bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Retrospective Study of Cognitive Improvement Following Electroconvulsive Therapy in Schizophrenia Inpatients
Authors: Seow Lee Seng Esmond , Subramaniam Mythily , Chan Yi Wen Christopher , Martin Donel M. , Abdin Edimansyah , Chong Siow Ann , Liu Jianlin , Peh Chao Xu , Tor Phern Chern 
Published: January 2019

Objectives
Findings on the cognitive effect of electroconvulsive therapy (ECT) in individuals with schizophrenia have brought mixed results, with few recent studies beginning to report cognitive improvements after treatment. Cognitive change in inpatients with schizophrenia who were referred for an acute course of ECT was examined in the current study. Furthermore, the study aimed to determine the profile of patients who experience cognitive improvement and the potential use of a brief cognitive battery to detect this positive cognitive change, if any.

Methods
Montreal Cognitive Assessment (MoCA) was conducted at baseline and posttreatment after 6 sessions of ECT. The Brief ECT Cognitive Screen was also administered to determine its predictive ability on cognitive gain of 2 points or higher in MoCA total scores for the 2 consecutive time points.

Results
A total of 81 inpatients were included in the study. Retrospective analysis revealed significant improvements in MoCA total score and domains of visuospatial/executive function and attention. Cognitive improvement was more pronounced among those who had worse pre-MoCA score before ECT.

Conclusions
The study provided support to the existing literature where cognitive improvement has been reported among individuals with schizophrenia after ECT. Future studies should consider the use of randomized controlled trials to examine the possible cognitive benefits of ECT. In a setting where there is a high volume of patients receiving ECT, the monitoring of patients' cognitive status through the course of ECT continues to be warranted and the Brief ECT Cognitive Screen may be useful as a quick measure to detect such ECT-related cognitive change.
Neuroimaging Biomarkers at Baseline Predict Electroconvulsive Therapy Overall Clinical Response in Depression
Authors: Levy Anna , Taib Simon , Arbus Christophe , Péran Patrice , Sauvaget Anne , Schmitt Laurent , Yrondi Antoine 
Published: January 2019

Objective
Major depressive disorder is a frequent and disabling disease and can be treated with antidepressant drugs. When faced with severe or resistant major depressive disorder, however, psychiatrists may resort to electroconvulsive therapy (ECT). Although very effective, the response falls short of 100%. A recent meta-analysis established clinical and biological predictive factors of the response to ECT. We decided to explore neuroimaging biomarkers that could be predictors of the ECT response.

Methods
We performed a systematic literature review up to January 1, 2018, using a Boolean combination of MeSH terms. We included 19 studies matching our inclusion criteria.

Results
Lower hippocampal, increased amygdala, and subgenual cingulate gyrus volumes were predictive for a better ECT response. Functional magnetic resonance imaging also found that the connectivity between the dorsolateral prefrontal cortex and posterior default-mode network is predictive of increased efficacy. Conversely, deep white matter hyperintensities in basal ganglia and Virchow-Robin spaces, medial temporal atrophy, ratio of left superior frontal to left rostral middle frontal cortical thickness, cingulate isthmus thickness asymmetry, and a wide range of gray and white matter anomalies were predictive for a poorer response.

Conclusions
Our review addresses the positive or negative predictive value of neuroimaging biomarkers for the ECT response, indispensable in a personalized medicine dynamic. These data could reduce the risk of nonresponders or resistance with earlier effective management. It might also help researchers elucidate the complex pathophysiology of depressive disorders and the functioning of ECT.
Survival of adult barn owls is linked to corticosterone levels
Authors: Béziers Paul , Korner-Nievergelt Fränzi , Jenni Lukas , Roulin Alexandre , Almasi Bettina 
Published: January 2019

AbstractGlucocorticoid hormones, such as corticosterone, are fundamental in the translation of external stimuli into physiological adjustments that promote the survival of an organism in face of changes in its environment. At baseline levels, corticosterone is crucial in regulating daily life metabolism and energy expenditure, whereas the acute corticosterone response promotes short-term physiological and behavioral responses to unpredictable environmental challenges. Given their different physiological effects and their role in mediating fitness components, it is still unclear whether and how inter-individual variation in baseline corticosterone levels and acute stress-response levels can affect the survival of organisms. We used 13 years of capture-recapture and dead recovery data combined with 11 years of corticosterone measurements taken on breeding barn owls (Tyto alba) to investigate how survival probability varies in relation to baseline and stress-induced corticosterone levels. Our study shows that males with a higher level of both baseline and stress-induced corticosterone levels have a higher probability of surviving than individuals with lower corticosterone levels. In females, survival probability was higher in individuals presenting elevated stress-induced corticosterone levels but was not significantly associated to baseline corticosterone levels. Our results suggest that in the barn owl the stress-induced corticosterone response is a better proxy of adult survival than baseline corticosterone levels. Further studies investigating the link between corticosterone levels and different fitness components as well as the environmental factors (e.g. weather, development conditions, disease and predation risk) leading to such endocrine phenotypes are needed to identify the costs and benefits of presenting high and low corticosterone profiles.
Identification and mitigation of pervasive off-target activity in CRISPR-Cas9 screens for essential non-coding elements
Authors: Tycko Josh , Wainberg Michael , Marinov Georgi K. , Ursu Oana , Hess Gaelen T. , Ego Braeden K. , Aradhana  , Li Amy , Truong Alisa , Trevino Alexandro E. , Spees Kaitlyn , Yao David , Kaplow Irene M. , Greenside Peyton G. , Morgens David W. , Phanstiel Douglas H. , Snyder Michael P. , Bintu Lacramioara , Greenleaf William J. , Kundaje Anshul , Bassik Michael C. 
Published: January 2019

AbstractPooled CRISPR-Cas9 screens have recently emerged as a powerful method for functionally characterizing regulatory elements in the non-coding genome, but off-target effects in these experiments have not been systematically evaluated. Here, we conducted a genome-scale screen for essential CTCF loop anchors in the K562 leukemia cell line. Surprisingly, the primary drivers of signal in this screen were single guide RNAs (sgRNAs) with low specificity scores. After removing these guides, we found that there were no CTCF loop anchors critical for cell growth. We also observed this effect in an independent screen fine-mapping the core motifs in enhancers of the GATA1 gene. We then conducted screens in parallel with CRISPRi and CRISPRa, which do not induce DNA damage, and found that an unexpected and distinct set of off-targets also caused strong confounding growth effects with these epigenome-editing platforms. Promisingly, strict filtering of CRISPRi libraries using GuideScan specificity scores removed these confounded sgRNAs and allowed for the identification of essential enhancers, which we validated extensively. Together, our results show off-target activity can severely limit identification of essential functional motifs by active Cas9, while strictly filtered CRISPRi screens can be reliably used for assaying larger regulatory elements.
Knowledge, attitude and practices on dengue fever among paediatric and adult in-patients in Metro Manila, Philippines
Authors: M. Herbuela Von Ralph Dane , de Guzman Ferdinand S. , Sobrepeña Girly D. , F. Claudio Andrew Benedict , V. Tomas Angelica Cecilia , Arriola-delos Reyes Carmina M. , Regalado Rachele A. , Teodoro Mariama M. , Watanabe Kozo 
Published: January 2019

ABSTRACTBackgroundKnowledge, attitude and practice (KAP) studies have included mainly community-based samples, yet, investigation on in-patients with Dengue fever (DF) through hospital-based surveillance has not been done.MethodsThis study aimed to assess and compare the KAP, identify its determinants and protective factors among 250 clinically or serologically confirmed paediatric (n = 233) and adult patients (n = 17) with DF and 250 youth (n = 233) and adult (n = 17) controls.ResultsPaediatric patients with DF had significantly higher knowledge (P < 0.05) and practice (P < 0.05) domains mean scores than adult patients with DF and significantly lower practice mean scores than youth controls (P < 0.05). Being senior high school, days in the hospital and rash determined increased KAP among paediatric patients with DF while no significant determinants were found among adult patients with DF. Mosquito-eating fish, screen windows and Dengue vaccine were protective factors against DF, though, further studies should confirm these results. Moreover, there was a significant positive correlation between knowledge and attitude (P < 0.01) of paediatric patients with DF, however, similar with adult patients with DF, these domains did not correlate with their practices against DF.ConclusionThis suggests that the translation of knowledge and attitude to better practices against DF was poor. Thus, it is necessary to structure health programs on models that facilitate behavioural change among children and adults.
RAI1 Regulates Activity-Dependent Nascent Transcription and Synaptic Scaling
Authors: Garay Patricia M. , Chen Alex , Tsukahara Takao , Kohen Rafi , Christian Althaus J. , Wallner Margarete A. , Giger Roman J. , Sutton Michael A. , Iwase Shigeki 
Published: January 2019

AbstractLong-lasting forms of synaptic plasticity such as synaptic scaling are critically dependent on transcription. Activity-dependent transcriptional dynamics in neurons, however, have not been fully characterized, because most previous efforts relied on measurement of steady-state mRNAs. Here, we profiled transcriptional dynamics of primary neuronal cultures undergoing network activity shifts using nascent RNA sequencing. We found pervasive transcriptional changes, in which ~45% of expressed genes respond to network activity shifts. Notably, the majority of these genes respond to increases or decreases of network activity uniquely, rather than reciprocally. We further linked the chromatin regulator Retinoic acid induced 1 (RAI1), the Smith-Magenis Syndrome gene, to the specific transcriptional program driven by reduced network activity. Finally, we show that RAI1 is essential for homeostatic synaptic upscaling but not downscaling. These results demonstrate the utility of bona fide transcription profiling to discover mechanisms of activity-dependent chromatin remodeling that underlie normal and pathological synaptic plasticity.
Capturing multiple-type interactions into practical predictors of type replacement following HPV vaccination
Authors: Man Irene , Auranen Kari , Wallinga Jacco , Bogaards Johannes A. 
Published: January 2019

AbstractCurrent HPV vaccines target a subset of the oncogenic human papillomavirus (HPV) types. If HPV types compete during infection, vaccination may trigger replacement by the non-targeted types. Existing approaches to assess the risk of type replacement have focussed on detecting competitive interactions between pairs of vaccine and non-vaccine types. However, methods to translate any inferred pairwise interactions into predictors of replacement have been lacking. In this paper, we develop practical predictors of type replacement in a multi-type setting, readily estimable from pre-vaccination longitudinal or cross-sectional prevalence data. The predictors we propose for replacement by individual non-targeted types take the form of weighted cross hazard ratios of acquisition versus clearance, or aggregate odds ratios of coinfection with the vaccine types. We elucidate how the hazard-based predictors incorporate potentially heterogeneous direct and indirect type interactions by appropriately weighting type-specific hazards and show when they are equivalent to the odds-based predictors. Additionally, pooling type-specific predictors proves to be useful for predicting increase in the overall non-vaccine-tvpe prevalence. Using simulations, we demonstrate good performance of the predictors under different interaction structures. We discuss potential applications and limitations of the proposed methodology in predicting type replacement, as compared to existing approaches.
The effectiveness and cost effectiveness of a hospital avoidance program in a residential aged care facility
Authors: Carter Hannah , Lee Xing , Dwyer Trudy , Jeffrey Dee , O’Neill Barbara , Doran Chris , Parkinson Lynne , Osborne Sonya , Reid-Searl Kerry , Graves Nicholas 
Published: January 2019

AbstractBackgroundResidential aged care facility residents experience high rates of hospital admissions which are stressful, costly and often preventable.DesignProspective pre-post cohort study and decision model analysisInterventionA decision-support tool was implemented to enable nursing staff to detect, refer and quickly respond to early signals of a deteriorating resident. Advanced clinical skills training, new diagnostic equipment and guided support from clinical lead nurses and nurse practitioners was provided to support nursing staff in the delivery of appropriate sub-acute care.Outcome measuresRate of hospital admissions; length of stay; incremental cost per QALY; net monetary benefit.ResultsThe hospital avoidance program was associated with a 19% reduction in annual hospital admissions and a 31% reduction in the average length of stay. When modelled in a cohort of 1,000 residents the program resulted in a total of 1,606 fewer hospital bed days per annum. This contributed to a total cost saving of $2.6 million and 0.62 incremental QALYs gained per 1,000 residents. The program had a positive net monetary benefit and was considered cost-effective, even when the willingness to pay for health care gains was set to zero. A probabilistic sensitivity analysis estimated that there was an 86% probability that the program was cost-effective after taking the uncertainty of the model inputs into account.ConclusionsThis study provides compelling evidence for the effectiveness and cost-effectiveness of a RACF nurse led sub-acute care program in preventing unnecessary hospital admissions.
Closely related Cryptococcus neoformans strains possess differential virulence both in humans and the mouse inhalation model
Authors: Mukaremera Liliane , MacDonald Tami R. , Nielsen Judith N. , Akampulira Andrew , Schutz Charlotte , Taseera Kabanda , Muzoora Conrad , Meintjes Graeme , Meya David B. , Boulware David R. , Nielsen Kirsten 
Published: January 2019

AbstractCryptococcal meningitis (CM) causes high rates of HIV-related mortality, yet Cryptococcus factors influencing patient outcome are not well understood. Pathogen-specific traits, such as the strain genotype and degree of antigen shedding, are associated with clinical outcome but the underlying biology remains elusive. In this study, we examined factors determining disease outcome in HIV-infected cryptococcal meningitis patients infected with C. neoformans strains with the same multi-locus sequence type. Both patient mortality and survival were observed during infections with the same sequence type. Disease outcome did not correlate with underlying patient immune deficiencies. Patient mortality was associated with higher antigen levels, fungal burden in the CSF, and low CSF fungal clearance. Virulence of a subset of clinical strains with the same sequence type were analyzed using the mouse inhalation model of cryptococcosis. We showed a strong correlation between human and mouse mortality rates, demonstrating the mouse inhalation model recapitulates human infection. Similar to human infection, the ability to multiply in vivo, demonstrated by high fungal burden in the lung and brain tissues, was associated with mouse mortality. Mortality rate was not associated with single C. neoformans virulence factors in vitro or in vivo; rather, a trend in mortality rate correlated with a suite of traits. These observations show that genotype similarities between C. neoformans strains do not necessarily translate into similar virulence either in the mouse model or in human patients. In addition, our results show that in vitro assays do not fully reproduce in vivo conditions that influence C. neoformans virulence.
A Simple Cross-Linking/Mass Spectrometry Workflow to Study System-Wide Protein Interactions
Authors: Götze Michael , Iacobucci Claudio , Ihling Christian , Sinz Andrea 
Published: January 2019

ABSTRACTWe present a cross-linking/mass spectrometry (XLMS) workflow for performing proteome-wide cross-linking analyses within one week. The workflow is based on the commercially available MS-cleavable cross-linker disuccinimidyl dibutyric urea (DSBU) and can be employed by every lab having access to a mass spectrometer with tandem MS capabilities. We provide an updated version 2.0 of the freeware software tool MeroX, available at www.StavroX.com, that allows conducting fully automated and reliable studies delivering insights into protein-protein interaction networks and protein conformations at the proteome level. We exemplify our optimized workflow for mapping protein-protein interaction networks in Drosophila melanogaster embryos on a system-wide level. From cross-linked Drosophila embryo extracts, we detected 18,037 cross-link spectrum matches corresponding to 5,129 unique cross-linked residues in biological triplicate experiments at 5% FDR (3,098 at 1% FDR). Among these, 1,237 interprotein cross-linking sites were identified that contain valuable information on protein-protein interactions. The remaining 3,892 intra-protein cross-links yield information on conformational changes of proteins in their cellular environment.
Tau pathology in early Alzheimer’s disease disrupts selective neurophysiological network dynamics
Authors: Kocagoncu Ece , Quinn Andrew , Firouzian Azadeh , Cooper Elisa , Greve Andrea , Gunn Roger , Green Gary , Woolrich Mark W. , Henson Richard N. , Lovestone Simon ,   Deep and Frequent Phenotyping study team, Rowe James B. 
Published: January 2019

AbstractThe role of aggregation of misfolded Tau protein in the pathogenesis of Alzheimer’s disease is the subject of rapid biomarker development and new therapeutic strategies to slow or prevent dementia. We tested the hypothesis that Tau pathology is associated with functional organization of widespread neurophysiological networks. We used electro-magnetoencephalography (E/MEG) in combination with [18F]AV1451 PET scanning to quantify Tau-dependent network disruption. Using a graph theoretical approach to MEG connectivity, we quantified nodal measures of functional segregation, centrality and efficiency of information transfer. We correlated these metrics against the nodes’ uptake of [18F]AV1451. There were both regional- and frequency-specific effects of Tau levels on the efficiency of information transfer and network segregation in early AD. Tau correlated with temporal regional participation coefficient (in delta, theta, beta bands); and temporal lobar eigenvector centrality (in theta, alpha, beta bands), but greater eccentricity at higher frequencies (gamma). The results support the translational development of neurophysiological “signatures” as biomarkers of Alzheimer’s disease, with potential to facilitate experimental medicines studies.
Comprehensive analysis of RNA-seq kits for standard, low and ultra-low quantity samples
Authors: Palomares Marie-Ange , Dalmasso Cyril , Bonnet Eric , Derbois Céline , Brohard-Julien Solène , Ambroise Christophe , Battail Christophe , Deleuze Jean-François , Olaso Robert 
Published: January 2019

ABSTRACTHigh-throughput RNA-sequencing has become the gold standard method for whole-transcriptome gene expression analysis, and is widely used in numerous applications to study cell and tissue transcriptomes. It is also being increasingly used in a number of clinical applications, including expression profiling for diagnostics and alternative transcript detection. However, despite its many advantages, RNA sequencing can be challenging in some situations, for instance in cases of low input amounts or degraded RNA samples. Several protocols have been proposed to overcome these challenges, and many are available as commercial kits. In this study, we comprehensively test three recent commercial technologies for RNA-seq library preparation (TruSeq, SMARTer and SMARTer Ultra-Low) on human reference tissue preparations, using standard (1μg), low (100 and 10 ng) and ultra-low (< 1 ng) input amounts, and for mRNA and total RNA, stranded or unstranded. The results are analyzed using read quality and alignment metrics, gene detection and differential gene expression metrics. Overall, we show that the TruSeq kit performs well with an input amount of 100 ng, while the SMARTer kit shows degraded performance for inputs of 100 and 10 ng, and the SMARTer Ultra-Low kit performs relatively well for input amounts < 1 ng. All the results are discussed in detail, and we provide guidelines for biologists for the selection of a RNA-seq library preparation kit.