bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAR405838: A Novel and Potent Inhibitor of the MDM2:p53 Axis for the Treatment of Dedifferentiated Liposarcoma
Authors: Bill Kate Lynn J. , Garnett Jeannine , Meaux Isabelle , Ma XiaoYen , Creighton Chad J. , Bolshakov Svetlana , Barriere Cedric , Debussche Laurent , Lazar Alexander J. , Prudner Bethany C. , Casadei Lucia , Braggio Danielle , Lopez Gonzalo , Zewdu Abbie , Bid Hemant , Lev Dina , Pollock Raphael E. 
Published: October 2015

Abstract
Purpose: Dedifferentiated liposarcoma (DDLPS) is an aggressive malignancy that can recur locally or disseminate even after multidisciplinary care. Genetically amplified and expressed MDM2, often referred to as a “hallmark” of DDLPS, mostly sustains a wild-type p53 genotype, substantiating the MDM2:p53 axis as a potential therapeutic target for DDLPS. Here, we report on the preclinical effects of SAR405838, a novel and highly selective MDM2 small-molecule inhibitor, in both in vitro and in vivo DDLPS models.
Experimental Design: The therapeutic effectiveness of SAR405838 was compared with the known MDM2 antagonists Nutlin-3a and MI-219. The effects of MDM2 inhibition were assessed in both in vitro and in vivo. In vitro and in vivo microarray analyses were performed to assess differentially expressed genes induced by SAR405838, as well as the pathways that these modulated genes enriched.
Results: SAR405838 effectively stabilized p53 and activated the p53 pathway, resulting in abrogated cellular proliferation, cell-cycle arrest, and apoptosis. Similar results were observed with Nutlin-3a and MI-219; however, significantly higher concentrations were required. In vitro effectiveness of SAR405838 activity was recapitulated in DDLPS xenograft models where significant decreases in tumorigenicity were observed. Microarray analyses revealed genes enriching the p53 signaling pathway as well as genomic stability and DNA damage following SAR405838 treatment.
Conclusions: SAR405838 is currently in early-phase clinical trials for a number of malignancies, including sarcoma, and our in vitro and in vivo results support its use as a potential therapeutic strategy for the treatment of DDLPS.
miR-138–Mediated Regulation of KINDLIN-2 Expression Modulates Sensitivity to Chemotherapeutics
Authors: Sossey-Alaoui Khalid , Plow Edward F. 
Published: October 2015

Abstract
Prostate cancer is the second leading cause of cancer-related death in men, second only to lung cancer, mainly due to disease reoccurrence as a result to lack of response to androgen deprivation therapies (ADT) after castration. Patients with metastatic castration–resistant prostate cancer (mCRPC) have very limited treatment options, with docetaxel as the first-line standard of care, for which resistance to this chemotherapeutic ultimately develops. Therefore, finding ways to sensitize tumors to chemotherapies and to limit chemoresistance provides a viable strategy to extend the survival of mCRPC patients. This study investigated the role of Kindlin-2 (FERMT2/K2), a member of the Kindlin family of FERM domain proteins and key regulators of the adhesive functions mediated by integrin, in the sensitization of mCRPC to chemotherapeutics. Loss of K2, which is overexpressed in prostate cancer cells derived from mCRPC tumors, compared with those cells derived from androgen-dependent tumors, significantly enhanced apoptosis and cell death of docetaxel-treated PC3 cells. Furthermore, it was determined that K2-mediated sensitization to docetaxel treatment is the result of inhibition of β1-integrin signaling. Finally, miR-138 specifically targeted K2 and inhibited its expression, thereby regulating a miR-138/K2/β1-integrin signaling axis in mCRPC that is critical for the modulation of sensitivity to chemotherapeutics. Thus, these data identify a novel signaling axis where K2 in combination with chemotherapeutics provides a new target for the treatment of mCRPC.
Implications: Targeted inhibition of Kindlin-2 in combination with chemotherapy represents an effective treatment option for mCRPC. Mol Cancer Res; 14(2); 228–38. ©2015 AACR.
Prognostic Importance of Changes in Cardiac Structure and Function in Heart Failure With Preserved Ejection Fraction and the Impact of Spironolactone
Authors: Shah Amil M. , Claggett Brian , Sweitzer Nancy K. , Shah Sanjiv J. , Deswal Anita , Anand Inder S. , Fleg Jerome L. , Pitt Bertram , Pfeffer Marc A. , Solomon Scott D. 
Published: October 2015

Background—
Limited data exist regarding the impact of aldosterone antagonist therapy on cardiac structure and function in heart failure with preserved ejection fraction and on the prognostic relevance of changes in cardiac structure and function in heart failure with preserved ejection fraction.

Methods and Results—
Cardiac structure and function were assessed by quantitative echocardiography at baseline and at 12- to 18-month follow-up in 239 patients with heart failure with preserved ejection fraction (left ventricular [LV] ejection fraction [LVEF] ≥45%) enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. The impact of spironolactone therapy on measures of cardiac structure and function was assessed in the study population overall, and change in echocardiographic measures was associated with the subsequent occurrence of the primary composite outcome of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest. Spironolactone was not associated with alterations in cardiac structure and function compared with placebo. Decrease in left atrial volume at follow-up was associated with a lower risk of subsequent occurrence of the primary outcome.

Conclusions—
Twelve to 18 months of spironolactone therapy was not associated with alterations in cardiac structure or function in patients with heart failure with preserved ejection fraction. Reduction in left atrial volume at follow-up was associated with a lower risk of subsequent occurrence of the primary composite outcome.

Clinical Trial Registration—

URL:
http:///www.clinicaltrials.gov
. Unique identifier: NCT00094302.
Arrhythmogenic Phenotype in Dilated Cardiomyopathy: Natural History and Predictors of Life‐Threatening Arrhythmias
Authors: Spezzacatene Anita , Sinagra Gianfranco , Merlo Marco , Barbati Giulia , Graw Sharon L. , Brun Francesca , Slavov Dobromir , Di Lenarda Andrea , Salcedo Ernesto E. , Towbin Jeffrey A. , Saffitz Jeffrey E. , Marcus Frank I. , Zareba Wojciech , Taylor Matthew R. G. , Mestroni Luisa ,   the Familial Cardiomyopathy Registry
Published: October 2015

Background

Patients with dilated cardiomyopathy (
DCM
) may present with ventricular arrhythmias early in the disease course, unrelated to the severity of left ventricular dysfunction. These patients may be classified as having an arrhythmogenic
DCM
(
AR
‐
DCM
). We investigated the phenotype and natural history of patients with
AR
‐
DCM
.

Methods and Results

Two hundred eighty‐five patients with a recent diagnosis of
DCM
(median duration of the disease 1 month, range 0 to 7 months) and who had Holter monitoring at baseline were comprehensively evaluated and followed for 107 months (range 29 to 170 months).
AR
‐
DCM
was defined by the presence of ≥1 of the following: unexplained syncope, rapid nonsustained ventricular tachycardia (≥5 beats, ≥150 bpm), ≥1000 premature ventricular contractions/24 hours, and ≥50 ventricular couplets/24 hours, in the absence of overt heart failure. The primary end points were sudden cardiac death (
SCD
), sustained ventricular tachycardia (
SVT
), or ventricular fibrillation (
VF
). The secondary end points were death from congestive heart failure or heart transplantation. Of the 285 patients, 109 (38.2%) met criteria for
AR
‐
DCM
phenotype.
AR
‐
DCM
subjects had a higher incidence of
SCD
/
SVT
/
VF
compared with non–
AR
‐
DCM
patients (30.3% vs 17.6%,
P
=0.022), with no difference in the secondary end points. A family history of
SCD
/
SVT
/
VF
and the
AR
‐
DCM
phenotype were statistically significant and cumulative predictors of
SCD
/
SVT
/
VF
.

Conclusions

One‐third of
DCM
patients may have an arrhythmogenic phenotype associated with increased risk of arrhythmias during follow‐up. A family history of ventricular arrhythmias in
DCM
predicts a poor prognosis and increased risk of
SCD
.
Association patterns and affiliative relationships outside a troop in wild male Japanese macaques, Macaca fuscata, during the non-mating season
Authors: Kawazoe Tatsuro 
Published: October 2015

In many mammals, males disperse more than females. Although males in some male-dispersing species form all-male groups, little is known about the association patterns or social relationships among them. Studies on male–male social relationships have primarily focused on competition over fertile females, but affiliative relationships among males have attracted much interest recently. I suggested a novel method for the classification of males based on their behaviour by principal component analysis (PCA), and investigated association patterns, and affiliative relationships in male Japanese macaques, Macaca fuscata, during the non-mating season. I observed 12 wild male Japanese macaques for 809 h during the non-mating season. The number of other animals within visual range, the amount of time that males spent in the vicinity of other animals, and the frequency of grooming interactions were examined. I classified males into two distinctive clusters (Cluster 1 and 2) according to their association and interaction patterns. Cluster 1 males associated with females and participated in grooming with them. Cluster 2 males had less visual encounters with females and did not groom them. Cluster 2 males showed proximity to other Cluster 2 males in all possible dyads. Although Cluster 2 males showed less proximity to each other than Cluster 1 males did, they frequently exchanged grooming among themselves. Cluster 2 males groomed Cluster 1 males more frequently than they were groomed by them. These results suggested that Cluster 1 were troop males, and Cluster 2 were non-troop males. Cluster 2 males had less opportunity for social interaction than Cluster 1 (troop) males, and they may form all-male groups. Males in all-male groups engaged in more frequent grooming than troop males. In addition, they groomed troop males more frequently than they were groomed. These results suggest that males could be separated by their behaviour. Male–male affiliative relationships might be influenced by within-group potential competition and imbalanced grooming appears to cause troop males to tolerate non-troop males which might be immigrated in near future.
Aggression and hierarchical steepness inhibit social play in adult wolves
Authors: Cordoni Giada , Palagi Elisabetta 
Published: October 2015

In canids, play dynamics seem to be more affected by dominance hierarchy rather than cooperative social bonds. To test this hypothesis we studied a colony of grey wolves (Canis lupus lupus). We quantified the dynamics of aggression and hierarchical changes in two periods (Sample 1 and Sample 2). Sample 2 was characterized by higher level of aggressiveness and by a more strict and steep linear hierarchy. The negative correlation between rank distance and play frequency characterizing both periods and the higher play asymmetry in Sample 2 suggest that rank rules dictate play rules thus highlighting the competitive side of wolf play behaviour. The overall affiliation rates showed no variation between the two samples. Yet, play performance was modified. In Sample 2, wolves reduced playful activity, limited the number of players per session and avoided playing during high competition contexts. Our findings support the hypothesis that wolf play is modulated by dominance relationships more than by cooperative social bonds.
Complications and Resource Utilization Associated With Mechanical Ventilation in a Medical Intensive Care Unit in 2013
Authors: Selvan Kavitha , Edriss Hawa , Sigler Mark , Nugent Kenneth M. 
Published: October 2015

Introduction: Evolving strategies for ventilator management could reduce the frequency of complications, but there is limited information about complications in contemporary intensive care units. Methods: We retrospectively collected information about patient demographics, chest x-ray abnormalities, complications, including pneumothoraces, ventilator-associated events, self-extubation, and resource utilization in 174 patients who required mechanical ventilation in 2013. Results: The mean age was 57.8 ± 16.8 years, the number of ventilator days was 7.5 ± 7, and the overall in-hospital mortality was 32.2%. The mean fluid balance per day during the mechanical ventilation period was 1539 ± 1721 mL. Three (1.7%) patients developed pneumothoraces, and 5 patients required chest tubes. Twenty-five (14.4%) patients had ventilator-associated events. Ten patients had episodes of self-extubation, and 11 had episodes of failed extubation. Chest X-rays showed new or increasing infiltrates in 113 (64.9%) patients and new or increasing pleural effusions in 29 (16.7%) patients. These patients had 1.2 ± 0.4 X-rays per day on the ventilator, and they had 10.0 ± 9.4 arterial blood gases and 0.7 ± 0.7 central lines. Conclusion: The frequency of ventilator-associated complications was low in this study. However, these patients frequently developed increasing infiltrates, and these outcomes need attention during patient management and are a potential focus for future studies.
A Retrospective Cohort Analysis of Pharmacologic VTE Prophylaxis and Padua Prediction Score in Hospitalized Patients With Chronic Liver Disease
Authors: Moorehead Kaitlyn J. , Jeffres Meghan N. , Mueller Scott W. 
Published: October 2015

Purpose: Coagulopathy resulting from chronic liver disease (CLD) creates uncertainty regarding the risks and efficacy of pharmacologic venous thromboembolism (VTE) prophylaxis (ppx). We aim to describe patient characteristics associated with VTE ppx and the clinical impact of ppx in hospitalized patients with CLD. Methods: This retrospective study included patients with CLD, an international normalized ratio (INR) of ≥1.3, and hospital stay of ≥72 hours. Baseline characteristics, incidence of VTE, and major bleeding were compared between patients given ppx and those not given ppx. Results: Of 300 patients with CLD included, 157 (52%) received VTE ppx. Characteristics associated with VTE ppx were lower activated partial thromboplastin time, INR, bilirubin, and Model for End-Stage Liver Disease (MELD) score as well as a higher Padua Prediction Score, hemoglobin, platelet count, and antiplatelet use. VTE occurred in 12 (7.6%) ppx versus 4 (2.8%) non-ppx patients ( P = .07). Major bleeding occurred in 47 (30%) ppx versus 49 (34.3%) non-ppx patients ( P = .46). Ppx was not associated with VTE or bleeding outcomes by multivariate regression. Conclusion: The use of VTE ppx in hospitalized patients with CLD was not associated with a lower risk of VTE nor did it increase the risk of bleeding. Further studies examining the risks and benefits of VTE ppx in this population are needed.
The SAVRY Improves Prediction of Reoffending
Authors: Åström Therese , Gumpert Clara Hellner , Andershed Anna-Karin , Forster Martin 
Published: October 2015

Purpose: This study investigated the utility of the risk assessment “Structured Assessment of Violence Risk in Youth” (SAVRY) within the social services in Stockholm County, Sweden. Method: SAVRY assessments of 56 adolescents were compared to assessments guided by another instrument (Adolescent Drug Abuse Diagnosis [ADAD]; n = 38) and assessments without support of a structured method ( n = 38). Results: The results showed that social workers conducting SAVRY assessments documented a significantly larger number of risk and protective factors compared to the other assessments, and these factors predicted, with a few exceptions, reoffending to a larger extent. SAVRY summary risk rating significantly predicted the occurrence of serious violent crimes (area under the curve [AUC] = .80, p < .01) and less serious violence (AUC = .70, p < .05). Conclusions: SAVRY performed at least as well in naturalistic settings as in previous studies conducted in more controlled environments. Furthermore, the SAVRY performed better than the other structured instrument (ADAD).
Mindfulness-Based Approaches in the Treatment of Disordered Gambling
Authors: Maynard Brandy R. , Wilson Alyssa N. , Labuzienski Elizabeth , Whiting Seth W. 
Published: October 2015

Background and Aims: To examine the effects of mindfulness-based interventions on gambling behavior and symptoms, urges, and financial outcomes. Method: Systematic review and meta-analytic procedures were employed to search, select, code, and analyze studies conducted between 1980 and 2014, assessing the effects of mindfulness-based interventions in the treatment of disordered gambling with adults. Results: Thirteen studies met criteria for this review and seven met criteria for meta-analysis. Effects were moderate to large for gambling behaviors/symptoms ( g = 0.68, 95% CI = [0.39, 0.98], p < .01), gambling urges ( g = 0.69, 95% CI = [0.18, 1.20], p < .01), and financial outcomes ( g = 0.75, 95% CI = [0.24, 1.26], p < .01). Heterogeneity was low and nonsignificant. Conclusions: The findings provide support for mindfulness-based interventions in the treatment of disordered gambling. However, these results are necessarily tentative, limited by the number and quality of eligible studies, and differing conceptualizations of mindfulness.
Effects of Multidimensional Family Therapy (MDFT) on Nonopioid Drug Abuse
Authors: Filges Trine , Andersen Ditte , Jørgensen Anne-Marie Klint 
Published: October 2015

Purpose: This review evaluates the evidence of the effects of multidimensional family therapy (MDFT) on drug use reduction in young people for the treatment of nonopioid drug use. Method: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized and nonrandomized trials. Meta-analytic methods were used to quantitatively synthesize study results. Results: The search yielded five studies that met inclusion criteria. MDFT was found to be more effective than other treatments on drug abuse problem severity and drug use frequency in the short run but not in the long run and demonstrated positive effects on treatment retention compared to control conditions. Discussion: While additional research is needed, the review offers support for MDFT as a treatment to young nonopioid drug abusers. The number of studies included in this review was limited, however, and this should be considered when interpreting the results.
Disentangling SLI and bilingualism using sentence repetition tasks: the impact of L1 and L2 properties
Authors: Meir Natalia , Walters Joel , Armon-Lotem Sharon 
Published: October 2015

The current study investigated performance on morpho-syntax in Russian–Hebrew sequential bilingual preschool children with and without specific language impairment (SLI) in both languages (L1 Russian and L2 Hebrew) using sentence repetition (SRep) tasks with a fundamental aim to disentangle the language abilities of bilingual children with typical language development (biTLD) from those of bilingual children with SLI (biSLI). Four groups of children participated ( N=85) in the study: 45 L1 Russian–L2 Hebrew sequential bilinguals (30 biTLD and 15 biSLI), 20 monolingual Russian-speaking children and 20 monolingual Hebrew-speaking children. The SRep tasks in Russian and in Hebrew were based on Language Impairment Testing in Multilingual Settings (LITMUS) SRep developed within COST Action IS0804 titled “Language Impairment in a Multilingual Society: Linguistic Patterns and the Road to Assessment”. The tasks in Russian and in Hebrew contained 56 sentences of different length and complexity. The bilingual–monolingual comparisons yielded differences only in L1 Russian, where the monolingual Russian-speaking children outperformed bilingual children with typical language development (TLD) in their first language. In L2 Hebrew, no significant differences emerged between monolingual speakers of Hebrew and bilinguals. Comparisons of bilingual children with and without SLI showed that both the quantity and the quality of errors differentiate the two bilingual groups. In both languages (L1 and L2), bilingual children with TLD outperformed their peers with SLI. Bilingual children with SLI produced specific error patterns like those previously reported for monolingual children with SLI, i.e. omission of coordinators and subordinators, omission of prepositions, and simplification of wh-questions and relative clauses. These error patterns are unique to children with SLI and cannot be attributed to L1–L2 influence, while the errors of children in the biTLD group can be traced to cross-linguistic influence (mostly L2 influence on L1). We conclude that SRep tasks are an effective means to bring us closer to distinguishing bilingual children with SLI from those with TLD. They allow us to make quantitative and qualitative comparisons of performance and errors. But, perhaps more importantly, they point to underlying grammatical representations, in particular those linked to cross-linguistic influence and reduced exposure, as a way of distinguishing bilingual children with and without SLI.
Assessment of weight status, dietary habits and beliefs, physical activity, and nutritional knowledge among university students
Authors: Yahia Najat , Wang Daniel , Rapley Melyssa , Dey Rajarshi 
Published: October 2015

Aims: The purpose of this study was to assess weight status, dietary habits, physical activity, dietary beliefs, and nutrition knowledge among a sample of students from Central Michigan University. Methods: A cross-sectional survey was conducted among a sample of undergraduate students in Fall 2011 and Spring 2012 at Central Michigan University. Participating students completed an online questionnaire that included questions related to their eating habits, physical activity and lifestyle, dietary beliefs, and nutritional knowledge. Weight, height, and waist circumference were measured. Percentage body fat and visceral fat score were determined using a Tanita body composition analyser (SC-331S). Results: Outcomes of this study indicated that 78% of female students were within the healthy weight range compared to 52% of male students. Visceral body fat and waist circumference scores were higher in males than in females. Most students showed ‘satisfactory’ dietary habits. Almost half of the students reported drinking two glasses of milk and consuming two cups of fruits and vegetables daily. Physical activity and lifestyle score indicated that most of the students were not physically active. Only 7% of students reported having a very active lifestyle, and 4% had quite good nutritional knowledge. Conclusion: The majority of students, particularly females, were within the healthy body weight range. Students’ dietary habits were satisfactory. However, physical activity, students’ knowledge of healthy and unhealthy diet habits, and nutritional knowledge needed improvement. Developing gender-specific programmes for promoting healthy lifestyle behaviours among students is recommended.