bluuebunny/crossref_metadata_2025_split huggingface dataset:
MET Amplification Identifies a Small and Aggressive Subgroup of Esophagogastric Adenocarcinoma With Evidence of Responsiveness to Crizotinib
Authors: Lennerz Jochen K. , Kwak Eunice L. , Ackerman Allison , Michael Michael , Fox Stephen B. , Bergethon Kristin , Lauwers Gregory Y. , Christensen James G. , Wilner Keith D. , Haber Daniel A. , Salgia Ravi , Bang Yung-Jue , Clark Jeffrey W. , Solomon Benjamin J. , Iafrate A. John 
Published: November 2011

Purpose Amplification of the MET proto-oncogene in gastroesophageal cancer (GEC) may constitute a molecular marker for targeted therapy. We examined a GEC cohort with follow-up and reported the clinical response of four additional patients with MET-amplified tumors to the small molecule inhibitor crizotinib as part of an expanded phase I cohort study. Patients and Methods From 2007 to 2009, patients with GEC were genetically screened as a consecutive series of 489 tumors (stages 0, I, and II, 39%; III, 25%; IV, 36%; n = 222 esophageal, including n = 21 squamous carcinomas). MET, EGFR, and HER2 amplification status was assessed by using fluorescence in situ hybridization. Results Ten (2%) of 489 patients screened harbored MET amplification; 23 (4.7%) harbored EGFR amplification; 45 (8.9%) harbored HER2 amplification; and 411 (84%) were wild type for all three genes (ie, negative). MET-amplified tumors were typically high-grade adenocarcinomas that presented at advanced stages (5%; n = 4 of 80). EGFR-amplified tumors showed the highest fraction of squamous cell carcinoma (17%; n = 4 of 23). HER2, MET, and EGFR amplification were, with one exception (MET and EGFR positive), mutually exclusive events. Survival analysis in patients with stages III and IV disease showed substantially shorter median survival in MET/EGFR-amplified groups, with a rank order for all groups by median survival (from most to least aggressive): MET (7.1 months; P < .001) less than EGFR (11.2 months; P = .16) less than HER2 (16.9 months; P = .89) when compared with the negative group (16.2 months). Two of four patients with MET-amplified tumors treated with crizotinib experienced tumor shrinkage (−30% and −16%) and experienced progression after 3.7 and 3.5 months. Conclusion MET amplification defines a small and aggressive subset of GEC with indications of transient sensitivity to the targeted MET inhibitor crizotinib (PF-02341066).
Use of Zidovudine and Interferon Alfa With Chemotherapy Improves Survival in Both Acute and Lymphoma Subtypes of Adult T-Cell Leukemia/Lymphoma
Authors: Hodson Andrew , Crichton Siobhan , Montoto Silvia , Mir Naheed , Matutes Estella , Cwynarski Kate , Kumaran Thurai , Ardeshna Kirit M. , Pagliuca Antonio , Taylor Graham P. , Fields Paul A. 
Published: November 2011

Purpose Adult T-cell leukemia/lymphoma (ATLL) is a mature (post-thymic) T-cell lymphoma associated with human T-lymphotropic virus type 1 infection. Survival in aggressive subtypes remains poor, and treatment resistance is frequent. Use of zidovudine (ZDV) and interferon alfa (IFN-α) has been associated with improved response rates in small studies and prolonged overall survival in leukemic ATLL subtypes in a recent meta-analysis. Patients and Methods We report the clinicopathologic characteristics, treatment, and outcome of 73 patients with aggressive ATLL (acute ATLL, 29; lymphoma ATLL, 44) diagnosed and treated in England between 1999 and 2009. The impact of ZDV/IFN-α on treatment response and survival was assessed. Results The overall response rate ranged from 49% with chemotherapy alone to 81% with combined first-line therapy (chemotherapy with concurrent/sequential ZDV/IFN-α). Median overall survival (OS) was 9 months: 7.5 months for acute ATLL and 10 months for lymphoma ATLL. Use of ZDV/IFN-α at any time prolonged survival in acute (P < .001) and lymphoma ATLL (P < .001) and was the sole factor associated with reduction in risk of death in aggressive ATLL (hazard ratio, 0.23; 95% CI, 0.09 to 0.60; P = .002). Combined first-line therapy prolonged median OS in acute (P = .0081) and lymphoma ATLL (P = .001) compared with chemotherapy alone. Conclusion These data support the use of low-dose ZDV/IFN-α with chemotherapy in first-line treatment of acute and lymphoma ATLL.
Genetic Activation of the MET Pathway and Prognosis of Patients With High-Risk, Radically Resected Gastric Cancer
Authors: Graziano Francesco , Galluccio Nadia , Lorenzini Paola , Ruzzo Annamaria , Canestrari Emanuele , D'Emidio Silvia , Catalano Vincenzo , Sisti Valerio , Ligorio Claudia , Andreoni Francesca , Rulli Eliana , Di Oto Enrico , Fiorentini Giammaria , Zingaretti Costantino , De Nictolis Michele , Cappuzzo Federico , Magnani Mauro 
Published: November 2011

Purpose To investigate whether prognosis of patients with high-risk gastric cancer may depend on MET copy number gain (CNG) or an activating truncation within a deoxyadenosine tract element (DATE) in the promoter region of the MET ligand HGF. Patients and Methods A single-institution cohort of 230 patients with stage II/III gastric cancer was studied. Formalin-fixed paraffin-embedded tumor specimens were used for DNA extraction. Quantitative polymerase chain reaction (qPCR) for MET CNG and sequencing for HGF DATE truncation (< 25 deoxyadenosines instead of 30) were used. Results were analyzed for association with disease-free survival (DFS) and overall survival (OS). To assess the reliability of the qPCR measurement, a random sample of cases was reanalyzed using an alternative assay (fluorescent in situ hybridization [FISH]) with calculation of the intracorrelation coefficient (ICC). Results In 216 assessable patients, MET CNG five or more copies and homozygous HGF-truncated DATE occurred in 21 patients (10%) and 30 patients (13%), respectively. Patients with MET CNG five or more copies (MET-positive) showed significantly worse prognosis with multivariate hazard ratio (HR) of 3.02 (95% CI, 1.71 to 5.33; P < .001) for DFS and multivariate HR of 2.91 (95% CI, 1.65 to 5.11; P < .001) for OS. The agreement between qPCR and FISH was high, with ICC = 0.9% (95% CI, 0.81% to 0.95%; the closer the ICC is to 1, the greater is the agreement). HGF-truncated DATE did not show relevant prognostic effect. Conclusion In this study, qPCR revealed approximately 10% of white patients with gastric cancer harboring MET CNG of five or more copies. This marker was significantly associated with unfavorable prognosis. This information is relevant to the current clinical development of anti-MET compounds.
Evaluating Survivorship Care Plans: Results of a Randomized, Clinical Trial of Patients With Breast Cancer
Authors: Grunfeld Eva , Julian Jim A. , Pond Gregory , Maunsell Elizabeth , Coyle Douglas , Folkes Amy , Joy Anil A. , Provencher Louise , Rayson Daniel , Rheaume Dorianne E. , Porter Geoffrey A. , Paszat Lawrence F. , Pritchard Kathleen I. , Robidoux André , Smith Sally , Sussman Jonathan , Dent Susan , Sisler Jeffrey , Wiernikowski Jennifer , Levine Mark N. 
Published: November 2011

Purpose An Institute of Medicine report recommends that patients with cancer receive a survivorship care plan (SCP). The trial objective was to determine if an SCP for breast cancer survivors improves patient-reported outcomes. Patients and Methods Women with early-stage breast cancer who completed primary treatment at least 3 months previously were eligible. Consenting patients were allocated within two strata: less than 24 months and ≥ 24 months since diagnosis. All patients were transferred to their own primary care physician (PCP) for follow-up. In addition to a discharge visit, the intervention group received an SCP, which was reviewed during a 30-minute educational session with a nurse, and their PCP received the SCP and guideline on follow-up. The primary outcome was cancer-related distress at 12 months, assessed by the Impact of Event Scale (IES). Secondary outcomes included quality of life, patient satisfaction, continuity/coordination of care, and health service measures. Results Overall, 408 survivors were enrolled through nine tertiary cancer centers. There were no differences between groups on cancer-related distress or on any of the patient-reported secondary outcomes, and there were no differences when the two strata were analyzed separately. More patients in the intervention than control group correctly identify their PCP as primarily responsible for follow-up (98.7% v 89.1%; difference, 9.6%; 95% CI, 3.9 to 15.9; P = .005). Conclusion The results do not support the hypothesis that SCPs are beneficial for improving patient-reported outcomes. Transferring follow-up to PCPs is considered an important strategy to meet the demand for scarce oncology resources. SCPs were no better than a standard discharge visit with the oncologist to facilitate transfer.
Duration of Short-Course Androgen Suppression Therapy and the Risk of Death As a Result of Prostate Cancer
Authors: D'Amico Anthony V. , Chen Ming-Hui , Crook Juanita , Armstrong John G. , Malone Shawn , Steigler Allison , Dunne Mary , Kantoff Philip W. , Denham James W. 
Published: November 2011

Purpose We evaluated whether the duration of androgen suppression therapy (AST) had an impact on the risk of prostate cancer–specific mortality (PCSM) in men with unfavorable-risk prostate cancer (PC) within established Gleason score (GS) categories. Patients and Methods Between February 2, 1996, and December 27, 2001, 761 men with unfavorable-risk PC were treated in Australia, New Zealand, Ireland, or the United States in a randomized trial with radiotherapy and 3, 4, or 6 months of AST (the study cohort). Competing risks regression was used to evaluate whether the duration of AST interacted with GS and was significantly associated with the risk of PCSM, adjusting for age, trial site, and PC prognostic factors. Results After a median follow-up of 10.9 years, 263 men died, 111 (42%) from PC. For all men, 6 versus 3 or 4 months of AST was associated with a reduced risk of PCSM (adjusted hazard ratio [AHR], 0.55; 95% CI, 0.36 to 0.82; P = .004). AHRs evaluating the impact of the duration of AST on the risk of PCSM were 0.67 (95% CI, 0.29 to 1.56; P = .35), 0.47 (95% CI, 0.25 to 0.85; P = .01), and 0.59 (95% CI, 0.30 to 1.19; P = .14) for men with GS ≤ 6, 7, and 8 to 10 PC, respectively. Therefore, the strongest evidence for this benefit was in men with GS 7 PC. Conclusion AST durations of no less than 6 months should be considered when treating GS 7 PC with conventional dose RT.
Growth Hormone Secretion After Conformal Radiation Therapy in Pediatric Patients With Localized Brain Tumors
Authors: Merchant Thomas E. , Rose Susan R. , Bosley Christina , Wu Shengjie , Xiong Xiaoping , Lustig Robert H. 
Published: November 2011

Purpose Growth hormone deficiency (GHD) after radiation therapy negatively affects growth and development and quality of life in children with brain tumors. Patients and Materials Between 1997 and 2008, 192 pediatric patients with localized primary brain tumors (ependymoma, n = 88; low-grade glioma, n = 51; craniopharyngioma, n = 28; high-grade glioma, n = 23; and other tumor types, n = 2) underwent provocative testing of GH secretion by using the secretogogues arginine and l-dopa before and after (6, 12, 36, and 60 months) conformal radiation therapy (CRT). A total of 664 arginine/l-dopa test procedures were performed. Results Baseline testing revealed preirradiation GHD in 22.9% of tested patients. On the basis of data from 118 patients, peak GH was modeled as an exponential function of time after CRT and mean radiation dose to the hypothalamus. The average patient was predicted to develop GHD with the following combinations of the time after CRT and mean dose to the hypothalamus: 12 months and more than 60 Gy; 36 months and 25 to 30 Gy; and 60 months and 15 to 20 Gy. A cumulative dose of 16.1 Gy to the hypothalamus would be considered the mean radiation dose required to achieve a 50% risk of GHD at 5 years (TD50/5). Conclusion GH secretion after CRT can be predicted on the basis of dose and time after irradiation in pediatric patients with localized brain tumors. These findings provide an objective radiation dose constraint for the hypothalamus.
Expression of hindbrain boundary markers is regulated by FGF3
Authors: Weisinger Karen , Kohl Ayelet , Kayam Galya , Monsonego-ornan Efrat , Sela-donenfeld Dalit 
Published: November 2011

Summary
Compartment boundaries act as organizing centers that segregate adjacent areas into domains of gene expression and regulation, and control their distinct fates via the secretion of signalling factors. During hindbrain development, a specialized cell-population forms boundaries between rhombomeres. These boundary cells demonstrate unique morphological properties and express multiple genes that differs them from intra-rhombomeric cells. Yet, little is known regarding the mechanisms that controls the expression or function of these boundary markers.
Multiple components of the FGF signaling system, including ligands, receptors, downstream effectors as well as proteoglycans are shown to localize to boundary cells in the chick hindbrain. These patterns raise the possibility that FGF signaling plays a role in regulating boundary properties. We provide evidence to the role of FGF signaling, particularly the boundary-derived FGF3, in regulating the expression of multiple markers at hindbrain boundaries. These findings enable further characterization of the unique boundary-cell population, and expose a new function for FGFs as regulators of boundary-gene expression in the chick hindbrain.
Improvement and validation of 125I-high-performance liquid chromatography method for determination of total human serum choline and ethanolamine plasmalogens
Authors: Maeba Ryouta , Yamazaki Yuya , Nezu Toru , Okazaki Tomoki 
Published: November 2011

Background Serum plasmalogens (Pls) have gained interest in several clinical symptoms such as metabolic syndrome/atherosclerosis or Alzheimer's disease possibly because of their antioxidant properties. We have developed a highly sensitive and simple method to determine plasmenylcholine (PlsCho; choline plasmalogen) and plasmenylethanolamine (PlsEtn; ethanolamine plasmalogen) separately, using a radioactive iodine and high-performance liquid chromatography (125I-HPLC method). The present study reports the improvement and validation of 125I-HPLC method by introducing a quantitative standard (QS) and online detection with a flow γ-counter. Methods 1-Alkenyl 2,3-cyclic glycerophosphate was prepared as QS from l- α-lyso plasmenylcholine by enzymatic treatment with phospholipase D. Online detection with a flow γ-counter was investigated to be available to quantify Pls. The method validation was carried out in terms of selectivity, sensitivity, linearity, precision, accuracy and recovery. Results Linearity was established over the concentration range 5–300 μmol/L for Pls and QS with regression coefficients >0.99. The accuracy and reliability were satisfactory. The method has been applied to the determination of human serum Pls from healthy subjects and the elderly with dementia or artery stenoses. Conclusions The improved 125I-HPLC method is useful as an autoanalytical system for a routine diagnostic test of human serum Pls.
Directional connectivity of resting state human fMRI data using cascaded ICA-PDC analysis
Authors: Silfverhuth Minna J , Remes Jukka , Starck Tuomo , Nikkinen Juha , Veijola Juha , Tervonen Osmo , Kiviniemi Vesa 
Published: November 2011

Background Directional connectivity measures, such as partial directed coherence (PDC), give us means to explore effective connectivity in the human brain. By utilizing independent component analysis (ICA), the original data-set reduction was performed for further PDC analysis. Purpose To test this cascaded ICA-PDC approach in causality studies of human functional magnetic resonance imaging (fMRI) data. Material and Methods Resting state group data was imaged from 55 subjects using a 1.5 T scanner (TR 1800 ms, 250 volumes). Temporal concatenation group ICA in a probabilistic ICA and further repeatability runs ( n = 200) were overtaken. The reduced data-set included the time series presentation of the following nine ICA components: secondary somatosensory cortex, inferior temporal gyrus, intracalcarine cortex, primary auditory cortex, amygdala, putamen and the frontal medial cortex, posterior cingulate cortex and precuneus, comprising the default mode network components. Re-normalized PDC (rPDC) values were computed to determine directional connectivity at the group level at each frequency. Results The integrative role was suggested for precuneus while the role of major divergence region may be proposed to primary auditory cortex and amygdala. Conclusion This study demonstrates the potential of the cascaded ICA-PDC approach in directional connectivity studies of human fMRI.
Acceptability and side-effects of colonoscopy and sigmoidoscopy in a screening setting
Authors: Senore Carlo , Ederle Andrea , Fantin Alberto , Andreoni Bruno , Bisanti Luigi , Grazzini Grazia , Zappa Marco , Ferrero Franco , Marutti Anna , Giuliani Orietta , Armaroli Paola , Segnan Nereo 
Published: November 2011

Objective Quantitative information on adverse reactions associated with colorectal cancer (CRC) screening tests is useful to estimate the balance between benefit and risk in different strategies. Setting Six Italian screening centres. Methods Thirty-day active follow-up (interview about side-effects and acceptability of the screening procedure and review of hospital admissions) among average-risk people undergoing flexible sigmoidoscopy (FS), total colonoscopy (TC), fecal immunochemical test (FIT) in a multicentre randomized trial of CRC screening. Multivariable logistic models were used to assess determinants of completion rate and self-reported pain. Results The attendance rate following the first invitation and mail reminder was 28.2% (1696/6018) in the FS and 23.0% (1382/6021) in the TC arm. Response rate to the 30-day follow-up questionnaire was 88.6% (1502/1696) among people undergoing FS, and 86.7% (1198/1382) among those undergoing TC. The proportion of people complaining of serious reactions following bowel preparation (odds ratio [OR], 5.17; 95% confidence interval [CI] 3.70–7.24) or reporting severe pain immediately after the exam (OR, 1.86; 95% CI 1.47–2.34) was higher for TC than for FS. The most common post-procedural complaints were abdominal distension and pain. People mentioning pain or bowel distension following preparation were more likely to report severe pain both after FS (OR, 2.13; 95% CI 1.52–2.97) and TC (OR: 2.03; 95% CI 1.41–2.90). The 30-day hospitalization rate was similar after FS, TC and FIT. Conclusions Screenees reported higher pain levels after TC than FS. The proportion of people complaining of severe side effects after discharge was similar. Bowel preparation was poorly tolerated by people undergoing TC. Subjects’ reactions to the bowel preparation was predictive of post-procedural discomfort. A commitment of at least 48 hours was required of people undergoing TC, compared with 3–4 for FS.
Evaluation of the nationwide cervical screening programme in Thailand: a case-control study
Authors: Kasinpila Chananya , Promthet Supannee , Vatanasapt Patravoot , Sasieni Peter , Parkin D Maxwell 
Published: November 2011

Objectives To evaluate the effectiveness of the Pap smear screening programme in Thailand in the prevention of invasive cervical cancer. Setting Four tertiary hospitals, in two provinces of north-east Thailand. Methods A hospital-based case-control study of women aged 30–64, who were resident in north-east Thailand. A total of 130 women with a diagnosis of invasive cervical cancer were compared with two groups of controls: a) hospital controls, b) hospital patient companions. Information on risk factors for cervical cancer and history of screening by cytology (Pap smear) were collected using a structured interview. Results Eighty percent of control subjects reported having had a Pap test in the past, and some two-thirds within the three years before interview. There was a significant protective effect for multiple (6+) previous screening tests as reported by 20% of controls. When women who had tests less than six months prior to the study were excluded, there was a strong, significant protective effect of the number of tests (for 1–5 tests: OR = 0.45 95% CI = 0.25 to 0.84, and for 6+ tests: OR = 0.29 95% CI = 0.11 to 0.82). Tests carried out 1–2 years and 3+ years before diagnosis were associated with an OR of 0.27 (95% CI = 0.13–0.56) and 0.42 (95% CI = 0.20–0.88), respectively. Conclusions The cervical screening programme in north-east Thailand has achieved excellent coverage and is preventing cervical cancer. Women who have been screened multiple times are at substantially lower risk than those only screened a few times suggesting that the quality of the screening could be improved.
Displaced fracture of the waist of the scaphoid
Authors: Dias J. J. , Singh H. P. 
Published: November 2011

A displaced fracture of the scaphoid is one in which the fragments have moved from their anatomical position or there is movement between them when stressed by physiological loads. Displacement is seen in about 20% of fractures of the waist of the scaphoid, as shown by translation, a gap, angulation or rotation. A CT scan in the true longitudinal axis of the scaphoid demonstrates the shape of the bone and displacement of the fracture more accurately than do plain radiographs. Displaced fractures can be treated in a plaster cast, accepting the risk of malunion and nonunion. Surgically the displacement can be reduced, checked radiologically, arthroscopically or visually, and stabilised with headless screws or wires. However, rates of union and deformity are unknown. Mild malunion is well tolerated, but the long-term outcome of a displaced fracture that healed in malalignment has not been established.This paper summarises aspects of the assessment, treatment and outcome of displaced fractures of the waist of the scaphoid.
Physical, mechanical and pharmacological properties of coloured bone cement with and without antibiotics
Authors: Galasso O. , Mariconda M. , Calonego G. , Gasparini G. 
Published: November 2011

Coloured bone cements have been introduced to make the removal of cement debris easier at the time of primary and revision joint replacement. We evaluated the physical, mechanical and pharmacological effects of adding methylene blue to bone cement with or without antibiotics (gentamicin, vancomycin or both). The addition of methylene blue to plain cement significantly decreased its mean setting time (570 seconds (sd 4) vs 775 seconds (sd 11), p = 0.01), mean compression strength (95.4 MPa (sd 3) vs 100.1 MPa (sd 6), p = 0.03), and mean bending strength (65.2 MPa (sd 5) vs 76.6 MPa (sd 4), p < 0.001) as well as its mean elastic modulus (2744 MPa (sd 97) vs 3281 MPa (sd 110), p < 0.001). The supplementation of the coloured cement with vancomycin and gentamicin decreased its mean bending resistance (55.7 MPa (sd 4) vs 65.2 MPa (sd 5), p < 0.001).The methylene blue significantly decreased the mean release of gentamicin alone (228.2 µg (sd 24) vs 385.5 µg (sd 26), p < 0.001) or in combination with vancomycin (498.5 µg (sd 70) vs 613 µg (sd 25), p = 0.018) from the bone cement. This study demonstrates several theoretical disadvantages of the antibiotic-loaded bone cement coloured with methylene blue.