bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternative exon skipping biases substrate preference of the deubiquitylase USP15 for mysterin/RNF213, the moyamoya disease susceptibility factor
Authors: Kotani Yuri , Morito Daisuke , Sakata Kenshiro , Ainuki Shiori , Sugihara Munechika , Hatta Tomohisa , Iemura Shun-ichiro , Takashima Seiji , Natsume Tohru , Nagata Kazuhiro 
Published: March 2017

AbstractThe deubiquitylating enzyme USP15 plays significant roles in multiple cellular pathways including TGF-β signaling, RNA splicing, and innate immunity. Evolutionarily conserved skipping of exon 7 occurs during transcription of the mRNAs encoding USP15 and its paralogue USP4, yielding two major isoforms for each gene. Exon 7 of USP15 encodes a serine-rich stretch of 29 amino acid residues located in the inter-region linker that connects the N-terminal putative regulatory region and the C-terminal enzymatic region. Previous findings suggested that the variation in the linker region leads to functional differences between the isoforms of the two deubiquitylating enzymes, but to date no direct evidence regarding such functional divergence has been published. We found that the long isoform of USP15 predominantly recognizes and deubiquitylates mysterin, a large ubiquitin ligase associated with the onset of moyamoya disease. This observation represents the first experimental evidence that the conserved exon skipping alters the substrate specificity of this class of deubiquitylating enzymes. In addition, we found that the interactomes of the short and long isoforms of USP15 only partially overlapped. Thus, USP15, a key gene in multiple cellular processes, generates two functionally different isoforms via evolutionarily conserved exon skipping.
High-efficient production and biophysical characterisation of nicastrin and its interaction with APPC100
Authors: Yu Kun , Yang Ge , Labahn Jörg 
Published: March 2017

AbstractNicastrin, the largest member among the four components of the γ-secretase complex, has been identified to be the substrate recognizer for the proteolytic activity of the complex. Here we report that full-length human nicastrin (hNCT) can be obtained by heterologous expression in E. coli. Milligram quantities of the target protein are purified in a two-step purification protocol using affinity chromatography followed by SEC. The FOS-choline 14 purified tetrameric hNCT exhibits a proper folding with 31% α-helix and 23% β-sheet content. Thermal stability studies reveal stable secondary and tertiary structure of the detergent purified hNCT. A physical interaction between nicastrin and the γ-secretase substrate APPC100 confirmed the functionality of hNCT as a substrate recognizer.
Analysis and design of coded apertures for defocus deblurring based on imaging system properties and optical features
Authors: Masoudifar Mina , Pourreza Hamid Reza 
Published: March 2017

As the physical size of single pixels in digital cameras grows smaller, the captured images are increasingly affected by defocused blurring and consequently valuable details are lost. Different aperture patterns have already been proposed to mitigate this problem based on presumed conditions, which maybe violated in practise. Sensor characteristics and current photometric scene properties have been largely ignored in the design of aperture patterns in the literature. In this study, a number of perceptually optimised coded apertures are introduced for defocused deblurring. These apertures are specifically designed considering illumination conditions, sensor specifications and human visual system characteristics. The designed patterns are compared with circular apertures of equal throughput and pinhole aperture. Experiments show signal‐to‐noise ratio (SNR) gains of up to 0.35 and 2 dB over circular and pinhole apertures, respectively. To study the trade‐off between diffraction and deblurring gains, the proposed binary masks are enhanced by smoothing and morphological operations, which can yield non‐binary and rounded binary patterns. The results of the authors’ study show that rounded binary patterns improve diffraction behaviour while maintaining the desired SNR level.
Realised safety impacts of electronic stability control in Finland
Authors: Öörni Risto , Luoma Juha 
Published: March 2017

The objective of the study is to estimate the realised safety effects of electronic stability control (ESC) in Finland in the current context. The modelling of impacts was based on a framework in which the outcomes of accidents are determined by exposure of road users, accident risk and accident severity. Exposure to risk was modelled in three ways: (i) by calculating the share of passenger cars equipped with ESC with a mathematical model, (ii) on the basis of an ESC fleet penetration estimate obtained from a survey targeted to car importers and (iii) with ESC fleet penetration taking into account the penetration estimate obtained from the survey weighted with the annual kilometrage of passenger cars. The results of the study suggest that around 37 fatalities and 747 injuries were avoided in Finland in 2014 because of ESC.
The Suction Test: A Novel Technique to Identify and Verify Successful Repair of Peripheral Triangular Fibrocartilage Complex Tears
Authors: Greene Ryan , Kakar Sanjeev 
Published: March 2017

Background The diagnoses of peripheral triangular fibrocartilage complex (TFCC) tears continue to be the subject of numerous investigations.
Case Description We describe a novel arthroscopic technique that may be used as an adjunct with other arthroscopic maneuvers to diagnose and confirm repair of peripheral sided TFCC injuries.
Literature Review The hook and trampoline tests are intraoperative techniques to diagnose TFCC tears.
Clinical Relevance The suction test provides a means to detect peripheral tears and to confirm restoration of its tension post repair.
Review of Metronidazole Dosing in Preterm Neonates
Authors: Dannelley Jennifer , Martin Erin , Chaaban Hala , Miller Jamie 
Published: March 2017

AbstractMetronidazole dosing recommendations vary significantly for premature infants in pediatric dosing references and can result in confusion for prescribers. We performed a literature search identifying articles evaluating the pharmacokinetics and dosing of metronidazole in premature infants. The search was limited to English-language articles in MEDLINE (January 1946 to December 2016), EMBASE (January 1974 to December 2016), and International Pharmaceutical Abstracts (January 1970 to December 2016). Reference citations from relevant articles were also reviewed. Six pharmacokinetic studies, representing 152 neonates, were included; however, only three of the well-defined studies were reviewed in depth, and the other three studies were considered foundational. The pharmacokinetic studies included in this review indicate that some published dosing recommendations in pediatric dosing references may result in subtherapeutic metronidazole concentrations. Therefore, postmenstrual age based dosing recommendations were provided by the authors of these pharmacokinetic studies based on a pharmacodynamic target of 6 to 8 mg/L; yet, these dosing recommendations differ from one another. The pharmacokinetic studies included in this review provide some guidance to dosing; however, a major limitation is that outcomes of clinical efficacy and safety were not evaluated. Future studies targeting the optimal dosing and serum concentrations required for clinical efficacy are needed.
Rab5-regulated endocytosis plays a crucial role in apical extrusion of transformed cells
Authors: Saitoh Sayaka , Maruyama Takeshi , Yako Yuta , Kajita Mihoko , Fujioka Yoichiro , Ohba Yusuke , Kasai Nobuhiro , Sugama Natsu , Kon Shunsuke , Ishikawa Susumu , Hayashi Takashi , Yamazaki Tomohiro , Tada Masazumi , Fujita Yasuyuki 
Published: March 2017

Significance
At the initial stage of carcinogenesis, transformation occurs in a single cell within the epithelium. However, it is not clearly understood what happens at the interface between the newly emerging transformed cells and the surrounding normal epithelial cells. Here, using mammalian cell culture and zebrafish embryo systems, we demonstrate that Rab5, an important regulator of endocytosis, is accumulated and that endocytosis is enhanced in RasV12-transformed cells surrounded by normal cells. The elevation of endocytosis disrupts E-cadherin–based cell–cell adhesions with the surrounding normal cells and modulates signaling pathways, eventually leading to apical elimination of the transformed cells. This report demonstrates that endocytosis plays a crucial role in cell competition between normal and transformed epithelial cells in mammals.
Weyl’s Theorem for pairs of commuting hyponormal operators
Authors: Chavan Sameer , Curto Raúl 
Published: March 2017

Let

T

\mathbf {T}

be a pair of commuting hyponormal operators satisfying the so-called quasitriangular property
\[

dim

ker

(

T

−
λ
)
≥

dim

ker

(

T

−

λ

)
∗

,

\textrm {dim} \; \textrm {ker} \; (\mathbf {T}-\boldsymbol \lambda ) \ge \textrm {dim} \; \textrm {ker} \; (\mathbf {T} - {\boldsymbol \lambda })^*,

\]
for every

λ
\boldsymbol \lambda

in the Taylor spectrum

σ
(

T

)

\sigma (\mathbf {T})

of

T

\mathbf {T}

. We prove that the Weyl spectrum of

T

\mathbf {T}

,

ω
(

T

)

\omega (\mathbf {T})

, satisfies the identity
\[

ω
(

T

)
=
σ
(

T

)
∖

π

00

(

T

)
,

\omega (\mathbf {T})=\sigma (\mathbf {T}) \setminus \pi _{00}(\mathbf {T}),

\]
where

π

00

(

T

)

\pi _{00}(\mathbf {T})

denotes the set of isolated eigenvalues of finite multiplicity.

Our method of proof relies on a (strictly

2
2

-variable) fact about the topological boundary of the Taylor spectrum; as a result, our proof does not hold for

d
d

-tuples of commuting hyponormal operators with

d
>
2

d>2

.
HLA-MA: simple yet powerful matching of samples using HLA typing results
Authors: Messerschmidt Clemens , Holtgrewe Manuel , Beule Dieter 
Published: March 2017

Abstract

Summary
We propose the simple method HLA-MA for consistency checking in pipelines operating on human HTS data. The method is based on the HLA typing result of the state-of-the-art method OptiType. Provided that there is sufficient coverage of the HLA loci, comparing HLA types allows for simple, fast and robust matching of samples from whole genome, exome and RNA-seq data. Our approach uses information from small but genetically highly variable regions and thus complements approaches that rely on genome or exon-wide variant profiles.

Availability and Implementation
The software is implemented In Python 3 and freely available under the MIT license at https://github.com/bihealth/hlama and via Bioconda.

Supplementary information
Supplementary data are available at Bioinformatics online.
When ecosystems and their services are not co-located: oceans and coasts
Authors: Drakou Evangelia G. , Pendleton Linwood , Effron Micah , Ingram Jane Carter , Teneva Lida 
Published: March 2017

Abstract
Local, regional, and global policies to manage protect and restore our oceans and coasts call for the inclusion of ecosystem services (ES) in policy-relevant research. Marine and coastal ES and the associated benefits to humans are usually assessed, quantified, and mapped at the ecosystem level to inform policy and decision-making. Yet those benefits may reach humans beyond the provisioning ecosystem, at the regional or even global level. Current efforts to map ES generated by a single ecosystem rarely consider the distribution of benefits beyond the ecosystem itself, especially at the regional or global level. In this article, we elaborate on the concept of “extra-local” ES to refer to those ES generating benefits that are enjoyed far from the providing ecosystem, focusing on the marine environment. We emphasize the spatial dimension of the different components of the ES provision framework and apply the proposed conceptual framework to food provision and climate regulation ES provided by marine and coastal ecosystems. We present the different extents of the mapping outputs generated by the ecosystem-based vs. the extra-local mapping approach and discuss practical and conceptual challenges of the approach. Lack of relevant ES mapping methodologies and lack of data appeared to be the most crucial bottlenecks in applying the extra-local approach for marine and coastal ES. We urge for more applications of the proposed framework that can improve marine and coastal ES assessments help fill in data gaps and generate more robust data. Such assessments could better inform marine and coastal policies, especially those linked to equal attribution of benefits, compensation schemes and poverty alleviation.
Keeping It Real in Experimental Research—Understanding When, Where, and How to Enhance Realism and Measure Consumer Behavior
Authors: Morales Andrea C , Amir On , Lee Leonard 
Published: March 2017

Abstract
In this article, we consider why employing realistic experimental designs and measuring actual behavior is important and beneficial for consumer research. More specifically, we discuss when, where, and how researchers might go about doing this in order to increase the veracity and believability of their work. We analyze the choice of independent variables (IVs) along the experimental-realism dimension, ranging from artificial to realistic, and the choice of dependent variables (DVs) along the behavioral-measures dimension ranging from hypothetical intention to actual behavior. Importantly, we also map various goals of consumer research along these two dimensions to highlight when it is most appropriate to enhance the realism and behavioral measures of an experiment. Using a number of illustrative examples from research in the extant literature, we specifically highlight how consumer researchers can increase experimental realism and utilize actual-behavior measures in their experiments in order to improve both the fidelity of the research and the likelihood that the research provides insight into real consumer behavior.
The Endoscopic Endonasal Transmaxillary Approach to Meckel's Cave Through the Inferior Orbital Fissure
Authors: Zhang Xin , Tabani Halima , El-Sayed Ivan , Russell Matthew , Feng Xuequan , Benet Arnau 
Published: March 2017

Abstract

BACKGROUND: Surgical access to Meckel's Cave (MC) is challenging due to its deep location and surrounding important neurovascular structures. Currently existing endoscopic endonasal (EE) approaches require dissecting near the internal carotid artery (ICA) or require transposition of the pterygopalatine neurovascular bundle.

OBJECTIVE: To describe a novel approach to access the anterolateral aspect of the MC using a minimally invasive EE route.

METHODS: The EE transmaxillary transinferior orbital fissure approach was simulated in 10 specimens. The approach included an ethmoidectomy followed by an extended medial maxillectomy with transposition of the nasolacrimal duct. The infraorbital fissure was opened, and the infraorbital neurovascular bundle was transposed inferiorly. A quadrilateral space, bound by the maxillary nerve inferomedially, ophthalmic nerve superomedially, infraorbital nerve inferolaterally, and floor of the orbit superolaterally, was exposed. The distances from the foramen rotundum (FR) to the ICA, orbital apex (OA), and infratemporal crest (ITC) and from the OA to the ICA and ITC were measured.

RESULTS: The distances obtained were FR-ICA = 19.42 ± 2.03 mm, FR-ITC = 18.76 ± 1.75 mm, FR-OA = 8.54 ± 1.34 mm, OA-ITC = 19.78 ± 2.63 mm, and OA-ICA = 20.64 ± 142 mm. Two imaginary lines defining safety boundaries were observed between the paraclival ICA and OA, and between the OA and ITC (safety lines 1 and 2).

CONCLUSION: The reported approach provides a less invasive route compared to contemporary approaches, allowing expanded views and manipulation anteromedial and anterolateral to MC. It may be safer than the existing approaches as it does not require transposition of the ICA, infratemporal fossa, and pterygopalatine fossa, and allows access to tumors located anteriorly on the floor of the middle cranial fossa.
Functional Outcome After Resection of Von Hippel-Lindau Disease-Associated Cauda Equina Hemangioblastomas: An Observational Cohort Study
Authors: Mehta Gautam U. , Montgomery Blake K. , Maggio Dominic M. , Chittiboina Prashant , Oldfield Edward H. , Lonser Russell R. 
Published: March 2017

Abstract

BACKGROUND: Cauda equina hemangioblastomas in von Hippel-Lindau (VHL) disease can cause significant neurological signs and symptoms. Despite their associated morbidity, the management of these tumors remains incompletely defined.

OBJECTIVE: To determine optimal management, we analyzed the functional outcomes after resection of these tumors.

METHODS: VHL patients who underwent surgical resection of cauda equina hemangioblastomas at the National Institutes of Health and the University of Virginia were included. Clinical and radiological follow-up was performed at 6- to 12-month intervals after surgery.

RESULTS: Fifteen patients underwent 18 operations for 21 cauda equina hemangioblastomas (median follow-up 5.9 years). Patients often presented with multiple symptoms, including pain (67%), numbness (50%), urinary complaints (33%), and weakness (11%). Median preoperative tumor volume was 1.2 cm3. Four tumors at 3 operations were not resected due to a motor nerve root origin. Gross total resection was achieved in 14 surgeries (93% of operations when resection was attempted). New mild (non-function limiting) neurological symptoms were noted after 11 operations (61%), which most often (64%) resolved within 2 weeks of surgery. At 6-month follow-up, 15 patients (83%) were stable, 2 (11%) were improved, and 1 (6%) was worse. Histological analysis revealed that all tumors originated from within the involved nerve fascicle.

CONCLUSIONS: VHL-associated cauda equina hemangioblastomas have an intrafascicular origin and require interruption of the rootlet of origin for complete resection. Motor nerve root involvement may preclude complete resection but strategies including bony decompression and/or interruption of vascular supply may provide a therapeutic option. Nevertheless, most VHL patients with symptom-producing lesions improve with resection.
Sodium-glucose cotransporter-2 inhibitors
Authors: Ashjian Emily , Tingen Jeffrey 
Published: March 2017

Abstract:
The number of patients with type 2 diabetes mellitus (T2DM) continues to increase in the United States. Glycemic control among patients with diabetes is important to prevent future complications, including microvascular and macrovascular disease. A novel class of medications, sodium-glucose cotransporter-2 inhibitors, presents an additional oral treatment option for patients with T2DM.
Medical Student Perceptions of Feedback and Feedback Behaviors Within the Context of the “Educational Alliance”
Authors: Bowen Lucy , Marshall Michelle , Murdoch-Eaton Deborah 
Published: March 2017

Purpose
Using the “educational alliance” as a conceptual framework, the authors explored medical students’ beliefs about feedback and how their feedback behaviors reflect their perceptions.

Method
Five focus groups (four to six medical students each) at one UK medical school in 2015 were used to capture and elucidate learners’ feedback perceptions and behaviors within the context of the learner–educator relationship. A map of key feedback opportunities across the program was used as a tool for exploring student engagement with the feedback process. Qualitative data were analyzed using an approach based on grounded theory principles.

Results
Three learner feedback behaviors emerged: recognizing, using, and seeking feedback. Five core themes influencing these behaviors were generated: learner beliefs, attitudes, and perceptions; relationships; teacher attributes; mode of feedback; and learning culture. Conceptual models illustrating the relationships between the themes and each behavior were developed. Learning culture influenced all three behaviors with a wide context of influences.

Conclusions
Ensuring that feedback leads to improved performance requires more than training educators in best practices. The conceptual models support the educational alliance framework and illustrate the context and complexity of learning culture surrounding the educational relationship, learner, and feedback exchange. The educational alliance approach is underpinned by a mutual understanding of purpose and responsibility. Enhancing learners’ feedback literacy skills seems to be the key aspect of the educational alliance in need of attention. Empowering learners to recognize, seek, and use feedback received within diverse learning cultures is essential.
Age Interactions on Pain Sensitization in Patients With Severe Knee Osteoarthritis and Controls
Authors: Petersen Kristian K. , Arendt-Nielsen Lars , Finocchietti Sara , Hirata Rogerio P. , Simonsen Ole , Laursen Mogens B. , Graven-Nielsen Thomas 
Published: March 2017

Objectives:
Widespread pressure hyperalgesia, facilitated temporal summation of pain (TSP), and impaired conditioned pain modulation (CPM) have been found in knee osteoarthritis (KOA) patients compared with controls and these parameters have further been suggested to be altered in the elderly. This study investigated the influence of age on pressure hyperalgesia, TSP, and CPM in patients with KOA and controls.

Materials and Methods:
One hundred thirty-three severe KOA patients and 50 age-matched and sex-matched asymptomatic controls were assessed by cuff algometry and handheld pressure algometry. Pain sensitivity was assessed around the head of the gastrocnemius muscle to identify mild pain detection threshold (MPDT) and pressure tolerance threshold (PTT). TSP was assessed by visual analogue scale scores of the pain evoked by 10 repetitive cuff stimulations. CPM was assessed as the difference in PTT before and during cuff-induced tonic arm pain. Pressure pain thresholds (PPTs) were assessed by handheld algometry at the tibialis anterior muscle. Two subgroups were analyzed in the age range below and above 65 years. Pearson correlations between age and pain parameters were applied.

Results:
Patients demonstrated reduced MPDT, PTT, and PPT (P<0.01), facilitated TSP (P<0.02), and a trend toward impaired CPM (P=0.06) compared with controls. A negative correlation was found between MPDT, PTT, and PPT and age (P<0.05) but no age-related association was found for TSP and CPM.

Discussion:
Pressure hyperalgesia was affected by age whereas dynamic pain mechanisms such as TSP and CPM were unaffected suggesting that these parameters are robust for a larger age range and reliable for long-term follow-up studies.