bluuebunny/crossref_metadata_2025 huggingface dataset:
Benefits of Impella and Peripheral Veno-Arterial Extra Corporeal Life Support Alliance
Authors: Colombier Sébastien , Quessard Astrid , Mastroianni Ciro , Schmidt Matthieu , Amour Julien , Leprince Pascal , Lebreton Guillaume
Published: December 2018

Peripheral veno-arterial extra corporeal life support (V-A ECLS) is an effective tool in treating refractory cardiogenic shock (RCS). Despite additional use of intra-aortic balloon pump, insufficient left ventricular unloading is a likely complication. We present herein our experience combining V-A ECLS and Impella to treat symptomatic, critical patients. A retrospective single-center review analyzed patients with V-A ECLS and intra-aortic balloon pump for RCS and subsequently benefiting from Impella implantation, between 2011 and 2015. From 1248 cases, 31 critical patients (2.5%) with a median SOFA score = 12 (7–15) were included. Median age was 53 years, and 74% were male. RCS resulted from myocardial ischemia (52%) and idiopathic dilated myocardiopathy (23%). Forty-seven percentage of patients were treated previously for chronic Heart Failure with reduced Ejection Fraction (HFrEF). Median time between V-A ECLS and Impella implantation was 84 hours (24–186). The Impella median support duration was 8 days (5–10). ECLS and Impella were weaned simultaneously in 26% of patients, 33% were switched to a long-term assistance, and 10% were transplanted. Overall, day-30 survival was 53%. Factors including diabetes, patients aged over 60 years, surgery using extracorporeal circulation, adrenalin infusion, acute myocardial infarction, and chronic HFrEF are associated with day-30 mortality. Chronic HFrEF was an independent risk factor for the day-30 mortality [hazard ratio = 5.28 (1.38–20.21), P = 0.015]. Impella and V-A ECLS combination is a promising association for critical patients presenting symptomatic insufficient LV unloading, for weaning V-A ECLS or testing the right ventricle before a switch to left ventricle assist device support.
Primary Family Caregivers' Reasons for Disclosing Versus Not Disclosing a Cancer Diagnosis in India
Authors: Chittem Mahati , Norman Paul , Harris Peter
Published: December 2018

Background

Nondisclosure of cancer diagnosis continues to be practiced in India, with many family caregivers concealing it from patients in order to protect them from emotional distress.

Objective

The aim of this study was to explore Indian primary family caregivers' reasons for, and experiences of, disclosure versus nondisclosure to patients about their cancer diagnosis.

Methods

Indian disclosing (n = 8) and nondisclosing (n = 7) primary family caregivers participated in semistructured interviews exploring their reasons for disclosure versus nondisclosure of cancer diagnosis to their patient. Qualitative content analysis was used to classify the reasons for and for not disclosing. Illustrative quotes were selected to highlight caregivers' motivations for, and experiences of, each reason.

Results

The findings revealed 6 main reasons for disclosing (emotional well-being, lack of control, preparing the patient, family reasons, patient's personality, and longevity/curability of the disease) and 6 reasons for not disclosing (emotional well-being, family reasons, patient's personality, longevity/curability of the disease, barriers to communication, and disease severity). Typically, disclosing caregivers considered reasons for as well as against disclosure, whereas nondisclosing caregivers considered reasons against disclosure.

Conclusions

Most of the reasons given for disclosing and not disclosing were the same, although these reasons operated differently for disclosing and nondisclosing caregivers. In addition, justification for these reasons demonstrated cognitive consistency effects that appeared to reduce any feelings of dissonance regarding caregivers' disclosure, or nondisclosure, decisions.

Implications for Practice

Cancer nurses should provide additional psychological support to nondisclosing caregivers, especially with regard to how they view and engage in their caregiving role.
Psychiatric Considerations Regarding Prehospital Administration of Ketamine for Agitation
Authors: Tian Lewis L. , Newman William J.
Published: December 2018

Recently, ketamine has seen increased use among emergency medical services in the prehospital setting as a first-line means of chemical restraint for agitated patients. In this case report, we explore an instance in which ketamine administration for nonpsychotic agitation before emergency department (ED) evaluation may have caused unexpected psychotic symptoms leading to a complicated ED course necessitating admission. As ketamine gains widespread use in the prehospital setting, the safety profile deserves reevaluation. In the following report, we review relevant literature and discuss important factors to consider regarding the use of prehospital ketamine, including psychiatric and substance abuse history.
Guilt Delusional Beliefs Increase the Risk of Suicidal Attempt in Elderly Unipolar Psychotic Depressives
Authors: Gournellis Rossetos , Efstathiou Vasiliki , Yotsidi Vasiliki , Tournikioti Kalliopi , Papazahos Costas , Ferentinos Panagiotis , Douzenis Athanasios , Michopoulos Ioannis
Published: December 2018

The aim of this study was to investigate the differential effect of various delusion categories, namely, guilt, paranoid, impending disaster, and somatic on suicidal attempts in elderly patients experiencing unipolar psychotic major depression (PMD), because the evidence on this is scarce. The sample consisted of 65 consecutively admitted patients 60 years or older, experiencing PMD, and assessed by means of Structured Clinical Interview for DSM-4 (Patient Edition), Hamilton Depression Rating Scale, Mini-Mental Status Examination (MMSE), and by a physical impairment rating scale. Patients with guilt delusional beliefs had 5.31 times higher odds (95% confidence interval, 1.37–25.40) of a suicidal attempt than the patients without guilt delusional beliefs, controlling for sex, age, prior history of suicide attempt, MMSE, and hallucinations. In addition, 17 PMD patients with lifetime suicidal attempt compared with 48 PMD patients without lifetime suicidal attempt presented only higher age of disorder onset (p = 0.008). Of the four categories of delusions assessed, only guilt delusions were associated with an increased risk for suicidal attempt.
Predicting Predischarge Anhedonia Among Inpatients With Schizophrenia and Schizoaffective Disorders
Authors: Ritsner Michael S. , Ratner Yael
Published: December 2018

This study sought to evaluate predischarge anhedonia level and its predictors in 125 inpatients with schizophrenia and schizoaffective disorders. Consecutively admitted inpatients were assessed before discharge from the hospital using the Specific Loss of Interest and Pleasure Scale (SLIPS) and a battery of measures for clinical and psychosocial variables. When symptoms, distress, and social anhedonia scores were controlled, the SLIPS score inversely correlated with self-constructs, social support, quality of life, recovery, and unmet needs. Using two cutoff points of the data set of SLIPS, we identified three groups: 19 (15.2%) patients reported “no loss of pleasure”; 46 (36.8%), “some loss of pleasure”; and 60 (48.0%), “marked diminishment of pleasure.” The SLIPS score is predicted by sensitivity, unmet needs, deficient interpersonal pleasure, poor quality of life, and friend support. The study underlines the importance of assessing anhedonia and related psychosocial factors in patients with serious mental illness.
Effect of Vision Therapy on Accommodative Lag in Myopic Children: A Randomized Clinical Trial
Authors: Ma Martin Ming-Leung , Shi Jingcheng , Li Na , Scheiman Mitchell , Chen Xiang
Published: December 2018

SIGNIFICANCE

Accommodative dysfunction has been suggested to be related to the development and progression of myopia. Office-based accommodative/vergence therapy (OBAVT) improved accommodative facility in Chinese myopic children, but it is unclear if such improvement has a role in decreasing myopic progression.

PURPOSE

The purpose of this study was to compare the effects of OBAVT with home reinforcement and office-based placebo therapy (OBPT) as a treatment to improve accommodative functions (i.e., lag, amplitude, and facility) in myopic children with poor accommodative accuracy.

METHODS

This was a prospective, single-masked, randomized clinical trial. Thirty-four Chinese children 8 to 12 years old with myopia and at least 1 diopter of lag of accommodation measured by autorefraction were enrolled. The participants were randomly assigned to the OBAVT or OBPT group. The primary outcome measure was the change in the monocular lag of accommodation from the baseline visit to the 13-week visit measured by a Shin-Nippon open-field autorefractor. Secondary outcome measures were changes in accommodative amplitude and monocular accommodative facility.

RESULTS

A total of 33 participants completed the study. After 12 weeks of treatment, there were significant improvements in the lag of accommodation in both the OBAVT and OBPT groups (OBAVT: −0.30 ± 0.29 diopters [P < .001; Cohen’s d effect size, 1.29]; OBPT: −0.24 ± 0.30 diopters [P = .005; Cohen’s d effect size, 1.24]). There was no statistically significant difference between the improvements in the two groups (P = .50). There was statistically significant improvement in monocular accommodative facility only in the OBAVT group (OBAVT: 7.7 ± 4.7 cycles per minute [P < .001; Cohen’s d effect size, 2.20]; OBPT: 1.9 ± 4.4 cycles per minute [P = .072]). The change in the OBAVT group was statistically significantly larger than that in the OBPT group (P < .001).

CONCLUSIONS

Office-based accommodative/vergence therapy was no more effective than OBPT in reducing the lag of accommodation in children 8 to 12 years old with low to moderate myopia. It did improve accommodative facility in Chinese myopic children, but it is unclear if such an improvement has a role in decreasing myopic progression.
Development and Psychometric Assessment of Novel Item Banks for Hereditary Retinal Diseases
Authors: Prem Senthil Mallika , Khadka Jyoti , De Roach John , Lamey Tina , McLaren Terri , Campbell Isabella , Fenwick Eva K. , Lamoureux Ecosse L. , Pesudovs Konrad
Published: December 2018

SIGNIFICANCE

This study develops psychometrically valid item banks across 10 areas of quality of life (QoL) specific to people with hereditary retinal diseases, which will enable clinicians and researchers to explore the impact of hereditary retinal diseases across all aspects of QoL.

PURPOSE

The purpose of this study was to assess the psychometric properties of hereditary retinal disease QoL item banks using Rasch analysis and demonstrate the effectiveness of a computerized adaptive testing (CAT) system in obtaining precise measurement of QoL using only a few items.

METHODS

The hereditary retinal disease item banks were answered by 233 participants (median age, 58 years; range, 18 to 94 years; female participants, 59%). The hereditary retinal disease item banks cover 10 QoL domains: activity limitation, mobility, emotional, social, convenience, economic, health concerns, visual symptoms, ocular comfort symptoms, and general symptoms. Rasch analysis assessed the psychometric properties of the 10 item banks and provided item calibrations for the development of CAT. Computerized adaptive testing simulations were performed to calculate the average number of items required to gain precise measurement of each QoL domain.

RESULTS

The convenience, economic, visual symptoms, and the social domains formed unidimensional scales. However, the activity limitation and health concerns domains demonstrated multidimensionality and required major modifications to resolve this, which resulted in four new QoL domains, namely, reading, driving, lighting, and concerns about the disease progression. In total, 10 item banks underwent CAT simulation testing, which indicated that 8 to 12 items were required to gain precise measurement of each QoL domain.

CONCLUSIONS

We have developed 10 psychometrically valid item banks to measure the QoL domains relevant to people with hereditary retinal diseases. On average, only 5 and 10 items were required to gain measurement at moderate and high precision, respectively.
Case Report: Sequelae of Bilateral Iris Pigment Epithelial Cysts Masquerading as Primary Pigmentary Glaucoma
Authors: Harpster Sandra Nelle , Flettner Juliane Grace , Mick Andrew Boyd
Published: December 2018

SIGNIFICANCE

Patients with pigment dispersion syndrome are frequently encountered in clinical practice. Iris abnormalities and the absence of key features of pigment dispersion syndrome can guide the discovery of secondary causes of pigmentary glaucoma, such as peripheral iris pigment epithelial cysts.

PURPOSE

The purpose of this study was to describe a patient initially diagnosed as having primary pigmentary glaucoma found to have multiple bilateral peripheral iris pigment epithelial cysts causing pigment liberation, focal angle closure, and advanced secondary glaucoma.

CASE REPORT

A 64-year-old man presented for follow-up after a recent diagnosis of primary pigmentary glaucoma in the left eye. Clinical examination revealed transillumination defects of both irides and a heavily pigmented trabecular meshwork. A midperipheral bulge of the iris was appreciated in the superior temporal quadrant of the left eye. Gonioscopic evaluation showed that the bulge focally obstructed the angle. Anterior segment optical coherence tomography demonstrated a normal iris insertion of both eyes, with the exception of a steepened approach superotemporally in the left eye. Ultrasound biomicroscopy revealed bilateral small- to medium-sized peripheral iris pigment epithelial cysts and confirmed a large cyst superotemporally in the left iris.

CONCLUSIONS

This case describes a patient with advanced secondary pigmentary glaucoma from iris pigment epithelial cysts. The mechanisms of glaucoma are likely twofold: (1) pigment liberation from the cysts contacting the lens zonules and, to a lesser extent, (2) focal angle closure at the site of the large peripheral cyst. The key features of pigmentary glaucoma, namely, posterior bowing of the iris, may not be present in secondary pigment dispersion. This case highlights the importance of careful evaluation of the iris and angle in making a correct diagnosis. The choice of topical agent to control intraocular pressure while not increasing the size of these cysts is also an important consideration.
The association of plasma lipids with white blood cell counts: Results from the Multi-Ethnic Study of Atherosclerosis
Authors: Lai Yong Chang , Woollard Kevin J. , McClelland Robyn L. , Allison Matthew A. , Rye Kerry-Anne , Ong Kwok Leung , Cochran Blake J.
Published: December 2018

Background and aims

Previous studies have demonstrated that elevated cholesterol results in increased white blood cell counts in mouse models. However, there is insufficient evidence to support this in humans. We, therefore, investigated the relationship of plasma lipids with white blood cell counts (basophils, eosinophils, monocytes, neutrophils and lymphocytes) in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods

The analysis included 2873 MESA participants at visit 5 with a complete white blood count and differential analysis. The cross-sectional association of total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride levels with different white blood cell counts was analyzed by multivariable linear regression.

Results

After adjusting sociodemographic and confounding factors including red blood cells counts, platelet counts, use of lipid-lowering medication, CVD risk factors and other lipid measures, and multiple testing correction, a 1-SD increment in total cholesterol and LDL cholesterol was associated with 2.8% and 2.3% (both p<0.001) lower total white blood cell counts. The same increment in ln-transformed triglyceride levels was associated with 2.3% higher total white blood cell counts, 2.9% higher lymphocyte counts and 2.7% lower monocyte counts (all p<0.001). HDL cholesterol was not associated with any white blood cell counts. Similar results were obtained after excluding participants taking lipid-lowering medication.

Conclusions

Whilst significant associations were observed, the heterogenous and modest nature of the relationships between plasma lipid levels and white blood cell populations make it hard to support the hypothesis that lipids are in the causal pathway for leukogenesis.
Modulation of ERK1/MAPK3 potentiates ERK nuclear signalling, facilitates neuronal cell survival and improves memory in mouse models of neurodegenerative disorders
Authors: Indrigo Marzia , Morella Ilaria , Orellana Daniel , d'Isa Raffaele , Papale Alessandro , Parra Riccardo , Gurgone Antonia , Lecca Daniela , Cavaccini Anna , Tigaret Cezar M , Ratto Gian Michele , Carta Anna R , Giustetto Maurizio , Middei Silvia , Tonini Raffaella , Hall Jeremy , Brooks Simon , Thomas Kerrie , Brambilla Riccardo , Fasano Stefania
Published: December 2018

Cell signalling mechanisms are central to neuronal activity and their dysregulation may lead to neurodegenerative processes and associated cognitive decline. So far, a major effort has been directed toward the dissection of disease specific pathways with the still unmet promise to develop precision medicine strategies. With a different approach, here we show that a selective genetic potentiation of neuronal ERK signalling prevents cell death in vitro and in vivo in the mouse brain while ERK attenuation does the opposite. This neuroprotective effect can also be induced pharmacologically by a cell permeable peptide mimicking the loss of ERK1 MAP kinase, leading to a selective enhancement of ERK2 mediated nuclear cell signalling. The drug treatment prevents neurodegeneration in mouse models of Huntington's (HD), Alzheimer's (AD), and Parkinson's disease (PD). Importantly, the selective potentiation of ERK2 signalling facilitates both structural and synaptic plasticity, enhances cognition in healthy mice and rescues mild cognitive impairments in both models of AD and HD. Altogether, our observation truly represents a remarkable example of a shared molecular mechanism across multiple neurodegenerative disorders and a potentially valuable therapeutic target for neuro-enhancement.
Electrostatic-assemblies of single-walled carbon nanotubes and sequence-tunable peptoid polymers detect a lectin protein and its target sugars
Authors: Chio Linda , Del Bonis-O’Donnell Jackson Travis , Kline Mark A. , Kim Jae Hong , McFarlane Ian R. , Zuckermann Ronald N. , Landry Markita P.
Published: December 2018

A primary limitation to real-time imaging of metabolites and proteins has been the selective detection of biomolecules that have no naturally-occurring or stable molecular recognition counterparts. We present developments in the design of synthetic near-infrared fluorescent nanosensors based on the fluorescence modulation of single-walled carbon nanotubes (SWNT) with select sequences of surface-adsorbedN-substituted glycine peptoid polymers. We assess the stability of the peptoid-SWNT nanosensor candidates under variable ionic strengths, protease exposure, and cell culture media conditions, and find that the stability of peptoid-SWNTs depends on the composition and length of the peptoid polymer. From our library, we identify a peptoid-SWNT assembly that can selectively detect lectin protein wheat germ agglutinin (WGA) with a sensitivity comparable to the concentration of serum proteins. This WGA protein nanosensor is characterized with near-infrared spectroscopy and microscopy to study protein-nanosensor interaction parameters. To demonstrate the retention of nanosensor-bound protein activity, we show that WGA on the nanosensor produces an additional fluorescent signal modulation upon exposure to the lectin’s conjugate sugars, suggesting the lectin protein selectively binds its target sugars through ternary molecular recognition interactions relayed to the nanosensor. Our results inform design considerations for developing synthetic molecular recognition elements by assembling peptoid polymers on SWNTs, and also demonstrate these assemblies can serve as optical nanosensors for lectin proteins and their target sugars. Together, these data suggest certain peptoid sequences can be assembled with SWNTs to serve as versatile optical probes to detect proteins and their molecular substrates.
Dashing: Fast and Accurate Genomic Distances with HyperLogLog
Authors: Baker Daniel N , Langmead Ben
Published: December 2018

Dashing is a fast and accurate software tool for estimating similarities of genomes or sequencing datasets. It uses the HyperLogLog sketch together with cardinality estimation methods that are specialized for set unions and intersections. Dashing summarizes genomes more rapidly than previous MinHash-based methods while providing greater accuracy across a wide range of input sizes and sketch sizes. It can sketch and calculate pairwise distances for over 87K genomes in 6 minutes. Dashing is open source and available athttps://github.com/dnbaker/dashing.
WRN Helicase is a Synthetic Lethal Target in Microsatellite Unstable Cancers
Authors: Chan Edmond , Shibue Tsukasa , McFarland James , Gaeta Benjamin , McPartlan Justine , Ghandi Mahmoud , Liu Jie Bin , Lazaro Jean-Bernard , Dumont Nancy , Gonzalez Alfredo , Apffel Annie , Ali Syed O , Leung Lisa , Roberts Emma , Rizvochenko Elizaveta , Islam Mirazul , Alimova Maria , Schenone Monica , Maruvka Yosef , Liu Yang , D'Andrea Alan , Root David , Boehm Jesse , Getz Gad , Golub Todd , Tserniak Aviad , Vazquez Francisca , Bass Adam J.
Published: December 2018

Synthetic lethality, an interaction whereby the co-occurrence of two or more genetic events lead to cell death but one event alone does not, can be exploited to develop novel cancer therapeutics. DNA repair processes represent attractive synthetic lethal targets since many cancers exhibit an impaired DNA repair pathway, which can lead these cells to become dependent on specific repair proteins. The success of poly (ADP-ribose) polymerase 1 (PARP-1) inhibitors in homologous recombination-deficient cancers highlights the potential of this approach in clinical oncology. Hypothesizing that other DNA repair defects would give rise to alternative synthetic lethal relationships, we asked if there are specific dependencies in cancers with microsatellite instability (MSI), which results from impaired DNA mismatch repair (MMR). Here we analyzed data from large-scale CRISPR/Cas9 knockout and RNA interference (RNAi) silencing screens and found that the RecQ DNA helicase was selectively essential in MSI cell lines, yet dispensable in microsatellite stable (MSS) cell lines. WRN depletion induced double-strand DNA breaks and promoted apoptosis and cell cycle arrest selectively in MSI models. MSI cancer models specifically required the helicase activity, but not the exonuclease activity of WRN. These findings expose WRN as a synthetic lethal vulnerability and promising drug target in MSI cancers.
Anesthesia-induced loss of consciousness disrupts auditory responses beyond primary cortex
Authors: Krom Aaron J , Marmelshtein Amit , Gelbard-Sagiv Hagar , Tankus Ariel , Hayat Hanna , Hayat Daniel , Matot Idit , Strauss Ido , Fahoum Firas , Soehle Martin , Boström Jan , Mormann Florian , Fried Itzhak , Nir Yuval
Published: December 2018

Despite its ubiquitous use in medicine, and extensive knowledge of its molecular and cellular effects, how anesthesia induces loss of consciousness (LOC) and affects sensory processing remains poorly understood. Specifically, it is unclear whether anesthesia primarily disrupts thalamocortical relay or intercortical signaling. Here we recorded intracranial EEG (iEEG), local field potentials (LFPs), and single-unit activity in patients during wakefulness and light anesthesia. Propofol infusion was gradually increased while auditory stimuli were presented and patients responded to a target stimulus until they became unresponsive. We found widespread iEEG responses in association cortices during wakefulness, which were attenuated and restricted to auditory regions upon LOC. Neuronal spiking and LFP responses in primary auditory cortex (PAC) persisted after LOC, while responses in higher-order auditory regions were variable, with neuronal spiking largely attenuated. Gamma power induced by word stimuli increased after LOC while its frequency profile slowed, thus differing from local spiking activity. In summary, anesthesia-induced LOC disrupts auditory processing in association cortices while relatively sparing responses in PAC, opening new avenues for future research into mechanisms of LOC and the design of anesthetic monitoring devices.
Simulating the Monty Hall problem in a DNA sequencing machine: Supplementary information
Authors: Mamet Noam , Harari Gil , Zamir Adva , Bachelet Ido
Published: December 2018

The Monty Hall problem is a decision problem with an answer that is surprisingly counter-intuitive yet provably correct. Here we simulate and prove this decision in a high- throughput DNA sequencing machine, using a simple encoding. All possible scenarios are represented by DNA oligonucleotides, and gameplay decisions are implemented by sequencing these oligonucleotides from specific positions, with a single run simulating more than 12,000,000 independent games. This work highlights high-throughput DNA sequencing as a new tool that could extend existing capabilities and enable new encoding schemes for problems in DNA computing.
Partial-resistance against aphids in wild barley involves phloem and mesophyll-based defences
Authors: Leybourne Daniel J , Valentine Tracy A , Robertson Jean AH , Pérez-Fernández Estefania , Main Angela M , Karley Alison J , Bos Jorunn IB
Published: December 2018

Aphids, including the bird cherry-oat aphid (Rhopalosiphum padi), are significant agricultural pests. Aphid populations are typically controlled using insecticides, but there is increasing demand for more sustainable pest management practices. The wild relative of barley,Hordeum spontaneum5 (Hsp5) has been described as partially-resistant toR. padi. Partial-resistance is proposed to involve higher thionin and lipoxygenase gene expression. However, the underlying mechanistic processes are unknown. In this study we compared Hsp5 with a susceptible cultivar of barley (Concerto) to test the extent to which partial-resistance affects aphid fitness. We used the electrical penetration graph technique to monitorR. padifeeding patterns to elucidate the tissue location of partial-resistance factors alongside molecular and biochemical analyses to identify potential mechanisms. We show that partial-resistance in Hsp5 extends to three aphid species and is mediated by phloem/mesophyll-based factors, leading to a three-fold increase in the time aphids take to establish sustained phloem ingestion. Partial-resistance likely involves elevated expression of defence and phytohormone genes alongside altered phloem amino acid composition. Further work is required to establish the function of these traits, however this study highlights plant tissues which are important in conferring broad-spectrum partial-resistance against aphids in barley.

Highlight

Partial-resistance against aphids in wild barley is based in the mesophyll and vascular tissue and is potentially associated with higher basal defence gene expression and altered phloem amino acid composition.
Estimating prevalence for limb-girdle muscular dystrophy based on public sequencing databases
Authors: Liu Wei , Pajusalu Sander , Lake Nicole J. , Zhou Geyu , Ioannidis Nilah , Mittal Plavi , Johnson Nicholas E. , Weihl Conrad C. , Williams Bradley A. , Albrecht Douglas E. , Rufibach Laura E. , Lek Monkol
Published: December 2018

Purpose

Limb Girdle Muscular Dystrophies (LGMD) are a genetically heterogeneous category of autosomal inherited muscle diseases. Many genes causing LGMD have been identified, and clinical trials are beginning for treatment of some genetic subtypes. However, even with the gene-level mechanisms known, it is still difficult to get a reliable and generalizable prevalence estimation for each subtype due to the limited amount of epidemiology data and the low incidence of LGMDs.

Methods

Taking advantage of recently published whole exome and genome sequencing data from the general population, we used a Bayesian method to develop a reliable disease prevalence estimator.

Results

This method was applied to nine recessive LGMD subtypes. The estimated disease prevalence calculated by this method were largely comparable to published estimates from epidemiological studies, however highlighted instances of possible under-diagnosis for LGMD2B and 2L.

Conclusion

The increasing size of aggregated population variant databases will allow for robust and reproducible prevalence estimates of recessive disease, which is critical for the strategic design and prioritization of clinical trials.
In silico prediction of blood cholesterol levels from genotype data
Authors: Reggiani Francesco , Carraro Marco , Belligoli Anna , Sanna Marta , dal Pra' Chiara , Favaretto Francesca , Ferrari Carlo , Vettor Roberto , Tosatto Silvio Carlo Ermanno
Published: December 2018

In this work we present a framework for blood cholesterol levels prediction from genotype data. The predictor is based on an algorithm for cholesterol metabolism simulation available in literature, implemented and optimized by our group in R language. Main weakness of the former simulation algorithm was the need of experimental data to simulate mutations in genes altering the cholesterol metabolism. This caveat strongly limited the application of the model in the clinical practice. In this work we present how this limitation could be bypassed thanks to an optimization of model parameters based on patients cholesterol levels retrieved from literature. Prediction performance has been assessed taking in consideration several scoring indices currently used for performance evaluation of machine learning methods. Our assessment shows how the optimization phase improved model performance, compared to the original version available in literature.
Anticorrelated inter-network electrophysiological activity varies dynamically with attentional performance and behavioral states
Authors: Kucyi Aaron , Daitch Amy , Raccah Omri , Zhao Baotian , Zhang Chao , Esterman Michael , Zeineh Michael , Halpern Casey H , Zhang Kai , Zhang Jianguo , Parvizi Josef
Published: December 2018

The default mode network (DMN) is thought to exhibit infraslow anticorrelated activity with dorsal attention (DAN) and salience (SN) networks across various behavioral states. To investigate the dynamics of activity across these networks on a finer timescale, we used human intracranial electroencephalography with simultaneous recordings within core nodes of the three networks. During attentional task performance, the three sites showed dissociable profiles of high-frequency broadband activity. Anticorrelated infraslow fluctuations of this activity were found across networks during task performance but also intermittently emerged during rest and sleep in concert with the expression of task-like network-level topographic patterns. Critically, on a finer timescale, DAN and SN activations preceded DMN deactivations by hundreds of milliseconds. Moreover, greater lagged, but not zero-lag, anticorrelation between DAN and DMN activity was associated with better attentional performance. These findings have implications for interpreting antagonistic network relationships and confirm the behavioral importance of time-lagged inter-network interactions.
Hyperinsulinemia promotes aberrant histone acetylation in triple negative breast cancer
Authors: Senapati Parijat , Thai Christine , Sanchez Angelica , Gallagher Emily J , LeRoith Derek , Seewaldt Victoria L. , Ann David K. , Schones Dustin E.
Published: December 2018

Excess levels of insulin relative to glucose in the blood, or hyperinsulinemia, is considered to be a poor prognostic indicator for patients with triple negative breast cancer (TNBC). While this association has been recognized for some time, the mechanistic role of hyperinsulinemia in promoting TNBC remains unclear. We show that insulin treatment leads to genome-wide increase in histone acetylation, in particular at H3K9, through the PI3K/AKT/mTOR pathway in MDA-MB-231 cells. Genome-wide analysis showed that the increase in histone acetylation occurs primarily at gene promoters. In addition, insulin induces higher levels of reactive oxygen species and DNA damage foci in cells. In vivo, hyperinsulinemia also enhances growth of MDA-MB-231 derived tumors through increased histone acetylation. These results demonstrate the impact of hyperinsulinemia on altered gene regulation through chromatin and the importance of targeting hyperinsulinemia-induced processes that lead to chromatin dysfunction in TNBC.
Identification of regulatory elements from nascent transcription using dREG
Authors: Wang Zhong , Chu Tinyi , Choate Lauren A. , Danko Charles G.
Published: December 2018

Our genomes encode a wealth of transcription initiation regions (TIRs) that can be identified by their distinctive patterns of actively elongating RNA polymerase. We previously introduced dREG to identify TIRs using PRO-seq data. Here, we introduce an efficient new implementation of dREG that uses PRO-seq data to identify both uni- and bidirectionally transcribed TIRs with 70% improvement in accuracy, three- to fourfold higher resolution, and >100-fold increases in computational efficiency. Using a novel strategy to identify TIRs based on their statistical confidence reveals extensive overlap with orthogonal assays, yet also reveals thousands of additional weakly transcribed TIRs that were not identified by H3K27ac ChIP-seq or DNase-seq. Novel TIRs discovered by dREG were often associated with RNA polymerase III initiation, bound by pioneer transcription factors, or located in broad domains marked by repressive chromatin modifications. Our results suggest that transcription initiation can be a powerful tool for expanding the catalog of functional elements.
In situ high-temperature EXAFS measurements on radioactive and air-sensitive molten salt materials
Authors: Smith Anna L. , Verleg Malte N. , Vlieland John , de Haas Dick , Ocadiz-Flores Jaen A. , Martin Philippe , Rothe Jörg , Dardenne Kathy , Salanne Mathieu , Gheribi Aimen E. , Capelli Elisa , van Eijck Lambert , Konings Rudy J. M.
Published: December 2018

The development at the Delft University of Technology (TU Delft, The Netherlands) of an experimental set-up dedicated to high-temperature in situ EXAFS measurements of radioactive, air-sensitive and corrosive fluoride salts is reported. A detailed description of the sample containment cell, of the furnace design, and of the measurement geometry allowing simultaneous transmission and fluorescence measurements is given herein. The performance of the equipment is tested with the room-temperature measurement of thorium tetrafluoride, and the Th—F and Th—Th bond distances obtained by fitting of the EXAFS data are compared with the ones extracted from a refinement of neutron diffraction data collected at the PEARL beamline at TU Delft. The adequacy of the sample confinement is checked with a mapping of the thorium concentration profile of molten salt material. Finally, a few selected salt mixtures (LiF:ThF4) = (0.9:0.1), (0.75:0.25), (0.5:0.5) and (NaF:ThF4) = (0.67:0.33), (0.5:0.5) are measured in the molten state. Qualitative trends along the series are discussed, and the experimental data for the (LiF:ThF4) = (0.5:0.5) composition are compared with the EXAFS spectrum generated from molecular dynamics simulations.
1-Diphenylphosphanyl-2-(diphenylphosphoryl)hydrazine
Authors: Höhne Martha , Aluri Bhaskar R. , Spannenberg Anke , Müller Bernd H. , Peulecke Normen , Rosenthal Uwe
Published: December 2018

The title compound, C24H22N2OP2, is an asymmetrically substituted hydrazine derivative bearing a phosphoryl and a phosphanyl substituent. The PNNP backbone has a torsion angle of −131.01 (8)°. In the crystal, molecules form centrosymmetric dimers by intermolecular N—H...O hydrogen bonds, which are further linked into a three-dimensional network by weak C—H...O and C—H...π interactions.
Adult workers in higher education: enhancing social mobility
Authors: Lopes Ana Sofia Patrício Pinto , Carreira Pedro Manuel Rodrigues
Published: December 2018

Purpose

The purpose of this paper is to verify if adult education can contribute to social mobility by analysing how the socioeconomic and professional background of the students affects dropout and graduation hazards in higher education.

Design/methodology/approach

An event history analysis approach, with competing risks and discrete time, implemented under a multinomial logit model, is used to investigate how an extensive set of covariates affects the risk of graduation, dropout and persistence of 834 adult student workers from a higher education institution in Portugal.

Findings

Adult education may indeed be effective in promoting social mobility, as academic achievement is higher for student workers that have low educated parents and low income levels. Also, the probability of achieving graduation seems to be higher for those seeking for higher transformation.

Practical implications

Adult education should be encouraged as it generates both efficiency and equity benefits. Some policy recommendations are suggested for the higher education system to adapt better to the particular characteristics of adult workers and provide conditions to improve the job–study–family conciliation, namely, by adjusting the schedule and composition of classes, appreciating the curriculum and providing orientation to candidates, and introducing shorter/simplified versions of the degrees.

Originality/value

A separate treatment is given to adult student workers, whose characteristics are very particular, enriching the literature on academic achievement that has been focussed on traditional students. Additionally, the studied data set merges five sources and provides extensive and original information on personal, degree and employment variables of the students.
Business students’ perspectives on employability skills post internship experience
Authors: Griffin Mamie , Coelhoso Pedro
Published: December 2018

Purpose

Employability skills of university graduates remain an ongoing topic for discussion and debate. Numerous studies highlight the expressed concerns of governments and industries about higher education’s ability to develop workforce ready graduates. An often cited solution is the use of internships to equip students with necessary employability skills. The purpose of this paper is to assess the status of employability skills from the perspective of students within a United Arab Emirates (UAE) institution based on their completion of a half-semester-long work placement experience.

Design/methodology/approach

Using a largely qualitative instrument, students reflected on their internship experience to report the essential skills needed in the workplace, classroom activities that most prepared them to use such skills in the workplace and the various challenges they encountered as interns.

Findings

Overall, students attributed a degree of importance to all skills addressed in the study with the greatest importance being attached to communication, teamwork and time management. Students indicated that most skills were addressed in the classroom; however, there appears to be a lack of awareness in the areas of critical thinking, self-management, intercultural skills and taking initiative.

Research limitations/implications

The present study only addressed the perceptions of business students at one all-female UAE-based institution of higher learning. Therefore, the data collected may not be representative of students enrolled in other degree programs or institutions. However, the understanding of these participants’ experiences adds to the body of literature featuring business undergraduate work experiences – particularly for the UAE and Gulf region.

Practical implications

Implications for academic and professional practitioners are discussed. Findings and recommendations are informative for curriculum development as well as economic and workforce development agencies.

Originality/value

The literature is well documented with studies from the perspectives of multiple entities including employers and university faculty, mostly in the western world. Fewer studies examine the perception of students, and even fewer studies are based on students in the UAE and other Gulf countries.
The effect of GST announcement on stock market volatility: evidence from intraday data
Authors: Haron Razali , Ayojimi Salami Mansurat
Published: December 2018

Purpose

The purpose of this paper is to examine the effect of GST announcements (pre and post) on Malaysian stock market index. This study also utilised intraday data to look into intraday market volatility post-GST announcement.

Design/methodology/approach

Both daily closing prices and intraday data of different frequencies are used to capture the extent of stock market volatility as well as the subsided period of the volatility. The period of study ranges from June 2009 to November 2016 and empirical estimation is based on the GARCH (1, 1) model for the pre- and post-GST announcements.

Findings

Persistent market volatility in the post-GST announcement is empirically recorded and the volatility is higher in the post-GST announcement than the pre-GST announcement. This demonstrates the unwillingness and reaction of the market towards the tax policy implementation. Market expectation on GST implementation towards the increase in the cost of living following the increase in the prices of goods and services in Malaysia is empirically supported in the post-GST announcement.

Practical implications

The finding on this study is consistent with the expectation of the market that GST implementation will increase the price of the goods and services and hence increase the cost of living. This is supported by a noticeable increase in the stock market volatility in the post-GST announcement. Although GST announcement could be classified as a scheduled announcement, unwillingness to accept the policy prevails as shown by the increase in the stock market volatility.

Originality/value

The effects of Asian and global financial crisis are the major focus of past studies on stock market volatility, whereas this study examines and highlights the effect of the GST announcement on stock market volatility and the use of intraday data to further examine the nature of the volatility.
On‐site calibration of air‐coil sensor for transient electromagnetic exploration
Authors: Wang Haowen , Fu Zhihong , Wang Yao , Tai Heng‐Ming , Chen Wenli
Published: December 2018

This paper proposes a time‐domain fitting method for on‐site calibration of the air‐coil sensor. The air‐coil sensor has been widely used in transient electromagnetic exploration. Due to limited bandwidth of the coil, the output signal is distorted, causing a phenomenon known as the transition process. To accurately measure the magnetic field from the output signals, the relationship between the coil induced electromotive force and the output voltage must be confirmed by on‐site calibration, which requires high calibration accuracy and demands simple operation, portable equipment, and adaptability to the environment. Conventional frequency response methods, however, requires a uniform magnetic field with various frequencies to obtain the frequency response curve of the air‐coil sensor. The time to acquire the signal correlates with the number of test frequencies, and the equipment used to generate a uniform magnetic field must be tailored to the shape of the air‐coil sensor under test. This paper constructs a relationship between the calibration file and the zero‐input response of the air‐coil sensor and designs an optimization algorithm to suppress the soil eddy current effect. This on‐site calibration method lifts the dependence on the uniform calibration field and reduces significantly the time required for calibration. The calibration source can be generated by cutting off the voltage source in parallel to the calibration coil, which greatly reduces the cost of the signal generator and provides a better solution for realizing the embedded self‐test devices. Experimental results show that the proposed method effectively improves the calculation accuracy of the apparent resistivity.
DNA barcoding fishes from the Congo and the Lower Guinean provinces: Assembling a reference library for poorly inventoried fauna
Authors: Sonet Gontran , Snoeks Jos , Nagy Zoltán T. , Vreven Emmanuel , Boden Gert , Breman Floris C. , Decru Eva , Hanssens Mark , Ibala Zamba Armel , Jordaens Kurt , Mamonekene Victor , Musschoot Tobias , Van Houdt Jeroen , Van Steenberge Maarten , Lunkayilakio Wamuini Soleil , Verheyen Erik
Published: December 2018

The Congolese and Lower Guinean ichthyological provinces are understudied hotspots of the global fish diversity. Here, we barcoded 741 specimens from the Lower and Middle Congo River and from three major drainage basins of the Lower Guinean ichthyological province, Kouilou‐Niari, Nyanga and Ogowe. We identified 194 morphospecies belonging to 82 genera and 25 families. Most morphospecies (92.8%) corresponded to distinct clusters of DNA barcodes. Of the four morphospecies present in both neighbouring ichthyological provinces, only one showed DNA barcode divergence <2.5%. A small fraction of the fishes barcoded here (12.9% of the morphospecies and 16.1% of the barcode clusters representing putative species) were also barcoded in a previous large‐scale DNA analysis of freshwater fishes of the Lower Congo published in 2011 (191 specimens, 102 morphospecies). We compared species assignments before and after taxonomic updates and across studies performed by independent research teams and observed that most cases of inconsistent species assignments were due to unknown diversity (undescribed species and unknown intraspecific variation). Our results report more than 17 putative new species and show that DNA barcode data provide a measure of genetic variability that facilitates the inventory of underexplored ichthyofaunae. However, taxonomic scrutiny, associated with revisions and new species descriptions, is indispensable to delimit species and build a coherent reference library.