bluuebunny/crossref_metadata_2025 huggingface dataset:
CoreTracker: accurate codon reassignment prediction, applied to mitochondrial genomes
Authors: Noutahi Emmanuel , Calderon Virginie , Blanchette Mathieu , Lang Franz B , El-Mabrouk Nadia
Published: June 2017

Motivation

Codon reassignments have been reported across all domains of life. With the increasing number of sequenced genomes, the development of systematic approaches for genetic code detection is essential for accurate downstream analyses. Three automated prediction tools exist so far: FACIL, GenDecoder and Bagheera; the last two respectively restricted to metazoan mitochondrial genomes and CUG reassignments in yeast nuclear genomes. These tools can only analyze a single genome at a time and are often not followed by a validation procedure, resulting in a high rate of false positives.

Results

We present CoreTracker, a new algorithm for the inference of sense-to-sense codon reassignments. CoreTracker identifies potential codon reassignments in a set of related genomes, then uses statistical evaluations and a random forest classifier to predict those that are the most likely to be correct. Predicted reassignments are then validated through a phylogeny-aware step that evaluates the impact of the new genetic code on the protein alignment. Handling simultaneously a set of genomes in a phylogenetic framework, allows tracing back the evolution of each reassignment, which provides information on its underlying mechanism. Applied to metazoan and yeast genomes, CoreTracker significantly outperforms existing methods on both precision and sensitivity.

Availability and implementation

CoreTracker is written in Python and available at https://github.com/UdeM-LBIT/CoreTracker.

Supplementary information

Supplementary data are available at Bioinformatics online.
Uterine responses to early pre-attachment embryos in the domestic dog and comparisons with other domestic animal species†
Authors: Graubner Felix R , Gram Aykut , Kautz Ewa , Bauersachs Stefan , Aslan Selim , Agaoglu Ali R , Boos Alois , Kowalewski Mariusz P
Published: June 2017

In the dog, there is no luteolysis in the absence of pregnancy. Thus, this species lacks any anti-luteolytic endocrine signal as found in other species that modulate uterine function during the critical period of pregnancy establishment. Nevertheless, in the dog an embryo-maternal communication must occur in order to prevent rejection of embryos. Based on this hypothesis, we performed microarray analysis of canine uterine samples collected during pre-attachment phase (days 10-12) and in corresponding non-pregnant controls, in order to elucidate the embryo attachment signal. An additional goal was to identify differences in uterine responses to pre-attachment embryos between dogs and other mammalian species exhibiting different reproductive patterns with regard to luteolysis, implantation, and preparation for placentation. Therefore, the canine microarray data were compared with gene sets from pigs, cattle, horses, and humans. We found 412 genes differentially regulated between the two experimental groups. The functional terms most strongly enriched in response to pre-attachment embryos related to extracellular matrix function and remodeling, and to immune and inflammatory responses. Several candidate genes were validated by semi-quantitative PCR. When compared with other species, best matches were found with human and equine counterparts. Especially for the pig, the majority of overlapping genes showed opposite expression patterns. Interestingly, 1926 genes did not pair with any of the other gene sets. Using a microarray approach, we report the uterine changes in the dog driven by the presence of embryos and compare these results with datasets from other mammalian species, finding common-, contrary-, and exclusively canine-regulated genes.
Variation in Bacterial and Eukaryotic Communities Associated with Natural and Managed Wild Blueberry Habitats
Authors: Yurgel Svetlana N. , Douglas Gavin M. , Comeau André M. , Mammoliti Melissa , Dusault Ashley , Percival David , Langille Morgan G. I.
Published: June 2017

We examined the differences between bacterial and eukaryotic soil communities associated with natural and managed habitats of wild blueberry, Vaccinium angustifolium. In total, 138 bacterial and 130 eukaryotic soil and rhizosphere communities across seven blueberry fields, all established at least 30 years ago and from two forest areas adjacent to some of these fields, were analyzed. We analyzed correlations between soil chemical factors and the structure of eukaryotic and bacterial communities, including differences in the microbiome between bulk and rhizosphere soils, and between rhizospheres of plants growing in natural and managed habitats. Characterization of a broad selection of fields across the province of Nova Scotia, Canada, allowed us to tentatively identify specific signatures from several distinct soil niches. Our data indicate that bacterial and eukaryotic communities differ in how they correlate with soil chemical properties. Also, while eukaryotic communities correlate stronger with soil fertility than bacterial communities, plant selection had a stronger effect on bacterial microbiomes than on eukaryote microbiomes. Additionally, we found that the composition of root-associated bacterial communities differs between managed and natural wild blueberry habitats, confirming previous reports that management can affect rhizosphere microbiomes.
An update on type 2 diabetes management in primary care
Authors: Waddell Jeffrey
Published: June 2017

Diabetes mellitus is a chronic disease impacting glucose metabolism. Type 2 diabetes mellitus (T2DM) stems from the inability of the body to utilize endogenous insulin properly. Approximately 90% to 95% of newly diagnosed cases of diabetes are T2DM. This article focuses on the initial treatment of T2DM based on the 2017 American Association of Clinical Endocrinologists and the American College of Endocrinology clinical practice guidelines. The 2017 update includes changes and additions regarding psychosocial management, physical activity, surgery, and hypoglycemia.
Videolaryngoscopy versus Fiber-optic Intubation through a Supraglottic Airway in Children with a Difficult Airway
Authors: Burjek Nicholas E. , Nishisaki Akira , Fiadjoe John E. , Adams H. Daniel , Peeples Kenneth N. , Raman Vidya T. , Olomu Patrick N. , Kovatsis Pete G. , Jagannathan Narasimhan ,   for the PeDI Collaborative Investigators
Published: June 2017

Background

The success rates and related complications of various techniques for intubation in children with difficult airways remain unknown. The primary aim of this study is to compare the success rates of fiber-optic intubation via supraglottic airway to videolaryngoscopy in children with difficult airways. Our secondary aim is to compare the complication rates of these techniques.

Methods

Observational data were collected from 14 sites after management of difficult pediatric airways. Patient age, intubation technique, success per attempt, use of continuous ventilation, and complications were recorded for each case. First-attempt success and complications were compared in subjects managed with fiber-optic intubation via supraglottic airway and videolaryngoscopy.

Results

Fiber-optic intubation via supraglottic airway and videolaryngoscopy had similar first-attempt success rates (67 of 114, 59% vs. 404 of 786, 51%; odds ratio 1.35; 95% CI, 0.91 to 2.00; P = 0.16). In subjects less than 1 yr old, fiber-optic intubation via supraglottic airway was more successful on the first attempt than videolaryngoscopy (19 of 35, 54% vs. 79 of 220, 36%; odds ratio, 2.12; 95% CI, 1.04 to 4.31; P = 0.042). Complication rates were similar in the two groups (20 vs. 13%; P = 0.096). The incidence of hypoxemia was lower when continuous ventilation through the supraglottic airway was used throughout the fiber-optic intubation attempt.

Conclusions

In this nonrandomized study, first-attempt success rates were similar for fiber-optic intubation via supraglottic airway and videolaryngoscopy. Fiber-optic intubation via supraglottic airway is associated with higher first-attempt success than videolaryngoscopy in infants with difficult airways. Continuous ventilation through the supraglottic airway during fiber-optic intubation attempts may lower the incidence of hypoxemia.
Combined Thoracic Ultrasound Assessment during a Successful Weaning Trial Predicts Postextubation Distress
Authors: Silva Stein , Ait Aissa Dalinda , Cocquet Pierre , Hoarau Lucille , Ruiz Jean , Ferre Fabrice , Rousset David , Mora Michel , Mari Arnaud , Fourcade Olivier , Riu Béatrice , Jaber Samir , Bataille Bénoît
Published: June 2017

Background

Recent studies suggest that isolated sonographic assessment of the respiratory, cardiac, or neuromuscular functions in mechanically ventilated patients may assist in identifying patients at risk of postextubation distress. The aim of the present study was to prospectively investigate the value of an integrated thoracic ultrasound evaluation, encompassing bedside respiratory, cardiac, and diaphragm sonographic data in predicting postextubation distress.

Methods

Longitudinal ultrasound data from 136 patients who were extubated after passing a trial of pressure support ventilation were measured immediately after the start and at the end of this trial. In case of postextubation distress (31 of 136 patients), an additional combined ultrasound assessment was performed while the patient was still in acute respiratory failure. We applied machine-learning methods to improve the accuracy of the related predictive assessments.

Results

Overall, integrated thoracic ultrasound models accurately predict postextubation distress when applied to thoracic ultrasound data immediately recorded before the start and at the end of the trial of pressure support ventilation (learning sample area under the curve: start, 0.921; end, 0.951; test sample area under the curve: start, 0.972; end, 0.920). Among integrated thoracic ultrasound data, the recognition of lung interstitial edema and the increased telediastolic left ventricular pressure were the most relevant predictive factors. In addition, the use of thoracic ultrasound appeared to be highly accurate in identifying the causes of postextubation distress.

Conclusions

The decision to attempt extubation could be significantly assisted by an integrative, dynamic, and fully bedside ultrasonographic assessment of cardiac, lung, and diaphragm functions.
Direct anterior approach total hip arthroplasty requires less supplemental acetabular screw fixation and fewer blood transfusions than posterior approach
Authors: Colacchio Nicholas D. , Cleary Mark X. , Reid Daniel , Trofa David , Pevear Mary E. , Smith Eric L.
Published: June 2017

Background:

This study evaluates the use of supplemental acetabular cup screw fixation during direct anterior approach (DAA) versus posterior approach total hip arthroplasty (THA).

Methods:

A retrospective review of all THAs performed by a single fellowship-trained total joint surgeon at a tertiary academic medical center between January 2010 and January 2013 identified 136 primary THAs (124 patients). The following variables were analyzed: age, body mass index (BMI), American Society of Anesthesiologists (ASA) score, operative side, surgical approach, operative time, estimated blood loss, blood transfusion, implant design, number of acetabular screws used, offset (high, standard, or coxa vara), cup anteversion, and cup abduction.

Results:

There were 31 DAA and 105 posterior-approach primary THAs performed. Significantly fewer acetabular screws were used in DAA compared to posterior approach (1.0 vs. 1.9 screws, P<0.001). Patients who received acetabular screws had a significantly increased likelihood of requiring a blood transfusion (OR=4.4). Patients who received blood transfusions had significantly more acetabular screws placed than patients who did not receive transfusions (2 vs. 1.2 screws, P<0.001). DAA patients had a significantly lower mean BMI than posterior approach patients (26.2 vs. 30.6). There were no significant differences in age, gender, operative time, cup abduction, cup anteversion, estimated blood loss, or blood transfusions between the two cohorts.

Conclusions:

The number of supplemental acetabular screws used in THA performed by DAA was significantly less than during a posterior surgical approach, and supplemental screw fixation was associated with a significantly increased likelihood of requiring a blood transfusion. Surgeons should consider these factors when deciding which THA approach may be best for an individual patient.
Application of Quality by Design Approach to Bioanalysis: Development of a Method for Elvitegravir Quantification in Human Plasma
Authors: Baldelli Sara , Marrubini Giorgio , Cattaneo Dario , Clementi Emilio , Cerea Matteo
Published: June 2017

Background:

The application of Quality by Design (QbD) principles in clinical laboratories can help to develop an analytical method through a systematic approach, providing a significant advance over the traditional heuristic and empirical methodology. In this work, we applied for the first time the QbD concept in the development of a method for drug quantification in human plasma using elvitegravir as the test molecule.

Methods:

The goal of the study was to develop a fast and inexpensive quantification method, with precision and accuracy as requested by the European Medicines Agency guidelines on bioanalytical method validation. The method was divided into operative units, and for each unit critical variables affecting the results were identified. A risk analysis was performed to select critical process parameters that should be introduced in the design of experiments (DoEs). Different DoEs were used depending on the phase of advancement of the study.

Results:

Protein precipitation and high-performance liquid chromatography–tandem mass spectrometry were selected as the techniques to be investigated. For every operative unit (sample preparation, chromatographic conditions, and detector settings), a model based on factors affecting the responses was developed and optimized. The obtained method was validated and clinically applied with success.

Conclusions:

To the best of our knowledge, this is the first investigation thoroughly addressing the application of QbD to the analysis of a drug in a biological matrix applied in a clinical laboratory. The extensive optimization process generated a robust method compliant with its intended use. The performance of the method is continuously monitored using control charts.
Tissue Expanders and Proton Beam Radiotherapy: What You Need to Know
Authors: Howarth Ashley L. , Niska Joshua R. , Brooks Kenneth , Anand Aman , Bues Martin , Vargas Carlos E. , Mahabir Raman C.
Published: June 2017

Proton beam radiotherapy (PBR) has gained acceptance for the treatment of breast cancer because of unique beam characteristics that allow superior dose distributions with optimal dose to the target and limited collateral damage to adjacent normal tissue, especially to the heart and lungs. To determine the compatibility of breast tissue expanders (TEs) with PBR, we evaluated the structural and dosimetric properties of 2 ex vivo models: 1 model with internal struts and another model without an internal structure. Although the struts appeared to have minimal impact, we found that the metal TE port alters PBR dynamics, which may increase proton beam range uncertainty. Therefore, submuscular TE placement may be preferable to subcutaneous TE placement to reduce the interaction of the TE and proton beam. This will reduce range uncertainty and allow for more ideal radiation dose distribution.
A Unique Lymphaticovenous Supermicrosurgery Training Curriculum: Reflections on Validation and Competency Thresholds
Authors: Pafitanis Georgios , Narushima Mitsunaga , Harima Mitsunobu , Ghanem Ali , Myers Simon , Koshima Isao
Published: June 2017

Supermicrosurgery is becoming a commonly used technique in various subspecialties of reconstructive surgery. However, there is a lack of standardization and validation in novel supermicrosurgical training. Current simulation training programs are not adequately focused on the challenges encountered during clinical supermicrosurgery practice. This article describes the authors’ experience utilizing a supermicrosurgery competency-based training curriculum, in a simulation-based environment, toward safe clinical practice for lymphatic submillimeter supermicrovascular surgery. This article demonstrates the senior authors’ (I.K.) Halstedian competency-based curriculum for lymphaticovenous anastomosis training. Further, a step-by-step training utilizing the chicken thigh and the living rat high fidelity simulation models, which subsequently allows supervised one-to-one clinical training with verified clinical competency outcomes, are demonstrated.
A systems analysis of ward rounds in plastic surgery at a single center
Authors: Agha Riaz
Published: June 2017

Introduction:

Ward rounds permeate health care delivery worldwide and form an important daily activity within all hospitals. In this study, the daily morning ward round in plastic surgery was examined from a teleological and systems point of view.

Methods:

Data were gathered from the following sources to inform the systems analysis: patient interviews, staff interviews, direct observations of the ward round on multiple occasions, and through process mapping.

Results:

To better understand the ward and its layout, a schematic of it was developed. Following observations of the ward round and the way in which decisions are made on it, an IDEF0 map was developed. Three patients were invited to take part in the study. Three members of staff were interviewed. The overarching themes from the interviews related to aspects of communication which this paper details.

Conclusions:

This small-scale study demonstrates how the ward round as a process can be assessed, including product quality, process quality, the measurement and management of capacity, the role of standardization, the role and significance of bottlenecks, the key information flows, including the role of feedback, and the motivation and incentives of system participants and ideas for improvement generated.
Randomized Trial of Reducing Ambulatory Malpractice and Safety Risk
Authors: Schiff Gordon D. , Reyes Nieva Harry , Griswold Paula , Leydon Nicholas , Ling Judy , Federico Frank , Keohane Carol , Ellis Bonnie R. , Foskett Cathy , Orav E. John , Yoon Catherine , Goldmann Don , Weissman Joel S. , Bates David W. , Biondolillo Madeleine , Singer Sara J.
Published: June 2017

Objective:

Evaluate application of quality improvement approaches to key ambulatory malpractice risk and safety areas.

Study Setting:

In total, 25 small-to-medium-sized primary care practices (16 intervention; 9 control) in Massachusetts.

Study Design:

Controlled trial of a 15-month intervention including exposure to a learning network, webinars, face-to-face meetings, and coaching by improvement advisors targeting “3+1” high-risk domains: test result, referral, and medication management plus culture/communication issues evaluated by survey and chart review tools.

Data Collection Methods:

Chart reviews conducted at baseline and postintervention for intervention sites. Staff and patient survey data collected at baseline and postintervention for intervention and control sites.

Principal Findings:

Chart reviews demonstrated significant improvements in documentation of abnormal results, patient notification, documentation of an action or treatment plan, and evidence of a completed plan (all P<0.001). Mean days between laboratory test date and evidence of completed action/treatment plan decreased by 19.4 days (P<0.001). Staff surveys showed modest but nonsignificant improvement for intervention practices relative to controls overall and for the 3 high-risk domains that were the focus of PROMISES.

Conclusions:

A consortium of stakeholders, quality improvement tools, coaches, and learning network decreased selected ambulatory safety risks often seen in malpractice claims.
State of Interprofessional Education in Nursing
Authors: Rutherford-Hemming Tonya , Lioce Lori
Published: June 2017

The aim of this systematic review was to synthesize research in the last 5 years to report the current state of the science related to interprofessional education (IPE) in nursing. Findings suggest that more studies with rigorous research designs are needed to compare outcomes for interprofessional interventions and to determine the effectiveness of IPE on patient outcomes.
Pediatric Procedural Sedation Using the Combination of Ketamine and Propofol Outside of the Emergency Department: A Report From the Pediatric Sedation Research Consortium
Authors: Grunwell Jocelyn R. , Travers Curtis , Stormorken Anne G. , Scherrer Patricia D. , Chumpitazi Corrie E. , Stockwell Jana A. , Roback Mark G. , Cravero Joseph , Kamat Pradip P.
Published: June 2017

Objectives:

Outcomes associated with a sedative regimen comprised ketamine + propofol for pediatric procedural sedation outside of both the pediatric emergency department and operating room are underreported. We used the Pediatric Sedation Research Consortium database to describe a multicenter experience with ketamine + propofol by pediatric sedation providers.

Design:

Prospective observational study of children receiving IV ketamine + propofol for procedural sedation outside of the operating room and emergency department using data abstracted from the Pediatric Sedation Research Consortium during 2007–2015.

Setting:

Procedural sedation services from academic, community, free-standing children’s hospitals, and pediatric wards within general hospitals.

Patients:

Children from birth to less than or equal to 21 years old.

Interventions:

None.

Measurements and Main Results:

A total of 7,313 pediatric procedural sedations were performed using IV ketamine + propofol as the primary sedative regimen. Median age was 84 months (range, < 1 mo to ≤ 21 yr; interquartile range, 36–144); 80.6% were American Society of Anesthesiologists-Physical Status less than III. The majority of sedation was performed in dedicated sedation or radiology units (76.1%). Procedures were successfully completed in 99.8% of patients. Anticholinergics (glycopyrrolate and atropine) or benzodiazepines (midazolam and lorazepam) were used in 14.2% and 41.3%, respectively. The overall adverse event and serious adverse event rates were 9.79% (95% CI, 9.12–10.49%) and 3.47% (95% CI, 3.07–3.92%), respectively. No deaths occurred. Risk factors associated with an increase in odds of adverse event included ASA status greater than or equal to III, dental suite, cardiac catheterization laboratory or radiology/sedation suite location, a primary diagnosis of having a gastrointestinal illness, and the coadministration of an anticholinergic.

Conclusions:

Using Pediatric Sedation Research Consortium data, we describe the diverse use of IV ketamine + propofol for procedural sedation in the largest reported cohort of children to date. Data from this study may be used to design sufficiently powered prospective randomized, double-blind studies comparing outcomes of sedation between commonly administered sedative and analgesic medication regimens.
Population Pharmacokinetics and Pharmacodynamic Target Attainment of Vancomycin in Neonates on Extracorporeal Life Support
Authors: Cies Jeffrey J. , Moore Wayne S. , Nichols Kristen , Knoderer Chad A. , Carella Dominick M. , Chopra Arun
Published: June 2017

Objectives:

To evaluate the population pharmacokinetics and pharmacodynamic target attainment of vancomycin in neonates with a contemporary ¼-inch extracorporeal life support circuit with a Quadrox-iD Pediatric oxygenator (Maquet Cardiovascular, LLC, Wayne, NJ).

Design:

Retrospective medical record review.

Setting:

Two free-standing tertiary/quaternary pediatric children’s hospitals.

Patients:

Neonates receiving either veno-arterial or veno-venous extracorporeal life support and vancomycin for empiric or definitive therapy with resulting serum concentrations.

Interventions:

None.

Measurements and Main Results:

Twelve patients with a median gestations age of 39 weeks (range 36–41 wk) and a median postnatal age of 9.5 days (range 0–28 d) accounted for 14 courses of vancomycin therapy while on extracorporeal life support and were included in the analysis. The median weight was 3.1 kg (range 2.2–4.41 kg) with five of 12 patients (41.7%) being female. Vancomycin concentrations were best described by an one-compartment model incorporating allometric scaling of estimated glomerular filtration rate on clearance. The mean total body clearance (mL/min/kg) for the population was 3.48 ± 1.31 mL/min/kg, and the mean total volume of distribution (L/kg) for the population was 1.2 ± 0.4 L/kg. The intermittent and continuous infusion dosing regimens that provided for the highest percentage of trough concentrations in the range of 10–20 mg/L were the 10 mg/kg/dose IV q8h, 12.5 mg/kg/dose IV q8–12h, 15 mg/kg/dose IV q12h, and 20 mg/kg/dose IV q12h, and the 20, 25, and 30 mg/kg/d continuous infusion regimens, respectively. All regimens allowed for an area under the concentration:minimum inhibitory concentration ratio of 400:1 for minimum inhibitory concentrations of less than or equal to 0.5 mg/L for a 90% PTA. None of the simulated regimens had a greater than 90% probability of achieving an area under the concentration:minimum inhibitory concentration ratio of 400:1 for vancomycin minimum inhibitory concentrations greater than or equal to 1 mg/L while maintaining trough concentrations in the range of 10–20 mg/L.

Conclusions:

To our knowledge, this is the first pharmacokinetic and pharmacodynamic study of neonates receiving vancomycin with a contemporary ¼-inch extracorporeal life support circuit including the Quadrox-iD Pediatric oxygenator (Maquet Cardiovascular, LLC). The data suggest differences in vancomycin pharmacokinetics compared with previous extracorporeal life support data, notably a more rapid clearance, which could result in lower vancomycin concentrations. Considering this, a more aggressive initial dosing regimen may need to be employed in infants on extracorporeal life support.
Differences in opioid prescribing in low back pain patients with and without depression: a cross-sectional study of a national sample from the United States
Authors: Smith Joyce A. , Fuino Robert L. , Pesis-Katz Irena , Cai Xueya , Powers Bethel , Frazer Maria , Markman John D.
Published: June 2017

Introduction:

Low back pain (LBP) is among the leading indications for the prescription of opioid analgesics in clinical practice. There is increasing evidence suggesting that these agents may have diminished efficacy in the treatment of LBP.

Objectives:

We evaluated the relationship between depression, the probability of receiving an opioid prescription, and the amount of morphine equivalent amounts prescribed per year among patients with LBP using nationwide data.

Methods:

A cross-sectional analysis was performed on existing data from the Medical Expenditure Panel Survey data set from the period 2004 to 2009. Demographic, medical condition, Patient Health Questionnaire-2 responses, and prescription drug information were obtained on 56,811,864 weighted person-years of data from individuals aged 18 to 65 with anICD-9code specific to LBP.

Results:

Increases in PHQ-2 score, as well a positive screen for depression, were associated with an increased probability of being prescribed opioid therapy and more morphine equivalents per year.

Conclusion:

Analysis of a nationwide sample of patients with LBP shows an association between depression and higher rates of opioid prescribing after controlling for several known cofounders. Clinicians prescribing opioids in LBP populations that rely on clinical trial results that exclude depressed patients may misjudge the risks and benefits of this class of therapy.
Directin vivomapping of functional suppressors in glioblastoma genome
Authors: Chow Ryan D. , Guzman Christopher D. , Wang Guangchuan , Schmidt Florian , Youngblood Mark W. , Ye Lupeng , Errami Youssef , Dong Matthew B. , Martinez Michael A. , Zhang Sensen , Renauer Paul , Bilguvar Kaya , Gunel Murat , Sharp Phillip A. , Zhang Feng , Platt Randall J. , Chen Sidi
Published: June 2017

Glioblastoma (GBM) is one of the deadliest cancers, with limited effective treatments and single-digit five-year survival1-7. A causative understanding of genetic factors that regulate GBM formation is of central importance8-19. However, a global, quantitative and functional understanding of gliomagenesis in the native brain environment has been lacking due to multiple challenges. Here, we developed an adeno-associated virus (AAV) mediated autochthonous CRISPR screen and directly mapped functional suppressors in the GBM genome. Stereotaxic delivery of an AAV library targeting significantly mutated genes into fully immunocompetent conditional Cas9 mice robustly led to gliomagenesis, resulting in tumors that recapitulate features of human GBM. Targeted capture sequencing revealed deep mutational profiles with diverse patterns across mice, uncoveringin vivoroles of previously uncharacterized factors in GBM such as immune regulatorB2m,zinc finger proteinZc3h13,transcription repressorCic,epigenetic regulatorsMll2/3andArid1b,alongside canonical tumor suppressorsNf1andPten. Comparative cancer genomics showed that the mutation frequencies across all genes tested in mice significantly correlate with those in human from two independent patient cohorts. Co-mutation analysis identified frequently co-occurring driver combinations, which were validated using AAV minipools, such asMll2, B2m-Nf1,Mll3-Nf1andZc3h13-Rb1. Distinct fromNf1-oncotype tumors,Rb1-oncotype tumors exhibit undifferentiated histopathology phenotype and aberrant activation of developmental reprogramming signatures such asHomeoboxgene clusters. The secondary addition ofZc3h13orPtenmutations drastically altered the gene expression profiles ofRb1mutants and rendered them more resistant to the GBM chemotherapeutic temozolomide. Our study provides a systematic functional landscape of GBM suppressors directlyin vivo, opening new paths for high-throughput molecular mapping and cancer phenotyping.
Pooled AAV-CRISPR Screen with Targeted Amplicon Sequencing
Authors: Wang Guangchuan , Chow Ryan D. , Ye Lupeng , Guzman Christopher D. , Dai Xiaoyun , Dong Matthew B. , Zhang Feng , Sharp Phillip A. , Platt Randall J. , Chen Sidi
Published: June 2017

High-resolution, high-throughput direct in vivo screening of functional genetic factors in native tissues has long been challenging. Adeno-associated viruses (AAV) are powerful carriers of transgenes and have been shown to mediate efficient genome editing in various organs in mice. Here, we developed a new technological approach,PooledAAV-CRISPRScreen withTargetedAmpliconSequencing (PASTAS), and demonstrated its application for directly mapping functional cancer driver variants in the mouse liver in an autochthonous manner. Intravenous delivery of an AAV-CRISPR library targeting a set of the most frequently mutated tumor suppressor genes into fully immunocompetent conditional Cas9 knock-in mice consistently generated highly complex autochthonous liver tumors. The molecular landscapes of these genetically diverse tumors were mapped out by deep direct readout of Cas9-generated variants at predicted sgRNA cut sites using molecular inversion probe sequencing. Co-occurrence and correlation analyses as well as validation with lower complexity minipools further confirmed the potency of various co-mutated drivers. The PASTAS method can be applied to virtually any gene sets, any cancer types, or any type of in vivo genetic studies other than cancer.
Neural Networks for Efficient Bayesian Decoding of Natural Images from Retinal Neurons
Authors: Parthasarathy Nikhil , Batty Eleanor , Falcon William , Rutten Thomas , Rajpal Mohit , Chichilnisky E.J. , Paninski Liam
Published: June 2017

Decoding sensory stimuli from neural signals can be used to reveal how we sense our physical environment, and is valuable for the design of brain-machine interfaces. However, existing linear techniques for neural decoding may not fully reveal or exploit the fidelity of the neural signal. Here we develop a new approximate Bayesian method for decoding natural images from the spiking activity of populations of retinal ganglion cells (RGCs). We sidestep known computational challenges with Bayesian inference by exploiting artificial neural networks developed for computer vision, enabling fast nonlinear decoding that incorporates natural scene statistics implicitly. We use a decoder architecture that first linearly reconstructs an image from RGC spikes, then applies a convolutional autoencoder to enhance the image. The resulting decoder, trained on natural images and simulated neural responses, significantly outperforms linear decoding, as well as simple point-wise nonlinear decoding. These results provide a tool for the assessment and optimization of retinal prosthesis technologies, and reveal that the retina may provide a more accurate representation of the visual scene than previously appreciated.
c-di-GMP-linked phenotypes are modulated by the interaction between a diguanylate cyclase and a polar hub protein
Authors: Nicastro Gianlucca G. , Kaihami Gilberto H. , Pulschen André A. , Hernandez-Montelongo Jacobo , Boechat Ana Laura , de O. Pereira Thays , Stefanello Eliezer , Colepicolo Pio , Bordi Christophe , Baldini Regina L.
Published: June 2017

c-di-GMP is a major player in the decision between biofilm and motile lifestyles. Several bacteria present a large number of c-di-GMP metabolizing proteins, thus a fine-tuning of this nucleotide levels may occur. It is hypothesized that some c-di-GMP metabolizing proteins would provide the global c-di-GMP levels inside the cell whereas others would maintain a localized pool, with the resulting c-di-GMP acting at the vicinity of its production. Although attractive, this hypothesis has yet to be proven inPseudomonas aeruginosa.We found that the diguanylate cyclase DgcP interacts with the cytosolic region of FimV, a peptidoglycan-binding protein involved in type IV pilus assembly. Moreover, DgcP is located at the cell poles in wild type cells, but scattered in the cytoplasm of cells lacking FimV. Overexpression of DgcP leads to the classical phenotypes of high c-di-GMP levels (increased biofilm and impaired motilities) in the wild-type strain, but not in aAfimVbackground. Therefore, our findings strongly suggest that DgcP is regulated by FimV and may provide the local c-di-GMP pool that can be sensed by other proteins at the cell pole, bringing to light a specialized function for a specific diguanylate cyclase.
An expected event, but unprecedented damage
Authors: Yeo Jungwon , K. Comfort Louise
Published: June 2017

Purpose

The purpose of this paper is to focus on the large-scale flood response coordination across sectors and jurisdictions, investigating the characteristics and gaps of the 2011 Thailand flood response operations.

Design/methodology/approach

The large-scale flood response coordination was measured as an inter-organizational network. An extensive content analysis of news reports was conducted to identify the participating organizations and relationships among them that emerged during the initial flood response operations. Social network analysis was used to examine the patterns and gaps of coordination among the organizations.

Findings

The research identified three major gaps that might weaken the response coordination. First, the coordination structure was highly fragmented with many isolated actors. Second, the benefit of inter-sector relationships was not well leveraged in the system due to weak reciprocal relationships across sectors. Third, provincial level organizations did not serve as a strong liaison between local actors (cities) and national actors.

Practical implications

Based on the findings, the research offers suggestions to improve the performance of response coordination in recurring flood disasters.

Originality/value

This study is distinctive in its examination of structural characteristics of large-scale, inter-sector and multi-jurisdictional flood response coordination in Thailand. Previous studies have explored how citizens were organized and responded to flood disasters at the local level, and measured indicators or causes of response resilience at the provincial level system. Yet, studies examining the patterns of coordination structure among response organizations across all affected-jurisdictional authorities and sectors have been lacking.
U-District Job Co-op: constructing a future vision for homeless young people and employment
Authors: Hendry David G. , Woelfer Jill Palzkill , Duong Thuy
Published: June 2017

Purpose

Addressing the question, how might socio-technical systems help homeless young people to succeed broadly in employment, the purpose of this paper is to present a future vision, the U-District Job Co-op, where youth take on “mini-jobs” offered by neighborhood stakeholders.

Design/methodology/approach

Drawing on value sensitive design, design-based, and qualitative research methods, the Job Co-op is explicated by reporting on three linked studies.

Findings

First, based on empirical research with varied neighborhood stakeholders, barriers and possible solutions to employment for homeless young people are presented. Second, three design insights for shaping a solution space of socio-technical systems for job search are presented and used analytically to examine six existing systems. Third, findings from a co-design study in which homeless young people expressed their understandings for web-based job services explicate the vision of the Job Co-op.

Social implications

This study offers a socio-technical approach, grounded in the neighborhood context, for supporting homeless young people in job search and related activities.

Originality/value

The studies reported in this paper demonstrate how methods for information system design can be used to generate and clarify opportunities for human benefit and for the development of socio-technical systems that account for human values.
Enhancing customer brand experience and loyalty through enterprise microblogs
Authors: Yang Jun , Zheng Rui , Zhao Ling , Gupta Sumeet
Published: June 2017

Purpose

As the social media platform becomes an ever more important communication channel between company and customer, companies are learning how they can best utilize social media to better communicate their brands with customers. The purpose of this paper is to explore the communication tactics adopted by the enterprise microblogs using a communication framework. Further, the authors hope to find out how these communication tactics influence customer brand experience (BE) and subsequently brand loyalty.

Design/methodology/approach

First, to identify the communication tactics used by enterprise microblogs, the authors recruited six active microblog users and listed all possible characteristics of enterprise microblogs that could increase customers’ fondness for the brand. Second, based on the listed 19 characteristics and existing theories, the authors pre-classified and conceptualized the content and style tactics categories. The authors also followed a sorting procedure to verify our classification. Finally, based on the sorted characteristics and previous research, the authors designed a questionnaire and 459 sets of valid data were collected from enterprise microblog users.

Findings

The communication tactics are classified into two dimensions, namely content tactics and style tactics. The content tactics include content diversity, content accuracy and content timeliness, and the style tactics include impression enhancement style and interactivity enhancement style. The results reveal that the communication content and style tactics significantly enhance overall customer BE and further brand loyalty. The study results also show that style tactics exert more influence on BE than content tactics.

Originality/value

This paper highlights the company’s important role in company-customer communication on social media, and categorizes the effective communication tactics used by the enterprise microblog within a communication framework. Companies could build brand loyalty by enhancing users’ BE using effective communication. The communication perspective and measures of the communication tactics in this study provide an ideal background for future research on IT-based company-customer interaction.
Neglecting human resource development in OBOR, a case of the China–Pakistan economic corridor (CPEC)
Authors: Ahmed Adeel , Arshad Mohd Anuar , Mahmood Arshad , Akhtar Sohail
Published: June 2017

Purpose

The purpose of this paper is to obtain greater insights into the implications for human resource development (HRD) in times of economic development, with a focus on China–Pakistan economic corridor (CPEC). In recent times of economic development, a number of economic corridors have emerged globally as tools of regional cooperation and development. In the context of Pakistan, there is a lack of appropriate attention to the field of HRD, which has suffered neglect through the decades (Abbasi and Burdey, 2008; Asrar-ul-Haq, 2015). With this conception, the present economic interventions merit a well-constructed and proper HRD policy for Pakistan. This study will provide HRD insights for policymakers, researchers, entrepreneurs and business executives.

Design/methodology/approach

The research approach of this study is purely based on literature review and on secondary data.

Findings

Based on the facts and literature reviews, this study concluded that One belt, One Road in general and CPEC in particular as an economic corridor can bring sustainable and long-lasting impact on the economy only if HRD is given proper attention.

Originality/value

To the best knowledge of the researchers, this is the first study that highlighted the HRD issue in CPEC.
Exploring suitability of cloud computing for small and medium-sized enterprises in India
Authors: Kumar Devesh , Samalia Harsh Vardhan , Verma Piyush
Published: June 2017

Purpose

The purpose of this paper is to evaluate the suitability of cloud computing for small and medium-sized enterprises (SMEs) in India.

Design/methodology/approach

Literature review is used to identify benefits, challenges, and factors concerning usage and adoption of cloud computing by SMEs. A conceptual framework was developed based on the existing theoretical models and factors identified from the literature. A survey based on questionnaire method was followed to collect data from 121 manufacturing SMEs in India. The conceptual framework was refined by using factor analysis, and multiple regression analysis was used to test the hypotheses.

Findings

Major benefits of cloud computing for SMEs include cost advantage, easy deployment process, easier access to latest information and communication technologies, automatic updates and upgrades, scalability, flexibility, and improved disaster recovery and back-up capabilities. The concern area includes perceived loss of control, vendor lock-in, security issues, reliability and availability issues, and internet connectivity and speed. The factors that are found significant include perceived benefits, top management support, competitive pressure, and perceived concerns. The model explained 73 percent of cloud computing adoption.

Research limitations/implications

The study is expected to make significant contribution toward body of knowledge pertaining to information technology adoption in SMEs.

Practical implications

The study is expected to provide SMEs an insight into real benefits and challenges associated with adopting cloud computing. The model can help SMEs in evaluating their readiness for adopting cloud computing and can ensure successful outcome of cloud computing adoption in SMEs. Providers are also going to be benefited through their enhanced understanding of SMEs’ requirements.

Originality/value

The proposed framework incorporates all the relevant factors including perceived benefits, perceived concerns, and other organizational and environmental factors to improve model’s predictive power.
Exploring the role of employee voice between high-performance work system and organizational innovation in small and medium enterprises
Authors: Rasheed Muhammad Athar , Shahzad Khuram , Conroy Christopher , Nadeem Sajid , Siddique Muhammad Usman
Published: June 2017

Purpose

Employee voice has emerged as a strong predictor of positive organizational outcomes. Grounding the theoretical model in resource-based theory; this study conceptualizes how high-performance work system (HPWS) can enhance organizational innovation of small and medium enterprises (SMEs) through voice behaviors. Specifically, the purpose of this paper is to empirically test if employee voice mediates the relationship between HPWS and organizational innovation.

Design/methodology/approach

This study used a quantitative strategy and cross-sectional survey method for the collection of data from SMEs operating in Pakistan. A list of SMEs was obtained from the federal government organization responsible for the development of SMEs in Pakistan. A self-administered structured questionnaire was distributed and 239 randomly selected SMEs responded to the survey.

Findings

Findings confirmed the conceptualized model and revealed that HPWS was significantly and positively related to employee voice and organizational innovation. Employee voice was found as a significant predictor of organizational innovation and mediating factor in the relationship between HPWS and organizational innovation.

Research limitations/implications

This study is limited in terms of variables included in the conceptual model and relatively small size of the sample that was derived from a single federal organization. More variables and SMEs can be included in future studies to get broader results and, potentially, better findings.

Practical implications

SME managers/owners can design HR function in such a way that employees will be encouraged to raise their voice and participate more in the organization. Scholars should study voice behaviors distinct from citizenship behaviors.

Originality/value

This study is the first of its kind to conceptualize the relationship between HPWS, employee voice, and organizational innovation in SMEs of Pakistan.