bluuebunny/crossref_metadata_2025 huggingface dataset:
Postbariatric Brachioplasty with Posteromedial Scar: Physical Model, Technical Refinements, and Clinical Outcomes
Authors: Simone Pierfranco , Carusi Carlo , Segreto Francesco , Iannuzzi Riccardo , Buscaglione Silvia , Gizzi Alessio , Giannitelli Sara , Rainer Alberto , Filippi Simonetta , Persichetti Paolo
Published: January 2018

Background:

Brachioplasty is an increasingly performed procedure following massive weight loss. A visible scar is the main hindrance to this surgery. The aims of the study were to develop a physical model to investigate the ideal location of the surgical incision and to present the authors’ technical refinements with the posteromedial scar approach.

Methods:

Twenty-four postbariatric patients underwent brachioplasty with posteromedial scar placement, concomitant liposuction, fascial plication, and axillary Z-plasty. Skin specimens were tested and a physical model of the arm was set up to investigate the difference in mechanical stress on the posteromedial and medial scars. The validated Patient and Observer Scar Assessment Scale, the Vancouver Scar Scale, and a questionnaire assessing subjective improvements were administered to patients. Preoperative and postoperative photographs were assessed by three independent plastic surgeons.

Results:

The physical model showed that stress intensity and distribution along the scar were reduced in the posteromedial location, with smaller scar displacement in the loading simulations. Twenty-three patients healed uneventfully. One (4.1 percent) had a 2-cm dehiscence. Mean Patient and Observer Scar Assessment Scale scores were, respectively, 2 ± 0.76 and 2.13 ± 0.64 in the patients’ and observers’ questionnaires. The mean Vancouver Scar Scale value was 3.5 ± 1.7. Questionnaires assessing the subjective outcomes showed a mean value of 3.45 ± 0.63 of 4. The surgeons’ assessment resulted in a score of 4.5 ± 0.4 of 5.

Conclusions:

The physical model demonstrated that the posteromedial scar was subjected to lower mechanical stress and displacement. The reported technical refinements allowed pleasant arm recontouring to be achieved with acceptable scarring and a low incidence of complications.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
The Keystone: Consistency in Restoring the Aesthetic Dorsum in Rhinoplasty
Authors: Afrooz Paul N. , Rohrich Rod J.
Published: January 2018

The keystone represents the union of six distinct anatomical structures between the bony vault and the cartilaginous midvault. In reshaping the nasal dorsum, the individual components of the nose respond variably as the fusion points of the keystone are released. In restoring the nasal dorsum, meticulous effort is made to equalize the width between the bony vault and the cartilaginous midvault. Techniques used for width equalization will yield gratifying long-term results and avoid common pitfalls such as the inverted-V deformity.
Gynecological Lymphoma: A Case Series and Review of the Literature
Authors: Slonimsky Einat , Korach Jacob , Perri Tamar , Davidson Tima , Apter Sara , Inbar Yael
Published: January 2018

Objective

The aim of the study was to evaluate the radiological characteristics of gynecological lymphoproliferative disease (LPD) and specific imaging features that may suggest the diagnosis.

Methods

Two readers conducted a retrospective evaluation of imaging studies of 13 female patients presenting with a gynecological LPD. A literature review was also performed.

Results

Of the 13 evaluated women, 9 had ovarian involvement, 3 had cervical involvement, and 1 had uterine involvement. The most common lesion characteristics were homogenous masses (11), with mild contrast enhancement (9), followed by soft-tissue necrosis (4), prominent blood vessels displaced by the lesions (4), linear arrangement of cysts at the periphery of the ovaries (3), and “touching” ovaries in all cases of bilateral ovarian involvement.

Conclusions

A solid large homogeneous mass with mild contrast enhancement should alert the radiologist to the possibility of the differential diagnosis of LPD. Radiologists should be “the gatekeepers” by raising this possibility to avoid unnecessary surgery and enable appropriate treatment.
Dependence of Scan Parameters on Nerve Fiber Crossing Depiction in Diffusion Spectrum Imaging in Clinical Practice
Authors: Tang Minghui , Oshinomi Kazuya , Ishizaka Kinya , Tha Khin Khin , Yamamoto Toru
Published: January 2018

Objective

The objective of this study was to show the effect of the number of sampling points (NS) and the maximum b value (b
max) on fiber crossing detection in diffusion spectrum imaging (DSI) in clinical practice.

Methods

We performed 3-Tesla DSI in which we changed the NS (62–258) while keeping b
max at 8000 s/mm2 and in which we changed the b
max (4000–8000 s/mm2) while keeping the NS at 129. The superior longitudinal fasciculus volume and the proportion of nerve voxels in which at least 2 (Rcr2) or 3 (Rcr3) nerve fiber bundles crossed were calculated.

Results

When b
max was set to 8000 s/mm2, mean Rcr2 and Rcr3 values and superior longitudinal fasciculus volumes significantly increased with higher NSs, but they did not significantly change when we varied b
max with 129 NS.

Conclusions

Depiction sensitivity of nerve fiber crossing in DSI improves at higher NS and b
max settings, but a b
max insensitivity appears at an intermediate NS such as 129.
Maximizing geographical efficiency: An analysis of the configuration of Colorado's trauma system
Authors: Jansen Jan O. , Moore Ernest E. , Wang Handing , Morrison Jonathan J. , Hutchison James D. , Campbell Marion K. , Sauaia Angela
Published: January 2018

BACKGROUND

Trauma center designation in excess of need risks dilution of experience, reduction in research and training opportunities, and increased costs. The objective of this study was to evaluate the use of a novel data-driven approach (whole-system mathematical modeling of patient flow) to compare the configuration of an existing trauma system with a mathematically optimized design, using the State of Colorado as a case study.

METHODS

Geographical network analysis and multiobjective optimization, 105,448 patients injured in the State of Colorado between 2009 and 2013, who met the criteria for inclusion in the state-mandated trauma registry maintained by the Colorado Department of Public Health and Environment were included. We used the Nondominant Sorting Genetic Algorithm II to conduct a multiobjective optimization of possible trauma system configurations, with the objectives of minimizing total system access time, and the number of casualties who could not reach the desired level of care.

RESULTS

Modeling suggested that system configurations with high-volume Level I trauma centers could be mathematically optimized with two centers rather than the current three (with an estimated annual volume of 970–1,020 and 715–722 severely injured patients per year), four to five Level II centers, and 12 to 13 Level III centers. Configurations with moderate volume Level I centers could be optimized with three such centers (with estimated institutional volumes of 439–502, 699–947, and 520–726 severely injured patients per year), two to five Level II centers, and eight to ten Level III centers.

CONCLUSION

The modeling suggested that the configuration of Colorado’s trauma system could be mathematically optimized with fewer trauma centers than currently designated. Consideration should be given to the role of optimization modeling to inform decisions about the ongoing efficiency of trauma systems. However, modeling on its own cannot guarantee improved patient outcome; thus, the use of model results for decision making should take into account wider contextual information.

LEVEL OF EVIDENCE

Epidemiological, Level IV.
Intraoperative combination of resuscitative endovascular balloon occlusion of the aorta and a median sternotomy in hemodynamically unstable patients with penetrating chest trauma: Is this feasible?
Authors: Ordoñez Carlos A. , Parra Michael W. , Manzano-Nunez Ramiro , Herrera-Escobar Juan P. , Serna Jose J. , Rodriguez Ossa Paola , Mejia David , Del Valle Ana M. , Salcedo Alexander , Salamea Juan C. , Rodriguez Fernando
Published: January 2018

BACKGROUND

Recent evidence suggests that resuscitative endovascular balloon occlusion of the aorta (REBOA) is an effective life-saving intervention in patients with severe torso trauma. However, the deployment of REBOA in patients with isolated penetrating intrathoracic injuries remains controversial. We propose that a median sternotomy be performed in conjunction with REBOA as a feasible and effective means of hemorrhage control in patients suffering from penetrating chest trauma who present hemodynamically unstable. The objective of our study was to present our initial experience with this approach.

METHODS

A prospectively collected case series of the use of REBOA (10 Fr) in conjunction with a median sternotomy from January 2015 to December 2016 at a Level I Trauma Center. We included hemodynamically unstable non-compressible torso hemorrhage patients with penetrating chest trauma who underwent intraoperative REBOA deployment plus median sternotomy.

RESULTS

A total of 68 trauma-related emergent thoracic surgeries were performed at our institution during the study period. Of these, seven suffered from penetrating chest trauma and non-compressible torso hemorrhage and underwent REBOA plus median sternotomy. Six out of the seven patients suffered intrathoracic vascular injuries: two subclavian arteries, two internal mammary arteries, two aortic arch, and five major central venous injuries. Four patients had an associated lung injury with AIS >3, of which two suffered a pulmonary hilar vessel disruption. REBOA-related complications included one case of upper gastrointestinal bleeding. Six out of the seven patients survived the 30-day follow-up. No adverse neurologic outcomes or deficits were observed in survivors.

CONCLUSION

The combined use of REBOA and median sternotomy could be a feasible and effective alternative to hemorrhage control in patients with non-compressible torso hemorrhage secondary to penetrating chest trauma. These findings challenge the recommendation against the use of REBOA in penetrating intrathoracic injuries. Future studies with stronger designs and larger sample sizes are required to confirm our results.

LEVEL OF EVIDENCE

Therapeutic, level V.
Avoiding Cribari gridlock: The standardized triage assessment tool improves the accuracy of the Cribari matrix method in identifying potential overtriage and undertriage
Authors: Roden-Foreman Jacob W. , Rapier Nakia R. , Yelverton Luanna , Foreman Michael L.
Published: January 2018

BACKGROUND

The Cribari matrix method (CMM) is the standard to identify potential overtriage and undertriage but requires case reviews to correct for the fact that Injury Severity Score does not account for physiology or comorbidities, nor is it well correlated with resource consumption. Further, the secondary reviews introduce undesirable subjectivity. This study assessed if the Standardized Triage Assessment Tool (STAT)—a combination of the CMM and the Need For Trauma Intervention—could more accurately determine overtriage and undertriage than the CMM alone.

METHODS

The registry of an American College of Surgeons verified Level I adult trauma center in Texas was queried for all new emergency department traumas 2013 to 2016 (n = 11,110). Binary logistic regressions were used to test the associations between the triage determinations of each metric against indicators of injury severity (risk factors, complications, and mortality) and resource consumption (number of procedures in 3 days and total length of stay).

RESULTS

Both metrics were associated with the indicators of injury severity and resource consumption in the expected directions, but STAT had stronger or equivalent associations with all variables tested. Using the CMM, there was 50.4% overtriage and 9.1% undertriage. Using STAT, overtriage was reduced to 30.8% (relative reduction = 38.9%) and undertriage was reduced to 3.3% (relative reduction = 63.7%).

CONCLUSION

Using the CMM with secondary case reviews makes valid multi-institutional triage rate comparisons impossible because of the subjective and unstandardized nature of these reviews. STAT’s out-of-box triage determinations (i.e., without manual case review) outperformed CMM in almost every tested variable for both over- and undertriage. STAT, an automatic, standardized method offers significant improvements compared to the current subjective system. Further, by accounting for both anatomic injury severity and resource consumption, STAT may allow trauma centers to better allocate resources and predict patient needs with fewer cases requiring manual review.

LEVEL OF EVIDENCE

Prognostic, level III.
Application and Interpretation of Functional Outcome Measures for Testing Individuals With Cognitive Impairment
Authors: Ross Christine M.
Published: January 2018

The prevalence of individuals living with dementia worldwide is expected to increase exponentially; yet these individuals receive minimal recommended quality of care. Physical therapists are a valuable component of the comprehensive medical care team serving individuals with cognitive impairment. Utilization of evidence-based outcome measures to determine optimal care is critical to improving the effectiveness of care for individuals with cognitive impairment, decreasing the variability in the evaluation process. The purpose of this article is to describe functional outcome tools to assist skilled physical therapists with the evaluation process, essential to enhancing the quality of the individualized plan of care.
#Alzheimer's and Dementia
Authors: Danilovich Margaret K. , Tsay Jonathan , Al-Bahrani Reda , Choudhary Alok , Agrawal Ankit
Published: January 2018

The authors performed Twitter data analysis to explore content relative to Alzheimer disease and dementia and then qualitatively coded tweets to explore themes. During a 1-month period, the authors collected 2739 tweets that referenced #alzheimer's, #Alz, #dementia, or #dimentia. Content was posted by (1) caregivers (n = 1391), (2) caregiving organizations (n = 214), (3) general public (n = 854), and (4) news outlets (n = 66). Twitter content themes referenced social support and advocacy. Results show people document experiences with Alzheimer disease and memory loss on Twitter. Twitter could be used to broadly reach persons affected by memory impairment for social support and services, warranting future research.
Cell adhesion and fluid flow jointly initiate genotype spatial distribution in biofilms
Authors: Martínez-García Ricardo , Nadell Carey D. , Hartmann Raimo , Drescher Knut , Bonachela Juan A.
Published: January 2018

Biofilms are microbial collectives that occupy a diverse array of surfaces. The function and evolution of biofilms are strongly influenced by the spatial arrangement of different strains and species within them, but how spatiotemporal distributions of different genotypes in biofilm populations originate is still underexplored. Here, we study the origins of biofilm genetic structure by combining model development, numerical simulations, and microfluidic experiments using the human pathogenVibrio cholerae. Using spatial correlation functions to quantify the differences between emergent cell lineage segregation patterns, we find that strong adhesion often, but not always, maximizes the size of clonal cell clusters on flat surfaces. Counterintuitively, our model predicts that, under some conditions, investing in adhesion can reduce rather than increase clonal group size. Our results emphasize that a complex interaction of fluid flow and cell adhesiveness can underlie emergent patterns of biofilm genetic structure. This structure, in turn, has an outsize influence on how biofilm-dwelling populations function and evolve.

Author summary

Biofilms are bacterial groups, often attached to surfaces, in which a broad variety of cooperative and competitive interactions typically occur. The spatial organization of different strains and species within biofilm communities strongly influences their global functioning, but little is known about how such structure arises. Combining experiments onV. choleraeand simulations of a cellular automaton, we show that the complex interaction between bacterial traits (cell adhesion) and environmental factors (fluid flow intensity) strongly influences the early origins of biofilm spatial structure. In most cases, we found that highly-adhesive strains form larger clusters than the weakly-adhesive ones. Against intuition, however, we also found the opposite outcome: weakly-adhesive tend to form larger clusters than the highly adhesive ones when flows are weak or the population density of colonizing cells is high.
The Specificity of IQGAP1 Toward the PI3K-Akt Pathway is Dependent on the IQ3 motif
Authors: Chen Mo , Wen Tianmu , Choi Suyong , Thapa Narendra , Jung Oisun , Lambert Paul F. , Rapraeger Alan C. , Anderson Richard A.
Published: January 2018

Epidermal growth factor receptor (EGFR) and its downstream phosphatidylinositol 3-kinase (PI3K) pathway are commonly deregulated in many cancers including head and neck cancer (HNC). Recently, we have shown that the IQ motif-containing GTPase-activating protein 1 (IQGAP1) provides a molecular platform to scaffold all the components from the PI3K-Akt pathway and results in the sequential generation of phosphatidylinositol-3,4,5-triphosphate (PI3,4,5P3). This makes the IQGAP1-PI3K scaffold a promising therapeutic target. In addition to the PI3K-Akt pathway, IQGAP1 also scaffolds the Ras-ERK pathway. To identify an IQGAP1 mutant that specifically loses IQGAP1-PI3K signaling but not other functions, we have focused on the IQ3 motif since this region binds with both the PIPK1α and PI3K enzymes and a short peptide derived from this sequence blocks binding and PI3K signaling. An IQ3 deletion mutant (ΔIQ3) in IQGAP1 was functionally compared with wild-type (WT) IQGAP1. We found that the IQ3 domain specifically mediates the PI3K-Akt pathway but does not regulate the Ras-ERK pathway. The IQ3 deletion mutant lost interactions with PI3K-Akt components but retained its binding of ERK pathway components and cell surface receptors, EGFR and integrins. In addition, the IQ3 deletion mutant lost regulation of cell migration. Consistently, the IQ3 motif derived peptide blocked Akt activation and led to the blockage of invasion mediated by EGFR organized into an integrin complex by syndecan-4. Taken together, this work has defined the IQGAP1 IQ3 motif as a specific target sequence for the scaffolding of the PI3K-AKT pathway.
Coordinated downregulation of the photosynthetic apparatus as a protective mechanism against UV exposure in the diatomCorethron hystrix
Authors: Read Robert W. , Vuono David C. , Neveux Iva , Staub Carl , Grzymski Joseph J.
Published: January 2018

The effect of ultraviolet radiation (UVR) on photosynthetic efficiency and the resulting mechanisms against UV exposure employed by phytoplankton are not completely understood. To address this knowledge gap, we developed a novel close-coupled, wavelength-configurable platform designed to produce precise and repeatablein vitroirradiation ofCorethron hystrix, a member of a genera found abundantly in the Southern Ocean where UV exposure is high. We aimed to determine its metabolic, protective, mutative, and repair mechanisms as a function of varying levels of specific electromagnetic energy. Our results show that the physiological responses to each energy level of UV have a negative linear decrease in the photosynthetic efficiency of photosystem II proportional to UV intensity, corresponding to a large increase in the turnover time of quinone re-oxidation. Gene expression changes of photosystem II related reaction center proteins D1, CP43 and CP47 showed coordinated downregulation whereas the central metabolic pathway demonstrated mixed expression of up and downregulated transcripts after UVR exposure. These results suggest that while UVR may damage photosynthetic machinery, oxidative damage may limit production of new photosynthetic and electron transport complexes as a result of UVR exposure.
Representation of real-world event schemas during narrative perception
Authors: Baldassano Christopher , Hasson Uri , Norman Kenneth A.
Published: January 2018

Understanding movies and stories requires maintaining a high-level situation model that abstracts away from perceptual details to describe the location, characters, actions, and causal relationships of the currently unfolding event. These models are built not only from information present in the current narrative, but also from prior knowledge about schematic event scripts, which describe typical event sequences encountered throughout a lifetime. We analyzed fMRI data from 44 human subjects presented with sixteen three-minute stories, consisting of four schematic events drawn from two different scripts (eating at a restaurant or going through the airport). Aside from this shared script structure, the stories varied widely in terms of their characters and storylines, and were presented in two highly dissimilar formats (audiovisual clips or spoken narration). One group was presented with the stories in an intact temporal sequence, while a separate control group was presented with the same events in scrambled order. Regions including the posterior medial cortex, medial prefrontal cortex (mPFC), and superior frontal gyrus exhibited schematic event patterns that generalized across stories, subjects, and modalities. Patterns in mPFC were also sensitive to overall script structure, with temporally scrambled events evoking weaker schematic representations. Using a Hidden Markov Model, patterns in these regions can predict the script (restaurant vs. airport) of unlabeled data with high accuracy, and can be used to temporally align multiple stories with a shared script. These results extend work on the perception of controlled, artificial schemas in human and animal experiments to naturalistic perception of complex narrative stimuli.

Significance Statement

In almost all situations we encounter in our daily lives, we are able to draw on our schematic knowledge about what typically happens in the world to better perceive and mentally represent our ongoing experiences. In contrast to previous studies that investigated schematic cognition using simple, artificial associations, we measured brain activity from subjects watching movies and listening to stories depicting restaurant or airport experiences. Our results reveal a network of brain regions that is sensitive to the shared temporal structure of these naturalistic situations. These regions abstract away from the particular details of each story, activating a representation of the general type of situation being perceived.
A quantitative evaluation of MIRU-VNTR typing against whole-genome sequencing for identifying Mycobacterium tuberculosis transmission: A prospective observational cohort study
Authors: Wyllie David , Davidson Jennifer , Walker Tim , Rathod Preeti , Crook Derrick , Peto Tim , Robinson Esther , Smith Grace , Campbell Colin
Published: January 2018

Summary

Background

Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR) typing is widely used in high-income countries for Mycobacterium tuberculosis typing. Whole-genome sequencing (WGS) is known to deliver greater specificity, but no quantitative prospective comparison has yet been undertaken.

Methods

We studied isolates from the English Midlands, sampled consecutively between 1 January 2012 and 31 December 2015. In addition to routinely performed MIRU-VNTR typing, DNA was extracted from liquid cultures and sequenced using Illumina technology. Demographic and epidemiological data were extracted from the Enhanced Tuberculosis Surveillance system maintained by Public Health England. Closely related samples, defined using a threshold of five single nucleotide variants (SNVs), were compared to samples with identical MIRU-VNTR profiles, with shared epidemiological risk factors, and to those with both characteristics.

Findings

1,999 patients were identified for whom at least one M. tuberculosis isolate had been MIRU-VNTR typed and sequenced. Comparing epidemiological risk factors with close genetic relatedness, only coresidence had a positive predictive value of over 5%. Excluding co-resident individuals, 18.6% of patients with identical MIRU-VNTR profiles were within 5 SNVs. Where patients also shared social risk factors and ethnic group, this rose to 48%. Only 8% of MIRU-VNTR linked pairs in lineage 1 were within 5 SNV, compared to 31% in lineage 4.

Interpretation

In the setting studied, MIRU-VNTR typing and epidemiological risk factors are poorly predictive of close genomic relatedness, assessed by SNV. MIRU-VNTR performance varies markedly by lineage.

Funding

Public Health England, National Institute of Health Research Oxford Biomedical Research Centre.
Detection of de novo copy number deletions from targeted sequencing of trios
Authors: Fu Jack M. , Leslie Elizabeth J. , Scott Alan F. , Murray Jeffrey C. , Marazita Mary L. , Beaty Terri H. , Scharpf Robert B. , Ruczinski Ingo
Published: January 2018

De novo copy number deletions have been implicated in many diseases, but there is no formal method to date however that identifies de novo deletions in parent-offspring trios from capture-based sequencing platforms. We developed Minimum Distance for Targeted Sequencing (MDTS) to fill this void. MDTS has similar sensitivity (recall), but a much lower false positive rate compared to less specific CNV callers, resulting in a much higher positive predictive value (precision). MDTS also exhibited much better scalability, and is available as open source software at github.com/JMF47/MDTS.
Optogenetically induced low-frequency correlations impair perception
Authors: Nandy Anirvan S. , Nassi Jonathan J. , Reynolds John H.
Published: January 2018

Deployment of covert attention to a spatial location can cause large decreases in low-frequency correlated variability among neurons in macaque area V4 whose receptive-fields lie at the attended location. It has been estimated that this reduction accounts for a substantial fraction of the attention-mediated improvement in sensory processing. These estimates depend on assumptions about how population signals are decoded and the conclusion that correlated variability impairs perception, is purely hypothetical. Here we test this proposal directly by optogenetically inducing low-frequency fluctuations, to see if this interferes with performance in an attention-demanding task. We find that low‐ frequency optical stimulation of neurons in V4 elevates correlations among pairs of neurons and impairs the animal’s ability to make fine sensory discriminations. Stimulation at higher frequencies does not impair performance, despite comparable modulation of neuronal responses. These results support the hypothesis that attention-dependent reductions in correlated variability contribute to improved perception of attended stimuli.
Detection of HPV E7 transcription at single-cell resolution in epidermis
Authors: Lukowski SW , Tuong ZK , Noske K , Senabouth A , Nguyen QH , Soyer HP , Frazer IH , Powell JE
Published: January 2018

Persistent human papillomavirus (HPV) infection is responsible for at least 5% of human malignancies. Most HPV-associated cancers are initiated by the HPV16 genotype, as confirmed by detection of integrated HPV DNA in cells of oral and anogenital epithelial cancers. However, single-cell RNA-sequencing (scRNA-seq) may enable prediction of HPV involvement in carcinogenesis at other sites. We conducted scRNA-seq on keratinocytes from a mouse transgenic for theE7gene of HPV16, and showed sensitive and specific detection of HPV16-E7mRNA, predominantly in basal keratinocytes. We showed that increasedE7mRNA copy number per cell was associated with increased expression of E7 induced genes. This technique enhances detection of viral transcripts in solid tissue and may clarify possible linkage of HPV infection to development of squamous cell carcinoma.
Charcot-Leyden Crystals activate the NLRP3 inflammasome and cause IL-1β inflammation
Authors: Rodríguez-Alcázar Juan Francisco , Ataide Marco Antonio , Engels Gudrun , Schmitt-Mabmunyo Christine , Garbi Natalio , Kastenmüller Wolfgang , Latz Eicke , Franklin Bernardo S
Published: January 2018

Charcot-Leyden crystals (CLCs) are Galectin-10 protein crystals that can form after eosinophils degranule. CLCs can appear and persist in tissues from patients with eosinophilic disorders, such as asthma, allergic reactions, fungal, and helminthic infections. Despite abundant reports of their occurrence in human disease, the inflammatory potential of CLCs has remained unknown. Here we show that CLCs induce IL-1β release upon their uptake by primary human macrophagesin vitro,and that they induce inflammationin vivoin mouse models of acute peritonitis and bronchitis. CLC-induced IL-1β was dependent on NLRP3 and caspase-1, and their instillation in inflammasome reporter mice promoted the assembly of ASC complexes and IL-1β secretion in the lungs. Our findings reveal that CLCs are recognized by the NLRP3 inflammasome, which may sustain inflammation that follows eosinophilic inflammatory processes.
SSPIM: a beam shaping toolbox for structured selective plane illumination microscopy
Authors: Aakhte Mostafa , Akhlaghi Ehsan A. , Müller H.-Arno J.
Published: January 2018

An important aim of the development of selective plane illumination microscopy (SPIM) is to present a completely open and flexible microscope set-up for nonspecialist users. Here, we report Structured SPIM (SSPIM), which provides an open-source, user-friendly and compact toolbox for beam shaping that can generate digital patterns for a wide range of illumination beams. SSPIM represents a toolbox to produce static, spherical Gaussian, Bessel and Airy beams by simple control of a Spatial Light Modulator (SLM). In addition, it is able to produce patterns for incoherent and coherent (lattice beam) array beam formation and tiling for all types of beams supported. We demonstrate the workflow and experimental and simulation results using the SSPIM toolbox. In final, the capability of the SSPIM is investigated with 3D imaging of Drosophila embryo using three different illumination beams such as scanned/dithered Gaussian, Bessel and Lattice beam which engineered with SSPIM. SSPIM toolbox is easy to use and applicable for a wide range of applications to generate and optimize the desired beam pattern and thus can help developing adaptation of the Open SPIM system towards a wider range of biological samples.
Structure-guided design of a cell penetrating peptide preventing cAMP modulation of HCN channels
Authors: Saponaro Andrea , Cantini Francesca , Porro Alessandro , Bucchi Annalisa , Di Francesco Dario , Maione Vincenzo , Donadoni Chiara , Introini Bianca , Mesirca Pietro , Mangoni Matteo E. , Thiel Gerhard , Banci Lucia , Santoro Bina , Moroni Anna
Published: January 2018

The auxiliary subunit TRIP8b prevents cAMP activation of HCN channels by antagonizing its binding to their cyclic-nucleotide binding domain (CNBD). By determining an NMR-derived structure of the complex formed by the HCN2 channel CNBD and a minimal TRIP8b fragment, TRIPnano, we show here a bipartite interaction between the peptide and CNBD which prevents cAMP binding in two ways: through direct competition for binding at the distal C-helix of the CNBD; and through an allosteric reduction in cAMP affinity induced by TRIP8b binding to the CNBD N-bundle loop. TRIPnano abolishes cAMP binding in all three isoforms, HCN1, HCN2 and HCN4 and can be used to prevent cAMP stimulation in native f-channels. Application of TRIP8bnano, or its delivery via a cell-penetrating sequence, in sinoatrial node myocytes, selectively inhibits beta-adrenergic stimulation of the native If current and mimics the physiological concentrations of acetylcholine leading to a 30% reduction in the spontaneus rate of action potential firing.
Beyond synthetic lethality: charting the landscape of clinically relevant genetic interactions in cancer
Authors: Magen Assaf , Das Avinash , Lee Joo Sang , Sharmin Mahfuza , Lugo Alexander , Gutkind J. Silvio , Schäffer Alejandro A. , Ruppin Eytan , Hannenhalli Sridhar
Published: January 2018

The phenotypic effect of perturbing a gene’s activity depends on the activity level of other genes, reflecting the notion that phenotypes are emergent properties of a network of functionally interacting genes. In the context of cancer, contemporary investigations have primarily focused on just one type of functional genetic interaction (GI) – synthetic lethality (SL). However, there may be additional types of GIs whose systematic identification would enrich the molecular and functional characterization of cancer. Here, we describe a novel data-driven approach called EnGIne, that applied to TCGA data identifies 71,946 GIs spanning 12 distinct types, only a small minority of which are SLs. The detected GIs explain cancer driver genes’ tissue-specificity and differences in patients’ response to drugs, and stratify breast cancer tumors into refined subtypes. These results expand the scope of cancer GIs and lay a conceptual and computational basis for future studies of additional types of GIs and their translational applications. The GI network is accessible online via a web portal [https://amagen.shinyapps.io/cancerapp/].
Comparing complex variants in family trios
Authors: Toptaş Berke Ç. , Rakocevic Goran , Kómár Péter , Kural Deniz
Published: January 2018

Motivation: Several tools exist to count Mendelian violations in family trios by comparing variants at the same genomic positions. This naive variant comparison however, fails to assess regions where multiple variants need to be examined together, resulting in reduced accuracy of existing Mendelian violation checking tools.

Results: We introduce VBT, a trio concordance analysis tool, that identifies Mendelian violations by approximately solving the 3-way variant matching problem to resolve variant representation differences in family trios. We show that VBT outperforms previous trio comparison methods by accuracy.

Availability: VBT is implemented in C++ and source code is available under GNU GPLv3 license at the following URL: https://github.com/sbg/VBT-TrioAnalysis.git

Contact:cagkantoptas@hotmail.com

Supplementary information: Supplementary materials are available at Biorxiv.
The Immune Deficiency Pathway Regulates Metabolic Homeostasis inDrosophila
Authors: Davoodi Saeideh , Galenza Anthony , Panteluk Andrew , Deshpande Rujuta , Ferguson Meghan , Grewal Savraj , Foley Edan
Published: January 2018

Immune and metabolic pathways collectively influence host responses to microbial invaders, and mutations in one pathway frequently disrupt activity in the other. We used theDrosophilamodel to characterize metabolic homeostasis in flies with modified Immune Deficiency (IMD) pathway activity. The IMD pathway is very similar to the mammalian Tumor Necrosis Factor-alpha pathway, a key regulator of vertebrate immunity and metabolism. We found that persistent activation of IMD resulted in hyperglycemia, depleted fat reserves, and developmental delays, implicating IMD in metabolic regulation. Consistent with this hypothesis, we found thatimdmutants weigh more, are hyperlipidemic, and have impaired glucose tolerance. To test the importance of metabolic regulation for host responses to bacterial infection, we challenged insulin pathway mutants with lethal doses of severalDrosophilapathogens. We found that loss-of-function mutations in the insulin pathway impacted host responses to infection in a manner that depends on the route of infection, and the identity of the infectious microbe. Combined, our results support a role for coordinated regulation of immune and metabolic pathways in host containment of microbial invaders.
Pressure-induced coherent sliding-layer transition in the excitonic insulator Ta2NiSe5
Authors: Nakano Akitoshi , Sugawara Kento , Tamura Shinya , Katayama Naoyuki , Matsubayashi Kazuyuki , Okada Taku , Uwatoko Yoshiya , Munakata Kouji , Nakao Akiko , Sagayama Hajime , Kumai Reiji , Sugimoto Kunihisa , Maejima Naoyuki , Machida Akihiko , Watanuki Tetsu , Sawa Hiroshi
Published: January 2018

The crystal structure of the excitonic insulator Ta2NiSe5has been investigated under a range of pressures, as determined by the complementary analysis of both single-crystal and powder synchrotron X-ray diffraction measurements. The monoclinic ambient-pressure excitonic insulator phase II transforms upon warming or under a modest pressure to give the semiconductingC-centred orthorhombic phase I. At higher pressures (i.e.>3 GPa), transformation to the primitive orthorhombic semimetal phase III occurs. This transformation from phase I to phase III is a pressure-induced first-order phase transition, which takes place through coherent sliding between weakly coupled layers. This structural phase transition is significantly influenced by Coulombic interactions in the geometric arrangement between interlayer Se ions. Furthermore, upon cooling, phase III transforms into the monoclinic phase IV, which is analogous to the excitonic insulator phase II. Finally, the excitonic interactions appear to be retained despite the observed layer sliding transition.
Knowledge artifacts: the implications of incommensurable dimensions for their design
Authors: Simone Carla
Published: January 2018

Purpose

The purpose of this paper is to overcome the confusion generated by a loose definition of the term knowledge artifact (KA) and its impacts on the design of technologies supporting their use.

Design/methodology/approach

The paper looks at the conceptual foundations underpinning the concept of KA that are related to the way in which knowledge is conceived, and revisits the outcomes of empirical investigations to shed light on different aspects of the use of KA in various settings.

Findings

The paper identifies a class of KAs and its role in relation to other classes of KAs, as it emerges from the empirical investigations.

Research limitations/implications

The focus is on documental artifacts that are, however, widely used in different domains and organizations. New empirical work is needed to consider other kinds of artifacts and their role in knowledge-intense activities.

Practical implications

The paper aims to drive the attention of the designer on phenomena that hinder the acceptance, appropriation and effectiveness of the technologies they design to support a crucial aspect of collaboration.

Originality/value

The paper is original in the following ways: first, documenting the interplay between a kind of KA that is poorly considered in the literature with other classes of KAs; second, highlighting a set of principles that should guide the construction of computational KAs of a different nature.
Rigor, relevance, and the knowledge “market”
Authors: Hamet Joanne , Michel Sylvie
Published: January 2018

Purpose

The “relevance literature” often moans that the publications of top-ranked academic journals are hardly relevant to managers, while actionable research struggles to get published. The purpose of this paper is to propose a theoretical explanation of this phenomenon.

Design/methodology/approach

This paper addresses the relevance debate in management science through the theoretical frame of the theories of the firm.

Findings

This paper proposes that business organizations should tend to internalize specific applied research. Applied to management research, this could explain why the “market” for academic publications might be more relevant for generalizable and conceptual research than for applied, contextualized research.

Research limitations/implications

The paper is conceptual. However, it provides a new prospect to the rigor-relevance debate and to the ranking of researchers and business schools.

Practical implications

Business organizations should tend to internalize specific, applied research. Consequently, academic publications should concentrate on generalizable, “Mode 1” research.

Social implications

The conclusions could justify the evolution of the rating of universities and researchers towards a multi-dimensional rating, including measures of the socio-economic impact of the research, instead on focusing on academic publications only.

Originality/value

This paper offers a new point of view on the rigor-relevance debate. It supports the idea that applied and conceptual research are different forms of knowledge and should be “traded”, produced and rewarded differently.
To what is the review process relevant?
Authors: Babin Barry J. , Moulard Julie Guidry
Published: January 2018

Purpose

The purpose of this paper is to consider various strengths and weaknesses of the academic review process with an emphasis on the effect the process has on the relevance of business journals, particularly in the marketing literature.

Design/methodology/approach

The authors not only highlight some of the literature addressing the review process but also present insight and opinion largely based on decades of experience editing, reviewing, writing and publishing.

Findings

Reviewers can help develop research papers, but reviewers remain gatekeepers who, theoretically, protect journals from publishing research that would diminish the truthful body of knowledge within a field. However, many inefficiencies, some of which involve volition, allow one to question whether the review process as we know it best accomplishes that purpose.

Practical implications

Recognizing that reviewers affect journal prestige, the paper concludes with a number of ideas for improving the gate-keeping and developmental functions for academic articles.

Social implications

Society should extract value from what appears in publicly circulated, academic, refereed journals. However, to the extent that the publication process interferes with objective dissemination of knowledge, that value is diminished and perhaps even absent.

Originality/value

The paper intends to stimulate frank conversation about the Academy’s refereed publication process and factors that tend to interfere with its function.
Rigorous and Relevant – introducing a critical discourse analysis to the relevance debate
Authors: Bäckström Izabelle , Ahlgren Kajsa
Published: January 2018

Purpose

The purpose of this paper is to explore how the notion of “relevance” is produced, distributed and consumed in the field of management research by applying a critical discourse analysis (CDA) as a theoretical lens. A CDA perspective offers a way to scrutinize the power relations that emerge with journal rankings and how these influence how the relevance discourse develops.

Design/methodology/approach

This paper illustrates how a CDA perspective can be fruitfully applied to the relevance literature, exemplifying such an application with two illustrative texts. The texts represent two distinct cases; one is a fictive story informally distributed among scholars, and the other is an extract of a published review on the relevance debate.

Findings

A CDA lens sheds light on how academic power relations are maintained in the production, distribution and consumption of the “relevance” notion. It shows the importance of individual awareness among management researchers of how the discourse is shaped.

Research limitations/implications

To increase the generalizability of the study, a CDA lens could be applied to a larger amount of texts in the relevance literature. The findings imply that the relevance literature would benefit from contributions bridging the gap between rigor and relevance, and questioning how power relations are maintained.

Originality/value

CDA adds a new perspective to the relevance debate, revealing how academic power relations are maintained with management scholars’ adherence to journal norms and the implications of this act.
The feasibility of online dispute resolution in the Islamic banking industry in Malaysia
Authors: Oseni Umar A. , Adewale Abideen Adeyemi , Omoola Sodiq O.
Published: January 2018

Purpose

The paper aims to examine the perceptions of three major stakeholders – bankers, lawyers and customers – in the Islamic banking industry in Malaysia to assess their behavioural intention to use the proposed online dispute resolution (ODR) mechanism.

Design/methodology/approach

The study modifies the unified theory of acceptance and use of technology (UTAUT) within the context of ODR and its feasibility in the Malaysian Islamic banking industry. The model was extended to include trust in technology and trust in bank, which might have significant influences on the intentions of major stakeholders to use ODR for banking-related disputes. Actual use of the ODR was not included in the model as specified in the original UTAUT. Based on an internet survey, responses were obtained from about 109 respondents. The data obtained were subjected to multivariate statistical analyses.

Findings

Results obtained indicate that trust in technology and effort expectancy are the most influencing determinants of the behavioural intention to use ODR among stakeholders in the Islamic banking industry in Malaysia. However, performance expectancy and social influence did not produce significant effects on behavioural intention.

Research limitations/implications

Applying ODR in the banking industry in Malaysia will contribute to sustainable banking businesses in major Islamic finance jurisdictions. Being the most advanced region in global Islamic banking business, Asia sets the pace through theoretical and empirical studies in exploring innovative ideals such as ODR to promote sustainable business that not only ensures proper customer relationship management but also promotes consume protection.

Practical implications

Results obtained suggest that the increasing use of internet banking will make ODR the preferable mechanism for dispute resolution in small-scale disputes in retail banking. This will also require some form of predictability, enforceability andShari‘ahcompliance in the process of dispute resolution for the major stakeholders to have full confidence in the ODR mechanism. The recently introduced Financial Ombudsman Scheme in the Islamic Financial Services Act 2013 of Malaysia is expected to serve as a good legal basis for the ODR mechanism.

Originality/value

This appears to be one of the earliest attempts to examine the application of ODR in resolving Islamic banking disputes with a detailed analysis on its legal basis and implication.
The role of international investment agreements in attracting FDI to developing countries
Authors: Beebeejaun Ambareen
Published: January 2018

Purpose

The study aims to focus on the effectiveness of international investment agreements (IIAs) in helping or facilitating the influx of foreign direct investment (FDI) to host developing countries.

Design/methodology/approach

To critically examine the topic, the black letter approach and the socio-legal analysis are adopted. The study has analysed how Mauritius, being a developing country, is responding to FDI needs from various bilateral and multilateral investment treaties concluded, and the research includes the analysis of official data publicly made available by the World Trade Organization, Organisation for Economic Co-operation and Development, International Monetary Fund and Mauritius governmental agencies’ reports.

Findings

From the methodologies used, it was found that other than IIAs, there are various key determinants which foreign investors consider prior to injecting their capital in developing countries in terms of environmental, social and cultural factors. Also, there are some inherent loopholes mostly in terms of monitoring, in the way IIAs are concluded and are applied in practice by and amongst signatory states.

Originality/value

This research is amongst the first studies to conclude the link between IIAs and FDI flows in developing countries with a particular focus on Mauritius. Additionally, an overwhelming number of studies have emphasised on the efforts to boost FDI, which are inspired mostly by action plans of developed nations, but this research will analyse the policy options adopted by China, being itself a developing country, and the extent to which such recommendations are applicable in the context of Mauritius will also be considered.