bluuebunny/crossref_metadata_2025_split huggingface dataset:
IgG-Switched CLL Has a Distinct Immunogenetic Signature from the Common MD Variant: Ontogenetic Implications
Authors: Vardi Anna , Agathangelidis Andreas , Sutton Lesley-Ann , Chatzouli Maria , Scarfò Lydia , Mansouri Larry , Douka Vassiliki , Anagnostopoulos Achilles , Darzentas Nikos , Rosenquist Richard , Ghia Paolo , Belessi Chrysoula , Stamatopoulos Kostas 
Published: November 2013

Abstract
Purpose: Immunoglobulin G–switched chronic lymphocytic leukemia (G-CLL) is a rare variant of CLL, whose origin and ontogenetic relationship to the common IgM/IgD (MD-CLL) variant remains undefined. Here, we sought for clues about the ontogeny of G-CLL versus MD-CLL by profiling the relevant IG gene repertoires.
Experimental Design: Using purpose-built bioinformatics methods, we performed detailed immunogenetic profiling of a multinational CLL cohort comprising 1,256 cases, of which 1,087 and 169 expressed IG mu/delta and gamma heavy chains, respectively.
Results: G-CLL has a highly skewed IG gene repertoire that is distinct from MD-CLL, especially in terms of (i) overuse of the IGHV4-34 and IGHV4-39 genes and (ii) differential somatic hypermutation (SHM) load. Repertoire differences were also found when comparing subgroups with similar SHM status and were mainly attributed to the exclusive representation in G-CLL of two major subsets with quasi-identical (stereotyped) B-cell receptors. These subsets, namely #4 (IGHV4-34/IGKV2-30) and #8 (IGHV4-39/IGKV1(D)-39), were found to display sharply contrasting SHM and clinical behavior.
Conclusions: G-CLL exhibits an overall distinct immunogenetic signature from MD-CLL, prompting speculations about distinct ontogenetic derivation and/or immune triggering. The reasons underlying the differential regulation of SHM among G-CLL cases remain to be elucidated. Clin Cancer Res; 20(2); 323–30. ©2013 AACR.
Tumor Growth Rate Is an Early Indicator of Antitumor Drug Activity in Phase I Clinical Trials
Authors: Ferté Charles , Fernandez Marianna , Hollebecque Antoine , Koscielny Serge , Levy Antonin , Massard Christophe , Balheda Rastislav , Bot Brian , Gomez-Roca Carlos , Dromain Clarisse , Ammari Samy , Soria Jean-Charles 
Published: November 2013

Abstract
Purpose: Response Evaluation Criteria in Solid Tumors (RECIST) evaluation does not take into account the pretreatment tumor kinetics and may provide incomplete information about experimental drug activity. Tumor growth rate (TGR) allows for a dynamic and quantitative assessment of the tumor kinetics. How TGR varies along the introduction of experimental therapeutics and is associated with outcome in phase I patients remains unknown.
Experimental Design: Medical records from all patients (N = 253) prospectively treated in 20 phase I trials were analyzed. TGR was computed during the pretreatment period (reference) and the experimental period. Associations between TGR, standard prognostic scores [Royal Marsden Hospital (RMH) score], and outcome [progression-free survival (PFS) and overall survival (OS)] were computed (multivariate analysis).
Results: We observed a reduction of TGR between the reference versus experimental periods (38% vs. 4.4%; P &lt; 0.00001). Although most patients were classified as stable disease (65%) or progressive disease (25%) by RECIST at the first evaluation, 82% and 65% of them exhibited a decrease in TGR, respectively. In a multivariate analysis, only the decrease of TGR was associated with PFS (P = 0.004), whereas the RMH score was the only variable associated with OS (P = 0.0008). Only the investigated regimens delivered were associated with a decrease of TGR (P &lt; 0.00001, multivariate analysis). Computing TGR profiles across different clinical trials reveals specific patterns of antitumor activity.
Conclusions: Exploring TGR in phase I patients is simple and provides clinically relevant information: (i) an early and subtle assessment of signs of antitumor activity; (ii) independent association with PFS; and (iii) it reveals drug-specific profiles, suggesting potential utility for guiding the further development of the investigational drugs. Clin Cancer Res; 20(1); 246–52. ©2013 AACR.
MUC4-Mediated Regulation of Acute Phase Protein Lipocalin 2 through HER2/AKT/NF-κB Signaling in Pancreatic Cancer
Authors: Kaur Sukhwinder , Sharma Neil , Krishn Shiv Ram , Lakshmanan Imay , Rachagani Satyanarayana , Baine Michael J. , Smith Lynette M. , Lele Subodh M. , Sasson Aaron R. , Guha Sushovan , Mallya Kavita , Anderson Judy M. , Hollingsworth Michael A. , Batra Surinder K. 
Published: November 2013

Abstract
Purpose: MUC4 shows aberrant expression in early pancreatic lesions and a high specificity for pancreatic cancer. It thus has a high potential to be a sensitive and specific biomarker. Unfortunately, its low serum level limits its diagnostic/prognostic potential. We here report that a multifaceted acute phase protein lipocalin 2, regulated by MUC4, could be a potential diagnostic/prognostic marker for pancreatic cancer.
Experimental Designs and Results: Overexpression/knockdown, luciferase reporter and molecular inhibition studies revealed that MUC4 regulates lipocalin 2 by stabilizing HER2 and stimulating AKT, which results in the activation of NF-κB. Immunohistochemical analyses of lipocalin 2 and MUC4 showed a significant positive correlation between MUC4 and lipocalin 2 in primary, metastatic tissues (Spearman correlation coefficient 0.71, P = 0.002) from rapid autopsy tissue sample from patients with pancreatic cancer as well as in serum and tissue samples from spontaneous KRASG12D mouse pancreatic cancer model (Spearman correlation coefficient 0.98, P &lt; 0.05). Lipocalin 2 levels increased progressively with disease advancement (344.2 ± 22.8 ng/mL for 10 weeks to 3067.2 ± 572.6 for 50 weeks; P &lt; 0.0001). In human pancreatic cancer cases, significantly elevated levels of lipocalin 2 were observed in patients with pancreatic cancer (148 ± 13.18 ng/mL) in comparison with controls (73.27 ± 4.9 ng/mL, P = 0.014). Analyses of pre- and postchemotherapy patients showed higher lipocalin 2 levels in prechemotherapy patients [121.7 ng/mL; 95% confidence interval (CI), 98.1–150.9] in comparison with the postchemotherapy (92.6 ng/mL; 95% CI, 76.7–111.6; P = 0.06) group.
Conclusions: This study delineates the association and the downstream mechanisms of MUC4-regulated elevation of lipocalin-2 (via HER2/AKT/NF-κB) and its clinical significance for prognosis of pancreatic cancer. Clin Cancer Res; 20(3); 688–700. ©2013 AACR.
Germline and Somatic Mutations in Homologous Recombination Genes Predict Platinum Response and Survival in Ovarian, Fallopian Tube, and Peritoneal Carcinomas
Authors: Pennington Kathryn P. , Walsh Tom , Harrell Maria I. , Lee Ming K. , Pennil Christopher C. , Rendi Mara H. , Thornton Anne , Norquist Barbara M. , Casadei Silvia , Nord Alexander S. , Agnew Kathy J. , Pritchard Colin C. , Scroggins Sheena , Garcia Rochelle L. , King Mary-Claire , Swisher Elizabeth M. 
Published: November 2013

Abstract
Purpose: Hallmarks of germline BRCA1/2-associated ovarian carcinomas include chemosensitivity and improved survival. The therapeutic impact of somatic BRCA1/2 mutations and mutations in other homologous recombination DNA repair genes is uncertain.
Experimental Design: Using targeted capture and massively parallel genomic sequencing, we assessed 390 ovarian carcinomas for germline and somatic loss-of-function mutations in 30 genes, including BRCA1, BRCA2, and 11 other genes in the homologous recombination pathway.
Results: Thirty-one percent of ovarian carcinomas had a deleterious germline (24%) and/or somatic (9%) mutation in one or more of the 13 homologous recombination genes: BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK1, CHEK2, FAM175A, MRE11A, NBN, PALB2, RAD51C, and RAD51D. Nonserous ovarian carcinomas had similar rates of homologous recombination mutations to serous carcinomas (28% vs. 31%, P = 0.6), including clear cell, endometrioid, and carcinosarcoma. The presence of germline and somatic homologous recombination mutations was highly predictive of primary platinum sensitivity (P = 0.0002) and improved overall survival (P = 0.0006), with a median overall survival of 66 months in germline homologous recombination mutation carriers, 59 months in cases with a somatic homologous recombination mutation, and 41 months for cases without a homologous recombination mutation.
Conclusions: Germline or somatic mutations in homologous recombination genes are present in almost one third of ovarian carcinomas, including both serous and nonserous histologies. Somatic BRCA1/2 mutations and mutations in other homologous recombination genes have a similar positive impact on overall survival and platinum responsiveness as germline BRCA1/2 mutations. The similar rate of homologous recombination mutations in nonserous carcinomas supports their inclusion in PARP inhibitor clinical trials. Clin Cancer Res; 20(3); 764–75. ©2013 AACR.
Pertuzumab Protects the Achilles' Heel of Trastuzumab—Emtansine
Authors: Gwin William R. , Spector Neil L. 
Published: November 2013

Abstract
Trastuzumab emtansine (T-DM1) represents a significant advancement in the treatment of HER2+ breast cancers. Its clinical efficacy however will be limited by the development of therapeutic resistance. In this report, the HER3 ligand neuregulin is shown to mediate T-DM1 resistance, which was overcome by administration of pertuzumab, a steric inhibitor of HER2 dimerization. Clin Cancer Res; 20(2); 278–80. ©2013 AACR.
Intracardiac Echocardiography for Detection of Thrombus in the Left Atrial Appendage
Authors: Baran Jakub , Stec Sebastian , Pilichowska-Paszkiet Ewa , Zaborska Beata , Sikora-Frąc Małgorzata , Kryński Tomasz , Michałowska Ilona , Łopatka Rafał , Kułakowski Piotr 
Published: November 2013

Background—
Transesophageal echocardiography (TEE) is the gold standard for the exclusion of thrombi in the left atrial appendage (LAA) before ablation for atrial fibrillation. Intracardiac echocardiography (ICE) is used to assist atrial fibrillation ablation; however, it can also be used for LAA imaging. The aim of our study was to determine whether ICE could replace TEE and to identify the optimal ICE placement for LAA visualization.

Methods and Results—

Seventy-six consecutive patients (56 men; mean age, 55±9.6 years) scheduled for atrial fibrillation ablation underwent TEE before the procedure and LAA assessment by ICE. An 8F AcuNav probe was introduced into right atrium, pulmonary artery, and coronary sinus. LAA structure was analyzed by the echocardiographer and electrophysiologist who were blinded to the results of TEE. ICE probe was positioned in the right atrium in all patients, in the pulmonary artery in 64 of 74 (86%) patients, and in the coronary sinus in 49 of 74 (66%) patients. The LAA was properly visualized in 56 of 64 (87.5%) patients from the pulmonary artery versus 13 of 49 (26%) patients from the coronary sinus (
P
<0.001). From the right atrium, the whole LAA cavity could not be seen in any patient. In those patients in whom LAA was visualized properly by ICE, a perfect agreement between ICE and TEE was obtained (both techniques detected LAA thrombus in 2 patients and excluded LAA thrombus in the remaining patients).

Conclusions—
ICE can be used safely and effectively for the evaluation of LAA in patients undergoing atrial fibrillation ablation. ICE imaging from pulmonary artery is accurate for LAA visualization.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01371279.
Complications of Catheter Ablation of Atrial Fibrillation
Authors: Gupta Aakriti , Perera Tharani , Ganesan Anand , Sullivan Thomas , Lau Dennis H. , Roberts-Thomson Kurt C. , Brooks Anthony G. , Sanders Prashanthan 
Published: November 2013

Background—
Atrial fibrillation ablation is an established therapy; however, limited data are available on associated complications. This systematic review determines the incidence and potential predictors of acute complications.

Methods and Results—

Electronic searches were conducted in MEDLINE and EMBASE for English scientific literature up to the 18th June 2012. A total of 2065 references were retrieved and evaluated for relevance. Reference lists of retrieved studies and review articles were examined to ensure all relevant studies were included. Data were extracted from 192 studies, total of 83 236 patients. The incidence of periprocedural complications for catheter ablation of atrial fibrillation was 2.9% (95% confidence interval, 2.6–3.2). There was a significant decrease in the acute complication rate in 2007 to 2012 compared with 2000 to 2006 (2.6% versus 4.0%;
P
=0.003). The complication rates reported were higher in prospective studies compared with those that retrospectively described complications (3.5% versus 2.7%;
P
=0.03). There were no significant associations among procedure duration, ablation time or ablation strategy, and acute complication rate.

Conclusions—
Catheter ablation of atrial fibrillation has a low incidence of periprocedural complications. The acute complication rate has decreased significantly in recent years. This may reflect improved catheter technology and experience. The use of different strategies across centers worldwide seems to be safe with no established relationship between procedural variables and complication rate.
Adenosine-Induced Pulmonary Vein Ectopy as a Predictor of Recurrent Atrial Fibrillation After Pulmonary Vein Isolation
Authors: Cheung Jim W. , Lin Frank S. , Ip James E. , Bender Seth R. , Siddiqi Faisal K. , Liu Christopher F. , Thomas George , Markowitz Steven M. , Lerman Bruce B. 
Published: November 2013

Background—
Adenosine can unmask dormant pulmonary vein (PV) conduction after PV isolation. Adenosine can also induce ectopy in electrically silent PVs after isolation, possibly via activation of autonomic triggers. We sought to identify the implications of adenosine-induced PV ectopy for atrial fibrillation (AF) recurrence after PV isolation.

Methods and Results—

A total of 152 patients (age, 60±11 years; 63% paroxysmal AF) undergoing PV isolation for AF were studied. After each PV was isolated, adenosine was administered and the presence of adenosine-induced PV reconnection and PV ectopy were recorded. Dormant conduction was targeted with additional ablation. Adenosine-induced PV ectopy was seen in 45 (30%) patients, and dormant conduction was seen in 44 (29%) patients. After a median follow-up of 374 days, 48 (32%) patients had recurrent AF after a single ablation procedure. Rates of freedom from AF among patients with adenosine-induced PV ectopy were significantly lower than patients without adenosine-induced PV ectopy (63% versus 76% at 1 year; log rank, 0.014). Rates of freedom from AF among patients with dormant conduction were also lower than patients without dormant conduction (64% versus 76% at 1 year; log rank, 0.062). With multivariate analysis, adenosine-induced PV ectopy was found to be the only independent predictor of AF after PV isolation (hazard ratio, 1.90; 95% confidence interval, 1.06–3.40;
P
=0.032).

Conclusions—
Adenosine-induced PV ectopy is a predictor of recurrent AF after PV isolation and may be a marker of increased susceptibility to autonomic triggers of AF.
Healthy and active ageing: Social capital in health promotion
Authors: Koutsogeorgou Eleni , Davies John Kenneth , Aranda Kay , Zissi Anastasia , Chatzikou Maria , Cerniauskaite Milda , Quintas Rui , Raggi Alberto , Leonardi Matilde 
Published: November 2013

Objectives: This paper examines the context of health promotion actions that are focused on/contributing to strengthening social capital by increasing community participation, reciprocal trust and support as the means to achieve better health and more active ageing. Method: The methodology employed was a literature review/research synthesis, and a thematic analysis. Results: Four core themes emerged from the analysis: a) active ageing; b) the relationship between social capital and ageing; c) the importance of social capital in health promotion; and d) policy implications. The role of social capital in health promotion stresses empowerment, intergenerational support, the building of social trust, and the need to tackle loneliness among older adults. The importance of community/social participation emerged from the literature review as a key contributor to the maintenance and promotion of a healthier ageing population. Conclusion: Supporting long-term social capital building within communities can lead to improved public health and well-being for an ageing population.
The effects of a physical exercise programme after radical cystectomy for urinary bladder cancer. A pilot randomized controlled trial
Authors: Porserud Andrea , Sherif Amir , Tollbäck Anna 
Published: November 2013

Objective: Assessment of feasibility and effects of an exercise training programme in patients following cystectomy due to urinary bladder cancer. Design: Single-blind, pilot, randomized controlled trial. Setting: University hospital, Sweden. Subjects: Eighteen patients (64–78 years), of 89 suitable, cystectomized due to urinary bladder cancer, were randomized after hospital discharge to intervention or control. Interventions: The 12-week exercise programme included group exercise training twice a week and daily walks. The control group received only standardized information at discharge. Main outcome measures: Trial eligibility and compliance to inclusion were registered. Assessments of functional capacity, balance, lower body strength and health-related quality of life (HRQoL) with SF-36. Results: Out of 122 patients 89 were eligible, but 64 did not want to participate/were not invited. Twenty-five patients were included, but 7 dropped out before randomization. Eighteen patients were randomized to intervention or control. Thirteen patients completed the training period. The intervention group increased walking distance more than the control group, 109 m (75–177) compared to 62 m (36–119) ( P = 0.013), and role physical domain in SF-36 more than the control group ( P = 0.031). Ten patients were evaluated one year postoperatively. The intervention group had continued increasing walking distance, 20 m (19–36), whereas the control group had shortened the distance −15.5 m (−43 to −5) ( P = 0.010). Conclusions: A 12-week group exercise training programme was not feasible for most cystectomy patients. However, functional capacity and the role-physical domain in HRQoL increased in the short and long term for patients in the intervention group compared with controls.
A multicentre postal survey investigating the contribution of illness perceptions, coping and optimism to quality of life and mood in adults with muscle disease
Authors: Graham Christopher D , Weinman John , Sadjadi Reza , Chalder Trudie , Petty Richard , Hanna Mike G , Turner Chris , Parton Matt , Maddison Paul , Radunovic Aleksandar , Longman Cheryl , Robb Yvonne , Bushby Kate , Hilton-Jones David , Rose Michael R 
Published: November 2013

Objective: To replicate the finding that illness perceptions influence quality of life in adults with muscle disease and to explore the additional influence of coping and optimism on quality of life and mood. Design: A postal survey including questionnaires recording quality of life, mood, illness perceptions, optimism, coping and functional impairment. Setting: National Health Service muscle clinics in the United Kingdom. Participants: A convenience sample of adults with muscle disease. Interventions: Not applicable. Main outcome measures: Individualised Neuromuscular Quality of Life Questionnaire, Hospital Anxiety and Depression Scale. Results: A total of 226 completed questionnaires were returned. Although functional impairment explained most of the variance in three out of eight quality of life domains, psychological factors explained greater amounts of variance (between 19% and 52% of variance) in all other quality of life domains and in both mood domains (between 45% and 48% of variance). Overall, illness perceptions explained much of the variance in quality of life and mood score (between 5% and 37% of variance), while coping (up to 8% of variance) and optimism (up to 15% of variance) explained smaller amounts of variance. Conclusion: The results confirm that illness perceptions are associated with quality of life in muscle disease and suggest that they also influence mood. The addition of optimism and coping variables into the analysis yielded small increases in the proportions of variance in quality of life and mood which were explained. These results have implications for the composition of future psychological interventions.
Efficacy of microcurrent therapy in infants with congenital muscular torticollis involving the entire sternocleidomastoid muscle: a randomized placebo-controlled trial
Authors: Kwon Dong Rak , Park Gi Young 
Published: November 2013

Objective: To compare the effects of a combination of therapeutic exercise and ultrasound with or without additional microcurrent therapy in infants with congenital muscular torticollis involving the entire sternocleidomastoid muscle. Design: Prospective, randomized, placebo-controlled trial. Setting: An outpatient rehabilitation clinic in a tertiary university hospital. Subjects: Infants ( n = 20) with congenital muscular torticollis involving the entire sternocleidomastoid muscle. Interventions: Group 1 comprised 10 infants who received therapeutic exercise with ultrasound alone and Group 2 comprised 10 infants who received the same treatment with microcurrent therapy. Main measures: Passive cervical rotational range of motion was measured at before treatment and one, two, three, and six months after initial treatment. Thickness, cross-sectional area, and red pixel intensity on colour histograms, which were all assessed before treatment and at three months after initial treatment. Additionally, the duration of treatment was measured. Results: The mean passive cervical rotational range of motion measured at three months posttreatment was significantly greater in Group 2 (101.1°) than that in Group 1 (86.4°), and the thickness, cross-sectional area, and red pixel intensity of the affected sternocleidomastoid muscle were all less in Group 2 (7.8 mm, 100.3 mm2, and 126.1, respectively) than those in Group 1 (9.6 mm, 121.5 mm2, and 140.5, respectively). The mean duration of treatment was significantly shorter in Group 2 (2.6 months) than in Group 1 (6.3 months). Conclusions: Microcurrent therapy may increase the efficacy of therapeutic exercise with ultrasound for the treatment of congenital muscular torticollis involving the entire sternocleidomastoid muscle.
A prominent lack of IgG1-Fc fucosylation of platelet alloantibodies in pregnancy
Authors: Kapur Rick , Kustiawan Iwan , Vestrheim Anne , Koeleman Carolien A. M. , Visser Remco , Einarsdottir Helga K. , Porcelijn Leendert , Jackson Dave , Kumpel Belinda , Deelder André M. , Blank Dennis , Skogen Björn , Killie Mette Kjaer , Michaelsen Terje E. , de Haas Masja , Rispens Theo , van der Schoot C. Ellen , Wuhrer Manfred , Vidarsson Gestur 
Published: November 2013

Key PointsAntibodies causing FNAIT have decreased Fc fucosylation, unlike in refractory thrombocytopenia. Decreased Fc fucose increases affinity to FcγRIIIa/b, enhances platelet phagocytosis, and correlates with increased disease severity.