bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of Active Tuberculosis in Lung Cancer Patients Receiving Immune Checkpoint Inhibitors
Authors: Fujita Kohei , Yamamoto Yuki , Kanai Osamu , Okamura Misato , Hashimoto Masayuki , Nakatani Koichi , Sawai Satoru , Mio Tadashi 
Published: April 2020

AbstractAlthough it ameliorates lung cancer, immunotherapy with immune checkpoint inhibitors (ICIs) presents complications of infectious diseases, including tuberculosis. Incidence of tuberculosis during immunotherapy remains unclear. We found that 1.7% of patients developed active tuberculosis during immunotherapy at our institution. In patients with a positive interferon-gamma release assay status before ICI therapy, physicians should pay close attention to developing tuberculosis.
Non-Abelian U -duality for membranes
Authors: Sakatani Yuho , Uehara Shozo 
Published: April 2020

Abstract
The $T$-duality of string theory can be extended to the Poisson–Lie $T$-duality when the target space has a generalized isometry group given by a Drinfel’d double. In M-theory, $T$-duality is understood as a subgroup of $U$-duality, but the non-Abelian extension of $U$-duality is still a mystery. In this paper we study membrane theory on a curved background with a generalized isometry group given by the $\mathcal E_n$ algebra. This provides a natural setup to study non-Abelian $U$-duality because the $\mathcal E_n$ algebra has been proposed as a $U$-duality extension of the Drinfel’d double. We show that the standard treatment of Abelian $U$-duality can be extended to the non-Abelian setup. However, a famous issue in Abelian $U$-duality still exists in the non-Abelian extension.
Sex Differences in Verbal Memory Predict Functioning Through Negative Symptoms in Early Psychosis
Authors: Buck Gabriella , Lavigne Katie M , Makowski Carolina , Joober Ridha , Malla Ashok , Lepage Martin 
Published: April 2020

AbstractVerbal memory (VM) is one of the most affected cognitive domains in first-episode psychosis (FEP) and is a robust predictor of functioning. Given that healthy females demonstrate superior VM relative to males and that female patients show less-severe illness courses than male patients, this study examined whether normative sex differences in VM extend to FEP and influence functioning. Four hundred and thirty-five patients (299 males, 136 females) with affective or nonaffective psychosis were recruited from a catchment-based specialized FEP intervention service and 138 nonclinical controls (96 males, 42 females) were recruited from the same community. One of the two neurocognitive batteries comprising six cognitive domains (VM, visual memory, working memory, attention, executive function, processing speed) were administered at baseline. In patients, positive and negative symptoms were evaluated at baseline and functioning was assessed at 1-year follow-up. Patients were more impaired than controls on all cognitive domains, but only VM showed sex differences (both patient and control males performed worse than females), and these results were consistent across batteries. In patients, better baseline VM in females was related to better functioning after 1 year, mediated through fewer baseline negative symptoms. Supplemental analyses revealed these results were not driven by affective psychosis nor by age and parental education. Thus, normative sex differences in VM are preserved in FEP and mediate functioning at 1-year follow-up via negative symptoms. This study highlights the importance of investigating sex effects for understanding VM deficits in early psychosis and suggests that sex may be a disease-modifying variable with important treatment implications.
Multiple Network Dysconnectivity in Adolescents with Psychotic Experiences: A Longitudinal Population-Based Study
Authors: O’Neill Aisling , Carey Eleanor , Dooley Niamh , Healy Colm , Coughlan Helen , Kelly Clare , Frodl Thomas , O’Hanlon Erik , Cannon Mary 
Published: April 2020

AbstractAbnormal functional connectivity (FC, the temporal synchronization of activation across distinct brain regions) of the default mode (DMN), salience (SN), central executive (CEN), and motor (MN) networks is well established in psychosis. However, little is known about FC in individuals, particularly adolescents, reporting subthreshold psychotic experiences (PE) and their trajectory over time. Thus, the aim of this study was to investigate the FC of these networks in adolescents with PE. In this population-based case-control study, 24 adolescents (mean age = 13.58) meeting the criteria for PE were drawn from a sample of 211 young people recruited and scanned for a neuroimaging study, with a follow-up scan 2 years later (n = 18, mean age = 15.78) and compared to matched controls drawn from the same sample. We compared FC of DMN, SN, CEN, and MN regions between PE and controls using whole-brain FC analyses. At both timepoints, the PE group displayed significant hypoconnectivity compared to controls. At baseline, FC in the PE group was decreased between MN and DMN regions. At follow-up, dysconnectivity in the PE group was more widespread. Over time, controls displayed greater FC changes than the PE group, with FC generally increasing between MN, DMN, and SN regions. Adolescents with PE exhibit hypoconnectivity across several functional networks also found to be hypoconnected in established psychosis. Our findings highlight the potential for studies of adolescents reporting PE to reveal early neural correlates of psychosis and support further investigation of the role of the MN in PE and psychotic disorders.
An International Perspective on Definitions and Terminology Used to Describe Serious Reportable Patient Safety Incidents: A Systematic Review
Authors: Hegarty Josephine , Flaherty Sarah Jane , Saab Mohamad M. , Goodwin John , Walshe Nuala , Wills Teresa , McCarthy Vera J.C. , Murphy Siobhan , Cutliffe Alana , Meehan Elaine , Landers Ciara , Lehane Elaine , Lane Aoife , Landers Margaret , Kilty Caroline , Madden Deirdre , Tumelty Mary , Naughton Corina 
Published: April 2020

Objectives
Patients are unintentionally, yet frequently, harmed in situations that are deemed preventable. Incident reporting systems help prevent harm, yet there is considerable variability in how patient safety incidents are reported. This may lead to inconsistent or unnecessary patterns of incident reporting and failures to identify serious patient safety incidents. This systematic review aims to describe international approaches in relation to defining serious reportable patient safety incidents.

Methods
Multiple electronic and gray literature databases were searched for articles published between 2009 and 2019. Empirical studies, reviews, national reports, and policies were included. A narrative synthesis was conducted because of study heterogeneity.

Results
A total of 50 articles were included. There was wide variation in the terminology used to represent serious reportable patient safety incidents. Several countries defined a specific subset of incidents, which are considered sufficiently serious, yet preventable if appropriate safety measures are taken. Terms such as “never events,” “serious reportable events,” or “always review and report” were used. The following dimensions were identified to define a serious reportable patient safety incident: (1) incidents being largely preventable; (2) having the potential for significant learning; (3) causing serious harm or have the potential to cause serious harm; (4) being identifiable, measurable, and feasible for inclusion in an incident reporting system; and (5) running the risk of recurrence.

Conclusions
Variations in terminology and reporting systems between countries might contribute to missed opportunities for learning. International standardized definitions and blame-free reporting systems would enable comparison and international learning to enhance patient safety.
Three-dimensional motion perception: comparing speed and speed change discrimination for looming stimuli
Authors: Lee Abigail R. I. , Ales Justin M. , Harris Julie M. 
Published: April 2020

AbstractJudging the speed of objects moving in three dimensions is important in our everyday lives, because we interact with objects in a three-dimensional world. However, speed perception has been seldom studied for motion in depth, particularly when using monocular cues such as looming. Here, we compared speed discrimination, and speed change discrimination, for looming stimuli, to better understand what visual information is used for these tasks. For the speed discrimination task, we manipulated the distance and duration information available, to investigate if participants were specifically using speed information. For speed change discrimination, total distance and duration were held constant, hence they could not be used to successfully perform that task. We found speed change discrimination thresholds were consistently higher than those for speed discrimination. Evidence suggested that participants used a variety of cues to complete the speed discrimination task, not always solely relying on speed. Further, our data suggested that participants may switch between cues on a trial to trial basis. We conclude that speed change discrimination for looming is more difficult than speed discrimination, and that naїve participants may not always exclusively use speed for speed discrimination.
Synaptic RTP801 Contributes to Motor Learning Dysfunction in Huntington’s Disease
Authors: Martín-Flores Núria , Pérez-Sisqués Leticia , Creus-Muncunill Jordi , Masana Mercè , Ginés Sílvia , Alberch Jordi , Pérez-Navarro Esther , Malagelada Cristina 
Published: April 2020

ABSTRACTRTP801/REDD1 is a stress responsive protein that mediates mutant huntingtin (mhtt) toxicity in cellular models and is up regulated in Huntington’s disease (HD) patients’ putamen. Here, we investigated whether RTP801 is involved in motor impairment in HD by affecting striatal synaptic plasticity.Ectopic mhtt was over expressed in cultured rat primary neurons. The protein levels of RTP801 were assessed in homogenates and crude synaptic fractions from human postmortem HD brains and mouse models of HD. Striatal RTP801 expression was knocked down with adeno-associated viral particles containing a shRNA in the R6/1 mouse model of HD and motor learning was then tested.Ectopic mhtt elevated RTP801 in synapses of cultured neurons. RTP801 was also up regulated in striatal synapses from HD patients and mouse models. Knocking down RTP801 in the R6/1 mouse striatum prevented motor learning impairment. RTP801 silencing normalized the Ser473 Akt hyperphosphorylation by downregulating Rictor and it induced synaptic elevation of calcium permeable GluA1 subunit and TrkB receptor levels, suggesting an enhancement in synaptic plasticity.These results indicate that mhtt-induced RTP801 mediates motor dysfunction in a HD murine model, revealing a potential role in the human disease. These findings open a new therapeutic framework focused on the RTP801/Akt/mTOR axis.
Island songbirds as windows into evolution in small populations
Authors: Leroy Thibault , Rousselle Marjolaine , Tilak Marie-Ka , Caizergues Aude E. , Scornavacca Céline , Recuerda María , Fuchs Jérôme , Illera Juan Carlos , De Swardt Dawie H. , Blanco Guillermo , Thébaud Christophe , Milá Borja , Nabholz Benoit 
Published: April 2020

SummaryDue to their limited ranges and inherent isolation, island species have long been recognized as crucial systems for tackling a range of evolutionary questions, including in the early study of speciation [1,2]. Such species have been less studied in the understanding of the evolutionary forces driving DNA sequence evolution. Island species usually have lower census population sizes (N) than continental species and, supposedly, lower effective population sizes (Ne). Given that both the rates of change caused by genetic drift and by selection are dependent uponNe, island species are theoretically expected to exhibit (i) lower genetic diversity, (ii) less effective natural selection against slightly deleterious mutations [3,4], and (iii) a lower rate of adaptive evolution [5–8, see also Note S1]. Here, we have used a large set of newly sequenced and published whole genome sequences of Passerida bird species or subspecies (14 insular and 11 continental) to test these predictions. We empirically confirm that island species exhibit lower census size andNe, supporting the hypothesis that the smaller area available on islands constrains the upper bound ofNe. In the insular species, we find significantly lower nucleotide diversity in coding regions, higher ratios of non-synonymous to synonymous polymorphisms, and lower adaptive substitution rates. Our results provide robust evidence that the lowerNeexperienced by island species has affected both the ability of natural selection to efficiently remove weakly deleterious mutations and also the adaptive potential of island species, therefore providing considerable empirical support for the nearly neutral theory. We discuss the implications for both evolutionary and conservation biology.
Neonicotinoids disrupt memory, circadian behaviour and sleep
Authors: Tasman Kiah , Hidalgo Sergio , Buhl Edgar , Rands Sean A. , Hodge James J.L. 
Published: April 2020

SummaryGlobally, neonicotinoids are still the most used insecticides, despite their well-documented sub-lethal effects on beneficial insects1. Neonicotinoids are agonists at the nicotinic acetylcholine receptors, the main mediator of synaptic transmission in the insect brain2–5, making them highly potent neurotoxins and insecticides6,7. Memory, circadian rhythmicity and sleep are essential for efficient foraging in many pollinating insects, and involve nicotinic acetylcholine receptor signalling2,4,8–10. The effect of field-relevant concentrations of European Union-banned neonicotinoids: imidacloprid, clothianidin and thiamethoxam, as well as the currently unbanned thiacloprid were tested onDrosophilamemory, circadian rhythms and sleep. Field-relevant concentrations of imidacloprid, clothianidin and thiamethoxam disrupted learning, behavioural rhythmicity and sleep whilst thiacloprid exposure only affected sleep. Exposure to imidacloprid and clothianidin directly affected neurophysiology, preventing the day/night remodelling and accumulation of pigment dispersing factor neuropeptide in the dorsal terminals of clock neurons. Knockdown of the neonicotinoid susceptible Dα1 and Dβ2 nicotinic acetylcholine receptor subunits in the mushroom bodies or clock neurons recapitulated the neonicotinoid like deficits in memory or circadian/sleep behaviour demonstrating that neonicotinoid effects are likely mediated in the mushroom body and clock circuitry. Disruption to learning, circadian rhythmicity and sleep are likely to have far-reaching detrimental effects on beneficial insects in the field.
Neural responses to happy, fearful and angry faces of varying identities in 5- and 7-month-old infants
Authors: Bayet Laurie , Perdue Katherine L. , Behrendt Hannah F. , Richards John E. , Westerlund Alissa , Cataldo Julia K. , Nelson Charles A. 
Published: April 2020

AbstractFacial emotion processing is an important social skill that develops throughout infancy and early childhood. Here we investigate the neural underpinnings of the ability to process facial emotion across changes in facial identity in cross-sectional groups of 5- and 7-month-old infants. We simultaneously measured neural metabolic, behavioral, and autonomic responses to happy, fearful, and angry faces of different female models using functional near-infrared spectroscopy (fNIRS), eye-tracking, and heart rate measures. We observed significant neural activation to these facial emotions in a distributed set of frontal and temporal brain regions, and longer looking to the mouth region of angry faces compared to happy and fearful faces. No differences in looking behavior or neural activations were observed between 5- and 7-month-olds, although several exploratory, age-independent associations between neural activations and looking behavior were noted. Overall, these findings suggest more developmental stability than previously thought in responses to emotional facial expressions of varying identities between 5- and 7-months of age.
More than just front or back: Parietal-striatal-thalamic circuits predict consciousness level
Authors: Afrasiabi Mohsen , Redinbaugh Michelle J. , Phillips Jessica M. , Kambi Niranjan A. , Mohanta Sounak , Raz Aeyal , Haun Andrew M. , Saalmann Yuri B. 
Published: April 2020

AbstractMajor theories of consciousness disagree on the key neural substrates. In Global Neuronal Workspace Theory and Higher-order Theories, consciousness depends on frontal cortex, whereas Integrated Information Theory and Recurrent Processing Theory highlight posterior contributions. Most theories omit subcortical influences. To test these theories, we performed simultaneous frontal, parietal, striatal and thalamic recordings from awake, sleeping and anesthetized macaques, further manipulating consciousness with deep-brain thalamic stimulation. Information theoretic measures and machine learning approaches suggested parietal cortex, striatum and thalamus contribute more to consciousness level than frontal cortex. While these findings provide greater support for Integrated Information Theory than the others, the theory does not incorporate subcortical structures such as the striatum. We therefore propose that thalamo-striatal circuits have a cause-effect structure to generate integrated information.One Sentence SummaryParietal, but not frontal, circuits incorporating striatum and thalamus predict consciousness.
A chemical strategy to control protein networks in vivo
Authors: Ziegler Michael J. , Yserentant Klaus , Middel Volker , Dunsing Valentin , Gralak Antoni J. , Pakari Kaisa , Bargstedt Jörn , Kern Christoph , Chiantia Salvatore , Strähle Uwe , Herten Dirk-Peter , Wombacher Richard 
Published: April 2020

ABSTRACTDirect control of protein interaction by chemically induced protein proximity (CIPP) holds great potential for cell- and synthetic biology as well as therapeutic applications. However, toxicity, low cell-permeability and lack of orthogonality currently limit the use of available chemical inducers of proximity (CIP). We present ‘Mandi’, a novel CIP and demonstrate its applicability in cell culture systems as well as living organisms for protein translocation, protein network shuttling and manipulation of endogenous proteins.
Deciphering the scopolamine challenge rat model by preclinical functional MRI
Authors: Somogyi Gergely , Hlatky Dávid , Spisák Tamás , Spisák Zsófia , Nyitrai Gabriella , Czurkó András 
Published: April 2020

ABSTRACTDuring preclinical drug testing, the systemic administration of scopolamine (SCO), a cholinergic antagonist, is widely used. However, it suffers important limitations, like non-specific behavioural effects partly due to its peripheral side-effects. Therefore, neuroimaging measures would enhance its translational value. To this end, in Wistar rats, we measured whisker-stimulation induced functional MRI activation after SCO, peripherally acting butylscopolamine (BSCO), or saline administration in a cross-over design. Besides the commonly used gradient-echo echo-planar imaging (GE EPI), we also used an arterial spin labeling method in isoflurane anesthesia. With the GE EPI measurement, SCO decreased the evoked BOLD response in the barrel cortex (BC), while BSCO increased it in the anterior cingulate cortex. In a second experiment, we used GE EPI and spin-echo (SE) EPI sequences in a combined (isoflurane + i.p. dexmedetomidine) anesthesia to account for anesthesia-effects. Here, we also examined the effect of donepezil. In the combined anesthesia, with the GE EPI, SCO decreased the activation in the BC and the inferior colliculus (IC). BSCO reduced the response merely in the IC. Our results revealed that SCO attenuated the evoked BOLD activation in the BC as a probable central effect in both experiments. The likely peripheral vascular actions of SCO with the given fMRI sequences depended on the type of anesthesia or its dose.
β-arrestin mediates communication between plasma membrane and intracellular GPCRs to regulate signaling
Authors: DeNies Maxwell S. , Smrcka Alan , Schnell Santiago , Liu Allen P. 
Published: April 2020

AbstractIt has become increasingly apparent that G protein-coupled receptor (GPCR) localization is a master regulator of cell signaling. However, the molecular mechanisms involved in this process are not well understood. To date, observations of intracellular GPCR activation can be organized into two categories: a dependence on OCT3 cationic channel-permeable ligands or the necessity of endocytic trafficking. Using CXC chemokine receptor 4 (CXCR4) as a model, we identified a third mechanism of intracellular GPCR signaling. We show that independent of membrane permeable ligands and endocytosis, upon stimulation, plasma membrane and internal pools of CXCR4 are post-translationally modified and collectively regulateEGR1transcription. We found that β-arrestin-1 (arrestin 2) is necessary to mediate communication between plasma membrane and internal pools of CXCR4. Notably, these observations may explain that while CXCR4 overexpression is highly correlated with cancer metastasis and mortality, plasma membrane localization is not. Together these data support a model were a small initial pool of plasma membrane-localized GPCRs are capable of activating internal receptor-dependent signaling events.
Ephaptic coupling in white matter fibre bundles modulates axonal transmission delays
Authors: Schmidt Helmut , Hahn Gerald , Deco Gustavo , Knösche Thomas R. 
Published: April 2020

AbstractAxonal connections are widely regarded as faithful transmitters of neuronal signals with fixed delays. The reasoning behind this is that extra-cellular potentials caused by spikes travelling along axons are too small to have an effect on other axons. Here we devise a computational framework that allows us to study the effect of extracellular potentials generated by spike volleys in axonal fibre bundles on axonal transmission delays. We demonstrate that, although the extracellular potentials generated by single spikes are of the order of microvolts, the collective extracellular potential generated by spike volleys can reach several millivolts. As a consequence, the resulting depolarisation of the axonal membranes increases the velocity of spikes, and therefore reduces axonal delays between brain areas. Driving a neural mass model with such spike volleys, we further demonstrate that only ephaptic coupling can explain the reduction of stimulus latencies with increased stimulus intensities, as observed in many psychological experiments.Author summaryAxonal fibre bundles that connect distant cortical areas contain millions of densely packed axons. When synchronous spike volleys travel through such fibre bundles, the extracellular potential within the bundles is perturbed. We use computer simulations to examine the magnitude and shape of this perturbation, and demonstrate that it is sufficiently strong to affect axonal transmission speeds. Since most spikes within a spike volley are positioned in an area where the extracellular potential is negative (relative to a distant reference), the resulting depolarisation of the axonal membranes accelerates the spike volley on average. This finding is in contrast to previous studies of ephaptic coupling effects between axons, where ephaptic coupling was found to slow down spike propagation. Our finding has consequences for information transmission and synchronisation between cortical areas.