bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patients unfit for neoadjuvant therapy may still undergo resection of locally advanced esophageal or esophagogastric junctional cancer with acceptable oncological results
Authors: O’Neill J. Robert , Kennedy Ewan D. , Save Vicki , Langdale-Brown Barbara , Wall Lucy , Skipworth Richard J.E. , Paterson-Brown Simon 
Published: January 2017

Introduction:
Neoadjuvant chemotherapy (NA) is routinely offered to patients undergoing resection for locally advanced (≥cT3Nx or cTxN+) esophageal or esophagogastric junctional (EGJ) cancer in the United Kingdom. Patients with comorbidity precluding the use of NA can be considered for resection yet the effect of omitting NA on survival is unclear.

Methods:
Retrospective review of prospectively collected clinical data from patients undergoing attempted curative therapy for ≥cT3Nx or cTxN+ esophageal or EGJ (Siewert type I-III) cancer between 2001 and 2013.

Results:
NA was commenced in 289 patients and primarily comprised 2 cycles of cisplatin and 5-fluorouracil (264 patients, 91%). Surgery alone was planned for 82 patients with NA omitted due to comorbidity. Patients undergoing surgery alone were matched for clinical variables and stage with those undergoing NA but were significantly older (mean=8 y, P<0.001). NA was associated with an improved median overall survival of 28.7 months, compared with 20.9 months for patients undergoing surgery alone (P=0.008). Patients undergoing surgery alone had a 90-day postoperative mortality rate of 10% compared with 3% for those undergoing NA (P=0.011). In patients discharged postoperatively, the median overall survival benefit of NA was 2.7 months (P=0.048). Those 19% of patients experiencing a significant histologic response to NA demonstrated further improved survival.

Conclusions:
NA improves survival in patients undergoing resection for locally advanced esophageal or EGJ cancer; however, the median benefit is <3 months in patients discharged postoperatively. Patients precluded from NA achieve acceptable oncological results but experience a higher risk of perioperative mortality.
Microbiota-targeted therapies on the intensive care unit
Authors: Haak Bastiaan W. , Levi Marcel , Wiersinga W. Joost 
Published: January 2017

Purpose of review
The composition and diversity of the microbiota of the human gut, skin, and several other sites is severely deranged in critically ill patients on the ICU, and it is likely that these disruptions can negatively affect outcome. We here review new and ongoing studies that investigate the use of microbiota-targeted therapeutics in the ICU, and provide recommendations for future research.

Recent findings
Practically every intervention in the ICU as well as the physiological effects of critical illness itself can have a profound impact on the gut microbiota. Therapeutic modulation of the microbiota, aimed at restoring the balance between ‘pathogenic’ and ‘health-promoting’ microbes is therefore of significant interest. Probiotics have shown to be effective in the treatment of ventilator-associated pneumonia, and the first fecal microbiota transplantations have recently been safely and successfully performed in the ICU. However, all-encompassing data in this vulnerable patient group remain sparse, and only a handful of novel studies that study microbiota-targeted therapies in the ICU are currently ongoing.

Summary
Enormous strides have been made in characterizing the gut microbiome of critically ill patients in the ICU, and an increasing amount of preclinical data reveals the huge potential of microbiota-targeted therapies. Further understanding of the causes and consequences of dysbiosis on ICU-related outcomes are warranted to push the field forward.
Incidence of Occult Intrahepatic Metastasis in Hepatocellular Carcinoma Treated With Transplantation Corresponds to Early Recurrence Rates After Partial Hepatectomy
Authors: Aufhauser David D. , Sadot Eran , Murken Douglas R. , Eddinger Kevin , Hoteit Maarouf , Abt Peter L. , Goldberg David S. , DeMatteo Ronald P. , Levine Matthew H. 
Published: January 2017

Objective:
This study aimed to compare the incidence of radiologically unrecognized (occult) hepatocellular carcinoma (HCC) lesions in explant hepatectomy specimens from orthotopic liver transplants (OLTs) performed for HCC with rates of HCC intrahepatic recurrence after resection.

Summary of Background Data:
Resection of HCC is associated with high rates of intrahepatic HCC recurrence. However, it is unclear whether these recurrences represent incomplete resection of unrecognized metastatic lesions from the primary tumor or subsequent de novo tumor formation due to inherent biological proclivity for HCC formation.

Methods:
We collected patient, tumor, and pathology data on HCC patients treated surgically from 3696 OLTs in the Organ Procurement and Transplantation (OPTN) national database, 299 OLTs at a single transplant center, and 232 partial hepatectomies from a hepatobiliary cancer center.

Results:
In the OPTN and high-volume transplant center cohorts, 37% and 42% of patients had occult HCC lesions on explant pathology, respectively. Among cancer center patients, the 2-year recurrence rate was 46%, and 74% of patients who recurred presented with liver only recurrence.

Conclusion:
Although the transplant and resection populations differ, occult multifocality is common in transplant explants and similar to the 46% early recurrence rate following partial hepatectomy. These data suggest that noncurative resection often results from occult intrahepatic multifocality present at the time of resection rather than a malignant predisposition of the remnant liver with de novo tumorigenesis.
DeeperBind: Enhancing Prediction of Sequence Specificities of DNA Binding Proteins
Authors: Hassanzadeh Hamid Reza , Wang May D. 
Published: January 2017

AbstractTranscription factors (TFs) are macromolecules that bind tocis-regulatory specific sub-regions of DNA promoters and initiate transcription. Finding the exact location of these binding sites (aka motifs) is important in a variety of domains such as drug design and development. To address this need, severalin vivoandin vitrotechniques have been developed so far that try to characterize and predict the binding specificity of a protein to different DNA loci. The major problem with these techniques is that they are not accurate enough in prediction of the binding affinity and characterization of the corresponding motifs. As a result, downstream analysis is required to uncover the locations where proteins of interest bind. Here, we propose DeeperBind, a long short term recurrent convolutional network for prediction of protein binding specificities with respect to DNA probes. DeeperBind can model the positional dynamics of probe sequences and hence reckons with the contributions made by individual sub-regions in DNA sequences, in an effective way. Moreover, it can be trained and tested on datasets containing varying-length sequences. We apply our pipeline to the datasets derived from protein binding microarrays (PBMs), an in-vitro high-throughput technology for quantification of protein-DNA binding preferences, and present promising results. To the best of our knowledge, this is the most accurate pipeline that can predict binding specificities of DNA sequences from the data produced by high-throughput technologies through utilization of the power of deep learning for feature generation and positional dynamics modeling.
Whole genome and RNA sequencing of 1,220 cancers reveals hundreds of genes deregulated by rearrangement of cis-regulatory elements
Authors: Zhang Yiqun , Chen Fengju , Fonseca Nuno A. , He Yao , Fujita Masashi , Nakagawa Hidewaki , Zhang Zemin , Brazma Alvis , Creighton Chad J. ,   on behalf of the PCAWG Transcriptome Working Group, PCAWG Structural Variation Working Group,   ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Network
Published: January 2017

AbstractUsing a dataset of somatic Structural Variants (SVs) in cancers from 2658 patients—1220 with corresponding gene expression data—we identified hundreds of genes for which the nearby presence (within 100kb) of an SV breakpoint was associated with altered expression. For the vast majority of these genes, expression was increased rather than decreased with corresponding SV event. Well-known up-regulated cancer-associated genes impacted by this phenomenon includedTERT,MDM2,CDK4,ERBB2,CD274,PDCD1LG2, andIGF2. SVs upstream ofTERTinvolved ~3% of cancer cases and were most frequent in liver-biliary, melanoma, sarcoma, stomach, and kidney cancers. SVs associated with up-regulation of PD1 and PDL1 genes involved ~1% of non-amplified cases. For many genes, SVs were significantly associated with either increased numbers or greater proximity of enhancer regulatory elements near the gene. DNA methylation near the gene promoter was often increased with nearby SV breakpoint, which may involve inactivation of repressor elements.AbbreviationsPCAWGthe Pan-Cancer Analysis of Whole Genomes projectSVStructural Variant
Toddlers later diagnosed with autism exhibit multiple structural abnormalities in temporal corpus callosum fibers
Authors: Fingher Noa , Dinstein Ilan , Ben-Shachar Michal , Haar Shlomi , Dale Anders M. , Eyler Lisa , Pierce Karen , Courchesne Eric 
Published: January 2017

AbstractInterhemispheric functional connectivity abnormalities are often reported in autism and it is thus not surprising that structural defects of the corpus callosum (CC) are consistently found using both traditional MRI and DTI techniques. Past DTI studies however, have subdivided the CC into 2 or 3 segments without regard for where fibers may project to within the cortex, thus placing limitations on our ability to understand the nature, timing and neurobehavioral impact of early CC abnormalities in autism. Leveraging a unique cohort of 97 toddlers (68 autism; 29 typical) we utilized a novel technique that identified seven CC tracts according to their cortical projections. Results revealed that younger (<2.5 years old), but not older toddlers with autism exhibited abnormally low mean, radial, and axial diffusivity values in the CC tracts connecting the occipital lobes and the temporal lobes. Fractional anisotropy and the cross sectional area of the temporal CC tract were significantly larger in young toddlers with autism. These findings indicate that water diffusion is more restricted and unidirectional in the temporal CC tract of young toddlers who develop autism. Such results may be explained by a potential overabundance of small caliber axons generated by excessive prenatal neural proliferation as proposed by previous genetic, animal model, and postmortem studies of autism. Furthermore, early diffusion measures in the temporal CC tract of the young toddlers were correlated with outcome measures of autism severity at later ages. These findings regarding the potential nature, timing, and location of early CC abnormalities in autism add to accumulating evidence, which suggests that altered inter-hemispheric connectivity, particularly across the temporal lobes, is a hallmark of the disorder.
Evaluation of Oxford Nanopore MinIONTMSequencing for 16S rRNA Microbiome Characterization
Authors: Ma Xiao , Stachler Elyse , Bibby Kyle 
Published: January 2017

AbstractIn this manuscript we evaluate the potential for microbiome characterization by sequencing of near-full length 16S rRNA gene region fragments using the Oxford Nanopore MinION (hereafter ‘Nanopore’) sequencing platform. We analyzed pure-cultureE. coliandP. fluorescens, as well as a low-diversity mixed community sample from hydraulic fracturing produced water. Both closed and open reference operational taxonomic unit (OTU) picking failed, necessitating the direct use of sequences without OTU picking. The Ribosomal Database Project classifier against the Green Genes database was found to be the optimal annotation approach, with average pure-culture annotation accuracies of 93.8% and 82.0% at the phyla and genus levels, respectively. Comparative analysis of an environmental sample using Nanopore and Illumina MiSeq sequencing identified high taxonomic similarity when using a weighted metric (Bray-Curtis), and significantly reduced similarity when using an unweighted metric (Jaccard). These results highlight the great potential of Nanopore sequencing to analyze broad microbial community trends, and the challenge of applying Nanopore sequencing to discern rare taxa in mixed microbial communities. Finally, we observed that between-run carryover following washes on the same flowcell accounted for >10% of sequence reads, necessitating future development to either prevent carryover or filter sequences of interest (e.g. barcoding).
Distributed Biotin-Streptavidin Transcription Roadblocks for Mapping Cotranscriptional RNA Folding
Authors: Strobel Eric J. , Watters Kyle E. , Lucks Julius B. 
Published: January 2017

AbstractRNA molecules fold cotranscriptionally as they emerge from RNA polymerase. Cotranscriptional folding is an important process for proper RNA structure formation as the order of folding can determine an RNA molecule’s structure, and thus its functional properties. Despite its fundamental importance, the experimental study of RNA cotranscriptional folding has been limited by the lack of easily approachable methods that can interrogate nascent RNA structures at nucleotide resolution during transcription. We previously developed cotranscriptional selective 2’-hydroxyl acylation analyzed by primer extension sequencing (SHAPE-seq) to simultaneously probe all of the intermediate structures an RNA molecule transitions through during transcription elongation. Here, we improve the broad applicability of cotranscriptional SHAPE-Seq by developing a sequence-independent streptavidin roadblocking strategy to simplify the preparation of roadblocking transcription templates. We determine the fundamental properties of streptavidin roadblocks and show that randomly distributed streptavidin roadblocks can be used in cotranscriptional SHAPE-Seq experiments to measure theBacillus cereus crcBfluoride riboswitch folding pathway. Comparison of EcoRIE111Qand streptavidin roadblocks in cotranscriptional SHAPE-Seq data shows that both strategies identify the same RNA structural transitions related to the riboswitch decision-making process. Finally, we propose guidelines to leverage the complementary strengths of each transcription roadblock for use in studying cotranscriptional folding.
Hovering stability of a model helicopter
Authors: Murat Koc Ilker , Franko Semuel , Ozsoy Can 
Published: January 2017

Purpose
The purpose of this paper is to investigate the stability of a small scale six-degree-of-freedom nonlinear helicopter model at translator velocities and angular displacements while it is transiting to hover with different initial conditions.

Design/methodology/approach
In this study, model predictive controller and linear quadratic regulator are designed and compared within each other for the stabilization of the open loop unstable nonlinear helicopter model.

Findings
This study shows that the helicopter is able to reach to the desired target with good robustness, low control effort and small steady-state error under disturbances such as parameter uncertainties, mistuned controller.

Originality/value
The purpose of using model predictive control for three axes of the autopilot is to decrease the control effort and to make the close-loop system insensitive against modeling uncertainties.
Tuning of controller for an aircraft flight control system based on particle swarm optimization
Authors: Kiyak Emre 
Published: January 2017

Purpose
This study aims to present a method for the conceptual design and simulation of an aircraft flight control system.

Design/methodology/approach
The design methodology is based on particle swarm optimization (PSO). PSO can be used to improve the performance of conventional controllers. The aim of the present study is threefold. First, it attempts to detect and isolate faults in an aircraft model. Second, it is to design a proportional (P) controller, a proportional derivative (PD) controller, a proportional-integral (PI) controller and a fuzzy controller for an aircraft model. Third, it is to design a PD controller for an aircraft using a PSO algorithm.

Findings
Conventional controllers, an intelligent controller and a PD controller-based PSO were investigated for flight control. It was seen that the P controller, the PI controller and the PD controller-based PSO caused overshoot. These overshoots were 18.5, 87.7 and 2.6 per cent, respectively. Overshoot was not seen using the PD controller or fuzzy controller. Steady state errors were almost zero for all controllers. The PD controller had the best settling time. The fuzzy controller was second best. The PD controller-based PSO was the third best, but the result was close to the others.

Originality/value
This study shows the implementation of the present algorithm for a specified space mission and also for study regarding variation of performance parameters. This study shows fault detection and isolation procedures and also controller gain choice for a flight control system. A comparison between conventional controllers and PD-based PSO controllers is presented. In this study, sensor fault detection and isolation are carried out, and, also, root locus, time domain analysis and Routh–Hurwitz methods are used to find the conventional controller gains which differ from other studies. A fuzzy controller is created by the trial and error method. Integral of squared time multiplied by squared error is used as a performance function type in PSO.
Flight controller design for aircraft low altitude airdrop
Authors: Liu Ri , Sun Xiuxia , Dong Wenhan 
Published: January 2017

Purpose
During low altitude airdrop operations, the heavy cargo moving inside and the sudden dropping out exert serious threats on the aircraft safety and mission performance. This paper aims to propose an efficient flight control method for the airdrop operations.

Design/methodology/approach
A novel controller which combines feedback linearization with nonlinear integral sliding mode control is proposed. The aircraft airdrop model is decoupled and linearized by using the feedback linearization technique. On this basis, an integral sliding mode controller is designed to stabilize the speed and pitch attitude of the aircraft. In the sliding manifold, one class of nonlinear functions with the property of “smaller errors correspond to bigger gains and bigger errors correspond to saturated gains” is introduced to form the integral term; thus, the overcompensation of the integral term to big errors is omitted, and the dynamic response performance is improved. Lyapunov-based stability analysis shows that the controller could completely reject model uncertainties by choosing proper controller parameters.

Findings
The flight control system with strong robustness could meet the low altitude airdrop indexes in the maximum weight cargo airdrop task.

Originality/value
This paper fulfils an urgent need to study how to control the aircraft to guarantee mission performance and flight safety during the low altitude airdrop operations.
Helicopter stabilizer optimization considering rotor downwash in forward-flight
Authors: Minervino Mauro , Vitagliano Pier Luigi , Quagliarella Domenico 
Published: January 2017

Purpose
The paper aims to reduce the aerodynamic drag of a rotorcraft stabilizer in forward flight by taking into account downwash effects from the main rotor wake (power-on conditions).

Design/methodology/approach
A shape design methodology based on numerical optimization, CAD-in-the-loop (CAD: computer-aided design) approach and high-fidelity Computational Fluid Dynamics (CFD) tools was set-up and applied to modify the horizontal empennage of a rotorcraft configuration. This included the integration of both commercial and in-house computer-aided engineering tools for parametric geometry handling, adaptive mesh generation, CFD solution and evolutionary optimization within a robust evaluation chain for the aerodynamic simulation of the different design candidates generated during the automatic design loop. Geometrical modifications addressed both the stabilizer planform and sections, together with its setting angle in cruise configuration, accounting for impacts on the equilibrium, stability and control characteristics of the empennage.

Findings
An overall improvement of 11.1 per cent over the rotorcraft drag was estimated at the design condition (cruise flight; power-on) for the stabilizer configuration with optimized planform shape, which is increased to 11.4 per cent when combined with the redesigned airfoil to generate the stabilizer surface.

Research limitations/implications
Critical design considerations are introduced with regard to structural and systems integration issues, and a design candidate alternative is identified and proposed as a compromise solution, achieving 8.3 per cent reduction of the rotorcraft configuration drag in cruise conditions with limited increase in the empennage aspect ratio and leading edge sweep angle when compared to the pure aerodynamic optimal design obtained from genetic algorithm evolution.

Originality/value
The proposed methodology faces the empennage design problem by explicitly taking into account the effects of main rotor wake impinging the stabilizer surface in forward flight conditions and using an automated optimization approach which directly incorporates professional CAD tools in the design loop.
Fuzzy logic estimator implemented in observation-tracking device control
Authors: Sobolewski Michal , Grzesik Norbert , Koruba Zbigniew , Nowicki Michal 
Published: January 2017

Purpose
Nowadays, various methods of observation from unmanned aerial vehicles (UAV) are being widely developed. There are many ways of increasing the amount of information retrieved from captured material. Unfortunately, hardware solutions consume a lot of energy, which is unacceptable in UAV applications, as it can have direct impact on the observing time on UAV. Those kinds of problems have been identified during the development phase of stabilizing platform in Polish Research Space Centre in Warsaw. As a result of that fact, energy saving control methods have been implemented, which estimates quality of stabilization process for the observation-tracking device (OTD).

Design/methodology/approach
Mathematical model has been designed and validated with real-life experiments for the purpose of optimization of stabilization and control process. Two types of controlling algorithms have been implemented: linear quadratic regulator and proportional derivative method for driving the mechanism. Based on numerical simulations of the mechanical model being controlled by the mentioned driver, it was possible to define membership functions. After the process of defuzzification, the controller predicts quality of stabilization under defined environmental working conditions.

Findings
An autonomous energy saving system has been created that can be implemented in many applications, where environmental conditions may change significantly.

Practical implications
To test the proposed fuzzy controller, OTD has been chosen as an example object of application. It is a mechanical platform which houses the optical observation system. It is designed to provide the best working conditions during flight.

Originality/value
That kind of decision-making unit has never been implemented before during observations which were carried out during flying of an object. That innovative controller should bring significant energy consumption savings.