bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lenalidomide Enhances Immune Checkpoint Blockade-Induced Immune Response in Multiple Myeloma
Authors: Görgün Güllü , Samur Mehmet K. , Cowens Kristen B. , Paula Steven , Bianchi Giada , Anderson Julie E. , White Randie E. , Singh Ahaana , Ohguchi Hiroto , Suzuki Rikio , Kikuchi Shohei , Harada Takeshi , Hideshima Teru , Tai Yu-Tzu , Laubach Jacob P. , Raje Noopur , Magrangeas Florence , Minvielle Stephane , Avet-Loiseau Herve , Munshi Nikhil C. , Dorfman David M. , Richardson Paul G. , Anderson Kenneth C. 
Published: May 2015

Abstract
Purpose: PD-1/PD-L1 signaling promotes tumor growth while inhibiting effector cell–mediated antitumor immune responses. Here, we assessed the impact of single and dual blockade of PD-1/PD-L1, alone or in combination with lenalidomide, on accessory and immune cell function as well as multiple myeloma cell growth in the bone marrow (BM) milieu.
Experimental Design: Surface expression of PD-1 on immune effector cells, and PD-L1 expression on CD138+ multiple myeloma cells and myeloid-derived suppressor cells (MDSC) were determined in BM from newly diagnosed (ND) multiple myeloma and relapsed/refractory (RR) multiple myeloma versus healthy donor (HD). We defined the impact of single and dual blockade of PD-1/PD-L1, alone and with lenalidomide, on autologous anti–multiple myeloma immune response and tumor cell growth.
Results: Both ND and RR patient multiple myeloma cells have increased PD-L1 mRNA and surface expression compared with HD. There is also a significant increase in PD-1 expression on effector cells in multiple myeloma. Importantly, PD-1/PD-L1 blockade abrogates BM stromal cell (BMSC)-induced multiple myeloma growth, and combined blockade of PD-1/PD-L1 with lenalidomide further inhibits BMSC-induced tumor growth. These effects are associated with induction of intracellular expression of IFNγ and granzyme B in effector cells. Importantly, PD-L1 expression in multiple myeloma is higher on MDSC than on antigen-presenting cells, and PD-1/PD-L1 blockade inhibits MDSC-mediated multiple myeloma growth. Finally, lenalidomide with PD-1/PD-L1 blockade inhibits MDSC-mediated immune suppression.
Conclusions: Our data therefore demonstrate that checkpoint signaling plays an important role in providing the tumor-promoting, immune-suppressive microenvironment in multiple myeloma, and that PD-1/PD-L1 blockade induces anti–multiple myeloma immune response that can be enhanced by lenalidomide, providing the framework for clinical evaluation of combination therapy. Clin Cancer Res; 21(20); 4607–18. ©2015 AACR.
Stroma, Stroma Everywhere (Far More Than You Think)
Authors: Olive Kenneth P. 
Published: May 2015

Abstract
Pancreatic ductal adenocarcinomas with high stromal content are shown to have greatly reduced overall survival, consistent with previous reports that stroma may limit drug delivery. In contrast to expectations, metastatic lesions were found to harbor as much stroma as primary tumors. Clin Cancer Res; 21(15); 3366–8. ©2015 AACR.
See related article by Whatcott et al., p. 3561
Patient Activity and Survival Following Implantable Cardioverter‐Defibrillator Implantation: The ALTITUDE Activity Study
Authors: Kramer Daniel B. , Mitchell Susan L. , Monteiro Joao , Jones Paul W. , Normand Sharon‐Lise , Hayes David L. , Reynolds Matthew R. 
Published: May 2015

Background

Physical activity data are collected automatically by implantable cardioverter‐defibrillators (
ICD
s). Though these data potentially provide a quantifiable and easily accessible measure of functional status, its relationship with survival has not been well studied.

Methods and Results

Patients enrolled in the Boston Scientific
LATITUDE
remote monitoring system from 2008 to 2012 with
ICD
s were eligible. Remote monitoring data were used to calculate mean daily activity at baseline (30 to 60 days after implantation), and longitudinally. Cox regression was used to examine the association between survival and increments of 30 minutes/day in both (1) mean baseline activity and (2) time‐varying activity, with both adjusted for demographic and device characteristics. A total of 98 437 patients were followed for a median of 2.2 years (mean age of 67.7±13.1 years; 71.7% male). Mean baseline daily activity was 107.5±66.2 minutes/day. The proportion of patients surviving after 4 years was significantly higher among those in the most versus least active quintile of mean baseline activity (90.5% vs. 50.0%; log‐rank
P
value, <0.001). Lower mean baseline activity (i.e., incremental difference of 30‐minutes/day) was independently associated with a higher risk of death (adjusted hazard ratio [
AHR
], 1.44; 95% confidence interval [
CI
], 1.427 to 1.462). Time‐varying activity was similarly associated with a higher risk of death (
AHR
, 1.48; 95%
CI
, 1.451 to 1.508), indicating that a patient having 30 minutes per day less activity in a given month has a 48% increased hazard for death when compared to a similar patient in the same month.

Conclusions

Patient activity measured by
ICD
s strongly correlates with survival following
ICD
implantation.
Romantic relationships and psychological distress among adolescents: Moderating role of friendship closeness
Authors: Chow Chong Man , Ruhl Holly , Buhrmester Duane 
Published: May 2015

Background: The formation of romantic relationships and friendships in adolescence is a defining milestone in the progression toward social maturity. Thus, examining adolescents’ friendship and romantic experiences serves a vital role in understanding their psychological adjustment. Aims: The main purposes of the current study were to examine (a) whether romantic involvement, romantic security, and friendship closeness were independently predictive of late adolescents’ depression and loneliness, and (b) whether friendship closeness would moderate the negative effects of adolescents’ lower degrees of romantic involvement and romantic security on depression and loneliness. Method: Data came from 12th grade adolescents ( N = 110, 53 females) as well as their parents and a same-sex best friend. Adolescents reported on their romantic involvement, romantic security, and psychological distress. Parent reports of adolescents’ depressive symptoms and friend reports of friendship closeness were also included. Results: Higher degrees of romantic involvement and friendship closeness were related to lower degrees of loneliness. Higher degrees of romantic security were related to lower degrees of depression and loneliness. The effect of romantic involvement on depression and loneliness was moderated by friendship closeness. Also, the effect of romantic security on loneliness was moderated by friendship closeness. Conclusion: Future research should focus on the interactive roles that friendships and romantic relationships play in the emergence of psychopathology during adolescence.
The audit report as an instrument for accountability in local governments: a proposal for Spanish municipalities
Authors: Rosa Carolina Pontones , Morote Rosario Perez 
Published: May 2015

This article explores the possibility that common standards for performance audit reports may result in increased objectivity and accountability, and that this could narrow the ‘audit expectations gap’ and contribute to good governance within local government. Inspired by the UK's external performance auditing model and considering the current scenario in Spain, a number of hypotheses are formulated whereby the audit of a set of aspects in the areas of managing finances, governing the business and managing resources leads to higher accountability as a result of the audit reports. These hypotheses are tested through a survey to internal and external auditors of the Spanish local government. The strong endorsement of these aspects in the survey responses leads to their inclusion in the content of the audit reports. In addition, this content is simplified through a factor analysis of the suitability of smaller municipalities, and a practical contribution is offered by providing a template for external audit reports. Points for practitioners In this article we identify a minimal content for the external audit reports issued for Spanish local government, providing a possible template. This content gathers a set of aspects of public management that should be reviewed by external auditors. The proposal originates in international experience and is validated for the Spanish context by the results of the survey. We believe that this could increase the capacity of the reports to achieve accountability and help to narrow the ‘audit expectation gap’. The simplification of the content of the reports undertaken pursues a greater adaptation of the audit work to the conditions of small municipalities.
Ultrasonography for Screening and Follow-Up of Diaphragmatic Dysfunction in the ICU
Authors: Mariani Lucie Fenet , Bedel Jêrome , Gros Antoine , Lerolle Nicolas , Milojevic Kolia , Laurent Virgine , Hilly Julia , Troché Gilles , Bedos Jean Pierre , Planquette Benjamin 
Published: May 2015

Purpose: Reversibility and impact of diaphragmatic dysfunction (DD) are unknown. The principal aim was to describe diaphragmatic function as assessed by ultrasonography during weaning trials. Materials and Methods: The present study is a 6-month single-center prospective study. All patients under mechanical ventilation for more than 7 days and eligible for a spontaneous breathing trial (SBT) were enrolled prospectively. Intervention: Two blinded ultrasonographers evaluated each hemidiaphragm during SBT. Prevalence of DD among weaning failure and death and interobserver reproducibility have been evaluated. Results: The 34 included patients had a mean Simplified Acute Physiology Score version II of 55.7 ± 14 and a median intensive care unit (ICU) stay length of 17 days (13-30). Diaphragmatic dysfunction was found in 13 (38%) patients, on both sides in 8. Bilateral DD resolved before ICU discharge in 5 of the 7 reevaluated patients. No weaning failures were recorded. The ICU mortality was higher in patients with DD (37% vs 5%, P = .048). Mean interobserver agreement rate was 91%. Reproducibility was better with M-mode. Conclusion: The ICU-acquired DD usually improves before ICU discharge but might constitute a marker for greater disease severity. The present preliminary results require confirmation in a larger prospective multicenter study.
Early Lupus Project – A multicentre Italian study on systemic lupus erythematosus of recent onset
Authors: Sebastiani G D , Prevete I , Piga M , Iuliano A , Bettio S , Bortoluzzi A , Coladonato L , Tani C , Spinelli F R , Fineschi I , Mathieu A 
Published: May 2015

Background Systemic lupus erythematosus (SLE) is an autoimmune disease with a high degree of variability at onset that is problematic for a correct and prompt diagnosis. We undertook this project with the purpose of collecting an inception cohort of Italian patients with recent-onset SLE, in order to obtain information on the main clinical and serological characteristics at the beginning of the disease. In this first report we describe the characteristics of this cohort at study entry. Methods All patients with a diagnosis of SLE (1997 ACR criteria) and a disease duration less than 12 months were consecutively enrolled between 1 January 2012 and 31 December 2013 in a multicentre prospective study. Information on clinical and serological characteristics at study entry and then every six months was collected into a specific electronic database. Statistical analysis was performed by means of the Openstat program. Results Among 122 patients enrolled (103 F) 94.3% were Caucasians. Mean age (SD) of patients at study entry was 37.3 (14.3) years, mean age at disease onset was 34.8 (14.3) years, mean age at diagnosis was 36.9 (14.3) years, and mean disease duration was 2.9 (3.9) months. The frequency of the manifestations included in the 1997 ACR criteria was as follows: ANA 97.5%, immunologic disorders (anti-dsDNA, anti-Sm, antiphospholipid antibodies) 85.2%, arthritis 61.8%, haematologic disorders 55.7%, malar rash 31.1%, photosensitivity 29.5%, serositis 27%, renal disorders 27%, oral/nasal ulcers 11.5%, neurologic disorders 8.2%, and discoid rash 5.7%. The cumulative frequency of mucocutaneous symptoms was 77.8%. At enrolment, autoantibody frequency was: ANA 100%, anti-dsDNA 83.6%, anti-SSA 28%, anticardiolipin 24.5%, anti-nRNP 20.4%, anti-beta2GPI 17.2%, lupus anticoagulant 16.3%, anti-Sm 16%, and anti-SSB 13.1%. Conclusions In this paper we describe the main clinical and serological characteristics of an Italian inception cohort of patients with recent-onset SLE. At disease onset, mucocutaneous manifestations, arthritis and haematologic manifestations were the most frequent symptoms; ANA, anti-dsDNA and complement reduction were the most frequent laboratory findings. Our data confirm that the diagnosis of SLE is a challenging one, and that SLE is a severe disease even at onset, since the majority of patients require at least a hospitalization before the diagnosis.
Distributed leadership through the lens of Activity Theory
Authors: Ho Jeanne Pau Yen , Victor Chen Der-Thanq , Ng David 
Published: May 2015

Purpose: Using Activity Theory as an interpretive lens to examine the distribution of leadership, this paper shares a case study on how leadership for an ICT project was distributed in a Singapore school. Method: The case study involved observations of 49 meetings and 34 interviews of leaders and the teachers who were involved in the ICT project. Findings: Applying the lens of third-generation Activity Theory helped to reveal two main interrelated activity systems, and the leadership actions performed by senior and middle management. The two activity systems comprised the school and the ICT project. The focus in Activity Theory on the social–cultural perspective highlighted the role played by social norms in mediating the leadership activity. Implications for future research: The conclusion focuses on the understanding of distributed leadership as analysed through the lens of Activity Theory and suggests future research directions. Activity Theory enables research on distributed leadership to identify and examine interrelated activity systems that various leaders are involved in, and how these impact the leadership provided.
Test-Retest Reliability of a Computerized Concussion Test
Authors: Littleton Ashley C. , Register-Mihalik Johna K. , Guskiewicz Kevin M. 
Published: May 2015

Background: Neurocognitive testing is an important concussion evaluation tool, but for neurocognitive tests to be useful, their psychometric properties must be well established. Test-retest reliability of computerized neurocognitive tests can influence their clinical utility. The reliability for a commonly used computerized neurocognitive test, CNS Vital Signs, is not well established. The purpose of this study was to examine test-retest reliability and reliable change indices for CNS Vital Signs in a healthy, physically active college population. Hypothesis: CNS Vital Signs yields acceptable test-retest reliability, with greater reliability between the second and third test administration compared with between the first and second administration. Study Design: Cohort study. Level of Evidence: Level 3. Methods: Forty healthy, active volunteers (16 men, 24 women; mean age, 21.05 ± 2.17 years) reported to a clinical laboratory for 3 sessions, 1 week apart. At each session, participants were administered CNS Vital Signs. Outcomes included standard scores for the following CNS Vital Signs domains: verbal memory, visual memory, psychomotor speed, cognitive flexibility, complex attention, processing speed, reaction time, executive functioning, and reasoning. Results: Participants performed significantly better on the second session and/or third session than they did on the first testing session on 6 of 9 neurocognitive domains. Pearson r test-retest correlations between sessions ranged from 0.11 to 0.87. Intraclass correlation coefficients ranged from 0.10 to 0.86. Conclusion: Clinicians should consider using reliable change indices to account for practice effects, identify meaningful score changes due to pathology, and inform clinical decisions. Clinical Relevance: This study highlights the importance of clinicians understanding the psychometric properties of computerized neurocognitive tests when using them in the management of sport-related concussion. If CNS Vital Signs is administered twice within a small time frame (such as 1 week), athletes should be expected to improve between the first and second administration.
Are Hip Precautions Necessary Post Total Hip Arthroplasty? A Systematic Review
Authors: Barnsley Lara , Barnsley Leslie , Page Richard 
Published: May 2015

Purpose: Total hip arthroplasty (THA) is a common and effective treatment of hip osteoarthritis. Activity restrictions known as hip precautions are widely practiced in rehabilitation post THA, aiming to foster healing and prevent hip dislocation. The focused clinical question was: Does the application of hip precautions in patients post THA versus unrestricted activities significantly decrease the risk of prosthetic dislocation? Methods: A comprehensive literature search was conducted for randomized controlled trials or cohort studies with a comparative group and minimum 6 months follow-up, with dislocation as an end point. Retrieved titles were assessed independently by 2 reviewers for inclusion and underwent standardized data extraction. Results: Title search produced 80 potentially relevant articles. Five articles were retrieved for data extraction of which 2 met a prior eligibility criteria. No eligible studies were found that concerned posterior approaches to hip arthroplasty, so the results of this review concern only anterolateral approaches. Neither included study showed any benefit of hip precautions in preventing dislocation. Conclusion: The rate of dislocation after anterolateral THA is low and is not improved by hip precautions. Hip precautions are associated with a slower return to activities, significant expense, and decreased patient satisfaction. Existing studies risk being compromised by a type II error, but a definitive study may be prohibitively large and expensive.
Dicer1 imparts essential survival cues in Notch-driven T-ALL via miR-21–mediated tumor suppressor Pdcd4 repression
Authors: Junker Fabian , Chabloz Antoine , Koch Ute , Radtke Freddy 
Published: May 2015

Key PointsDicer1-mediated miRNA biogenesis is essential for induction and maintenance of Notch1-driven T-ALL. miR-21 regulates survival of T-ALL, in part through the repression of the tumor suppressor gene Pdcd4.
Warfarin-induced venous limb ischemia/gangrene complicating cancer: a novel and clinically distinct syndrome
Authors: Warkentin Theodore E. , Cook Richard J. , Sarode Ravi , Sloane Debi A. , Crowther Mark A. 
Published: May 2015

Key PointsWarfarin-induced venous gangrene in cancer affects limb with DVT and features platelet fall after stopping heparin and supratherapeutic INR. Persisting thrombin generation occurs despite elevated INR, indicating severe PC depletion that occurs in parallel with reduced factor VII.
Pain Perception in Acute Model Mice of Parkinson's Disease Induced by 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP)
Authors: Park Jihye , Lim Chae-Seok , Seo Hyunhyo , Park Chung-Ah , Zhuo Min , Kaang Bong-Kiun , Lee Kyungmin 
Published: May 2015

Background Pain is the most prominent non-motor symptom observed in patients with Parkinson's disease (PD). However, the mechanisms underlying the generation of pain in PD have not been well studied. We used a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD to analyze the relationship between pain sensory abnormalities and the degeneration of dopaminergic neurons. Results The latency to fall off the rotarod and the total distance traveled in round chamber were significantly reduced in MPTP-induced PD mice, consistent with motor dysfunction. MPTP-treated mice also showed remarkably shorter nociceptive response latencies compared to saline-treated mice and the subcutaneous injection of L-3,4-dihydroxyphenylalanine (L-DOPA) partially reversed pain hypersensitivity induced by MPTP treatment. We found that degeneration of cell bodies and fibers in the substantia nigra pars compacta and the striatum of MPTP-treated mice. In addition, astrocytic and microglial activation was seen in the subthalamic nucleus and neuronal activity was significantly increased in the striatum and globus pallidus. However, we did not observe any changes in neurons, astrocytes, and microglia of both the dorsal and ventral horns in the spinal cord after MPTP treatment. Conclusions These results suggest that the dopaminergic nigrostriatal pathway may have a role in inhibiting noxious stimuli, and that abnormal inflammatory responses and neural activity in basal ganglia is correlated to pain processing in PD induced by MPTP treatment.
Functional fingerprinting of human mesenchymal stem cells using high-throughput RNAi screening
Authors: Erdmann Gerrit , Suchanek Michael , Horn Patrick , Graf Fabian , Volz Christian , Horn Thomas , Zhang Xian , Wagner Wolfgang , Ho Anthony D. , Boutros Michael 
Published: May 2015

AbstractMesenchymal stem cells (MSCs) are promising candidates for cellular therapies ranging from tissue repair in regenerative medicine to immunomodulation in graft versus host disease after allogeneic transplantation or in autoimmune diseases. Nonetheless, progress has been hampered by their enormous phenotypic as well as functional heterogeneity and the lack of uniform standards and guidelines for quality control. In this study, we describe a method to perform cellular phenotyping by high-throughput RNA interference in primary human bone marrow MSCs. We have shown that despite heterogeneity of MSC populations, robust functional assays can be established that are suitable for high-throughput and high-content screening. We profiled primary human MSCs against human fibroblasts. Network analysis showed a kinome fingerprint that differs from human primary fibroblasts as well as fibroblast cell lines. In conclusion, this study shows that high-throughput screening in primary human MSCs can be reliably used for kinome fingerprinting.