bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-Dimensional Affordable Stone Models for Cleft Lip Markings
Authors: Kantar Rami S. , Gonchar Marina , Maliha Samantha G. , Ramly Elie P. , Alfonso Allyson R. , Cohen Oriana , Eisemann Bradley S. , Diaz-Siso J. Rodrigo , Saadeh Pierre B. , Flores Roberto L.
Published: April 2019

Introduction

Knowledge of surgical markings for unilateral cleft lip (UCL) repair is critical for surgical competency. However, few appropriate models are accessible to residents and affordable and accurately reproduce this 3-dimensional (3D) deformity. We propose that cleft care units have the capability of creating affordable 3D stone models to teach UCL markings.

Methods

Polyvinyl siloxane and SnapStone were used to create UCL stone models. Thirteen plastic surgery residents were prospectively recruited, provided with a textbook chapter and online module for studying surgical markings for UCL repair, and then asked to perform the markings on a UCL stone model and standardized patient photograph. Learner satisfaction was evaluated using a modified survey based on the Student Evaluation of Educational Quality survey.

Results

The production time of each model was 10 minutes, whereas the cost was $1.84. Participants reported that the stone model was more stimulating (4.77 ± 0.44 vs 3.92 ± 0.86; U = 38.0; P = 0.008), increased their interest more (4.70 ± 0.48 vs 3.53 ± 1.20; U = 33.5; P = 0.005), allowed better learning (4.61 ± 0.51 vs 3.08 ± 0.86; U = 10.0; P < 0.001), was clearer (4.62 ± 0.51 vs 3.15 ± 0.90; U = 12.5; P < 0.001), and was more effective for learning cleft lip markings (4.77 ± 0.44 vs 3.08 ± 1.04; U = 9.0; P < 0.001). They were also more likely to recommend it (4.85 ± 0.38 vs 3.15 ± 1.07; U = 7.0; P < 0.001).

Conclusions

Plastic surgery residents report that 3D cleft lip stone models are superior training tools to learn cleft lip markings compared with patient photographs. These educational tools have the potential to overcome significant financial, logistic, and time constraints in teaching cleft lip surgery markings.
Combined Surgical Treatment for Chronic Upper Extremity Lymphedema Patients
Authors: Leppäpuska Ida-Maria , Suominen Erkki , Viitanen Tiina , Rannikko Eeva , Visuri Mikko , Mäki Maija , Saarikko Anne , Hartiala Pauliina
Published: April 2019

Background

Upper limb lymphedema is a common problem after axillary lymph node dissection. Lymphatic drainage can be improved by microvascular lymph node transfer, whereas liposuction can be used to reduce arm volume and excess of adipose tissue. We present the results of chronic lymphedema patients who have undergone lymph node transfer and liposuction simultaneously in 1 operation and compare the results with patients who have undergone lymph node transfer without liposuction.

Methods

During May 2007 to February 2015, 20 postmastectomy patients and 1 Hodgkin's lymphoma patient presenting with chronic nonpitting lymphedema (age between 37 and 74 years, average 56.7 years) were operated using the combined technique and 27 postmastectomy patients presenting with early-stage lymphedema (age between 31 and 68 years, average age 50.2 years) were operated using only the lymph node transfer. Compression therapy was started immediately after the operation and the patients used compression 24 h/d at least 6 months postoperatively. Changes in clinical parameters (number of erysipelas infections, pain), arm volume, transport indexes calculated form lymphoscintigraphy images, and daily usage of compression garments were compared preoperatively and postoperatively and between groups (combined technique vs lymph node transfer). The study was a retrospective observational study.

Results

In the combined technique group, the average arm volume excess decreased postoperatively 87.7%, and in 7 of 10 patients, the edema volume did not increase even without compression. Seventeen of 21 patients were able to reduce the use of compression garment. Lymphoscintigraphy results were improved in 12 of 15 patients and the improvement was significantly greater in the combined technique group than in the lymph node transfer group (P = 0.01). The number of erysipelas infections was decreased in 7 of 10 patients and the decrease was significantly greater in the combined technique group than in the lymph node transfer group (P = 0.02). In the lymph node transfer group, the average excess volume decreased postoperatively 27.5%. Fourteen of 27 patients were able to reduce the use of compression garments. Lymphoscintigraphy results were improved in 8 of 19 patients, and the number of erysipelas infections was decreased in 1 of 3 patients.

Conclusions

Liposuction can safely be performed with lymph node transfer in 1 operation to achieve optimal results in patients with chronic lymphedema. The combined technique provides immediate volume reduction and further regenerative effects on the lymphatic circulation. The significantly greater reduction in lymphoscintigraphy values and erysipelas infections suggests that the combined technique might be better for late-stage lymphedema patients than lymph node transfer alone.
Utilizing Machine Learning Methods for Preoperative Prediction of Postsurgical Mortality and Intensive Care Unit Admission
Authors: Chiew Calvin J. , Liu Nan , Wong Ting Hway , Sim Yilin E. , Abdullah Hairil R.
Published: April 2019

Objective:

To compare the performance of machine learning models against the traditionally derived Combined Assessment of Risk Encountered in Surgery (CARES) model and the American Society of Anaesthesiologists-Physical Status (ASA-PS) in the prediction of 30-day postsurgical mortality and need for intensive care unit (ICU) stay >24 hours.

Background:

Prediction of surgical risk preoperatively is important for clinical shared decision-making and planning of health resources such as ICU beds. The current growth of electronic medical records coupled with machine learning presents an opportunity to improve the performance of established risk models.

Methods:

All patients aged 18 years and above who underwent noncardiac and nonneurological surgery at Singapore General Hospital (SGH) between 1 January 2012 and 31 October 2016 were included. Patient demographics, comorbidities, preoperative laboratory results, and surgery details were obtained from their electronic medical records. Seventy percent of the observations were randomly selected for training, leaving 30% for testing. Baseline models were CARES and ASA-PS. Candidate models were trained using random forest, adaptive boosting, gradient boosting, and support vector machine. Models were evaluated on area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC).

Results:

A total of 90,785 patients were included, of whom 539 (0.6%) died within 30 days and 1264 (1.4%) required ICU admission >24 hours postoperatively. Baseline models achieved high AUROCs despite poor sensitivities by predicting all negative in a predominantly negative dataset. Gradient boosting was the best performing model with AUPRCs of 0.23 and 0.38 for mortality and ICU admission outcomes respectively.

Conclusions:

Machine learning can be used to improve surgical risk prediction compared to traditional risk calculators. AUPRC should be used to evaluate model predictive performance instead of AUROC when the dataset is imbalanced.
Laparoscopic Versus Open Pancreaticoduodenectomy
Authors: Nickel Felix , Haney Caelán Max , Kowalewski Karl Friedrich , Probst Pascal , Limen Eldridge Frederick , Kalkum Eva , Diener Marcus K. , Strobel Oliver , Müller-Stich Beat Peter , Hackert Thilo
Published: April 2019

Objective:

To compare perioperative outcomes of laparoscopic pancreaticoduodenectomy (LPD) to open pancreaticoduodenectomy (OPD) using evidence from randomized controlled trials (RCTs).

Background:

LPD is used more commonly, but this surge is mostly based on observational data.

Methods:

We searched CENTRAL, Medline and Web of Science for RCTs comparing minimally invasive to OPD for adults with benign or malignant disease requiring elective pancreaticoduodenectomy. Main outcomes were 90-day mortality, Clavien-Dindo ≥3 complications, and length of hospital stay (LOS). Secondary outcomes were postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), bile leak, blood loss, reoperation, readmission, oncologic outcomes (R0-resection, lymph nodes harvested), and operative times. Data were pooled as odds ratio (OR) or mean difference (MD) with a random-effects model. Risk of bias was assessed using the Cochrane Tool and the GRADE approach (Prospero registration ID: CRD42019120363).

Results:

Three RCTs with a total of 224 patients were included. Meta-analysis showed there were no significant differences regarding 90-day mortality, Clavien-Dindo ≥3 complications, LOS, POPF, DGE, PPH, bile leak, reoperation, readmission, or oncologic outcomes between LPD and OPD. Operative times were significantly longer for LPD {MD [95% confidence interval (CI)] 95.44 minutes (24.06–166.81 minutes)}, whereas blood loss was lower for LPD [MD (CI) −150.99 mL (−168.54 to −133.44 mL)]. Certainty of evidence was moderate to very low.

Conclusions:

At current level of evidence, LPD shows no advantage over OPD. Limitations include high risk of bias and moderate to very low certainty of evidence. Further studies should focus on patient safety during LPD learning curves and the potential role of robotic surgery.
Endovascular Treatment of Post Type A Chronic Aortic Arch Dissection With a Branched Endograft
Authors: Verscheure Dorian , Haulon Stéphan , Tsilimparis Nikolaos , Resch Timothy , Wanhainen Anders , Mani Kevin , Dias Nuno , Sobocinski Jonathan , Eagleton Matthew , Ferreira Marcelo , Schurink Geert Willem , Modarai Bijan , Abisi Said , Kasprzak Piotr , Adam Donald , Cheng Stephen , Maurel Blandine , Jakimowicz Thomasz , Watkins Amelia Claire , Sonesson Björn , Claridge Martin , Fabre Dominique , Kölbel Tilo
Published: April 2019

Objective:

The objective of this study was to evaluate the outcome of endovascular aortic arch repair for chronic dissection with a custom-made branched endograft.

Background:

Acute type A aortic dissections are often treated with prosthetic replacement of the ascending aorta. During follow-up, repair of an aneurysmal evolution of the false lumen distal to the ascending prosthesis can be a challenge both for the surgeon and the patient.

Methods:

We conducted a multicenter, retrospective study of consecutive patients from 14 vascular units treated with a custom-made, inner-branched device (Cook Medical, Bloomington, IN) for chronic aortic arch dissection. Rates of in-hospital mortality and stroke, technical success, early and late complications, reinterventions, and mortality during follow-up were evaluated.

Results:

Seventy consecutive patients were treated between 2011 and 2018. All patients were considered unfit for conventional surgery. In-hospital combined mortality and stroke rate was 4% (n = 3), including 1 minor stroke, 1 major stroke causing death, and 1 death following multiorgan failure. Technical success rate was 94.3%. Twelve (17.1%) patients required early reinterventions: 8 for vascular access complication, 2 for endoleak correction, and 2 for pericardial effusion drainage. Median follow-up was 301 (138–642) days. During follow-up, 20 (29%) patients underwent secondary interventions: 9 endoleak corrections, 1 open repair for prosthetic kink, and 10 distal extensions of the graft to the thoracic or thoracoabdominal aorta. Eight patients (11%) died during follow-up because of nonaortic-related cause in 7 cases.

Conclusions:

Endovascular treatment of aortic arch chronic dissections with a branched endograft is associated with low mortality and stroke rates but has a high reintervention rate. Further follow-up is required to confirm the benefits of this novel approach.
Eye tracking-based estimation and compensation of chromatic offsets for multi-wavelength retinal microstimulation with foveal cone precision
Authors: Domdei Niklas , Linden Michael , Reiniger Jenny L. , Holz Frank G. , Harmening Wolf M.
Published: April 2019

Multi-wavelength ophthalmic imaging and stimulation of photoreceptor cells requires consideration of chromatic dispersion of the eye, manifesting in longitudinal and transverse chromatic aberrations. Current image-based techniques to measure and correct transverse chromatic aberration (TCA) and the resulting transverse chromatic offset (TCO) in an adaptive optics retinal imaging system are precise, but lack compensation of small but significant shifts in eye position occurring during in vivo testing. Here we present a method that requires only a single measurement of TCO during controlled movements of the eye to map retinal chromatic image shifts to the image space of a pupil camera. After such calibration, TCO can be compensated by continuously monitoring eye position during experimentation and by interpolating correction vectors from a linear fit to the calibration data. The average change rate of TCO per head shift and the correlation between Kappa and the individual foveal TCA are close to the expectations based on a chromatic eye model. Our solution enables continuous correction of TCO with high spatial precision and avoids high light intensities required for re-measuring TCO after eye position changes, which is necessary for foveal cone-targeted psychophysical experimentation.
Development of Pavlovian-to-instrumental transfer (PIT) task to examine the effects of reward-predicting cues on behavioral activation in young adults
Authors: da Costa Raquel Quimas Molina , Furukawa Emi , Hoefle Sebastian , Moll Jorge , Tripp Gail , Mattos Paulo
Published: April 2019

There is a growing recognition that much of human behavior is governed by the presence of classically conditioned cues. The Pavlovian-to-Instrumental Transfer (PIT) paradigm offers a way to measure the effects of classically conditioned stimuli on behavior. In the current study, a novel PIT paradigm was developed for use in conjunction with an fMRI classical conditioning task. This could allow for a measurement of BOLD responses to anticipated rewards, unconfounded by operant responses, while providing a behavioral measure of conditioning effects. Twenty-four healthy young adults completed 1) instrumental training, 2) Pavlovian conditioning, and 3) Transfer test. During instrumental training, participants learned to apply force on a handgrip to win money from slot machines pictured on a computer screen. During Pavlovian conditioning, slot machines appeared with one of two abstract symbols (cues), one symbol was predictive of monetary reward. During the Transfer test, participants again applied force on a handgrip to win more money. This time, slot machines were presented with the Pavlovian cues, but with the outcomes hidden. The results indicated increased effort on the instrumental task, i.e., higher response frequency and greater force, in the presence of a reward-predicting cue. Our findings add to a growing number of studies demonstrating PIT effects in humans. This paradigm was proved to be useful in measuring the effects of a conditioned stimulus on behavioral activation.
The budding yeast heterochromatic protein Sir3 modulates genome-wide gene expression through transient direct contacts with euchromatin
Authors: Bhattacharjee Pritha , Camasses Alain , Galić Hrvoje , Hrgovčić Ana , Demont Lara , Nguyen Linh Thuy , Vasseur Pauline , Radman-Livaja Marta
Published: April 2019

The SIR complex (Silent Information Regulator) is the building block of heterochromatic structures that silence underlying genes. It is well established that the silenced state is epigenetically inherited but it is not known how the SIR complex is maintained through cell divisions in optimal or variable growth conditions. The biological function of heterochromatin located in subtelomeric regions is also unclear since heterochromatin coverage appears to be limited to a few kbps near chromosome ends and the expression of subtelomeric genes is only marginally affected in the absence of the SIR complex. We use a three pronged approach to address these questions. First, nanopore-MetID, an in vivo foot printing technique similar to DamID that uses nanopore sequencing technology, identified over a thousand new transient contacts between Sir3 and euchromatic genes that are not detectable by ChIP-seq and revealed a previously undocumented low-density mode of Sir3 binding to subtelomeric regions that extends 15kbps downstream of subtelomeric SIR nucleation sites. Second, our measurements of genome-wide Sir3 exchange rates after exit from starvation show that heterochromatin is a highly dynamic structure in optimal growth conditions. Third, “spike-in” RNA-seq time course experiments in the same conditions reveal that Sir3 modulates global mRNA levels in correlation with fluctuations in nutrient availability. We now propose that subtelomeric regions serve as Sir3 hubs from which Sir3 is brought over to distal sites down the chromosome arm where it transiently contacts euchromatic genes in its path. We hypothesize that contacts between Sir3 and actively transcribed genes facilitate the removal of stalled transcription complexes and allow for optimal genome-wide transcription, which gives wt cells a competitive advantage oversir3Δcells when nutrients are limited.
Sox1a mediates the ability of the parapineal to impart habenular left-right asymmetry
Authors: Lekk Ingrid , Duboc Véronique , Faro Ana , Nicolaou Stephanos , Blader Patrick , Wilson Stephen W.
Published: April 2019

Left-right asymmetries in the zebrafish habenular nuclei are dependent upon the formation of the parapineal, a unilateral group of neurons that arise from the medially positioned pineal complex. In this study, we show that both the left and right habenula are competent to adopt left-type molecular character and efferent connectivity upon the presence of only a few parapineal cells. This ability to impart left-sided character is lost in parapineal cells lacking Sox1a function, despite the normal specification of the parapineal itself. Precisely timed laser ablation experiments demonstrate that the parapineal influences neurogenesis in the left habenula at early developmental stages as well as neurotransmitter phenotype and efferent connectivity during subsequent stages of habenular differentiation. These studies reveal a tight coordination between the formation of the unilateral parapineal nucleus and emergence of asymmetric habenulae, ensuring that appropriate lateralised character is propagated within left and right-sided circuitry.
Chemical biofilm dislodgement with chelating and reducing agents in comparison to sonication: implications for the diagnosis of implant associated infection
Authors: Karbysheva Svetlana , Butini Maria Eugenia , Di Luca Mariagrazia , Winkler Tobias , Schütz Michael , Trampuz Andrej
Published: April 2019

Sonication of removed devices improved the microbiological diagnosis of infection. Recently, chemical agents have been investigated for dislodgement of biofilms, including the chelating agent ethylenediaminetetraacetic acid (EDTA) and the reducing agent dithiothreitol (DTT). We compared the efficacy of chemical methods (EDTA and DTT) to sonication for biofilm dislodgement. Staphylococcus epidermidis (ATCC 35984) and Pseudomonas aeruginosa (ATCC 53278) biofilms were grown on porous glass beads for 3 days. After biofilm formation, beads were exposed to 0.9% saline, sonication and/or chemical agents. Quantitative and qualitative biofilm analyses were performed by colony counting (CFU/ml), isothermal microcalorimetry and scanning electron microscopy. The colony counts after treatment with EDTA and DTT were similar to those after exposure to 0.9% saline (6.3, 6.1 and 6.0 log CFU/ml, respectively) for S. epidermidis biofilms, and (5.1, 5.2 and 5.0 log CFU/ml, respectively) for P. aeruginosa biofilm. Sonication detected higher CFU counts (7.5 log CFU/ml) for S. epidermidis; (p<0.05) and 6.5 log for P. aeruginosa biofilm (p <0.05). Concordant results were detected with isothermal microcalorimetry and scanning electron microscopy. In conclusion, the CFU count after treatment of S. epidermidis or P. aeruginosa biofilms with EDTA and DTT was similar to those observed after 0.9% saline used as control. In contrast, sonication was superior to chemical methods for biofilm dislodgment and detection of microorganisms in sonication fluid. In conclusion, our study showed that sonication is superior to chemical method to dislodge bacterial biofilm from artificial surface and should be considered as standard diagnostic method for biofilm detection in implant-associated infections.
Pharmacological inhibition of soluble epoxide hydrolase as a new therapy for Alzheimer’s Disease
Authors: Griñán-Ferré Christian , Codony Sandra , Pujol Eugènia , Yang Jun , Leiva Rosana , Escolano Carmen , Puigoriol-Illamola Dolors , Companys-Alemany Júlia , Corpas Rubén , Sanfeliu Coral , Loza M. Isabel , Brea José , Morisseau Christophe , Hammock Bruce D. , Vázquez Santiago , Pallàs Mercè , Galdeano Carles
Published: April 2019

The inhibition of the enzyme soluble epoxide hydrolase (sEH) has demonstrated clinical therapeutic effects in several peripheral inflammatory-related diseases, with two compounds that have entered clinical trials. However, the role of this enzyme in the neuroinflammation process has been largely neglected. Herein, we disclose the pharmacological validation of sEH as a novel target for the treatment of Alzheimer’s Disease (AD). Of interest, we have found that sEH is upregulated in brains from AD patients. We have evaluated the cognitive impairment and the pathological hallmarks in two models of age-related cognitive decline and AD using three structurally different and potent sEH inhibitors as chemical probes. Our findings supported our expectations on the beneficial effects of central sEH inhibition, regarding of reducing cognitive impairment, tau hyperphosphorylation pathology and the number of amyloid plaques. Interestingly, our results suggest that reduction of inflammation in the brain is a relevant therapeutic strategy for all stages of AD.
Antibiotics select for novel pathways of resistance in biofilms
Authors: Trampari Eleftheria , Holden Emma R , Wickham Gregory J , Ravi Anuradha , Prischi Filippo , de Oliveira Martins Leonardo , Savva George M , Bavro Vassiliy N. , Webber Mark A
Published: April 2019

Most bacteria in nature exist in aggregated communities known as biofilms. Bacteria within biofilms are inherently highly resistant to antibiotics. Current understanding of the evolution and mechanisms of antibiotic resistance is largely derived from work from cells in liquid culture and it is unclear whether biofilms adapt and evolve in response to sub-inhibitory concentrations of drugs. Here we used a biofilm evolution model to show that biofilms of a model food borne pathogen,SalmonellaTyphimurium rapidly evolve in response to exposure to three clinically important antibiotics. Whilst the model strongly selected for improved biofilm formation in the absence of any drug, once antibiotics were introduced the need to adapt to the drug was more important than the selection for improved biofilm formation. Adaptation to antibiotic stress imposed a marked cost in biofilm formation, particularly evident for populations exposed to cefotaxime and azithromycin. We identified distinct resistance phenotypes in biofilms compared to corresponding planktonic control cultures and characterised new mechanisms of resistance to cefotaxime and azithromycin. Novel substitutions within the multidrug efflux transporter, AcrB were identified and validated as impacting drug export as well as changes in regulators of this efflux system. There were clear fitness costs identified and associated with different evolutionary trajectories. Our results demonstrate that biofilms adapt rapidly to low concentrations of antibiotics and the mechanisms of adaptation are novel. This work will be a starting point for studies to further examine biofilm specific pathways of adaptation which inform future antibiotic use.
A new approach to crop model calibration: phenotyping plus post-processing
Authors: Casadebaig Pierre , Debaeke Philippe , Wallach Daniel
Published: April 2019

Crop models contain a number of genotype-dependent parameters, which need to be estimated for each genotype. This is a major difficulty in crop modeling. We propose a hybrid method for adapting a crop model to new genotypes. The genotype-dependent parameters of the model could be obtained by phenotyping (or gene-based modeling). Then field data for example from variety trials could be used to provide a simple empirical correction to the model, of the form a+b times an environmental variable. This approach combines the advantages of phenotyping, namely that the genotype-specific parameters have a clear meaning and are comparable between genotypes, and the advantages of fitting the model to field data, namely that the corrected model is adapted to a specific target population. It has the advantage of being very simple to apply, and furthermore gives useful information as to which environmental variables are not fully accounted for in the initial model. In this study, this empirical correction is applied to the SUNFLO crop model for sunflower, using field data from a multi-environment trial network. The empirical correction reduced mean squared error (MSE) on the average by 54% for prediction of yield and by 26% for prediction of oil content, compared to the initial model. Most of the improvement came from eliminating bias, with some further improvement from the environmental term in the regression.
Can hot temperatures limit disease transmission? A test of mechanisms in a zooplankton-fungus system
Authors: Shocket Marta S. , Magnante Alexandra , Duffy Meghan A. , Cáceres Carla E. , Hall Spencer R.
Published: April 2019

unimodally to temperature, i.e., be maximized at intermediate temperatures and constrained at extreme low and high temperatures. However, empirical evidence linking hot temperatures to decreased transmission in nature remains limited.

We tested the hypothesis that hot temperatures constrain transmission in a zooplankton-fungus (Daphnia dentifera-Metschnikowia bicuspidata) disease system where autumnal epidemics typically start after lakes cool from their peak summer temperatures. This pattern suggested that maximally hot summer temperatures could be inhibiting disease spread.

Using a series of lab experiments, we examined the effects of high temperatures on five mechanistic components of transmission. We found that (1) high temperatures increased exposure to parasites by speeding up foraging rate but (2) did not alter infection success post-exposure. (3) High temperatures lowered parasite production (due to faster host death and an inferred delay in parasite growth). (4) Parasites made in hot conditions were less infectious to the next host (instilling a parasite ‘rearing’ or ‘trans-host’ effect of temperature during the prior infection). (5) High temperatures in the free-living stage also reduce parasite infectivity, either by killing or harming parasites.

We then assembled the five mechanisms into an index of disease spread. The resulting unimodal thermal response was most strongly driven by the rearing effect. Transmission peaked at intermediate-hot temperatures (25-26°C) and then decreased at maximally hot temperatures (30-32°C). However, transmission at these maximally hot temperatures only trended slightly lower than the baseline control (20°C), which easily sustains epidemics in laboratory conditions and in nature. Overall, we conclude that while exposure to hot epilimnetic temperatures does somewhat constrain disease, we lack evidence that this effect fully explains the lack of summer epidemics in this natural system. This work demonstrates the importance of experimentally testing hypothesized mechanisms of thermal constraints on disease transmission. Furthermore, it cautions against drawing conclusions based on field patterns and theory alone.
Development of a KDM6b shRNA conditional knock down mouse model
Authors: Prier Julia E. , Blewitt Marnie E. , Dickins Ross A. , Turner Stephen J.
Published: April 2019

Antigen-specific CD8+T cell differentiation in response to infection is associated with specific changes in the chromatin landscape resulting in acquisition of the lineage-specific effector functions required for pathogen clearance. Lysine (K)-specific demethylase 6B (KDM6b) is a histone demethylase that specifically recognizes and removes methyl groups from K27 tri/dimethylation on histone 3. This histone modification is associated with a repressive transcriptional state, or, in combination with the active H3K4me3 mark, a bivalent epigenetic state. Resolution of bivalency at fundamental transcription factor loci has been shown to be a key mechanism for the initiation of CD8+T cell differentiation. To begin to address the role of KDM6b in regulating H3K27me3 demethylation in CD8+T cell responses to infection, a model whereby KDM6b levels can be modulated is needed. To address this, we developed a conditional short hairpin RNA (shRNA) mouse model targeting KDM6b. Here we demonstrate that KDM6b knockdown results in diminished naive, CD4+and virus-specific CD4+and CD8+T cell response in response to influenza A infection. To address the molecular mechanism, we demonstrate that KDM6b knockdown resulted in reduced H3K27me3 removal from theTbx21bivalent promoter, compared to luciferase hairpin controls. Surprisingly, this did not necessarily impact T-BET expression, or resolution of other bivalent transcription factor promoters. These data suggest that KDM6b knockdown resulting in diminished IAV-specific CD8+ T cell responses may reflect a demethylase independent function.
Longitudinal stability of the brain functional connectome is associated with episodic memory performance in aging
Authors: Ousdal Olga Therese , Kaufmann Tobias , Kolskår Knut , Vik Alexandra , Wehling Eike , Lundervold Astri J. , Lundervold Arvid , Westlye Lars T.
Published: April 2019

The brain functional connectome forms a relatively stable and idiosyncratic backbone that can be used for identification or “fingerprinting” of individuals with a high level of accuracy. While previous cross-sectional evidence has demonstrated increased stability and distinctiveness of the brain connectome during the course of childhood and adolescence, less is known regarding the longitudinal stability in middle and old age. Here we collected structural and resting state functional MRI data at two time-points separated by 2-3 years in 75 middle-aged and older adults (age 49-80, SD = ± 6.91 years) which allowed us to assess the long-term stability of the functional connectome. We show that the connectome backbone generally remains stable over a 2-3 year time frame in middle- and old age. Independent of age, cortical volume was associated with the connectome stability of several canonical resting-state networks, suggesting that the connectome backbone relates to the structural integrity of the cortex. Moreover, individual longitudinal stability of subcortical and default mode networks were associated with differences in cross-sectional and longitudinal measures of episodic memory performance, supporting the functional relevance. The findings encourage the use of connectome stability analyses for understanding individual differences in cognitive aging. Furthermore, the observation that age-related changes in episodic memory performance relates to the stability of subcortical and default mode networks, provides new longitudinal evidence for the importance of these networks in maintaining mnemonic processing in old age.
The Israeli Acute Paralysis Virus IRES captures host ribosomes by mimicking a ribosomal state with hybrid tRNAs
Authors: Acosta-Reyes Francisco , Neupane Ritam , Frank Joachim , Fernández Israel S.
Published: April 2019

TheColonyCollapseDisorder or CCD is a multi-faceted syndrome decimating bee populations worldwide[1]. A group of viruses of the widely distributedDicistroviridaefamily have been identified as a causing agent of CCD[2]. This family of viruses employ non-coding RNA sequences, calledInternalRibosomalEntrySite (IRES), to precisely exploit the host machinery for protein production. Using single-particle cryo-electron microscopy (cryo-EM) we have characterized at high resolution how the IRES of the intergenic region of theIsraeliAcuteParalysisVirus (IAPV) captures and redirects translating ribosomes towards viral messengers. Through a series of six structures at nominal resolutions close to 3Å, we could reconstruct the trajectory of IAPV-IRES from an early small subunit recruitment to a final post-translocated state in the ribosome. An early commitment of IRES/ribosome complexes for global pre-translocation mimicry explains the high efficiency observed for this IRES. The presented structures will help guide on-going efforts directed towards fighting CCD through RNA-interference technology [3].
Machine Source Localization ofTursiops truncatusWhistle-like Sounds in a Reverberant Aquatic Environment
Authors: Woodward SF , Reiss D , Magnasco MO
Published: April 2019

Most research into bottlenose dolphins’ (Tursiops truncatus’) capacity for communication has centered on tonal calls termedwhistles, in particular individually distinctive contact calls referred to assignature whistles. While “non-signature” whistles exist, and may be important components of bottlenose dolphins’ communicative repertoire, they have not been studied extensively. This is in part due to the difficulty of attributing whistles to specific individuals, a challenge that has limited the study of not only non-signature whistles but the study of general acoustic exchanges among socializing dolphins. In this paper, we propose the first machine-learning-based approach to identifying the source locations of semi-stationary, tonal, whistle-like sounds in a highly reverberant space, specifically a half-cylindrical dolphin pool. We deliver estimated time-difference-of-arrivals (TDOA’s) and normalized cross-correlation values computed from pairs of hydrophone signals to a random forest model for high-feature-volume classification and feature selection, and subsequently deliver the selected features into linear discriminant analysis, linear and quadratic Support Vector Machine (SVM), and Gaussian process models. In our 14-source-location setup, we achieve perfect accuracy in localization by classification and high accuracy in localization by regression (median absolute deviation of 0.66 m, interquartile range of 0.34 m - 1.57 m), with fewer than 10,000 features. By building a parsimonious (minimum-feature) classification tree model for the same task, we show that a minimally sufficient feature set is consistent with the information valued by a strictly geometric, time-difference-of-arrival-based approach to sound source localization. Ultimately, our regression models yielded better accuracy than the established Steered-Response Power (SRP) method when all training data were used, and comparable accuracy along the pool surface when deprived of training data at testing sites; our methods additionally boast improved computation time and the potential for superior localization accuracy in all dimensions with more training data.
Compact undulator line for a high-brilliance soft-X-ray free-electron laser at MAX IV
Authors: Mak Alan , Salén Peter , Goryashko Vitaliy
Published: April 2019

The optimal parameter space for an X-ray free-electron laser (FEL) in the self-amplified spontaneous emission (SASE) operation mode is examined. This study focuses on FEL operation with a shorter undulator period and higher undulator strength made available through recent developments in in-vacuum, cryogenic and superconducting undulators. Progress on short-period undulator technologies is surveyed and FEL output characteristics versus undulator parameters are computed. The study is performed on a case of the planned soft-X-ray FEL at the MAX IV Laboratory in Sweden. An extension of the SASE mode into the harmonic lasing self-seeded mode is also analysed.
Crystal structures and properties of two hydrated conglomerate forms of the heart-rate-lowering agent ivabradine hydrochloride
Authors: Zhou Xin-Bo , Zhu Jian-Rong , Liu Ji-Yong , Jin Zhi-Ping , Tang Fei-Yu , Hu Xiu-Rong
Published: April 2019

Ivabradine hydrochloride (IVA-HCl) (systematic name: {[3,4-dimethoxybicyclo[4.2.0]octa-1(6),2,4-trien-7-yl]methyl}[3-(7,8-dimethoxy-2-oxo-2,3,4,5-tetrahydro-1H-3-benzazepin-3-yl)propyl]methylazanium), is a novel medication used for the symptomatic management of stable angina pectoris. In many recent patents, it has been claimed to exist in a very large number of polymorphic, hydrated and solvated phases, although no detailed analysis of the structural features of these forms has been published to date. Here, we have successfully crystallized the tetrahydrate form of IVA-HCl (form β), C27H37N2O5
+·Cl−·4H2O, and elucidated its structure for the first time. Simultaneously, a new crystal form of IVA-HCl, i.e. the hemihydrate (form II), C27H37N2O5
+·Cl−·0.5H2O, was discovered. Its crystal structure was also accurately determined and compared to that of the tetrahydrate form. While the tetrahydrate form of IVA-HCl crystallized in the orthorhombic space group P212121, the new form (hemihydrate) was solved in the monoclinic space group P21. Detailed conformational and packing comparisons between the two forms have allowed us to understand the role of water in the crystal assembly of this hydrochloride salt. The stabilities of the two forms were compared theoretically by calculating the binding energy of the water in the crystal lattice using differential scanning calorimetry (DSC). The stability experiments show that the tetrahydrate is stable under high-humidity conditions, while the hemihydrate is stable under high-temperature conditions.
The impact of using different keyboards on free-text keystroke dynamics authentication for Arabic language
Authors: Alsuhibany Suliman A. , Almushyti Muna , Alghasham Noorah , Alkhudhayr Fatimah
Published: April 2019

Purpose

Nowadays, there is a high demand for online services and applications. However, there is a challenge to keep these applications secured by applying different methods rather than using the traditional approaches such as passwords and usernames. Keystroke dynamics is one of the alternative authentication methods that provide high level of security in which the used keyboard plays an important role in the recognition accuracy. To guarantee the robustness of a system in different practical situations, there is a need to examine how much the performance of the system is affected by changing the keyboard layout. This paper aims to investigate the impact of using different keyboards on the recognition accuracy for Arabic free-text typing.

Design/methodology/approach

To evaluate how much the performance of the system is affected by changing the keyboard layout, an experimental study is conducted by using two different keyboards which are a Mac’s keyboard and an HP’s keyboard.

Findings

By using the Mac’s keyboard, the results showed that the false rejection rate (FRR) was 0.20, whilst the false acceptance rate (FAR) was 0.44. However, these values have changed when using the HP’s keyboard where the FRR was equal to 0.08 and the FAR was equal to 0.60.

Research limitations/implications

The number of participants in the experiment, as the authors were targeting much more participants.

Originality/value

These results showed for the first time the impact of the keyboards on the system’s performance regarding the recognition accuracy when using Arabic free-text.
Indicating restaurant firms’ financial constraints: a new composite index
Authors: Mun Sung Gyun , Jang SooCheong (Shawn)
Published: April 2019

Purpose

The purpose of this study is to develop an index for financial constraints, specifically for restaurant firms, and to further validate the developed financial constraint index.

Design/methodology/approach

This study used logistic regression with a composite criterion based on the dividend payout ratio, KZ index and Cleary index to estimate restaurant firms’ financial constraints. Then, a fixed-effects regression was used to verify the validity of the measurement of restaurant firms’ financial constraints.

Findings

A restaurant firm’s operating profit, financial leverage, asset tangibility, sale of fixed assets and percentage change in number of employees are critical indicators for identifying financial constraints. The results indicated that in cases with positive operating cash flows, the effect of operating cash flow on capital investments continuously decreased as restaurant firms’ financial constraints increased.

Originality/value

This study is unique in that the specific financial and operational characteristics of restaurant firms were included in the model to determine financial constraint indicators, such as sale of fixed assets and percentage change in number of employees.
Sign consumption and sign promotion in visitor attractions
Authors: Paraskevaidis Pavlos , Weidenfeld Adi
Published: April 2019

Purpose

Drawing upon Baudrillard’s concept of sign-value, this study aims to investigate consumer behavior and sign perception in visitor attractions.

Design/methodology/approach

By adopting netnography, 133 customer-to-customer reviews sourced from TripAdvisor were analyzed regarding visitors’ online post-visit impressions.

Findings

The findings reveal that netnography contributes to a deeper understanding of sign consumption and sign promotion and examines how visitors attribute symbolic meanings to their experience in Titanic Belfast.

Practical implications

The findings show that the co-creation and reevaluation of the visitor experience through consumers’ online reviews should be taken into account by both managers and marketers. Furthermore, advertising should avoid creating excessive expectations to visitors to decrease the possibility of negative disconfirmation, which can be easily and instantly spread online. Another implication concerns the winning awards of visitor attractions, hotels and restaurants of a destination which may be used as a basis of co-branding marketing campaigns to enhance destination brand image.

Social implications

This study continues the debate on the commodification of the visitor experience and the commercialization of visitor attractions.

Originality/value

This paper provides better understanding of sign-value, sign consumption and sign promotion in the visitor attraction sector.
Exploring Indian post-disaster temporary housing strategy through a comparative review
Authors: Biswas Arindam
Published: April 2019

Purpose

Natural disasters not only cause dilapidated buildings and damaged infrastructure but also delay crucial aid for those affected in the event of a disaster and post-disaster recovery. An institutionally well-managed post-disaster housing strategy provides opportunities for physical and mental healing of its occupant. The time requires occupiers to remain in the temporary housing varies with circumstances. This paper aims to review post-disaster housing scenarios in India in comparison to two Asian cases from Indonesia and Japan. The study focuses on understanding Indian post-disaster housing strategies through a comparative review.

Design/methodology/approach

The research selects coastal cities of Tamil Nadu state, where the post-disaster temporary shelter and rehabilitation was planned and implemented after the Tsunami in 2004. The Tsunami created havoc in Nagapattinam and Kanyakumari district of Tamil Nadu. Nagapattinam district reported 6,051 fatalities and many more homeless people. After the Tsunami, the government took measures to supply safe, secured and on-site shelter provisions. Surprisingly, many such shelters were never occupied. In many instances, people actually preferred to spend years in a temporary shelter rather occupying government housing. This paper evaluates such events and investigates India’s post-disaster shelter strategy against the derived best practices. This study is based on the sequential/logical reasoning and understanding of the facts. Discussions and findings from this study can be further generalised into a comprehensive policy discussion.

Findings

The paper finds that the manner of planning and design of post-disaster housing programmes influence medium- to long-term recovery of its occupant. A certain element of trade-off between implementation and quality of habitation results into compromises to achieving the desired outcome. When faced with socio-political, economic and financial constraints, the decision-makers are required to make trade-offs in deciding the manner and quantum of allocating resources. Coordination among these agencies is troublesome. It is true for all countries and there is no distinct answer to it. Public consultation and community participation in long-term rehabilitation are crucial to meet the aspiration of the local people.

Originality/value

The paper contributes in discussing a comparison of post-disaster housing rehabilitation between India and the two cases from Indonesia and Japan. As a review paper, the objective is to highlight the synthesis and overall understanding of post-disaster housing strategies from two cases and compare it with India.
An integrative review
Authors: Abubakar A. Mohammed , Foroutan Taraneh , Megdadi Khaled Jamal
Published: April 2019

Purpose

Psychological capital (PsyCap) and future time perspective (FTP) are ambassadors of positivity among incumbent employees in organisations. However, remarkably little is known regarding the effectiveness of high-performance work systems (HPWS) in nurturing these constructs. The purpose of this study is to contribute and provide a complete frame of reference linking HPWS to PsyCap and FTP.

Design/methodology/approach

A synthesis analysis of existing literature was carried out to formulate managerial and practical propositions.

Findings

Drawing on the conservation of resources theory, affective events theory and Job Demands-Resources (JD-R) model, the present study proposes a research framework that links HPWS, FTP and PsyCap, with possible mediation effect of FTP in HPWS–PsyCap relationship and PsyCap in HPWS–FTP relationship.

Practical implications

Although this paper did not test the model empirically, it offers important practical implications in terms of PsyCap and FTP perception development through HPWS practices.

Originality/value

A set of propositions that explain the relationships between the study variables is presented to enrich the understanding with organisation’s HRM practices and its possible impact on employees.
Dynamic analysis of a cracked bar by the method of characteristics
Authors: Ayas Hillal , Chabaat Mohamed , Amara Lyes
Published: April 2019

Purpose

The purpose of this paper is to introduce a new numerical approach for studying a cantilever bar having a transverse crack. The crack is modeled by an elastic longitudinal spring with a stiffness K according to Castiglione’s theorem.

Design/methodology/approach

The bar is excited by different longitudinal impulse forces. The considered problem based on the differential equation of motion is solved by the method of characteristics (MOC) after splitting the second-order motion equation into two first-order equivalent equations.

Findings

In this study, effects of the crack size and crack’s position on the reflected waves from the crack are investigated. The results indicate that the presence of the crack in the cantilever bar generates additional waves caused by the reflection of the incident wave by the crack.

Originality/value

A numerical approach developed in this paper is used for detecting the extent of the damage in cracked bars by the measurement of the difference between the dynamic response of an uncracked bar and a cracked bar.