bluuebunny/crossref_metadata_2025_split huggingface dataset:
Technical Note: Millimeter precision in ultrasound based patient positioning: Experimental quantification of inherent technical limitations
Authors: Ballhausen Hendrik , Hieber Sheila , Li Minglun , Belka Claus , Reiner Michael 
Published: August 2014

Purpose:To identify the relevant technical sources of error of a system based on three‐dimensional ultrasound (3D US) for patient positioning in external beam radiotherapy. To quantify these sources of error in a controlled laboratory setting. To estimate the resulting end‐to‐end geometric precision of the intramodality protocol.Methods:Two identical free‐hand 3D US systems at both the planning‐CT and the treatment room were calibrated to the laboratory frame of reference. Every step of the calibration chain was repeated multiple times to estimate its contribution to overall systematic and random error. Optimal margins were computed given the identified and quantified systematic and random errors.Results:In descending order of magnitude, the identified and quantified sources of error were: alignment of calibration phantom to laser marks 0.78 mm, alignment of lasers in treatment vs planning room 0.51 mm, calibration and tracking of 3D US probe 0.49 mm, alignment of stereoscopic infrared camera to calibration phantom 0.03 mm. Under ideal laboratory conditions, these errors are expected to limit ultrasound‐based positioning to an accuracy of 1.05 mm radially.Conclusions:The investigated 3D ultrasound system achieves an intramodal accuracy of about 1 mm radially in a controlled laboratory setting. The identified systematic and random errors require an optimal clinical tumor volume to planning target volume margin of about 3 mm. These inherent technical limitations do not prevent clinical use, including hypofractionation or stereotactic body radiation therapy.
Draft Genome Sequence of a Symbiotic Bacterium, Rhizobium vignae CCBAU 05176T
Authors: Liu Yang , Yi Zhiwei , Zeng Runying 
Published: August 2014

ABSTRACTTheRhizobium vignaestrain CCBAU 05176Twas isolated from a root nodule ofAstragalus dahuricusgrown in Hebei Province, China. It grows on yeast mannitol agar (YMA) supplemented with 0 to 2% (wt/vol) NaCl. We report the annotated genome sequence of this strain in a 6.34-Mb scaffold.
Draft Genomes of Three Strains Representative of the Bacillus anthracis Diversity Found in France
Authors: Girault Guillaume , Parisot Nicolas , Peyretaillade Eric , Peyret Pierre , Derzelle Sylviane 
Published: August 2014

ABSTRACT

We report here the draft genomes of three
Bacillus anthracis
strains isolated in France: 08-8_20 (A.Br.001/002), 99-100 (A.Br.011/009), and 00-82 (B.Br CNEVA). The total lengths of assemblies are 5,440,708 bp, 5,446,472 bp, and 5,436,014 bp for 08-8_20, 99-100, and 00-82, respectively.
Sports-related concussion increases the risk of subsequent injury by about 50% in elite male football players
Authors: Nordström Anna , Nordström Peter , Ekstrand Jan 
Published: August 2014

BackgroundLittle is known about the short-term and long-term sequelae of concussion, and about when athletes who have sustained such injuries can safely return to play.PurposeTo examine whether sports-related concussion increases the risk of subsequent injury in elite male football players.Study designProspective cohort study.MethodsInjuries were registered for 46 male elite football teams in 10 European countries in the 2001/2002–2011/2102 seasons. Two survival models were used to analyse whether concussion increased the subsequent risk of an injury in the first year.ResultsDuring the follow-up period, 66 players sustained concussions and 1599 players sustained other injuries. Compared with the risk following other injuries, concussion was associated with a progressively increased risk of a subsequent injury in the first year (0 to <3 months, HR=1.56, 95% CI 1.09 to 2.23; 3 to <6 months, HR=2.78, 95% CI 1.58 to 4.89; 6–12 months, HR=4.07, 95% CI 2.14 to 7.76). In the second model, after adjustment for the number of injuries in the year preceding the concussion, this injury remained significantly associated with the risk of subsequent injury in the first year (HR=1.47, 95% CI 1.05 to 2.05).ConclusionsConcussion was a risk factor for sustaining subsequent injury within the following year. In-depth medical evaluation, which includes neurological and cognitive assessment, is warranted within the concussion management and return-to- play process.
To see or not to see: a qualitative interview study of patients’ views on their own diagnostic images
Authors: Carlin Leslie E , Smith Helen E , Henwood Flis 
Published: August 2014

ObjectivesTo ascertain what meaning individuals attach to perceiving images of their own interior body and how the images and their meanings affect the clinical consultation.DesignFace-to-face semistructured interviews.Participants25 adult patients in southern England who, within the preceding 12 months, had been referred for diagnostic imaging.SettingCommunity.ResultsFor patients, being shown their own X-rays, MRIs or CT images creates a variety of effects: (1) a sense of better understanding of the diagnosis; (2) validation of their sensory and emotional response to the illness or injury and (3) an alteration to the tenor and nature of the clinical encounter between patient and physician. In addition to meanings attached to these images, patients also impute meaning to the physician's decisionnotto share an image with them. The desire to see their image was greater in those patients with a skeletal injury; patients are less keen on viewing abdominal or other soft tissue images.ConclusionsViewing images of one's interior, invisible body is powerful and resonant in a number of ways. The experience of not seeing, whether through the patient's or the physician's choice, is also fraught with meaning.
Investigating the organisational impacts of quality improvement: a protocol for a realist evaluation of improvement approaches drawing on the Resource Based View of the Firm
Authors: Burton Christopher R , Rycroft Malone Jo , Robert Glenn , Willson Alan , Hopkins Angela 
Published: August 2014

IntroductionLittle is understood about the role of quality improvement in enabling health organisations to survive and thrive in the contemporary context of financial and economic challenges. We will draw on the theoretical foundations of the ‘Resource Based View of the Firm’ (RBV) to develop insights into why health organisations engage in improvement work, how impacts are conceptualised, and ‘what works’ in delivering these impacts. Specifically, RBV theorises that the mix and use of resources across different organisations may explain differences in performance. Whether improvement work influences these resources is unclear.Methods and analysisCase study research will be conducted across health organisations participating in four approaches to improvement, including: a national improvement programme; a multiorganisational partnership around implementation; an organisational strategy for quality improvement; and a coproduction project designed to enhance the experience of a clinical service from the perspective of patients. Data will comprise in-depth interviews with key informants, observation of key events and documents; analysed within and then across cases. Adopting a realist perspective, the core tenets of RBV will be evaluated as a programme theory, focusing on the interplay between organisational conditions and behavioural or resource responses that are reported through engagement in improvement.Ethics and disseminationThe study has been approved by Bangor University Ethics Committee. The investigation will not judge the relative merits of different approaches to healthcare quality improvement. Rather, we will develop unique insights into the organisational consequences, and dependencies of quality improvement, providing an opportunity to add to the explanatory potential of RBV in this and other contexts. In addition to scientific and lay reports of the study findings, research outputs will include a framework for constructing the economic impacts of quality improvement and practical guidance for health service managers that maximises the impacts of investment in quality improvement.
Minimally invasive endoscopic staging for mediastinal lymphadenopathy in lung cancer: a systematic review protocol
Authors: Liu Hong , Zhou Jie , Feng Qiao-ling , Wan Gang , Xie Yong-jun , Gu Hai-tao 
Published: August 2014

IntroductionMinimally invasive endoscopic biopsy techniques have been widely available as potential alternatives for mediastinal lesions staging in patients with known or suspected lung cancer. Previous efforts have been made to evaluate the diagnostic performance of specific endoscopic modality alone at the level of the mediastinum for staging lung cancer, however, few studies focus on the accuracy of comparisons between different endoscopic modalities, especially at the level of any individual lymph node station. The objective of our study is to determine the diagnostic yields of different endoscopic modalities for staging mediastinal lymphadenopathy in lung cancer, especially concerning the individual lymph node station.Methods/designA systematic electronic search of MEDLINE, EMBASE, SinoMed and ISI Web of Science were performed to identify studies evaluating endoscopic modalities accuracy with restriction of English and Chinese languages from inception to an update until May 2014. Data were extracted with the patient as the unit of analysis with regards to the abilities of different endoscopic modalities at the level of mediastinum and particular lymph node station. The methodological quality was assessed independently according to the Quality Assessment of Diagnostic Accuracy Study (QADAS) criteria. An exact binomial rendition of bivariate mixed-effects regression model was used to estimate the pooled sensitivity and specificity. Also, pre–post probability analysis, publication bias analysis and sensitivity analysis were performed for a synthesis of knowledge of this context.DisseminationThe findings will advance our better available knowledge of optimal clinical decision-making when dealing with staging of mediastinal metastasis in lung cancer.Trial registration numberPROSPERO—NIHR Prospective Register of Systematic Reviews (CRD42014009792).
Are recent graduates enough prepared to perform obstetric skills in their rural and compulsory year? A study from Ecuador
Authors: Sánchez del Hierro Galo , Remmen Roy , Verhoeven Veronique , Van Royen Paul , Hendrickx Kristin 
Published: August 2014

ObjectivesThe aim of this study was to assess the possible mismatch of obstetrical skills between the training offered in Ecuadorian medical schools and the tasks required for compulsory rural service.SettingPrimary care, rural health centres in Southern Ecuador.ParticipantsA total of 92 recent graduated medical doctors during their compulsory rural year.Primary and secondary outcomes measuresA web-based survey was developed with 21 obstetrical skills. The questionnaire was sent to all rural doctors who work in Loja province, Southern Ecuador, at the Ministry of Health (n=92).We measured two categories‘importance of skills in rural practice’ with a five-point Likert-type scale (1= strongly disagree; 5= strongly agree); and ‘clerkship experience’ using a nominal scale divided in five levels: level 1 (not seen, not performed) to level 5 (performed 10 times or more). Spearman's rank correlation coefficient (r) was used to observe associations.ResultsA negative correlation was found in the skills: ‘episiotomy and repair’, ‘umbilical vein catheterisation’, ‘speculum examination’, ‘evaluation of cervical dilation during active labour’, ‘neonatal resuscitation’ and ‘vacuum-assisted vaginal delivery’. For instance ‘Episiotomy and repair’ is important (strongly agree and agree) to 100% of respondents, but in practice, only 38.9% of rural doctors performed the task three times and 8.3% only once during the internship, similar pattern is seen in the others.ConclusionsIn this study we have noted the gap between the medical needs of populations in rural areas and training provided during the clerkship experiences of physicians during their rural service year. It is imperative to ensure that rural doctors are appropriately trained and skilled in the performance of routine obstetrical duties. This will help to decrease perinatal morbidity and mortality in rural Ecuador.
Crowdsourced Monolingual Translation
Authors: Hu Chang , Resnik Philip , Bederson Benjamin B. 
Published: August 2014

An enormous potential exists for solving certain classes of computational problems through rich collaboration among crowds of humans supported by computers. Solutions to these problems used to involve human professionals, who are expensive to hire or difficult to find. Despite significant advances, fully automatic systems still have much room for improvement. Recent research has involved recruiting large crowds of skilled humans (“crowdsourcing”), but crowdsourcing solutions are still restricted by the availability of those skilled human participants. With translation, for example, professional translators incur a high cost and are not always available; machine translation systems have been greatly improved recently but still can only provide passable translation; and crowdsourced translation is limited by the availability of bilingual humans.
This article describes crowdsourced monolingual translation, where monolingual translation is translation performed by monolingual people. Crowdsourced monolingual translation is a collaborative form of translation performed by two crowds of people who speak the source or the target language, respectively, with machine translation as the mediating device.
This article describes a general protocol to handle crowdsourced monolingual translation and analyzes three systems that implemented the protocol. These systems were studied in various settings and were found to supply significant improvement in quality over both machine translation and monolingual editing of machine translation output (“postediting”).
CSF1/CSF1R Blockade Reprograms Tumor-Infiltrating Macrophages and Improves Response to T-cell Checkpoint Immunotherapy in Pancreatic Cancer Models
Authors: Zhu Yu , Knolhoff Brett L. , Meyer Melissa A. , Nywening Timothy M. , West Brian L. , Luo Jingqin , Wang-Gillam Andrea , Goedegebuure S. Peter , Linehan David C. , DeNardo David G. 
Published: August 2014

Abstract
Cancer immunotherapy generally offers limited clinical benefit without coordinated strategies to mitigate the immunosuppressive nature of the tumor microenvironment. Critical drivers of immune escape in the tumor microenvironment include tumor-associated macrophages and myeloid-derived suppressor cells, which not only mediate immune suppression, but also promote metastatic dissemination and impart resistance to cytotoxic therapies. Thus, strategies to ablate the effects of these myeloid cell populations may offer great therapeutic potential. In this report, we demonstrate in a mouse model of pancreatic ductal adenocarcinoma (PDAC) that inhibiting signaling by the myeloid growth factor receptor CSF1R can functionally reprogram macrophage responses that enhance antigen presentation and productive antitumor T-cell responses. Investigations of this response revealed that CSF1R blockade also upregulated T-cell checkpoint molecules, including PDL1 and CTLA4, thereby restraining beneficial therapeutic effects. We found that PD1 and CTLA4 antagonists showed limited efficacy as single agents to restrain PDAC growth, but that combining these agents with CSF1R blockade potently elicited tumor regressions, even in larger established tumors. Taken together, our findings provide a rationale to reprogram immunosuppressive myeloid cell populations in the tumor microenvironment under conditions that can significantly empower the therapeutic effects of checkpoint-based immunotherapeutics. Cancer Res; 74(18); 5057–69. ©2014 AACR.
Serum 25-Hydroxyvitamin D Concentrations and Risk of Prostate Cancer: Results from the Prostate Cancer Prevention Trial
Authors: Schenk Jeannette M. , Till Cathee A. , Tangen Catherine M. , Goodman Phyllis J. , Song Xiaoling , Torkko Kathleen C. , Kristal Alan R. , Peters Ulrike , Neuhouser Marian L. 
Published: August 2014

AbstractBackground: Epidemiologic studies have reported inconsistent associations of vitamin D and prostate cancer risk; however, few have adequately controlled for detection bias related to prostate-specific antigen (PSA) screening, and the results of many studies may be affected by occult prostate cancers among controls.Methods: Data for this nested case–control analysis (n = 1,695 cases/1,682 controls) are from the Prostate Cancer Prevention Trial. Baseline serum was analyzed for 25-hydroxyvitamin D [25(OH)D]. The presence or absence of cancer was subsequently determined by prostate biopsy. Polytomous logistic regression models were used to estimate associations of 25(OH)D with risk of total, Gleason 2–6, Gleason 7, and Gleason 8–10 prostate cancer. Results are presented for placebo and finasteride arms separately and combined.Results: There were no associations of serum 25(OH)D with total prostate cancer risk. For Gleason 2–6 cancers, results were inconsistent across treatment arms with a suggestion of increased risk in the placebo arm only; however, there was no dose–response relationship. For Gleason 8–10 prostate cancers, 25(OH)D concentrations were associated with a linear decrease in risk among combined treatment arms [quartile 4 vs. 1: OR, 0.55; 95% confidence interval (CI), 0.32–0.94; Ptrend = 0.04]. These findings were somewhat stronger among men ≥65 versus 55–64 years at baseline (quartile 4 vs. 1: OR, 0.40; 95% CI, 0.18–0.88 vs. OR, 0.73; 95% CI, 0.35–1.52, respectively; Pinteraction = 0.52).Conclusions: Higher serum 25(OH)D may modestly increase risk of Gleason 2–6 disease and more substantially reduce risk of Gleason 8–10 prostate cancer.Impact: Vitamin D may have different effects for different stages of prostate cancers. Cancer Epidemiol Biomarkers Prev; 23(8); 1484–93. ©2014 AACR.
Calpain-Mediated Integrin Deregulation as a Novel Mode of Action for the Anticancer Gallium Compound KP46
Authors: Jungwirth Ute , Gojo Johannes , Tuder Theresa , Walko Gernot , Holcmann Martin , Schöfl Thomas , Nowikovsky Karin , Wilfinger Nastasia , Schoonhoven Sushilla , Kowol Christian R. , Lemmens-Gruber Rosa , Heffeter Petra , Keppler Bernhard K. , Berger Walter 
Published: August 2014

Abstract
On the basis of enhanced tumor accumulation and bone affinity, gallium compounds are under development as anticancer and antimetastatic agents. In this study, we analyzed molecular targets of one of the lead anticancer gallium complexes [KP46, Tris(8-quinolinolato)gallium(III)] focusing on colon and lung cancer. Within a few hours, KP46 treatment at low micromolar concentrations induced cell body contraction and loss of adhesion followed by prompt cell decomposition. This rapid KP46-induced cell death lacked classic apoptotic features and was insensitive toward a pan–caspase inhibitor. Surprisingly, however, it was accompanied by upregulation of proapoptotic Bcl-2 family members. Furthermore, a Bax- but not a p53-knockout HCT-116 subline exhibited significant KP46 resistance. Rapid KP46-induced detachment was accompanied by downregulation of focal adhesion proteins, including several integrin subunits. Loss of integrin-β1 and talin plasma membrane localization corresponded to reduced binding of RGD (Arg–Gly–Asp) peptides to KP46-treated cells. Accordingly, KP46-induced cell death and destabilization of integrins were enhanced by culture on collagen type I, a major integrin ligand. In contrast, KP46-mediated adhesion defects were partially rescued by Mg2+ ions, promoting integrin-mediated cell adhesion. Focal adhesion dynamics are regulated by calpains via cleavage of multiple cell adhesion molecules. Cotreatment with the cell-permeable calpain inhibitor PD150606 diminished KP46-mediated integrin destabilization and rapid cell death induction. KP46 treatment distinctly inhibited HCT-116 colon cancer xenograft in vivo by causing reduced integrin plasma membrane localization, tissue disintegration, and intense tumor necrosis. This study identifies integrin deregulation via a calpain-mediated mechanism as a novel mode of action for the anticancer gallium compound KP46. Mol Cancer Ther; 13(10); 2436–49. ©2014 AACR.
Nanolipolee-007, a Novel Nanoparticle-Based Drug Containing Leelamine for the Treatment of Melanoma
Authors: Gowda Raghavendra , Madhunapantula SubbaRao V. , Sharma Arati , Kuzu Omer F. , Robertson Gavin P. 
Published: August 2014

Abstract
Malignant melanoma is a difficult cancer to treat due to the rapid development of resistance to drugs targeting single proteins. One response to this observation is to identify single pharmacologic agents that, due to a unique mechanism of action, simultaneously target multiple key pathways involved in melanoma development. Leelamine has been identified as functioning in this manner but has poor bioavailability in animals and causes lethality when administered intravenously. Therefore, a nanoliposomal-based delivery system has been developed, called Nanolipolee-007, which stably loads 60% of the compound. The nanoparticle was as effective at killing melanoma cells as leelamine dissolved in DMSO and was more effective at killing cultured melanoma compared with normal cells. Mechanistically, Nanolipolee-007 inhibited PI3K/Akt, STAT3, and MAPK signaling mediated through inhibition of cholesterol transport. Nanolipolee-007 inhibited the growth of preexisting xenografted melanoma tumors by an average of 64% by decreasing cellular proliferation, reducing tumor vascularization, and increasing cellular apoptosis, with negligible toxicity. Thus, a unique clinically viable nanoparticle-based drug has been developed containing leelamine for the treatment of melanoma that acts by inhibiting the activity of major signaling pathways regulating the development of this disease. Mol Cancer Ther; 13(10); 2328–40. ©2014 AACR.
Ser70 phosphorylation of Bcl-2 by selective tyrosine nitration of PP2A-B56δ stabilizes its antiapoptotic activity
Authors: Low Ivan Cherh Chiet , Loh Thomas , Huang Yiqing , Virshup David M. , Pervaiz Shazib 
Published: August 2014

Key Points
O2− modifies B56δ at Y289 to block the PP2A holoenzyme assembly. This results in S70 Bcl-2 phosphorylation and promotes tumor chemoresistance. Primary lymphomas with low SOD1 have high B56δ tyrosine nitration and S70pBcl-2.
Glucocorticoid receptor binds half sites as a monomer and regulates specific target genes
Authors: Schiller Benjamin J , Chodankar Rajas , Watson Lisa C , Stallcup Michael R , Yamamoto Keith R 
Published: August 2014

Abstract
Background
Glucocorticoid receptor (GR) is a hormone-activated, DNA-binding transcriptional regulatory factor that controls inflammation, metabolism, stress responses, and other physiological processes. In vitro, GR binds as an inverted dimer to a motif consisting of two imperfectly palindromic 6 bp half sites separated by 3 bp spacers. In vivo, GR employs different patterns of functional surfaces of GR to regulate different target genes. The relationships between GR genomic binding and functional surface utilization have not been defined.

Results
We find that A477T, a GR mutant that disrupts the dimerization interface, differs from wild-type GRα in binding and regulation of target genes. Genomic regions strongly occupied by A477T are enriched for a novel half site motif. In vitro, GRα binds half sites as a monomer. Through the overlap between GRα- and A477T-bound regions, we identify GRα-bound regions containing only half sites. We further identify GR target genes linked with half sites and not with the full motif.

Conclusions
Genomic regions bound by GR differ in underlying DNA sequence motifs and in the GR functional surfaces employed for regulation. Identification of GR binding regions that selectively utilize particular GR surfaces may discriminate sub-motifs, including the half site motif, that favor those surfaces. This approach may contribute to predictive models for GR activity and therapy.