bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating multiple molecular sources into a clinical risk prediction signature by extracting complementary information
Authors: Hieke Stefanie , Benner Axel , Schlenl Richard F. , Schumacher Martin , Bullinger Lars , Binder Harald 
Published: August 2016

AbstractBackgroundHigh-throughput technology allows for genome-wide measurements at different molecular levels for the same patient, e.g. single nucleotide polymorphisms (SNPs) and gene expression. Correspondingly, it might be beneficial to also integrate complementary information from different molecular levels when building multivariable risk prediction models for a clinical endpoint, such as treatment response or survival. Unfortunately, such a high-dimensional modeling task will often be complicated by a limited overlap of molecular measurements at different levels between patients, i.e. measurements from all molecular levels are available only for a smaller proportion of patients.ResultsWe propose a sequential strategy for building clinical risk prediction models that integrate genome-wide measurements from two molecular levels in a complementary way. To deal with partial overlap, we develop an imputation approach that allows us to use all available data. This approach is investigated in two acute myeloid leukemia applications combining gene expression with either SNP or DNA methylation data. After obtaining a sparse risk prediction signature e.g. from SNP data, an automatically selected set of prognostic SNPs, by componentwise likelihood-based boosting, imputation is performed for the corresponding linear predictor by a linking model that incorporates e.g. gene expression measurements. The imputed linear predictor is then used for adjustment when building a prognostic signature from the gene expression data. For evaluation, we consider stability, as quantified by inclusion frequencies across resampling data sets. Despite an extremely small overlap in the application example with gene expression and SNPs, several genes are seen to be more stably identified when taking the (imputed) linear predictor from the SNP data into account. In the application with gene expression and DNA methylation, prediction performance with respect to survival also indicates that the proposed approach might work well.ConclusionsWe consider imputation of linear predictor values to be a feasible and sensible approach for dealing with partial overlap in complementary integrative analysis of molecular measurements at different levels. More generally, these results indicate that a complementary strategy for integrating different molecular levels can result in more stable risk prediction signatures, potentially providing a more reliable insight into the underlying biology.
Fold-specific sequence scoring improves protein sequence matching
Authors: Leelananda Sumudu P. , Kloczkowski Andrzej , Jernigan Robert L. 
Published: August 2016

Abstract
Background
Sequence matching is extremely important for applications throughout biology, particularly for discovering information such as functional and evolutionary relationships, and also for discriminating between unimportant and disease mutants. At present the functions of a large fraction of genes are unknown; improvements in sequence matching will improve gene annotations. Universal amino acid substitution matrices such as Blosum62 are used to measure sequence similarities and to identify distant homologues, regardless of the structure class. However, such single matrices do not take into account important structural information evident within the different topologies of proteins and treats substitutions within all protein folds identically. Others have suggested that the use of structural information can lead to significant improvements in sequence matching but this has not yet been very effective. Here we develop novel substitution matrices that include not only general sequence information but also have a topology specific component that is unique for each CATH topology. This novel feature of using a combination of sequence and structure information for each protein topology significantly improves the sequence matching scores for the sequence pairs tested. We have used a novel multi-structure alignment method for each homology level of CATH in order to extract topological information.

Results
We obtain statistically significant improved sequence matching scores for 73 % of the alpha helical test cases. On average, 61 % of the test cases showed improvements in homology detection when structure information was incorporated into the substitution matrices. On average z-scores for homology detection are improved by more than 54 % for all cases, and some individual cases have z-scores more than twice those obtained using generic matrices. Our topology specific similarity matrices also outperform other traditional similarity matrices and single matrix based structure methods. When default amino acid substitution matrix in the Psi-blast algorithm is replaced by our structure-based matrices, the structure matching is significantly improved over conventional Psi-blast. It also outperforms results obtained for the corresponding HMM profiles generated for each topology.

Conclusions
We show that by incorporating topology-specific structure information in addition to sequence information into specific amino acid substitution matrices, the sequence matching scores and homology detection are significantly improved. Our topology specific similarity matrices outperform other traditional similarity matrices, single matrix based structure methods, also show improvement over conventional Psi-blast and HMM profile based methods in sequence matching. The results support the discriminatory ability of the new amino acid similarity matrices to distinguish between distant homologs and structurally dissimilar pairs.
A genetic algorithm-based weighted ensemble method for predicting transposon-derived piRNAs
Authors: Li Dingfang , Luo Longqiang , Zhang Wen , Liu Feng , Luo Fei 
Published: August 2016

Abstract
Background
Predicting piwi-interacting RNA (piRNA) is an important topic in the small non-coding RNAs, which provides clues for understanding the generation mechanism of gamete. To the best of our knowledge, several machine learning approaches have been proposed for the piRNA prediction, but there is still room for improvements.

Results
In this paper, we develop a genetic algorithm-based weighted ensemble method for predicting transposon-derived piRNAs. We construct datasets for three species: Human, Mouse and Drosophila. For each species, we compile the balanced dataset and imbalanced dataset, and thus obtain six datasets to build and evaluate prediction models. In the computational experiments, the genetic algorithm-based weighted ensemble method achieves 10-fold cross validation AUC of 0.932, 0.937 and 0.995 on the balanced Human dataset, Mouse dataset and Drosophila dataset, respectively, and achieves AUC of 0.935, 0.939 and 0.996 on the imbalanced datasets of three species. Further, we use the prediction models trained on the Mouse dataset to identify piRNAs of other species, and the models demonstrate the good performances in the cross-species prediction.

Conclusions
Compared with other state-of-the-art methods, our method can lead to better performances. In conclusion, the proposed method is promising for the transposon-derived piRNA prediction. The source codes and datasets are available in https://github.com/zw9977129/piRNAPredictor.
Solid organ fabrication: comparison of decellularization to 3D bioprinting
Authors: Jung Jangwook P. , Bhuiyan Didarul B. , Ogle Brenda M. 
Published: August 2016

Abstract
Solid organ fabrication is an ultimate goal of Regenerative Medicine. Since the introduction of Tissue Engineering in 1993, functional biomaterials, stem cells, tunable microenvironments, and high-resolution imaging technologies have significantly advanced efforts to regenerate in vitro culture or tissue platforms. Relatively simple flat or tubular organs are already in (pre)clinical trials and a few commercial products are in market. The road to more complex, high demand, solid organs including heart, kidney and lung will require substantive technical advancement. Here, we consider two emerging technologies for solid organ fabrication. One is decellularization of cadaveric organs followed by repopulation with terminally differentiated or progenitor cells. The other is 3D bioprinting to deposit cell-laden bio-inks to attain complex tissue architecture. We reviewed the development and evolution of the two technologies and evaluated relative strengths needed to produce solid organs, with special emphasis on the heart and other tissues of the cardiovascular system.
A branched TAT cell-penetrating peptide as a novel delivery carrier for the efficient gene transfection
Authors: Jeong Chanuk , Yoo Jisang , Lee DaeYong , Kim Yeu-Chun 
Published: August 2016

Abstract

Background
Cell penetrating peptides (CPPs) as one class of non-viral vectors, have been widely explored as a delivery tool due to their cell-penetrating capability with low cytotoxicity. However, CPPs have reported to have low gene transfection efficiency mainly due to the fact that DNA is larger than other biomolecules. On the other hand, the conventional linear CPPs are unstable for constructing the DNA complexes with it. Thus, here we designed a branched CPP using disulfide bridges based on the linear TAT peptide, to enhance the gene delivery efficiency in a better way.

Results
The branched TAT (BTAT) was synthesized by the DMSO oxidation method and showed high-molecular-weight about 294 kDa. The resulting BTAT was complexed with plasmid green fluorescence protein (pGFP) gene at various N/P ratios. The gene transfection efficiency was assessed on HeLa cells after treating with BTAT/pGFP complexes, showed high gene transfection efficiency as conformed by flowcytometry followed by confocal laser scanning microscopy (CLSM) visualization.

Conclusion
The novel BTAT/pGFP complex exhibited significantly higher stability and redox cleavability by reducing agent. In addition, BTAT showed higher transfection efficiency approximately 40-fold than those of the TAT and mTAT complexes. Our primary experiments demonstrated the potential of BTAT as a suitable candidate for gene delivery and it could be applied for various types of gene delivery platforms.
HER2 Gene Amplification Testing by Fluorescent In Situ Hybridization (FISH): Comparison of the ASCO-College of American Pathologists Guidelines With FISH Scores Used for Enrollment in Breast Cancer International Research Group Clinical Trials
Authors: Press Michael F. , Sauter Guido , Buyse Marc , Fourmanoir Hélène , Quinaux Emmanuel , Tsao-Wei Denice D. , Eiermann Wolfgang , Robert Nicholas , Pienkowski Tadeusz , Crown John , Martin Miguel , Valero Vicente , Mackey John R. , Bee Valerie , Ma Yanling , Villalobos Ivonne , Campeau Anaamika , Mirlacher Martina , Lindsay Mary-Ann , Slamon Dennis J. 
Published: August 2016

Purpose ASCO and the College of American Pathologists (ASCO-CAP) recently recommended further changes to the evaluation of human epidermal growth factor receptor 2 gene (HER2) amplification by fluorescent in situ hybridization (FISH). We retrospectively assessed the impact of these new guidelines by using annotated Breast Cancer International Research Group (BCIRG) -005, BCIRG-006, and BCIRG-007 clinical trials data for which we have detailed outcomes. Patients and Methods The HER2 FISH status of BCIRG-005/006/007 patients with breast cancers was re-evaluated according to current ASCO-CAP guidelines, which designates five different groups according to HER2 FISH ratio and average HER2 gene copy number per tumor cell: group 1 (in situ hybridization [ISH]–positive): HER2-to-chromosome 17 centromere ratio ≥ 2.0, average HER2 copies ≥ 4.0; group 2 (ISH-positive): ratio ≥ 2.0, copies < 4.0; group 3 (ISH-positive): ratio < 2.0, copies ≥ 6.0; group 4 (ISH-equivocal): ratio < 2.0, copies ≥ 4.0 and < 6.0; and group 5 (ISH-negative): ratio < 2.0, copies < 4.0. We assessed correlations with HER2 protein, clinical outcomes by disease-free survival (DFS) and overall survival (OS) and benefit from trastuzumab therapy (hazard ratio [HR]). Results Among 10,468 patients with breast cancers who were successfully screened for trial entry, 40.8% were in ASCO-CAP ISH group 1, 0.7% in group 2; 0.5% in group 3, 4.1% in group 4, and 53.9% in group 5. Distributions were similar in screened compared with accrued subpopulations. Among accrued patients, FISH group 1 breast cancers were strongly correlated with immunohistochemistry 3+ status (P < .0001), whereas groups 2, 3, 4, and 5 were not; however, groups 2, 4 and, 5 were strongly correlated with immunohistochemistry 0/1+ status (all P < .0001), whereas group 3 was not. Among patients accrued to BCIRG-005, group 4 was not associated with significantly worse DFS or OS compared with group 5. Among patients accrued to BCIRG-006, only group 1 showed a significant benefit from trastuzumab therapy (DFS HR, 0.71; 95% CI, 0.60 to 0.83; P < .0001; OS HR, 0.69; 95% CI, 0.55 to 0.85; P = .0006), whereas group 2 did not. Conclusion Our findings support the original categorizations of HER2 by FISH status in BCIRG/Translational Research in Oncology trials.
How Does Caregiver Well-Being Relate to Perceived Quality of Care in Patients With Cancer? Exploring Associations and Pathways
Authors: Litzelman Kristin , Kent Erin E. , Mollica Michelle , Rowland Julia H. 
Published: August 2016

Purpose Perceived quality of care (QOC) is an increasingly important metric of care quality and can be affected by such factors among patients with cancer as quality of life and physician trust. This study sought to evaluate whether informal caregiver well-being was also associated with perceived QOC among patients with cancer and assessed potential pathways that link these factors. Methods This study used data from the Cancer Care Outcomes Research and Surveillance (CanCORS) consortium. Patients with lung and colorectal cancer enrolled in CanCORS (N = 689) nominated an informal caregiver to participate in a caregiving survey. Both groups self-reported sociodemographic, psychosocial, and caregiving characteristics; cancer characteristics were obtained from the CanCORS core data set. Multivariable logistic regression was used to assess the association between caregiver psychosocial factors and subsequent patient-perceived QOC, controlling for earlier patient-perceived QOC and covariates. Secondary analysis examined potential pathways that link these factors. Results Patients whose informal caregiver had higher levels of depressive symptoms were significantly more likely to report fair or poor QOC (odds ratio, 1.06; 95% CI, 1.01 to 1.13). When caregivers reported fair or poor self-rated health, patients were more than three times more likely to report fair or poor perceived QOC (odds ratio, 3.76; 95% CI, 1.76 to 9.55). Controlling for patient psychosocial factors and physician communication and coordination of medical care reduced the effect size and/or statistical significance of these relationships. Conclusion Informal caregivers are an important part of the care team and their well-being is associated with patient-perceived QOC. Engaging informal cancer caregivers as part of the care team and conducting ongoing risk stratification screening and intervention to optimize their health may improve patient-reported outcomes and QOC.
Phase II Weekly Vinblastine for Chemotherapy-Naïve Children With Progressive Low-Grade Glioma: A Canadian Pediatric Brain Tumor Consortium Study
Authors: Lassaletta Alvaro , Scheinemann Katrin , Zelcer Shayna M. , Hukin Juliette , Wilson Beverley A. , Jabado Nada , Carret Anne Sophie , Lafay-Cousin Lucie , Larouche Valerie , Hawkins Cynthia E. , Pond Gregory Russell , Poskitt Ken , Keene Daniel , Johnston Donna L. , Eisenstat David D. , Krishnatry Rahul , Mistry Matthew , Arnoldo Anthony , Ramaswamy Vijay , Huang Annie , Bartels Ute , Tabori Uri , Bouffet Eric 
Published: August 2016

Purpose Vinblastine monotherapy has shown promising activity and a low-toxicity profile in patients with pediatric low-grade glioma (PLGG) who experienced treatment failure after initial treatment with chemotherapy and/or radiation. The aim of this study was to assess the activity of vinblastine in therapy-naïve children. Patients and Methods Patients < 18 years old with unresectable and/or progressive therapy-naïve PLGG were eligible. Vinblastine was administered once per week at a dose of 6 mg/m2 intravenously over a period of 70 weeks. Vision, quality of life, neurofibromatosis type 1 (NF1) status, and BRAF mutation/fusion status were also determined and correlated with outcome. Results Fifty-four patients were enrolled onto the study, with a median age of 8 years (range, 0.7 to 17.2 years). Most patients had chiasmatic/hypothalamic tumors (55.5%), and 13 patients (24.1%) had NF1. The most common histology was pilocytic astrocytoma (46.3%). Seventeen patients were diagnosed using radiologic criteria alone. Best response to chemotherapy was centrally reviewed with a response rate (complete, partial, or minor response) of 25.9%. Disease stabilization (complete, partial, or minor response or stable disease) was achieved in 47 patients (87.0%). Visual improvement was observed in 20% of patients with optic pathway glioma. Five-year overall survival and progression-free survival (PFS) rates were 94.4% (95% CI, 88.5% to 100%) and 53.2% (95% CI, 41.3% to 68.5%), respectively, for the entire cohort. Patients with NF1 had a significantly better PFS (85.1%; 95% CI, 68.0% to 100%) when compared with patients without NF1 (42.0%; 95% CI, 29.1% to 60.7%; P = .012). Age< 3 years or > 10 years was not associated with poor outcome. Treatment was well tolerated, and quality of life was not affected during treatment. In this trial, there was no correlation between BRAF alterations and outcome. Conclusion Vinblastine administered once per week is well tolerated in children with treatment naïve PLGG. Overall survival and PFS are comparable to current therapies, with a favorable toxicity profile and a maintained quality of life.
Applying machine learning to automated segmentation of head and neck tumour volumes and organs at risk on radiotherapy planning CT and MRI scans
Authors: Chu Carlton , De Fauw Jeffrey , Tomasev Nenad , Paredes Bernardino Romera , Hughes Cían , Ledsam Joseph , Back Trevor , Montgomery Hugh , Rees Geraint , Raine Rosalind , Sullivan Kevin , Moinuddin Syed , D'Souza Derek , Ronneberger Olaf , Mendes Ruheena , Cornebise Julien 
Published: August 2016

Radiotherapy is one of the main ways head and neck cancers are treated; radiation is used to kill cancerous cells and prevent their recurrence. Complex treatment planning is required to ensure that enough radiation is given to the tumour, and little to other sensitive structures (known as organs at risk) such as the eyes and nerves which might otherwise be damaged. This is especially difficult in the head and neck, where multiple at-risk structures often lie in extremely close proximity to the tumour. It can take radiotherapy experts four hours or more to pick out the important areas on planning scans (known as segmentation). This research will focus on applying machine learning algorithms to automatic segmentation of head and neck planning computed tomography (CT) and magnetic resonance imaging (MRI) scans at University College London Hospital NHS Foundation Trust patients. Through analysis of the images used in radiotherapy DeepMind Health will investigate improvements in efficiency of cancer treatment pathways.
Shedding new light on old algae: Matching names and sequences in the brown algal genus Lobophora (Dictyotales, Phaeophyceae)
Authors: Vieira Christophe , Camacho Olga , Wynne Michael J. , Mattio Lydiane , Anderson Robert J. , Bolton John J. , Sansón Marta , D'hondt Sofie , Leliaert Frederik , Fredericq Suzanne , Payri Claude , De Clerck Olivier 
Published: August 2016

AbstractThe existence of massive cryptic diversity in algae makes linking DNA‐based lineages to existing taxa exceedingly difficult. A better integration of historical collections into modern taxonomic research is therefore highly desirable. Using the brown algal genus Lobophora as a test case, we explore the feasibility of linking taxonomic names to clades in modern phylogenies. Despite Lobophora being a pantropical genus with probably more than 100 species, traditionally only a handful of species have been recognized. In this study we reevaluated the identity of 17 historical taxa thought to belong to Lobophora by attempting DNA amplification of herbarium material as well as specimens recently collected from the type localities (epitypes). In an attempt to assign them to Molecular Operational Taxonomic Units, the obtained sequences were integrated in a global Lobophora phylogeny based upon data derived from more than 650 specimens. Our results indicate that although five sequences were obtained from type specimens, exclusive reliance on information preserved in type specimens is problematic. Epitype material proved a more successful way forward, but this route often comes with a considerable degree of uncertainty, especially in tropical regions where the extent of sympatry among Lobophora lineages is often considerable. More problematic from a broader perspective is the fact that for 35% of historical taxa, either the type could not be traced or permission was not granted to extract DNA from the types. Such a low accessibility rate may reduce our reliance on type material and jeopardize future efforts to integrate historical taxa into a framework of a modern DNA‐based taxonomy.
A revised generic classification of vittarioid ferns (Pteridaceae) based on molecular, micromorphological, and geographic data
Authors: Schuettpelz Eric , Chen Cheng-Wei , Kessler Michael , Pinson Jerald B. , Johnson Gabriel , Davila Alex , Cochran Alyssa T. , Huiet Layne , Pryer Kathleen M. 
Published: August 2016

AbstractVittarioid ferns compose a well‐supported clade of 100–130 species of highly simplified epiphytes in the family Pteridaceae. Generic circumscriptions within the vittarioid clade were among the first in ferns to be evaluated and revised based on molecular phylogenetic data. Initial analyses of rbcL sequences revealed strong geographic structure and demonstrated that the two largest vittarioid genera, as then defined, each had phylogenetically distinct American and Old World components. The results of subsequent studies that included as many as 36 individuals of 33 species, but still relied on a single gene, were generally consistent with the early findings. Here, we build upon the previous datasets, incorporating many more samples (138 individuals representing 72 species) and additional plastid markers (atpA, chlN, rbcL, rpoA). Analysis of our larger dataset serves to better characterize known lineages, reveals new lineages, and ultimately uncovers an underlying geographic signal that is even stronger than was previously appreciated. In our revised generic classification, we recognize a total of eleven vittarioid genera. Each genus, including the new genus Antrophyopsis (Benedict) Schuettp., stat. nov., is readily diagnosable based on morphology, with micromorphological characters related to soral paraphyses and spores complementing more obvious features such as venation and the distribution of sporangia. A key to the currently recognized vittarioid genera, brief generic descriptions, and five new species combinations are provided.