bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rab5 and its effector FHF contribute to neuronal polarity through dynein-dependent retrieval of somatodendritic proteins from the axon
Authors: Guo Xiaoli , Farías Ginny G. , Mattera Rafael , Bonifacino Juan S. 
Published: August 2016

Significance
Ras-related proteins in brain (Rab) GTPases are general regulators of intracellular traffic in eukaryotic cells, but their specialized roles in neurons are poorly understood. Here we report that Rab5 contributes to the somatodendritic polarity of various surface receptors by mediating their retrieval from the axon. This retrieval is dependent on the Rab5 effector Fused Toes (FTS)–Hook–FTS and Hook-interacting protein (FHIP) (FHF), which in turn interacts with the minus-end–directed microtubule motor dynein–dynactin to drive retrograde transport of receptor-containing carriers from the axon to the soma. These findings reveal a mechanism for coupling axonal retrograde carriers to dynein–dynactin and demonstrate that the somatodendritic polarity of various receptors results from a combination of biosynthetic sorting, the barrier function of the axon initial segment, and retrieval from the axon.
Combination therapy with BPTES nanoparticles and metformin targets the metabolic heterogeneity of pancreatic cancer
Authors: Elgogary Amira , Xu Qingguo , Poore Brad , Alt Jesse , Zimmermann Sarah C. , Zhao Liang , Fu Jie , Chen Baiwei , Xia Shiyu , Liu Yanfei , Neisser Marc , Nguyen Christopher , Lee Ramon , Park Joshua K. , Reyes Juvenal , Hartung Thomas , Rojas Camilo , Rais Rana , Tsukamoto Takashi , Semenza Gregg L. , Hanes Justin , Slusher Barbara S. , Le Anne 
Published: August 2016

Significance
There are no effective therapies currently available for advanced pancreatic cancer. We show that there are two populations of cancer cells within a pancreatic tumor that require targeting by different metabolic inhibitors for effective tumor control. Rapidly dividing cells use glutamine, and can be effectively killed by administration of a nanoparticle containing an inhibitor of glutamine metabolism. Hypoxic cells, which are slowly dividing cells, metabolize glucose and can be targeted by metformin, a drug used for the treatment of diabetes. Clinical trials are needed to determine whether combination therapy, with drugs that effectively block the metabolism of glutamine and glucose, improves the survival of patients with pancreatic cancer.
Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset autoinflammatory disease
Authors: Zhou Qing , Yu Xiaomin , Demirkaya Erkan , Deuitch Natalie , Stone Deborah , Tsai Wanxia Li , Kuehn Hye Sun , Wang Hongying , Yang Dan , Park Yong Hwan , Ombrello Amanda K. , Blake Mary , Romeo Tina , Remmers Elaine F. , Chae Jae Jin , Mullikin James C. , Güzel Ferhat , Milner Joshua D. , Boehm Manfred , Rosenzweig Sergio D. , Gadina Massimo , Welch Steven B. , Özen Seza , Topaloglu Rezan , Abinun Mario , Kastner Daniel L. , Aksentijevich Ivona 
Published: August 2016

Significance
We describe a human disease linked to mutations in the linear deubiquitinase (DUB) OTULIN, which functions as a Met1-specific DUB to remove linear polyubiquitin chains that are assembled by the linear ubiquitin assembly complex (LUBAC). OTULIN has a role in regulating Wnt and innate immune signaling complexes. Hydrolysis of Met1-linked ubiquitin chains attenuates inflammatory signals in the NF-κB and ASC-mediated pathways. OTULIN-deficient patients have excessive linear ubiquitination of target proteins, such as NEMO, RIPK1, TNFR1, and ASC, leading to severe inflammation. Cytokine inhibitors have been efficient in suppressing constitutive inflammation in these patients. This study, together with the identification of haploinsufficiency of A20 (HA20), suggests a category of human inflammatory diseases, diseases of dysregulated ubiquitination.
Population Characteristics and the Suppression of Nonnative Burbot
Authors: Klein Zachary B. , Quist Michael C. , Rhea Darren T. , Senecal Anna C. 
Published: August 2016

Abstract
Burbot Lota lota were illegally introduced into the Green River, Wyoming, drainage and have since proliferated throughout the system. Burbot in the Green River pose a threat to native species and to socially, economically, and ecologically important recreational fisheries. Therefore, managers of the Green River are interested in implementing a suppression program for Burbot. We collected demographic data on Burbot in the Green River (summer and autumn 2013) and used the information to construct an age-based population model (female-based Leslie matrix) to simulate the population-level response of Burbot to the selective removal of different age-classes. Burbot in the Green River grew faster, matured at relatively young ages, and were highly fecund compared with other Burbot populations within the species’ native distribution. The age-structured population model, in conjunction with demographic information, indicated that the Burbot population in the Green River could be expected to increase under current conditions. The model also indicated that the Burbot population in the Green River would decline once total annual mortality reached 58%. The population growth of Burbot in the Green River was most sensitive to age-0 and age-1 mortality. The age-structured population model indicated that an increase in mortality, particularly for younger age-classes, would result in the effective suppression of the Burbot population in the Green River.
Received May 27, 2015; accepted March 20, 2016 Published online August 24, 2016
Baseline and Change in Uric Acid Concentration Over Time Are Associated With Incident Hypertension in Large Korean Cohort
Authors: Sung Ki-Chul , Byrne Christopher D. , Ryu Seungho , Lee Jong-Young , Lee Sung Ho , Kim Jang-Young , Kim Seong Hwan , Wild Sarah H. , Guallar Eliseo 
Published: August 2016

Abstract

BACKGROUND
It is uncertain whether high-baseline uric acid (UA) or change in UA concentration over time is related to development of incident hypertension. To investigate relationships between: (i) baseline serum UA concentration and (ii) change in UA concentration and incident hypertension.

METHODS
About 96,606 Korean individuals (with follow-up UA data available for 56,085 people) participating in a health check program was undertaken. Cox regression models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for incident hypertension according to UA quartiles regarding the lowest UA quartile as the reference, and also according to change in UA concentration comparing individuals with an increase in UA to those with a decrease in UA concentration over time.

RESULTS
Total follow up time was 8 years (median follow-up 3.3 years; interquartile range, 1.9–5.1). About 10,405 cases of incident hypertension occurred. In the fully adjusted regression models, the HRs (95% CI) for incident hypertension comparing the highest vs. the lowest quartiles of UA were 1.29 (1.19–1.38) in men and 1.24 (1.09–1.42) in women, with statistically significant P for trend for both gender. Additionally, stable or increasing UA concentration over time was associated with increased risk of incident hypertension, particularly in participants with baseline UA concentration ≥median (aHRs 1.14; 95% CI (1.03–1.26) and 1.18; 95% CI (0.98–1.40) in men and women, respectively).

CONCLUSIONS
High initial UA concentration and increases in UA concentration over time should be considered independent risk factors for hypertension.
Fast-SNP: a fast matrix pre-processing algorithm for efficient loopless flux optimization of metabolic models
Authors: Saa Pedro A. , Nielsen Lars K. 
Published: August 2016

Motivation: Computation of steady-state flux solutions in large metabolic models is routinely performed using flux balance analysis based on a simple LP (Linear Programming) formulation. A minimal requirement for thermodynamic feasibility of the flux solution is the absence of internal loops, which are enforced using ‘loopless constraints’. The resulting loopless flux problem is a substantially harder MILP (Mixed Integer Linear Programming) problem, which is computationally expensive for large metabolic models.
Results: We developed a pre-processing algorithm that significantly reduces the size of the original loopless problem into an easier and equivalent MILP problem. The pre-processing step employs a fast matrix sparsification algorithm—Fast- sparse null-space pursuit (SNP)—inspired by recent results on SNP. By finding a reduced feasible ‘loop-law’ matrix subject to known directionalities, Fast-SNP considerably improves the computational efficiency in several metabolic models running different loopless optimization problems. Furthermore, analysis of the topology encoded in the reduced loop matrix enabled identification of key directional constraints for the potential permanent elimination of infeasible loops in the underlying model. Overall, Fast-SNP is an effective and simple algorithm for efficient formulation of loop-law constraints, making loopless flux optimization feasible and numerically tractable at large scale.
Availability and Implementation: Source code for MATLAB including examples is freely available for download at http://www.aibn.uq.edu.au/cssb-resources under Software. Optimization uses Gurobi, CPLEX or GLPK (the latter is included with the algorithm).
Contact: lars.nielsen@uq.edu.au
Supplementary information: Supplementary data are available at Bioinformatics online.
Discoal: flexible coalescent simulations with selection
Authors: Kern Andrew D. , Schrider Daniel R. 
Published: August 2016

Summary: Here we describe discoal, a coalescent simulator able to generate population samples that include selective sweeps in a feature-rich, flexible manner. discoal can perform simulations conditioning on the fixation of an allele due to drift or either hard or soft sweeps—even those occurring a large genetic distance away from the simulated locus. discoal can simulate sweeps with recurrent mutation to the adaptive allele, recombination, and gene conversion, under non-equilibrium demographic histories and without specifying an allele frequency trajectory in advance.Availability and Implementation: discoal is implemented in the C programming language. Source code is freely available on GitHub (https://github.com/kern-lab/discoal) under a GNU General Public License.Contact: kern@dls.rutgers.edu or dan.schrider@rutgers.eduSupplementary information: Supplementary data are available at Bioinformatics online.
AlmostSignificant: simplifying quality control of high-throughput sequencing data
Authors: Ward Joseph , Cole Christian , Febrer Melanie , Barton Geoffrey J. 
Published: August 2016

Abstract
Motivation: The current generation of DNA sequencing technologies produce a large amount of data quickly. All of these data need to pass some form of quality control (QC) processing and checking before they can be used for any analysis. The large number of samples that are run through Illumina sequencing machines makes the process of QC an onerous and time-consuming task that requires multiple pieces of information from several sources.
Results: AlmostSignificant is an open-source platform for aggregating multiple sources of quality metrics as well as run and sample meta-data associated with DNA sequencing runs from Illumina sequencing machines. AlmostSignificant is a graphical platform to streamline the QC of DNA sequencing data, to store these data for future reference together with extra meta-data associated with the sequencing runs not typically retained. This simplifies the challenge of monitoring the volume of data produced by Illumina sequencers. AlmostSignificant has been used to track the quality of over 80 sequencing runs covering over 2500 samples produced over the last three years.
Availability and Implementation: The code and documentation for AlmostSignificant is freely available at https://github.com/bartongroup/AlmostSignificant.
Contacts: c.cole@dundee.ac.uk or g.j.barton@dundee.ac.uk
Supplementary information: Supplementary data are available at Bioinformatics online.
Cas-analyzer: an online tool for assessing genome editing results using NGS data
Authors: Park Jeongbin , Lim Kayeong , Kim Jin-Soo , Bae Sangsu 
Published: August 2016

Abstract

Summary
Genome editing with programmable nucleases has been widely adopted in research and medicine. Next generation sequencing (NGS) platforms are now widely used for measuring the frequencies of mutations induced by CRISPR-Cas9 and other programmable nucleases. Here, we present an online tool, Cas-Analyzer, a JavaScript-based implementation for NGS data analysis. Because Cas-Analyzer is completely used at a client-side web browser on-the-fly, there is no need to upload very large NGS datasets to a server, a time-consuming step in genome editing analysis. Currently, Cas-Analyzer supports various programmable nucleases, including single nucleases and paired nucleases.

Availability and Implementation
Free access at http://www.rgenome.net/cas-analyzer/.

Supplementary information
Supplementary data are available at Bioinformatics online.
Patients learning to read their doctors’ notes: the importance of reminders
Authors: Mafi John N , Mejilla Roanne , Feldman Henry , Ngo Long , Delbanco Tom , Darer Jonathan , Wee Christina , Walker Jan 
Published: August 2016

Abstract
Objective To examine whether patients invited to review their clinicians’ notes continue to access them and to assess the impact of reminders on whether patients continued to view notes.
Materials and methods We followed OpenNotes trial participants for 2 years at Beth Israel Deaconess Medical Center (BIDMC) and Geisinger Health System (GHS). Electronic invitations alerting patients to signed notes stopped at GHS after year 1, creating a natural experiment to assess the impact of reminders. We used generalized linear models to measure whether notes were viewed within 30 days of availability.
Results We identified 14 360 patients (49 271 visits); mean age 52.2; 57.8% female. In year 1, patients viewed 57.5% of their notes, and their interest in viewing notes persisted over time. In year 2, BIDMC patients viewed notes with similar frequency. In contrast, GHS patients viewed notes far less frequently, a change starting when invitations ceased (RR 0.29 [0.26–0.32]) and persisting to the end of the study (RR 0.20 [0.17–0.23]). A subanalysis of BIDMC patients revealed that black and other/multiracial patients also continued to view notes, although they were overall less likely to view notes compared with whites (RR 0.75 [0.67–0.83] and 0.93 [0.89–0.98], respectively).
Discussion As millions of patients nationwide increasingly gain access to clinicians’ notes, explicit email invitations to review notes may be important for fostering patient engagement and patient-doctor communication.
Conclusion Note viewing persists when accompanied by email alerts, but may decline substantially in their absence. Non-white patients at BIDMC viewed notes less frequently than whites, although their interest also persisted.
Human Immunodeficiency Virus-1 Sequence Changes and Drug Resistance Mutation Among Virologic Failures of Lopinavir/Ritonavir Monotherapy: AIDS Clinical Trials Group Protocol A5230
Authors: Vardhanabhuti Saran , Katzenstein David , Bartlett John , Kumarasamy Nagalingeswaran , Wallis Carole L. 
Published: August 2016

Abstract
Background.  The mechanism of virologic failure (VF) of lopinavir/ritonavir (LPV/r) monotherapy is not well understood. We assessed sequence changes in human immunodeficiency virus-1 reverse-transcriptase (RT) and protease (PR) regions.
Methods.  Human immunodeficiency virus-1 pol sequences from 34 participants who failed second-line LPV/r monotherapy were obtained at study entry (SE) and VF. Sequence changes were evaluated using phylogenetic analysis and hamming distance.
Results.  Human immunodeficiency virus-1 sequence change was higher over drug resistance mutation (DRM) sites (median genetic distance, 2.2%; Q1 to Q3, 2.1%–2.5%) from SE to VF compared with non-DRM sites (median genetic distance, 1.3%; Q1 to Q3, 1.0%–1.4%; P &lt; .0001). Evolution over DRM sites was mainly driven by changes in the RT (median genetic distance, 2.7%; Q1 to Q3, 2.2%–3.2%) compared with PR (median genetic distance, 1.1%; Q1 to Q3, 0.0%–1.1%; P &lt; .0001). Most RT DRMs present at SE were lost at VF. At VF, 19 (56%) and 26 (76%) were susceptible to efavirenz/nevirapine and etravirine (ETV)/rilpivirine (RPV), respectively, compared with 1 (3%) and 12 (35%) at SE. Participants who retained nonnucleoside reverse-transcriptase inhibitor (NNRTI) DRMs and those without evolution of LPV/r DRMs had significantly shorter time to VF.
Conclusions.  The selection of LPV/r DRMs in participants with longer time to VF suggests better adherence and more selective pressure. Fading NNRTI mutations and an increase in genotypic susceptibility to ETV and RPV could allow for the reuse of NNRTI. Further studies are warranted to understand mechanisms of PR failure.
Binaural Hearing Ability With Bilateral Bone Conduction Stimulation in Subjects With Normal Hearing: Implications for Bone Conduction Hearing Aids
Authors: Zeitooni Mehrnaz , Mäki-Torkko Elina , Stenfelt Stefan 
Published: August 2016

Objectives:
The purpose of this study is to evaluate binaural hearing ability in adults with normal hearing when bone conduction (BC) stimulation is bilaterally applied at the bone conduction hearing aid (BCHA) implant position as well as at the audiometric position on the mastoid. The results with BC stimulation are compared with bilateral air conduction (AC) stimulation through earphones.

Design:
Binaural hearing ability is investigated with tests of spatial release from masking and binaural intelligibility level difference using sentence material, binaural masking level difference with tonal chirp stimulation, and precedence effect using noise stimulus.

Results:
In all tests, results with bilateral BC stimulation at the BCHA position illustrate an ability to extract binaural cues similar to BC stimulation at the mastoid position. The binaural benefit is overall greater with AC stimulation than BC stimulation at both positions. The binaural benefit for BC stimulation at the mastoid and BCHA position is approximately half in terms of decibels compared with AC stimulation in the speech based tests (spatial release from masking and binaural intelligibility level difference). For binaural masking level difference, the binaural benefit for the two BC positions with chirp signal phase inversion is approximately twice the benefit with inverted phase of the noise. The precedence effect results with BC stimulation at the mastoid and BCHA position are similar for low frequency noise stimulation but differ with high-frequency noise stimulation.

Conclusions:
The results confirm that binaural hearing processing with bilateral BC stimulation at the mastoid position is also present at the BCHA implant position. This indicates the ability for binaural hearing in patients with good cochlear function when using bilateral BCHAs.
Extensive Postradiation Ocular and Diffuse Cranial Neuromyotonia Mimicking Myasthenia Gravis
Authors: Hardy Todd A. , Lee Andrew W. , Yiannikas Con , Chen Celia S. , Reddel Stephen W. 
Published: August 2016

Background:
Ocular neuromyotonia is a rare, but well-recognized, complication of cranial irradiation.

Case Report:
Using figures and videos, we report a 52-year-old man with extensive ocular, brainstem, and lower cranial nerve neuromyotonia postradiation therapy for a fourth ventricle glioma who, in the context of an apparently positive edrophonium test, was initially misdiagnosed with myasthenia gravis.

Conclusions:
This is the first case of postirradiation neuromyotonia to be reported with such extensive cranial nerve and brainstem involvement.
Is Single-Stage Prosthetic Reconstruction Cost Effective? A Cost-Utility Analysis for the Use of Direct-to-Implant Breast Reconstruction Relative to Expander-Implant Reconstruction in Postmastectomy Patients
Authors: Krishnan Naveen M. , Fischer John P. , Basta Marten N. , Nahabedian Maurice Y. 
Published: August 2016

Background:
Prosthetic breast reconstruction is most commonly performed using the two-stage (expander-implant) technique. However, with the advent of skin-sparing mastectomy and the use of acellular dermal matrices, one-stage prosthetic reconstruction has become more feasible. Prior studies have suggested that one-stage reconstruction has economic advantages relative to two-stage reconstruction despite a higher revision rate. This is the first cost-utility analysis to compare the cost and quality of life of both procedures to guide patient care.

Methods:
A comprehensive literature review was conducted using the MEDLINE, EMBASE, and Cochrane databases to include studies directly comparing matched patient cohorts undergoing single-stage or staged prosthetic reconstruction. Six studies were selected examining 791 direct-to-implant reconstructions and 1142 expander-implant reconstructions. Costs were derived adopting both patient and third-party payer perspectives. Utilities were derived by surveying an expert panel. Probabilities of clinically relevant complications were combined with cost and utility estimates to fit into a decision tree analysis.

Results:
The overall complication rate was 35 percent for single-stage reconstruction and 34 percent for expander-implant reconstruction. The authors’ baseline analysis using Medicare reimbursement revealed a cost decrease of $525.25 and a clinical benefit of 0.89 quality-adjusted life-year when performing single-stage reconstructions, yielding a negative incremental cost-utility ratio. When using national billing, the incremental cost-utility further decreased, indicating that direct-to-implant breast reconstruction was the dominant strategy. Sensitivity analysis confirmed the robustness of the authors’ conclusions.

Conclusions:
Direct-to-implant breast reconstruction is the dominant strategy when used appropriately. Surgeons are encouraged to consider single-stage reconstruction when feasible in properly selected patients.
Fat Grafting for Gluteal Augmentation: A Systematic Review of the Literature and Meta-Analysis
Authors: Condé-Green Alexandra , Kotamarti Vasanth , Nini Kevin T. , Wey Philip D. , Ahuja Naveen K. , Granick Mark S. , Lee Edward S. 
Published: August 2016

Background:
With the increasing demand for gluteal fat augmentation, reports of fatal complications have surfaced. Therefore, the authors proposed to analyze the published techniques and compare different protocols, to identify those of potential concern.

Methods:
A systematic review of the literature was performed with a search of 21 terms on the PubMed, MEDLINE, Cochrane, and Scientific Electronic Library Online databases. Nineteen articles meeting our predetermined criteria were analyzed, and data from the different steps of the procedure were classified, allowing evaluation and comparison of techniques. Independent-samples t test and one-way analysis of variance were used for statistical analysis.

Results:
Seventeen case series and two retrospective studies including 4105 patients were reviewed. Most articles were authored in Colombia, Mexico, and Brazil. Most procedures were performed on adult female patients under general anesthesia. Fat was harvested using a tumescent technique from the lower extremities and the back, with machine-vacuum suction. A mean of 400 ml of decanted lipoaspirate was injected into each gluteal region, mostly subcutaneously and intramuscularly with 60-ml syringes. Most patients rated their results as “excellent.” The mean complication rate was 7 percent (6.7 percent minor, 0.32 percent major), with no significant relation to the planes of injection.

Conclusions:
Fat grafting is an effective and predictable way to remodel the gluteal region; however, the procedure is not without risks. Avoiding gluteal vessel damage may prevent most feared complications, such as fat embolism. Accurate analysis, systematization of the procedure, and reporting cases in the fat grafting registry may provide the foundation for optimization of outcomes.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.