bluuebunny/crossref_metadata_2025_split huggingface dataset:
High tandem repeat content in the genome of the short-lived annual fish Nothobranchius furzeri: a new vertebrate model for aging research
Authors: Reichwald Kathrin , Lauber Chris , Nanda Indrajit , Kirschner Jeanette , Hartmann Nils , Schories Susanne , Gausmann Ulrike , Taudien Stefan , Schilhabel Markus B , Szafranski Karol , Glöckner Gernot , Schmid Michael , Cellerino Alessandro , Schartl Manfred , Englert Christoph , Platzer Matthias 
Published: March 2009

Abstract
Background
The annual fish Nothobranchius furzeri is the vertebrate with the shortest known life span in captivity. Fish of the GRZ strain live only three to four months under optimal laboratory conditions, show explosive growth, early sexual maturation and age-dependent physiological and behavioral decline, and express aging related biomarkers. Treatment with resveratrol and low temperature significantly extends the maximum life span. These features make N. furzeri a promising new vertebrate model for age research.

Results
To contribute to establishing N. furzeri as a new model organism, we provide a first insight into its genome and a comparison to medaka, stickleback, tetraodon and zebrafish. The N. furzeri genome contains 19 chromosomes (2n = 38). Its genome of between 1.6 and 1.9 Gb is the largest among the analyzed fish species and has, at 45%, the highest repeat content. Remarkably, tandem repeats comprise 21%, which is 4-12 times more than in the other four fish species. In addition, G+C-rich tandem repeats preferentially localize to centromeric regions. Phylogenetic analysis based on coding sequences identifies medaka as the closest relative. Genotyping of an initial set of 27 markers and multi-locus fingerprinting of one microsatellite provides the first molecular evidence that the GRZ strain is highly inbred.

Conclusions
Our work presents a first basis for systematic genomic and genetic analyses aimed at understanding the mechanisms of life span determination in N. furzeri.
Cancer Patient Assessment and Reports of Excellence: Reliability and Validity of Advanced Cancer Patient Perceptions of the Quality of Care
Authors: Teno Joan M. , Lima Julie C. , Lyons Kathleen Doyle 
Published: March 2009

Purpose Consumer perceptions are important measures of the quality of cancer care. This article describes the validation of new measures of the quality of cancer care at the time of diagnosis and treatment for advanced cancer with life-limiting prognosis. Methods Focus groups, review of guidelines, and an expert panel were used to construct two surveys of the quality of cancer care. A prospective cohort study examined the reliability and validity of three problem scores (ie, counts of the opportunities to improve the quality of care) that examine care at the time of diagnosis and initial treatment. Results At the first interview, 58% of 206 cancer patients (54.9% females; 27.5% with lung cancer; 5.4% with pancreatic cancer; 30.4% with colorectal cancer; 18.6% with breast cancer; mean age, 66.6 years) identified one or more concerns with communication about being diagnosed with advanced cancer. At the second interview, 57.0% of the respondents voiced one or more concerns about treatment communication, and 30.2% expressed one or more concerns about the experience of treatment. Each of the problem scores demonstrated both internal consistency with Cronbach's α > .75 and short-term stability of responses in a subsample that had the survey administered twice in 72 hours. Factor analysis largely confirmed the proposed scale structure. All three measures demonstrated moderate correlations suggesting evidence of construct validity. Conclusion The three proposed problem scores demonstrate evidence of reliability and validity that warrants further testing to examine their responsiveness and discriminate validity in larger, more generalizable samples.
Hematologic Response to Three Alternative Dosing Schedules of Azacitidine in Patients With Myelodysplastic Syndromes
Authors: Lyons Roger M. , Cosgriff Thomas M. , Modi Sanjiv S. , Gersh Robert H. , Hainsworth John D. , Cohn Allen L. , McIntyre Heidi J. , Fernando Indra J. , Backstrom Jay T. , Beach C.L. 
Published: March 2009

Purpose Azacitidine (AZA) is effective treatment for myelodysplastic syndromes (MDS) at a dosing schedule of 75 mg/m2/d subcutaneously for 7 days every 4 weeks. The initial phase of this ongoing multicenter, community-based, open-label study evaluated three alternative AZA dosing schedules without weekend dosing. Patients and Methods MDS patients were randomly assigned to one of three regimens every 4 weeks for six cycles: AZA 5-2-2 (75 mg/m2/d subcutaneously for 5 days, followed by 2 days no treatment, then 75 mg/m2/d for 2 days); AZA 5-2-5 (50 mg/m2/d subcutaneously for 5 days, followed by 2 days no treatment, then 50 mg/m2/d for 5 days); or AZA 5 (75 mg/m2/d subcutaneously for 5 days). Results Of patients randomly assigned to AZA 5-2-2 (n = 50), AZA 5-2-5 (n = 51), or AZA 5 (n = 50), most were French-American-British (FAB) lower risk (refractory anemia [RA]/RA with ringed sideroblasts/chronic myelomonocytic leukemia with < 5% bone marrow blasts, 63%) or RA with excess blasts (30%), and 79 (52%) completed ≥ six treatment cycles. Hematologic improvement (HI) was achieved by 44% (22 of 50), 45% (23 of 51), and 56% (28 of 50) of AZA 5-2-2, AZA 5-2-5, and AZA 5 arms, respectively. Proportions of RBC transfusion–dependent patients who achieved transfusion independence were 50% (12 of 24), 55% (12 of 22), and 64% (16 of 25), and of FAB lower-risk transfusion-dependent patients were 53% (nine of 17), 50% (six of 12), and 61% (11 of 18), respectively. In the AZA 5-2-2, AZA 5-2-5, and AZA 5 groups, 84%, 77%, and 58%, respectively, experienced ≥ 1 grade 3 to 4 adverse events. Conclusion All three alternative dosing regimens produced HI, RBC transfusion independence, and safety responses consistent with the currently approved AZA regimen. These results support AZA benefits in transfusion-dependent lower-risk MDS patients.
Prospective Evaluation of Whole-Body Cancer Screening With Multiple Modalities Including [18F]Fluorodeoxyglucose Positron Emission Tomography in a Healthy Population: A Preliminary Report
Authors: Nishizawa Sadahiko , Kojima Shinsuke , Teramukai Satoshi , Inubushi Masayuki , Kodama Hironobu , Maeda Yoshiki , Okada Hiroyuki , Zhou Bin , Nagai Yoji , Fukushima Masanori 
Published: March 2009

Purpose To prospectively evaluate the utility of whole-body cancer screening with multiple modalities including [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) in a healthy population. This report summarizes the results of the first three annual screenings. Participants and Methods A total of 1,197 healthy volunteers ≥ 35 years old were enrolled between August 2003 and July 2004 and offered annual cancer screening for 5 years with subsequent long-term follow-up. Screening modalities included were whole-body FDG-PET, chest and abdominal computed tomography (CT), brain and pelvic magnetic resonance imaging, several tumor markers, and fecal occult blood testing. Results As of the end of 2006, 22 primary cancers were pathologically confirmed. Nineteen of 22 were detected by the screening; 18 in the initial, one in the second, and none in the third. Three were diagnosed after development of symptoms. Of the 18 detected in the initial screening (six thyroid, four lung, three prostate, three breast, one endometrial, and one thymic), 12 were at stage I and 11 were PET positive. PET-negative cancers were detected by CT or the prostate-specific antigen (PSA) test. Sensitivity and specificity were 50.0% (11 of 22) and 93.2% (1,095 of 1,175), respectively, for FDG-PET alone and 81.8% (18 of 22) and 82.0% (963 of 1,175), respectively, for the combination of imaging modalities and PSA. Conclusion While FDG-PET alone is insufficient, whole-body cancer screening with selected modalities including FDG-PET has initial performance supporting possible utility by detecting a wide variety of early-stage cancers with reasonable sensitivity. However, the detection of many indolent cancers and false positives necessitate continuing study for appropriate evaluation.
Relationship Over Time Between Psychological Distress and Physical Activity in Colorectal Cancer Survivors
Authors: Chambers Suzanne K. , Lynch Brigid M. , Aitken Joanne , Baade Peter 
Published: March 2009

Purpose Increased physical activity in patients with colorectal cancer is related to improved recurrence-free and overall survival. Psychological distress after cancer may place patients at risk of reduced physical activity, but paradoxically may also act as a motivator for lifestyle change. The relationship between psychological distress and physical activity after cancer over time has not been described. Methods A prospective survey of 1,966 (57% response) colorectal cancer survivors assessed the psychological distress variables of anxiety, depression, somatization, and cancer threat appraisal as predictors of physical activity at 5, 12, 24, and 36 months postdiagnosis; 978 respondents had valid data for all time points. Results Higher somatization was associated with greater physical inactivity (relative risk ratio [RRR] = 1.12; 95% CI, 1.1 to 1.2) and insufficient physical activity (RRR = 1.05; 95% CI, 0.90 to 1.0). Respondents with a more positive appraisal of their cancer were significantly (P = .031) less likely to be inactive (RRR = 0.95; 95% CI, 0.90 to 1.0) or insufficiently active (RRR = 0.96). Fatigued and obese respondents and current smokers were more inactive. Respondents whose somatization increased between two time periods were less likely to increase their physical activity over the same period (P < .001). Respondents with higher anxiety at one time period were less likely to have increased their activity at the next assessment (P = .004). There was no association between depression and physical activity. Conclusion Cancer survivors who experience somatization and anxiety are at greater risk of physical inactivity. The lack of a clear relationship between higher psychological distress and increasing physical activity argues against distress as a motivator to exercise in these patients.
Steps and Time to Process Clinical Trials at the Cancer Therapy Evaluation Program
Authors: Dilts David M. , Sandler Alan B. , Cheng Steven K. , Crites Joshua S. , Ferranti Lori B. , Wu Amy Y. , Finnigan Shanda , Friedman Steven , Mooney Margaret , Abrams Jeffrey 
Published: March 2009

Purpose To examine the processes and document the calendar time required for the National Cancer Institute's Cancer Therapy Evaluation Program (CTEP) and Central Institutional Review Board (CIRB) to evaluate and approve phase III clinical trials. Methods Process steps were documented by (1) interviewing CTEP and CIRB staff regarding the steps required to activate a trial from initial concept submission to trial activation by a cooperative group, (2) reviewing standard operating procedures, and (3) inspecting trial records and documents for selected trials to identify any additional steps. Calendar time was collected from initial concept submission to activation using retrospective data from the CTEP Protocol and Information Office. Results At least 296 distinct processes are required for phase III trial activation: at least 239 working steps, 52 major decision points, 20 processing loops, and 11 stopping points. Of the 195 trials activated during the January 1, 2000, to December 31, 2007, study period, a sample of 167 (85.6%) was used for gathering timing data. Median calendar days from initial formal concept submission to CTEP to trial activation by a cooperative group was 602 days (interquartile range, 454 to 861 days). This time has not significantly changed over the past 8 years. There is a high variation in the time required to activate a clinical trial. Conclusion Because of their complexity, the overall development time for phase III clinical trials is lengthy, process laden, and highly variable. To streamline the process, a solution must be sought that includes all parties involved in developing trials.
Phase I Study of Individualized Stereotactic Body Radiotherapy of Liver Metastases
Authors: Lee Mark T. , Kim John J. , Dinniwell Robert , Brierley James , Lockwood Gina , Wong Rebecca , Cummings Bernard , Ringash Jolie , Tse Regina V. , Knox Jennifer J. , Dawson Laura A. 
Published: March 2009

Purpose To report on the outcomes of a phase I study of stereotactic body radiotherapy (SBRT) for treatment of liver metastases. Patients and Methods Patients with liver metastases that were inoperable or medically unsuitable for resection, and who were not candidates for standard therapies, were eligible for this phase I study of individualized SBRT. Individualized radiation doses were chosen to maintain the same nominal risk of radiation-induced liver disease (RILD) for three estimated risk levels (5%, 10%, and 20%). Additional patients were treated at the maximal study dose (MSD) in an expanded cohort. Median SBRT dose was 41.8 Gy (range, 27.7 to 60 Gy) in six fractions over 2 weeks. Results Sixty-eight patients with inoperable colorectal (n = 40), breast (n = 12), or other (n = 16) liver metastases were treated. Median tumor volume was 75.2 mL (range, 1.19 to 3,090 mL). The highest RILD risk level investigated was safe, with no dose-limiting toxicity. Two grade 3 liver enzyme changes occurred, but no RILD or other grade 3 to 5 liver toxicity was seen, for a low estimated risk of serious liver toxicity (95% CI, 0 to 5.3%). Six (9%) acute grade 3 toxicities (two gastritis, two nausea, lethargy, and thrombocytopenia) and one (1%) grade 4 toxicity (thrombocytopenia) were seen. The 1-year local control rate was 71% (95 CI, 58% to 85%). The median overall survival was 17.6 months (95% CI, 10.4 to 38.1 months). Conclusion Individualized six-fraction liver metastases SBRT is safe, with sustained local control observed in the majority of patients.
Phase I and Pharmacokinetic Study of Sorafenib in Patients With Hepatic or Renal Dysfunction: CALGB 60301
Authors: Miller Antonius A. , Murry Daryl J. , Owzar Kouros , Hollis Donna R. , Kennedy Erin B. , Abou-Alfa Ghassan , Desai Apurva , Hwang Jimmy , Villalona-Calero Miguel A. , Dees E. Claire , Lewis Lionel D. , Fakih Marwan G. , Edelman Martin J. , Millard Fred , Frank Richard C. , Hohl Raymond J. , Ratain Mark J. 
Published: March 2009

Purpose We sought to characterize the pharmacokinetics (PK) and determine a tolerable dose of oral sorafenib in patients with hepatic or renal dysfunction. Patients and Methods Patients were assigned to one of nine cohorts: cohort 1, bilirubin ≤ upper limit of normal (ULN) and AST ≤ ULN and creatinine clearance (CC) ≥ 60 mL/min; cohort 2, bilirubin more than ULN but ≤ 1.5× ULN and/or AST more than ULN; cohort 3, CC between 40 and 59 mL/min; cohort 4, bilirubin more than 1.5× ULN to ≤ 3× ULN (any AST); cohort 5, CC between 20 and 39 mL/min; cohort 6, bilirubin more than 3× ULN to 10× ULN (any AST); cohort 7, CC less than 20 mL/min; cohort 8, albumin less than 2.5 mg/dL (any bilirubin/AST); and cohort 9, hemodialysis. Sorafenib was administered as a 400-mg dose on day 1 for PK, and continuous daily dosing started on day 8. Results Of 150 registered patients, 138 patients were treated. With the exception of cohorts 6 and 7, at least 12 patients per cohort were assessable, and the dose level with prospectively defined dose-limiting toxicity in less than one third of patients by day 29 was considered tolerable. No significant associations between the sorafenib PK and cohort were found. Conclusion We recommend the following empiric sorafenib starting doses by cohort: cohort 1, 400 mg twice a day; cohort 2, 400 mg twice a day; cohort 3, 400 mg twice a day; cohort 4, 200 mg twice a day; cohort 5, 200 mg twice a day; cohort 6, not even 200 mg every third day tolerable; cohort 7, not defined; cohort 8, 200 mg each day; and cohort 9, 200 mg each day.
Prophylaxis of deep-vein thrombosis in fractures below the knee
Authors: Goel D. P. , Buckley R. , deVries G. , Abelseth G. , Ni A. , Gray R. 
Published: March 2009

The incidence of deep-vein thrombosis and the need for thromboprophylaxis following isolated trauma below the knee is uncertain. We have investigated this with a prospective randomised double-blind controlled trial using low molecular weight heparin with saline injection as placebo in patients aged between 18 and 75 years who had sustained an isolated fracture below the knee which required operative fixation. All patients had surgery within 48 hours of injury and were randomised to receive either the placebo or low molecular weight heparin for 14 days, after which they underwent bilateral lower limb venography, interpreted by three independent radiologists. Further follow-up was undertaken at two, six, eight and 12 weeks. A total of 238 patients fulfilled all the inclusion criteria, with 127 in the low molecular weight heparin group and 111 in the placebo group, all of whom underwent bilateral venography. There was no statistically significant difference in the incidence of deep-vein thrombosis between those patients treated with low molecular weight heparin or the placebo (p = 0.22). The number of deep-vein thromboses in the two groups was 11 (8.7%) and 14 (12.6%), respectively. Age and the type of fracture were significantly associated with the rate of deep-vein thrombosis (p = 0.001 and p = 0.009, respectively) but gender, comorbidities and the body mass index were not. The overall incidence of deep-vein thrombosis in this series was 11%. There was no clinical or statistical significant reduction in the incidence of deep-vein thrombosis with the use of thromboprophylaxis. However, we accept that owing to a cessation of funding, recruitment to this trial had to be ended prior to establishing the necessary sample size. Our results cannot, therefore, categorically exclude the possibility that low molecular weight heparin treatment could be beneficial. We recommend a further multicentre trial be undertaken to resolve this matter.
Ankle fusion for bone loss around the ankle joint using the Ilizarov technique
Authors: Kovoor C. C. , Padmanabhan V. , Bhaskar D. , George V. V. , Viswanath S. 
Published: March 2009

We present the results of ankle fusion using the Ilizarov technique for bone loss around the ankle in 20 patients. All except one had sustained post-traumatic bone loss. Infection was present in 17. The mean age was 33.1 years (7 to 71). The mean size of the defect was 3.98 cm (1.5 to 12) and associated limb shortening before the index procedure varied from 1 cm to 5 cm. The mean time in the external fixator was 335 days (42 to 870). Tibiotalar fusion was performed in 19 patients and tibiocalcaneal fusion in one. Associated problems included diabetes in one patient, pelvic and urethral injury in one, visual injury in one patient and ipsilateral tibial fracture in five. At the final mean follow-up of 51.55 months (24 to 121) fusion had been achieved in 19 of 20 patients. A total of 16 patients were able to return to work. The results were graded as good in 11 patients, fair in six and poor in three. The mean external fixation index was 8.8 days/mm (0 to 30). One patient with diabetes developed severe infection which required early removal of the fixator. Refractures occurred in three patients, two of which were at the site of fusion and one at a previous tibial shaft fracture site. Equinus deformity of the ankle fusion occurred after a further fracture in one patient. There were two patients with residual forefoot equinus, and one developed late valgus at the fusion site. Poor consolidation of the regenerated bone in two patients was treated by bone grafting in one and by bone and fibular strut grafting in the other. Residual soft-tissue infection was still present in two patients.
Percutaneous vertebroplasty for the treatment of osteoporotic vertebral compression fractures
Authors: Muijs S. P. J. , Nieuwenhuijse M. J. , Van Erkel A. R. , Dijkstra P. D. S. 
Published: March 2009

In a prospective study between August 2002 and August 2005, we studied the quantitative clinical and radiological outcome 36 months after percutaneous vertebroplasty for intractable type-II osteoporotic vertebral compression fractures which had been unresponsive to conservative treatment for at least eight weeks. We also examined the quality of life (QoL). The clinical follow-up involved the use of a pain intensity numerical rating scale (PI-NRS, 0 to 10), the Short-Form 36 (SF-36) QoL questionnaire and an anamnestic questionnaire before and at seven days (PI-NRS only), and one, three, 12 and 36 months post-operatively. A total of 30 consecutive patients received percutaneous vertebroplasty for 62 vertebral compression fractures with a mean time between fracture and treatment of 7.7 months (2.2 to 39). An immediate, significant and lasting reduction in the average and worst back pain was found, represented by a decrease of 3.1 and 2.7 points after seven days and 3.1 and 2.8 points after 36 months, respectively (p < 0.00). Comparison of the pre- and post-vertebroplasty scores on the various SF-36 domains showed an ultimate significant increase in six of eight domains and both summary scores. Asymptomatic leakage of cement was found in 47 of 58 (81%) of treated vertebrae. Two minor complications occurred, an asymptomatic pulmonary cement embolism and a cement spur along the needle track. Percutaneous vertebroplasty in the treatment of chronic vertebral compression fractures results in an immediate, significant and lasting reduction in back pain, and overall improvement in physical and mental health.
Extracorporeal irradiation for pelvic reconstruction in Ewing’s sarcoma
Authors: Krieg A. H. , Mani M. , Speth B. M. , Stalley P. D. 
Published: March 2009

We review the treatment of pelvic Ewing’s sarcoma by the implantation of extracorporeally-irradiated (ECI) autografts and compare the outcome with that of other reported methods. We treated 13 patients with ECI autografts between 1994 and 2004. There were seven males and six females with a median age of 15.7 years (interquartile range (IQR) 12.2 to 21.7). At a median follow-up of five years (IQR 1.8 to 7.4), the disease-free survival was 69% overall, and 75% if one patient with local recurrence after initial treatment elsewhere was excluded. Four patients died from distant metastases at a mean of 17 months (13 to 23). There were three complications which required operative intervention; one was a deep infection which required removal of the graft. The functional results gave a mean Musculoskeletal Tumor Society score of 85% (60% to 97%), a mean Toronto extremity salvage score of 86% (69% to 100%) and a mean Harris hip score of 92 (67 to 100). We conclude that ECI grafting is a suitable form of treatment for localised and resectable pelvic Ewing’s sarcoma.
Imageless computer navigation for placement of the femoral component in resurfacing arthroplasty of the hip
Authors: Olsen M. , Davis E. T. , Waddell J. P. , Schemitsch E. H. 
Published: March 2009

We have investigated the accuracy of placement of the femoral component using imageless navigation in 100 consecutive Birmingham Hip Resurfacings. Pre-operative templating determined the native neck-shaft angle and planned stem-shaft angle of the implant. The latter were verified post-operatively using digital anteroposterior unilateral radiographs of the hip.The mean neck-shaft angle determined before operation was 132.7° (118° to 160°). The mean planned stem-shaft angle was a relative valgus alignment of 9.7° (sd 2.6). The stem-shaft angle after operation differed from that planned by a mean of 2.8° (sd 2.0) and in 86% of cases the final angle measured within ± 5° of that planned. We had no instances of notching of the neck or varus alignment of the implant in our series. A learning curve was observed in the time taken for navigation, but not for accurate placement of the implant.Navigation in hip resurfacing may afford the surgeon a reliable and accurate method of placement of the femoral component.