bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized Comparison of Surveillance Intervals in Familial Colorectal Cancer
Authors: Hennink Simone D. , van der Meulen-de Jong Andrea E. , Wolterbeek Ron , Crobach A. Stijn L.P. , Becx Marco C.J.M. , Crobach Wiet F.S.J. , van Haastert Michiel , ten Hove W. Rogier , Kleibeuker Jan H. , Meijssen Maarten A.C. , Nagengast Fokko M. , Rijk Marno C.M. , Salemans Jan M.J.I. , Stronkhorst Arnold , Tuynman Hans A.R.E. , Vecht Juda , Verhulst Marie-Louise , de Vos tot Nederveen Cappel Wouter H. , Walinga Herman , Weinhardt Olaf K. , Westerveld Dik , Witte Anne M.C. , Wolters Hugo J. , Cats Annemieke , Veenendaal Roeland A. , Morreau Hans , Vasen Hans F.A. 
Published: November 2015

Purpose Colonoscopic surveillance is recommended for individuals with familial colorectal cancer (CRC). However, the appropriate screening interval has not yet been determined. The aim of this randomized trial was to compare a 3-year with a 6-year screening interval. Patients and Methods Individuals between ages 45 and 65 years with one first-degree relative with CRC age < 50 years or two first-degree relatives with CRC were selected. Patients with zero to two adenomas at baseline were randomly assigned to one of two groups: group A (colonoscopy at 6 years) or group B (colonoscopy at 3 and 6 years). The primary outcome measure was advanced adenomatous polyps (AAPs). Risk factors studied included sex, age, type of family history, and baseline endoscopic findings. Results A total of 528 patients were randomly assigned (group A, n = 262; group B, n = 266). Intention-to-treat analysis showed no significant difference in the proportion of patients with AAPs at the first follow-up examination at 6 years in group A (6.9%) versus 3 years in group B (3.5%). Also, the proportion of patients with AAPs at the final follow-up examination at 6 years in group A (6.9%) versus 6 years in group B (3.4%) was not significantly different. Only AAPs at baseline was a significant predictor for the presence of AAPs at first follow-up. After correction for the difference in AAPs at baseline, differences between the groups in the rate of AAPs at first follow-up and at the final examination were statistically significant. Conclusion In view of the relatively low rate of AAPs at 6 years and the absence of CRC in group A, we consider a 6-year surveillance interval appropriate. A surveillance interval of 3 years might be considered in patients with AAPs and patients with ≥ three adenomas.
Randomized Phase Ib/II Study of Gemcitabine Plus Placebo or Vismodegib, a Hedgehog Pathway Inhibitor, in Patients With Metastatic Pancreatic Cancer
Authors: Catenacci Daniel V.T. , Junttila Melissa R. , Karrison Theodore , Bahary Nathan , Horiba Margit N. , Nattam Sreenivasa R. , Marsh Robert , Wallace James , Kozloff Mark , Rajdev Lakshmi , Cohen Deirdre , Wade James , Sleckman Bethany , Lenz Heinz-Josef , Stiff Patrick , Kumar Pankaj , Xu Peng , Henderson Les , Takebe Naoko , Salgia Ravi , Wang Xi , Stadler Walter M. , de Sauvage Frederic J. , Kindler Hedy L. 
Published: November 2015

Purpose Sonic hedgehog (SHH), an activating ligand of smoothened (SMO), is overexpressed in > 70% of pancreatic cancers (PCs). We investigated the impact of vismodegib, an SHH antagonist, plus gemcitabine (GV) or gemcitabine plus placebo (GP) in a multicenter phase Ib/randomized phase II trial and preclinical PC models. Patients and Methods Patients with PC not amenable to curative therapy who had received no prior therapy for metastatic disease and had Karnofsky performance score ≥ 80 were enrolled. Patients were randomly assigned in a one-to-one ratio to GV or GP. The primary end point was progression-free-survival (PFS). Exploratory correlative studies included serial SHH serum levels and contrast perfusion computed tomography imaging. To further investigate putative biologic mechanisms of SMO inhibition, two autochthonous pancreatic cancer models (KrasG12D; p16/p19fl/fl; Pdx1-Cre and KrasG12D; p53R270H/wt; Pdx1-Cre) were studied. Results No safety issues were identified in the phase Ib portion (n = 7), and the phase II study enrolled 106 evaluable patients (n = 53 in each arm). Median PFS was 4.0 and 2.5 months for GV and GP arms, respectively (95% CI, 2.5 to 5.3 and 1.9 to 3.8, respectively; adjusted hazard ratio, 0.81; 95% CI, 0.54 to 1.21; P = .30). Median overall survival (OS) was 6.9 and 6.1 months for GV and GP arms, respectively (95% CI, 5.8 to 8.0 and 5.0 to 8.0, respectively; adjusted hazard ratio, 1.04; 95% CI, 0.69 to 1.58; P = .84). Response rates were not significantly different. There were no significant associations between correlative markers and overall response rate, PFS, or OS. Preclinical trials revealed no significant differences with vismodegib in drug delivery, tumor growth rate, or OS in either model. Conclusion The addition of vismodegib to gemcitabine in an unselected cohort did not improve overall response rate, PFS, or OS in patients with metastatic PC. Our preclinical and clinical results revealed no statistically significant differences with respect to drug delivery or treatment efficacy using vismodegib.
Cognitive Function in Patients With Colorectal Cancer Who Do and Do Not Receive Chemotherapy: A Prospective, Longitudinal, Controlled Study
Authors: Vardy Janette L. , Dhillon Haryana M. , Pond Gregory R. , Rourke Sean B. , Bekele Tsegaye , Renton Corrinne , Dodd Anna , Zhang Haibo , Beale Philip , Clarke Stephen , Tannock Ian F. 
Published: November 2015

Purpose Cognitive dysfunction is reported in people with cancer. Therefore, we evaluated longitudinal changes in cognitive function and underlying mechanisms in people with colorectal cancer (CRC) and healthy controls (HCs). Patients and Methods Participants completed cognitive assessments and questionnaires reporting cognitive symptoms, fatigue, quality of life, and anxiety/depression at baseline (before chemotherapy, if given) and 6, 12, and 24 months. Blood tests included cytokines, clotting factors, apolipoprotein E genotype, and sex hormones. Primary end point was overall cognitive function measured by the Global Deficit Score at 12 months. Results We recruited 289 patients with localized CRC (173 received chemotherapy; median age, 59 years; 63% male), 73 patients with limited metastatic/recurrent CRC, and 72 HCs. Cognitive impairment was more frequent in patients with localized CRC than HCs at baseline (43% v 15%, respectively; P < .001) and 12 months (46% v 13%, respectively; P < .001), with no significant effect of chemotherapy. Attention/working memory, verbal learning/memory, and complex processing speed were most affected. Cognitive impairment was similar in patients with localized and metastatic CRC. Cytokine levels were elevated in patients with CRC compared with HCs. There was no association between overall cognitive function and fatigue, quality of life, anxiety/depression, or any blood test. Cognitive symptoms at 12 months were reported in 25% of patients with localized CRC versus 17% of HCs (P = .19). More participants who received chemotherapy had cognitive symptoms at 6 months (32%) versus those who did not (16%; P = .007), with no significant difference at 12 months (29% v 21%, respectively; P = .19). Objective cognitive function was only weakly associated with cognitive symptoms. Conclusion Patients with CRC had substantially more cognitive impairment at every assessment than HCs, with no significant added effect of chemotherapy. Mechanisms of cognitive impairment remain unknown.
Adjuvant Fluorouracil, Leucovorin, and Oxaliplatin in Stage II to III Colon Cancer: Updated 10-Year Survival and Outcomes According to BRAF Mutation and Mismatch Repair Status of the MOSAIC Study
Authors: André Thierry , de Gramont Armand , Vernerey Dewi , Chibaudel Benoist , Bonnetain Franck , Tijeras-Raballand Annemilaï , Scriva Aurelie , Hickish Tamas , Tabernero Josep , Van Laethem Jean Luc , Banzi Maria , Maartense Eduard , Shmueli Einat , Carlsson Goran U. , Scheithauer Werner , Papamichael Demetris , Möehler Marcus , Landolfi Stefania , Demetter Pieter , Colote Soudhir , Tournigand Christophe , Louvet Christophe , Duval Alex , Fléjou Jean-François , de Gramont Aimery 
Published: November 2015

Purpose The MOSAIC (Multicenter International Study of Oxaliplatin/Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer) study has demonstrated 3-year disease-free survival (DFS) and 6-year overall survival (OS) benefit of adjuvant oxaliplatin in stage II to III resected colon cancer. This update presents 10-year OS and OS and DFS by mismatch repair (MMR) status and BRAF mutation. Methods Survival actualization after 10-year follow-up was performed in 2,246 patients with resected stage II to III colon cancer. We assessed MMR status and BRAF mutation in 1,008 formalin-fixed paraffin-embedded specimens. Results After a median follow-up of 9.5 years, 10-year OS rates in the bolus/infusional fluorouracil plus leucovorin (LV5FU2) and LV5FU2 plus oxaliplatin (FOLFOX4) arms were 67.1% versus 71.7% (hazard ratio [HR], 0.85; P = .043) in the whole population, 79.5% versus 78.4% for stage II (HR, 1.00; P = .980), and 59.0% versus 67.1% for stage III (HR, 0.80; P = .016) disease. Ninety-five patients (9.4%) had MMR-deficient (dMMR) tumors, and 94 (10.4%) had BRAF mutation. BRAF mutation was not prognostic for OS (P = .965), but dMMR was an independent prognostic factor (HR, 2.02; 95% CI, 1.15 to 3.55; P = .014). HRs for DFS and OS benefit in the FOLFOX4 arm were 0.48 (95% CI, 0.20 to 1.12) and 0.41 (95% CI, 0.16 to 1.07), respectively, in patients with stage II to III dMMR and 0.50 (95% CI, 0.25 to 1.00) and 0.66 (95% CI, 0.31 to 1.42), respectively, in those with BRAF mutation. Conclusion The OS benefit of oxaliplatin-based adjuvant chemotherapy, increasing over time and with the disease severity, was confirmed at 10 years in patients with stage II to III colon cancer. These updated results support the use of FOLFOX in patients with stage III disease, including those with dMMR or BRAF mutation.
AP-2-complex-mediated endocytosis of Drosophila Crumbs regulates polarity by antagonizing Stardust
Authors: Lin Ya-Huei , Currinn Heather , Pocha Shirin Meher , Rothnie Alice , Wassmer Thomas , Knust Elisabeth 
Published: November 2015

ABSTRACT
Maintenance of epithelial polarity depends on the correct localization and levels of polarity determinants. The evolutionarily conserved transmembrane protein Crumbs is crucial for the size and identity of the apical membrane, yet little is known about the molecular mechanisms controlling the amount of Crumbs at the surface. Here, we show that Crumbs levels on the apical membrane depend on a well-balanced state of endocytosis and stabilization. The adaptor protein 2 (AP-2) complex binds to a motif in the cytoplasmic tail of Crumbs that overlaps with the binding site of Stardust, a protein known to stabilize Crumbs on the surface. Preventing endocytosis by mutation of AP-2 causes expansion of the Crumbs-positive plasma membrane domain and polarity defects, which can be partially rescued by removing one copy of crumbs. Strikingly, knocking down both AP-2 and Stardust leads to the retention of Crumbs on the membrane. This study provides evidence for a molecular mechanism, based on stabilization and endocytosis, to adjust surface levels of Crumbs, which are essential for maintaining epithelial polarity.
Pseudotumour incidence, cobalt levels and clinical outcome after large head metal-on-metal and conventional metal-on-polyethylene total hip arthroplasty
Authors: van der Veen H. C. , Reininga I. H. F. , Zijlstra W. P. , Boomsma M. F. , Bulstra S. K. , van Raay J. J. A. M. 
Published: November 2015

We compared the incidence of pseudotumours after large head metal-on-metal (MoM) total hip arthroplasty (THA) with that after conventional metal-on-polyethylene (MoP) THA and assessed the predisposing factors to pseudotumour formation. From a previous randomised controlled trial which compared large head (38 mm to 60 mm) cementless MoM THA with conventional head (28 mm) cementless MoP THA, 93 patients (96 THAs: 41 MoM (21 males, 20 females, mean age of 64 years, standard deviation (sd) 4) and 55 MoP (25 males, 30 females, mean age of 65 years, sd 5) were recruited after a mean follow-up of 50 months (36 to 64). The incidence of pseudotumours, measured using a standardised CT protocol was 22 (53.7%) after MoM THA and 12 (21.8%) after MoP THA. Women with a MoM THA were more likely to develop a pseudotumour than those with a MoP THA (15 vs 7, odds ratio (OR) = 13.4, p < 0.001). There was a similar incidence of pseudotumours in men with MoM THAs and those with MoP THAs (7 vs 5, OR = 2.1, p = 0.30). Elevated cobalt levels (≥ 5 microgram/L) were only associated with pseudotumours in women with a MoM THA. There was no difference in mean Oxford and Harris hip scores between patients with a pseudotumour and those without. Contrary to popular belief, pseudotumours occur frequently around MoP THAs. Women with a MoM THA and an elevated cobalt level are at greatest risk. In this study, pseudotumours had no effect on the functional outcome after either large head MoM or conventional MoP THA. Cite this article: Bone Joint J 2015;97-B:1481–7.
Iatrogenic vascular injuries during arthroplasty of the hip
Authors: Alshameeri Z. , Bajekal R. , Varty K. , Khanduja V. 
Published: November 2015

Vascular injuries during total hip arthroplasty (THA) are rare but when they occur, have serious consequences. These have traditionally been managed with open exploration and repair, but more recently there has been a trend towards percutaneous endovascular management.We performed a systematic review of the literature to assess if this change in trend has led to an improvement in the overall reported rates of morbidity and mortality during the last 22 years in comparison with the reviews of the literature published previously.We found a total of 61 articles describing 138 vascular injuries in 124 patients. Injuries because of a laceration were the most prevalent (n = 51, 44%) and the most common presenting feature, when recorded, was bleeding (n = 41, 53.3%). Delay in diagnosis was associated with the type of vascular lesion (p < 0.001) and the clinical presentation (p = 0.002).Open exploration and repair was the most common form of management, however percutaneous endovascular intervention was used in one third of the injuries and more constantly during the last 13 years.The main overall reported complications included death (n = 9, 7.3%), amputation (n = 2, 1.6%), and persistent ischaemia (n = 9, 7.3%). When compared with previous reviews there was a similar rate of mortality but lower rates of amputation and permanent disability, especially in patients managed by endovascular strategies.Cite this article: Bone Joint J 2015;97-B:1447–55.
Delayed diagnosis of developmental dysplasia of the hip in Northern Ireland
Authors: Donnelly K. J. , Chan K. W. , Cosgrove A. P. 
Published: November 2015

Developmental dysplasia of the hip (DDH) should be diagnosed as early as possible to optimise treatment. The current United Kingdom recommendations for the selective screening of DDH include a clinical examination at birth and at six weeks. In Northern Ireland babies continue to have an assessment by a health visitor at four months of age. As we continue to see late presentations of DDH, beyond one year of age, we hypothesised that a proportion had missed an opportunity for earlier diagnosis. We expect those who presented to our service with Tonnis grade III or IV hips and decreased abduction would have had clinical signs at their earlier assessments. We performed a retrospective review of all patients born in Northern Ireland between 2008 and 2010 who were diagnosed with DDH after their first birthday. There were 75 856 live births during the study period of whom 645 children were treated for DDH (8.5 per 1000). The minimum follow-up of our cohort from birth, to detect late presentation, was four years and six months. Of these, 32 children (33 hips) were diagnosed after their first birthday (0.42 per 1000). With optimum application of our selective screening programme 21 (65.6%) of these children had the potential for an earlier diagnosis, which would have reduced the incidence of late diagnosis to 0.14 per 1000. As we saw a peak in diagnosis between three and five months our findings support the continuation of the four month health visitor check. Our study adds further information to the debate regarding selective versus universal screening. Cite this article: Bone Joint J 2015;97-B:1572–6.
Comparison of simple arm sling and figure of eight clavicular bandage for midshaft clavicular fractures
Authors: Ersen A. , Atalar A. C. , Birisik F. , Saglam Y. , Demirhan M. 
Published: November 2015

Only a few randomised, controlled studies have compared different non-operative methods of treatment of mid-shaft fractures of the clavicle.In this prospective, randomised controlled study of 60 participants (mean age 31.6 years; 15 to 75) we compared the broad arm sling with the figure of eight bandage for the treatment of mid-shaft clavicle fractures. Our outcome measures were pain, Constant and American Shoulder and Elbow Surgeons scores and radiological union.The mean visual analogue scale (VAS) pain score on the first day after treatment was significantly higher (VAS 1 6.8; 4 to 9) in the figure of eight bandage group than the broad arm sling group (VAS 1 5.6; 3 to 8, p = 0.034). A mean shortening of 9 mm (3 to 17) was measured in the figure of eight bandage group, versus 7.5 mm (0 to 24) in the broad arm sling group (p = 0.30).The application of the figure of eight bandage is more difficult than of the broad arm sling, and patients experience more pain during the first day when treated with this option. We suggest the broad arm sling is preferable because of the reduction of early pain and ease of application.Cite this article: Bone Joint J 2015;97-B:1562–5.
The cement spacer with multiple indentations
Authors: Salih S. , Paskins A. , Nichol T. , Smith T. , Hamer A. 
Published: November 2015

We investigated whether the indentation of bone cement spacers used in revision of infected joint arthroplasty with a MacDonald dissector increased the elution of antibiotic in vitro. A total of 24 cement discs containing either 0.17 g (0.88% w/w), 0.25 g (1.41% w/w), or 0.33 g (1.75% w/w) gentamicin of constant size were made. Of these, 12 were indented with the dissector. Each disc was immersed in ammonium acetate buffer in a sealed container, and fluid from each container was sampled at zero, one, three, six, 24, 48 and 72 hours and at one, and two weeks. The concentration of gentamicin in the fluid was analysed using high performance liquid chromatography mass spectrometry. The fluid sampled at 72 hours from the indented discs containing 0.17 g gentamicin (0.88% w/w) contained a mean of 113 mcg/ml (90.12 to 143.5) compared with 44.5 mcg/ml (44.02 to 44.90) in the fluid sampled from the plain discs (p = 0.012). In discs containing 0.33 g gentamicin (1.75% w/w), the concentration eluted from the indented discs at 72 hours was a mean of 316 mcg/ml (223 to 421) compared with a mean of 118 mcg/ml (100 to 140) from the plain discs (p < 0.001). At two weeks, these significant differences persisted. At nine weeks the indented discs eluted a greater concentration for all gentamicin doses, but the difference was only significant for the discs containing 0.17 g (0.88% w/w, p = 0.006). However if the area under the curve is taken as a measure of the total antibiotic eluted, the indented discs eluted more gentamicin than the plain discs for the 0.17 g (0.88% w/w, p = 0.031), the 0.25 g (1.41% w/w, p < 0.001) and the 0.33 g (1.75% w/w, p < 0.001) discs. When preparing antibiotic spacers for use in staged revision arthroplasty surgery we recommend indenting the spacer with a MacDonald dissector to increase the elution of antibiotic. Cite this article: Bone Joint J 2015;97-B:1519–24.
Communicating Forest Sector Sustainability: Results from Four European Countries
Authors: Korhonen Elina , Toppinen Anne , Lähtinen Katja , Ranacher Lea , Werner Andrea , Stern Tobias , Kutnar Andreja 
Published: November 2015

Abstract
Communication is an important tool in maintaining legitimacy and acceptability of forest sector operations and activities, and expectations by the general public on the forest sector conduct in Europe are in general very high. Despite this, there is scarce research in cross-national contexts on how forest sector sustainability is communicated to the general public and what development areas can be identified in terms of communication content. This study applies a qualitative content analysis in four forestry-rich European countries (Austria, Finland, Germany, and Slovenia). The state of online communication of 61 companies and 19 industry associations was qualitatively analyzed in 2014 with a focus on eight core sustainability topics of interest that were identified via an international forest sector stakeholder feedback process. Our results show some great similarities, but also some interesting differences in terms of communication frequency and weight of hot topics across countries. The most frequently communicated area was economic contribution of forests (in Finland and Austria), followed by debate over forest conservation versus production (Germany) and the concept-added value of wood (in Slovenia). With the exception of Slovenia, the role of forests in combating global warming was emphasized more frequently within industry associations than among individual forest industry companies. Characteristically, current content of sustainability communication focuses on supplying factual information. Thus, there is a need for developing more targeted and bidirectional forms of stakeholder communication in the future, emphasizing also more active use of social media channels and empowering organizations to promote interactive communication and collaborative learning.
ELECTRODYNAMIC LOUDSPEAKER-DRIVEN ACOUSTIC COMPRESSOR
Authors: Šoltés Martin , Červenka Milan 
Published: November 2015

<p>An acoustic compressor is built using the acoustic resonator which shape was optimized for a maximum acoustic pressure amplitude and a low-cost compression driver. Acoustic compressor is built by installing a suction port in the resonator wall where the standing wave has its pressure node and a delivery port with a valve in the resonator wall where the standing wave has its pressure anti-node. Different reeds, serving as delivery valves, are tested and their performance is investigated. It was shown that the performance of such simple compressor is comparable, or better, than the acoustic compressors built previously by other researchers using non-optimally shaped resonators with more sophisticated driving mechanisms and valve arrangements.</p>
The Innovative Use of Biblical Traditions for Ritual Power: The Crucifixion of Jesus on a Coptic Exorcistic Spell (Brit. Lib. Or. 6796[4], 6796) as a Test Case
Authors: Sanzo Joseph E. 
Published: November 2015

Abstract In this paper, I explore the creative use of biblical traditions in so-called “magical” texts through a detailed analysis of the crucifixion tradition on Brit. Lib. Or. 6796(4), 6796, a seventh-century CE spell for exorcism. I examine three overlapping ways in which the practitioner interacts with the crucifixion story: selection and arrangement of pre-existing traditions; invention of new elements of the story; and the juxtaposition of word and image. I then reflect on the implications of the crucifixion tradition in this spell for analyzing the relationship between biblical traditions and metonymy in “magical” texts, more generally.