bluuebunny/crossref_metadata_2025_split huggingface dataset:
National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene trial: Advancing the science of recruitment and breast cancer risk assessment in minority communities
Authors: McCaskill-Stevens Worta , Wilson John W , Cook Elise D , Edwards Cora L , Gibson Regina V , McElwain Diane L , Figueroa-Moseley Colmar D , Paskett Electra D , Roberson Noma L , Wickerham D Lawrence , Wolmark Norman 
Published: January 2013

Background One of the first chemoprevention trials conducted in the western hemisphere, the National Surgical Adjuvant Breast and Bowel Project’s (NSABP) Breast Cancer Prevention Trial (BCPT), demonstrated the need to evaluate all aspects of recruitment in real time and to implement strategies to enroll racial and ethnic minority women. Purpose The purpose of this report is to review various patient recruitment efforts the NSABP developed to enhance the participation of racial and ethnic minority women in the Study of Tamoxifen and Raloxifene (STAR) trial and to describe the role that the recruitment process played in the implementation and understanding of breast cancer risk assessment in minority communities. Methods The NSABP STAR trial was a randomized, double-blinded study comparing the use of tamoxifen 20 mg/day to raloxifene 60 mg/day, for a 5-year period, to reduce the risk of developing invasive breast cancer. Eligible postmenopausal women were required to have a 5-year predicted breast cancer risk of 1.66% based on the modified Gail Model. For the current report, eligibility and enrollment data were tabulated by race/ethnicity for women who submitted STAR risk assessment forms (RAFs). Results A total of 184,460 RAFs were received, 145,550 (78.9%) from white women and 38,910 (21.1%) from minority women. Of the latter group, 21,444 (11.6%) were from African Americans/blacks, 7913 (4.5%) from Hispanics/Latinas, and 9553 (5.2%) from other racial or ethnic groups. The percentages of risk-eligible women among African Americans, Hispanics/Latinas, others, and whites were 14.2%, 23.3%, 13.7%, and 57.4%, respectively. Programs targeting minority enrollment submitted large numbers of RAFs, but the eligibility rates of the women referred from those groups tended to be lower than the rates among women referred outside of those programs. The average number of completed risk assessments increased among minority women over the course of the recruitment period compared to those from whites. Limitations We have not addressed all identified barriers to the recruitment of minorities in clinical research. Our risk assessments and recruitment results do not reflect the modified Gail Model for African Americans. Conclusions Recruitment strategies used in STAR for racial and ethnic minorities contributed to doubling the minority enrollment compared to that in the BCPT and increased the awareness of breast cancer risk assessment in minority communities. Incorporation of new information into models to improve the risk estimation of diverse populations should prove beneficial.
A novel B-domain O-glycoPEGylated FVIII (N8-GP) demonstrates full efficacy and prolonged effect in hemophilic mice models
Authors: Stennicke Henning R. , Kjalke Marianne , Karpf Ditte M. , Balling Kristoffer W. , Johansen Peter B. , Elm Torben , Øvlisen Kristine , Möller Flemming , Holmberg Heidi L. , Gudme Charlotte N. , Persson Egon , Hilden Ida , Pelzer Hermann , Rahbek-Nielsen Henrik , Jespersgaard Christina , Bogsnes Are , Pedersen Anette A. , Kristensen Anne K. , Peschke Bernd , Kappers Wendy , Rode Frederik , Thim Lars , Tranholm Mikael , Ezban Mirella , Olsen Eva H. N. , Bjørn Søren E. 
Published: January 2013

Key PointsGlycoPEGylated FVIII (N8-GP) demonstrates the same efficacy and prolonged effect in animal models as native FVIII. Circulatory half-life of glycoPEGylated FVIII (N8-GP) is prolonged by approximately twofold in several species.
MYC status in concert with BCL2 and BCL6 expression predicts outcome in diffuse large B-cell lymphoma
Authors: Horn Heike , Ziepert Marita , Becher Claudia , Barth Thomas F. E. , Bernd Heinz-Wolfram , Feller Alfred C. , Klapper Wolfram , Hummel Michael , Stein Harald , Hansmann Martin-Leo , Schmelter Christopher , Möller Peter , Cogliatti Sergio , Pfreundschuh Michael , Schmitz Norbert , Trümper Lorenz , Siebert Reiner , Loeffler Markus , Rosenwald Andreas , Ott German 
Published: January 2013

Key PointsOutcome prediction in DLBCL. MYC status in concert with BCL2 and BCL6.
Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency
Authors: Drewniak Agata , Gazendam Roel P. , Tool Anton T. J. , van Houdt Michel , Jansen Machiel H. , van Hamme John L. , van Leeuwen Ester M. M. , Roos Dirk , Scalais Emmanuel , de Beaufort Carine , Janssen Hans , van den Berg Timo K. , Kuijpers Taco W. 
Published: January 2013

Key Points
Human CARD9 deficiency is characterized by a selective neutrophil killing defect, resulting in invasive candidiasis.
Ikaros inhibits megakaryopoiesis through functional interaction with GATA-1 and NOTCH signaling
Authors: Malinge Sébastien , Thiollier Clarisse , Chlon Timothy M. , Doré Louis C. , Diebold Lauren , Bluteau Olivier , Mabialah Vinciane , Vainchenker William , Dessen Philippe , Winandy Susan , Mercher Thomas , Crispino John D. 
Published: January 2013

Key PointsIkaros inhibits megakaryocyte specification and terminal differentiation by suppressing key megakaryocyte genes. The GATA switch inhibits Ikaros expression during megakaryocyte development.
Mutations in the A3 domain of Von Willebrand factor inducing combined qualitative and quantitative defects in the protein
Authors: Legendre Paulette , Navarrete Ana-Maria , Rayes Julie , Casari Caterina , Boisseau Pierre , Ternisien Catherine , Caron Claudine , Fressinaud Edith , Goudemand Jenny , Veyradier Agnès , Denis Cécile V. , Lenting Peter J. , Christophe Olivier D. 
Published: January 2013

Key PointsVWF A3 domain mutations inducing defective collagen binding and impaired protein production.
Platelet activation and inhibition in polycythemia vera and essential thrombocythemia
Authors: Patrono Carlo , Rocca Bianca , De Stefano Valerio 
Published: January 2013

Abstract
Persistently enhanced platelet activation has been characterized in polycythemia vera (PV) and essential thrombocythemia (ET) and shown to contribute to a higher risk of both arterial and venous thrombotic complications. The incidence of major bleeding complications is also somewhat higher in PV and ET than in the general population. Although its efficacy and safety was assessed in just 1 relatively small trial in PV, low-dose aspirin is currently recommended in practically all PV and ET patients. Although for most patients with a thrombosis history the benefit/risk profile of antiplatelet therapy is likely to be favorable, in those with no such history this balance will depend critically on the level of thrombotic and hemorrhagic risks of the individual patient. Recent evidence for a chemopreventive effect of low-dose aspirin may tilt the balance of benefits and harm in favor of using aspirin more broadly, but the potential for additional benefits needs regulatory scrutiny and novel treatment guidelines. A clear pharmacodynamic rationale and analytical tools are available for a personalized approach to antiplatelet therapy in ET, and an improved regimen of low-dose aspirin therapy should be tested in a properly sized randomized trial.
Non-parsimonious evolution of hagfish Dlx genes
Authors: Fujimoto Satoko , Oisi Yasuhiro , Kuraku Shigehiro , Ota Kinya G , Kuratani Shigeru 
Published: January 2013

AbstractBackgroundThe number of members of theDlxgene family increased during the two rounds of whole-genome duplication that occurred in the common ancestor of the vertebrates. Because theDlxgenes are involved in the development of the cranial skeleton, brain, and sensory organs, their expression patterns have been analysed in various organisms in the context of evolutionary developmental biology. SixDlxgenes have been isolated in the lampreys, a group of living jawless vertebrates (cyclostomes), and their expression patterns analysed. However, little is known about theDlxgenes in the hagfish, the other cyclostome group, mainly because the embryological analysis of this animal is difficult.ResultsTo identify the hagfishDlxgenes and describe their expression patterns, we cloned the cDNA from embryos of the Japanese inshore hagfishEptatretus burgeri. Our results show that the hagfish has at least sixDlxgenes and one pseudogene. In a phylogenetic analysis, the hagfishDlxgenes and those of the lampreys tended to be excluded from the clade of the gnathostomeDlxgenes. In several cases, the lampreyDlxgenes clustered with the clade consisting of two hagfish genes, suggesting that independent gene duplications have occurred in the hagfish lineage. Analysis of the expression of these genes showed distinctive overlapping expression patterns in the cranial mesenchymal cells and the inner ear.ConclusionsIndependent duplication, pseudogenization, and loss of theDlxgenes probably occurred in the hagfish lineage after its split from the other vertebrate lineages. This pattern is reminiscent of the non-parsimonious evolution of its morphological traits, including its inner ear and vertebrae, which indicate that this group is an early-branching lineage that diverged before those characters evolved.
Late HIV diagnosis is a major risk factor for intensive care unit admission in HIV-positive patients: a single centre observational cohort study
Authors: Shrosbree Julia , Campbell Lucy J , Ibrahim Fowzia , Hopkins Phillip , Vizcaychipi Marcela , Strachan Stephanie , Post Frank A 
Published: January 2013

Abstract

Background
HIV positive patients are at risk of infectious and non-infectious complications that may necessitate intensive care unit (ICU) admission. While the characteristics of patients requiring ICU admission have been described previously, these studies did not include information on the denominator population from which these cases arose.

Methods
We conducted an observational cohort study of ICU admissions among 2751 HIV positive patients attending King’s College Hospital, South London, UK. Poisson regression models were used to identify factors associated with ICU admission.

Results
The overall incidence rate of ICU admission was 1.0 [95% CI 0.8, 1.2] per 100 person-years of follow up, and particularly high early (during the first 3 months) following HIV diagnosis (12.4 [8.7, 17.3] per 100 person-years compared to 0.37 [0.27, 0.50] per 100 person-years thereafter; incidence rate ratio 33.5 [23.4, 48.1], p < 0.001). In time-updated analyses, AIDS and current CD4 cell counts of less than 200 cells/mm3 were associated with an increased incidence of ICU admission while receipt of combination antiretroviral therapy (cART) was associated with a reduced incidence of ICU admission. Late HIV diagnosis (initial CD4 cell count <350 or AIDS within 3 months of HIV diagnosis) applied to 81% of patients who were first diagnosed HIV positive during the study period and who required ICU admission. Late HIV diagnosis was significantly associated with ICU admission in the first 3 months following HIV diagnosis (adjusted incidence rate ratio 8.72, 95% CI 2.76, 27.5).

Conclusions
Late HIV diagnosis was a major risk factor for early ICU admission in our cohort. Earlier HIV diagnosis allowing cART initiation at CD4 cell counts of 350 cells/mm3 is likely to have a significant impact on the need for ICU care.
Early application of pulsed electromagnetic field in the treatment of postoperative delayed union of long-bone fractures: a prospective randomized controlled study
Authors: Shi Hong-fei , Xiong Jin , Chen Yi-xin , Wang Jun-fei , Qiu Xu-sheng , Wang Yin-he , Qiu Yong 
Published: January 2013

AbstractBackgroundPulsed electromagnetic field (PEMF) is reported to be an effective adjunct for the management of nonunion long-bone fractures. Most studies implement PEMF treatment after 6 months or longer of delayed union or nonunion following fracture treatment. Despite these variations in treatment, the early application of PEMF following a diagnosis of a postoperative delayed union has not been specifically analyzed. In this study, the outcomes of postoperative delayed union of long-bone fractures treated with an early application of PEMF were evaluated as compared with a sham-treated control group.MethodsIn this prospective, randomized controlled study, a total of 58 long-bone fracture patients, who presented with delayed union of between 16 weeks and 6 months, were randomly split into two groups and subjected to an early application of PEMF or sham treatment. Clinical and radiological assessments were performed to evaluate the healing status. Treatment efficacy was assessed at three month intervals.ResultsPatients in the PEMF group showed a higher rate of union than those in the control group after the first three months of treatment, but this difference failed to achieve statistical significance. At the end of the study, PEMF treatment conducted for an average of 4.8 months led to a success rate of 77.4%. This was significantly higher than the control, which had an average duration of 4.4 months and a success rate of 48.1%. The total time from operation to the end of the study was a mean of 9.6 months for patients in the PEMF group.ConclusionsFracture patients treated with an early application of PEMF achieved a significantly increased rate of union and an overall reduced suffering time compared with patients that receive PEMF after the 6 months or more of delayed union, as described by others.
Effects of microcurrent stimulation on Hyaline cartilage repair in immature male rats (Rattus norvegicus)
Authors: de Campos Ciccone Carla , Zuzzi Denise Cristina , Neves Lia Mara Grosso , Mendonça Josué Sampaio , Joazeiro Paulo Pinto , Esquisatto Marcelo Augusto Marretto 
Published: January 2013

AbstractBackgroundIn this study, we investigate the effects of microcurrent stimulation on the repair process of xiphoid cartilage in 45-days-old rats.MethodsTwenty male rats were divided into a control group and a treated group. A 3-mm defect was then created with a punch in anesthetized animals. In the treated group, animals were submitted to daily applications of a biphasic square pulse microgalvanic continuous electrical current during 5 min. In each application, it was used a frequency of 0.3 Hz and intensity of 20 μA. The animals were sacrificed at 7, 21 and 35 days after injury for structural analysis.ResultsBasophilia increased gradually in control animals during the experimental period. In treated animals, newly formed cartilage was observed on days 21 and 35. No statistically significant differences in birefringent collagen fibers were seen between groups at any of the time points. Treated animals presented a statistically larger number of chondroblasts. Calcification points were observed in treated animals on day 35. Ultrastructural analysis revealed differences in cell and matrix characteristics between the two groups. Chondrocyte-like cells were seen in control animals only after 35 days, whereas they were present in treated animals as early as by day 21. The number of cuprolinic blue-stained proteoglycans was statistically higher in treated animals on days 21 and 35.ConclusionWe conclude that microcurrent stimulation accelerates the cartilage repair in non-articular site from prepuberal animals.
Predictive factors affecting cecal intubation failure in colonoscopy trainees
Authors: Park Hong-Jun , Hong Jin-Heon , Kim Hyun-Soo , Kim Bo-Ra , Park So-Yeon , Jo Ki-Won , Kim Jae-Woo 
Published: January 2013

Abstract

Background
Successful cecal intubation (SCI) is not only a quality indicator but also an important marker in a colonoscopy trainee’s progress. We conducted this study to determine factors predicting SCI in colonoscopy trainees, and to compare these factors before and after trainees achieve technical competence.

Methods
Design of this study was a cross-sectional studies of two time series design for one year at a single center. From March 2011 to February 2012, a total 2,050 subjects who underwent colonoscopy by four first-year gastrointestinal fellows were enrolled at Christian hospital, Wonju, Republic of Korea. Four gastrointestinal fellows have filled out the colonoscopic documentation. Main outcome measurement was predictive factors affecting cecal intubation failure and learning curves.

Results
Colonoscopy was successfully completed to the cecum in 1,720 patients (83.9%). Success rates gradually increased as trainees performed more colonoscopies: the rate of SCI was 62% in the first 50 cases, and grew to 93% by the 250th case. Logistic regression analysis of factors affecting cecal intubation failure showed that female gender, low BMI (BMI < 18.5 kg/m2), poor bowel preparation, and past history of stomach surgery were more often associated with cecal intubation failure, particularly before the trainees achieved technical competence.

Conclusion
Several patient characteristics were identified that may predict difficulty of cecal intubation in colonoscopy trainees. Particularly, low BMI, inadequate bowel cleansing, and previous stomach operation were predictors of cecal intubation failure before the trainees have reached technical competency. The results could be informative so that trainees enhance the success rate regarding better colonoscopy training programs.
Cryo-electron tomography reveals four-membrane architecture of the Plasmodium apicoplast
Authors: Lemgruber Leandro , Kudryashev Mikhail , Dekiwadia Chaitali , Riglar David T , Baum Jake , Stahlberg Henning , Ralph Stuart A , Frischknecht Friedrich 
Published: January 2013

AbstractBackgroundThe apicoplast is a plastid organelle derived from a secondary endosymbiosis, containing biosynthetic pathways essential for the survival of apicomplexan parasites. TheToxoplasmaapicoplast clearly possesses four membranes but in relatedPlasmodiumspp. the apicoplast has variably been reported to have either three or four membranes.MethodsCryo-electron tomography was employed to image merozoites ofPlasmodium falciparumandPlasmodium bergheifrozen in their near-native state. Three-dimensional reconstructions revealed the number of apicoplast membranes and the association of the apicoplast with other organelles. Routine transmission electron microscopy of parasites preserved by high-pressure freezing followed by freeze substitution techniques was also used to analyse apicoplast morphology.ResultsCryo-preserved parasites showed clearly four membranes surrounding the apicoplast. A wider gap between the second and third apicoplast membranes was frequently observed. The apicoplast was found in close proximity to the nucleus and to the rhoptries. The apicoplast matrix showed ribosome-sized particles and membranous whorls.ConclusionsThePlasmodiumapicoplast possesses four membranes, as do the apicoplasts of other apicomplexan parasites. This is consistent with a four-membraned secondary endosymbiotic plastid ancestor.
ARTD10 substrate identification on protein microarrays: regulation of GSK3β by mono-ADP-ribosylation
Authors: Feijs Karla LH , Kleine Henning , Braczynski Anne , Forst Alexandra H , Herzog Nicolas , Verheugd Patricia , Linzen Ulrike , Kremmer Elisabeth , Lüscher Bernhard 
Published: January 2013

Abstract

Background
Although ADP-ribosylation has been described five decades ago, only recently a distinction has been made between eukaryotic intracellular poly- and mono-ADP-ribosylating enzymes. Poly-ADP-ribosylation by ARTD1 (formerly PARP1) is best known for its role in DNA damage repair. Other polymer forming enzymes are ARTD2 (formerly PARP2), ARTD3 (formerly PARP3) and ARTD5/6 (formerly Tankyrase 1/2), the latter being involved in Wnt signaling and regulation of 3BP2. Thus several different functions of poly-ADP-ribosylation have been well described whereas intracellular mono-ADP-ribosylation is currently largely undefined. It is for example not known which proteins function as substrate for the different mono-ARTDs. This is partially due to lack of suitable reagents to study mono-ADP-ribosylation, which limits the current understanding of this post-translational modification.

Results
We have optimized a novel screening method employing protein microarrays, ProtoArrays®, applied here for the identification of substrates of ARTD10 (formerly PARP10) and ARTD8 (formerly PARP14). The results of this substrate screen were validated using in vitro ADP-ribosylation assays with recombinant proteins. Further analysis of the novel ARTD10 substrate GSK3β revealed mono-ADP-ribosylation as a regulatory mechanism of kinase activity by non-competitive inhibition in vitro. Additionally, manipulation of the ARTD10 levels in cells accordingly influenced GSK3β activity. Together these data provide the first evidence for a role of endogenous mono-ADP-ribosylation in intracellular signaling.

Conclusions
Our findings indicate that substrates of ADP-ribosyltransferases can be identified using protein microarrays. The discovered substrates of ARTD10 and ARTD8 provide the first sets of proteins that are modified by mono-ADP-ribosyltransferases in vitro. By studying one of the ARTD10 substrates more closely, the kinase GSK3β, we identified mono-ADP-ribosylation as a negative regulator of kinase activity.
Relationship between parent and child pedometer-determined physical activity: a sub-study of the CANPLAY surveillance study
Authors: Craig Cora L , Cameron Christine , Tudor-Locke Catrine 
Published: January 2013

Abstract

Background
Understanding parental influences on their children’s physical activity (PA) provides insight into developing effective family-based interventions. This study examines whether children’s objectively monitored PA is associated with that of their parents.

Methods
Participants (children and parents) were recruited to a sub-study of the Canadian Fitness and Lifestyle Research Institute’s annual Canadian Physical Activity Levels among Youth (CANPLAY) surveillance study. In total, 539 of 1,187 eligible children (age range 5–19 years) and at least one of their parents participated. Participants logged pedometer steps for 7 days. Descriptive statistics were used to examine parental mean daily steps by their children’s age, sex and steps/day. Associations between steps/day for parents and children (controlling for their age and sex) were estimated using general linear and logistic regression.

Results
Children’s mean steps/day did not differ by parents’ age or sex, nor by whether one or both parents participated in the study. There were quantifiable relationships between parents’ and children’s steps/day. For every 1,000 step increase in a father’s steps/day, his son’s increased by 329–407 steps/day and his daughter’s increased by 273 steps/day (adjusted model only). Every 1,000 step increase in a mother’s steps/day was associated with 263–439 extra steps/day for her son’s steps/day and 195–219 steps/day for her daughter. A 3,000 step increment in a father’s or mother’s steps/day was associated with 1.9-2.5 fold increase in the odds that their child’s activity level would be in the upper two tertiles of steps/day.

Conclusions
These cross-sectional data indicate that children’s PA is related to that of their parents in distinct and quantifiable ways. Interventions are warranted to evaluate the direction of this relationship, confirm the magnitude of influence, and illuminate mediating and moderating mechanisms by which both parents may have influence over their own children’s PA.