bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of the monoaminergic stabiliser (−)-OSU6162 on mental fatigue following stroke or traumatic brain injury
Authors: Nilsson Marie K.L. , Johansson Birgitta , Carlsson Maria L. , Schuit Robert C. , Rönnbäck Lars
Published: May 2020

Objective:

The purpose of the present study was to evaluate the efficacy and safety of (−)-OSU6162 in doses up to 30 mg b.i.d. in patients suffering from mental fatigue following stroke or traumatic brain injury (TBI).

Methods:

This 4 + 4 weeks double-blind randomised cross-over study included 30 patients afflicted with mental fatigue following a stroke or head trauma occurring at least 12 months earlier. Efficacy was assessed using the Mental Fatigue Scale (MFS), the Self-rating Scale for Affective Syndromes [Comprehensive Psychopathological Rating Scale (CPRS)], the Frenchay Activity Index (FAI), and a battery of neuropsychological tests. Safety was evaluated by recording spontaneously reported adverse events (AEs).

Results:

There were significant differences on the patients’ total FAI scores (p = 0.0097), the subscale FAI outdoor scores (p = 0.0243), and on the trail making test (TMT-B) (p = 0.0325) in favour of (−)-OSU6162 treatment. Principal component analysis showed a clear overall positive treatment effect in 10 of 28 patients; those who responded best to treatment had their greatest improvements on the MFS. Reported AEs were mild or moderate in severity and did not differ between the (−)-OSU6162 and the placebo period.

Conclusion:

The most obvious beneficial effects of (−)-OSU6162 were on the patients’ activity level, illustrated by the improvement on the FAI scale. Moreover, a subgroup of patients showed substantial improvements on the MFS. Based on these observed therapeutic effects, in conjunction with the good tolerability of (−)-OSU6162, this compound may offer promise for treating at least part of the symptomatology in patients suffering from stroke- or TBI-induced mental fatigue.
The Electoral System, the Party System and Accountability in Parliamentary Government
Authors: KAM CHRISTOPHER , BERTELLI ANTHONY M. , HELD ALEXANDER
Published: May 2020

Electoral accountability requires that voters have the ability to constrain the incumbent government’s policy-making power. We express the necessary conditions for this claim as an accountability identity in which the electoral system and the party system interact to shape the accountability of parliamentary governments. Data from 400 parliamentary elections between 1948 and 2012 show that electoral accountability is contingent on the party system’s bipolarity, for example, with parties arrayed in two distinct blocs. Proportional electoral systems achieve accountability as well as majoritarian ones when bipolarity is strong but not when it is weak. This is because bipolarity decreases the number of connected coalitions that incumbent parties can join to preserve their policy-making power. Our results underscore the limitations that party systems place on electoral reform and the benefits that bipolarity offers for clarifying voters’ choices and intensifying electoral competition.
Irradiation of early immature Anastrepha ludens stages for the rearing of Doryctobracon areolatus (Hymenoptera: Braconidae), a fruit fly parasitoid
Authors: López-Arriaga Florida , Gordillo Victor Hugo , Cancino Jorge , Montoya Pablo
Published: May 2020

Doryctobracon areolatus is a native parasitoid of the Neotropical region that presents the highest percentages of natural parasitism of fruit flies of the genus Anastrepha. In the Moscafrut Program SADER-SENASICA, located in Metapa de Domínguez, Chiapas, Mexico, a laboratory colony of this species is maintained on Anastrepha ludens, the Mexican fruit fly, with the aim to scale the production of the parasitoid up to massive levels. In order to eliminate unwanted emergence of adult flies during the rearing process, this study evaluated the effect of irradiation (at doses of 20, 30, 40, and 50 Gy) applied to eggs, and first and second instar larvae of A. ludens; all irradiated stages were subsequently exposed as second instar larvae to adult females of D. areolatus. Irradiation did not affect the eclosion of A. ludens eggs but, at doses of 40 and 50 Gy, it did cause delayed larval development and pupation, as well as lower larval weight. Adult fly emergence was suppressed at all doses, except in eggs irradiated at 20 Gy. Doses of 20 and 30 Gy applied to the eggs and larvae did not affect the emergence, survival, fecundity or flight ability of the emerged parasitoids, but the second instar larvae were easily handled during the rearing process. Our results suggest that D. areolatus can be successfully produced in second instar larvae of A. ludens irradiated at 30 Gy.
Skin surface temperature of the mammary gland, measured by infrared thermography, in primiparous Girolando cows fed diets containing different lipid sources
Authors: Wanderley Alysson M. , Ítavo Luís C. V. , dos Santos Geraldo T. , Ítavo Camila C. B. F. , Dias Alexandre M. , Mateus Rodrigo G. , Pereira Luiz C. , Gonçalves Ariadne B. , Kohl Endyara S. , Lima Celso R. C.
Published: May 2020

This research communication describes the influence of diet, mammary quarter position and milking process on the temperature of teats and udder of cows fed diets containing different lipid sources. Five primiparous cows were fed diets containing cottonseed, sunflower seed, soybeans or soybean oil as a source of lipids and a reference diet without the inclusion of lipid sources in a 5 × 5 Latin Square design. Milk yield was determined in the last five days of each period. Milk samples were collected for SCC analysis on the last two days of each experimental period. The images of the mammary gland were obtained using an infrared camera and were analyzed with appropriate computer software. Milk yield was 14.8% higher for cows fed soybeans as a source of lipids. Diets and somatic cell counts did not influence the temperature of teats and udder. The milking process reduced the temperature of teats and udder by 0.79°C. Rear teats and rear quarters had higher surface temperatures than front teats and fore quarters. Changes in temperature of teats and mammary quarters occurred as a function of the milking process and quarter position. However, the diet and the SCC did not influence the temperature of teats and mammary quarters in this experiment.
The impact of childhood deprivation on adult neuropsychological functioning is associated with ADHD symptom persistence
Authors: Golm Dennis , Sarkar Sagari , Mackes Nuria K. , Fairchild Graeme , Mehta Mitul A. , Rutter Michael ,   ERA Young Adult Follow Up study team, Sonuga-Barke Edmund J.
Published: May 2020

Background

Institutional deprivation in early childhood is associated with neuropsychological deficits in adolescence. Using 20-year follow-up data from a unique natural experiment – the large-scale adoption of children exposed to extreme deprivation in Romanian institutions in the 1980s –we examined, for the first time, whether such deficits are still present in adulthood and whether they are associated with deprivation-related symptoms of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).

Methods

Adult neuropsychological functioning was assessed across five domains (inhibitory control, emotion recognition, decision-making, prospective memory and IQ) in 70 previously institutionalized adoptees (mean age = 25.3, 50% female) and 22 non-deprived UK adoptees (comparison group, mean age = 24.6, 41% female). ADHD and ASD symptoms were assessed using parent-completed questionnaires.

Results

Early institutionalization was associated with impaired performance on all tasks in adulthood. Prospective memory deficits persisted after controlling for IQ. ADHD and ASD symptoms were positively correlated. After controlling for ASD symptoms, ADHD symptoms remained associated with deficits in IQ, prospective memory, proactive inhibition, decision-making quality and emotion recognition. ASD symptoms were not independently associated with neuropsychological deficits when accounting for their overlap with ADHD symptoms. Multiple regression analysis revealed that the link between childhood deprivation and adult ADHD symptoms was statistically explained by deprivation-related differences in adult IQ and prospective memory.

Conclusions

These results represent some of the most compelling evidence to date of the enduring power of early, time-limited childhood adversity to impair long-term neuropsychological functioning across the lifespan – effects that are linked specifically to deprivation-related adult ADHD symptoms.
Characterization of flowing liquid films as a regenerating plasma mirror for high repetition-rate laser contrast enhancement
Authors: Underwood C. I. D. , Gan G. , He Z.-H. , Murphy C. D. , Thomas A. G. R. , Krushelnick K. , Nees J.
Published: May 2020

In this paper, we characterize a high repetition-rate regenerating plasma mirror produced by the thin film of liquid formed when two laminar streams collide. The use of a flowing liquid film is inexpensive and the interaction surface refreshes automatically, avoiding buildup of on-target debris. The composition of the liquid material and the relative angle of the film-generating nozzles was optimized for this application. Spectra measured in reflection from a water-based plasma mirror showed a blue shift but an optical reflectivity of up to 30%. The thickness of the film was found to be of the order of 2 ${\rm \mu}$m, and the stability of the reflected spot was ${\approx }1$ mrad. The reflected beam profile was highly distorted but stable. Further optimization of the nozzles to affect the fluid flow should enable significant improvements in control of the fluid films and increase in the reflectivity of these mirrors.
Influence of the solenoid magnetic field on the self-modulation mechanism
Authors: Zhao Xiao-ying , Yang Yang-yang , Jia Huan , Xie Zai-peng , Qi Xin , Wang Zhi-jun , He Yuan
Published: May 2020

For the guarantee of the long-distance transport of the bunches of China Initiative Accelerator Driven System (CIADS), a new scheme is proposed that extra magnetic field is used in the accelerator-target coupling section before the windowless target to minimize the self-modulation (SM) mechanism. Particle-in-cell simulations are carried out to study the influence of the solenoidal magnetic field on the self-modulation mechanism when long proton bunches move in the background plasmas. The long proton bunches used in the simulations are similar to these in the linear accelerator of CIADS. It is found that the presence of the solenoidal magnetic field will significantly inhibit the self-modulation process. For the strong magnetic field, the longitudinal separation and transverse focusing of the long bunches disappear. We attribute these phenomena to the reason that the strong solenoidal magnetic field restricts the transverse movement of plasma electrons. Thus, there are not enough electrons around the bunch to compensate the space charge effect. Moreover, without transverse current, the longitudinal pinched effect disappears, and the long bunch can not be separated into small pulses anymore.
Development of a health technology assessment module for evaluating mobile medical applications
Authors: Moshi Magdalena Ruth , Tooher Rebecca , Merlin Tracy
Published: May 2020

Objective

The aim of this study was to develop a module which could be used to facilitate the assessment of mobile medical applications (MMA) for regulatory and reimbursement purposes.

Methods

In-depth interviews were conducted with policymakers, healthcare practitioners, and application developers to determine possible pathways and impediments to MMA reimbursement. These findings were integrated with our previous research on MMA reimbursement and regulation to create a module that could be used with existing health technology assessment (HTA) methodological frameworks to guide the evaluation of MMAs.

Results

Stakeholders indicated that they trust how traditional medical devices are currently appraised for reimbursement. They were concerned that there was a lack of clarity regarding which entity in the health system was responsible for determining app quality. They were also concerned about the digital health literacy of medical practitioners and patients. Concepts emerging from our previous research were reinforced by the interview findings, including that the connectivity and cybersecurity of apps need to be considered, along with an assessment of software reliability. It is also critical that the credibility of the information presented in apps is assessed as it could potentially mislead patients and clinicians.

Conclusion

An MMA evaluation module was created that would enable an existing HTA process to be adapted for the assessment of MMA technology. These adaptations include making provisions for an assessment of app cybersecurity, the impact on MMA clinical utility of software updates, and compatibility issues. Items to address concerns around practitioner responsibility and app misinformation were also incorporated into the module.
Impact of vaccination on invasive pneumococcal disease in Italy 2007–2017: surveillance challenges and epidemiological changes
Authors: Monali R. , De Vita E. , Mariottini F. , Privitera G. , Lopalco P. L. , Tavoschi L.
Published: May 2020

Surveillance of new cases of invasive pneumococcal disease (IPD) in Italy was started in 2007 by the Ministry of Health (MoH). In 2012, pneumococcal childhood vaccination was introduced at the national level and, in 2017, for citizens aged 65 years and over. We describe here IPD epidemiology in Italy over the past 10 years investigating the impact of the vaccine programme on disease burden. Reports of IPD cases, data on serotype and vaccination coverage (VC) data were obtained from MoH annual reports, for the period 2007–2017. IPD notification rate and proportion by year, region, age and serotype were calculated. In 2007, 525 cases were reported (rate 0.88/100 000), rising to 1703 cases (rate 2.82/100 000) in 2017. The distribution of IPD cases by age group over time registered the largest share among individuals aged 65 years and over. A decreasing trend in notification rate was observed among those aged 0–4 years. During the same period, the 24-month VC increased, ranging from 80.9% to 96.7% in 2017. Molecular data indicated re-emergence of PPSV23-specific serotypes and non-vaccine serotypes. We observed an increase in IPD notifications during 2007–2017, likely due to an improved surveillance system, at least in some regions, with the relative quota of IPD notifications decreasing among vaccinated children cohorts. Further strengthening of IPD surveillance system, including molecular and vaccine coverage data, would be needed to assess and inform pneumococcal vaccination strategies in Italy.
Pointer chasing via triangular discrimination
Authors: Yehudayoff Amir
Published: May 2020

We prove an essentially sharp
$\tilde \Omega (n/k)$
lower bound on the k-round distributional complexity of the k-step pointer chasing problem under the uniform distribution, when Bob speaks first. This is an improvement over Nisan and Wigderson’s
$\tilde \Omega (n/{k^2})$
lower bound, and essentially matches the randomized lower bound proved by Klauck. The proof is information-theoretic, and a key part of it is using asymmetric triangular discrimination instead of total variation distance; this idea may be useful elsewhere.
Ukrainian ‘Working through the Past’ in the Context of the Polish–Ukrainian Dialogue on Volhynia-43. Asymmetry of Memory
Authors: Rysicz-Szafraniec Julia
Published: May 2020

The modern Polish–Ukrainian dialogue is the second interstate dialogue of the twentieth century, in the development of which the historical and political discourses have played an important role. The so-called Volhynia discourse poses the most serious challenge in this dialogue, while at the same time being its main component. The article claims the Volhynia discourse plays a major role in bringing about the asymmetry of historical memory between the two states. The events of Volhynia-43 have remained in Polish historical memory as an act of genocide perpetrated in 1941–1943 by Ukrainian nationalists, mainly from the Ukrainian Insurgent Army (UPA), on over 100,000 Poles and citizens of the Polish state inhabiting Galicia and Eastern Małopolska, including Volhynia. These territories, considered by the Ukrainian nationalist party OUN as indigenously Ukrainian, were to be included in the future independent Ukrainian state. The Ukrainian historiography, apart from sparse exceptions, avoids the term ‘massacre’ and ‘genocide’ in reference to the events in Volhynia, defining them as a conflict or a Polish–Ukrainian war with a comparable number of casualties on both sides. The article, analysing speeches and announcements by political leaders of Poland and Ukraine, focuses on explaining the causes and effects of this shift in accentuation in the Ukrainian discourse on Volhynia, and, broadly, in Ukraine working through its past.
Inequality in Nineteenth-Century Manhattan: Evidence from the Housing Market
Authors: Gray Rowena
Published: May 2020

Historical inequality is difficult to measure, especially at the subcountry level and beyond the top income shares. This article presents new evidence on the level of inequality in Manhattan from 1880 to 1910 using housing rents. Rental prices and characteristics, including geocodable locations, were collected from newspapers and provide extensive geographic coverage of the island, relevant for the overwhelming majority of its population where renting predominated. This provides a measure of consumption inequality at the household level, which helps to develop the picture of urban inequality for this period, when income and wealth measures are scarce. For large American cities, but particularly for New York, housing made up a large share of consumption expenditure and its consumption cannot be substituted, so this is a reliable and feasible way to identify the true trends in urban inequality across space and time.
CD36 gene polymorphism -31118 G > A	(rs1761667) is associated with overweight and obesity but not with fat	preferences in Mexican children
Authors: Enciso-Ramírez Mayra , Reyes-Castillo Zyanya , Llamas-Covarrubias Mara Anaís , Guerrero Luis , López-Espinoza Antonio , Valdés-Miramontes Elia Herminia
Published: May 2020

Abstract. CD36 glycoprotein is a candidate receptor involved in the gustatory detection of lipids and emerging evidence has suggested that genetic variations in CD36 may modulate the oral perception threshold to fatty acids. Here, we analyzed the association of -31118 G > A polymorphism in CD36 gene with nutritional status and preferences for fatty foods in Mexican children. Genotyping of SNP rs1761667 was performed in school-age children (n = 63) in addition to sensory tests evaluating the preference and satisfaction score assigned to oil-based sauces of different fatty acid composition. The G allele was associated with high BMI z-score in children (OR = 2.43, 95% (CI 1.02–5.99); p = 0.02) but CD36 genotypes (AA, GA, and GG) did not show significant association with the preference and satisfaction scores assigned to oil-based sauces. The BMI z-score showed no association with the preference to oil-based sauces; however, children with normal weight gave higher satisfaction scores to sauces with a high content of unsaturated fatty acids than to sauces rich in saturated fatty acids (0.56 ± 1.26 vs. 0.06 ± 1.22; p = 0.02). Therefore, the G allele of -31118 G > A SNP in CD36 gene is associated with overweight and obesity in Mexican children but do not appear to modulate the preferences and satisfaction scores to fat.
How Substance Use Treatment Professionals Manage Organisational Tensions
Authors: Storbjörk Jessica
Published: May 2020

Abstract. Aims: The study examined how substance use treatment professionals managed problems and tensions in their work, and explored if the strategies varied by organisational features related to New Public Management (NPM). Methods: A total of 69 semi-structured interviews (2017–2018) with treatment staff in nine sampled local/regional areas formed the basis for constructing a web survey administered to staff across Sweden in 2019 (n=606). The means showed how often the different strategies were used. Regression analyses examined organisational differences, and central strategies were illustrated by the interview study. Results: Treatment professionals in general reported satisfactory freedom in their work. Staff in more NPM-like organisations were less likely to report autonomy and more inclined to report conflicting demands. When conflicts emerged, the staff used both passive strategies indicating adaptation or resignation, and active strategies including boundary spanning, protest, and liberty-taking. Some challenging strategies such as looking for other jobs or reporting one thing but doing another were more common in more NPM-like organisations. The opposite was found for customer orientation. Conclusions: While NPM features on customer orientation and steering methods appeared to create fewer problems, more NPM-like organisations appeared to be less favourable overall and should be applied with caution.
Multidisciplinary Study of Subsidence and Sinkhole Occurrences in the Acque Albule Basin (Roma, Italy)
Authors: De Ritis R. , Nardi A. , Materni V. , Venuti A. , Stefanelli P. , Rotella G. , Sapia V. , Carpentieri E. , Tolomei C. , Civico R. , Coltorti M. , Nanni T. , Argentieri A. , Del Gaudio P. , Chiappini M.
Published: May 2020

We present the results of a combined analysis of remote sensing and geophysical‐geotechnical data carried out in the Acque Albule Basin, a sinkhole prone area located close to the city of Roma, where a wide travertine wedge is present. We carried out geophysical measurements and borehole drillings over two test areas to image the subsoil where paroxysmal surficial dynamics occur. One site is marked by subsidence occurring at least since the early 2000s, whereas the other site hosts the “La Regina” and “Colonnelle” sinkhole lakes, which discharge sulfur‐carbonated waters. The stability of these two sites threatens highway, railway, and airport facilities, and this study helps to assess the geological hazard. For example, InSAR and LiDAR data helped define wide scale subsidence over the last 20 years and previously undetected small‐scale morphologies. Geophysical measurements of the latter revealed shallow and deep dissolution affecting the travertine and driving surficial paroxysmal events. Both study sites were found to lie inside a large depression located at the junction between Jurassic carbonate and Plio‐Pleistocene units in association with paleo karst morphologies in the travertine deposits and affected by the present‐past spillage of sulfurous waters. Given these elements, multidisciplinary geophysical observations are crucial for assessing and mitigating the geological risk and guiding land use planning and management.
A Survey of Small‐Scale Waves and Wave‐Like Phenomena in Jupiter's Atmosphere Detected by JunoCam
Authors: Orton Glenn S. , Tabataba‐Vakili Fachreddin , Eichstädt Gerald , Rogers John , Hansen Candice J. , Momary Thomas W. , Ingersoll Andrew P. , Brueshaber Shawn , Wong Michael H. , Simon Amy A. , Fletcher Leigh N. , Ravine Michael , Caplinger Michael , Smith Dakota , Bolton Scott J. , Levin Steven M. , Sinclair James A. , Thepenier Chloe , Nicholson Hamish , Anthony Abigail
Published: May 2020

In the first 20 orbits of the Juno spacecraft around Jupiter, we have identified a variety of wave‐like features in images made by its public‐outreach camera, JunoCam. Because of Juno's unprecedented and repeated proximity to Jupiter's cloud tops during its close approaches, JunoCam has detected more wave structures than any previous surveys. Most of the waves appear in long wave packets, oriented east‐west and populated by narrow wave crests. Spacing between crests were measured as small as ~30 km, shorter than any previously measured. Some waves are associated with atmospheric features, but others are not ostensibly associated with any visible cloud phenomena and thus may be generated by dynamical forcing below the visible cloud tops. Some waves also appear to be converging, and others appear to be overlapping, possibly at different atmospheric levels. Another type of wave has a series of fronts that appear to be radiating outward from the center of a cyclone. Most of these waves appear within 5° of latitude from the equator, but we have detected waves covering planetocentric latitudes between 20°S and 45°N. The great majority of the waves appear in regions associated with prograde motions of the mean zonal flow. Juno was unable to measure the velocity of wave features to diagnose the wave types due to its close and rapid flybys. However, both by our own upper limits on wave motions and by analogy with previous measurements, we expect that the waves JunoCam detected near the equator are inertia‐gravity waves.
Non-antibiotic pharmaceuticals enhance the transmission of exogenous antibiotic resistance genes through bacterial transformation
Authors: Wang Yue , Lu Ji , Engelstädter Jan , Zhang Shuai , Ding Pengbo , Mao Likai , Yuan Zhiguo , Bond Philip L , Guo Jianhua
Published: May 2020

Antibiotic resistance is a serious global threat for public health. Considering the high abundance of cell-free DNA encoding antibiotic resistance genes (ARGs) in both clinical and environmental settings, natural transformation is an important horizontal gene transfer pathway to transmit antibiotic resistance. It is acknowledged that antibiotics are key drivers for disseminating antibiotic resistance, yet the contributions of non-antibiotic pharmaceuticals on transformation of ARGs are overlooked. In this study, we report that some commonly consumed non-antibiotic pharmaceuticals, at clinically and environmentally relevant concentrations, significantly facilitated the spread of antibiotic resistance through the uptake of exogenous ARGs. This included nonsteroidal anti-inflammatories, ibuprofen, naproxen, diclofenac, the lipid-lowering drug, gemfibrozil, and the β-blocker propranolol. Based on the results of flow cytometry, whole-genome RNA sequencing and proteomic analysis, the enhanced transformation of ARGs was affiliated with promoted bacterial competence, enhanced stress levels, over-produced reactive oxygen species and increased cell membrane permeability. In addition, a mathematical model was proposed and calibrated to predict the dynamics of transformation during exposure to non-antibiotic pharmaceuticals. Given the high consumption of non-antibiotic pharmaceuticals, these findings reveal new concerns regarding antibiotic resistance dissemination exacerbated by non-antibiotic pharmaceuticals.
Looking into the genetic bases of OCD dimensions: a pilot genome-wide association study
Authors: Alemany-Navarro María , Cruz Raquel , Real Eva , Segalàs Cinto , Bertolín Sara , Rabionet Raquel , Carracedo Ángel , Menchón Jose M. , Alonso Pino
Published: May 2020

The multidimensional nature of obsessive-compulsive disorder (OCD) has been consistently reported. Clinical and biological characteristics have been associated with OCD dimensions in different ways. Studies suggest the existence of specific genetic bases for the different OCD dimensions. In this study, we analyze the genomic markers, genes, gene ontology and biological pathways associated with the presence of aggressive/checking, symmetry/order, contamination/cleaning, hoarding, and sexual/religious symptoms, as assessed via the Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS) in 399 probands. Logistic regression analyses were performed at the single-nucleotide polymorphism (SNP) level. Gene-based and enrichment analyses were carried out for common (SNPs) and rare variants. No SNP was associated with any dimension at a genome-wide level (p < 5 × 10−8). Gene-based analyses showed one gene to be associated with hoarding (SETD3, p = 1.89 × 10−08); a gene highly expressed in the brain and which plays a role in apoptotic processes and transcriptomic changes, and another gene associated with aggressive symptoms (CPE; p = 4.42 × 10−6), which is involved in neurotrophic functions and the synthesis of peptide hormones and neurotransmitters. Different pathways or biological processes were represented by genes associated with aggressive (zinc ion response and lipid metabolism), order (lipid metabolism), sexual/religious (G protein-mediated processes) and hoarding (metabolic processes and anion transport) symptoms after FDR correction; while no pathway was associated with contamination. Specific genomic bases were found for each dimension assessed, especially in the enrichment analyses. Further research with larger samples and different techniques, such as next-generation sequencing, are needed to better understand the differential genetics of OCD dimensions.
Closed-loop digital meditation for neurocognitive and behavioral development in adolescents with childhood neglect
Authors: Mishra Jyoti , Sagar Rajesh , Parveen Sana , Kumaran Senthil , Modi Kiran , Maric Vojislav , Ziegler David , Gazzaley Adam
Published: May 2020

Adverse childhood experiences are linked to poor attentive behaviors during adolescence, as well as increased risk for mental health disorders in adults. However, no study has yet tested targeted interventions to optimize neurocognitive processes in this population. Here, we investigated closed-loop digital interventions in a double-blind randomized controlled study in adolescents with childhood neglect, and evaluated the outcomes using multimodal assessments of neuroimaging, cognitive, behavioral, and academic evaluations. In the primary neuroimaging results, we demonstrate that a closed-loop digital meditation intervention can strengthen functional connectivity of the dorsal anterior cingulate cortex (dACC) in the cingulo-opercular network, which is critically developing during the adolescent period. Second, this intervention enhanced sustained attention and interference-resolution abilities, and also reduced behavioral hyperactivity at a 1-year follow-up. Superior academic performance was additionally observed in adolescents who underwent the digital meditation intervention. Finally, changes in dACC functional connectivity significantly correlated with improvements in sustained attention, hyperactivity, and academic performance. This first study demonstrates that closed-loop digital meditation practice can facilitate development of important aspects of neurocognition and real-life behaviors in adolescents with early childhood neglect.
Anterior insula stimulation suppresses appetitive behavior while inducing forebrain activation in alcohol-preferring rats
Authors: Haaranen Mia , Scuppa Giulia , Tambalo Stefano , Järvi Vilja , Bertozzi Sine M. , Armirotti Andrea , Sommer Wolfgang H. , Bifone Angelo , Hyytiä Petri
Published: May 2020

The anterior insular cortex plays a key role in the representation of interoceptive effects of drug and natural rewards and their integration with attention, executive function, and emotions, making it a potential target region for intervention to control appetitive behaviors. Here, we investigated the effects of chemogenetic stimulation or inhibition of the anterior insula on alcohol and sucrose consumption. Excitatory or inhibitory designer receptors (DREADDs) were expressed in the anterior insula of alcohol-preferring rats by means of adenovirus-mediated gene transfer. Rats had access to either alcohol or sucrose solution during intermittent sessions. To characterize the brain network recruited by chemogenetic insula stimulation we measured brain-wide activation patterns using pharmacological magnetic resonance imaging (phMRI) and c-Fos immunohistochemistry. Anterior insula stimulation by the excitatory Gq-DREADDs significantly attenuated both alcohol and sucrose consumption, whereas the inhibitory Gi-DREADDs had no effects. In contrast, anterior insula stimulation failed to alter locomotor activity or deprivation-induced water drinking. phMRI and c-Fos immunohistochemistry revealed downstream activation of the posterior insula and medial prefrontal cortex, as well as of the mediodorsal thalamus and amygdala. Our results show the critical role of the anterior insula in regulating reward-directed behavior and delineate an insula-centered functional network associated with the effects of insula stimulation. From a translational perspective, our data demonstrate the therapeutic potential of circuit-based interventions and suggest that potentiation of insula excitability with neuromodulatory methods, such as repetitive transcranial magnetic stimulation (rTMS), could be useful in the treatment of alcohol use disorders.
Evidence-based umbrella review of 162 peripheral biomarkers for major mental disorders
Authors: Carvalho André F. , Solmi Marco , Sanches Marcos , Machado Myrela O. , Stubbs Brendon , Ajnakina Olesya , Sherman Chelsea , Sun Yue Ran , Liu Celina S. , Brunoni Andre R. , Pigato Giorgio , Fernandes Brisa S. , Bortolato Beatrice , Husain Muhammad I. , Dragioti Elena , Firth Joseph , Cosco Theodore D. , Maes Michael , Berk Michael , Lanctôt Krista L. , Vieta Eduard , Pizzagalli Diego A. , Smith Lee , Fusar-Poli Paolo , Kurdyak Paul A. , Fornaro Michele , Rehm Jürgen , Herrmann Nathan
Published: May 2020

The literature on non-genetic peripheral biomarkers for major mental disorders is broad, with conflicting results. An umbrella review of meta-analyses of non-genetic peripheral biomarkers for Alzheimer’s disease, autism spectrum disorder, bipolar disorder (BD), major depressive disorder, and schizophrenia, including first-episode psychosis. We included meta-analyses that compared alterations in peripheral biomarkers between participants with mental disorders to controls (i.e., between-group meta-analyses) and that assessed biomarkers after treatment (i.e., within-group meta-analyses). Evidence for association was hierarchically graded using a priori defined criteria against several biases. The Assessment of Multiple Systematic Reviews (AMSTAR) instrument was used to investigate study quality. 1161 references were screened. 110 met inclusion criteria, relating to 359 meta-analytic estimates and 733,316 measurements, on 162 different biomarkers. Only two estimates met a priori defined criteria for convincing evidence (elevated awakening cortisol levels in euthymic BD participants relative to controls and decreased pyridoxal levels in participants with schizophrenia relative to controls). Of 42 estimates which met criteria for highly suggestive evidence only five biomarker aberrations occurred in more than one disorder. Only 15 meta-analyses had a power >0.8 to detect a small effect size, and most (81.9%) meta-analyses had high heterogeneity. Although some associations met criteria for either convincing or highly suggestive evidence, overall the vast literature of peripheral biomarkers for major mental disorders is affected by bias and is underpowered. No convincing evidence supported the existence of a trans-diagnostic biomarker. Adequately powered and methodologically sound future large collaborative studies are warranted.
Rapamycin increases the incidence of neuropsychiatric illness in kidney transplant patients through the suppression of neural stem cells
Authors: Kim Yangsik , Lee Jung Sun , Joo Yeon Ho
Published: May 2020

Rapamycin inhibits protein translation in cells, including neural stem cells (NSCs), by suppressing the mechanistic target of rapamycin (mTOR). This drug has been widely used together with calcineurin inhibitors in transplantation patients to prevent graft rejection. Previous studies have reported an association between mTOR and depression, but few investigations of this have occurred in transplant recipients. We have here tested the psychiatric effects of rapamycin in mice. The animals treated with rapamycin showed decreased locomotion and sugar consumption. In these rapamycin-treated mice also, the granule cells in the dentate gyrus (DG), which actively differentiate and proliferate from NSC, showed decreases in both excitatory and inhibitory synaptic transmission. Furthermore, the SOX2/NeuN ratio in the DG was decreased in mice treated with rapamycin. We further show that kidney transplantation patients who are receiving rapamycin have more psychiatric disorder such as adjustment disorder. Clinical attention is thus needed when administering rapamycin to transplant recipients due to its behavioral effects and its impact on NSC.
Aerobic exercise impacts the anterior cingulate cortex in adolescents with subthreshold mood syndromes: a randomized controlled trial study
Authors: Lin Kangguang , Stubbs Brendon , Zou Wenjin , Zheng Wenjing , Lu Weicong , Gao Yanling , Chen Kun , Wang Shengli , Liu Jie , Huang Yanxiong , Guan Lijie , Wong Mabel Ngai Kiu , Wang Runhua , Lam Bess Yin-Hung , Xu Guiyun
Published: May 2020

Aerobic exercise is effective in alleviating mood symptoms while the mechanism is poorly understood. There are limited clinical trials that investigated the effect of exercise on the anterior cingulate cortex (ACC), a key brain region involved in mood regulations, in adolescents with subthreshold mood syndromes. This randomized controlled trial (RCT) of aerobic exercise was undertaken in a middle school in Guangzhou, China. Participants were adolescents aged 12–14 with subthreshold mood syndromes including depressive and manic symptoms and were randomly assigned to an aerobic exercise intervention or a psychoeducation control group. Participants in the exercise group received moderate-intensity exercise intervention, consisting of 30 mins running, 4 days per week for 3 months. The primary outcome in this study was structural changes in the ACC from baseline to post intervention. The trial was registered with ClinicalTrial.gov (NCT03300778). Of 56 participants who met the criteria for subthreshold mood syndromes, 39 (41.03% males) had complete MRI data, with 20 and 19 subjects in the exercise and control group, respectively. At baseline, demographic information (e.g., age and sex), clinical symptoms, and the gray matter volume and cortical thickness of ACC were matched between the two groups. After 12 weeks of treatment, participants in the exercise group displayed increased gray matter volume of the left rostral ACC (F1,30 = 5.73, p = 0.02) and increased cortical thickness of the right rostral ACC (F1,30 = 7.83, p = 0.01) when compared with the control group. No significant differences were found for caudal ACC cortical thickness and gray matter volume. Our data demonstrate that 12-week, moderate-intensity aerobic exercise can induce structural changes in the rostral ACC in adolescents with subthreshold mood syndromes.
Inhibition of the NLRP3-inflammasome prevents cognitive deficits in experimental autoimmune encephalomyelitis mice via the alteration of astrocyte phenotype
Authors: Hou Baohua , Zhang Yahui , Liang Peiyu , He Yuan , Peng Biwen , Liu Wanhong , Han Song , Yin Jun , He Xiaohua
Published: May 2020

Multiple sclerosis (MS) is a chronic disease that is characterized by demyelination and axonal damage in the central nervous system. Cognitive deficits are recognized as one of the features of MS, and these deficits affect the patients’ quality of life. Increasing evidence from experimental autoimmune encephalomyelitis (EAE), the animal model of MS, has suggested that EAE mice exhibit hippocampal impairment and cognitive deficits. However, the underlying mechanisms are still unclear. The NLRP3 inflammasome is a key contributor to neuroinflammation and is involved in the development of MS and EAE. Activation of the NLRP3 inflammasome in microglia is fundamental for subsequent inflammatory events. Activated microglia can convert astrocytes to the neurotoxic A1 phenotype in a variety of neurological diseases. However, it remains unknown whether the NLRP3 inflammasome contributes to cognitive deficits and astrocyte phenotype alteration in EAE. In this study, we demonstrated that severe memory deficits occurred in the late phase of EAE, and cognitive deficits were ameliorated by treatment with MCC950, an inhibitor of the NLRP3 inflammasome. In addition, MCC950 alleviated hippocampal pathology and synapse loss. Astrocytes from EAE mice were converted to the neurotoxic A1 phenotype, and this conversion was prevented by MCC950 treatment. IL-18, which is the downstream of NLRP3 inflammasome, was sufficient to induce the conversion of astrocytes to the A1 phenotype through the NF-κB pathway. IL-18 induced A1 type reactive astrocytes impaired hippocampal neurons through the release of complement component 3 (C3). Altogether, our present data suggest that the NLRP3 inflammasome plays an important role in cognitive deficits in EAE, possibly via the alteration of astrocyte phenotypes. Our study provides a novel therapeutic strategy for hippocampal impairment in EAE and MS.
Bim, Puma and Noxa upregulation by Naftopidil sensitizes ovarian cancer to the BH3-mimetic ABT-737 and the MEK inhibitor Trametinib
Authors: Florent Romane , Weiswald Louis-Bastien , Lambert Bernard , Brotin Emilie , Abeilard Edwige , Louis Marie-Hélène , Babin Guillaume , Poulain Laurent , N’Diaye Monique
Published: May 2020

Ovarian cancer represents the first cause of mortality from gynecologic malignancies due to frequent chemoresistance occurrence. Increasing the [BH3-only Bim, Puma, Noxa proapoptotic]/[Bcl-xL, Mcl-1 antiapoptotic] proteins ratio was proven to efficiently kill ovarian carcinoma cells and development of new molecules to imbalance Bcl-2 member equilibrium are strongly required. Drug repurposing constitutes an innovative approach to rapidly develop therapeutic strategies through exploitation of established drugs already approved for the treatment of noncancerous diseases. This strategy allowed a renewed interest for Naftopidil, an α1-adrenergic receptor antagonist commercialized in Japan for benign prostatic hyperplasia. Naftopidil was reported to decrease the incidence of prostate cancer and its derivative was described to increase BH3-only protein expression in some cancer models. Based on these arguments, we evaluated the effects of Naftopidil on ovarian carcinoma and showed that Naftopidil reduced cell growth and increased the expression of the BH3-only proteins Bim, Puma and Noxa. This effect was independent of α1-adrenergic receptors blocking and involved ATF4 or JNK pathway depending on cellular context. Finally, Naftopidil-induced BH3-only members sensitized our models to ABT-737 and Trametinib treatments, in vitro as well as ex vivo, in patient-derived organoid models.
Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies
Authors: Yi Chunyan , Sun Xiaoyu , Ye Jing , Ding Longfei , Liu Meiqin , Yang Zhuo , Lu Xiao , Zhang Yaguang , Ma Liyang , Gu Wangpeng , Qu Aidong , Xu Jianqing , Shi Zhengli , Ling Zhiyang , Sun Bing
Published: May 2020

Coronavirus disease 2019 (COVID-19), caused by the novel human coronavirus SARS-CoV-2, is currently a major threat to public health worldwide. The viral spike protein binds the host receptor angiotensin-converting enzyme 2 (ACE2) via the receptor-binding domain (RBD), and thus is believed to be a major target to block viral entry. Both SARS-CoV-2 and SARS-CoV share this mechanism. Here we functionally analyzed the key amino acid residues located within receptor binding motif of RBD that may interact with human ACE2 and available neutralizing antibodies. The in vivo experiments showed that immunization with either the SARS-CoV RBD or SARS-CoV-2 RBD was able to induce strong clade-specific neutralizing antibodies in mice; however, the cross-neutralizing activity was much weaker, indicating that there are distinct antigenic features in the RBDs of the two viruses. This finding was confirmed with the available neutralizing monoclonal antibodies against SARS-CoV or SARS-CoV-2. It is worth noting that a newly developed SARS-CoV-2 human antibody, HA001, was able to neutralize SARS-CoV-2, but failed to recognize SARS-CoV. Moreover, the potential epitope residues of HA001 were identified as A475 and F486 in the SARS-CoV-2 RBD, representing new binding sites for neutralizing antibodies. Overall, our study has revealed the presence of different key epitopes between SARS-CoV and SARS-CoV-2, which indicates the necessity to develop new prophylactic vaccine and antibody drugs for specific control of the COVID-19 pandemic although the available agents obtained from the SARS-CoV study are unneglectable.
AI for social good: unlocking the opportunity for positive impact
Authors: Tomašev Nenad , Cornebise Julien , Hutter Frank , Mohamed Shakir , Picciariello Angela , Connelly Bec , Belgrave Danielle C. M. , Ezer Daphne , Haert Fanny Cachat van der , Mugisha Frank , Abila Gerald , Arai Hiromi , Almiraat Hisham , Proskurnia Julia , Snyder Kyle , Otake-Matsuura Mihoko , Othman Mustafa , Glasmachers Tobias , Wever Wilfried de , Teh Yee Whye , Khan Mohammad Emtiyaz , Winne Ruben De , Schaul Tom , Clopath Claudia
Published: May 2020

Advances in machine learning (ML) and artificial intelligence (AI) present an opportunity to build better tools and solutions to help address some of the world’s most pressing challenges, and deliver positive social impact in accordance with the priorities outlined in the United Nations’ 17 Sustainable Development Goals (SDGs). The AI for Social Good (AI4SG) movement aims to establish interdisciplinary partnerships centred around AI applications towards SDGs. We provide a set of guidelines for establishing successful long-term collaborations between AI researchers and application-domain experts, relate them to existing AI4SG projects and identify key opportunities for future AI applications targeted towards social good.
mRNA display with library of even-distribution reveals cellular interactors of influenza virus NS1
Authors: Du Yushen , Hultquist Judd F. , Zhou Quan , Olson Anders , Tseng Yenwen , Zhang Tian-hao , Hong Mengying , Tang Kejun , Chen Liubo , Meng Xiangzhi , McGregor Michael J. , Dai Lei , Gong Danyang , Martin-Sancho Laura , Chanda Sumit , Li Xinming , Bensenger Steve , Krogan Nevan J. , Sun Ren
Published: May 2020

A comprehensive examination of protein-protein interactions (PPIs) is fundamental for the understanding of cellular machineries. However, limitations in current methodologies often prevent the detection of PPIs with low abundance proteins. To overcome this challenge, we develop a mRNA display with library of even-distribution (md-LED) method that facilitates the detection of low abundance binders with high specificity and sensitivity. As a proof-of-principle, we apply md-LED to IAV NS1 protein. Complementary to AP-MS, md-LED enables us to validate previously described PPIs as well as to identify novel NS1 interactors. We show that interacting with FASN allows NS1 to directly regulate the synthesis of cellular fatty acids. We also use md-LED to identify a mutant of NS1, D92Y, results in a loss of interaction with CPSF1. The use of high-throughput sequencing as the readout for md-LED enables sensitive quantification of interactions, ultimately enabling massively parallel experimentation for the investigation of PPIs.
Structural and biochemical characterization of the exopolysaccharide deacetylase Agd3 required for Aspergillus fumigatus biofilm formation
Authors: Bamford Natalie C. , Le Mauff François , Van Loon Jaime C. , Ostapska Hanna , Snarr Brendan D. , Zhang Yongzhen , Kitova Elena N. , Klassen John S. , Codée Jeroen D. C. , Sheppard Donald C. , Howell P. Lynne
Published: May 2020

The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Deletion of a gene encoding a putative deacetylase, Agd3, leads to defects in GAG deacetylation, biofilm formation, and virulence. Here, we show that Agd3 deacetylates GAG in a metal-dependent manner, and is the founding member of carbohydrate esterase family CE18. The active site is formed by four catalytic motifs that are essential for activity. The structure of Agd3 includes an elongated substrate-binding cleft formed by a carbohydrate binding module (CBM) that is the founding member of CBM family 87. Agd3 homologues are encoded in previously unidentified putative bacterial exopolysaccharide biosynthetic operons and in other fungal genomes.