model, progestin effectively inhibited the cell growth, inducing G0/G1 arrest rather than apoptosis without p21/WAF-1 induction. Using DNA microarray analysis, we identified 24 genes whose expression increased more than 10-fold on progestin treatment. Of these genes, we paid special attention to forkhead box transcription factor FOXO1, known as a key gene for endometrial decidualization. Progestin markedly induced FOXO1 gene expression mainly in the nuclei in vitro and in vivo. This induction was not due to the canonical activation of FOXO1 via protein dephosphorylation but due to FOXO1 promoter activation and mRNA induction. siRNA inhibition of FOXO1 significantly attenuated the effects of progestin to inhibit endometrial epithelial cell growth. Disrupting Akt activity by the introduction of the dominant negative form of Akt increased nuclear FOXO1 accumulation and enhanced the effect of progestin.
Conclusion: These findings suggest that FOXO1 is a direct target of progestin, implicating novel molecular mechanisms of progestin to eradicate endometrial neoplasia. Clin Cancer Res; 17(3); 525–37. ©2010 AACR.
Bayesian Hierarchical Changepoint Methods in Modeling the Tumor Growth Profiles in Xenograft Experiments
Authors: Zhao Lili , Morgan Meredith A. , Parsels Leslie A. , Maybaum Jonathan , Lawrence Theodore S. , Normolle Daniel 
Published: December 2010

Abstract
Purpose: The standard approach of using tumor doubling time to assess growth delay may not accurately represent tumor response, especially if the growth rates are not constant. Therefore, we developed a method to compare the antitumor activities of different treatments in xenograft experiments that uses the entire growth curve to estimate nonconstant growth rates.
Experimental Design: A Bayesian hierarchical changepoint (BHC) method was used to model logarithmically transformed tumor volumes (TV). Each tumor was assumed to have a growth profile, represented by a prenadir regression rate, a regression period, a nadir volume, and a postnadir regrowth rate. Confidence intervals were calculated to compare these features between different treatments. We used data from a study assessing the effects of radiation, gemcitabine, and a Chk1/2 inhibitor on MiaPaCa-2 xenografts.
Results: We found that the BHC model provided a good fit to the data and more descriptive features than the tumor doubling approach. This model detected significant tumor regression in the AZD7762 + 1 Gy and GEM + 1 Gy that was not detected when comparing the tumor doubling times. The BHC model also provided evidence that the growth inhibition resulted from a direct tumor effect rather than an indirect effect on the tumor bed, as evidenced by dramatic tumor regression in response to effective treatments and similar postnadir regrowth rates across all treatment groups.
Conclusions: Compared with the tumor doubling time approach, the BHC model utilizes all data, providing more descriptive features that address mechanisms underlying tumor growth inhibition and maximize the biological information obtained from tumor xenografts studies. Clin Cancer Res; 17(5); 1057–64. ©2010 AACR.
Phase I Dose-Escalation Study of the Novel Antiandrogen BMS-641988 in Patients with Castration-Resistant Prostate Cancer
Authors: Rathkopf Dana , Liu Glenn , Carducci Michael A. , Eisenberger Mario A. , Anand Aseem , Morris Michael J. , Slovin Susan F. , Sasaki Yasutsuna , Takahashi Shunji , Ozono Seiichiro , Fung Nga Kit Eliza , Cheng Shinta , Gan Jinping , Gottardis Marco , Obermeier Mary T. , Reddy Jyotsna , Zhang Steven , Vakkalagadda Blisse J. , Alland Leila , Wilding George , Scher Howard I. 
Published: December 2010

Abstract
Purpose: BMS-641988 is an androgen receptor antagonist with increased potency relative to bicalutamide in both in vitro and in vivo prostate cancer models. A first-in-man phase I study was conducted to define the safety and tolerability of oral BMS-641988 in patients with castration-resistant prostate cancer (CRPC).
Experimental Design: Doses were escalated from 5 to 150 mg based on discrete pharmacokinetic parameters in cohorts of three to six subjects. After establishing safety with 20 mg of BMS-641988 in the United States, a companion study was opened in Japan to assess differences in drug metabolism between populations.
Results: Sixty-one men with CRPC were treated with daily BMS-641988. The pharmacokinetics (PK) of BMS-641988 and its active metabolites were proportional to dose. One patient experienced an epileptic seizure at a dose of 60 mg administered twice. Despite achieving target drug exposures, antitumor activity was limited to one partial response. Seventeen of 23 evaluable patients (74%) exhibited stable disease on imaging (median 15 weeks; range 8–32), and 10 of 61 patients (16%) achieved a ≥30% decline in levels of prostate-specific antigen (PSA). Partial agonism was seen within the context of this study upon removal of the drug as evidenced by a decrease in PSA.
Conclusions: Although the clinical outcomes of predominantly stable disease and partial agonism were similar to what was observed in the preclinical evaluation of the compound, the limited antitumor activity of BMS-641988 at therapeutic dose levels coupled with an episode of seizure activity led to study closure. Clin Cancer Res; 17(4); 880–7. ©2010 AACR.
Endocardial Unipolar Voltage Mapping to Detect Epicardial Ventricular Tachycardia Substrate in Patients With Nonischemic Left Ventricular Cardiomyopathy
Authors: Hutchinson Mathew D. , Gerstenfeld Edward P. , Desjardins Benoit , Bala Rupa , Riley Michael P. , Garcia Fermin C. , Dixit Sanjay , Lin David , Tzou Wendy S. , Cooper Joshua M. , Verdino Ralph J. , Callans David J. , Marchlinski Francis E. 
Published: December 2010

Background—

Patients with nonischemic left ventricular cardiomyopathy (LVCM) and ventricular tachycardia (V
t
) have complex 3-dimensional substrate with variable involvement of the endocardium (ENDO) and epicardium (EPI). The purpose of this study was to determine whether ENDO unipolar (UNI) mapping with a larger electric field of view could identify EPI low bipolar (BIP) voltage regions in patients with LVCM undergoing V
t
ablation.

Methods and Results—

The reference value for normal ENDO unipolar voltage was determined from 6 patients without structural heart disease. Consecutive patients undergoing V
t
ablation over an 8-year period with detailed (>100 points) LV ENDO and EPI mapping and normal LV ENDO BIP voltage were identified. From this cohort, we compared patients with structurally normal hearts and normal EPI BIP voltage (EPI−, group 1) with patients with LVCM and low LV EPI BIP voltage regions present (EPI+, group 2). Confluent regions of ENDO UNI and EPI BIP low voltage (>2 cm
2
) were measured. The normal signal amplitude was >8.27 mV for LV ENDO UNI electrograms. Detailed LV ENDO-EPI maps in 5 EPI− patients were compared with 11 EPI+ patients. Confluent ENDO UNI low-voltage regions were seen in 9 of 11 (82%) of the EPI+ (group 2) patients compared with none of 5 EPI− (group 1) patients (
P
<0.001). In all 9 patients with ENDO UNI low voltage, the ENDO UNI low-voltage regions were directly opposite to an area of EPI BIP low voltage (61% ENDO UNI-EPI BIP low-voltage area overlap).

Conclusions—
EPI arrhythmia substrate can be reliably identified in most patients with LVCM using ENDO UNI voltage mapping in the absence of ENDO BIP abnormalities.
Type 2 Diabetes Care and Insulin Intensification
Authors: Cuddihy Robert M. , Philis-Tsimikas Athena , Nazeri A. 
Published: December 2010

Purpose The purpose of this study was to investigate the opinions of primary care physicians (PCPs) and diabetes specialists on their perceived role in tackling type 2 diabetes (T2D) and the challenges they face, particularly regarding insulin intensification. Methods Six hundred physicians from Germany, Japan, Spain, Turkey, the United Kingdom, and the United States were recruited to complete an online survey. Screening criteria included T2D patients seen per week (Europe/Japan: all ≥2; United States: PCPs ≥5; specialists ≥10) and years in practice (3—30 years). Results Most physicians had seen an increase in TD2 patients in the past 5 years, and almost all agreed that the burden of diabetes is increasing. Notable proportions of PCPs never initiate/modify insulin and never/rarely intensify insulin. Main barriers to insulin intensification cited were lack of experience and lack of time to educate patients. Better collaboration between primary and secondary care was considered one of the most important factors in improving insulin treatment of T2D. Conclusions PCPs are less involved in the initiation and intensification of insulin than specialists; however, all physicians appreciate the need for increased PCP involvement. A multidisciplinary approach that includes using the skills of diabetes educators will assist physicians in improving management of T2D.
Effects of the sliding rehabilitation machine on balance and gait in chronic stroke patients – a controlled clinical trial
Authors: Byun Seung-Deuk , Jung Tae-Du , Kim Chul-Hyun , Lee Yang-Soo 
Published: December 2010

Objective: To investigate the effects of a sliding rehabilitation machine on balance and gait in chronic stroke patients. Design: A non-randomized crossover design. Setting: Inpatient rehabilitation in a general hospital. Subjects: Thirty patients with chronic stroke who had medium or high falling risk as determined by the Berg Balance Scale. Interventions: Participants were divided into two groups and underwent four weeks of training. Group A ( n = 15) underwent training with the sliding rehabilitation machine for two weeks with concurrent conventional training, followed by conventional training only for another two weeks. Group B ( n = 15) underwent the same training in reverse order. The effect of the experimental period was defined as the sum of changes during training with sliding rehabilitation machine in each group, and the effect of the control period was defined as those during the conventional training only in each group. Main measures: Functional Ambulation Category, Berg Balance Scale, Six-Minute Walk Test, Timed Up and Go Test, Korean Modified Barthel Index, Modified Ashworth Scale and Manual Muscle Test. Results: Statistically significant improvements were observed in all parameters except Modified Ashworth Scale in the experimental period, but only in Six-Minute Walk Test ( P <  0.01) in the control period. There were also statistically significant differences in the degree of change in all parameters in the experimental period as compared to the control period. Conclusions: The sliding rehabilitation machine may be a useful tool for the improvement of balance and gait abilities in chronic stroke patients.
Outcomes of social work intervention in the context of evidence-based practice
Authors: Mullen Edward J , Shuluk Joseph 
Published: December 2010

• Summary: This article explores the general outcomes of social work interventions as reported in journal review articles that have examined that question since 1990. • Findings: There is now a large body of evidence supporting the effectiveness of a wide range of social work interventions with a wide range of social problems and populations. It is reasonable to conclude that approximately two-thirds of clients served by social workers benefit in measurable ways. These positive outcomes remain, even after controlling for publication and investigator bias. The reviews examined in this article also suggest that theoretical orientation does not account for differential outcomes, however, differential intervention outcomes have been found when contrasting alternate interventions and specifying target problem or condition. • Applications: What are currently needed are studies and systematic reviews that contrast credible, alternative intervention options under highly specific conditions. Using comparative effectiveness strategies, specification of differential effectiveness should now be a focus of research to answer questions such as what intervention, under what circumstances, for what problem, under what conditions, in what population, has what effect and at what cost. Evidence-based practice will be strengthened and enriched to the extent such systematic reviews become available. Additionally, findings are sufficiently encouraging to recommend that promising social work interventions with specific social problems and specific populations be more carefully studied with particular attention to questions of cost-effectiveness since few studies have used designs or measures that examine cost-effectiveness or cost—benefit questions.
Sustainability of collaborative care interventions in primary care settings
Authors: Palinkas Lawrence A , Ell Kathleen , Hansen Marissa , Cabassa Leopoldo , Wells Anjanette 
Published: December 2010

• Summary: We assessed patient and provider barriers and facilitators to sustainability of a collaborative depression care model for depression treatment in predominantly Hispanic diabetes patients in safety net care clinics. • Findings: Semi-structured interviews and focus groups were conducted with patients and providers at two community clinics participating in a randomized controlled effectiveness trial of the Multi-faceted Depression and Diabetes Program (MDDP), a socioculturally adapted collaborative care model. Analysis identified eight themes grouped into three categories: barriers, facilitators, and recommendations for program sustainability. Barriers included patient concerns about use of medication and provider concerns about use of psychotherapy, increased workload for clinic staff, delay in receiving outcomes data, and lack of resources to sustain the program. Facilitators included patient benefits such as improved clinical outcomes, quality of care received, access, and satisfaction; provider benefits such as increased awareness and reduced anxiety; and clinic benefits in the form of reduced costs of care. Recommendations included changes in communication patterns among providers, specific changes in procedures, changes in resources, and changes in clinic organizational culture. • Applications: Sustainable adoption of collaborative depression care for underserved populations in safety net care systems by organizational decision-makers and providers requires: stable funding and qualified staff; technologies to facilitate provider access to easily applied treatment guidelines, information exchange between primary care physicians and depression care providers, and routine monitoring of patient depression symptoms and treatment adherence and satisfaction; and treatment consistent with patient preferences.
The quest for evidence-based practice: A view from the United States
Authors: Thyer Bruce A , Myers Laura L 
Published: December 2010

• Summary: This article describes how a reliance upon social and behavioral science research is the feature distinguishing modern professional social work from prior non-professional efforts at providing social care. A number of formal efforts that attempted to more closely link science and practice are described, including the empirical clinical practice movement, the empirically supported treatments initiative, and, most recently, evidence-based practice (EBP). • Findings: EBP is correctly seen as a process of inquiry intended to help practitioners and their clients make important decisions about the services the clients receive. EBP is a process, a verb, not a noun. There is no such thing as evidence-based practices, since in EBP one decides what services to provide by taking into account not only research evidence but also client preferences and values, situational circumstances, professional ethics, the practitioner’s existing skills, and available resources. • Applications: From this perspective it is a misuse of the term EBP to refer to specific interventions or assessment methods as evidence-based. At best, interventions or techniques may be labeled as empirically supported or research-supported. The current status of EBP within American social work is seen as healthy and growing, although misconceptions regarding this process are common.
Bridging science and practice in child welfare and children’s mental health service systems through a two-decade research center trajectory
Authors: Landsverk John , Garland Ann , Rolls Reutz Jennifer , Davis Inger 
Published: December 2010

• Summary: Over the past two decades, research on social work practice has experienced substantial growth in the United States, indicated by both the establishment of the Society for Social Work Research in 1994 and increased funding from the National Institutes of Health (NIH). Recently, this growth has carried an increasing emphasis on research to establish the evidence base for social work practice and an emphasis on understanding dissemination and implementation of evidence-based interventions or practice models in usual care settings within service systems that have historic and professional linkages to the social work discipline, such as child welfare and mental health. • Findings: This article illustrates this growth and emphases on evidence-based practice in the social work research areas, child abuse and neglect, child welfare and child mental health through the two-decade experience of a large-scale and multi-disciplinary research center in San Diego County, California, the Child and Adolescent Services Research Center (CASRC). Evidence for understanding and improving care in these two service systems served by social work practice has been developed through center studies of clinical epidemiology, mental health services, effectiveness of evidence-based interventions, and the dissemination and implementation of these interventions in usual care settings. • Applications: This evolving research agenda was shown to be well linked to the NIH Roadmap initiative and highly competitive for NIH funding.
Megakaryocyte-matrix interaction within bone marrow: new roles for fibronectin and factor XIII-A
Authors: Malara Alessandro , Gruppi Cristian , Rebuzzini Paola , Visai Livia , Perotti Cesare , Moratti Remigio , Balduini Cesare , Tira Maria Enrica , Balduini Alessandra 
Published: December 2010

AbstractThe mechanisms by which megakaryocytes (MKs) differentiate and release platelets into the circulation are not well understood. However, growing evidence indicates that a complex regulatory mechanism involving MK-matrix interactions may contribute to the quiescent or permissive microenvironment related to platelet release within bone marrow. To address this hypothesis, in this study we demonstrate that human MKs express and synthesize cellular fibronectin (cFN) and transglutaminase factor XIII-A (FXIII-A). We proposed that these 2 molecules are involved in a new regulatory mechanism of MK-type I collagen interaction in the osteoblastic niche. In particular, we demonstrate that MK adhesion to type I collagen promotes MK spreading and inhibits pro-platelet formation through the release and relocation to the plasma membrane of cFN. This regulatory mechanism is dependent on the engagement of FN receptors at the MK plasma membrane and on transglutaminase FXIII-A activity. Consistently, the same mechanism regulated the assembly of plasma FN (pFN) by adherent MKs to type I collagen. In conclusion, our data extend the knowledge of the mechanisms that regulate MK-matrix interactions within the bone marrow environment and could serve as an important step for inquiring into the origins of diseases such as myelofibrosis and congenital thrombocytopenias that are still poorly understood.
A role for Blimp1 in the transcriptional network controlling natural killer cell maturation
Authors: Kallies Axel , Carotta Sebastian , Huntington Nicholas D. , Bernard Nicholas J. , Tarlinton David M. , Smyth Mark J. , Nutt Stephen L. 
Published: December 2010

Abstract
Natural killer (NK) cells are innate lymphocytes capable of immediate effector functions including cytokine production and cytotoxicity. Compared with B and T cells, the factors that control the peripheral maturation of NK cells are poorly understood. We show that Blimp1, a transcriptional repressor required for the differentiation of plasma cells and short-lived effector T cells, is expressed by NK cells throughout their development. Interleukin 15 (IL-15) is required for the early induction of Blimp1 in NK cells, with expression increasing in the most mature subsets of mouse and human NK cells. We show that Blimp1 is required for NK-cell maturation and homeostasis and for regulating their proliferative potential. It is also essential for high granzyme B expression, but not for most cytokine production and cytotoxicity. Surprisingly, interferon regulatory factor 4 (IRF4) and B-cell lymphoma 6 (Bcl6), 2 transcription factors crucial for the regulation of Blimp1 in B and T cells, are largely dispensable for Blimp1 expression in NK cells. T-bet deficiency, however, leads to attenuated Blimp1 expression. We have identified NK cells as the first hematopoietic cell type in which the IRF4-Blimp1-Bcl6 regulatory axis is not in operation, highlighting the distinct nature of the NK-cell gene-regulatory network.