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24,283,779	Decision analysis in the clinical neurosciences: a systematic review of the literature.	Clinical decision analysis can be a useful scientific tool for individual patient management, for planning of clinical research and for reaching consensus about clinical problems. We systematically reviewed the decision analytic studies in the clinical neurosciences that were published between 1975 and July 1994. All studies were assessed on aspects of clinical applicability: presence of case and context description, completeness of the analysed strategies from a clinical point of view, extendibility of the analyses to different patient profiles, and up-to-date-ness. Fifty-nine decision analyses of twenty-eight different clinical problems were identified. Twenty-eight analyses were based on the theory of subjective expected utility, twelve on cost-effectiveness analysis. Four studies used ROC analysis, and fifteen were risk-, or risk-benefit analyses. At least six studies could have been improved by more elaborately disclosing the context of the clinical problem that was addressed. In eleven studies, the effect of different, yet plausible assumptions was not explored, and in eighteen studies the reader was not informed how to extend the results of the analysis to patients with (slightly) different clinical characterisitics. All studies had, by nature, the potential to promote insight into the clinical problem and focus the discussion on clinically important aspects, and gave clinically useful advice. We conclude that clinical decision analysis, as an explicit, quantitative approach to uncertainty in decision making in the clinical neurosciences will fulfill a growing need in the near future.	European journal of neurology	1,995	12
33,941,233	A maximum flow-based network approach for identification of stable noncoding biomarkers associated with the multigenic neurological condition, autism.	Machine learning approaches for predicting disease risk from high-dimensional whole genome sequence (WGS) data often result in unstable models that can be difficult to interpret, limiting the identification of putative sets of biomarkers. Here, we design and validate a graph-based methodology based on maximum flow, which leverages the presence of linkage disequilibrium (LD) to identify stable sets of variants associated with complex multigenic disorders.	BioData mining	2,021	5
32,860,876	Uncovering memory-related gene expression in contextual fear conditioning using ribosome profiling.	Contextual fear conditioning (CFC) in rodents is the most widely used behavioural paradigm in neuroscience research to elucidate the neurobiological mechanisms underlying learning and memory. It is based on the pairing of an aversive unconditioned stimulus (US; e.g. mild footshock) with a neutral conditioned stimulus (CS; e.g. context of the test chamber) in order to acquire associative long-term memory (LTM), which persists for days and even months. Using genome-wide analysis, several studies have generated lists of genes modulated in response to CFC in an attempt to identify the "memory genes", which orchestrate memory formation. Yet, most studies use naïve animals as a baseline for assessing gene-expression changes, while only few studies have examined the effect of the US alone, without pairing to context, using genome-wide analysis of gene-expression. Herein, using the ribosome profiling methodology, we show that in male mice an immediate shock, which does not lead to LTM formation, elicits pervasive translational and transcriptional changes in the expression of Immediate Early Genes (IEGs) in dorsal hippocampus (such as Fos and Arc), a fact which has been disregarded by the majority of CFC studies. By removing the effect of the immediate shock, we identify and validate a new set of genes, which are translationally and transcriptionally responsive to the association of context-to-footshock in CFC, and thus constitute salient "memory genes".	Progress in neurobiology	2,021	2
26,255,155	Neuropeptide Y family receptors Y1 and Y2 from sea lamprey, Petromyzon marinus.	The vertebrate gene family for neuropeptide Y (NPY) receptors expanded by duplication of the chromosome carrying the ancestral Y1-Y2-Y5 gene triplet. After loss of some duplicates, the ancestral jawed vertebrate had seven receptor subtypes forming the Y1 (including Y1, Y4, Y6, Y8), Y2 (including Y2, Y7) and Y5 (only Y5) subfamilies. Lampreys are considered to have experienced the same chromosome duplications as gnathostomes and should also be expected to have multiple receptor genes. However, previously only a Y4-like and a Y5 receptor have been cloned and characterized. Here we report the cloning and characterization of two additional receptors from the sea lamprey Petromyzon marinus. Sequence phylogeny alone could not with certainty assign their identity, but based on synteny comparisons of P. marinus and the Arctic lamprey, Lethenteron camtschaticum, with jawed vertebrates, the two receptors most likely are Y1 and Y2. Both receptors were expressed in human HEK293 cells and inositol phosphate assays were performed to determine the response to the three native lamprey peptides NPY, PYY and PMY. The three peptides have similar potencies in the nanomolar range for Y1. No obvious response to the three peptides was detected for Y2. Synteny analysis supports identification of the previously cloned receptor as Y4. No additional NPY receptor genes could be identified in the presently available lamprey genome assemblies. Thus, four NPY-family receptors have been identified in lampreys, orthologs of the same subtypes as in humans (Y1, Y2, Y4 and Y5), whereas many other vertebrate lineages have retained additional ancestral subtypes.	General and comparative endocrinology	2,015	10
32,814,022	The Persistence of Privilege for a Healthy Retina.	A minor haplotype of chromosome 10q26 accounts for much of the genetic risk of age-related macular degeneration (AMD). In this issue of Immunity, Beguier et al. demonstrate that carriers of the 10q26 AMD-risk haplotype overexpress the peptidase HTRA1, which in turns results in mononuclear phagocyte persistence in an immune privileged site and pathogenic inflammation.	Immunity	2,020	8
31,434,803	Transcription factor EB overexpression prevents neurodegeneration in experimental synucleinopathies.	The synucleinopathies Parkinson's disease (PD) and Multiple system atrophy (MSA) - characterized by α-synuclein intracytoplasmic inclusions into, respectively, neurons and oligodendrocytes - are associated with impairment of the autophagy-lysosomal pathways (ALP). Increased expression of the master regulator of ALP, transcription factor EB (TFEB), is hypothesized to promote the clearance of WT α-synuclein and survival of dopaminergic neurons. Here, we explore the efficacy of targeted TFEB overexpression either in neurons or oligodendrocytes to reduce the pathological burden of α-synuclein in a PD rat model and a MSA mouse model. While TFEB neuronal expression was sufficient to prevent neurodegeneration in the PD model, we show that only TFEB oligodendroglial overexpression leads to neuroprotective effects in the MSA model. These beneficial effects were associated with a decreased accumulation of α-synuclein into oligodendrocytes through recovery of the ALP machinery. Our study demonstrates that the cell type where α-synuclein aggregates dictates the target of TFEB overexpression in order to be protective, paving the way for adapted therapies.	JCI insight	2,019	8
32,700,055	The extended autonomic system, dyshomeostasis, and COVID-19.	The pandemic viral illness COVID-19 is especially life-threatening in the elderly and in those with any of a variety of chronic medical conditions. This essay explores the possibility that the heightened risk may involve activation of the "extended autonomic system" (EAS). Traditionally, the autonomic nervous system has been viewed as consisting of the sympathetic nervous system, the parasympathetic nervous system, and the enteric nervous system. Over the past century, however, neuroendocrine and neuroimmune systems have come to the fore, justifying expansion of the meaning of "autonomic." Additional facets include the sympathetic adrenergic system, for which adrenaline is the key effector; the hypothalamic-pituitary-adrenocortical axis; arginine vasopressin (synonymous with anti-diuretic hormone); the renin-angiotensin-aldosterone system, with angiotensin II and aldosterone the main effectors; and cholinergic anti-inflammatory and sympathetic inflammasomal pathways. A hierarchical brain network-the "central autonomic network"-regulates these systems; embedded within it are components of the Chrousos/Gold "stress system." Acute, coordinated alterations in homeostatic settings (allostasis) can be crucial for surviving stressors such as traumatic hemorrhage, asphyxiation, and sepsis, which throughout human evolution have threatened homeostasis; however, intense or long-term EAS activation may cause harm. While required for appropriate responses in emergencies, EAS activation in the setting of chronically decreased homeostatic efficiencies (dyshomeostasis) may reduce thresholds for induction of destabilizing, lethal vicious cycles. Testable hypotheses derived from these concepts are that biomarkers of EAS activation correlate with clinical and pathophysiologic data and predict outcome in COVID-19 and that treatments targeting specific abnormalities identified in individual patients may be beneficial.	Clinical autonomic research : official journal of the Clinical Autonomic Research Society	2,020	8
32,937,277	In silico characterization of adipokinetic hormone receptor and screening for pesticide candidates against stick insect, Carausius morosus.	Adipokinetic hormone (AKH) is an insect neuropeptide that plays crucial roles in a variety of physiological functions such as regulation of heartbeat frequency, blood hemolymph trehalose levels, and protein synthesis. It exerts its functions through binding to its cognate G protein-coupled receptor (GPCR), named adipokinetic hormone receptor (AKHR). The aim of this study is to characterize AKHR of stick insect, Carausius morosus, which becomes an agricultural and forest pest during its outbreaks, and to screen pesticide candidates that would act through inhibition of AKHR. To this aim, the sequence of the receptor and its ligand were obtained from previously published transcriptome data and homology modeling, molecular docking, and molecular dynamics (MD) simulations were combined to find the ligand-binding pocket of AKHR. As a result, crucial residues in ligand binding were identified. These residues were located at the 6th and 7th transmembrane (TM) domains and the 2nd extracellular loop (ECL) of AKHR model. In order to propose pesticide candidates, virtual screening was performed, and candidate ligands were obtained. Considering the binding energies and the stability of the interaction between the ligand and the receptor, four hit compounds were selected. In conclusion, this study revealed a possible ligand-binding pocket of AKHR and proposed some high-affinity small-molecules to block its function, which would further facilitate pesticide design studies against the same receptor of various pests.	Journal of molecular graphics & modelling	2,020	12
33,007,292	Seizure burden fluctuates with the female reproductive cycle in a mouse model of chronic temporal lobe epilepsy.	Women with catamenial epilepsy often experience increased seizure burden near the time of ovulation (periovulatory) or menstruation (perimenstrual). To date, a rodent model of chronic temporal lobe epilepsy (TLE) that exhibits similar endogenous fluctuations in seizures has not been identified. Here, we investigated whether seizure burden changes with the estrous cycle in the intrahippocampal kainic acid (IHKA) mouse model of TLE. Adult female IHKA mice and saline-injected controls were implanted with EEG electrodes in the ipsilateral hippocampus. At one and two months post-injection, 24/7 video-EEG recordings were collected and estrous cycle stage was assessed daily. Seizures were detected using a custom convolutional neural network machine learning process. Seizure burden was compared within each mouse between diestrus and combined proestrus and estrus days (pro/estrus) at two months post-injection. IHKA mice showed higher seizure burden on pro/estrus compared with diestrus, characterized by increased time in seizures and longer seizure duration. When all IHKA mice were included, no group differences were observed in seizure frequency or EEG power. However, increased baseline seizure burden on diestrus was correlated with larger cycle-associated differences, and when analyses were restricted to mice that showed the severe epilepsy typical of the IHKA model, increased seizure frequency on pro/estrus was also revealed. Controls showed no differences in EEG parameters with cycle stage. These results suggest that the stages of proestrus and estrus are associated with higher seizure burden in IHKA mice. The IHKA model may thus recapitulate at least some aspects of reproductive cycle-associated seizure clustering.	Experimental neurology	2,020	12
32,822,613	Two Brain Pathways Initiate Distinct Forward Walking Programs in Drosophila.	An animal at rest or engaged in stationary behaviors can instantaneously initiate goal-directed walking. How descending brain inputs trigger rapid transitions from a non-walking state to an appropriate walking state is unclear. Here, we identify two neuronal types, P9 and BPN, in the Drosophila brain that, upon activation, initiate and maintain two distinct coordinated walking patterns. P9 drives forward walking with ipsilateral turning, receives inputs from central courtship-promoting neurons and visual projection neurons, and is necessary for a male to pursue a female during courtship. In contrast, BPN drives straight, forward walking and is not required during courtship. BPN is instead recruited during and required for fast, straight, forward walking bouts. Thus, this study reveals separate brain pathways for object-directed walking and fast, straight, forward walking, providing insight into how the brain initiates context-appropriate walking programs.	Neuron	2,020	11
30,054,671	Correction to: α-Synuclein's Uniquely Long Amphipathic Helix Enhances its Membrane Binding and Remodeling Capacity.	The original version of the article unfortunately contained error in author group; two authors were not submitted and published in the original version. Also the funding information is erroneously omitted.	The Journal of membrane biology	2,018	12
32,992,634	Musculoskeletal Ultrasound in Monitoring Clinical Response to Treatment in Acute Symptomatic Psoriatic Dactylitis: Results from a Multicentre Prospective Observational Study.	This observational and prospective study evaluated the clinical correlations of sonographic lesions in consecutive psoriatic arthritis (PsA) dactylitis cases. Eighty-three dactylitic digits were evaluated clinically and sonographically before treatment and at one-month (T1) and three-month (T3) follow-up. Clinical evaluation included the Leeds Dactylitis Index-basic (LDI-b) score and the visual analogue scales for pain (VAS-p) and functional impairment (VAS-FI). High-frequency ultrasound with grey scale (GS) and power Doppler (PD) assessed flexor tenosynovitis (FT), soft tissue oedema (STO), extensor tendon paratenonitis, and joint synovitis. There was a statistically significant correlation between the clinical parameters (VAS-p, VAS-FI, and LDI-b) and FT and STO at T1 and T3. We found statistically significant improvement in FT and STO for the cases with clinically meaningful treatment responses (	Journal of clinical medicine	2,020	9
26,035,784	Neuroscience: teleporting mind into body and space.	Brain imaging and a novel 'body-swop' illusion reveals distinct parietal-premotor and parietal-hippocampal networks involved in constructing a sense of body-ownership and self-location, with the posterior cingulate mediating between them.	Current biology : CB	2,015	6
29,733,675	Implications of Attachment Theory and Neuroscience for the Psychotherapeutic Treatment of Obesity and Overeating.	This article examines psychological sequelae underlying dysregulated eating in the overweight and obese patient and proposes a psychotherapy approach informed by classical and modern attachment theory, developmental trauma, and neuroscience to address these structural deficits.	American journal of psychotherapy	2,018	7
30,689,922	Prognostic Characterization of Higher-Grade Meningiomas: A Histopathological Score to Predict Progression and Outcome.	Higher-grade meningiomas (WHO grade II and III) represent a diagnostic and prognostic challenge. We assessed the pathological and molecular characteristics of 94 higher-grade meningiomas (85 grade II, 9 grade III) to identify novel prognostic parameters. Higher mitotic count (p = 0.018), diffuse (≥50%) prominent nucleoli (p < 0.001), and sheeting (p < 0.001) were associated with recurrence. Lower SSTR2a-positive cells median rate (p = 0.048) and TERT promoter mutations (p = 0.014) were associated with recurrence and patient death, respectively; further analyses did not identify other outcome associations. Presence of Ki67 hot spots was associated with a shorter progression-free survival (PFS), independently of WHO grade at multivariate analysis (HR = 3.35, p = 0.008). Necrosis was related to a poorer overall survival (OS) at univariate (focal: HR = 4.55, p = 0.041 and diffuse: HR = 7.38, p = 0.020) and Kaplan-Meier analyses. A prognostic score was designed based on previous results: Presence of diffuse (≥50%) prominent nucleoli (0/1 point), diffuse (≥50%) sheeting (0/1 point), focal (<50%) or diffuse (≥50%) necrosis (0/1/2 points), and Ki67 hot spots (0/1 point). A total score ≥4 predicted poorer PFS and OS by Kaplan-Meier (PFS: 1.7 vs 6.4 years, p < 0.001 and OS: 5.2 vs 10.8 years, p = 0.001) and multivariate (PFS: HR = 5.98, p < 0.001 and OS: HR = 2.99, p = 0.048) analyses. These results were confirmed in an independent series of 58 grade II meningiomas (PFS: HR = 7.22, p = 0.002 and OS: HR = 9.69, p = 0.003). These associations and the integrated score could complement WHO grading.	Journal of neuropathology and experimental neurology	2,019	3
32,356,130	Is There an Association Between Diet, Physical Activity and Depressive Symptoms in the Perinatal Period? An Analysis of the UPBEAT Cohort of Obese Pregnant Women.	Depression is a common morbidity of the perinatal period (during pregnancy and up to one year postpartum). There is evidence for an association between diet and physical activity, and depression in the non-pregnant population but this association has been relatively less explored during the perinatal period; particularly poorly understood is the relationship between specific dietary components and depression. The aim of this study was to explore the association between glycaemic load, saturated fat intake and physical activity and depressive symptoms in a high-risk population of obese pregnant women.	Maternal and child health journal	2,020	12
28,009,269	Shaping Early Networks to Rule Mature Circuits: Little MiRs Go a Long Way.	Normative cortical processing depends on precise interactions between excitatory and inhibitory neurons. In this issue of Neuron, Lippi et al. (2016) identify miR-101 as a master regulator coordinating molecular programs during development that ultimately impact the activity of mature networks.	Neuron	2,016	12
33,017,964	Inter-subject correlations during natural viewing: A filter-bank approach.	A central question in neuroscience is how the brain processes real-world sensory input. For decades most classical studies focus on carefully controlled artificial stimuli. More recently researchers started to investigate brain activity under more realistic conditions. The main challenge in this setting is the analysis of the complex signals obtained with modern neuroimaging methods in response to natural stimuli. Inter-subject correlations (ISCs) have become a popular paradigm to study brain activation under natural stimulation. The underlying assumption of this analysis is that features of natural stimuli that are perceived and processed by all subjects exposed to the same stimulus result in similar activation patterns across subjects. Higher degrees of realism in stimulation, for instance audiovisual stimulation is more realistic than auditory stimulation, is usually associated with higher ISC values. We can confirm these findings in experiments in which we present a movie stimulus with varying degrees of realism. Extending previous findings we highlight the importance of artifact removal when evaluating ISCs and show that the impact of realism in natural stimulation on ISCs is frequency-dependent. A major challenge associated with this type of analysis is that it can be difficult to attribute the correlation strength to the physiological process of interest. In this study, we demonstrate that ISCs of neural activation as measured by electroencephalogram (EEG) recordings are influenced significantly by non-neural artifacts such as occulograms. Our findings highlight the potential of inter-subject correlations as a biomarker for immersion: If more realistic stimuli consistently lead to higher inter-subject correlations, then inter-subject correlations can serve as a quantitative marker for how engaging audiovisual stimuli are perceived.Clinical relevance- Future research will evaluate if correlation levels among subjects, who are exposed to natural stimuli are affected by neurological diseases such as Alzheimers, Parkinsons, and Schizophrenia among others.	Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference	2,020	7
33,814,164	[Use of virtual reality in eating disorders].	Virtual reality is a new technology that can be used to model an environment with which an individual can interact using all five senses. It is notably used in psychiatry for anxiety disorders and addictions, and its use in eating disorders has been growing in recent years. Indeed, virtual reality offers interesting advantages, such as its ability to personalize any environment, which is also more secure and controllable. Recent studies show promising results in the understanding, evaluation, and therapeutic management of eating disorders. The use of avatars in anorexia nervosa allows for a correct assessment of the perceptual (body image distortion) and cognitive-affective (body dissatisfaction) components of the body image disorder in a similar way to conventional methods, but also for a better understanding of them. Moreover, avatars allow the development of innovative therapeutic protocols and are thus used in the context of exposure therapy. The new body swapping protocol, based on a multisensory illusion, offers particularly promising results in the reduction of body image disorder. For bulimia nervosa and binge eating disorder, virtual reality has made it possible to better characterize the triggering mechanisms of binge eating episodes through studies that have observed different responses to food-related environments and stimuli. At the therapeutic level, virtual reality cue exposure therapy has the most empirical support. Its aim is to reduce or eliminate the anxiety and craving felt by a patient in response to exposure to food or other food-related cues by preventing the patient from consuming food, and results show clear reductions in anxiety, craving and binge eating episodes. While all these results seem to indicate a bright future for virtual reality in eating disorders, further studies are needed to validate the positive impact of its use, but also its limitations. Notably, cyber sickness could alter the smooth running of virtual reality therapy sessions by causing nausea and disorientation. Moreover, it is important to verify that a therapeutic protocol does not lose its effectiveness when it is transposed into virtual reality. However, virtual reality seems to be a therapeutic tool that is better accepted by patients, and even better by adolescents, which is very interesting for eating disorders since adolescents are the most affected. Virtual reality could therefore help motivate patients to pursue treatment and reduce the dropout rate while offering good therapeutic results. Thus, studies conducted in recent years have shown that virtual reality is a promising tool in the understanding, assessment and treatment of eating disorders, and future research should confirm this, particularly in the adolescent population.	L'Encephale	2,021	6
32,515,514	Dysphagia, dysarthria and aphasia following a first acute ischaemic stroke: incidence and associated factors.	Dysphagia, dysarthria and aphasia are common symptoms following acute stroke; however, limited data are available from recent prospective clinical trials. The aim of this study was to determine the incidence and associated factors of dysphagia, dysarthria and aphasia following a first acute ischaemic stroke in patients admitted to a comprehensive stroke center.	European journal of neurology	2,020	10
33,098,150	MKK7 deficiency in mature neurons impairs parental behavior in mice.	c-Jun N-terminal kinases (JNKs) are constitutively activated in mammalian brains and are indispensable for their development and neural functions. MKK7 is an upstream activator of all JNKs. However, whether the common JNK signaling pathway regulates the brain's control of social behavior remains unclear. Here, we show that female mice in which Mkk7 is deleted specifically in mature neurons (Mkk7	Genes to cells : devoted to molecular & cellular mechanisms	2,021	1
29,367,629	Lighting-from-above prior in biological motion perception.	The visual system is able to recognize body motion from impoverished stimuli. This requires combining stimulus information with visual priors. We present a new visual illusion showing that one of these priors is the assumption that bodies are typically illuminated from above. A change of illumination direction from above to below flips the perceived locomotion direction of a biological motion stimulus. Control experiments show that the underlying mechanism is different from shape-from-shading and directly combines information about body motion with a lighting-from-above prior. We further show that the illusion is critically dependent on the intrinsic luminance gradients of the most mobile parts of the moving body. We present a neural model with physiologically plausible mechanisms that accounts for the illusion and shows how the illumination prior might be encoded within the visual pathway. Our experiments demonstrate, for the first time, a direct influence of illumination priors in high-level motion vision.	Scientific reports	2,018	1
12,845,420	Reinstatement of punishment-suppressed opioid self-administration in rats: an alternative model of relapse to drug abuse.	Animal models of relapse to drug abuse typically assess the ability of various manipulations to reinstate responding that has ceased due to non-reinforcement (extinction). However, there is a lack of information concerning the reinstatement of responding that has ceased for reasons other than extinction.	Psychopharmacology	2,003	7
28,569,411	Regional and district peer effects in obesity: A UK panel data analysis.	Most research concerning the causes of obesity has focused on macroeconomic trends or individual-level determinants relating to socioeconomic status. There is now growing interest in the psychosocial determinants of obesity. Little research has been conducted into wide-scale peer effects and so the aim of this study was to determine whether regional and district peer effects determine individual-level obesity in the UK. Data from the British Household Panel Survey (for the years 2004 and 2006) were used to model individual-level BMI and probability of obesity as a function of regional and district BMI, controlling for a variety of other variables. Instrumental variable techniques were used to investigate simultaneity bias. We found no statistically significant regional peer effect in the UK. For men, we found that a 1 point increase in average district BMI increased individual BMI by 0.640 and probability of being obese by 1.9% points; for women, BMI increased by 0.230 and probability of being obese by 1.6% points. Men appear to be more susceptible to these effects than women. Peer effects at the district level may have played a significant role in the rise of obesity in the UK. Further research must aim to disentangle the two routes by which these processes are theorised to function.	Health & social care in the community	2,018	1
32,563,935	7, 8-Dihydroxy-4-methylcoumarin reverses depression model-induced depression-like behaviors and alteration of dendritic spines in the mood circuits.	Major depressive disorder (MDD) is a common mental disorder characterized by a persistent feeling of sadness, slow thought, impaired focus and loss of interest but the underlying mechanisms are largely unknown. Dendritic spines play an important role in the formation and maintenance of emotional circuits in the brain. Abnormalities in this process can lead to psychiatric diseases. 7,8-Dihydroxy-4-methylcoumarin (Dhmc), a precursor in the synthesis of derivatives of 4-methyl coumarin, plays an important role in protecting the nervous system from developing diseases and its most distinctive feature is safety. The aim of this study was to investigate whether Dhmc alleviates chronic unpredictable mild stress (CUMS)-induced depression-like behaviors and reverses CUMS-induced alterations in dendritic spines of principal neurons in brain areas of the emotional circuits including the hippocampus, medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and basolateral amygdala (BLA) in male rats. Our results showed that CUMS-induced depression-like behaviors were accompanied by a decrease in spine density in pyramidal neurons of both the hippocampal CA3 area and the mPFC, and an increase in spine density in both the neurons of BLA and the medium spiny neurons (MSNs) of the NAc, as well as a decrease in the levels of the AMPA receptor subunit GluA1 and Kalirin-7 in the hippocampus compared with the control group. Intraperitoneal injection (i.p.) of Dhmc to the CUMS-exposed rats ameliorated CUMS-induced depression-like behaviors and reversed CUMS-mediated alterations in spine density and the levels of both GluA1 and Kalirin-7. Our results show an important role of Dhmc in reversing CUMS-induced depression-like behaviors and CUMS-mediated alterations in spine density.	Psychoneuroendocrinology	2,020	9
30,625,365	Human and rodent temporal lobe epilepsy is characterized by changes in O-GlcNAc homeostasis that can be reversed to dampen epileptiform activity.	Temporal Lobe Epilepsy (TLE) is frequently associated with changes in protein composition and post-translational modifications (PTM) that exacerbate the disorder. O-linked-β-N-acetyl glucosamine (O-GlcNAc) is a PTM occurring at serine/threonine residues that is derived from and closely associated with metabolic substrates. The enzymes O-GlcNActransferase (OGT) and O-GlcNAcase (OGA) mediate the addition and removal, respectively, of the O-GlcNAc modification. The goal of this study was to characterize OGT/OGA and protein O-GlcNAcylation in the epileptic hippocampus and to determine and whether direct manipulation of these proteins and PTM's alter epileptiform activity. We observed reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue. Inhibiting OGA with Thiamet-G elevated protein O-GlcNAcylation, and decreased both seizure duration and epileptic spike events, suggesting that OGA may be a therapeutic target for seizure control. These findings suggest that loss of O-GlcNAc homeostasis in the kainate model and in human TLE can be reversed via targeting of O-GlcNAc related pathways.	Neurobiology of disease	2,019	4
33,075,423	Aging and non-native speech perception: A phonetic training study.	Cognitive decline is evident in the elderly and it affects speech perception and foreign language learning. A listen-and-repeat training with a challenging speech sound contrast was earlier found to be effective in young monolingual adults and even in advanced L2 university students at the attentive and pre-attentive levels. This study investigates foreign language speech perception in the elderly with the same protocol used with the young adults. Training effects were measured with attentive behavioural measures (N = 9) and with electroencephalography measuring the pre-attentive mismatch negativity (MMN) response (N = 10). Training was effective in identification, but not in discrimination and there were no changes in the MMN. The most attention demanding perceptual functions which benefit from experience-based linguistic knowledge were facilitated through training, whereas pre-attentive processing was unaffected. The elderly would probably benefit from different training types compared to younger adults.	Neuroscience letters	2,021	1
32,289,451	Quantitative MRI and laser ablation-inductively coupled plasma-mass spectrometry imaging of iron in the frontal cortex of healthy controls and Alzheimer's disease patients.	Accumulation of iron within the cortex of Alzheimer's disease (AD) patients has been reported by numerous MRI studies using iron-sensitive methods. Validation of iron-sensitive MRI is important for the interpretation of in vivo findings. In this study, the relation between the spatial iron distribution and T	NeuroImage	2,020	7
32,415,550	CSF p-tau/Aβ	To know whether mild cognitive impairment (MCI) patients will develop Alzheimer's disease (AD) dementia in very short time or remain stable is of crucial importance, also considering new experimental drugs usually tested within very short time frames. Here we combined cerebrospinal fluid (CSF) AD biomarkers and a neurodegeneration marker such as brain FDG-PET to define an objective algorithm, suitable not only to reliably detect MCI converters to AD dementia but also to predict timing of conversion.	European journal of nuclear medicine and molecular imaging	2,020	12
29,745,426	Human neural stem cells dispersed in artificial ECM form cerebral organoids when grafted in vivo.	Human neural stem cells (hNSC) derived from induced pluripotent stem cells can be differentiated into neurons that could be used for transplantation to repair brain injury. In this study we dispersed such hNSC in a three-dimensional artificial extracellular matrix (aECM) and compared their differentiation in vitro and following grafting into the sensorimotor cortex (SMC) of postnatal day (P)14 rat pups lesioned by localised injection of endothelin-1 at P12. After 10-43 days of in vitro differentiation, a few cells remained as PAX6	Journal of anatomy	2,018	8
32,185,490	Cannabis use influence on peripheral brain-derived neurotrophic factor levels in antipsychotic-naïve first-episode psychosis.	The objective of this study is to determine whether cannabis influences BDNF levels in patients with psychosis (FEP) and healthy volunteers (HV) to help understand the role of BDNF in psychosis. We assessed the association between BDNF and cannabis in a cohort of FEP antipsychotic-naïve patients and HV, whilst controlling for other potential confounding factors. 70 FEP drug-naive patients and 57 HV were recruited. A sociodemographic variable collection, structured clinical interview, weight and height measurement, substance use determination, and blood collection to determine BDNF levels by ELISA analysis were done. In FEP patients, cannabis use was associated with BDNF levels (high cannabis use was associated with lower BDNF levels). Moreover, cannabis use was statistically significantly associated with age (high use of cannabis was associated with younger age). In HV, no relationship between cannabis use and BDNF levels was observed. Otherwise, cannabis use was significantly associated with tobacco use, so that high cannabis users were also high tobacco users. This study showed a different association between cannabis use and BDNF levels in FEP patients compared with HV, particularly, with high doses of cannabis. These findings may help understand the deleterious effects of cannabis in some vulnerable individuals, as well as discrepancies in the literature.	European archives of psychiatry and clinical neuroscience	2,020	10
30,127,427	Mononuclear phagocytes locally specify and adapt their phenotype in a multiple sclerosis model.	Mononuclear phagocytes are key regulators of both tissue damage and repair in neuroinflammatory conditions such as multiple sclerosis. To examine divergent phagocyte phenotypes in the inflamed CNS, we introduce an in vivo imaging approach that allows us to temporally and spatially resolve the evolution of phagocyte polarization in a murine model of multiple sclerosis. We show that the initial proinflammatory polarization of phagocytes is established after spinal cord entry and critically depends on the compartment they enter. Guided by signals from the CNS environment, individual phagocytes then switch their phenotype as lesions move from expansion to resolution. Our study thus provides a real-time analysis of the temporospatial determinants and regulatory principles of phagocyte specification in the inflamed CNS.	Nature neuroscience	2,018	9
21,889,538	Automated detection and analysis of neuronal persistent activity.	Cortical neurons receive individual as well as synchronized synaptic events. The latter may drive a neuron into an active state where a persistently depolarized membrane potential lasts for several seconds. Visual inspection and manual detection of these persistent events is labor-intensive. We built a set of scripts in MATLAB with the goal of having a core software package for the systematic and objective detection of persistent neural activity out of large time-series data. This analysis software includes multiple steps, from a pre-processing stage, event detection, user-interactive detection reviewing, and filtering/graphing. Analysis scripts and brief usage information are freely available upon request.	Journal of neuroscience methods	2,011	10
32,877,644	Wistar rats and C57BL/6 mice differ in their motivation to seek social interaction versus food in the Social versus Food Preference Test.	Here we characterized the Social versus Food Preference Test, a behavioral paradigm designed to investigate the competition between the choice to seek social interaction versus the choice to seek food. We assessed how this competition was modulated by internal cues (social isolation, food deprivation), external cues (stimulus salience), sex (males, females), age (adolescents, adults), and rodent model (Wistar rats, C57BL/6 mice). We found that changes in stimulus preference in response to the internal and external cue manipulations were similar across cohorts. Specifically, social over food preference scores were reduced by food deprivation and social familiarly in Wistar rats and C57BL/6 mice of both sexes. Interestingly, the degree of food deprivation-induced changes in stimulus investigation patterns were greater in adolescents compared to adults in Wistar rats and C57BL/6 mice. Strikingly, baseline stimulus preference and investigation times varied greatly between rodent models: across manipulations, Wistar rats were generally more social-preferring and C57BL/6 mice were generally more food-preferring. Adolescent Wistar rats spent more time investigating the social and food stimuli than adult Wistar rats, while adolescent and adult C57BL/6 mice investigated the stimuli a similar amount. Social isolation did not alter behavior in the Social versus Food Preference Test. Together, our results indicate that the Social versus Food Preference Test is a flexible behavioral paradigm suitable for future interrogations of the peripheral and central systems that can coordinate the expression of stimulus preference related to multiple motivated behaviors.	Physiology & behavior	2,020	12
27,220,833	An elderly-onset limb girdle muscular dystrophy type 1B (LGMD1B) with pseudo-hypertrophy of paraspinal muscles.	Mutations in LMNA, encoding A-type lamins, lead to diverse disorders, collectively called "laminopathies," which affect the striated muscle, cardiac muscle, adipose tissue, skin, peripheral nerve, and premature aging. We describe a patient with limb-girdle muscular dystrophy type 1B (LGMD1B) carrying a heterozygous p.Arg377His mutation in LMNA, in whom skeletal muscle symptom onset was at the age of 65 years. Her weakness started at the erector spinae muscles, which showed marked pseudo-hypertrophy even at the age of 72 years. Her first episode of syncope was at 44 years; however, aberrant cardiac conduction was not revealed until 60 years. The p.Arg377His mutation has been previously reported in several familial LMNA-associated myopathies, most of which showed muscle weakness before the 6th decade. This is the first report of pseudo-hypertrophy of paravertebral muscles in LMNA-associated myopathies. The pseudo-hypertrophy of paravertebral muscles and the elderly-onset of muscle weakness make this case unique and reportable.	Neuromuscular disorders : NMD	2,016	9
32,985,978	The dynamic interplay between ATP/ADP levels and autophagy sustain neuronal migration in vivo.	Cell migration is a dynamic process that entails extensive protein synthesis and recycling, structural remodeling, and considerable bioenergetic demand. Autophagy is one of the pathways that maintain cellular homeostasis. Time-lapse imaging of autophagosomes and ATP/ADP levels in migrating cells in the rostral migratory stream of mouse revealed that decreases in ATP levels force cells into the stationary phase and induce autophagy. Pharmacological or genetic impairments of autophagy in neuroblasts using either bafilomycin, inducible conditional mice, or CRISPR/Cas9 gene editing decreased cell migration due to the longer duration of the stationary phase. Autophagy is modulated in response to migration-promoting and inhibiting molecular cues and is required for the recycling of focal adhesions. Our results show that autophagy and energy consumption act in concert in migrating cells to dynamically regulate the pace and periodicity of the migratory and stationary phases to sustain neuronal migration.	eLife	2,020	9
31,331,628	The Projected Care Trajectory for Persons with Epilepsy.	Epilepsy is a complex neurologic disease that requires both medical management and self-management. People with epilepsy and their families complete many transitions throughout the health care system in managing this disease. This article reviews key transitions for people with epilepsy and discusses strategies for improving these transitions.	The Nursing clinics of North America	2,019	9
33,748,358	Data on the effects of COVID-19 pandemic on people's expectations about their future.	The worldwide spread of the COVID-19 pandemic has unpredictably changed the way people live, by influencing their behaviors and beliefs. This article presents the raw data that have been used to investigate how the pandemic affected people's beliefs and expectations about their future. A total of 3991 participants (18-85 years old) were recruited through an online survey using the Qualtrics platform. The data collection was carried out during the Italian lockdown, between April 1st and April 20th, 2020. This survey collected information about psychological and socioeconomic variables related to the COVID-19 emergency. Respondents filled out a battery of questionnaires that included five measures. Three of the measures were specifically developed by the authors: 1. Expected repercussions of COVID-19; 2. Forethought scale; and 3. Perceived financial resources. The two other measures were standardized questionnaires: the Zimbardo Time Perspective Inventory Short Version (ZTPI-short) and the Positive and Negative Affect Schedule (PANAS). Data from tailored measures on the COVID-19 pandemic reflect people's beliefs about the future, in terms of expectation about the pandemic's effect, estimation of the time needed for the pandemic to resolve, and estimation of how long people could endure the lockdown situation from a financial perspective. The ZTPI questionnaire was administered to measure people's differences in terms of Deviation from Balanced Time Perspective (DBTP). The PANAS questionnaire, instead, was administered to investigate people's differences in terms of emotional mood states. The provided dataset could be useful to other researchers, considering that the data were collected during the lockdown imposed on Italian citizens to face the unprecedented emergency due to the COVID-19 pandemic. Therefore, the collected data may help to understand how people coped with the pandemic, both from a psychological and socioeconomic perspective. Finally, this dataset can be included in the broad context of data, procedures, and experimental materials that have been used to expand our knowledge in the study of time perspective, beliefs, and emotions.	Data in brief	2,021	4
33,034,389	Involvement of circulating factors in the transmission of paternal experiences through the germline.	Environmental factors can change phenotypes in exposed individuals and offspring and involve the germline, likely via biological signals in the periphery that communicate with germ cells. Here, using a mouse model of paternal exposure to traumatic stress, we identify circulating factors involving peroxisome proliferator-activated receptor (PPAR) pathways in the effects of exposure to the germline. We show that exposure alters metabolic functions and pathways, particularly lipid-derived metabolites, in exposed fathers and their offspring. We collected data in a human cohort exposed to childhood trauma and observed similar metabolic alterations in circulation, suggesting conserved effects. Chronic injection of serum from trauma-exposed males into controls recapitulates metabolic phenotypes in the offspring. We identify lipid-activated nuclear receptors PPARs as potential mediators of the effects from father to offspring. Pharmacological PPAR activation in vivo reproduces metabolic dysfunctions in the offspring and grand-offspring of injected males and affects the sperm transcriptome in fathers and sons. In germ-like cells in vitro, both serum and PPAR agonist induce PPAR activation. Together, these results highlight the role of circulating factors as potential communication vectors between the periphery and the germline.	The EMBO journal	2,020	12
34,498,439	[Raising awareness for dementia risk reduction through a public health campaign: a pre-post study].	This study evaluates a public health campaign initiated by the Alzheimer Center Limburg of Maastricht University. The aim was to increase awareness of the influence of a healthy lifestyle on lowering the risk of dementia in community-dwelling inhabitants of the Province of Limburg (aged 40 - 75 years). The campaign used mass media and public events, supported by a campaign website and mobile application (MijnBreincoach app). An additional district-oriented approach was chosen in the municipalities of Roermond, Landgraaf and Brunssum, in which local stakeholders were involved in the design and execution of campaign-related events. Population-level difference in awareness before and after the campaign was assessed in two independent samples. No pre-post difference was observed in the level of awareness of dementia risk reduction. An additional analyses in the post-campaign sample revealed that the group that reported to have heard of the campaign, was more often aware of dementia risk reduction and reported higher motivation for behavioural change than the group that had not heard of the campaign. The district-oriented approach resulted in better recognition of campaign-material and the mobile application. With regard to the individual lifestyle factors, healthy diet and physical activity were identified more often post-campaign. Cognitive activity was identified most often at both pre- and post-assessment, but there was no increase in awareness after the campaign.	Tijdschrift voor gerontologie en geriatrie	2,021	6
33,344,697	Reproductive status impact on tau phosphorylation induced by chronic stress.	Sex and exposure to chronic stress have been identified as risk factors for developing Alzheimer's disease (AD). Although AD has been demonstrated to be more prevalent in females, sex is often overlooked in research studies, likely due to the complexity of the hormonal status. In female rats, the reproductive status can modulate the well-known increase in tau phosphorylation (pTau) caused by the exposure to acute physical and psychological stressors. To test the hypothesis that reproductive status can impact hippocampal pTau induced by chronic stress, cohorts of virgin, lactating (4-5 days pp), and post-maternal (1-month post-weaned) rats were subjected to a daily 30-min episode of restraint stress for 14 days and were sacrificed either 20 min or 24 h after their last stress/handling episode. Western blot analysis of two well-characterized AD-relevant pTau epitopes (AT8 and PHF-1) and upstream pTau mechanisms (e.g. GSK3β) analysis, showed that stressed post-maternal rats have increased pTau in comparison to stressed lactating rats 20 min after their last stress episode. Furthermore, an increase in pTau was also seen 24 h after the last stress episode in stressed post-maternal rats in comparison to their non-stressed controls in the detergent-soluble fraction. GSK3 analysis showed an increase in total levels of GSK3β in virgin rats and an increase of inactive levels of GSK3β in post-maternal rats, which suggests a different stress response in pTau after the rat has gone through the maternal experience. Interestingly, post-maternal rats also presented the more variability in their estrous cycles in response to stress. Besides no differences in pTau, non-stressed lactating rats showed an increase in inactive GSK3β 24 h after the last handling episode. Immunohistochemical detection of the PHF-1 epitope revealed increased pTau in the CA4/hilar subfield of the hippocampus of virgin and post-maternal rats exposed to chronic stress shortly after their last stress episode. Overall, lactating rats remained unresponsive to chronic restraint stress. These results suggest increased sensitivity of the virgin and post-maternal rats to hippocampal stress-induced pTau with chronic restraint stress compared to lactating rats. Because no differences were detected in response to stress by lactating rats and an exaggerated response was observed in post-maternal rats, current results support the hypothesis that lactation affects tau processing in the brain of the female.	Neurobiology of stress	2,020	11
33,300,551	Recalibrating the epigenetic clock: implications for assessing biological age in the human cortex.	Human DNA methylation data have been used to develop biomarkers of ageing, referred to as 'epigenetic clocks', which have been widely used to identify differences between chronological age and biological age in health and disease including neurodegeneration, dementia and other brain phenotypes. Existing DNA methylation clocks have been shown to be highly accurate in blood but are less precise when used in older samples or in tissue types not included in training the model, including brain. We aimed to develop a novel epigenetic clock that performs optimally in human cortex tissue and has the potential to identify phenotypes associated with biological ageing in the brain. We generated an extensive dataset of human cortex DNA methylation data spanning the life course (n = 1397, ages = 1 to 108 years). This dataset was split into 'training' and 'testing' samples (training: n = 1047; testing: n = 350). DNA methylation age estimators were derived using a transformed version of chronological age on DNA methylation at specific sites using elastic net regression, a supervised machine learning method. The cortical clock was subsequently validated in a novel independent human cortex dataset (n = 1221, ages = 41 to 104 years) and tested for specificity in a large whole blood dataset (n = 1175, ages = 28 to 98 years). We identified a set of 347 DNA methylation sites that, in combination, optimally predict age in the human cortex. The sum of DNA methylation levels at these sites weighted by their regression coefficients provide the cortical DNA methylation clock age estimate. The novel clock dramatically outperformed previously reported clocks in additional cortical datasets. Our findings suggest that previous associations between predicted DNA methylation age and neurodegenerative phenotypes might represent false positives resulting from clocks not robustly calibrated to the tissue being tested and for phenotypes that become manifest in older ages. The age distribution and tissue type of samples included in training datasets need to be considered when building and applying epigenetic clock algorithms to human epidemiological or disease cohorts.	Brain : a journal of neurology	2,020	12
32,999,299	A partial least squares analysis of functional status, disability, and quality of life after surgical decompression for degenerative cervical myelopathy.	Previous studies aimed at identifying predictors of clinical outcomes following surgical decompression for degenerative cervical myelopathy (DCM) are limited by multicollinearity among predictors, whereby the high degree of correlation between covariates precludes detection of potentially significant findings. We apply partial least squares (PLS), a data-driven approach, to model multi-dimensional variance and dissociate patient phenotypes associated with functional, disability, and quality of life (QOL) outcomes in DCM. This was a post-hoc analysis of DCM patients enrolled in the prospective, multi-center AOSpine CSM-NA/CSM-I studies. Baseline clinical covariates evaluated as predictors included demographic (e.g., age, sex), clinical presentation (e.g., signs and symptoms), and treatment (e.g., surgical approach) characteristics. Outcomes evaluated included change in functional status (∆mJOA), disability (∆NDI), and QOL (∆SF-36) at 2 years. PLS was used to derive latent variables (LVs) relating specific clinical covariates with specific outcomes. Statistical significance was estimated using bootstrapping. Four hundred and seventy-eight patients met eligibility criteria. PLS identified 3 significant LVs. LV1 indicated an association between presentation with hand muscle atrophy, treatment by an approach other than laminectomy alone, and greater improvement in physical health-related QOL outcomes (e.g., SF-36 Physical Component Summary). LV2 suggested the presence of comorbidities (respiratory, rheumatologic, psychological) was associated with lesser improvements in functional status post-operatively (i.e., mJOA score). Finally, LV3 reflected an association between more severe myelopathy presenting with gait impairment and poorer mental health-related QOL outcomes (e.g., SF-36 Mental Component Summary). Using PLS, this analysis uncovered several novel insights pertaining to patients undergoing surgical decompression for DCM that warrant further investigation: (1) comorbid status and frailty heavily impact functional outcome; (2) presentation with hand muscle atrophy is associated with better physical QOL outcomes; and (3) more severe myelopathy with gait impairment is associated with poorer mental QOL outcomes.	Scientific reports	2,020	9
32,927,256	Assessing future health care practitioners' knowledge and attitudes of musculoskeletal pain; development and measurement properties of a new questionnaire.	Healthcare practitioner beliefs influence patients' beliefs and health outcomes in musculoskeletal (MSK) pain. A validated questionnaire based on modern pain neuroscience assessing Knowledge and Attitudes of Pain (KNAP) was unavailable.	Musculoskeletal science & practice	2,020	12
32,583,940	Baseline sensorimotor GABA levels shape neuroplastic processes induced by motor learning in older adults.	Previous research in young adults has demonstrated that both motor learning and transcranial direct current stimulation (tDCS) trigger decreases in the levels of gamma-aminobutyric acid (GABA) in the sensorimotor cortex, and these decreases are linked to greater learning. Less is known about the role of GABA in motor learning in healthy older adults, a knowledge gap that is surprising given the established aging-related reductions in sensorimotor GABA. Here, we examined the effects of motor learning and subsequent tDCS on sensorimotor GABA levels and resting-state functional connectivity in the brains of healthy older participants. Thirty-six older men and women completed a motor sequence learning task before receiving anodal or sham tDCS to the sensorimotor cortex. GABA-edited magnetic resonance spectroscopy of the sensorimotor cortex and resting-state (RS) functional magnetic resonance imaging data were acquired before and after learning/stimulation. At the group level, neither learning nor anodal tDCS significantly modulated GABA levels or RS connectivity among task-relevant regions. However, changes in GABA levels from the baseline to post-learning session were significantly related to motor learning magnitude, age, and baseline GABA. Moreover, the change in functional connectivity between task-relevant regions, including bilateral motor cortices, was correlated with baseline GABA levels. These data collectively indicate that motor learning-related decreases in sensorimotor GABA levels and increases in functional connectivity are limited to those older adults with higher baseline GABA levels and who learn the most. Post-learning tDCS exerted no influence on GABA levels, functional connectivity or the relationships among these variables in older adults.	Human brain mapping	2,020	9
32,920,030	Cerebellar and prefrontal-cortical engagement during higher-order rule learning in older adulthood.	To date most aging research has focused on cortical systems and networks, ignoring the cerebellum which has been implicated in both cognitive and motor function. Critically, older adults (OA) show marked differences in cerebellar volume and functional networks, suggesting it may play a key role in the behavioral differences observed in advanced age. OA may be less able to recruit cerebellar resources due to network and structural differences. Here, 26 young adults (YA) and 25 OA performed a second-order learning task, known to activate the cerebellum in the fMRI environment. Behavioral results indicated that YA performed significantly better and learned more quickly compared to OA. Functional imaging detailed robust parietal and cerebellar activity during learning (compared to control) blocks within each group. OA showed increased activity (relative to YA) in the left inferior parietal lobe in response to instruction cues during learning (compared to control); whereas, YA showed increased activity (relative to OA) in the left anterior cingulate to feedback cues during learning, potentially explaining age-related performance differences. Visual interpretation of effect size maps showed more bilateral posterior cerebellar activation in OA compared to YA during learning blocks, but early learning showed widespread cerebellar activation in YA compared to OA. There were qualitatively large age-related differences in cerebellar recruitment in terms of effect sizes, yet no statistical difference. These findings serve to further elucidate age-related differences and similarities in cerebellar and cortical brain function and implicate the cerebellum and its networks as regions of interest in aging research.	Neuropsychologia	2,020	11
33,563,767	Bilateral mandibular block improves pain relief and morphine consumption in mandibular osteotomies: a prospective, randomized, double-blind, placebo-controlled clinical trial.	The sensory innervation of the lower jaw mainly depends on the third root of the trigeminal nerve, the mandibular nerve (V3). The aim of this single-center, prospective, randomized, double-blind, placebo-controlled study was to evaluate the effectiveness of bilateral V3 block for postoperative analgesia management in mandibular osteotomies.	Regional anesthesia and pain medicine	2,021	4
23,351,048	When order matters: last-come first-served effect in sequential arithmetic operations.	Cognitive psychologists have relied on dual-task interference experiments to understand the low-capacity and serial nature of conscious mental operations. Two widely studied paradigms, the Attentional Blink (AB) and the Psychological Refractory Period (PRP) have demonstrated a first-come first-served policy; processing a stimulus either impedes conscious access (AB) or postpones treatment (PRP) of a concurrent stimulus. Here we explored the transition from dual-task paradigms to multi-step human cognition. We studied the relative weight of individual addends in a sequential arithmetic task, where number notation (symbolic/non-symbolic) and presentation speed were independently manipulated. For slow presentation and symbolic notation, the decision relied almost equally on all addends, whereas for fast or non-symbolic notation, the decision relied almost exclusively on the last item reflecting a last-come first-served policy. We suggest that streams of stimuli may be chunked in events in which the last stimuli may override previous items from sensory buffers.	Journal of integrative neuroscience	2,012	12
31,185,943	Clinical relevance of alerts from a decision support system, PHARAO, for drug safety assessment in the older adults.	PHARAO is a decision support system developed to evaluate the risk for a set of either common or serious side-effects resulting from a combination of pharmacodynamic effects from a patient's medications. The objective of this study was to investigate the validity of the risk scores for the common side-effects generated by PHARAO in older patients.	BMC geriatrics	2,019	6
33,083,594	Screening for potential school shooters through the weight of evidence.	The challenge of automatically screening for potential school shooters involves several difficulties. In this paper, we present a simple and interpretable methodology for screening for potential school shooters through (1) the psychological textual signature of the shooter and (2) Jaynes approach for measuring the weight of evidence. We have tested our proposed approach on a dataset of texts written by shooters and non-shooters alike (N = 5047). Our major finding is that the methodology can successfully support the screening for potential shooters in interpretable way. The major implication for stakeholders is that there is great potential in developing screening systems for improving the safely of schools. However, developing such a system is a project that must be actualized within an integrated system of "command and control".	Heliyon	2,020	10
32,639,900	Humans sacrifice decision-making for action execution when a demanding control of movement is required.	A growing body of evidence suggests that decision-making and action execution are governed by partly overlapping operating principles. Especially, previous work proposed that a shared decision urgency/movement vigor signal, possibly computed in the basal ganglia, coordinates both deliberation and movement durations in a way that maximizes the reward rate. Recent data support one aspect of this hypothesis, indicating that the urgency level at which a decision is made influences the vigor of the movement produced to express this choice. Here we investigated whether, conversely, the motor context in which a movement is executed determines decision speed and accuracy. Twenty human subjects performed a probabilistic decision task in which perceptual choices were expressed by reaching movements toward targets whose size and distance from a starting position varied in distinct blocks of trials. We found strong evidence for an influence of the motor context on most of the subjects' decision policy, but contrary to the predictions of the "shared regulation" hypothesis, we observed that slow movements executed in the most demanding motor blocks in terms of accuracy were often preceded by faster and less accurate decisions compared with blocks of trials in which big targets allowed expression of choices with fast and inaccurate movements. These results suggest that decision-making and motor control are not regulated by one unique "invigoration" signal determining both decision urgency and action vigor, but more likely by independent, yet interacting, decision urgency and movement vigor signals.	Journal of neurophysiology	2,020	8
33,076,433	A Novel CCT5 Missense Variant Associated with Early Onset Motor Neuropathy.	Diseases associated with acquired or genetic defects in members of the chaperoning system (CS) are increasingly found and have been collectively termed chaperonopathies. Illustrative instances of genetic chaperonopathies involve the genes for chaperonins of Groups I (e.g., Heat shock protein 60,	International journal of molecular sciences	2,020	10
33,028,591	Preclinical Comparison of the Blood-brain barrier Permeability of Osimertinib with Other EGFR TKIs.	Osimertinib is a potent and selective EGFR tyrosine kinase inhibitor (EGFR-TKI) of both sensitizing and T790M resistance mutations. To treat metastatic brain disease, blood-brain barrier (BBB) permeability is considered desirable for increasing clinical efficacy.	Clinical cancer research : an official journal of the American Association for Cancer Research	2,021	1
33,017,586	A closer look at the role of insulin for the regulation of male reproductive function.	While insulin demonstrates to have a considerable influence on the reproductive system, there are various unanswered questions regarding its precise sites, mechanisms of action, and roles for the developing and functioning of the adult male reproductive system. Apart from its effects on glucose level, insulin has an important role in the reproductive system directly by binding on insulin and IGF receptors in the brain and testis. To date, however, the effect of insulin or its alterations on blood-testis-barrier, as an important regulator of normal spermatogenesis and fertility, has not yet been studied. This review aimed to focus on the experimental and clinical studies to describe mechanisms by which insulin affects the hypothalamic-pituitary-gonadal (HPG) axis, testicular cells, spermatozoa, and sexual behavior. Moreover, we discussed the mechanism and impact of insulin changes in type 1 (insulin deficiency along with persisted or even increased sensitivity) and 2 (insulin resistance along with increased insulin level at the early stages of disease) diabetes and obesity on the male reproductive tract.	General and comparative endocrinology	2,021	1
32,931,800	The role of cannabinoid 1 receptor in the nucleus accumbens on tramadol induced conditioning and reinstatement.	Previous investigations demonstrated that tramadol, as a painkiller, similar to morphine induces tolerance and dependence. Furthermore, the cannabinoid receptor 1 (CB1R) located in the nucleus accumbens (NAc) plays a critical role in morphine-induced conditioning. Therefore, the main objective of this study was to evaluate the role of NAc CB1R in tramadol induced conditioning and reinstatement.	Life sciences	2,020	11
25,139,923	Post-traumatic iridodialysis, crystalline dislocation and vitreous haemorrhage: how to manage.	A 66-year-old man, while taking care of his horse, sustained a blunt, non-penetrating injury to the right side of his face, which damaged his eye. On slit lamp examination, iris dialysis and crystalline dislocation in the vitreous chamber were observed. On presentation, his best correct visual acuity was hand motion. A 23 G vitrectomy and subsequently an iris reconstruction and a glued intraocular lens implant were performed. Visual acuity reached +0.1 logMAR 1 month after surgery and remained stable after 12 months' follow-up.	BMJ case reports	2,014	8
33,179,332	Cerebrospinal Fluid Levels of Kininogen-1 Indicate Early Cognitive Impairment in Parkinson's Disease.	Cognitive impairment is common in patients with PD. Core markers of Alzheimer's dementia have been related also to PD dementia, but no disease-specific signature to predict PD dementia exists to date.	Movement disorders : official journal of the Movement Disorder Society	2,020	11
31,314,848	Guillaume-Benjamin Duchenne: a miserable life dedicated to science.	Duchenne de Boulogne is known mainly by the disease eponymously named "Duchenne muscular dystrophy", or pseudohypertrophic muscular dystrophy, although some experts consider that the original description of this disease does not belong to him. Less well known are the facts related to the tragic death of his beloved wife shortly after the birth of his only child, the unjustifiable distance he was forced to keep from this son for more than 30 years, and of being humiliated and professionally despised by his peers. These events made the life of this physician, physiologist, researcher and inventor extremely arduous. We emphasize some aspects of the history of this man, his work and his life, a true genius of few friends.	Arquivos de neuro-psiquiatria	2,019	7
38,560,585	Chronic elevation of cardiac troponin I predicts the extent of coronary disease in hemodialysis patients presenting with acute enzyme elevation.	Elevation of cardiac troponin I (cTn-I) is associated with coronary artery disease (CAD) in asymptomatic patients with end-stage renal disease (ESRD) receiving hemodialysis. We aim to investigate the diagnostic value of chronically elevated cTn-I in ESRD patients presenting with an acute rise in serum cTn-I levels.	American heart journal plus : cardiology research and practice	2,021	2
23,433,881	[Benefit of a short atherosclerosis prevention program on post-stroke vascular risk reduction].	Atherosclerosis is a major cause of ischemic stroke. Despite important therapeutic advances, the risk of recurrence of vascular events remains very high. The partial failure of these strategies is to some extent related to the lack of patient adherence to their treatments and to the fact that therapeutic targets are not reached. The aim of the present study was to evaluate the influence of a short atherosclerosis prevention program on vascular risk reduction in stroke patients.	Revue neurologique	2,013	4
25,962,048	DNA methylation: dynamic and stable regulation of memory.	Epigenetic mechanisms have emerged as a central process in learning and memory. Histone modifications and DNA methy-lation are epigenetic events that can mediate gene transcription. Interesting features of these epigenetic changes are their transient and long lasting potential. Recent advances in neuroscience suggest that DNA methylation is both dynamic and stable, mediating the formation and maintenance of memory. In this review, we will further illustrate the recent hypothesis that DNA methylation participates in the transcriptional regulation necessary for memory.	Biomolecular concepts	2,011	12
18,640,240	Both MHC and non-MHC genes regulate development of experimental neuropathic pain in rats.	We have previously demonstrated that differences in neuropathic pain-like behaviors after sciatic nerve injury genetically maps to the major histocompatibility complex (MHC) in rats carrying RT1(c) or RT1(av1) haplotypes on the Piebald Virol Glaxo (PVG) background. In order to further explore the genetic contribution to neuropathic pain, we have here examined the MHC-congenic rat strains PVG-RT1(n) and PVG-RT1(av1) and the inbred strains PVG (RT1(c)) and Brown-Norway (BN; RT1(n)). All studied strains developed mechanical hypersensitivity (allodynia-like behavior) of the hind paw after photochemically induced sciatic nerve injury. However, the PVG-RT1(n) and PVG strains displayed significantly more allodynia than PVG-RT1(av1) and BN rats. In addition, the BN strain demonstrated an elevated threshold for the baseline response. The results demonstrate that both MHC and non-MHC genes influence experimental neuropathic pain in rats and also suggest that allelic variation contained in the RT1(av1) haplotype on the PVG background protects against neuropathic pain.	Neuroscience letters	2,008	9
32,586,899	Iron leakage owing to blood-brain barrier disruption in small vessel disease CADASIL.	To assess the relationship among iron accumulation, blood-brain barrier (BBB) damage, and cognitive function in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).	Neurology	2,020	9
12,777,845	[Intermittent microinjection method in freely-moving rats and its application to neuropharmacology].	Intermittent delivery of drugs into a discrete brain region has proven to be a useful technique. Described here is a micro-pump injection unit with miniature step-motors. This injection system is reliable, easy to operate and inexpensive to construct. The application of intermittent injection systems to study reward neurochemical circuits is discussed.	Nihon yakurigaku zasshi. Folia pharmacologica Japonica	2,003	4
32,857,435	Seizures and early onset dementia: D2HGA1 inborn error of metabolism in adults.	D-2-hydroxyglutaric aciduria type 1 (D2HGA1) is a rare inherited metabolic disorder usually manifesting in infancy/early childhood with seizures and significant central nervous system involvement. We report two siblings with D2HGA1 presenting with mild intellectual disability, and the onset of seizures in adulthood. One of them was misdiagnosed as tuberous sclerosis due to her presentation and the presence of subependymal nodules on brain imaging. Both further developed early onset dementia. This report expands the phenotype of D2HGA1 to include late-onset seizures and early onset dementia in adults.	Annals of clinical and translational neurology	2,020	10
30,543,827	The relevance of buffer system ionic strength in immunoassay development.	The best validated immunoassays for neurodegeneration have been developed for class III and IV intermediate filaments. There are a number of unique biochemical features of the intrinsically unstructured polyampholytic tail regions of these proteins which affect domain structure and thereby affinity and epitope recognition of antibodies used in immunoassays. Here one of these intermediate filaments, the neurofilament heavy chain, is chosen to demonstrate the effect of the ionic strength of a buffer system on the analytical signal to noise ratio. Higher ionic strengths gave better results. Next, a dose-dependent effect is demonstrated for barbitone to increase epitope recognition and protein quantification. The described effects of the buffer systems may be found helpful for future immunoassay developments.	Journal of immunological methods	2,019	2
33,126,459	Sequence Transpositions Restore Genes on the Highly Degenerated W Chromosomes of Songbirds.	The female-specific W chromosomes of most Neognathae birds are highly degenerated and gene-poor. Previous studies have demonstrated that the gene repertoires of the Neognathae bird W chromosomes, despite being in small numbers, are conserved across bird species, likely due to purifying selection maintaining the regulatory and dosage-sensitive genes. Here we report the discovery of DNA-based sequence duplications from the Z to the W chromosome in birds-of-paradise (Paradisaeidae, Passeriformes), through sequence transposition. The original transposition involved nine genes, but only two of them (	Genes	2,020	10
33,050,414	Dissecting Cellular Mechanisms of Long-Chain Acylcarnitines-Driven Cardiotoxicity: Disturbance of Calcium Homeostasis, Activation of Ca	Long-chain acylcarnitines (LCAC) are implicated in ischemia-reperfusion (I/R)-induced myocardial injury and mitochondrial dysfunction. Yet, molecular mechanisms underlying involvement of LCAC in cardiac injury are not sufficiently studied. It is known that in cardiomyocytes, palmitoylcarnitine (PC) can induce cytosolic Ca	International journal of molecular sciences	2,020	10
32,461,087	Body representations and basic symptoms in schizophrenia.	Patients with schizophrenia report a wide range of anomalous body experiences. According to the basic symptom model of schizophrenia, disturbances of body perception and awareness are among the most powerful predictors of the changes in the subjective experience of the self in schizophrenia. In this study we first investigated the body structural representation (BSR), a specific aspect of body awareness, and its association to basic symptoms in patients with schizophrenia. Using a finger localization task, we found that patients are significantly less accurate than healthy controls when asked to identify pairs of fingers touched by the experimenter, when the hand is hidden from view. Most importantly, patients' performance at the finger localization task was negatively associated to basic symptoms: the worse the individual accuracy, the higher the SPI-A total score. Moreover, the accuracy at the finger localization task was also negatively correlated with the malleability of the sense of body ownership: the less the individual ability to localize fingers, the stronger the rubber hand illusion. These results are in agreement with the idea that self-disorders in schizophrenia reveal a disconnectedness that can be regarded as a problem of disembodiment and traced back to abnormal body experiences.	Schizophrenia research	2,020	8
32,963,899	Probability of COVID-19 Being the Culprit in Neurocognitive Deception: A Case Series of Incidental Strokes in ICU Patients With COVID-19.	The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, originated in Wuhan, China, and spread rapidly throughout the world, infecting millions and killing thousands. Although some patients have mild or even asymptomatic responses to this infection, hospitalized patients present with symptoms such as fever, cough, and difficulty breathing. Some patients have a severe response to the insult and experience rapid progression to acute respiratory distress and multiorgan failure. Furthermore, many patients developed complications due to this infection. Here, we present three patients who had strokes during their hospitalization for COVID-19 pneumonia.	Cureus	2,020	8
32,656,879	Correcting frequency and phase offsets in MRS data using robust spectral registration.	An algorithm for retrospective correction of frequency and phase offsets in MRS data is presented. The algorithm, termed robust spectral registration (rSR), contains a set of subroutines designed to robustly align individual transients in a given dataset even in cases of significant frequency and phase offsets or unstable lipid contamination and residual water signals. Data acquired by complex multiplexed editing approaches with distinct subspectral profiles are also accurately aligned. Automated removal of unstable lipid contamination and residual water signals is applied first, when needed. Frequency and phase offsets are corrected in the time domain by aligning each transient to a weighted average reference in a statistically optimal order using nonlinear least-squares optimization. The alignment of subspectra in edited datasets is performed using an approach that specifically targets subtraction artifacts in the frequency domain. Weighted averaging is then used for signal averaging to down-weight poorer-quality transients. Algorithm performance was assessed on one simulated and 67 in vivo pediatric GABA-/GSH-edited HERMES datasets and compared with the performance of a multistep correction method previously developed for aligning HERMES data. The performance of the novel approach was quantitatively assessed by comparing the estimated frequency/phase offsets against the known values for the simulated dataset or by examining the presence of subtraction artifacts in the in vivo data. Spectral quality was improved following robust alignment, especially in cases of significant spectral distortion. rSR reduced more subtraction artifacts than the multistep method in 64% of the GABA difference spectra and 75% of the GSH difference spectra. rSR overcomes the major challenges of frequency and phase correction.	NMR in biomedicine	2,020	10
34,589,873	Deletion of indoleamine 2,3 dioxygenase (Ido)1 but not Ido2 exacerbates disease symptoms of MOG	Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) with pathological features of inflammation, demyelination, and neurodegeneration. Several lines of evidence suggest that the enzymes indoleamine 2,3-dioxygenase (Ido)1 and/or Ido2 influences susceptibility to autoimmune diseases. Deletion of	Brain, behavior, & immunity - health	2,020	8
32,920,043	VEGF-D Downregulation in CA1 Pyramidal Neurons Exerts Asymmetric Changes of Dendritic Morphology without Correlated Electrophysiological Alterations.	The morphology of dendritic arbors determines the location, strength and interaction of synaptic inputs. It is therefore important to understand the factors regulating dendritic arborization both during development and in situations of physiological or pathological plasticity. We have recently shown that VEGF-D (Vascular Endothelial Growth Factor D) is required to maintain length and complexity of basal dendrites in mouse hippocampal pyramidal cells. Lack of VEGF-D resulted in long-term memory deficits, suggesting a link between dendritic morphology and cognitive function. Here, we compared the effect of VEGF-D expression on basal versus apical dendrites of CA1 pyramidal cells, as well as its importance for synaptic processing of network oscillations. We report opposing, layer-specific effects of VEGF-D knockdown which resulted in shrinkage of basal and increased complexity of apical dendrites. Synaptic potentials and layer-specific voltage gradients during network oscillations remained, however, unaltered. These findings reveal a high spatial selectivity of VEGF-D effects at the sub-cellular level, and strong homeostatic mechanisms which keep spatially segregated synaptic inputs in a balance.	Neuroscience	2,020	11
33,069,752	Differential effects of progesterone on social recognition and the avoidance of pathogen threat by female mice.	Although pathogen threat affects social and sexual responses across species, relatively little is known about the underlying neuroendocrine mechanisms. Progesterone has been speculated to be involved in the mediation of pathogen disgust in women, though with mixed experimental support. Here we considered the effects of acute progesterone on the disgust-like avoidance responses of female mice to pathogen threat. Estrous female mice discriminated and avoided the urinary and associated odors of males subclinically infected with the murine nematode parasite, Heligmosomoides polygyrus. These avoidance responses were not significantly affected by pre-treatment with progesterone. Likewise, brief (1 min) exposure to the odors of infected males attenuated the subsequent responses of females to the odors of the normally preferred unfamiliar males and enhanced their preferences for familiar males. Neither progesterone nor allopregnanolone, a central neurosteroid metabolite of progesterone, had any significant effects on the avoidance of unfamiliar males elicited by pre-exposure to a parasitized male. Progesterone and allopregnanolone, did, however, significantly attenuate the typical preferences of estrous females for unfamiliar uninfected males, suggestive of effects on social recognition. These findings with mice indicate that progesterone may have minimal effects on the responses to specific parasite threat and the expression of pathogen disgust but may influence more general social recognition and preferences.	Hormones and behavior	2,021	1
32,769,034	Rasmussen's encephalitis: From immune pathogenesis towards targeted-therapy.	Rasmussen encephalitis (RE) is a unilateral hemispheric encephalitis whose main clinical features include refractory focal epilepsy or epilepsia partialis continua, hemiparesis, and progressive cognitive decline. Despite the autoimmune pathogenesis of RE, the only definitive therapeutic option is currently represented by surgery. We review the clinical features, the immune pathogenesis, and the available therapeutic options for RE, with special focus on immunosuppressive agents. The research includes systematic reviews, meta-analyses, observational studies, clinical trials, cases series and reports, until 2020. The use of immunosuppressive agents in RE is supported by the evidence of an autoimmune involvement of the central nervous system in this condition. Although often insufficient to modify the disease course and to achieve symptomatic control, immune therapy can be effective in patients with slow disease progression or in patients in which surgery is not applicable. Moreover, the documentation of T-cell involvement in the pathogenesis of RE, with a specific cytokine pattern, opens a window of opportunity for the use of T-targeted therapies and biologic drugs (i.e. anti-TNFα agents) in the treatment of this disease.	Seizure	2,020	10
32,658,389	The renin-angiotensin-aldosterone system: Role in pathogenesis and potential therapeutic target in COVID-19.	Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 novel coronavirus, has spread worldwide causing high fatality rates. Neither a vaccine nor specific therapeutic approaches are available, hindering the fight against this disease and making better understanding of its pathogenesis essential. Despite similarities between SARS-CoV-2 and SARS-CoV, the former has unique characteristics which represent a great challenge to physicians. The mechanism of COVID-19 infection and pathogenesis is still poorly understood. In the present review, we highlight possible pathways involved in the pathogenesis of COVID-19 and potential therapeutic targets, focusing on the role of the renin-angiotensin-aldosterone system.	Pharmacology research & perspectives	2,020	8
33,197,578	Update in immunosuppressive therapy of myasthenia gravis.	Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction. Immunosuppressive treatments are part of the therapeutic armamentarium in MG. Long-term systemic steroid administration carry considerable risks and adverse events. Consequently, steroid-free immunosuppressive therapy is necessary to reduce the dose or discontinue steroids. First immunosuppressive drug trials in MG were performed in the mid-60s using standard and nonspecific immunosuppression. Since then, only few randomized controlled clinical trials were conducted in MG and assesed drug efficacy in terms of its steroid-sparing capacity and the ability to reduce myasthenic signs and symptoms. Treatment strategy in MG is quite challenging, mainly due to the disease heterogeneity in terms of clinical presentation, immunopathogenesis and drug response. To solve this dilemma, emerging treatment are based on biological drugs and use new targets of the immune pathway.	Autoimmunity reviews	2,021	1
32,827,576	Using consumption and reward simulations to increase the appeal of plant-based foods.	The production of meat is a main contributor to current dangerous levels of greenhouse gas emissions. However, the shift to more plant-based diets is hampered by consumers finding meat-based foods more attractive than plant-based foods. How can plant-based foods best be described to increase their appeal to consumers? Based on the grounded cognition theory of desire, we suggest that descriptions that trigger simulations, or re-experiences, of eating and enjoying a food will increase the attractiveness of a food, compared to descriptions emphasizing ingredients. In Study 1, we first examined the descriptions of ready meals available in four large UK supermarkets (N = 240). We found that the labels of meat-based foods contained more references to eating simulations than vegetarian foods, and slightly more than plant-based foods, and that this varied between supermarkets. In Studies 2 and 3 (N = 170, N = 166, pre-registered), we manipulated the labels of plant-based and meat-based foods to either include eating simulation words or not. We assessed the degree to which participants reported that the description made them think about eating the food (i.e., induced eating simulations), and how attractive they found the food. In Study 2, where either sensory or eating context words were added, we found no differences with control labels. In Study 3, however, where simulation-based labels included sensory, context, and hedonic words, we found that simulation-based descriptions increased eating simulations and attractiveness. Moreover, frequent meat eaters found plant-based foods less attractive, but this was attenuated when plant-based foods were described with simulation-inducing words. We suggest that language that describes rewarding eating experiences can be used to facilitate the shift toward healthy and sustainable diets.	Appetite	2,020	12
33,002,861	Risk factors, comorbidities, quality of life, and complications after surgery in idiopathic normal pressure hydrocephalus: review of the INPH-CRasH study.	Idiopathic normal pressure hydrocephalus (INPH) is a dementia treatable by insertion of a shunt that drains CSF. The cause of the disease is unknown, but a vascular pathway has been suggested. The INPH-CRasH (Comorbidities and Risk Factors Associated with Hydrocephalus) study was a modern epidemiological case-control study designed to prospectively assess parameters regarding comorbidities and vascular risk factors (VRFs) for INPH, quality of life (QOL), and adverse events in patients with shunted INPH. The objective of this review was to summarize the findings of the INPH-CRasH study.	Neurosurgical focus	2,020	10
32,956,103	Blood pressure excursions in acute ischemic stroke patients treated with intravenous thrombolysis.	To investigate the association of blood pressure BP excursions, defined as greater than 185 SBP or greater than 105 DBP, with the probability of intracranial hemorrhage (ICH) and worse functional outcomes in patients with acute ischemic stroke (AIS) treated with tissue plasminogen activator (tPA).	Journal of hypertension	2,021	2
33,227,537	Intranasal oxytocin administration facilitates the induction of long-term potentiation and promotes cognitive performance of maternally separated rats.	Maternal separation (MS) is known to induce permanent changes in the central nervous system and is associated with increased levels of anxiety and cognitive impairments. The neuropeptide oxytocin (OT) has been implicated in a broad spectrum of social and nonsocial and behaviors. Since it plays a significant role in learning and memory and enhances synaptic plasticity, we hypothesized that OT may affect MS-induced changes in synaptic plasticity and cognitive performance. Rat pups underwent MS protocol for 180 min/day from postnatal day (PND) 1-21. OT was administered intranasally (2 μg/μl, 7 days) to control and MS groups from PND 22-34. Plasma corticosterone (CORT) levels, anxiety-like behavior, sociability, learning and memory were measured in adolescent rats. In addition, extracellular evoked field excitatory postsynaptic potentials (fEPSP) were also recorded from hippocampal slices. MS induced higher plasma CORT levels and impaired social interaction, learning and memory. Moreover, MS reduced locomotor activity and increased anxiety-like behavior. Intranasal OT could overcome MS-induced deficits and promoted sociability, learning and memory of MS rats. OT also enhanced locomotor activity in the open field and decreased anxiety-like behavior. Obtained results showed that long term potentiation (LTP) was not induced in MS animals. However, OT injection overcame the MS-induced impairment in LTP generation in CA1 area of the hippocampus.	Psychoneuroendocrinology	2,021	1
33,516,788	Bacteroides ovatus Promotes IL-22 Production and Reduces Trinitrobenzene Sulfonic Acid-Driven Colonic Inflammation.	The intestinal microbiota influences the development and function of the mucosal immune system. However, the exact mechanisms by which commensal microbes modulate immunity is not clear. We previously demonstrated that commensal Bacteroides ovatus ATCC 8384 reduces mucosal inflammation. Herein, we aimed to identify immunomodulatory pathways employed by B. ovatus. In germ-free mice, mono-association with B. ovatus shifted the CD11b	The American journal of pathology	2,021	4
33,098,008	Exparel for Postoperative Pain Management: a Comprehensive Review.	Multimodal pain management is the most effective way to treat postsurgical pain. However, the use of opioids for acute pain management has unfortunately been a significant contributor to the current opioid epidemic. The use of opioids should be limited and only considered a "rescue" pain medication after other modalities of pain management have been utilized.	Current pain and headache reports	2,020	10
32,665,510	Original Research: Understanding Nursing Home Staff Attitudes Toward Death and Dying: A Survey.	Nearly 70% of nursing home residents are eligible for palliative care, yet few receive formal palliative care outside of hospice. Little is known about nursing home staff attitudes, knowledge, skills, and behaviors related to palliative care.	The American journal of nursing	2,020	8
32,669,388	Precise memory for pure tones is predicted by measures of learning-induced sensory system neurophysiological plasticity at cortical and subcortical levels.	Despite identical learning experiences, individuals differ in the memory formed of those experiences. Molecular mechanisms that control the neurophysiological bases of long-term memory formation might control how precisely the memory formed reflects the actually perceived experience. Memory formed with sensory specificity determines its utility for selectively cueing subsequent behavior, even in novel situations. Here, a rodent model of auditory learning capitalized on individual differences in learning-induced auditory neuroplasticity to identify and characterize neural substrates for sound-specific (vs. general) memory of the training signal's acoustic frequency. Animals that behaviorally revealed a naturally induced signal-"specific" memory exhibited long-lasting signal-specific neurophysiological plasticity in auditory cortical and subcortical evoked responses. Animals with "general" memories did not exhibit learning-induced changes in these same measures. Manipulating a histone deacetylase during memory consolidation biased animals to have more signal-specific memory. Individual differences validated this brain-behavior relationship in both natural and manipulated memory formation, such that the degree of change in sensory cortical and subcortical neurophysiological responses could be used to predict the behavioral precision of memory.	Learning & memory (Cold Spring Harbor, N.Y.)	2,020	8
32,994,116	The physiological responses to acute stress in alcohol-dependent patients: A systematic review.	Dysregulation of physiological stress reactivity plays a key role in the development and relapse risk of alcohol dependence. This article reviews studies investigating physiological responses to experimentally induced acute stress in patients with alcohol dependence. A systematic search from electronic databases resulted in 3641 articles found and after screening 62 articles were included in our review. Studies are analyzed based on stress types (i.e., social stress tasks and nonsocial stress tasks) and physiological markers (i.e., the nervous system, the endocrine system, somatic responses and the immune system). In studies applying nonsocial stress tasks, alcohol-dependent patients were reported to show a blunted stress response compared with healthy controls in the majority of studies applying markers of adrenocorticotropic hormone and cortisol. In studies applying social stress tasks, findings are inconsistent, with less than half of the studies reporting altered physiological stress responses in patients. We discuss the impact of duration of abstinence, comorbidities, baseline physiological arousal and intervention on the discrepancy of study findings. Furthermore, we review evidence for an association between blunted physiological stress responses and the relapse risk among patients with alcohol dependence.	European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology	2,020	12
33,188,183	Molecular estimation of neurodegeneration pseudotime in older brains.	The temporal molecular changes that lead to disease onset and progression in Alzheimer's disease (AD) are still unknown. Here we develop a temporal model for these unobserved molecular changes with a manifold learning method applied to RNA-Seq data collected from human postmortem brain samples collected within the ROS/MAP and Mayo Clinic RNA-Seq studies. We define an ordering across samples based on their similarity in gene expression and use this ordering to estimate the molecular disease stage-or disease pseudotime-for each sample. Disease pseudotime is strongly concordant with the burden of tau (Braak score, P = 1.0 × 10	Nature communications	2,020	11
25,097,576	A survey to establish current methods of venous thromboembolism prophylaxis in stroke patients practiced by Polish neurologists.	Venous thromboembolism (VTE) is associated with considerable morbidity and mortality in stroke patients. The purpose of our survey was to establish the current methods of VTE prophylaxis practiced by Polish neurologists. We also aimed to determine whether there is enough variation in practice to justify the development of an evidence-based guideline for VTE prevention.	Archives of medical science : AMS	2,014	6
29,738,912	Functionally separated networks for self-paced and externally-cued motor execution in Parkinson's disease: Evidence from deep brain recordings in humans.	Spatially segregated cortico-basal ganglia networks have been proposed for the control of goal-directed and habitual behavior. In Parkinson's disease, selective loss of dopaminergic neurons regulating sensorimotor (habitual) behavior might therefore predominantly cause deficits in habitual motor control, whereas control of goal-directed movement is relatively preserved. Following this hypothesis, we examined the electrophysiology of cortico-basal ganglia networks in Parkinson patients emulating habitual and goal-directed motor control during self-paced and externally-cued finger tapping, respectively, while simultaneously recording local field potentials in the subthalamic nucleus (STN) and surface EEG. Only externally-cued movements induced a pro-kinetic event-related beta-desynchronization, whereas beta-oscillations were continuously suppressed during self-paced movements. Connectivity analysis revealed higher synchronicity (phase-locking value) between the STN and central electrodes during self-paced and higher STN to frontal phase-locking during externally-cued movements. Our data provide direct electrophysiological support for the existence of functionally segregated cortico-basal ganglia networks controlling motor behavior in Parkinson patients, and corroborate the assumption of Parkinson patients being shifted from habitual towards goal-directed behavior.	NeuroImage	2,018	8
32,997,560	Detection Methods of COVID-19.	Since being first detected in China, coronavirus disease 2019 (COVID-19) has spread rapidly across the world, triggering a global pandemic with no viable cure in sight. As a result, national responses have focused on the effective minimization of the spread. Border control measures and travel restrictions have been implemented in a number of countries to limit the import and export of the virus. The detection of COVID-19 is a key task for physicians. The erroneous results of early laboratory tests and their delays led researchers to focus on different options. Information obtained from computed tomography (CT) and radiological images is important for clinical diagnosis. Therefore, it is worth developing a rapid method of detection of viral diseases through the analysis of radiographic images. We propose a novel method of detection of COVID-19. The purpose is to provide clinical decision support to healthcare workers and researchers. The article is to support researchers working on early detection of COVID-19 as well as similar viral diseases.	SLAS technology	2,020	12
30,801,223	Insights into microbiome research 6: The role of consortia in studying the role of microbes in health and disease.	Consortia are large, multidisciplinary research efforts that carry the power of numbers. In addition, they enable the sharing of protocols and strategies, ultimately resulting in credible, reproducible, and groundbreaking discoveries. Several consortia are currently investigating the role of bacteria in health and disease, including the International Multiple Sclerosis Microbiome Study (iMSMS), whose effort is dedicated to multiple sclerosis.	Multiple sclerosis (Houndmills, Basingstoke, England)	2,019	3
33,130,409	Modeling brain development and diseases with human cerebral organoids.	Understanding the mechanisms that underlie human brain development and neurological and neuropsychiatric disorders is one of the key topics of neurobiology. Because of the poor accessibility of human and non-human primate brain tissues, the current perception and understanding of human brain development have been mainly derived from studies of rodents. However, some human-specific features of neural development cannot be well characterized by these animal models. Thanks to the advances in stem cell technologies, brain organoids are being under rapid development, showing the promising applications in decoding the human brain development and uncovering the pathology of brain diseases. In this review, we mainly summarized the recent advances in the development of brain organoid technology and discussed the limitations, applications and future prospects of this promising field.	Current opinion in neurobiology	2,021	2
33,140,310	The potential use of tideglusib as an adjuvant radio-therapeutic treatment for glioblastoma multiforme cancer stem-like cells.	Glioblastoma multiforme (GBM), a stage IV astrocytoma, is the most common brain malignancy among adults. Conventional treatments of surgical resection followed by radio and/or chemotherapy fail to completely eradicate the tumor. Resistance to the currently available therapies is mainly attributed to a subpopulation of cancer stem cells (CSCs) present within the tumor bulk that self-renew leading to tumor relapse with time. Therefore, identification of characteristic markers specific to these cells is crucial for the development of targeted therapies. Glycogen synthase kinase 3 (GSK-3), a serine-threonine kinase, is deregulated in a wide range of diseases, including cancer. In GBM, GSK-3β is overexpressed and its suppression in vitro has been shown to induce apoptosis of cancer cells.	Pharmacological reports : PR	2,021	2
32,593,032	Somatosensory area 3b is selectively unaffected in corticobasal syndrome: combining MRI and histology.	An increasing number of neuroimaging studies addressing patients with corticobasal syndrome use macroscopic definitions of brain regions. As a closer link to functionally relevant units, we aimed at identifying magnetic resonance-based atrophy patterns in regions defined by probability maps of cortical microstructure. For this purpose, three analyses were conducted: (1) Whole-brain cortical thickness was compared between 36 patients with corticobasal syndrome and 24 controls. A pattern of pericentral atrophy was found, covering primary motor area 4, premotor area 6, and primary somatosensory areas 1, 2, and 3a. Within the central region, only area 3b was without atrophy. (2) In 18 patients, longitudinal measures with follow-ups of up to 59 months (mean 21.3 ± 15.4) were analyzed. Areas 1, 2, and 6 showed significantly faster atrophy rates than primary somatosensory area 3b. (3) In an individual autopsy case, longitudinal in vivo morphometry and postmortem pathohistology were conducted. The rate of magnetic resonance-based atrophy was significantly correlated with tufted-astrocyte load in those cytoarchitectonically defined regions also seen in the group study, with area 3b being selectively unaffected.	Neurobiology of aging	2,020	10
33,103,375	Glial Interfaces: Advanced Materials and Devices to Uncover the Role of Astroglial Cells in Brain Function and Dysfunction.	Research over the past four decades has highlighted the importance of certain brain cells, called glial cells, and has moved the neurocentric vision of structure, function, and pathology of the nervous system toward a more holistic perspective. In this view, the demand for technologies that are able to target and both selectively monitor and control glial cells is emerging as a challenge across neuroscience, engineering, chemistry, and material science. Frequently neglected or marginally considered as a barrier to be overcome between neural implants and neuronal targets, glial cells, and in particular astrocytes, are increasingly considered as active players in determining the outcomes of device implantation. This review provides a concise overview not only of the previously established but also of the emerging physiological and pathological roles of astrocytes. It also critically discusses the most recent advances in biomaterial interfaces and devices that interact with glial cells and thus have enabled scientists to reach unprecedented insights into the role of astroglial cells in brain function and dysfunction. This work proposes glial interfaces and glial engineering as multidisciplinary fields that have the potential to enable significant advancement of knowledge surrounding cognitive function and acute and chronic neuropathologies.	Advanced healthcare materials	2,021	1
32,888,180	Sex Differences in Electrophysiological Properties of Mouse Medial Preoptic Area Neurons Revealed by In Vitro Whole-cell Recordings.	Despite extensive characterization of sex differences in the medial preoptic area (mPOA) of the hypothalamus, we know surprisingly little about whether or how male and female mPOA neurons differ electrophysiologically, especially in terms of neuronal firing and behavioral pattern generation. In this study, by performing whole-cell patch clamp recordings of the mPOA, we investigated the influences of sex, cell type, and gonadal hormones on the electrophysiological properties of mPOA neurons. Notably, we uncovered significant sex differences in input resistance (male > female) and in the percentage of neurons that displayed post-inhibitory rebound (male > female). Furthermore, we found that the current mediated by the T-type Ca	Neuroscience bulletin	2,021	2
22,294,228	Fear-potentiated startle and light-enhanced startle models in drug discovery.	Described in this unit are the fear-potentiated startle (FPS) and light-enhanced startle (LES) tests. These protocols have proven reliable in detecting the anxiolytic properties of test compounds. The principle of these tests is that the magnitude of the acoustic startle reflex is an index of anxiety. The FPS test includes two training sessions in which an intrinsically aversive foot shock is paired with a neutral cue light. In the test session presentation of this cue light is subsequently used to elicit startle potentiation. In the LES test startle reactivity is increased by presentation of bright light. Because LES is based on the innate aversion of rodents for bright light it does not require training sessions. Although LES has been used less frequently than FPS for screening compounds, it has an advantage in that drug effects on startle potentiation are independent of memory retrieval. Further, the contextual anxiety measured in the LES test could be more relevant for pathological anxiety than the conditioned fear associated with the FPS test.	Current protocols in pharmacology	2,008	6
32,619,708	Serotonergic psychedelics LSD & psilocybin increase the fractal dimension of cortical brain activity in spatial and temporal domains.	Psychedelic drugs, such as psilocybin and LSD, represent unique tools for researchers investigating the neural origins of consciousness. Currently, the most compelling theories of how psychedelics exert their effects is by increasing the complexity of brain activity and moving the system towards a critical point between order and disorder, creating more dynamic and complex patterns of neural activity. While the concept of criticality is of central importance to this theory, few of the published studies on psychedelics investigate it directly, testing instead related measures such as algorithmic complexity or Shannon entropy. We propose using the fractal dimension of functional activity in the brain as a measure of complexity since findings from physics suggest that as a system organizes towards criticality, it tends to take on a fractal structure. We tested two different measures of fractal dimension, one spatial and one temporal, using fMRI data from volunteers under the influence of both LSD and psilocybin. The first was the fractal dimension of cortical functional connectivity networks and the second was the fractal dimension of BOLD time-series. In addition to the fractal measures, we used a well-established, non-fractal measure of signal complexity and show that they behave similarly. We were able to show that both psychedelic drugs significantly increased the fractal dimension of functional connectivity networks, and that LSD significantly increased the fractal dimension of BOLD signals, with psilocybin showing a non-significant trend in the same direction. With both LSD and psilocybin, we were able to localize changes in the fractal dimension of BOLD signals to brain areas assigned to the dorsal-attenion network. These results show that psychedelic drugs increase the fractal dimension of activity in the brain and we see this as an indicator that the changes in consciousness triggered by psychedelics are associated with evolution towards a critical zone.	NeuroImage	2,020	10
31,462,281	Funding research, a Chinese perspective.	Funding research is a challenge faced by most scientists around the world. Genome Biology has invited four scientists based in three different countries to share their own experience and opinions regarding funding, the difficulties young scientists must overcome, and how the process of securing funding can be improved. Here, Hui Yang discusses the funding opportunities open to scientists conducting research in China.	Genome biology	2,019	8
32,817,358	Efficacy and safety of adjunctive lacosamide in the treatment of primary generalised tonic-clonic seizures: a double-blind, randomised, placebo-controlled trial.	To evaluate efficacy and safety of lacosamide (up to 12 mg/kg/day or 400 mg/day) as adjunctive treatment for uncontrolled primary generalised tonic-clonic seizures (PGTCS) in patients (≥4 years) with idiopathic generalised epilepsy (IGE).	Journal of neurology, neurosurgery, and psychiatry	2,020	10

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