bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Mesenchymal Stem Cells Densities When Injected as Suspension in Joints with Osteochondral Defects
Authors: Mahmoud Elhussein Elbadry , Kamei Naosuke , Kamei Goki , Nakasa Tomoyuki , Shimizu Ryo , Harada Yohei , Adachi Nobuo , Misk Nabil Ahmed , Ochi Mitsuo 
Published: May 2017

Objective The aim of this study was to evaluate an intraarticular injection of different doses of autologous mesenchymal stem cells (MSCs) for improving repair of midterm osteochondral defect. Design At 4 weeks postoperative marrow stimulation model bilaterally (3 mm diameter; 4 mm depth) in the medial femoral condyle, autologous MSCs were injected into knee joint. Twenty-four Japanese rabbits aged 6 months were divided randomly into 4 groups ( n = 6 per group): the control group and and MSC groups including 0.125, 1.25, and 6.25 million MSCs. Repaired tissue was assessed macroscopically and histologically at 4 and 12 weeks after intraarticular injection of MSCs. Results At 12 weeks, there was no repair tissue in the control group. The gross appearance of the 1.25 and 6.25 million MSC groups revealed complete repair of the defect with white to pink tissue at 12 weeks. An osteochondral repair was histologically significantly better in the 1.25 and 6.25 million MSC groups than in the control and 0.125 million MSC groups at 4 and 12 weeks, due to presence of hyaline-like tissue in the deep layer at 4 weeks, and at 12 weeks hyaline cartilage formation at the periphery and fibrous tissue containing some chondrocytes in the deep layer of the center of the defect. Subchondral bone was restructured in the 1.25 and 6.25 million MSC groups, although it did not resemble the normal bone. Conclusion An intraarticular injection of 1.25 or 6.25 million MSCs could promote the repair of subchondral bone, even in the case of midterm osteochondral defect.
GLI3 repressor determines Hedgehog pathway activation and is required for response to SMO antagonist glasdegib in AML
Authors: Chaudhry Parvesh , Singh Mohan , Triche Timothy J. , Guzman Monica , Merchant Akil A. 
Published: May 2017

Key Points
GLI3R inhibits Hh signaling and is required for response to SMO antagonist in AML. GLI3 is silenced in AML, and decitabine restores GLI3 expression and leads to modulation of Hh signaling.
Current understanding of bleeding with ibrutinib use: a systematic review and meta-analysis
Authors: Caron François , Leong Darryl P. , Hillis Christopher , Fraser Graeme , Siegal Deborah 
Published: May 2017

Abstract
Ibrutinib therapy was associated with an increased risk of bleeding in previous trials. In this systematic review and meta-analysis of published trials including patients treated with ibrutinib, the relative risk (95% confidence interval [CI]) of overall bleeding was significantly higher in ibrutinib recipients (2.72 [1.62-6.58]), but major bleeding did not show a significant difference (1.66 [0.96-2.85]). The incidences (95% CI) of major bleeding and any bleeding were 3.0 (2.3-3.7) and 20.8 (19.1-22.1) per 100 patient-years, respectively. This analysis is limited by reporting bias from variable ascertainment of bleeding and lack of allocation concealment in some studies and differing exposures between groups, leading to potential overestimation of event rates in the ibrutinib group.
Proliferation through activation: hemophagocytic lymphohistiocytosis in hematologic malignancy
Authors: Vick Eric J. , Patel Kruti , Prouet Philippe , Martin Mike G. 
Published: May 2017

AbstractHemophagocytic lymphohistiocytosis (HLH) is a syndrome of cytokine-driven immune activation. Cardinal features include fever, hemophagocytosis, hepatosplenomegaly, lymphocytic infiltration, and hypercytokinemia that result in multisystem organ dysfunction and failure. Familial HLH is genetically driven, whereas secondary HLH (SHL) is caused by drugs, autoimmune disease, infection, or cancer. SHL is associated with worse outcomes, with a median overall survival typically of less than 1 year. This reflects difficulty in both diagnostic accuracy and in establishing reliable treatments, especially in cases of malignancy-induced SHL, which have significantly worse outcomes. Malignancy-induced HLH is seen almost exclusively with hematologic malignancies, constituting 97% of cases in the literature over the past 2 years. In these situations, the native immune response driven by CD8 T cells produces an overabundance of T helper 1 cytokines, notably interferon-γ, tumor necrosis factor-α, and interleukin-6, which establish a positive feedback loop of inflammation, enhancing replication of hematologic malignancies while leaving the host immune system in disarray. In this paper, we present 2 case studies of secondary HLH driven by HM, followed by a review of the literature discussing the cytokines driving HLH, diagnostic criteria, and current treatments used or undergoing investigation.
Anthracycline induced cardiotoxicity: biomarkers and “Omics” technology in the era of patient specific care
Authors: Moazeni Shayan , Cadeiras Martin , Yang Eric H. , Deng Mario C. , Nguyen Kim‐Lien 
Published: May 2017

AbstractAnthracyclines are highly effective against a variety of malignancies. However, their dose‐dependent cardiotoxic effects can potentially limit their use. In the past decade, serum biomarkers have been used to diagnose, monitor, predict, and prognosticate disease. Biomarkers such as cardiac troponin and natriuretic peptides have some predictive value, but still lack reliability in this patient population. Novel biomarkers such as galectin‐3, soluble ST‐2 proteins, myeloperoxidase, and fibrocytes are being explored as potential biomarkers to reliably predict the onset of cardiotoxicity. Leveraging multiomics technology to map highly sensitive biomarkers in an integrated approach through pattern deconvolution may better define those at highest risk of developing cardiotoxicity and further the goal of precision medicine. In this work, we aim to provide a brief overview of traditional serum biomarkers, summarize current investigations on novel circulating biomarkers, and discuss a systems‐based approach to anthracycline‐induced cardiotoxicity through “omics” technology.
A fast image simulation algorithm for scanning transmission electron microscopy
Authors: Ophus Colin 
Published: May 2017

AbstractImage simulation for scanning transmission electron microscopy at atomic resolution for samples with realistic dimensions can require very large computation times using existing simulation algorithms. We present a new algorithm named PRISM that combines features of the two most commonly used algorithms, namely the Bloch wave and multislice methods. PRISM uses a Fourier interpolation factor f that has typical values of 4–20 for atomic resolution simulations. We show that in many cases PRISM can provide a speedup that scales with f4 compared to multislice simulations, with a negligible loss of accuracy. We demonstrate the usefulness of this method with large-scale scanning transmission electron microscopy image simulations of a crystalline nanoparticle on an amorphous carbon substrate.
Tai Chi Chih Compared With Cognitive Behavioral Therapy for the Treatment of Insomnia in Survivors of Breast Cancer: A Randomized, Partially Blinded, Noninferiority Trial
Authors: Irwin Michael R. , Olmstead Richard , Carrillo Carmen , Sadeghi Nina , Nicassio Perry , Ganz Patricia A. , Bower Julienne E. 
Published: May 2017

Purpose Cognitive behavioral therapy for insomnia (CBT-I) and Tai Chi Chih (TCC), a movement meditation, improve insomnia symptoms. Here, we evaluated whether TCC is noninferior to CBT-I for the treatment of insomnia in survivors of breast cancer. Patients and Methods This was a randomized, partially blinded, noninferiority trial that involved survivors of breast cancer with insomnia who were recruited from the Los Angeles community from April 2008 to July 2012. After a 2-month phase-in period with repeated baseline assessment, participants were randomly assigned to 3 months of CBT-I or TCC and evaluated at months 2, 3 (post-treatment), 6, and 15 (follow-up). Primary outcome was insomnia treatment response—that is, marked clinical improvement of symptoms by the Pittsburgh Sleep Quality Index—at 15 months. Secondary outcomes were clinician-assessed remission of insomnia; sleep quality; total sleep time, sleep onset latency, sleep efficiency, and awake after sleep onset, derived from sleep diaries; polysomnography; and symptoms of fatigue, sleepiness, and depression. Results Of 145 participants who were screened, 90 were randomly assigned (CBT-I: n = 45; TCC: n = 45). The proportion of participants who showed insomnia treatment response at 15 months was 43.7% and 46.7% in CBT-I and TCC, respectively. Tests of noninferiority showed that TCC was noninferior to CBT-I at 15 months ( P = .02) and at months 3 ( P = .02) and 6 ( P < .01). For secondary outcomes, insomnia remission was 46.2% and 37.9% in CBT-I and TCC, respectively. CBT-I and TCC groups showed robust improvements in sleep quality, sleep diary measures, and related symptoms (all P < .01), but not polysomnography, with similar improvements in both groups. Conclusion CBT-I and TCC produce clinically meaningful improvements in insomnia. TCC, a mindful movement meditation, was found to be statistically noninferior to CBT-I, the gold standard for behavioral treatment of insomnia.
AKT Inhibition in Solid Tumors With AKT1 Mutations
Authors: Hyman David M. , Smyth Lillian M. , Donoghue Mark T.A. , Westin Shannon N. , Bedard Philippe L. , Dean Emma J. , Bando Hideaki , El-Khoueiry Anthony B. , Pérez-Fidalgo José A. , Mita Alain , Schellens Jan H.M. , Chang Matthew T. , Reichel Jonathan B. , Bouvier Nancy , Selcuklu S. Duygu , Soumerai Tara E. , Torrisi Jean , Erinjeri Joseph P. , Ambrose Helen , Barrett J. Carl , Dougherty Brian , Foxley Andrew , Lindemann Justin P.O. , McEwen Robert , Pass Martin , Schiavon Gaia , Berger Michael F. , Chandarlapaty Sarat , Solit David B. , Banerji Udai , Baselga José , Taylor Barry S. 
Published: May 2017

Purpose AKT1 E17K mutations are oncogenic and occur in many cancers at a low prevalence. We performed a multihistology basket study of AZD5363, an ATP-competitive pan-AKT kinase inhibitor, to determine the preliminary activity of AKT inhibition in AKT-mutant cancers. Patients and Methods Fifty-eight patients with advanced solid tumors were treated. The primary end point was safety; secondary end points were progression-free survival (PFS) and response according to Response Evaluation Criteria in Solid Tumors (RECIST). Tumor biopsies and plasma cell-free DNA (cfDNA) were collected in the majority of patients to identify predictive biomarkers of response. Results In patients with AKT1 E17K–mutant tumors (n = 52) and a median of five lines of prior therapy, the median PFS was 5.5 months (95% CI, 2.9 to 6.9 months), 6.6 months (95% CI, 1.5 to 8.3 months), and 4.2 months (95% CI, 2.1 to 12.8 months) in patients with estrogen receptor–positive breast, gynecologic, and other solid tumors, respectively. In an exploratory biomarker analysis, imbalance of the AKT1 E17K–mutant allele, most frequently caused by copy-neutral loss-of-heterozygosity targeting the wild-type allele, was associated with longer PFS (hazard ratio [HR], 0.41; P = .04), as was the presence of coincident PI3K pathway hotspot mutations (HR, 0.21; P = .045). Persistent declines in AKT1 E17K in cfDNA were associated with improved PFS (HR, 0.18; P = .004) and response ( P = .025). Responses were not restricted to patients with detectable AKT1 E17K in pretreatment cfDNA. The most common grade ≥ 3 adverse events were hyperglycemia (24%), diarrhea (17%), and rash (15.5%). Conclusion This study provides the first clinical data that AKT1 E17K is a therapeutic target in human cancer. The genomic context of the AKT1 E17K mutation further conditioned response to AZD5363.
Factors Influencing Quality of Pain Management in a Physician Staffed Helicopter Emergency Medical Service
Authors: Oberholzer Nicole , Kaserer Alexander , Albrecht Roland , Seifert Burkhardt , Tissi Mario , Spahn Donat R. , Maurer Konrad , Stein Philipp 
Published: May 2017

BACKGROUND:
Pain is frequently encountered in the prehospital setting and needs to be treated quickly and sufficiently. However, incidences of insufficient analgesia after prehospital treatment by emergency medical services are reported to be as high as 43%. The purpose of this analysis was to identify modifiable factors in a specific emergency patient cohort that influence the pain suffered by patients when admitted to the hospital.

METHODS:
For that purpose, this retrospective observational study included all patients with significant pain treated by a Swiss physician-staffed helicopter emergency service between April and October 2011 with the following characteristics to limit selection bias: Age > 15 years, numerical rating scale (NRS) for pain documented at the scene and at hospital admission, NRS > 3 at the scene, initial Glasgow coma scale > 12, and National Advisory Committee for Aeronautics score < VI. Univariate and multivariable logistic regression analyses were performed to evaluate patient and mission characteristics of helicopter emergency service associated with insufficient pain management.

RESULTS:
A total of 778 patients were included in the analysis. Insufficient pain management (NRS > 3 at hospital admission) was identified in 298 patients (38%). Factors associated with insufficient pain management were higher National Advisory Committee for Aeronautics scores, high NRS at the scene, nontrauma patients, no analgesic administration, and treatment by a female physician. In 16% (128 patients), despite ongoing pain, no analgesics were administered. Factors associated with this untreated persisting pain were short time at the scene (below 10 minutes), secondary missions of helicopter emergency service, moderate pain at the scene, and nontrauma patients. Sufficient management of severe pain is significantly better if ketamine is combined with an opioid (65%), compared to a ketamine or opioid monotherapy (46%, P = .007).

CONCLUSIONS:
In the studied specific Swiss cohort, nontrauma patients, patients on secondary missions, patients treated only for a short time at the scene before transport, patients who receive no analgesic, and treatment by a female physician may be risk factors for insufficient pain management. Patients suffering pain at the scene (NRS > 3) should receive an analgesic whenever possible. Patients with severe pain at the scene (NRS ≥ 8) may benefit from the combination of ketamine with an opioid. The finding about sex differences concerning analgesic administration is intriguing and possibly worthy of further study.
The role of microRNA-449 in Human Breast Cancer
Authors: Shah Ajay 
Published: May 2017

In 2010, an estimated 173 800 cases of cancer were diagnosed in Canada and 76 200 of these cases were expected to be fatal. Current treatment options are often very invasive, harmful, and ineffective. The purpose of this experiment was to mitigate tumour growth by manipulation of micro-RNA (mRNA) levels. mRNAs are small proteins, and levels of specific mRNAs are deregulated in cancer cells. In this experiment, levels of micro-RNA 449, which is deregulated in breast cancer cell lines, were returned to their baseline levels. Numerous tests were then conducted to test the viability of the resulting cells. Replicable experiments showed that the strength, motility and invasiveness of the breast cancer cells was greatly diminished after mRNA-449 levels returned to baseline levels. Furthermore, research indicated that 4 potential genes (CRIP2, XBP1, TAF4B, and SFXN2) can be manipulated in future experiments to further diminish the viability of the breast cancer tumours. En 2015, 25220 cas estimés de cancer du sein ont été diagnostiqués au Canada et 5060 de ces cas étaient prévus d’être fatales. Les options de traitement courantes sont souvent très envahissantes, nuisibles et inefficaces. L’objet de cette expérience était d’atténuer la croissance de la tumeur en manipulant les niveaux d’ARN-Micro. ARNm sont de petites molécules qui codent pour des protéines et en cellules de cancer, les niveaux de certains ARNms sont dérégulés. Les niveaux d’ARN-micro 449, qui sont dérégulés dans les lignées cellulaires de cancer du sein, ont été retournées à leurs niveaux de base dans cette expérience. La viabilité des cellules ainsi obtenues a été analysé par plusieurs tests. Les expériences reproductibles ont indiqué que la force, la mobilité et le caractère invasif des cellules de cancer du sein ont été diminués après que les niveaux d’ARN-micro 449 sont retournés à leurs niveaux de base. En outre, l’étude a révélé que quatre gènes potentiels (CRIP2, XBP1, TAF4B, et SFXN2) pourraient être manipulés à l’avenir pour réduire davantage la viabilité des tumeurs du cancer du sein.
Political Federalism and Innovation: Are de jure Labor Regulations Absolute?
Authors: Ghosh Saibal 
Published: May 2017

Abstract
The importance of labour regulation in influencing innovative activity has attracted significant attention in the literature. What has not been adequately explored is the role played by different categories of such laws. In this context, employing state-level data for India during 1992–2010, we investigate how political federalism interacts with labour laws to influence innovative activity. Our findings suggest that although certain labour laws foster innovation, its complementarities with political federalism end up dampening innovation. These results call into question the widely held view of the innovation-enhancing effects of labour laws and suggest that the hitherto unaddressed political channel might have an important role to play in this regard.
A full-process chain assessment for nanoimprint technology on 200-mm industrial platform
Authors: Teyssedre Hubert , Landis Stefan , Thanner Christine , Laure Maria , Khan Jonas , Bos Sandra , Eibelhuber Martin , Chouiki Mustapha , May Michael , Brianceau Pierre , Pollet Olivier , Hazart Jerome , Laviron Cyrille , Pain Laurent , Wimplinger Markus 
Published: May 2017

Abstract
To evaluate the maturity of the wafer-scale NanoImprint lithography (NIL) process, laboratory of electronic and communication technology (LETI) and EV Group (EVG) launched the Imprint Nanopatterning Solution Platform for Industrial Assessment program (INSPIRE), which aims at building a nanoimprint solution platform for industrial assessment and provide a unique open ecosystem for the standardization of the nanoimprint process. This program enabled to gather EVG know-how for the tool manufacturing and its long expertise in bonding activities, and the established methods and advanced microelectronic environment. Presented as an upstream phase, metrology and defectivity were performed on dedicated assessment designs to address critical dimension uniformity (CDU) at wafer scale for a large number of imprints, defectivity on imprints and masters, and alignment capabilities of the nanoimprint HERCULES® platform of EVG. We demonstrate that the critical points are the anti-sticking layer for the defectivity, the CD shrinkage for the CDU, and the stiffness of the soft stamp for the overlay uniformity. Thus, we bring to light the actual capabilities of the HERCULES® platform, and open the discussions on the opportunities for this technology with the possible improvements for the process.
Interaction in qualitative questionnaires: From self-report to intersubjective achievement
Authors: Wernicke Meike , Talmy Steven 
Published: May 2017

AbstractSurvey questionnaires are among the most widely-used research methods in applied linguistics, adopted for everything from large-scale quantitative studies measuring social-psychological variables to qualitative studies that solicit participant views on a range of different topics. Despite the variety of purposes that survey questionnaires are used for, the most common approaches to analysis of the data they yield involve content analysis using descriptive or inferential statistics and/or enumeration of emergent themes. The study reported in this article conceives of questionnaire data in notably different terms: as occasioned (conditionally-relevant responses sequentially-projected by a question), recipient-designed (devised for the research context and researcher), and thus, as thoroughly interactional phenomena (Drew 2006; Sacks 1992). The study examines the identity construction of French as a second language (FSL) teachers on a professional development sojourn in France, drawing on a data-set in part comprised of participants’ open-ended responses to a 48-item questionnaire concerning whether their “confidence as French language teachers” increased as a result of their involvement in the sojourn. However, rather than conceiving of participants’ answers as revelations of changes in their interior states, the study draws on insights from conversation analysis and membership categorization analysis to examine how “confidence” was recruited as a discursive resource to “do being” a particular kind of L2 French teacher. We demonstrate how the presence and problematics of a (French) native-speaker archetype for the FSL teachers was in part formulated through close analytic attention to both the sequential and categorial features of researcher/respondent interactions occasioned by one open-ended response item in the questionnaire. This alternative approach to analyzing questionnaire data offers important insights about L2 teacher identity. It also addresses more fundamental questions concerning the discursive and interactional basis of ostensibly non-interactional research methods like survey questionnaires. Additionally, the insistence on an explicit methodological framing of the research process promotes greater theoretical and methodological consistency, and of particular importance, a significantly expanded conception of and accounting for researcher reflexivity.
Does microfinance reduce poverty? Some international evidence
Authors: Zhang Quanda 
Published: May 2017

AbstractIn this paper, the hypothesis that microfinance is an effective tool for reducing poverty at the macro level is tested using a unique cross-country panel data set from 106 countries for the period 1998–2013. Taking into account the potential problem of sample selection bias and endogeneity, this paper shows that microfinance has a negative effect on poverty. The results are robust to the choice of microfinance measures and poverty indicators. They suggest that in developing and emerging countries, the establishment of more MFIs should be encouraged, and more funds should be directed from development agencies and governments into MFIs, to reduce poverty.
Neck circumference is similarly predicting for impairment of glucose tolerance as classic anthropometric parameters among healthy and obese children and adolescents
Authors: Junge Jennifer , Engel Christoph , Vogel Mandy , Naumann Stephanie , Löffler Markus , Thiery Joachim , Kratzsch Jürgen , Kiess Wieland , Körner Antje 
Published: May 2017

AbstractBackground:The objective of the study was to investigate the association of neck circumference (NC) to parameters of glucose homeostasis compared to classical anthropometric parameters of lean and obese children.Methods:Three dimensional (3D)-body scanning quantified anthropometric (height, weight, NC, hip/waist circumference, BMI) and metabolic parameters (fasting plasma glucose [FPG], insulin, HbAResults:NC was positively correlated with all metabolic parameters, except for FPG. For HbAConclusions:We suggest that NC is comparable or additive to established anthropometric parameters but might not be superior to them. However NC is simple to measure, reproducible and may be considered in clinical practice as an additional measurement tool.