bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reactive transport modelling of iron–bentonite interaction within the KBS-3H disposal concept: the Olkiluoto site as a case study
Authors: Wersin Paul , Birgersson Martin 
Published: May 2014

Abstract
The interaction of steel with bentonite used as buffer material in high-level waste repositories may result in changes to the properties of the buffer. One of the repository designs (KBS-3H) developed by Posiva and SKB foresees the horizontal emplacement of so-called supercontainers, consisting of copper canisters surrounded by compacted bentonite and an outer perforated steel shell. The corrosion of the steel shell and the interaction of iron with the clay may impair the long-term safety functions of the buffer.
The corrosion and iron–clay interaction processes within the KBS-3H concept were assessed with a kinetically based reactive transport model and a comprehensive thermodynamic database. The large uncertainty related to precipitation rates of corrosion products and iron silicates was considered by defining a series of test cases. The results generally indicate a limited effect on the stability of montmorillonite, thus affecting only a few centimetres next to the iron source. Upon complete corrosion only insignificant changes are predicted. These results are explained by (i) the diffusional constraint of mass transfer, (ii) low solubility of corrosion products and (iii) slow transformation kinetics of montmorillonite. Model results further suggest that the largest impact arises from ‘indirect’ processes, such as microbial sulphate reduction, which may lead to a strong increase in pH.
Thermo-hydraulic modelling of the bentonite buffer in deposition hole 6 of the Prototype Repository
Authors: Malmberg D. , Kristensson O. 
Published: May 2014

Abstract
The Prototype Repository is an on-going full-scale trial of a final disposal of spent nuclear fuel designed in close agreement with the Swedish KBS-3V design. It provides an excellent opportunity to test our modelling capabilities and our ability to predict evolution of conditions in the planned repository for nuclear waste in Sweden. Here we describe our current efforts to simulate the experiment and compare results with available measured data. To reduce the computational demand, a modelling strategy was adopted in which large-scale low-resolution models (including the entire experiment and a large volume of surrounding rock) were used to determine boundary conditions for local-scale high-resolution models (including one deposition hole). The results obtained so far generally show reasonably good agreement with measurements available from the field experiment.
Loss of the Polycomb Mark from Bivalent Promoters Leads to Activation of Cancer-Promoting Genes in Colorectal Tumors
Authors: Hahn Maria A. , Li Arthur X. , Wu Xiwei , Yang Richard , Drew David A. , Rosenberg Daniel W. , Pfeifer Gerd P. 
Published: May 2014

Abstract
In colon tumors, the transcription of many genes becomes deregulated by poorly defined epigenetic mechanisms that have been studied mainly in established cell lines. In this study, we used frozen human colon tissues to analyze patterns of histone modification and DNA cytosine methylation in cancer and matched normal mucosa specimens. DNA methylation is strongly targeted to bivalent H3K4me3- and H3K27me3-associated promoters, which lose both histone marks and acquire DNA methylation. However, we found that loss of the Polycomb mark H3K27me3 from bivalent promoters was accompanied often by activation of genes associated with cancer progression, including numerous stem cell regulators, oncogenes, and proliferation-associated genes. Indeed, we found many of these same genes were also activated in patients with ulcerative colitis where chronic inflammation predisposes them to colon cancer. Based on our findings, we propose that a loss of Polycomb repression at bivalent genes combined with an ensuing selection for tumor-driving events plays a major role in cancer progression. Cancer Res; 74(13); 3617–29. ©2014 AACR.
Oxidative Stress Activates SIRT2 to Deacetylate and Stimulate Phosphoglycerate Mutase
Authors: Xu Yanping , Li Fulong , Lv Lei , Li Tingting , Zhou Xin , Deng Chu-Xia , Guan Kun-Liang , Lei Qun-Ying , Xiong Yue 
Published: May 2014

Abstract
Glycolytic enzyme phosphoglycerate mutase (PGAM) plays an important role in coordinating energy production with generation of reducing power and the biosynthesis of nucleotide precursors and amino acids. Inhibition of PGAM by small RNAi or small molecule attenuates cell proliferation and tumor growth. PGAM activity is commonly upregulated in tumor cells, but how PGAM activity is regulated in vivo remains poorly understood. Here we report that PGAM is acetylated at lysine 100 (K100), an active site residue that is invariably conserved from bacteria, to yeast, plant, and mammals. K100 acetylation is detected in fly, mouse, and human cells and in multiple tissues and decreases PGAM2 activity. The cytosolic protein deacetylase sirtuin 2 (SIRT2) deacetylates and activates PGAM2. Increased levels of reactive oxygen species stimulate PGAM2 deacetylation and activity by promoting its interaction with SIRT2. Substitution of endogenous PGAM2 with an acetylation mimetic mutant K100Q reduces cellular NADPH production and inhibits cell proliferation and tumor growth. These results reveal a mechanism of PGAM2 regulation and NADPH homeostasis in response to oxidative stress that impacts cell proliferation and tumor growth. Cancer Res; 74(13); 3630–42. ©2014 AACR.
Blocking and Randomization to Improve Molecular Biomarker Discovery
Authors: Qin Li-Xuan , Zhou Qin , Bogomolniy Faina , Villafania Liliana , Olvera Narciso , Cavatore Magali , Satagopan Jaya M. , Begg Colin B. , Levine Douglas A. 
Published: May 2014

Abstract
Randomization and blocking have the potential to prevent the negative impacts of nonbiologic effects on molecular biomarker discovery. Their use in practice, however, has been scarce. To demonstrate the logistic feasibility and scientific benefits of randomization and blocking, we conducted a microRNA study of endometrial tumors (n = 96) and ovarian tumors (n = 96) using a blocked randomization design to control for nonbiologic effects; we profiled the same set of tumors for a second time using no blocking or randomization. We assessed empirical evidence of differential expression in the two studies. We performed simulations through virtual rehybridizations to further evaluate the effects of blocking and randomization. There was moderate and asymmetric differential expression (351/3,523, 10%) between endometrial and ovarian tumors in the randomized dataset. Nonbiologic effects were observed in the nonrandomized dataset, and 1,934 markers (55%) were called differentially expressed. Among them, 185 were deemed differentially expressed (185/351, 53%) and 1,749 not differentially expressed (1,749/3,172, 55%) in the randomized dataset. In simulations, when randomization was applied to all samples at once or within batches of samples balanced in tumor groups, blocking improved the true-positive rate from 0.95 to 0.97 and the false-positive rate from 0.02 to 0.002; when sample batches were unbalanced, randomization was associated with the true-positive rate (0.92) and the false-positive rate (0.10) regardless of blocking. Normalization improved the detection of true-positive markers but still retained sizeable false-positive markers. Randomization and blocking should be used in practice to more fully reap the benefits of genomics technologies. Clin Cancer Res; 20(13); 3371–8. ©2014 AACR.
T-Cell and NK-Cell Infiltration into Solid Tumors: A Key Limiting Factor for Efficacious Cancer Immunotherapy
Authors: Melero Ignacio , Rouzaut Ana , Motz Greg T. , Coukos George 
Published: May 2014

Abstract
Summary: Cancer immunotherapy has great promise, but is limited by diverse mechanisms used by tumors to prevent sustained antitumor immune responses. Tumors disrupt antigen presentation, T/NK–cell activation, and T/NK–cell homing through soluble and cell-surface mediators, the vasculature, and immunosuppressive cells such as myeloid-derived suppressor cells and regulatory T cells. However, many molecular mechanisms preventing the efficacy of antitumor immunity have been identified and can be disrupted by combination immunotherapy. Here, we examine immunosuppressive mechanisms exploited by tumors and provide insights into the therapies under development to overcome them, focusing on lymphocyte traffic. Cancer Discov; 4(5); 522–6. ©2014 AACR.
Finding the Right Balance of BRAF Inhibition in Melanoma
Authors: Davies Michael A. 
Published: May 2014

Abstract
Summary: Paradoxical activation of the mitogen-activated protein kinase pathway can cause secondary malignancies in patients treated with inhibitors of BRAFV600 proteins. Characterization of a patient with concurrent BRAF-mutant melanoma and NRAS-mutant leukemia treated intermittently with combined BRAF and MEK inhibition provides new insights into the potential clinical and molecular effects of this therapeutic strategy. Cancer Discov; 4(5); 510–2. ©2014 AACR.
See related article by Abdel-Wahab et al., p. 538
From Breaking Bad to Worse: Exploiting Homologous DNA Repair Deficiency in Cancer
Authors: Hemann Michael T. 
Published: May 2014

Abstract
Summary: DNA repair deficiencies are common among cancer cells and represent a potential vulnerability that might be exploited by targeting compensatory repair pathways. However, the identification of synthetically lethal combinations of DNA repair defects, although of significant clinical relevance, has been somewhat anecdotal. Although numerous models have been proposed to explain synthetic lethality among DNA repair mutations, we have only a limited understanding of why a given mutation should render cells sensitive to another. In this issue of Cancer Discovery, Dietlein and colleagues define a general connection between mutations in genes involved in homologous recombination and sensitivity to inhibitors of non-homologous end joining. In doing so, they provide a mechanism to demarcate a set of seemingly diverse tumors that may be highly responsive to established DNA repair–targeted therapeutics. Cancer Discov; 4(5); 516–8. ©2014 AACR.
See related article by Dietlein et al., p. 592
MTOR Mutations in the Crosshairs of Targeted Therapy
Authors: Rejto Paul A. , Abraham Robert T. 
Published: May 2014

Abstract
Summary: The identification of genetic lesions that affect tumor sensitivity to targeted therapies is a major objective of precision medicine. Two reports in this issue combine tumor genome analyses with functional characterization to uncover activating mutations in MTOR that confer sensitivity to a clinically used mTOR inhibitor. Cancer Discov; 4(5); 513–5. ©2014 AACR.
See related article by Wagle et al., p. 546
See related article by Grabiner et al., p. 554
The Incidence of Kidney Injury for Patients Treated With a High‐Potency Versus Moderate‐Potency Statin Regimen After an Acute Coronary Syndrome
Authors: Sarma Amy , Cannon Christopher P. , de Lemos James , Rouleau Jean L. , Lewis Eldrin F. , Guo Jianping , Mega Jessica L. , Sabatine Marc S. , O'Donoghue Michelle L. 
Published: May 2014

Background
Observational studies have raised concerns that high‐potency statins increase the risk of acute kidney injury. We therefore examined the incidence of kidney injury across 2 randomized trials of statin therapy.

Methods and Results

PROVE IT
‐
TIMI
22 enrolled 4162 subjects after an acute coronary syndrome (
ACS)
and randomized them to atorvastatin 80 mg/day versus pravastatin 40 mg/day. A‐to‐Z enrolled 4497 subjects after
ACS
and randomized them to a high‐potency (simvastatin 40 mg/day×1 months, then simvastatin 80 mg/day) versus a delayed moderate‐potency statin strategy (placebo×4 months, then simvastatin 20 mg/day). Serum creatinine was assessed centrally at serial time points. Adverse events (AEs) relating to kidney injury were identified through database review. Across both trials, mean serum creatinine was similar between treatment arms at baseline and throughout follow‐up. In A‐to‐Z, the incidence of a 1.5‐fold or ≥0.3 mg/
dL
rise in serum creatinine was 11.4% for subjects randomized to a high‐potency statin regimen versus 12.4% for those on a delayed moderate‐potency regimen (odds ratio [
OR],
0.91; 95% confidence interval [CI], 0.76 to 1.10;
P
=0.33). In
PROVE IT
‐
TIMI
22, the incidence was 9.4% for subjects randomized to atorvastatin 80 mg/day and 10.6% for subjects randomized to pravastatin 40 mg/day (
OR,
0.88; 95% CI, 0.71 to 1.09;
P
=0.25). Consistent results were observed for different kidney injury thresholds and in individuals with diabetes mellitus or with moderate renal dysfunction. The incidence of kidney injury‐related adverse events (AEs) was not statistically different for patients on a high‐potency versus moderate‐potency statin regimen (
OR,
1.06; 95%
CI,
0.68 to 1.67;
P
=0.78).

Conclusions

For patients enrolled in 2 large randomized trials of statin therapy after
ACS
, the use of a high‐potency statin regimen did not increase the risk of kidney injury.
An Analysis of Vestibular Evoked Myogenic Potentials in Patients With Benign Paroxysmal Positional Vertigo
Authors: Yetiser Sertac , Ince Dilay , Gul Murat 
Published: May 2014

Objective: Vestibular evoked myogenic potentials (VEMPs) selectively test the vestibular end-organ. The aim of this study was to analyze how the site of the diseased canal, type of particulate deposition, duration of symptoms, severity of nystagmus, recurrence, and age affect the VEMP in patients with benign paroxysmal positional vertigo (BPPV). Methods: One hundred two patients were enrolled in the study between 2009 and 2012. There were 36 men and 66 women with ages ranging from 16 to 71 years (mean age, 42.28 ± 11.29 years). Patients with BPPV were tested with roll-on and head-hanging maneuvers under video-electronystagmography monitoring and with air conduction cervical VEMP testing. Patients were grouped for duration, severity, recurrence, age, site of canal involvement, and so on, and the results were compared in each subgroup. Kruskal–Wallis and Mann–Whitney U tests were used for the comparative analysis. Results: Twenty-four patients (23.5%) had a gross VEMP abnormality (absence of VEMP in 6 and greater than 25% depression of the amplitude in 18). Abnormality of VEMPs was not correlated with factors including age, severity of nystagmus, number of maneuvers applied, and the site of canal involvement ( P < .05). However, persistence or recurrence of symptoms has an effect on VEMP results ( P = .016). Conclusion: Vestibular evoked myogenic potential is a useful tool to study the otolithic function in patients with BPPV and should be included in the test battery.
Effect of employee background on perceived organizational justice: managerial implications
Authors: Tessema Mussie T , Tsegai Goitom , Ready Kathryn , Embaye Abel , Windrow Brian 
Published: May 2014

The study examines the effect employee background (gender, education level and affiliation to the government) on organizational justice perceptions using the three-factor model (distributive, procedural and interactional justice). Selected demographic and attitudinal data were collected from a sample of 313 employees representing 10 public organizations. The findings of this study show that gender had a significant effect on distributive and interactional justice but not procedural justice; education level had a significant effect on distributive and procedural justice but not interactional justice; and affiliation to the government had a significant effect on all the three dimensions of justice. Managerial implications of these findings and future research directions are also discussed. Points for practitioners Gaining a better insight into the effects of demographic factors (gender, education level and affiliation to the government) on the three dimensions of organizational justice indicates to policymakers and public managers where improvements can be made, and helps them to develop strategies and policies that could improve the perceived justice. Another important implication of this study for countries emerging from a civil war, liberation struggle or other similar conflict (for example, South Sudan, Libya, Afghanistan) is regarding converting former fighters into civil servants and their management afterwards. It is crucial to provide them employment opportunities in a civil service provided that they are placed based on the principle of the right persons on the right positions and then treat them as equal as their counterparts: non-ex-fighter civil servants. They only need to be given some (special) kind of training (at the beginning) that expedites their socialization and integration into the main stream way of thinking and doing things.
Dopamine D2/3 receptor availability and amphetamine-induced dopamine release in obesity
Authors: van de Giessen Elsmarieke , Celik Funda , Schweitzer Dave H , van den Brink Wim , Booij Jan 
Published: May 2014

Introduction: The neurotransmitter dopamine is important in the regulation of food intake. It is hypothesised that obese people experience less reward from food due to lower striatal dopamine release, which consequently leads to overeating. This study is the first to assess whether obese subjects have blunted striatal dopamine release. Method: We measured striatal dopamine D2/3 receptor (DRD2/3) availability and amphetamine-induced striatal dopamine release in 15 obese and 15 age-matched, normal-weight women using [123I]iodobenzamide single photon emission computed tomography (SPECT) imaging. In addition, correlations with food craving were examined. Results: Baseline striatal DRD2/3 availability was lower in obese subjects (0.91±0.16) compared to controls (1.09±0.16; p=0.006). Amphetamine-induced dopamine release was significant in controls (7.5%±9.2; p=0.007) and not in obese subjects (1.2%±17.7; p=0.802), although the difference in release between groups ( d=0.45) was not significant. Dopamine release positively correlated with the trait food craving in obese subjects. Conclusion: This study replicates previous findings of lower striatal DRD2/3 availability in obesity and provides preliminary data that obesity is associated with blunted dopamine release. The positive correlation between dopamine release and food craving in obesity may seem contradictory with the latter finding but is presumably related to heterogeneity within the obese subjects.
A Replication of Failure, Not a Failure to Replicate
Authors: Holden Gary , Barker Kathleen , Kuppens Sofie , Rosenberg Gary , LeBreton Jonathan 
Published: May 2014

Purpose: The increasing role of systematic reviews in knowledge production demands greater rigor in the literature search process. The performance of the Social Work Abstracts (SWA) database has been examined multiple times over the past three decades. The current study is a replication within this line of research. Method: Issue-level coverage was examined for the same 33 SWA core journals and the same time period as our 2009 study. Results: The mean percentage of issues missing in the current study was 20%. The mean percentage of issues missing in the current study was significantly greater than the mean percentage of issues missing in the 2009 study. Discussion: The research of other groups, and that of our own, has failed to prompt the National Association of Social Workers Press (NASW-P) to act. SWA was failing, it is failing, and NASW-P has failed to correct those failures.
A retrospective study of cognitive function in doctors and dentists with suspected performance problems: an unsuspected but significant concern
Authors: Kataria Neha , Brown Nick , McAvoy Pauline , Majeed Azeem , Rhodes Martin 
Published: May 2014

Summary Objective To examine the performance assessments and cognitive function of practitioners referred to the National Clinical Assessment Service (NCAS). Design Retrospective observational study. Setting Practitioners referred to NCAS for performance assessment due to suspected performance problems. Participants One hundred and nine practitioners over the age of 45 years referred to NCAS between 1 September 2008 and 30 June 2012. Main outcome measures Reasons for referral of practitioners and their characteristics; details of their assessments including screening for cognition using Addenbrooke's Cognitive Examination Revised (ACE-R); outcome of the process. Results Reasons for referral included ‘clinical difficulties’ and ‘governance or safety issues’. Eighty-seven practitioners scored above 88 on ACE-R. Twenty-two were found to have an ACE-R score of ≤88. On further assessment, 14 of these 22 practitioners were found to have cognitive impairment. The majority of all practitioners were found to be performing below the expected level of practice for someone at their grade and specialty. Of those scoring ≤88 on the screening, only seven continued in clinical practice. Conclusions A high proportion of practitioners scoring poorly on ACE-R were found to have cognitive impairment following detailed neuropsychological testing, the youngest aged 46 years. Many were working in isolation. Nearly all practitioners scoring poorly on ACE-R were international medical graduates; reasons for this are unclear. Performance assessment results showed persisting failings in the practitioners' record keeping and in their assessment of patients. Our findings highlight the need for increased vigilance and training of responsible officers to recognise performance problems and emphasise the importance of comprehensive assessment.
Evaluation of the impact of a flowchart-type leaflet for cancer inpatients
Authors: Suzuki Shinya , Enokida Tomohiro , Kobayashi Takehiko , Yajima Yoko , Ishiki Hiroto , Izumi Keishiro , Endo Kazushi , Tahara Makoto 
Published: May 2014

Objectives: This study aimed to evaluate the benefits of an interactive and visual flowchart-type leaflet for head and neck cancer inpatients who received induction chemotherapy, docetaxel, cisplatin, and 5-fluorourasil (DCF), or docetaxel, cisplatin, and S-1 (DCS) from September 2009 to April 2012. The flowchart-type leaflet group used a flowchart-type leaflet during chemotherapy, while the non-flowchart-type leaflet group did not. Methods: A retrospective cohort study was performed using patient records. The endpoints of this study were to determine the following: the number of emergency hospital admissions/visits, incidence of Grade 2 or higher non-haematological adverse drug reactions, nonadherence to treatment, and the number of telephone calls from subjects. Results: A total of 109 subjects were identified as follows: 49 in the flowchart-type leaflet group (139 chemotherapy sessions) and 60 in the non-flowchart-type leaflet group (163 chemotherapy sessions). No significant differences were observed in age, performance status, or chemotherapy regimen. The incidence of emergency hospital admissions was significantly lower in the flowchart-type leaflet than in the non-flowchart-type leaflet group (1% vs 10%, p < 0.01). No difference was seen between groups (12% vs 19%, p = 0.1) in the nonadherence rate of supportive medication for adverse drug reactions. Telephone call rates were significantly higher in the flowchart-type leaflet (16%, 30 calls) than in the non-flowchart-type leaflet group (7%, 11 calls) in each chemotherapy regimen. Of the 30 calls from patients in the FCL group, 24 (80%) were made to the hospital, compared with only 5 (45%) of the 11 calls from patients in the non-flowchart-type leaflet group. Conclusions: Our results suggest that the flowchart-type leaflet can reduce nonadherence and improve patient judgment during chemotherapy, leading to a decrease in emergency hospital admissions.