bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carotid replacement with Dacron graft in 292 patients
Authors: Koncar Igor , Ribac Jelena Z , Ilic Nikola S , Dragas Marko , Mutavdzic Perica , Tomic Ivan Z , Ristanovic Natasa , Kostic Dusan , Davidovic Lazar 
Published: January 2016

Introduction In case of highly atherosclerotic carotid process, carotid graft replacement might be a potential solution for successful procedure. Many studies evaluated the results of vein and polytetrafluorethilen (PTFE) graft usage at the carotid bifurcation, while the experience on the Dacron graft due to extensive atherosclerotic process is missing. The aim of our study was to evaluate 30-day and long-term results of the Dacron graft on carotid artery used in patients with extensive atherosclerotic disease. Material and methods This retrospective study analysed early and long-term neurological outcome as well as Dacron graft patency in patients operated with carotid reconstruction. Early results were confirmed by follow-up clinical examination, whereas late results were assessed by follow-up clinical examination as well as duplex sonographic examination at least 1 year after the surgery. As for statistical methods we used descriptive analysis tests, Chi-square test, and logistic regression. Results Carotid graft replacement was performed in 292 patients, before endarterectomy in 155 (53.09%), or after already attempted unsuccessful eversion endarterectomy in 137 (46.91%). Nineteen (6.5%) patients had a stroke due to ipsilateral and contralateral ischaemia or haemorrhagic in 17 (5.8%), 1 (0.3%) and 1 (0.3%) patients, respectively. Significantly higher rate of strokes occurred when the graft reconstruction was used after the failure of endarterectomy (8.5% vs. 3.5%, p = 0.029). Stroke and death rate was 7.19%. Factors that increased risk of early stroke were the length of plaque in the internal carotid artery measured intraoperatively ( p = 0.025) and the surgical tactic to perform graft reconstruction after attempted extensive endarterectomy ( p = 0.029). Conclusion Low number of patients with carotid stenosis has extensive atherosclerotic process longer than 4 cm that might jeopardise eversion endarterectomy. Carotid graft replacement with Dacron graft provide early results that are comparable with other conduits; however, in such patients reconstruction should be selected individually based on surgical experience and anatomical distribution of stenotic disease. Due to high risk of stroke, only symptomatic patients with such extensive atherosclerotic disease should be operated.
Association between diverticulosis and colonic neoplastic lesions in individuals with a positive faecal immunochemical test
Authors: Morini Sergio , Ridola Lorenzo , Hassan Cesare , Lorenzetti Roberto , Boggi Roberto , Napoli Massimo , Tomao Silverio , Zullo Angelo 
Published: January 2016

BackgroundThe association between diverticulosis and colonic neoplastic lesions has been suggested, but data in literature are conflicting. This study aimed to investigate such a relationship in patients participating in a colorectal cancer screening program who underwent high‐quality colonoscopy.MethodsData from consecutive individuals 50–75 years of age with a positive faecal immunological test were considered. Diverticulosis was categorised as present or absent. The prevalence of neoplastic lesions (adenoma, advanced adenoma, and cancer) between individuals with and those without diverticula was compared. A multivariate analysis was performed.ResultsOverall, data from 970 consecutive individuals were evaluated, and diverticulosis was detected in 354 (36.5%) cases. At least one adenoma was detected in 490 (50.5%) people, at least one advanced adenoma in 264 (27.2%), multiple adenoma in 71 (7.3%), whilst a cancer was diagnosed in 48 (4.9%) cases. At univariate analysis, the adenoma detection rate in patients with diverticula was significantly higher than in controls (55.9% vs 47.4%; p  = 0.011). At multivariate analysis, presence of diverticulosis was an independent risk factor for both adenoma detection rate (OR = 1.58; 95% CI = 1.14–2.18; p  = 0.006) and advanced adenoma (OR = 1.57; 95% CI = 1.10–2.24; p  = 0.013), but not for colorectal cancer.ConclusionsIn a colorectal screening setting, the adenoma detection rate was significantly higher in individuals with diverticulosis than in controls.
Functional nanostructures of montmorillonite with conducting polyaniline
Authors: Tokarský Jonáš , Peikertová Pavlína , Kulhánková Lenka , Kutláková Kateřina Mamulová , Neuwirthová Lucie , Matějka Vlastimil , Stýskala Vítězslav , Pavla Čapková  
Published: January 2016

AbstractThe present work describes the effect of montmorillonite (MMT) particles on the alignment of conducting polyaniline (PANI) chains in a PANI/MMT composite. The composite was prepared both as a powder, pressed into pellets, and as thin films deposited on glass surfaces. For comparison, pure PANI was also prepared in these two forms. A combination of X-ray powder diffraction analysis and molecular modelling confirmed the successful intercalation of the PANI into theMMT, while Raman spectroscopy confirmed the presence of the conducting form of PANI (i.e. the emeraldine salt) in all samples. Scanning electron microscopy, transmission electron microscopy and atomic force microscopy were used to study the morphologies of all samples. Conductivity measurements showed that the presence of the MMT particles in the PANI/MMT composites contributes to a significant increase in the electrical conductivity in comparison with the pure PANI samples. Moreover, in the pressed pellets the presence of theMMT particles led to an extremely high electrical anisotropy. TheUV-VIS spectroscopy results showed that the PANI/MMT thin film exhibited a selective transmittance in the range 450–650 nm; therefore, the PANI/MMT thin film is not only conductive, but also suitable for use in various optical applications.
High-density bimodal bentonite blends for hydraulic sealings at the Ibbenbüren coalmine
Authors: Wolters Felicitas , Baille Wiebke , Emmerich Katja , Schmidt Eva , Wolters Christian , Königer Franz , Kunz Jürgen , Krase Volker , Schellhorn Matthias 
Published: January 2016

AbstractThe two high-pressure water-retaining dams at the Ibbenbüren coalmine in Münsterland (Germany) have to perform reliably under the induced tension caused by further exploitation of the current mining area. The load-bearing and the sealing functions of the new barriers were separated and new sealing materials were developed. An innovative multilayer sealing system of bentonite and sandwiched equipotential layers (SANDWICH) supporting homogeneous swelling and sealing, independent of formation water (Nüesch et al., 2002), was applied in this project. A testing program of strain-controlled swelling pressure tests on compacted bentonite specimens and on a bentonite/sand mixture was conducted to ensure an adequate potential for swelling-pressure development.The measurements under constant volume for dry densities between 1.45 g/cm3 and 1.67 g/cm3 showed an evolving swelling pressure between 1.04 and 1.8 MPa for 100% bentonite samples. Straincontrolled oedometer tests for zero strain and step-wise applied strain up to 2% revealed that a sufficient magnitude of swelling pressure existed at maximum applied strain.
Megakaryocyte- and megakaryocyte precursor–related gene therapies
Authors: Wilcox David A. 
Published: January 2016

AbstractHematopoietic stem cells (HSCs) can be safely collected from the body, genetically modified, and re-infused into a patient with the goal to express the transgene product for an individual’s lifetime. Hematologic defects that can be corrected with an allogeneic bone marrow transplant can theoretically also be treated with gene replacement therapy. Because some genetic disorders affect distinct cell lineages, researchers are utilizing HSC gene transfer techniques using lineage-specific endogenous gene promoters to confine transgene expression to individual cell types (eg, ITGA2B for inherited platelet defects). HSCs appear to be an ideal target for platelet gene therapy because they can differentiate into megakaryocytes which are capable of forming several thousand anucleate platelets that circulate within blood vessels to establish hemostasis by repairing vascular injury. Platelets play an essential role in other biological processes (immune response, angiogenesis) as well as diseased states (atherosclerosis, cancer, thrombosis). Thus, recent advances in genetic manipulation of megakaryocytes could lead to new and improved therapies for treating a variety of disorders. In summary, genetic manipulation of megakaryocytes has progressed to the point where clinically relevant strategies are being developed for human trials for genetic disorders affecting platelets. Nevertheless, challenges still need to be overcome to perfect this field; therefore, strategies to increase the safety and benefit of megakaryocyte gene therapy will be discussed.
Understanding platelet generation from megakaryocytes: implications for in vitro–derived platelets
Authors: Sim Xiuli , Poncz Mortimer , Gadue Paul , French Deborah L. 
Published: January 2016

Abstract
Platelets are anucleate cytoplasmic discs derived from megakaryocytes that circulate in the blood and have major roles in hemostasis, thrombosis, inflammation, and vascular biology. Platelet transfusions are required to prevent the potentially life-threatening complications of severe thrombocytopenia seen in a variety of medical settings including cancer therapy, trauma, and sepsis. Platelets used in the clinic are currently donor-derived which is associated with concerns over sufficient availability, quality, and complications due to immunologic and/or infectious issues. To overcome our dependence on donor-derived platelets for transfusion, efforts have been made to generate in vitro–based platelets. Work in this area has advanced our understanding of the complex processes that megakaryocytes must undergo to generate platelets both in vivo and in vitro. This knowledge has also defined the challenges that must be overcome to bring in vitro–based platelet manufacturing to a clinical reality. This review will focus on our understanding of committed megakaryocytes and platelet release in vivo and in vitro, and how this knowledge can guide the development of in vitro–derived platelets for clinical application.
Sprouty 2: a novel attenuator of B-cell receptor and MAPK-Erk signaling in CLL
Authors: Shukla Ashima , Rai Karan , Shukla Vipul , Chaturvedi Nagendra K. , Bociek R. Gregory , Pirruccello Samuel J. , Band Hamid , Lu Runqing , Joshi Shantaram S. 
Published: January 2016

Key PointsSPRY2 is downregulated in CLL cells from patients with poor prognosis. SPRY2 is negative regulator of Syk-mediated BCR and MAPK-Erk signaling in CLL.
Protein Sequence Annotation Tool (PSAT): a centralized web-based meta-server for high-throughput sequence annotations
Authors: Leung Elo , Huang Amy , Cadag Eithon , Montana Aldrin , Soliman Jan Lorenz , Zhou Carol L. Ecale 
Published: January 2016

Abstract
Background
Here we introduce the Protein Sequence Annotation Tool (PSAT), a web-based, sequence annotation meta-server for performing integrated, high-throughput, genome-wide sequence analyses. Our goals in building PSAT were to (1) create an extensible platform for integration of multiple sequence-based bioinformatics tools, (2) enable functional annotations and enzyme predictions over large input protein fasta data sets, and (3) provide a web interface for convenient execution of the tools.

Results
In this paper, we demonstrate the utility of PSAT by annotating the predicted peptide gene products of Herbaspirillum sp. strain RV1423, importing the results of PSAT into EC2KEGG, and using the resulting functional comparisons to identify a putative catabolic pathway, thereby distinguishing RV1423 from a well annotated Herbaspirillum species. This analysis demonstrates that high-throughput enzyme predictions, provided by PSAT processing, can be used to identify metabolic potential in an otherwise poorly annotated genome.

Conclusions
PSAT is a meta server that combines the results from several sequence-based annotation and function prediction codes, and is available at http://psat.llnl.gov/psat/. PSAT stands apart from other sequence-based genome annotation systems in providing a high-throughput platform for rapid de novo enzyme predictions and sequence annotations over large input protein sequence data sets in FASTA. PSAT is most appropriately applied in annotation of large protein FASTA sets that may or may not be associated with a single genome.
Charcot-Marie-Tooth 2b associated Rab7 mutations cause axon growth and guidance defects during vertebrate sensory neuron development
Authors: Ponomareva Olga Y. , Eliceiri Kevin W. , Halloran Mary C. 
Published: January 2016

Abstract

Background
Charcot-Marie-Tooth2b (CMT2b) is an axonal form of a human neurodegenerative disease that preferentially affects sensory neurons. CMT2b is dominantly inherited and is characterized by unusually early onset, presenting in the second or third decade of life. Five missense mutations in the gene encoding Rab7 GTPase have been identified as causative in human CMT2b disease. Although several studies have modeled CMT2b disease in cultured neurons and in Drosophila, the mechanisms by which defective Rab7 leads to disease remain poorly understood.

Results
We used zebrafish to investigate the effects of CMT2b-associated Rab7 mutations in a vertebrate model. We generated transgenic animals expressing the CMT2b-associated mutant forms of Rab7 in sensory neurons, and show that these Rab7 variants cause neurodevelopmental defects, including defects in sensory axon growth, branching and pathfinding at early developmental stages. We also find reduced axon growth and branching in neurons expressing a constitutively active form of Rab7, suggesting these defects may be caused by Rab7 gain-of-function. Further, we use high-speed, high-resolution imaging of endosome transport in vivo and find that CMT2b-associated Rab7 variants cause reduced vesicle speeds, suggesting altered transport may underlie axon development defects.

Conclusions
Our data provide new insight into how disease-associated alterations in Rab7 protein disrupt cellular function in vertebrate sensory neurons. Moreover, our findings suggest that defects in axon development may be a previously unrecognized component of CMT2b disease.
Annual Hazard Rates of Recurrence for Breast Cancer During 24 Years of Follow-Up: Results From the International Breast Cancer Study Group Trials I to V
Authors: Colleoni Marco , Sun Zhuoxin , Price Karen N. , Karlsson Per , Forbes John F. , Thürlimann Beat , Gianni Lorenzo , Castiglione Monica , Gelber Richard D. , Coates Alan S. , Goldhirsch Aron 
Published: January 2016

Purpose Predicting the pattern of recurrence can aid in the development of targeted surveillance and treatment strategies. We identified patient populations that remain at risk for an event at a median follow-up of 24 years from the diagnosis of operable breast cancer. Patients and Methods International Breast Cancer Study Group clinical trials I to V randomly assigned 4,105 patients between 1978 and 1985. Annualized hazards were estimated for breast cancer–free interval (primary end point), disease-free survival, and overall survival. Results For the entire group, the annualized hazard of recurrence was highest during the first 5 years (10.4%), with a peak between years 1 and 2 (15.2%). During the first 5 years, patients with estrogen receptor (ER) – positive disease had a lower annualized hazard compared with those with ER-negative disease (9.9% v 11.5%; P = .01). However, beyond 5 years, patients with ER-positive disease had higher hazards (5 to 10 years: 5.4% v 3.3%; 10 to 15 years: 2.9% v 1.3%; 15 to 20 years: 2.8% v 1.2%; and 20 to 25 years: 1.3% v 1.4%; P < .001). Among patients with ER-positive disease, annualized hazards of recurrence remained elevated and fairly stable beyond 10 years, even for those with no axillary involvement (2.0%, 2.1%, and 1.1% for years 10 to 15, 15 to 20, and 20 to 25, respectively) and for those with one to three positive nodes (3.0%, 3.5%, and 1.5%, respectively). Conclusion Patients with ER-positive breast cancer maintain a significant recurrence rate during extended follow up. Strategies for follow up and treatments to prevent recurrences may be most efficiently applied and studied in patients with ER-positive disease followed for a long period of time.
Serum Human Epidermal Growth Factor 2 Extracellular Domain as a Predictive Biomarker for Lapatinib Treatment Efficacy in Patients With Advanced Breast Cancer
Authors: Lee Chee Khoon , Davies Lucy , Gebski Val J. , Lord Sarah J. , Di Leo Angelo , Johnston Stephen , Geyer Charles , Cameron David , Press Michael F. , Ellis Catherine , Loi Sherene , Marschner Ian , Simes John , de Souza Paul 
Published: January 2016

Purpose We examined the prognostic and predictive value of serum human epidermal growth factor 2 (HER2) extracellular domain (sHER2) in patients with advanced breast cancer treated with lapatinib using data from three randomized trials. Patients and Methods We analyzed sHER2 and tissue HER2 (tHER2) data from 1,902 patients (84%) who were randomly assigned to receive lapatinib or control in the trials EGF30001, EGF30008, and EGF100151. Cox regression analyses were performed to correlate both biomarkers with progression-free survival (PFS) and overall survival (OS). Results Median sHER2 levels were 25.1 and 10.1 ng/mL in tHER2-amplified (tHER-positive) and nonamplified (tHER-negative) populations, respectively (r = 0.42 for sHER2-tHER2 correlation). Lapatinib had significant PFS benefit over control (hazard ratio [HR], 0.855; P = .004), but not OS (HR, 0.941; P = .33). Lapatinib PFS benefit is independently predicted by higher sHER2 values (HR per 10-ng/mL increase in sHER2: lapatinib-containing therapies, 1.009 v nonlapatinib-containing therapies, 1.044; Pinteraction < .001) and by positive tHER2 (HR [lapatinib v nonlapatinib]: tHER2 positive, 0.638 v tHER2 negative, 0.940; Pinteraction = .001). Within the tHER2-positive subpopulation (n = 515), higher sHER2 values still independently predicted lapatinib PFS benefit (HR per 10-ng/mL increase in sHER2: lapatinib-containing therapies, 1.017 v nonlapatinib-containing therapies, 1.041; Pinteraction = .008). In control arms (n = 936), higher sHER2 was associated with worse prognosis in multivariable analyses (PFS HR per 10 ng/mL: PFS, 1.024; P < .001; and OS, 1.018; P < .001). Conclusion Higher sHER2 predicts greater PFS benefit with lapatinib independent of tHER2 status. High sHER2 is also independently prognostic for worse survival in patients who received nonlapatinib-containing therapies. The predictive role of sHER2 for other anti-HER2 agents requires further research.
CD33 Expression and Its Association With Gemtuzumab Ozogamicin Response: Results From the Randomized Phase III Children’s Oncology Group Trial AAML0531
Authors: Pollard Jessica A. , Loken Michael , Gerbing Robert B. , Raimondi Susana C. , Hirsch Betsy A. , Aplenc Richard , Bernstein Irwin D. , Gamis Alan S. , Alonzo Todd A. , Meshinchi Soheil 
Published: January 2016

Purpose CD33 is variably expressed on acute myeloid leukemia (AML) blasts and is targeted by gemtuzumab ozogamicin (GO). GO has shown benefit in both adult and pediatric AML trials, yet limited data exist about whether GO response correlates with CD33 expression level. Patients and Methods CD33 expression levels were prospectively quantified by multidimensional flow cytometry in 825 patients enrolled in Children’s Oncology Group AAML0531 and correlated with response to GO. Results Patients with low CD33 expression (lowest quartile of expression [Q1]) had no benefit with the addition of GO to conventional chemotherapy (relapse risk [RR]: GO 36% v No-GO 34%, P = .731; event-free survival [EFS]: GO 53% v No-GO 58%, P = .456). However, patients with higher CD33 expression (Q2 to Q4) had significantly reduced RR (GO 32% v No-GO 49%, P < .001) and improved EFS (GO 53% v No-GO 41%, P = .005). This differential effect was observed in all risk groups. Specifically, low-risk (LR), intermediate-risk (IR), and high-risk (HR) patients with low CD33 expression had similar outcomes regardless of GO exposure, whereas the addition of GO to conventional chemotherapy resulted in a significant decrease in RR and disease-free survival (DFS) for patients with higher CD33 expression (LR RR, GO 13% v No-GO 35%, P = .001; LR DFS, GO 79% v No-GO 59%, P = .007; IR RR, GO 44% v No-GO 57%, P = .044; IR DFS, GO 51% v No-GO 40%, P = .078; HR RR, GO 40% v No-GO 73%, P = .016; HR DFS, GO 47% v No-GO 28%, P = .135). Conclusion We demonstrate that GO lacks clinical benefit in patients with low CD33 expression but significantly reduces RR and improves EFS in patients with high CD33 expression, which suggests a role for CD33-targeted therapeutics in subsets of pediatric AML.
Gemtuzumab Ozogamicin Versus Best Supportive Care in Older Patients With Newly Diagnosed Acute Myeloid Leukemia Unsuitable for Intensive Chemotherapy: Results of the Randomized Phase III EORTC-GIMEMA AML-19 Trial
Authors: Amadori Sergio , Suciu Stefan , Selleslag Dominik , Aversa Franco , Gaidano Gianluca , Musso Maurizio , Annino Luciana , Venditti Adriano , Voso Maria Teresa , Mazzone Carla , Magro Domenico , De Fabritiis Paolo , Muus Petra , Alimena Giuliana , Mancini Marco , Hagemeijer Anne , Paoloni Francesca , Vignetti Marco , Fazi Paola , Meert Liv , Ramadan Safaa Mahmoud , Willemze Roel , de Witte Theo , Baron Frédéric 
Published: January 2016

Purpose To compare single-agent gemtuzumab ozogamicin (GO) with best supportive care (BSC) including hydroxyurea as first-line therapy in older patients with acute myeloid leukemia unsuitable for intensive chemotherapy. Patients and Methods In this trial, patients at least 61 years old were centrally randomized (1:1) to receive either a single induction course of GO (6 mg/m2 on day 1 and 3 mg/m2 on day 8) or BSC. Patients who did not progress after GO induction could receive up to eight monthly infusions of the immunoconjugate at 2 mg/m2. Randomization was stratified by age, WHO performance score, CD33 expression status, and center. The primary end point was overall survival (OS) by intention-to-treat analysis. Results A total of 237 patients were randomly assigned (118 to GO and 119 to BSC). The median OS was 4.9 months (95% CI, 4.2 to 6.8 months) in the GO group and 3.6 months (95% CI, 2.6 to 4.2 months) in the BSC group (hazard ratio, 0.69; 95% CI, 0.53 to 0.90; P = .005); the 1-year OS rate was 24.3% with GO and 9.7% with BSC. The OS benefit with GO was consistent across most subgroups, and was especially apparent in patients with high CD33 expression status, in those with favorable/intermediate cytogenetic risk profile, and in women. Overall, complete remission (CR [complete remission] + CRi [CR with incomplete recovery of peripheral blood counts]) occurred in 30 of 111 (27%) GO recipients. The rates of serious adverse events (AEs) were similar in the two groups, and no excess mortality from AEs was observed with GO. Conclusion First-line monotherapy with low-dose GO, as compared with BSC, significantly improved OS in older patients with acute myeloid leukemia who were ineligible for intensive chemotherapy. No unexpected AEs were identified and toxicity was manageable.