bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sparse‐view proton computed tomography using modulated proton beams
Authors: Lee Jiseoc , Kim Changhwan , Min Byungjun , Kwak Jungwon , Park Seyjoon , Lee Se Byeong , Park Sungyong , Cho Seungryong 
Published: February 2015

Purpose:Proton imaging that uses a modulated proton beam and an intensity detector allows a relatively fast image acquisition compared to the imaging approach based on a trajectory tracking detector. In addition, it requires a relatively simple implementation in a conventional proton therapy equipment. The model of geometric straight ray assumed in conventional computed tomography (CT) image reconstruction is however challenged by multiple‐Coulomb scattering and energy straggling in the proton imaging. Radiation dose to the patient is another important issue that has to be taken care of for practical applications. In this work, the authors have investigated iterative image reconstructions after a deconvolution of the sparsely view‐sampled data to address these issues in proton CT.Methods:Proton projection images were acquired using the modulated proton beams and the EBT2 film as an intensity detector. Four electron‐density cylinders representing normal soft tissues and bone were used as imaged object and scanned at 40 views that are equally separated over 360°. Digitized film images were converted to water‐equivalent thickness by use of an empirically derived conversion curve. For improving the image quality, a deconvolution‐based image deblurring with an empirically acquired point spread function was employed. They have implemented iterative image reconstruction algorithms such as adaptive steepest descent‐projection onto convex sets (ASD‐POCS), superiorization method–projection onto convex sets (SM‐POCS), superiorization method–expectation maximization (SM‐EM), and expectation maximization‐total variation minimization (EM‐TV). Performance of the four image reconstruction algorithms was analyzed and compared quantitatively via contrast‐to‐noise ratio (CNR) and root‐mean‐square‐error (RMSE).Results:Objects of higher electron density have been reconstructed more accurately than those of lower density objects. The bone, for example, has been reconstructed within 1% error. EM‐based algorithms produced an increased image noise and RMSE as the iteration reaches about 20, while the POCS‐based algorithms showed a monotonic convergence with iterations. The ASD‐POCS algorithm outperformed the others in terms of CNR, RMSE, and the accuracy of the reconstructed relative stopping power in the region of lung and soft tissues.Conclusions:The four iterative algorithms, i.e., ASD‐POCS, SM‐POCS, SM‐EM, and EM‐TV, have been developed and applied for proton CT image reconstruction. Although it still seems that the images need to be improved for practical applications to the treatment planning, proton CT imaging by use of the modulated beams in sparse‐view sampling has demonstrated its feasibility.
Dynamics of Infant Gut Microbiota Are Influenced by Delivery Mode and Gestational Duration and Are Associated with Subsequent Adiposity
Authors: Dogra Shaillay , Sakwinska Olga , Soh Shu-E , Ngom-Bru Catherine , Brück Wolfram M. , Berger Bernard , Brüssow Harald , Lee Yung Seng , Yap Fabian , Chong Yap-Seng , Godfrey Keith M. , Holbrook Joanna D. 
Published: February 2015

ABSTRACT We found that the relatively simple microbiota of young infants shifts predictably to a more mature anaerobic microbiota during infancy and the dynamics of this shift are influenced by environmental factors. In this longitudinal study of 75 infants, we demonstrate high interindividual variability within the normal range of birth outcomes, especially in the rate of microbiota progression. Most had acquired a microbiota profile high in Bifidobacterium and Collinsella by 6 months of age, but the time point of this acquisition was later in infants delivered by caesarean section and those born after a shorter duration of gestation. Independently of the delivery mode and gestation duration, infants who acquired a profile high in Bifidobacterium and Collinsella at a later age had lower adiposity at 18 months of age.IMPORTANCE  This study shows that the acquisition of the early microbiota is strongly influenced by environmental factors such as the delivery mode and duration of gestation, even in healthy neonates. The composition of the early microbiota has been linked with long-lasting effects on health and disease. Here we show that the rate of acquisition of certain microbiota predicts adiposity at 18 months of age and so potentially the risk of later obesity.
A Burkholderia pseudomallei Colony Variant Necessary for Gastric Colonization
Authors: Austin C. R. , Goodyear A. W. , Bartek I. L. , Stewart A. , Sutherland M. D. , Silva E. B. , Zweifel A. , Vitko N. P. , Tuanyok A. , Highnam G. , Mittelman D. , Keim P. , Schweizer H. P. , Vázquez-Torres A. , Dow S. W. C. , Voskuil M. I. 
Published: February 2015

ABSTRACT

Diverse colony morphologies are a hallmark of
Burkholderia pseudomallei
recovered from infected patients. We observed that stresses that inhibit aerobic respiration shifted populations of B. pseudomallei from the canonical white colony morphotype toward two distinct, reversible, yet relatively stable yellow colony variants (YA and YB). As accumulating evidence supports the importance of B. pseudomallei enteric infection and gastric colonization, we tested the response of yellow variants to hypoxia, acidity, and stomach colonization. Yellow variants exhibited a competitive advantage under hypoxic and acidic conditions and alkalized culture media. The YB variant, although highly attenuated in acute virulence, was the only form capable of colonization and persistence in the murine stomach. The accumulation of extracellular DNA (eDNA) was a characteristic of YB as observed by 4′,6-diamidino-2-phenylindole (DAPI) staining of gastric tissues, as well as in an
in vitro
stomach model where large amounts of eDNA were produced without cell lysis. Transposon mutagenesis identified a transcriptional regulator (BPSL1887, designated YelR) that when overexpressed produced the yellow phenotype. Deletion of
yelR
blocked a shift from white to the yellow forms. These data demonstrate that YB is a unique B. pseudomallei pathovariant controlled by YelR that is specifically adapted to the harsh gastric environment and necessary for persistent stomach colonization.

IMPORTANCE
Seemingly uniform populations of bacteria often contain subpopulations that are genetically identical but display unique characteristics which offer advantages when the population is faced with infrequent but predictable stresses. The pathogen
Burkholderia pseudomallei
is capable of forming several reversible colony types, and it interconverted between one white type and two yellow types under certain environmental stresses. The two yellow forms exhibited distinct advantages in low-oxygen and acidic environments. One yellow colony variant was the only form capable of chronic stomach colonization. Areas of gastric infection were marked by bacteria encased in a DNA matrix, and the yellow forms were able to produce large amounts of extracellular DNA
in vitro
. We also identified the regulator in control of yellow colony variant formation. These findings demonstrate a role in infection for colony variation and provide a mechanism for chronic stomach colonization—a frequently overlooked niche in melioidosis.
Older doctors and progression through specialty training in the UK: a cohort analysis of General Medical Council data
Authors: Pyne Yvette , Ben-Shlomo Yoav 
Published: February 2015

ObjectiveTo determine whether older age at graduation is associated with any difference in outcomes from the annual specialty training progression assessment.DesignAn open cohort of 38 308 doctors who graduated from a UK medical school with annual assessments of progression in their specialty training programme with data centrally collected by the General Medical Council between 5 August 2009 to 31 July 2012.ResultsMature junior doctors (≥29 years at graduation) were more likely to have problems with progression on their annual review of competence progression record of in training assessment (ARCP/RITA) than their younger colleagues (OR 1.34, 95% CI 1.22 to 1.49, p<0.001). This association was, if anything, even stronger (OR 1.57, 95% CI 1.41 to 1.74, p<0.001) after adjustment for gender, ethnicity, type of University and specialty. The same was true when only looking at the most extreme ARCP outcome (4) which is being asked to leave their specialist programme (OR 1.81, 95% CI 1.34 to 2.44, p<0.001).ConclusionsMature doctors are a growing part of the medical workforce and they are likely to broaden the spectrum of doctors by bring different life experience to the profession. These results suggest that they are more likely to have problems with progressing through their specialist training programme. More research is required to determine the reasons behind these associations and how mature doctors can be supported both in choosing the best training programme and in coping with the complex demands of higher training at a later stage in their lives.
Intravascular device administration sets: replacement after standard versus prolonged use in hospitalised patients—a study protocol for a randomised controlled trial (The RSVP Trial)
Authors: Rickard Claire M , Marsh Nicole M , Webster Joan , Gavin Nicole C , McGrail Matthew R , Larsen Emily , Corley Amanda , Long Debbie , Gowardman John R , Murgo Marghie , Fraser John F , Chan Raymond J , Wallis Marianne C , Young Jeanine , McMillan David , Zhang Li , Choudhury Md Abu , Graves Nicholas , Playford E Geoffrey 
Published: February 2015

IntroductionVascular access devices (VADs), such as peripheral or central venous catheters, are vital across all medical and surgical specialties. To allow therapy or haemodynamic monitoring, VADs frequently require administration sets (AS) composed of infusion tubing, fluid containers, pressure-monitoring transducers and/or burettes. While VADs are replaced only when necessary, AS are routinely replaced every 3–4 days in the belief that this reduces infectious complications. Strong evidence supports AS use up to 4 days, but there is less evidence for AS use beyond 4 days. AS replacement twice weekly increases hospital costs and workload.Methods and analysisThis is a pragmatic, multicentre, randomised controlled trial (RCT) of equivalence design comparing AS replacement at 4 (control) versus 7 (experimental) days. Randomisation is stratified by site and device, centrally allocated and concealed until enrolment. 6554 adult/paediatric patients with a central venous catheter, peripherally inserted central catheter or peripheral arterial catheter will be enrolled over 4 years. The primary outcome is VAD-related bloodstream infection (BSI) and secondary outcomes are VAD colonisation, AS colonisation, all-cause BSI, all-cause mortality, number of AS per patient, VAD time in situ and costs. Relative incidence rates of VAD-BSI per 100 devices and hazard rates per 1000 device days (95% CIs) will summarise the impact of 7-day relative to 4-day AS use and test equivalence. Kaplan-Meier survival curves (with log rank Mantel-Cox test) will compare VAD-BSI over time. Appropriate parametric or non-parametric techniques will be used to compare secondary end points. p Values of <0.05 will be considered significant.Ethics and disseminationRelevant ethical approvals have been received. CONSORT Statement recommendations will be used to guide preparation of any publication. Results will be presented at relevant conferences and sent to the major organisations with clinical practice guidelines for VAD care.Trial registration numberAustralian New Zealand Clinical Trial Registry (ACTRN 12610000505000).
Occupational position, work stress and depressive symptoms: a pathway analysis of longitudinal SHARE data
Authors: Hoven H , Wahrendorf M , Siegrist J 
Published: February 2015

BackgroundSeveral studies tested whether stressful work mediates the association between socioeconomic position (SEP) and health. Although providing moderate support, evidence is still inconclusive, partly due to a lack of theory-based measures of SEP and work stress, and because of methodological limitations. This contribution aims at overcoming these limitations.MethodsWe conduct pathway analysis and investigate indirect effects of SEP on mental health via stressful work. Data are derived from the first two waves of the ‘Survey of Health, Ageing and Retirement in Europe’ (SHARE) with information from employed men and women aged 50–64 across 11 European countries (N=2798). SEP is measured according to two alternative measures of occupational position: occupational class (focus on employment relations) and occupational status (focus on prestige). We assess work stress according to the effort-reward imbalance and the demand-control model (wave 1), and we use newly occurring depressive symptoms as health outcome (wave 2).ResultsEffort-reward imbalance and, less consistently, low control mediate the effect of occupational class and occupational status on depressive symptoms.ConclusionsOur findings point to two important aspects of work stress (effort-reward imbalance and low control) in explaining socioeconomic differences in health. Further, we illustrate the significance of two alternative dimensions of occupational position, occupational class and occupational status.
Foundation doctors and dyslexia: a qualitative study of their experiences and coping strategies
Authors: Newlands Freda , Shrewsbury Duncan , Robson Jean 
Published: February 2015

ABSTRACT

Background
Dyslexia is the most common form of specific learning difficulty affecting approximately 6% of the general UK population and believed to affect approximately 2% of UK medical students. The impact of dyslexia on early practice has not been studied.

Objectives
To develop an understanding of the challenges faced by doctors with dyslexia in the first year of practice and their support requirements.

Methods
Semistructured telephone interviews were conducted with seven foundation year 1 doctors with dyslexia from Scottish hospitals between March 2013 and August 2013.

Results
Foundation doctors indicated that due to their dyslexia, they experience difficulty with all forms of communication, time management and anxiety. There were concerns about disclosure of their dyslexia to colleagues and supervisors. Coping strategies used frequently were safety-netting and planning; technology solutions did offer some assistance.

Conclusions
Although technological interventions have the potential to offer benefits to foundation doctors with dyslexia, increased openness about a diagnosis of dyslexia with discussion between doctor and supervisors about the challenges and anxieties is likely to provide the most benefit.
ERK5 Is a Critical Mediator of Inflammation-Driven Cancer
Authors: Finegan Katherine G. , Perez-Madrigal Diana , Hitchin James R. , Davies Clare C. , Jordan Allan M. , Tournier Cathy 
Published: February 2015

Abstract
Chronic inflammation is a hallmark of many cancers, yet the pathogenic mechanisms that distinguish cancer-associated inflammation from benign persistent inflammation are still mainly unclear. Here, we report that the protein kinase ERK5 controls the expression of a specific subset of inflammatory mediators in the mouse epidermis, which triggers the recruitment of inflammatory cells needed to support skin carcinogenesis. Accordingly, inactivation of ERK5 in keratinocytes prevents inflammation-driven tumorigenesis in this model. In addition, we found that anti-ERK5 therapy cooperates synergistically with existing antimitotic regimens, enabling efficacy of subtherapeutic doses. Collectively, our findings identified ERK5 as a mediator of cancer-associated inflammation in the setting of epidermal carcinogenesis. Considering that ERK5 is expressed in almost all tumor types, our findings suggest that targeting tumor-associated inflammation via anti-ERK5 therapy may have broad implications for the treatment of human tumors. Cancer Res; 75(4); 742–53. ©2015 AACR.
BMX Negatively Regulates BAK Function, Thereby Increasing Apoptotic Resistance to Chemotherapeutic Drugs
Authors: Fox Joanna L. , Storey Alan 
Published: February 2015

Abstract
The ability of chemotherapeutic agents to induce apoptosis, predominantly via the mitochondrial (intrinsic) apoptotic pathway, is thought to be a major determinant of the sensitivity of a given cancer to treatment. Intrinsic apoptosis, regulated by the BCL2 family, integrates diverse apoptotic signals to determine cell death commitment and then activates the nodal effector protein BAK to initiate the apoptotic cascade. In this study, we identified the tyrosine kinase BMX as a direct negative regulator of BAK function. BMX associates with BAK in viable cells and is the first kinase to phosphorylate the key tyrosine residue needed to maintain BAK in an inactive conformation. Importantly, elevated BMX expression prevents BAK activation in tumor cells treated with chemotherapeutic agents and is associated with increased resistance to apoptosis and decreased patient survival. Accordingly, BMX expression was elevated in prostate, breast, and colon cancers compared with normal tissue, including in aggressive triple-negative breast cancers where BMX overexpression may be a novel biomarker. Furthermore, BMX silencing potentiated BAK activation, rendering tumor cells hypersensitive to otherwise sublethal doses of clinically relevant chemotherapeutic agents. Our finding that BMX directly inhibits a core component of the intrinsic apoptosis machinery opens opportunities to improve the efficacy of existing chemotherapy by potentiating BAK-driven cell death in cancer cells. Cancer Res; 75(7); 1345–55. ©2015 AACR.
Associations between Environmental Exposures and Incident Colorectal Cancer by ESR2 Protein Expression Level in a Population-Based Cohort of Older Women
Authors: Tillmans Lori S. , Vierkant Robert A. , Wang Alice H. , Samadder Niloy Jewel , Lynch Charles F. , Anderson Kristin E. , French Amy J. , Haile Robert W. , Harnack Lisa J. , Potter John D. , Slager Susan L. , Smyrk Thomas C. , Thibodeau Stephen N. , Cerhan James R. , Limburg Paul J. 
Published: February 2015

Abstract
Background: Cigarette smoking (smoking), hormone therapy (MHT), and folate intake (folate) are each thought to influence colorectal cancer risk, but the underlying molecular mechanisms remain incompletely defined. Expression of estrogen receptor β (ESR2) has been associated with colorectal cancer stage and survival.
Methods: In this prospective cohort study, we examined smoking, MHT, and folate-associated colorectal cancer risks by ESR2 protein expression level among participants in the Iowa Women's Health Study (IWHS). Self-reported exposure variables were assessed at baseline. Archived, paraffin-embedded colorectal cancer tissue specimens were collected and evaluated for ESR2 protein expression by IHC. Multivariate Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI) for associations between smoking, MHT, or folate and ESR2-defined colorectal cancer subtypes.
Results: Informative environmental exposure and protein expression data were available for 491 incident colorectal cancer cases. Positive associations between ESR2-low and -high tumors and several smoking-related variables were noted, most prominently with average number of cigarettes per day (RR, 4.24; 95% CI, 1.81–9.91 for ESR2-low and RR, 2.15; 95% CI, 1.05–4.41 for ESR2-high for ≥40 cigarettes compared with nonsmokers). For MHT, a statistically significant association with ESR2-low tumors was observed with longer duration of exposure (RR, 0.54; 95% CI, 0.26–1.13 for &gt;5 years compared with never use). No associations were found for folate.
Conclusions: In this study, smoking and MHT were associated with ESR2 expression patterns.
Impact: These data support possible heterogeneous effects from smoking and MHT on ERβ-related pathways of colorectal carcinogenesis in older women. Cancer Epidemiol Biomarkers Prev; 24(4); 713–9. ©2015 AACR.
The Association between Fatalistic Beliefs and Late Stage at Diagnosis of Lung and Colorectal Cancer
Authors: Lyratzopoulos Georgios , Liu Michael Pang-Hsiang , Abel Gary A. , Wardle Jane , Keating Nancy L. 
Published: February 2015

AbstractBackground: Fatalistic beliefs may be implicated in longer help-seeking intervals, and consequently, greater risk of advanced stage at cancer diagnosis.Methods: We examined associations between fatalism and stage at diagnosis in a population-based cohort of 4,319 U.S. patients with newly diagnosed lung or colorectal cancer participating in the Cancer Care Outcomes and Research Surveillance (CanCORS) study. Fatalistic beliefs were assessed with an established measure. A fatalism score (range, 4–16) was created by summing Likert scale responses to four items. Cancer stage at diagnosis was abstracted from medical records by trained staff. Logistic regression was used to assess the association between fatalism score and advanced stage at diagnosis (IV vs. I–III), adjusting for sociodemographic and clinical characteristics.Results: Overall, 917 (21%) patients had stage IV cancers (lung: 28%, colorectal: 16%). The mean fatalism score was 10.7 (median = 11; interquartile range, 9–12). In adjusted analyses, a higher fatalism score was associated with greater odds of stage IV diagnosis (OR per unit increase in fatalism = 1.05; 95% confidence interval 1.02–1.08; P = 0.003). Patients with the highest fatalism score had an adjusted 8.9% higher frequency of stage IV diagnosis compared with patients with the lowest score (25.4% vs. 16.5%).Discussion: In this large and socioeconomically, geographically, and ethnically diverse population of patients with lung and colorectal cancer, fatalistic beliefs were associated with higher risk of advanced stage at diagnosis. Longitudinal studies are needed to confirm causation.Impact: These findings support the value of incorporating information about the curability of early-stage cancers in public education campaigns. Cancer Epidemiol Biomarkers Prev; 24(4); 720–6. ©2015 AACR.