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32,498,971	Nothing Is Yet Set in (Hi)stone: Novel Post-Translational Modifications Regulating Chromatin Function.	Histone post-translational modifications (PTMs) have emerged as exciting mechanisms of biological regulation, impacting pathways related to cancer, immunity, brain function, and more. Over the past decade alone, several histone PTMs have been discovered, including acylation, lipidation, monoaminylation, and glycation, many of which appear to have crucial roles in nucleosome stability and transcriptional regulation. In this review, we discuss novel histone PTMs identified within the past 10 years, with an extended focus on enzymatic versus nonenzymatic mechanisms underlying modification and adduction. Furthermore, we consider how these novel histone PTMs might fit within the framework of a so-called 'histone code', emphasizing the physiological relevance of these PTMs in metabolism, development, and disease states.	Trends in biochemical sciences	2,020	10
29,024,648	Mapping Brain Activity onto Molecularly Defined Cells.	The brain processes information and generates behavior by employing a wide array of different cell types. In this issue of Neuron, Wu et al. (2017) report a novel method that enables the efficient identification of molecularly defined cells that participate in a specific brain function.	Neuron	2,017	10
33,186,043	[	Intracerebral hemorrhage (ICH), being the most severe cerebrovascular disease, accounts for 10-15% of all strokes. Hematoma expansion is one of the most important factors associated with poor outcome in intracerebral hemorrhage (ICH). Several studies have suggested that an "ischemic penumbra" might arise when the hematoma has a large expansion, but clinical studies are inconclusive. We performed a preclinical study to demonstrate the presence of hypoxic-ischemic tissue around the hematoma by means of longitudinal [	Molecular pharmaceutics	2,020	12
33,554,149	Intranuclear immunostaining-based FACS protocol from embryonic cortical tissue.	Cell sorting can be used to purify cell populations for cell type-specific molecular probing. Fluorescence-activated cell sorting (FACS) coupled with high-throughput sequencing affords molecular signature identification for specific cell types. FACS has many challenges that limit comprehensive cell purification from the brain, leading to incomplete molecular characterization. Here, we present the intranuclear immunostaining-based FACS protocol with several modified steps, which allows optimized nuclei/cell sorting from mouse or human embryonic cortical tissue for distinct downstream molecular investigation of basal intermediate progenitors.	STAR protocols	2,021	3
32,652,172	Distribution of VTA Glutamate and Dopamine Terminals, and their Significance in CA1 Neural Network Activity.	Reciprocal connection between the ventral tegmental area (VTA) and the hippocampus forms a loop that controls information entry into long-term memory. Compared with the widely studied VTA dopamine system, VTA glutamate terminals are anatomically dominant in the hippocampus and less understood. The current study employs anterograde and retrograde labeling of VTA dopamine and glutamate neurons to map the distribution of their terminals within the layers of the hippocampus. Also, functional tracing of VTA dopamine and glutamate projections to the hippocampus was performed by photostimulation of VTA cell bodies during CA1 extracellular voltage sampling in vivo. VTA dopamine terminals predominantly innervate the CA1 basal dendrite layer and modulate the firing rate of active putative neurons. In contrast, anatomical dominance of VTA glutamate terminals in the CA1 pyramidal cell and apical dendrite layers suggests the possible involvement of these terminals in excitability regulation. In support of these outcomes, photostimulation of VTA dopamine neurons increased the firing rate but not intrinsic excitability parameters for putative pyramidal units. Conversely, activation of VTA glutamate neurons increased CA1 network firing rate and burst rate. In addition, VTA glutamate inputs reduced the interspike and interburst intervals for putative CA1 neurons. Taken together, we deduced that layer-specific distribution of presynaptic dopamine and glutamate terminals in the hippocampus determinines VTA modulation (dopamine) or regulation (glutamate) of excitability in the CA1 neural network.	Neuroscience	2,020	10
33,740,797	A hormetic approach to understanding antidepressant effectiveness and the development of antidepressant tolerance - A conceptual view.	Antidepressants such as the selective serotonin reuptake inhibitors (SSRIs) have complex temporal effects. They may worsen symptoms during early treatment, they may reduce depressive symptoms over several weeks of treatment, and they may lose effectiveness over more prolonged treatment or after repeated treatment trials. Conceptually, these effects fall within the domain of hormesis, which refers to a biphasic or multiphasic response to a drug or toxin. Hormetic effects are commonly triggered when a drug interacts with homeostatic mechanisms. We develop and evaluate a theoretical framework for understanding how adaptations to SSRIs that restore synaptic homeostasis may partially contribute to their hormetic effects. Specifically, the serotonin system adapts to SSRIs by suppressing the firing of serotonergic neurons, inhibiting the synthesis of serotonin, and reducing the overall content of serotonin in the brain. Moreover, rodent models such as inescapable shock show that serotonin neurotransmission to specific forebrain regions is a necessary, but insufficient cause of depressive symptoms. Our review suggests: (1) early worsening of symptoms may be related to the direct effects of SSRIs on synaptic serotonin; (2) the symptom-reducing effects could be related to the loss of serotonin content in the brain during SSRI exposure; (3) the loss of efficacy over prolonged exposure could be related to the central nervous system equilibrating to the SSRIs. The serotonin system's adaptations to SSRIs may play a clinically meaningful role in their hormetic effects on depressive symptoms. A complete understanding of SSRIs' hormetic effects will require exploring temporal dynamics in other neurotransmitter systems.	Psychiatria polska	2,020	12
33,301,105	European Society of Emergency Radiology: guideline on radiological polytrauma imaging and service (short version).	Although some national recommendations for the role of radiology in a polytrauma service exist, there are no European guidelines to date. Additionally, for many interdisciplinary guidelines, radiology tends to be under-represented. These factors motivated the European Society of Emergency Radiology (ESER) to develop radiologically-centred polytrauma guidelines.	Insights into imaging	2,020	12
28,176,341	Dr. Eugene Roberts.	This is an obituary for Eugene Roberts (1920-2016), an outstanding neurobiochemist who was the first to report on the discovery of gamma-aminobutyric acid (GABA) in the brain, and whose research focused on the important role of GABA in human health and disease.	Journal of neurochemistry	2,017	3
27,864,104	Pharmacological response sensitization in nerve cell networks exposed to the antibiotic gentamicin.	Gentamicin is an aminoglycoside antibiotic that is used in clinical, organismic, and agricultural applications to combat gram-negative, aerobic bacteria. The clinical use of gentamicin is widely linked to various toxicities, but there is a void in our knowledge about the neuromodulatory or neurotoxicity effects of gentamicin. This investigation explored the electrophysiologic effects of gentamicin on GABAergic pharmacological profiles in spontaneously active neuronal networks in vitro derived from auditory cortices of E16 mouse embryos and grown on microelectrode arrays. Using the GABA	European journal of pharmacology	2,017	1
28,216,411	A summary of the Proceedings of the Thirteenth International Symposium on the Neurobiology and Neuroendocrinology of Aging, Bregenz, Austria July 17-22, 2016.	A summary of the Thirteenth International Symposium on the Neurobiology and Neuroendocrinology of Aging that was held July 17-22, 2016 in Bregenz, Austria, is presented. Nineteen of the speakers that presented at the conference submitted review papers covering the topic of their presentation as well as an overview of their respective fields and are included in this special issue. The abstracts from each poster presentation as well as twenty-two of the speaker abstracts are also included at the end of the preface to the special issue.	Experimental gerontology	2,017	8
28,748,998	[Paul Cézanne, the lonely precursor of modern painting].	Paul Cézanne is an acknowledged pioneer of modern painting. His work was poorly recognized during most of his solitary life. He progressively withdrew from people and society during his life, in part due to his introverted personality and a supreme effort to obtain a unique form of expression of his art, in which nature and its inner secrets played a pivotal role. In this review, we discuss aspects of his life and art, his pathological personal relationships and how they influenced his transcendental work.	Revista medica de Chile	2,017	4
33,327,067	Spike-phase coupling as an order parameter in a leaky integrate-and-fire model.	It is known that the leaky integrate-and-fire neural model shows a transition from irregular to synchronous firing by increasing the coupling between the neurons. However, a quantitative characterization of this order-disorder transition, that is, the determination of the order of transition and also the critical exponents in the case of continuous transition, is not entirely known. In this work, we consider a network of N excitatory neurons with local connections, residing on a square lattice with periodic boundary conditions. The cooperation between neurons K plays the role of the control parameter that generates criticality when the critical cooperation strength K_{c} is adopted. We introduce the population-averaged voltage (PAV) as a representative value of the network's cooperative activity. Then, we show that the coupling between the timing of spikes and the phase of temporal fluctuations of PAV defined as m resorts to identify a Kuramoto order parameter. By increasing K, we find a continuous transition from irregular spiking to a phase-locked state at the critical point K_{c}. We deploy the finite-size scaling analysis to calculate the critical exponents of this transition. To explore the formal indicator of criticality, we study the neuronal avalanches profile at this critical point and find a scaling behavior with the exponents in a fair agreement with the experimental values both in vivo and in vitro.	Physical review. E	2,020	11
32,448,637	Goltz against cerebral localization: Methodology and experimental practices.	In the late 19th century, physiologists such as David Ferrier, Eduard Hitzig, and Hermann Munk argued that cerebral brain functions are localized in discrete structures. By the early 20th century, this became the dominant position. However, another prominent physiologist, Friedrich Goltz, rejected theories of cerebral localization and argued against these physiologists until his death in 1902. I argue in this paper that previous historical accounts have failed to comprehend why Goltz rejected cerebral localization. I show that Goltz adhered to a falsificationist methodology, and I reconstruct how he designed his experiments and weighted different kinds of evidence. I then draw on the exploratory experimentation literature from recent philosophy of science to trace one root of the debate to differences in how the German localizers designed their experiments and reasoned about evidence. While Goltz designed his experiments to test hypotheses about the functions of predetermined cerebral structures, the localizers explored new functions and structures in the process of constructing new theories. I argue that the localizers relied on untested background conjectures to justify their inferences about functional organization. These background conjectures collapsed a distinction between phenomena they produced direct evidence for (localized symptoms) and what they reached conclusions about (localized functions). When citing this paper, please use the full journal title Studies in History and Philosophy of Biological and Biomedical Sciences.	Studies in history and philosophy of biological and biomedical sciences	2,020	12
29,894,263	Sharing expertise: when immunology meets psychiatry and neuroscience.	A radio programme investigating how a 'rogue' immune system could affect mental health led second-year nursing student at Kingston and St George's University Leo Honey to research the subject further, [email protected].	British journal of nursing (Mark Allen Publishing)	2,018	6
33,277,253	Multiple sclerosis iPS-derived oligodendroglia conserve their properties to functionally interact with axons and glia in vivo.	Remyelination failure in multiple sclerosis (MS) is associated with a migration/differentiation block of oligodendroglia. The reason for this block is highly debated. It could result from disease-related extrinsic or intrinsic regulators in oligodendroglial biology. To avoid confounding immune-mediated extrinsic effect, we used an immune-deficient mouse model to compare induced pluripotent stem cell-derived oligodendroglia from MS and healthy donors following engraftment in the developing CNS. We show that the MS-progeny behaves and differentiates into oligodendrocytes to the same extent as controls. They generate equal amounts of myelin, with bona fide nodes of Ranvier, and promote equal restoration of their host slow conduction. MS-progeny expressed oligodendrocyte- and astrocyte-specific connexins and established functional connections with donor and host glia. Thus, MS oligodendroglia, regardless of major immune manipulators, are intrinsically capable of myelination and making functional axo-glia/glia-glia connections, reinforcing the view that the MS oligodendrocyte differentiation block is not from major intrinsic oligodendroglial deficits.	Science advances	2,020	12
29,300,916	Effects of Perinatal Exposure to Phthalates and a High-Fat Diet on Maternal Behavior and Pup Development and Social Play.	Humans are ubiquitously exposed to many phthalates, a class of endocrine-disrupting chemicals commonly used in many consumer goods, and diet, especially fatty food, is presumed to be a major source of exposure. Here, we use a rat model of human prenatal exposure to investigate the potential interactive effects of an environmentally relevant mixture of phthalates and a maternal high-fat diet (HFD). From gestation through postnatal day (P)10, dams consumed the mixture of phthalates (0, 200, or 1000 μg/kg/d) and were fed a control diet or HFD. In males, perinatal exposure to the mixture of phthalates decreased prepubertal body weight and, in a dose-specific manner, periadolescent social play behavior. A dose-specific effect from phthalates with HFD was also seen in increased time alone in females during social play. HFD resulted in dams consuming more calories, having greater gestational weight gain, and licking and nursing their pups more, such that an early postnatal HFD generally increased pup body weight. There also was a tendency for increased oxidative stress markers at P10 within the medial prefrontal cortex of males exposed to the relatively high dose of phthalates and HFD. Effects on gene expression were inconsistent at P10 and P90 in both the medial prefrontal cortex and hypothalamus. Overall, this study demonstrates that phthalates and a maternal HFD only rarely interacted, except in oxidative stress markers in males. Additionally, perinatal exposure to an environmentally relevant mixture of phthalates can have a modest, but lasting, impact on social behaviors in both males and females.	Endocrinology	2,018	2
18,374,310	A method for recording miniature inhibitory postsynaptic currents in the central nervous system suitable for quantal analysis.	Quantal analysis of transmitter release is useful in examining presynaptic mechanisms involved in synaptic transmission. However, in central neurons, the presence of multiple synapses makes it difficult to use the traditional quantal analysis, developed for the neuromuscular transmission. We developed a method to minimize these difficulties. Experiments were performed, using the whole-cell patch-clamp recording technique, on rat CA1 pyramidal neurons in a hippocampal slice preparation. When the stratum radiatum was stimulated, mixed current signals including, miniature inhibitory postsynaptic currents (mIPSCs), miniature excitatory postsynaptic currents (mEPSCs), evoked inhibitory postsynaptic currents (eIPSCs) and evoked excitatory postsynaptic currents (eEPSCs), could be observed in CA1 pyramidal cells while slices were superfused with the normal, Na(+)-containing, medium. The mIPSCs could be blocked by bicuculline (10 microm). mEPSCs, eEPSCs and eIPSCs could not be observed when the Na(+)-containing perfusion medium was replaced by a Na(+)-free medium but reappeared when the Na(+)-containing medium was re-introduced. When a polarizing electrode was placed near the recorded neuron, while slices were superfused with the Na(+)-free medium, and depolarizing rectangular current pulses of different magnitudes were applied, the number of mIPSCs increased with increasing amount of the current. Amplitudes of the mIPSCs showed a Gaussian distribution and the coefficient of variation was small. These observations indicate that a combination of the Na(+)-free superfusing medium and local depolarizations with a polarizing electrode is useful for recording mIPSCs from a localized area of the recorded neuron and for quantal analysis.	Brain research	2,008	5
23,597,518	Limb-girdle muscular dystrophy type 2a with mutation in CAPN3: the first report in Taiwan.	The autosomal recessive limb-girdle muscular dystrophy type 2A (LGMD2A) is caused by mutations in the calpain 3 (CAPN3) gene, and it is characterized by selective atrophy and weakness of proximal limb and girdle muscles. We report a 33-year-old woman with initial presentations of exercise intolerance and running difficulty at age 15 years. At presentation, waddling gait, positive Gowers' sign, and marked muscle atrophy in pelvic and leg muscles were noted. Muscle computed tomography (CT) imaging demonstrated symmetric involvement of the posterior thigh muscles with relative sparing of vastus lateralis, sartorius, and gracilis. Muscle biopsy revealed a dystrophic change and many lobulated fibers on NADH-tetrazolium reductase staining. Genetic analysis of the CAPN3 gene identified a novel homozygous mutation of c2047_2050 del4, p.Lys683fs mutation, confirming the first LGMD2A patient in Taiwan.	Pediatrics and neonatology	2,015	2
32,571,741	The iliac pillar - Definition of an osseous fixation pathway for internal and external fixation.	Increasing numbers of unstable pelvic ring fractures, due to the ongoing demographic change and improvements in the rescue of high-energy traumatic events, are challenging trauma and orthopedic surgeons. While initial installation of an external fixation device is often necessary, placement of iliac crest pins can be difficult due to the complex osteology of the ilium.	Orthopaedics & traumatology, surgery & research : OTSR	2,020	9
27,649,834	Disciplinary Crossings.	Eighteen months ago, I left a permanent professorship in a generously interdisciplinary department of sociology and took an impermanent, lower-paying job at a university where I had to apply to something called the "Committee on Distinction" to retain the title of "Professor." Some people say, "That's what happens when Oxford calls." But it wasn't just that. It was the opportunity to engage in a groundbreaking experiment: to embed and integrate ethics within the Oxford Department of Psychiatry and Neuroscience. It's a dream job, for which I was willing to cross the disciplinary line into the medical sciences. In the United Kingdom, many bioethicists still work in departments outside science and medicine; similarly, those of us who work on neuroethics and psychiatric ethics tend to inhabit departments of philosophy, law, or sociology. I can report already that interdisciplinarity from this side feels and looks different.	The Hastings Center report	2,016	9
28,424,398	[Brodmann Areas 27, 28, 36 and 37: The Parahippocampal and the Fusiform Gyri].	First, Brodmann areas 27, 28, 36 and 37, were anatomically defined in the beginning of this review. These areas exist in the parahippocampal or fusiform gyrus of the ventral temporal lobe in humans. Subsequently, the current understanding of their functions was summarized on the basis of recent findings mainly through human functional neuroimaging studies and animal studies. Rodent studies have shown the existence of neuronal activities for representing space, such as those involving head-direction cells or grid cells, in areas 27 (the parasubicular cortex) and 28 (the ventral entorhinal cortex). Recent human neuroimaging studies have provided support for the idea that grid cells may also exist in the human entorhinal cortex. Many previous animal studies have shown that area 36 (the lateral perirhinal cortex) is crucial for various types of associative learning. Earlier human neuroimaging studies have also indicated that faces, bodies and visual word forms are represented in different regions of area 37 in the posterior fusiform gyrus. Recent neuroimaging studies in humans have shown substantial functional differentiation between face-related regions in areas 37 and 36, which is similar to that seen in macaque monkeys, as shown through their face patches. This implies the crucial involvement of both areas in face processing.	Brain and nerve = Shinkei kenkyu no shinpo	2,017	4
24,024,915	STICH 2: does decompression have a role in superficial intracerebral hematoma?	The recently published second Surgical Trial in Intracerebral Haemorrhage (STICH-2) tested whether surgical evacuation of superficial spontaneous intracerebral haemorrhage was effective at reducing death and disability at 6 months after onset. Participants were randomised to a policy of early surgical intervention or initial medical management alone within 48 hours of symptom onset. After enrolling 601 patients across 78 centres in 27 countries, intention to treat analysis showed no difference in outcome. Time to intervention was a median of 26 hours after symptom onset in the surgical arm, and craniotomy accounted for 98% of all surgical procedures. The interpretation of the overall neutral result is confounded by a high proportion of crossovers from the medical management arm of the study, predominantly of more severely affected patients. Further analysis may clarify whether decompressive surgery late after superficial intracerebral haemorrhage has any role in management.	International journal of stroke : official journal of the International Stroke Society	2,013	10
33,430,353	Being a Gambler during the COVID-19 Pandemic: A Study with Italian Patients and the Effects of Reduced Exposition.	The COVID-19 pandemic, with the consequent lockdown of about 3 months, can be viewed as an experimental model to observe the impact of the depletion of environmental factors that stimulate gambling, particularly electronic gambling machines (EGMs) that were set to zero. The effects of some structural characteristics of gambling activities that increase gambling behavior were studied among disordered gamblers in treatment in this unique scenario. In fact, studies investigating the effects of the lockdown on problem gamblers (PGs) under treatment are missing. The aims of this study were to analyze patients' gambling behavior and craving during the lockdown and to conduct a comparison between gambling disorder (GD) symptoms at the beginning of the treatment and during lockdown. The study was conducted in Italy, the European country with the largest gambling market and the first to be affected by the virus. Data were collected through a semi-structured telephone interview conducted by healthcare professionals. Participants were 135 PGs under treatment (109 males, mean age = 50.07). Results showed that most PGs achieved a significant improvement in their quality of life, with less gambling behavior, GD symptoms, and lower craving. No shift toward online gambling and very limited shift towards other potential addictive and excessive behaviors occurred. The longer the treatment, the more monitoring is present and the better the results in terms of symptoms reduction. Individual and environmental characteristics during the lockdown favored the reduction in symptoms. Consideration for prevention and treatment are discussed.	International journal of environmental research and public health	2,021	1
32,583,478	Comparing integrative cognitive-affective therapy and guided self-help cognitive-behavioral therapy to treat binge-eating disorder using standard and naturalistic momentary outcome measures: A randomized controlled trial.	Innovative treatments and outcome measures are needed for binge-eating disorder (BED). This randomized controlled trial compared Integrative Cognitive-Affective Therapy (ICAT-BED), an individual psychotherapy targeting momentary behavioral and emotional precipitants of binge eating, with an established cognitive-behavioral guided self-help (CBTgsh) treatment using standard and ecological momentary assessment (EMA) outcome measures.	The International journal of eating disorders	2,020	9
33,242,116	Density-based clustering of static and dynamic functional MRI connectivity features obtained from subjects with cognitive impairment.	Various machine-learning classification techniques have been employed previously to classify brain states in healthy and disease populations using functional magnetic resonance imaging (fMRI). These methods generally use supervised classifiers that are sensitive to outliers and require labeling of training data to generate a predictive model. Density-based clustering, which overcomes these issues, is a popular unsupervised learning approach whose utility for high-dimensional neuroimaging data has not been previously evaluated. Its advantages include insensitivity to outliers and ability to work with unlabeled data. Unlike the popular k-means clustering, the number of clusters need not be specified. In this study, we compare the performance of two popular density-based clustering methods, DBSCAN and OPTICS, in accurately identifying individuals with three stages of cognitive impairment, including Alzheimer's disease. We used static and dynamic functional connectivity features for clustering, which captures the strength and temporal variation of brain connectivity respectively. To assess the robustness of clustering to noise/outliers, we propose a novel method called recursive-clustering using additive-noise (R-CLAN). Results demonstrated that both clustering algorithms were effective, although OPTICS with dynamic connectivity features outperformed in terms of cluster purity (95.46%) and robustness to noise/outliers. This study demonstrates that density-based clustering can accurately and robustly identify diagnostic classes in an unsupervised way using brain connectivity.	Brain informatics	2,020	11
29,173,431	Managing the Complex Patient with Degenerative Cervical Myelopathy: How to Handle the Aging Spine, the Obese Patient, and Individuals with Medical Comorbidities.	Degenerative cervical myelopathy (DCM) is the most common cause of nontraumatic spinal cord injury worldwide. Even relatively mild impairment in functional scores can significantly impact daily activities. Surgery is an effective treatment for DCM, but outcomes are dependent on more than technique and preoperative neurologic deficits.	Neurosurgery clinics of North America	2,018	1
34,189,487	COVID-19: A pandemic that threatens physical and mental health by promoting physical inactivity.	Ever since the outbreak of Coronavirus disease 2019 (COVID-19) in late 2019, it has killed millions of people worldwide. Even people not stricken by this disease are not spared from its negative economic, social, and health-related drawbacks. This commentary provides insight into the potential mechanisms involved in the development of depression and emotional negativity escalating during the current pandemic. In particular, preventive measures of COVID-19, such as staying at home, are sedentarism measures that decrease physical activity. Physical inactivity alters gut microbiome structure in a fashion that promotes gut dysbiosis and flaring of systemic inflammation, leading to the buildup of body fat. Obesity, which contributes to a trail of health-depleting disorders, furthers gut microbial disintegration while fat tissue stimulates the release of cytokines, promotes metabolic resistance, and alters signaling involved in the production of antioxidants. As a result, the body gets flooded by toxic molecules such pro-inflammatory mediators, free radicals, and advanced glycation end products. These toxic molecules alter cellular function in all body tissues, including those of the brain. Neuroinflammation is associated with progressive declines in cognitive and motor functions along with dysregulation in emotions. Counteracting the sedentarism enforced by the COVID-19 pandemic through the participation in suitable indoors activities and the intake of healthy food is likely to protect against or revert physiological impairments that may affect people retreating to their homes during the current crisis, eventually restoring physical and mental health.	Sports medicine and health science	2,020	12
21,153,128	Estrogen modulation of two subpopulations of β-endorphin neurons in ovariectomized guinea pigs distinguished by peripherally injected fluorogold.	β-endorphin released by neurons in the arcuate nucleus affects the output of several neuroendocrine systems and estrogen levels modulate the production and secretion of β-endorphin. We used intraperitoneal injection of fluorogold to retrogradely label the cell bodies of neurons that project outside the blood-brain-barrier in conjunction with immunohistochemistry for β-endorphin to dual label the subpopulation of β-endorphin neurons that project to the median eminence or other sites of access to the peripheral circulation. We found that some identified β-endorphin neurons in the arcuate nucleus of ovariectomized guinea pigs sequestered fluorogold. Approximately 7% of β-endorphin-containing cells co-localized with fluorogold. The effect of estrogen on the number of identified β-endorphin cells was examined. A single estradiol benzoate injection to ovariectomized guinea pigs 24 h prior to sacrifice dramatically decreased the total number of β-endorphin cells identified in the rostral, medial and the caudal portions of the arcuate nucleus. Also, a significantly smaller percentage of fluorogold-filled cells was found to contain β-endorphin immunoreactivity in the estrogen-treated group. These data suggest that a subpopulation of β-endorphin neurons has access to the peripheral circulation and may alter the output of neurosecretory terminals at the level of the median eminence. Furthermore, estrogen affects this subpopulation and the general population of β-endorphin neurons in the arcuate nucleus in a similar manner.	Endocrine	1,995	11
32,827,687	Nutritional domains in frailty tools: Working towards an operational definition of nutritional frailty.	Different methods have been proposed for the assessment of the nutritional status in frailty phenotypes. In the present narrative review article, we have summarized the number and specifications of nutritional items in existing frailty tools, in order to develop a possible means of assessment and operational definition of the nutritional frailty phenotype. In six different databases until December 2019, we searched for original articles regarding frailty tools (i.e., scales, indexes, scores, questionnaires, instruments, evaluations, screening, indicators), analyzing each tool regarding nutritional items. We identified 160 articles describing 71 frailty tools. Among the selected frailty tools, 54 were community-based (70 %), 17 hospital-based (22 %), 4 validated in long-term care institutions for older adults (LTCIOA) (5.1 %) and 2 validated in both community- and hospital-based settings, including LTCIOA (2.5 %). Fifty-two of these tools (73 %) included at least one nutritional item. Twenty-two (42 %) reported two or more nutritional items. The items were grouped in the following categories: A) anthropometric measurements, B) laboratory measurements, and C) other nutritional-related measurements. Anthropometric measurements stood out compared to all other items. Nutritional items are included in the majority of frailty tools, strengthening the concept that they may have a direct implication on an increased risk of adverse health-related outcomes in frail subjects. This supports the development of the concept of nutritional frailty as an independent frailty phenotype. Subsequent steps will be to assess the contribution of each nutritional item to a possible operational definition of nutritional frailty and define the items that may best identify this new frailty phenotype.	Ageing research reviews	2,020	12
25,252,586	Ependymal damage in a Plasmodium yoelii yoelii lethal murine malaria model.	Malaria continues to be a major global health problem, and over 40% of the world's population is at risk. Severe or complicated malaria is defined by clinical or laboratory evidence of vital organ dysfunction, including dysfunction of the central nervous system (CNS). The pathogenesis of complicated malaria has not been completely elucidated; however, the development of the multiorgan affection seems to play an important role in the disruption of the blood brain barrier (BBB) that protects the CNS against chemical insults. Historically, the BBB has received more attention in the pathogenesis of malaria than have the cerebrospinal fluid-brain barrier (CSFBB) and ependymal cells. This perspective may be misguided because, in the context of disease or toxicity, the CSFBB is more vulnerable to many foreign invaders than are the capillaries. Given the lack on studies of the damage to the CSFBB and ependymal epithelium in experimental murine malaria, the present study evaluated morphological changes in the ependymal cells of CD-1 male mice infected with lethal Plasmodium yoelii yoelii (Pyy) via histopathology and scanning electron microscopy (SEM). Samples were taken two, four and six days post-infection (PI). No lesions were observed upon the initial infection. By the fourth day PI, fourth ventricle ependymal samples exhibited disruptions and roughened epithelia. More severe injuries were observed at six days PI and included thickened cilia and deep separations between the ependymal intercellular spaces. In some of the analyzed areas, the absence of microvilli and cell layer detachment were observed, and some areas exhibited blebbing surfaces. The ependymal cell lesions observed in the CD1 male mice infected with lethal Pyy seemed to facilitate the paracellular permeability of the CSFBB and consequently promote the access of inflammatory mediators and toxic molecules through the barrier, which resulted in damage to the brain tissue. Understanding the mechanism of ependymal disruption during lethal murine malaria could help to elucidate the local and systemic factors that are involved in the pathogenesis of the disease and may provide essential clues for the prevention and treatment of complicated human malaria.	Histology and histopathology	2,015	2
33,413,673	Increased P450 aromatase levels in post-menopausal women after acute ischemic stroke.	Sex differences in stroke have been attributed to the neuroprotective effects of estrogen, yet most clinical trials of estrogen supplementation for stroke prevention have failed. The contribution of sex hormones to stroke outcome remains a subject of debate. Aromatization of testosterone to estradiol in neural tissue leads to sexual differentiation. Emerging data suggests aromatase activity increases in response to brain injury, and increased aromatase expression is seen in the ischemic penumbra in animal models. The objective of this study was to examine the levels of endogenous sex steroids after acute ischemic stroke and determine if levels of sex steroids were associated with acute stroke outcomes.	Biology of sex differences	2,021	1
33,529,846	NK/T cell ratios associate with interleukin-2 receptor alpha chain expression and shedding in multiple sclerosis.	NK/T-cell ratios predict disease activity in relapsing remitting multiple sclerosis (RRMS). We investigated in 50 RRMS patients whether interleukin-2 receptor alpha-chain (IL-2Rα) expression and shedding associates with NK/T-cell balance, as suggested by daclizumab-trials in RRMS. A subsample (N = 31) was genotyped for IL2RA-associated MS risk SNPs. CD56	Journal of neuroimmunology	2,021	4
24,551,007	Multiple intracranial abscesses: Heralding asymptomatic venosus ASD.	A case of multiple intracranial abscesses in an immune-competent young girl is reported. She had chicken pox. Two weeks later, she presented with multiple intracranial abscesses. No significant cardiac abnormality was detected on transthoracic echocardiogram (TTE). The condition was treated medically. However, one of the abscesses adjacent to the CSF pathways enlarged on treatment and caused obstructive hydrocephalus that required stereotactic aspiration. Gram stain showed gram positive cocci in chain. Pus was sterile on culture. She was treated with broad spectrum IV antibiotics based on Gram staining report for 6 weeks followed by another 8 weeks of oral antibiotics. She made good recovery and had been leading a normal life. The abscess capsules took 30 months to resolve completely on MRI. A repeat TTE done in the follow up showed enlarged right heart chambers with a suggestion of a venosus ASD. A trans-esophageal echocardiogram (TEE) confirmed the presence of sinus venosus ASD from the SVC side with mainly left to right shunt. There was also partial anomalous drainage of the pulmonary veins. The patient underwent correction of the defect and has been doing well.	Asian journal of neurosurgery	2,013	10
32,624,427	In silico assessment of binding affinities of three dementia-protective Human Leukocyte Antigen (HLA) alleles to nine human herpes virus antigens.	Human herpes viruses (HHV) have been implicated in dementia. Class II Human Leukocyte Antigens (HLA) play a critical role in host protection from foreign antigens including herpes viruses through stimulating antibody production against them. In the present study we investigated the in silico binding affinity of 9 H HV to three Class II HLA alleles that have been found to protect against dementia: DRB101:01, DRB113:02, and DRB1*15:01.	Current research in translational medicine	2,020	11
33,190,469	Real-Time Monitoring System to Manage Mental Healthcare Emergency Unit.	Real-time relevant information helps guide the healthcare decision-making process in daily clinical practice as well as the management and optimization of healthcare processes. However, proprietary business intelligence suite solutions supporting the production of decision-making information requires investment that is out of reach of small and mediumsized healthcare facilities or those with limited resources, particularly in developing countries. This paper describes our experience in designing and implementing a real-time healthcare monitoring system solution to manage healthcare emergency units.	Healthcare informatics research	2,020	10
33,870,218	Purification of differentiated tumor cells from medulloblastoma for transplantation into mouse cerebellum.	This protocol provides the procedures for isolating differentiated tumor cells from medulloblastoma (MB) in mice. Procedures for transplantation into cerebella are also included to examine the tumorigenesis of differentiated MB cells. This protocol outlines the detailed steps required for (1) isolation of tumor cells from mouse MB, (2) purification of differentiated tumor cells by fluorescence-activated cell sorting, and (3) transplantation of tumor cells into cerebella. This protocol is useful to purify differentiated tumor cells for investigating mechanisms underlying MB progression. For complete details on the use and execution of this protocol, please refer to Cheng et. al. (2020).	STAR protocols	2,021	6
32,675,335	Black Dipole or White Dipole: Using Susceptibility Phase Imaging to Differentiate Cerebral Microbleeds from Intracranial Calcifications.	Phase imaging helps determine a lesion's susceptibility. However, various inhomogenous phase patterns could be observed in the serial phase images of a lesion and render image interpretation challenging. We evaluated the diagnostic accuracy of differentiating cerebral microbleeds and calcifications from phase patterns in axial locations.	AJNR. American journal of neuroradiology	2,020	8
32,682,638	Movement disorders in children with congenital Zika virus syndrome.	Congenital Zika Virus Syndrome (CZVS) denotes the neurologic and developmental sequelae of congenital infection of the Zika virus. While prior studies have detailed the associated clinical phenotypes, new findings continue to be identified. Abnormal postures and movements have been previously described in children with CZVS, but not in detail.	Brain & development	2,020	11
32,697,329	Nicotine increases alcohol self-administration in male rats via a μ-opioid mechanism within the mesolimbic pathway.	Alcohol and nicotine use disorders are commonly comorbid. Both alcohol and nicotine can activate opioid systems in reward-related brain regions, leading to adaptive changes in opioid signalling upon chronic exposure. The potential role of these adaptations for comorbidity is presently unknown. Here, we examined the contribution of μ and κ-opioid receptors to nicotine-induced escalation of alcohol self-administration in rats.	British journal of pharmacology	2,020	10
33,466,971	The "	We are glad to introduce the ninth Journal Club. This edition is focused on several relevant studies published in the last few years in the field of Exercise-Induced Immune Response, chosen by our Editorial Board members and their colleagues. We hope to stimulate your curiosity in this field and to share with you the passion for sport seen also from the scientific point of view. The Editorial Board members wish you an inspiring lecture.	Journal of functional morphology and kinesiology	2,018	7
33,777,575	Transient Ischemic Attack and Hypoventilation 12 Hours After Intra-vitreal Aflibercept Injection.	Given the role the vascular endothelial growth factor (VEGF) plays in controlling and preserving the integrity of the vascular endothelium intravitreal administration of anti-VEGF agents may affect the risk of thromboembolic events. This is particularly noticeable in patients who are at risk for atherosclerosis. Here, we present one of the first case reports of transient ischemic attack (TIA) together with hypoventilation secondary to aflibercept injection. A 63-year-old female suffered TIA together with hypoventilation about 12 hours after the third administration of intravitreal aflibercept, which is a VEGF inhibitor for diabetic macular edema (DME). Upon presentation, she was confused, had right-sided weakness and her respiratory rate was six breaths per minute, all of these resolved within the next 24 hours. The serum tests, cerebrospinal fluid (CSF) analysis, brain imaging, and carotid Doppler ultrasound were unremarkable. An ophthalmic exam revealed signs of bilateral proliferative diabetic retinopathy with left macular edema. Detailed reports of similar cases are lacking in the literature. Hypoventilation and thromboembolic could be possible side effects of aflibercept that necessitate more investigation.	Cureus	2,021	2
32,976,646	Time of referral to older adult liaison psychiatry service and other factors affecting length of stay in the general hospital.	To explore the relationship between social and clinical factors with (1) Time to referral to an older adult liaison psychiatry service, and (2) Length of stay (LOS), in a sample of older adults admitted to an acute general medical hospital receiving liaison psychiatry intervention, in London, United Kingdom, over a 3-year period.	International journal of geriatric psychiatry	2,021	3
29,535,907	A Comprehensive Review of Medical Imaging Equipment Used in Cadaveric Studies.	Medical imaging techniques have led to great advances in clinical anatomy and forensic pathology. New and emerging technologies allow healthcare professionals to view and understand the human body from different perspectives. This gives way to new and improved interventions, treatment plans, and an overall understanding of the human body. Herein, we present a comprehensive review of the various medical imaging equipment used in cadaveric studies along with their individual strengths and limitations.	Cureus	2,018	1
33,032,028	Validity of the patient health questionnaire-2 (PHQ-2) for the detection of depression in primary care in Colombia.	The PHQ-2 is a screening test for major depressive disorder (MDD) derived from PHQ-9, which has shown to be useful in the detection of cases of clinical significance in previous studies. The psychometric properties of PHQ-2 in the Colombian population are unknown.	Journal of affective disorders	2,021	1
32,741,526	Alteration of orexin-A and PKCα in the postmortem brain of pure-opioid and multi-drug abusers.	Finding changes induced by the drug of abuse is one of the most important approaches to design new drugs for the treatment of substance use disorders (SUD). Postmortem study is the most reliable method for detecting alteration in the brain of SUD patients. Recently, the role of orexinergic system in SUD is in consideration. In the current study, we evaluated the level of orexin-A in the CSF and protein kinase Cα (PKCα) in the brain of pure-opioid (POA) and multi-drug abusers (MDA). A total of 56 POA, 45 MDA, and 13 matched control brains were collected from the legal medicine center, Tehran, Iran. The CSF was gathered from the third ventricle immediately after opening the skull and kept at -80 °C. The medial prefrontal cortex (mPFC), lateral prefrontal cortex (lPFC), orbitofrontal cortex (OFC), nucleus accumbens (NAc), and amygdala were dissected from fresh brain, frozen with liquid nitrogen and kept at -80 °C. The level of orexin-A evaluated in the CSF. Using western blotting, the level of PKCα assessed in the brain. Obtained data revealed that the level of orexin-A increased in POA and MDA compared with the control group (p < 0.05). In addition, the level of PKCα increased in the prefrontal cortex and amygdala of the abusers compared with the control group, although we did not detect changes in the level of PKCα in the NAc. Along with animal studies, the current results showed that the level of orexin increased in the CSF of drug abusers, which might be related to increases in the activation of lateral hypothalamic orexinergic neurons faced with the drug of abuse. Enhancement in the level of PKCα in the drug reward circuits might be adaptational changes induced by orexin and drugs of abuse.	Neuropeptides	2,020	10
32,691,472	Volumetric imaging of myelin in vivo using 3D inversion recovery-prepared ultrashort echo time cones magnetic resonance imaging.	Direct myelin imaging is promising for characterization of multiple sclerosis (MS) brains at diagnosis and in response to therapy. In this study, a 3D inversion recovery-prepared ultrashort echo time cones (IR-UTE-Cones) sequence was used for both morphological and quantitative imaging of myelin on a clinical 3 T scanner. Myelin powder phantoms with different myelin concentrations were imaged with the 3D UTE-Cones sequence and it showed a strong correlation between concentrations and UTE-Cones signals, demonstrating the ability of the UTE-Cones sequence to directly image myelin in the brain. Quantitative myelin imaging with multi-echo IR-UTE-Cones sequences show similar T	NMR in biomedicine	2,020	10
33,212,887	The Antioxidant Role of One-Carbon Metabolism on Stroke.	One-carbon (1C) metabolism is a metabolic network that is centered on folate, a B vitamin; it integrates nutritional signals with biosynthesis, redox homeostasis, and epigenetics. This metabolic pathway also reduces levels of homocysteine, a non-protein amino acid. High levels of homocysteine are linked to increased risk of hypoxic events, such as stroke. Several preclinical studies have suggested that 1C metabolism can impact stroke outcome, but the clinical data are unclear. The objective of this paper was to review preclinical and clinical research to determine whether 1C metabolism has an antioxidant role on stroke. To accomplish the objective, we searched for publications using the following medical subject headings (MeSH) keywords: antioxidants, hypoxia, stroke, homocysteine, one-carbon metabolism, folate, methionine, and dietary supplementation of one-carbon metabolism. Both pre-clinical and clinical studies were retrieved and reviewed. Our review of the literature suggests that deficiencies in 1C play an important role in the onset and outcome of stroke. Dietary supplementation of 1C provides beneficial effects on stroke outcome. For stroke-affected patients or individuals at high risk for stroke, the data suggest that nutritional modifications in addition to other therapies could be incorporated into a treatment plan.	Antioxidants (Basel, Switzerland)	2,020	11
33,155,057	Green Light Exposure Improves Pain and Quality of Life in Fibromyalgia Patients: A Preliminary One-Way Crossover Clinical Trial.	Fibromyalgia is a functional pain disorder in which patients suffer from widespread pain and poor quality of life. Fibromyalgia pain and its impact on quality of life are not effectively managed with current therapeutics. Previously, in a preclinical rat study, we demonstrated that exposure to green light-emitting diodes (GLED) for 8 hours/day for 5 days resulted in antinociception and reversal of thermal and mechanical hypersensitivity associated with models of injury-related pain. Given the safety of GLED and the ease of its use, our objective is to administer GLED as a potential therapy to patients with fibromyalgia.	Pain medicine (Malden, Mass.)	2,021	2
24,283,480	Diagnostic problems in "clinically definite" multiple sclerosis patients with normal CSF and multiple MRI abnormalities.	Among patients who underwent cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) examination during a 5-year period, we found 18 patients at the multiple sclerosis center of the University of Rome and clinically definite multiple sclerosis, MRI white matter abnormalities, normal CSF examination, a disease duration of at least 1 year and an upper age of < 45 years at onset These patients were examined again with a variety of tests screening for different diseases mimicking multiple sclerosis. Alternative diagnoses reached after laboratory tests were: Lyme disease, two cases of vasculitis, mitochondrial encephalomyopathy, multiple ischemic lesions caused by atrial septum aneurysm and olivopontocerebellar atrophy. Hence, six of these 18 patients had a final diagnosis other than multiple sclerosis, while 12 remained with a final diagnosis of "MS with normal CSF". Our study suggests that in patients with a clinical picture of multiple sclerosis and disseminated white matter MRI lesions but no CSF abnormalities, the classical clinical criteria may not be sufficiently specific, unless confirmed by a very prolonged clinical history with repeated MRI.	European journal of neurology	1,994	11
27,158,651	Data on copula modeling of mixed discrete and continuous neural time series.	Copula is an important tool for modeling neural dependence. Recent work on copula has been expanded to jointly model mixed time series in neuroscience ("Hu et al., 2016, Joint Analysis of Spikes and Local Field Potentials using Copula" [1]). Here we present further data for joint analysis of spike and local field potential (LFP) with copula modeling. In particular, the details of different model orders and the influence of possible spike contamination in LFP data from the same and different electrode recordings are presented. To further facilitate the use of our copula model for the analysis of mixed data, we provide the Matlab codes, together with example data.	Data in brief	2,016	6
20,433,273	Disseminated enterogenous cells at the cervicomedullary junction causing communicating hydrocephalus.	The authors present a unique case of a patient with communicating hydrocephalus and repeated ventriculoperitoneal shunt obstructions resulting from mucin-secreting enterogenous cell deposits at the cervicomedullary junction. Pathological examinations revealed that these cellular deposits lacked characteristic cystic architecture and the patient had no history of previous cyst with dissemination. Because of the repeated shunt obstructions and inability to surgically resect the lesion in its entirety, the authors elected radiation therapy to the cervicomedullary junction, encompassing the radiological abnormality. As of this writing, the patient has remained at neurological baseline and has not required further shunt revisions for obstruction.	Journal of neurosurgery	2,010	12
31,109,741	An Optical Exposé of Cortical Function.	Neural imaging benefits from optical access to widespread brain areas. A recent study (Ghanbari et al. Nat. Commun. 2019;10;1500) introduces See-Shell, a transparent polymer skull that reveals the entire dorsal cortex in mice. See-Shells are 3D-printed, customizable, and modifiable for combined neural recording and manipulation, offering advantages for high-resolution, multiscale measures of in vivo brain function.	Trends in neurosciences	2,019	8
32,731,199	Nine Hole Peg Test asymmetry in refining upper limb assessment in multiple sclerosis.	The Expanded Disability Status Scale (EDSS) is the most frequently used scale to measure neurologic impairment and quantify the level of disability in Multiple Sclerosis (MS) even though the scale focuses on ambulation and undervalues upper limb (UL) impairment. The 9-Hole Peg Test (9-HPT) is the gold standard for UL assessment in MS, calculating a mean score from right and left arms, even though subjects with MS often show a lateralization of neurological deficit.	Multiple sclerosis and related disorders	2,020	10
33,098,256	Quantification of Myelinated Nerve Fraction and Degeneration in Spinal Cord Neuropil by SHIFT MRI.	Neurodegeneration is a complex cellular process linked to prompt changes in myelin integrity and gradual neuron loss. Current imaging techniques offer estimations of myelin volumes in lesions/remyelinated areas but are limited to detect subtle injury.	Journal of magnetic resonance imaging : JMRI	2,021	4
32,289,070	Virus infection-induced host mRNA degradation and potential application of live cell imaging.	Viruses exist wherever there is life. They can cause allergy, immune response, inflammation, and even fatal diseases directly or indirectly. Accumulating evidence shows that host RNA undergoes rapid degradation during virus infection. Herein, we focus on several possible mechanisms of infection-induced host RNA turnover, which seems to be a common strategy for both prokaryotic and eukaryotic viruses during the very early stage of infection and a potential application of live cell imaging on its visualization.	Radiology of infectious diseases (Beijing, China)	2,018	12
31,170,999	Reactive microglia and IL1β/IL-1R1-signaling mediate neuroprotection in excitotoxin-damaged mouse retina.	Microglia and inflammation have context-specific impacts upon neuronal survival in different models of central nervous system (CNS) disease. Herein, we investigate how inflammatory mediators, including microglia, interleukin 1 beta (IL1β), and signaling through interleukin 1 receptor type 1 (IL-1R1), influence the survival of retinal neurons in response to excitotoxic damage.	Journal of neuroinflammation	2,019	6
32,598,984	Agmatine reverses memory deficits induced by Aβ	Agmatine is a biogenic amine synthesized following decarboxylation of L-arginine by the enzyme arginine decarboxylase and exhibits favourable outcome in neurodegenerative disorders. Present study was designed to examine the relationship between agmatine and the imidazoline receptors in memory deficits induced by Aβ	Pharmacology, biochemistry, and behavior	2,020	9
32,144,421	Compression of Cerebellar Functional Gradients in Schizophrenia.	Our understanding of cerebellar involvement in brain disorders has evolved from motor processing to high-level cognitive and affective processing. Recent neuroscience progress has highlighted hierarchy as a fundamental principle for the brain organization. Despite substantial research on cerebellar dysfunction in schizophrenia, there is a need to establish a neurobiological framework to better understand the co-occurrence and interaction of low- and high-level functional abnormalities of cerebellum in schizophrenia. To help to establish such a framework, we investigated the abnormalities in the distribution of sensorimotor-supramodal hierarchical processing topography in the cerebellum and cerebellar-cerebral circuits in schizophrenia using a novel gradient-based resting-state functional connectivity (FC) analysis (96 patients with schizophrenia vs 120 healthy controls). We found schizophrenia patients showed a compression of the principal motor-to-supramodal gradient. Specifically, there were increased gradient values in sensorimotor regions and decreased gradient values in supramodal regions, resulting in a shorter distance (compression) between the sensorimotor and supramodal poles of this gradient. This pattern was observed in intra-cerebellar, cerebellar-cerebral, and cerebral-cerebellar FC. Further investigation revealed hyper-connectivity between sensorimotor and cognition areas within cerebellum, between cerebellar sensorimotor and cerebral cognition areas, and between cerebellar cognition and cerebral sensorimotor areas, possibly contributing to the observed compressed pattern. These findings present a novel mechanism that may underlie the co-occurrence and interaction of low- and high-level functional abnormalities of cerebellar and cerebro-cerebellar circuits in schizophrenia. Within this framework of abnormal motor-to-supramodal organization, a cascade of impairments stemming from disrupted low-level sensorimotor system may in part account for high-level cognitive cerebellar dysfunction in schizophrenia.	Schizophrenia bulletin	2,020	9
33,440,196	Common and distinct neural correlates of music and food-induced pleasure: A coordinate-based meta-analysis of neuroimaging studies.	Neuroimaging studies have shown that, despite the abstractness of music, it may mimic biologically rewarding stimuli (e.g., food) in its ability to engage the brain's reward circuitry. However, due to the lack of research comparing music and other types of reward, it is unclear to what extent the recruitment of reward-related structures overlaps among domains. To achieve this goal, we performed a coordinate-based meta-analysis of 38 neuroimaging studies (703 subjects) comparing the brain responses specifically to music and food-induced pleasure. Both engaged a common set of brain regions, including the ventromedial prefrontal cortex, ventral striatum, and insula. Yet, comparative analyses indicated a partial dissociation in the engagement of the reward circuitry as a function of the type of reward, as well as additional reward type-specific activations in brain regions related to perception, sensory processing, and learning. These results support the idea that hedonic reactions rely on the engagement of a common reward network, yet through specific routes of access depending on the modality and nature of the reward.	Neuroscience and biobehavioral reviews	2,021	4
33,264,598	SCENITH: A Flow Cytometry-Based Method to Functionally Profile Energy Metabolism with Single-Cell Resolution.	Energetic metabolism reprogramming is critical for cancer and immune responses. Current methods to functionally profile the global metabolic capacities and dependencies of cells are performed in bulk. We designed a simple method for complex metabolic profiling called SCENITH, for single-cell energetic metabolism by profiling translation inhibition. SCENITH allows for the study of metabolic responses in multiple cell types in parallel by flow cytometry. SCENITH is designed to perform metabolic studies ex vivo, particularly for rare cells in whole blood samples, avoiding metabolic biases introduced by culture media. We analyzed myeloid cells in solid tumors from patients and identified variable metabolic profiles, in ways that are not linked to their lineage or their activation phenotype. SCENITH's ability to reveal global metabolic functions and determine complex and linked immune-phenotypes in rare cell subpopulations will contribute to the information needed for evaluating therapeutic responses or patient stratification.	Cell metabolism	2,020	12
31,169,691	Radiomics signature on 3T dynamic contrast-enhanced magnetic resonance imaging for estrogen receptor-positive invasive breast cancers: Preliminary results for correlation with Oncotype DX recurrence scores.	To evaluate the ability of a radiomics signature based on 3T dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to distinguish between low and non-low Oncotype DX (OD) risk groups in estrogen receptor (ER)-positive invasive breast cancers.Between May 2011 and March 2016, 67 women with ER-positive invasive breast cancer who performed preoperative 3T MRI and OD assay were included. We divided the patients into low (OD recurrence score [RS] <18) and non-low risk (RS ≥18) groups. Extracted radiomics features included 8 morphological, 76 histogram-based, and 72 higher-order texture features. A radiomics signature (Rad-score) was generated using the least absolute shrinkage and selection operator (LASSO). Univariate and multivariate logistic regression analyses were performed to investigate the association between clinicopathologic factors, MRI findings, and the Rad-score with OD risk groups, and the areas under the receiver operating characteristic curves (AUC) were used to assess classification performance of the Rad-score.The Rad-score was constructed for each tumor by extracting 10 (6.3%) from 158 radiomics features. A higher Rad-score (odds ratio [OR], 65.209; P <.001), Ki-67 expression (OR, 17.462; P = .007), and high p53 (OR = 8.449; P = .077) were associated with non-low OD risk. The Rad-score classified low and non-low OD risk with an AUC of 0.759.The Rad-score showed the potential for discrimination between low and non-low OD risk groups in patients with ER-positive invasive breast cancers.	Medicine	2,019	6
33,554,779	MOTS-c reduces myostatin and muscle atrophy signaling.	Obesity and type 2 diabetes are metabolic diseases, often associated with sarcopenia and muscle dysfunction. MOTS-c, a mitochondrial-derived peptide, acts as a systemic hormone and has been implicated in metabolic homeostasis. Although MOTS-c improves insulin sensitivity in skeletal muscle, whether MOTS-c impacts muscle atrophy is not known. Myostatin is a negative regulator of skeletal muscle mass and also one of the possible mediators of insulin resistance-induced skeletal muscle wasting. Interestingly, we found that plasma MOTS-c levels are inversely correlated with myostatin levels in human subjects. We further demonstrated that MOTS-c prevents palmitic acid-induced atrophy in differentiated C2C12 myotubes, whereas MOTS-c administration decreased myostatin levels in plasma in diet-induced obese mice. By elevating AKT phosphorylation, MOTS-c inhibits the activity of an upstream transcription factor for myostatin and other muscle wasting genes, FOXO1. MOTS-c increases mTORC2 and inhibits PTEN activity, which modulates AKT phosphorylation. Further upstream, MOTS-c increases CK2 activity, which leads to PTEN inhibition. These results suggest that through inhibition of myostatin, MOTS-c could be a potential therapy for insulin resistance-induced skeletal muscle atrophy as well as other muscle wasting phenotypes including sarcopenia.	American journal of physiology. Endocrinology and metabolism	2,021	4
32,971,217	Anorexia nervosa and gut microbiota: A systematic review and quantitative synthesis of pooled microbiological data.	Alterations of gut microbiota may play a role in Anorexia Nervosa (AN) through perturbations of the gut-brain axis. Some studies found differences in the gut microbiota of patients with AN compared to healthy controls, but results are heterogeneous. The aim of this work was to systematically review the existing studies comparing gut microbial composition in AN and healthy controls, and to perform a quantitative synthesis of the pooled clinical and microbiological data, when available.	Progress in neuro-psychopharmacology & biological psychiatry	2,021	3
33,037,478	Comparison of effectiveness of trihexyphenidyl and levodopa on motor symptoms in Parkinson's disease.	Despite anti-cholinergics being the oldest type of medication used for the treatment of Parkinson's disease (PD), the mechanism of action and exact benefit is unclear. This study compared the effectiveness of trihexyphenidyl (THP) and levodopa (LD) on motor symptoms in patients with PD. Patients with PD who are currently taking or had taken THP were recruited. UPDRS-III was done following overnight medication OFF state and 30 min, 60 min, 90 min, and 120 min after THP (4 mg). After a forty-eight-hour interval, UPDRS-III was assessed one hour after Levodopa/carbidopa (200/50 mg) in an overnight OFF state. Twenty patients with a mean age of 57.9 ± 7.8 years and mean duration of illness of 5.1 ± 3.6 years were recruited. UPDRS-III score reduction (%) with THP was maximum in the tremor sub-score (53.8 ± 22.8) and was significantly better compared to improvement in total-UPDRS-III (27.0 ± 14.7), bradykinesia-UPDRS-III (22.2 ± 27.2), rigidity-UPDRS-III (29.5 ± 28.0) and axial-UPDRS-III (8.1 ± 13.3) sub-score. In comparison, respective LD improvement was 67.1 ± 22.9 (tremor-UPDRS-III), 61.3 ± 14.4 (total-UPDRS-III), 67.9 ± 32.1 (bradykinesia-UPDRS-III), 65.3 ± 25.5 (rigidity-UPDRS-III) and 50.7 ± 16.0 (axial-UPDRS-III). Improvement (%) in tre-UPDRS-III post-THP was comparable to that of post-LD (53.8 ± 22.8 vs. 67.1 ± 22.9, p = 0.057). Those with same or better tremor response with THP had significantly milder baseline tremor severity than those who had better response with LD (tre-UPDRS-III-OFF, 10.0 ± 2.8 vs. 5.8 ± 4.0, p = 0.013). Both THP and LD showed significant improvement in UPDRS-III. With THP, the maximum degree of improvement was in the tremor sub-score and not significantly different to that obtained by LD. Those with better tremor response on THP had milder tremor severity.	Journal of neural transmission (Vienna, Austria : 1996)	2,020	12
33,676,189	Altered cortico-striatal functional connectivity in people with high levels of schizotypy: A longitudinal resting-state study.	Cortico-striatal functional connectivity has been implicated in the neuropathology of schizophrenia. However, the longitudinal relationship between the cortico-striatal connectivity and schizotypy remains unknown. We examined the resting-state fMRI connectivity in 27 individuals with a high level of schizotypy and 20 individuals with a low level of schizotypy at baseline and 18 months later. Correlations between changes in cortico-striatal connectivity and changes in schizotypy scores over time were examined.	Asian journal of psychiatry	2,021	4
29,453,490	Goal-directed reaching: the allocentric coding of target location renders an offline mode of control.	Reaching to a veridical target permits an egocentric spatial code (i.e., absolute limb and target position) to effect fast and effective online trajectory corrections supported via the visuomotor networks of the dorsal visual pathway. In contrast, a response entailing decoupled spatial relations between stimulus and response is thought to be primarily mediated via an allocentric code (i.e., the position of a target relative to another external cue) laid down by the visuoperceptual networks of the ventral visual pathway. Because the ventral stream renders a temporally durable percept, it is thought that an allocentric code does not support a primarily online mode of control, but instead supports a mode wherein a response is evoked largely in advance of movement onset via central planning mechanisms (i.e., offline control). Here, we examined whether reaches defined via ego- and allocentric visual coordinates are supported via distinct control modes (i.e., online versus offline). Participants performed target-directed and allocentric reaches in limb visible and limb-occluded conditions. Notably, in the allocentric task, participants reached to a location that matched the position of a target stimulus relative to a reference stimulus, and to examine online trajectory amendments, we computed the proportion of variance explained (i.e., R	Experimental brain research	2,018	4
33,200,442	Consensus guidelines for the diagnosis and management of pyridoxine-dependent epilepsy due to α-aminoadipic semialdehyde dehydrogenase deficiency.	Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is an autosomal recessive condition due to a deficiency of α-aminoadipic semialdehyde dehydrogenase, which is a key enzyme in lysine oxidation. PDE-ALDH7A1 is a developmental and epileptic encephalopathy that was historically and empirically treated with pharmacologic doses of pyridoxine. Despite adequate seizure control, most patients with PDE-ALDH7A1 were reported to have developmental delay and intellectual disability. To improve outcome, a lysine-restricted diet and competitive inhibition of lysine transport through the use of pharmacologic doses of arginine have been recommended as an adjunct therapy. These lysine-reduction therapies have resulted in improved biochemical parameters and cognitive development in many but not all patients. The goal of these consensus guidelines is to re-evaluate and update the two previously published recommendations for diagnosis, treatment, and follow-up of patients with PDE-ALDH7A1. Members of the International PDE Consortium initiated evidence and consensus-based process to review previous recommendations, new research findings, and relevant clinical aspects of PDE-ALDH7A1. The guideline development group included pediatric neurologists, biochemical geneticists, clinical geneticists, laboratory scientists, and metabolic dieticians representing 29 institutions from 16 countries. Consensus guidelines for the diagnosis and management of patients with PDE-ALDH7A1 are provided.	Journal of inherited metabolic disease	2,021	1
32,728,903	Surgical management for large vestibular schwannomas: a systematic review, meta-analysis, and consensus statement on behalf of the EANS skull base section.	The optimal management of large vestibular schwannomas continues to be debated. We constituted a task force comprising the members of the EANS skull base committee along with international experts to derive recommendations for the management of this problem from a European perspective.	Acta neurochirurgica	2,020	11
26,552,643	BRCA2-positive spinal intramedullary ovarian metastatic disease: case report.	Ovarian cancer is the fourth leading cause of cancer death in women, but advances in treatment have led to longer survival among these patients. Tied to these advances and increased survival, however, have been new patterns of metastatic spread.	The spine journal : official journal of the North American Spine Society	2,016	3
32,564,090	Olig2-Induced Semaphorin Expression Drives Corticospinal Axon Retraction After Spinal Cord Injury.	Axon regeneration is limited in the central nervous system, which hinders the reconstruction of functional circuits following spinal cord injury (SCI). Although various extrinsic molecules to repel axons following SCI have been identified, the role of semaphorins, a major class of axon guidance molecules, has not been thoroughly explored. Here we show that expression of semaphorins, including Sema5a and Sema6d, is elevated after SCI, and genetic deletion of either molecule or their receptors (neuropilin1 and plexinA1, respectively) suppresses axon retraction or dieback in injured corticospinal neurons. We further show that Olig2+ cells are essential for SCI-induced semaphorin expression, and that Olig2 binds to putative enhancer regions of the semaphorin genes. Finally, conditional deletion of Olig2 in the spinal cord reduces the expression of semaphorins, alleviating the axon retraction. These results demonstrate that semaphorins function as axon repellents following SCI, and reveal a novel transcriptional mechanism for controlling semaphorin levels around injured neurons to create zones hostile to axon regrowth.	Cerebral cortex (New York, N.Y. : 1991)	2,020	10
33,007,248	Immune Receptor Signaling and the Mushroom Body Mediate Post-ingestion Pathogen Avoidance.	In spite of the positive effects of bacteria on health, certain species are harmful, and therefore, animals must weigh nutritional benefits against negative post-ingestion consequences and adapt their behavior accordingly. Here, we use Drosophila to unravel how the immune system communicates with the brain, enabling avoidance of harmful foods. Using two different known fly pathogens, mildly pathogenic Erwinia carotovora (Ecc15) and highly virulent Pseudomonas entomophila (Pe), we analyzed preference behavior in naive flies and after ingestion of either of these pathogens. Although survival assays confirmed the harmful effect of pathogen ingestion, naive flies preferred the odor of either pathogen to air and also to harmless mutant bacteria, suggesting that flies are not innately repelled by these microbes. By contrast, feeding assays showed that, when given a choice between pathogenic and harmless bacteria, flies-after an initial period of indifference-shifted to a preference for the harmless strain, a behavior that lasted for several hours. Flies lacking synaptic output of the mushroom body (MB), the fly's brain center for associative memory formation, lost the ability to distinguish between pathogenic and harmless bacteria, suggesting this to be an adaptive behavior. Interestingly, this behavior relied on the immune receptors PGRP-LC and -LE and their presence in octopaminergic neurons. We postulate a model wherein pathogen ingestion triggers PGRP signaling in octopaminergic neurons, which in turn relay the information about the harmful food source directly or indirectly to the MB, where an appropriate behavioral output is generated.	Current biology : CB	2,020	12
32,059,984	Seizures in Mouse Models of Rare Neurodevelopmental Disorders.	Genetic neurodevelopmental disorders - that often include epilepsy as part of their phenotype - are a heterogeneous and clinically challenging spectrum of disorders in children. Although seizures often contribute significantly to morbidity in these affected populations, the mechanisms of epileptogenesis in these conditions remain poorly understood. Different model systems have been developed to aid in unraveling these mechanisms, which include a number of specific mutant mouse lines which genocopy specific general types of mutations present in patients. These mouse models have not only allowed for assessments of behavioral and electrographic seizure phenotypes to be ascertained, but also have allowed effects on the neurodevelopmental alterations and cognitive impairments associated with these disorders to be examined. In addition, these models play a role in advancing our understanding of these epileptic processes and developing preclinical therapeutics. The concordance of seizure phenotypes - in a select group of rare, genetic, neurodevelopmental disorders and epileptic encephalopathies - found between human patients and their model counterparts will be summarized. This review aims to assess whether models of Rett syndrome, CDKL5 deficiency disorder, Fragile-X syndrome, Dravet syndrome, and Ohtahara syndrome phenocopy the seizures seen in human patients.	Neuroscience	2,020	10
32,854,587	An acetylcholinesterase inhibitor, donepezil, increases anxiety and cortisol levels in adult zebrafish.	A potent acetylcholinesterase inhibitor, donepezil is a cognitive enhancer clinically used to treat neurodegenerative diseases. However, its complete pharmacological profile beyond cognition remains unclear. The zebrafish (	Journal of psychopharmacology (Oxford, England)	2,020	12
32,725,449	Neuroinvasion, neurotropic, and neuroinflammatory events of SARS-CoV-2: understanding the neurological manifestations in COVID-19 patients.	Respiratory viruses are opportunistic pathogens that infect the upper respiratory tract in humans and cause severe illnesses, especially in vulnerable populations. Some viruses have neuroinvasive properties and activate the immune response in the brain. These immune events may be neuroprotective or they may cause long-term damage similar to what is seen in some neurodegenerative diseases. The new "Severe Acute Respiratory Syndrome Coronavirus 2" (SARS-CoV-2) is one of the Respiratory viruses causing highly acute lethal pneumonia coronavirus disease 2019 (COVID-19) with clinical similarities to those reported in "Severe Acute Respiratory Syndrome Coronavirus"(SARS-CoV) and the "Middle East Respiratory Syndrome Coronavirus"(MERS-CoV) including neurological manifestation. To examine the possible neurological damage induced by SARS-CoV-2, it is necessary to understand the immune reactions to viral infection in the brain, and their short- and long-term consequences. Considering the similarities between SARS-CoV and SARS-CoV-2, which will be discussed, cooperative homological and phylogenetical studies lead us to question if SARS-CoV-2 can have similar neuroinvasive capacities and neuroinflammatiory events that may lead to the same short- and long-term neuropathologies that SARS-CoV had shown in human and animal models. To explain the neurological manifestation caused by SARS-CoV-2, we will present a literature review of 765 COVID-19 patients, in which 18% had neurological symptoms and complications, including encephalopathy, encephalitis and cerebrovascular pathologies, acute myelitis, and Guillain-Barré syndrome. Clinical studies describe anosmia or partial loss of the sense of smell as the most frequent symptom in COVID19 patients, suggesting that olfactory dysfunction and the initial ultrarapid immune responses could be a prognostic factor.	Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology	2,020	10
32,652,677	Expansion of the phenotypic spectrum of de novo missense variants in kinesin family member 1A (KIF1A).	Defects in the motor domain of kinesin family member 1A (KIF1A), a neuron-specific ATP-dependent anterograde axonal transporter of synaptic cargo, are well-recognized to cause a spectrum of neurological conditions, commonly known as KIF1A-associated neurological disorders (KAND). Here, we report one mutation-negative female with classic Rett syndrome (RTT) harboring a de novo heterozygous novel variant [NP_001230937.1:p.(Asp248Glu)] in the highly conserved motor domain of KIF1A. In addition, three individuals with severe neurodevelopmental disorder along with clinical features overlapping with KAND are also reported carrying de novo heterozygous novel [NP_001230937.1:p.(Cys92Arg) and p.(Pro305Leu)] or previously reported [NP_001230937.1:p.(Thr99Met)] variants in KIF1A. In silico tools predicted these variants to be likely pathogenic, and 3D molecular modeling predicted defective ATP hydrolysis and/or microtubule binding. Using the neurite tip accumulation assay, we demonstrated that all novel KIF1A variants significantly reduced the ability of the motor domain of KIF1A to accumulate along the neurite lengths of differentiated SH-SY5Y cells. In vitro microtubule gliding assays showed significantly reduced velocities for the variant p.(Asp248Glu) and reduced microtubule binding for the p.(Cys92Arg) and p.(Pro305Leu) variants, suggesting a decreased ability of KIF1A to move along microtubules. Thus, this study further expanded the phenotypic characteristics of KAND individuals with pathogenic variants in the KIF1A motor domain to include clinical features commonly seen in RTT individuals.	Human mutation	2,020	10
19,137,346	Neuronal functional diversity and collective behaviors: a scientific case.	A major issue in today's neuroscience is how the brain complex and highly flexible organization emerges from its individual components. Robustness of neuronal properties with weak linkages between regulatory processes are suggested to account for the adaptive, tunable, multistable dynamics, the coding schemes and the complexity of neuronal functional (sub)systems. Interneurons and neurotransmitter diversity, resonance phenomena due to properties of the cell or network, time/frequency-dependent activation of dedicated neuronal assemblies, code- and frequency-specific oscillations interact in determining the brain functional setup and operations. Despite the scientific relevance, comprehensive theories are not yet available, but the scenario--however incomplete and incompletely characterized--is promising and warrants further investigation.	Cognitive processing	2,009	2
33,468,604	Association between vaping and health outcomes in patients with opioid use disorder: a systematic review protocol.	Vaping behaviour has increased in popularity and is particularly important to examine how it effects health outcomes in vulnerable populations, including those with opioid use disorder (OUD). With polysubstance use including cigarette and cannabis use being highly prevalent in the OUD population and cannabis/nicotine increasingly being consumed by vaping, vaping may have an important contribution to health outcomes in these individuals. The primary objective of this review is to systematically assess the literature related to patients with OUD and the effects vaping has shown on their physical and mental health.	BMJ open	2,021	1
33,020,978	The role of SCF	A proper balance between proliferation and differentiation of cerebellar granule cell precursors (GCPs) is required for appropriate cerebellar morphogenesis. The Skp1-Cullin1-F-box (SCF) complex, an E3 ubiquitin ligase complex, is involved in polyubiquitination and subsequent degradation of various cell cycle regulators and transcription factors. However, it remains unknown how the SCF complex affects proliferation and differentiation of GCPs. In this study, we found that the scaffold protein Cullin1, and F-box proteins Skp2, β-TrCP1 and β-TrCP2 are expressed in the external granule layer (EGL). Knockdown of these molecules in the EGL showed that Cullin1, Skp2 and β-TrCP2 enhanced differentiation of GCPs. We also observed accumulation of cyclin-dependent kinase inhibitor p27 in GCPs when treated with a Cullin1 inhibitor or proteasome inhibitor. Furthermore, knockdown of p27 rescued enhancement of differentiation by Cullin1 knockdown. These results suggest that the SCF complex is involved in the maintenance of the proliferative state of GCPs through p27 degradation. In addition, inhibition of Cullin1 activity also prevented cell proliferation and enhanced accumulation of p27 in Daoy cells, a cell line derived from the sonic hedgehog subtype of medulloblastoma. This suggested that excess degradation of p27 through the SCF complex causes overproliferation of medulloblastoma cells.	Genes to cells : devoted to molecular & cellular mechanisms	2,020	12
33,129,802	Neuroablative surgical treatments for pain due to cancer.	Cancer pain is common and challenging to manage - it is estimated that approximately 30% of cancer patients have pain that is not adequately controlled by analgesia. This paper discusses safe and effective neuroablative treatment options for refractory cancer pain. Current management of cancer pain predominantly focuses on the use of medications, resulting in a relative loss of knowledge of these surgical techniques and the erosion of the skills required to perform them. Here, we review surgical methods of modulating various points of the neural axis with the aim to expand the knowledge base of those managing cancer pain. Integration of neuroablative approaches may lead to higher rates of pain relief, and the opportunity to dose reduce analgesic agents with potential deleterious side effects. With an ever-increasing population of cancer patients, it is essential that neurosurgeons maintain or train in these techniques in tandem with the oncological multi-disciplinary team.	Neuro-Chirurgie	2,021	4
32,927,026	FMRP-absence-induced up-regulation of hypothalamic MAP1B expression decreases AgRP level linking with reduces in food intake and body weight.	Fragile X mental retardation protein (FMRP), strongly associated with fragile X syndrome, plays important roles by regulating gene expression via interacting with other RNA binding proteins in the brain. However, the role of FMRP in hypothalamus, a central part responsible for metabolic control, is poorly known. Our study shows that FMRP is primarily located in the hypothalamic arcuate nucleus (ARC). Using proteomic analysis, we identified 56 up-regulated and 22 down-regulated proteins in the hypothalamus of Map1b KO mice, with microtubule-associated protein 1 B (MAP1B) being the most outstanding increased protein (more than 10 folds). Immunofluorescent assays showed that MAP1B significantly increased in the Map1b-KO ARC, in which the number of agouti-related peptide (AgRP)-staining neurons significantly reduced, but not altered for pro-opiomelanocortin (POMC) neurons. We further showed an age-dependent reduces in food intake and body weight of the KO mice, along with the decreases of MAP1B and AgRP at the same time points. In hypothalamic GT1-7 cells, the AgRP expression decreased upon knockdown of FMRP or overexpression of MAP1B, and increased in response to overexpression of FMRP or knockdown of MAP1B. Co-knockdown or co-overexpression of FMRP and MAP1B led to a reverse expression of AgRP compared to overexpression of knockdown of FMRP alone, demonstrating that MAP1B is essential for the regulatory effect of FMRP on AgRP expression. Taken together, these data suggest that FMRP-deficiency-induced increase of hypothalamic MAP1B and decrease of AgRP might be associated with reduces in food intake and body weight.	Neurochemistry international	2,020	11
28,381,652	Treatment Outcome of Carotid Artery Stenting Underwent within 14 Days of Stroke Onset - Consideration of Safety and Efficacy of Urgent Carotid Artery Stenting for Neurologically Progressing Patients.	As the safety and effectiveness of urgent carotid artery stenting (CAS) for neurologically progressing patients remain controversial, we retrospectively analyzed the outcome of urgent CAS based on the patients' pathophysiological condition and neuroimaging findings. We divided 71 patients who underwent CAS within 14 days of stroke onset into two groups. Group 1 (n = 35) was comprised of patients with progressing neurologic signs and a reversible ischemic penumbra on magnetic resonance images (MRI). They were treated by urgent CAS. Group 2 (n = 36) was neurologically stable and underwent prophylactic CAS. In all patients we recorded the National Institutes of Health Stroke Scale (NIHSS) score and the modified Rankin scale (mRS). Urgent CAS resulted in significant improvement in the NIHSS score, when compared before and after CAS in group 1 (5.3 ± 4.3, P < 0.01). The rate of good outcomes (mRS 0-2 at 3 months post-CAS) was 48.6% in group 1, and 75% in group 2. The cumulative incidence of ipsilateral stroke between 31 days and 1 year was 5.9% in group 1, and 0% in group 2. The procedural complication rate was similar in both groups (group 1: 5.7%, n = 2; group 2: 5.6%, n = 2). No patient suffered a symptomatic intracerebral hemorrhage. When the pathophysiological status and neuroimaging findings are used to determine patient eligibility for urgent CAS, this treatment improve neurologic outcome and can be performed as safely as prophylactic CAS in our cohort of patients with acute ischemic stroke.	Neurologia medico-chirurgica	2,017	6
33,092,197	A Comprehensive Proteomics Analysis of the JC Virus (JCV) Large and Small Tumor Antigen Interacting Proteins: Large T Primarily Targets the Host Protein Complexes with V-ATPase and Ubiquitin Ligase Activities While Small t Mostly Associates with Those Having Phosphatase and Chromatin-Remodeling Functions.	The oncogenic potential of both the polyomavirus large (LT-Ag) and small (Sm t-Ag) tumor antigens has been previously demonstrated in both tissue culture and animal models. Even the contribution of the MCPyV tumor antigens to the development of an aggressive human skin cancer, Merkel cell carcinoma, has been recently established. To date, the known primary targets of these tumor antigens include several tumor suppressors such as pRb, p53, and PP2A. However, a comprehensive list of the host proteins targeted by these proteins remains largely unknown. Here, we report the first interactome of JCV LT-Ag and Sm t-Ag by employing two independent "affinity purification/mass spectroscopy" (AP/MS) assays. The proteomics data identified novel targets for both tumor antigens while confirming some of the previously reported interactions. LT-Ag was found to primarily target the protein complexes with ATPase (v-ATPase and Smc5/6 complex), phosphatase (PP4 and PP1), and ligase (E3-ubiquitin) activities. In contrast, the major targets of Sm t-Ag were identified as Smarca1/6, AIFM1, SdhA/B, PP2A, and p53. The interactions between "LT-Ag and SdhB", "Sm t-Ag and Smarca5", and "Sm t-Ag and SDH" were further validated by biochemical assays. Interestingly, perturbations in some of the LT-Ag and Sm t-Ag targets identified in this study were previously shown to be associated with oncogenesis, suggesting new roles for both tumor antigens in novel oncogenic pathways. This comprehensive data establishes new foundations to further unravel the new roles for JCV tumor antigens in oncogenesis and the viral life cycle.	Viruses	2,020	10
24,412,740	Spatial primes produce dissociated inhibitory effects on saccadic latencies and trajectories.	In masked priming, a briefly presented prime can facilitate or inhibit responses to a subsequent target. In most instances, targets with an associated response that is congruent with the prime direction speed up reaction times to the target (a positive compatibility effect; PCE). However, under certain circumstances, slower responses for compatible primes are obtained (a negative compatibility effect; NCE). NCEs can be found when a long pre-target delay is used. During the delay, inhibition is assumed to take place, and therefore an effect on saccade trajectories may also be expected. In a previous study, we found the effects of inhibition on response times and trajectories to be dissociated, but this experiment varied the timing of several aspects of the stimulus sequence and it is therefore unclear what caused the dissociation. In the present study, we varied only one aspect of the timing, but replicated the dissociation. By varying just the pre-target delay, we found a PCE for a short delay, and an NCE for a long delay, but saccade trajectories deviated away from prime directions in both conditions. This suggests dissociated inhibitory effects of primes on response times and saccade trajectories.	Vision research	2,014	3
33,176,802	Multiple lifestyle factors and depressed mood: a cross-sectional and longitudinal analysis of the UK Biobank (N = 84,860).	There is now evolving data exploring the relationship between depression and various individual lifestyle factors such as diet, physical activity, sleep, alcohol intake, and tobacco smoking. While this data is compelling, there is a paucity of longitudinal research examining how multiple lifestyle factors relate to depressed mood, and how these relations may differ in individuals with major depressive disorder (MDD) and those without a depressive disorder, as 'healthy controls' (HC).	BMC medicine	2,020	11
33,170,010	Enhanced Validation of Antibodies Enables the Discovery of Missing Proteins.	The localization of proteins at a tissue- or cell-type-specific level is tightly linked to the protein function. To better understand each protein's role in cellular systems, spatial information constitutes an important complement to quantitative data. The standard methods for determining the spatial distribution of proteins in single cells of complex tissue samples make use of antibodies. For a stringent analysis of the human proteome, we used orthogonal methods and independent antibodies to validate 5981 antibodies that show the expression of 3775 human proteins across all major human tissues. This enhanced validation uncovered 56 proteins corresponding to the group of "missing proteins" and 171 proteins of unknown function. The presented strategy will facilitate further discussions around criteria for evidence of protein existence based on immunohistochemistry and serves as a useful guide to identify candidate proteins for integrative studies with quantitative proteomics methods.	Journal of proteome research	2,020	12
22,134,865	[DGRW-update: neurology--from empirical strategies towards evidence based interventions].	Stroke, Multiple Sclerosis (MS), traumatic brain injuries (TBI) and neuropathies are the most important diseases in neurological rehabilitation financed by the German Pension Insurance. The primary goal is vocational (re)integration. Driven by multiple findings of neuroscience research the traditional holistic approach with mainly empirically derived strategies was developed further and improved by new evidence-based interventions. This process had been, and continues to be, necessary to meet the health-economic pressures for ever shorter and more efficient rehab measures. Evidence-based interventions refer to symptom-oriented measures, to team-management concepts, as well as to education and psychosocial interventions. Drug therapy and/or neurophysiological measures can be added to increase neuroregeneration and neuroplasticity. Evidence-based aftercare concepts support sustainability and steadiness of rehab results.Mirror therapy, robot-assisted training, mental training, task-specific training, and above all constraint-induced movement therapy (CIMT) can restore motor arm and hand functions. Treadmill training and robot-assisted training improve stance and gait. Botulinum toxine injections in combination with physical and redressing methods are superior in managing spasticity. Guideline-oriented management of associated pain syndromes (myofascial, neuropathic, complex-regional=dystrophic) improve primary outcome and quality of life. Drug therapy with so-called co-analgetics and physical therapy play an important role in pain management. Swallowing disorders lead to higher mortality and morbidity in the acute phase; stepwise diagnostics (screening, endoscopy, radiology) and specific swallowing therapy can reduce these risks and frequently can restore normal eating und drinking.In our modern industrial societies communicative and cognitive disturbances are more impairing than the above mentioned disorders. Speech and language therapy (SLT) is dominant in communicative disorders; the therapists use communicative and/or linguistics-oriented strategies. SLT must begin early after disease onset and with high frequency to elicit good results. PC-assisted (self-)training, possibly telemedically applied, can increase training frequency and time and, hence, improve outcome in aphasia. High-frequency and task-specific training, often PC-assisted, were found to be relevant for improving cognitive functions in all dimensions. Several strategies seem to be efficient in neglect. Visual field deficits can be treated restitutively and compensatingly by PC-assisted training. Attention, memory and executive dysfunctions each require multimodal specific treatment strategies, performed in single and group therapy and in PC-assisted training. Also, education of patients to cope with their impairments and disabilities is another important part. Combined medically and vocationally oriented rehabilitation settings are necessary for raising the rate of return-to-work, especially in patients with motor hand impairments or cognitive disorders. Education of patients and relatives to cope with the chronic neurological diseases and disablements highly improve the sustainability of rehab results and can, in the long run, also reduce mortality and admission to nursing homes. Appropriate physical activity and sports are relevant in the phase of aftercare, by stabilizing both motor coordination and cognitive factors; in MS patients fatigue can be diminished effectively.The main mental comorbidities are anxiety and depression. Pharmacological and psychological treatments have been found to be equally important in this context. Frequently, these mental disorders appear in the phase of aftercare and long-term course only, then worsening outcome sustainability. Efficient concepts to deal with this aspect are still missing. The ambulatory health care system can not cope with it until now.The multitude of evidence-based interventions have over the last 20 years after the Rehab Commission of the Federation of the German Pension Insurance Institutes contributed decisively to even improving primary outcomes and quality of life of neurological patients in spite of shortened length of stay and other restrictions. Neurorehabilitative research, especially the clinically oriented part, had a major influence on the process of professionalization of all members in the neurorehabilitative team. This fact enables new and more efficient organizational structures and working processes within the team; the discussion on this topic has however only just started.	Die Rehabilitation	2,011	12
32,632,744	Thinking about Others' Minds: Mental State Inference in Boys with Conduct Problems and Callous-Unemotional Traits.	Children with conduct problems (CP) and high levels of callous-unemotional traits (CP/HCU) have been found to have an intact ability to represent other minds, however, they behave in ways that indicate a reduced propensity to consider other people's thoughts and feelings. Here we report findings from three tasks assessing different aspects of mentalising in 81 boys aged 11-16 [Typically developing (TD) n = 27; CP/HCU n = 28; CP and low levels of callous-unemotional traits (CP/LCU) n = 26]. Participants completed the Movie Assessment of Social Cognition (MASC), a task assessing ability/propensity to incorporate judgements concerning an individual's mind into mental state inference; provided a written description of a good friend to assess mind-mindedness; and completed the Social Judgement Task (SJT), a new measure assessing mentalising about antisocial actions. Boys with CP/HCU had more difficulty in accurately inferring others' mental states in the MASC than TD and CP/LCU boys. There were no group differences in the number of mind-related comments as assessed by the mind-mindedness protocol or in responses to the SJT task. These findings suggest that although the ability to represent mental states is intact, CP/HCU boys are less likely to update mental state inferences as a function of different minds.	Journal of abnormal child psychology	2,020	10
33,561,407	Disgust: Internal Context Matters.	Novel research suggests the rhythms in our stomachs can influence our response to disgusting stimuli. Monetary reward will only encourage people to engage with disgusting stimuli after a peripherally acting drug alters gastric signals.	Current biology : CB	2,021	2
32,610,086	The role of interoception in understanding others' affect. Dissociation between superficial and detailed appraisal of facial expressions.	Embodied models of social cognition argue that others' emotional states are processed by re-enacting a representation of the same state in the observer, along with associated somatic and physiological responses. In this framework, previous studies tested whether a strong sensitivity to interoceptive signals (i.e., inputs arising from within one's body) facilitates the understanding of others' affect, leading to mixed results. Such heterogeneity in the literature could reflect methodological differences in paradigms employed, with some probing classification of a precise condition, and others requiring the assessment of supra-ordinal dimensions orthogonal to many states. Here, we engaged fifty young women in a study where they evaluated others' naturalistic facial reactions to painful and disgusting stimuli of comparable unpleasantness. Separately, we measured their interoceptive abilities through a well-known heartbeat counting task. We found that individuals that were more accurate in tracking their heartbeats across time were also more prone to judge facial expressions as more unpleasant (supra-ordinal assessment). However, when specifically asked to discriminate between comparably-unpleasant pain and disgust (state-specific assessment), participants' performance was not influenced by their interoceptive abilities. Although confined to a female sample, this study extends our knowledge on the role of interoception in the understanding of others, which influences only the evaluation of general features such as unpleasantness (common between pain and disgust), without extending to the appraisal of a precise state. This finding supports multi-componential models of social cognition, suggesting that only part of our ability to assess others' affect is mediated by a representation of one's affective/somatic responses.	Cortex; a journal devoted to the study of the nervous system and behavior	2,020	9
32,981,667	The Effect of Adherence to the Mediterranean Diet on Late-Life Cognitive Disorders: A Systematic Review.	Although some results are conflicting, numerous investigations have demonstrated that the Mediterranean Diet (MedDiet) has positive effects on brain health. This review intends to provide an update on the scientific evidence regarding the effects of adherence to the MedDiet on late-life cognitive disorders.	Journal of the American Medical Directors Association	2,020	10
33,163,545	Simultaneous two-photon activation and imaging of neural activity based on spectral-temporal modulation of supercontinuum light.	Recent advances in nonlinear optics in neuroscience have focused on using two ultrafast lasers for activity imaging and optogenetic stimulation. Broadband femtosecond light sources can obviate the need for multiple lasers by spectral separation for chromatically targeted excitation.	Neurophotonics	2,020	10
32,524,199	DNA hypomethylation of the Krüppel-like factor 11 (KLF11) gene promoter: a putative biomarker of depression comorbidity in panic disorder and of non-anxious depression?	Panic disorder (PD) is one of the most common anxiety disorders and often occurs comorbidly with major depressive disorder (MDD). Altered methylation of the monoamine oxidase A (MAOA) gene has been implicated in the etiology of both PD and MDD. The Krüppel-like factor 11 (KLF11; alias TIEG2), an activating transcription factor of the MAOA gene, has been found to be increased in MDD, but has not yet been investigated in PD. In an effort to further delineate the effects of the KLF11-MAOA pathway in anxiety and affective disorders, KLF11 promoter methylation was analyzed via pyrosequencing of sodium bisulfite-treated DNA isolated from human peripheral blood in two independent samples of PD patients with or without comorbid MDD in a case-control design (sample 1: N = 120) as well as MDD patients with and without anxious depression (sample 2: N = 170). Additionally, in sample 1, KLF11 methylation was correlated with Beck Depression Inventory (BDI-II) scores. No overall association of KLF11 promoter methylation with PD was detected. However, PD patients with comorbid MDD showed significant hypomethylation relative to both healthy controls (p = 0.010) and PD patients without comorbid MDD (p = 0.008). Furthermore, KLF11 methylation was negatively correlated with BDI-II scores in PD patients (p = 0.013). MDD patients without anxious features showed nominally decreased KLF11 methylation in comparison to MDD patients with anxious depression (p = 0.052). The present results suggest KLF11 promoter hypomethylation as a potential epigenetic marker of MDD comorbidity in PD or of non-anxious depression, respectively, possibly constituting a differential pathomechanism in anxiety and mood disorders.	Journal of neural transmission (Vienna, Austria : 1996)	2,020	11
29,506,025	The therapeutic 'make-over' of dementias-an introduction.	The online themed collection of 15 papers recently published provides an update on the advances of pharmacological and non-pharmacological interventions in dementia over the last 15 years. The published studies reflect the efficacy of the current anti-dementia treatments, preventive treatments of cardio and cerebrovascular incidents (known to be risk factors for dementia), alongside the use of antidepressant medication and non-pharmacological interventions for treatment of behavioural and psychopathological symptoms of dementia. We also address the future preventative steps and therapeutic strategies currently in development to combat the devastating consequences of dementia.	Age and ageing	2,018	5
33,414,390	Knockout serotonin transporter in rats moderates outcome and stimulus generalization.	Understanding the common dimension of mental disorders (such as anxiety, depression, and drug addiction) might contribute to the construction of biological frameworks (Research Domain Criteria, RDoC) for novel ways of treatment. One common dimension at the behavioral level observed across these disorders is a generalization. Testing generalization in serotonin transporter (5-HTT) knockout (KO) rats, an animal model showing depression/anxiety-like behaviors and drug addiction-like behaviors, could therefore provide more insights into this framework. We tested the outcome and stimulus generalization in wild-type (WT) and 5-HTT KO rats. Using a newly established touchscreen-based task, subjects directly responded to visual stimuli (Gabor patch images). We measured the response time and outcome in a precise manner. We found that 5-HTT KO rats processed visual information faster than WT rats during outcome generalization. Interestingly, during stimulus generalization, WT rats gradually responded faster to the stimuli as the sessions progressed, while 5-HTT KO rats responded faster than WT in the initial sessions and did not change significantly as the sessions progressed. This observation suggests that KO rats, compared to WT rats, may be less able to update changes in information. Taken together, KO 5-HTT modulates information processing when the environment changes.	Translational psychiatry	2,021	1
29,203,336	Spontaneous recovery of traumatic brain injury-induced functional deficits is not hindered by daily administration of lorazepam.	Agitation and aggression are common sequelae of traumatic brain injury (TBI) and pose a challenge to physicians and other health providers during acute patient care and subsequent neurorehabilitation. Antipsychotic drugs (APDs) are routinely administered to manage TBI patients displaying such maladaptive behaviors despite several clinical and preclinical studies demonstrating that they hinder recovery. A potentially viable alternative to APDs may be the benzodiazepines, which have differing mechanisms of action. Hence, the aim of the study was to test the hypothesis that lorazepam (LOR) would not impede recovery after TBI. Anesthetized adult male rats received a cortical impact or sham injury and then were intraperitoneally administered LOR (0.1mg/kg, 1.0mg/kg, or 2.0mg/kg) or vehicle (VEH; 1mL/kg) commencing 24-h after surgery and once daily for 19days. Motor and cognitive outcomes were assessed on post-operative days 1-5 and 14-19, respectively. No differences were revealed among the four sham control groups and thus they were pooled into one inclusive SHAM group. The SHAMs performed better than all TBI groups on all assessments (p<0.05). Regarding TBI, the 2.0mg/kg LOR group performed better than the VEH and 0.1mg/kg or 1.0mg/kg LOR groups on every task (p<0.05); no differences were observed among the latter three groups on any endpoint (p>0.05). Overall, these preclinical behavioral data support the hypothesis and reveal a therapeutic benefit with the higher dose of LOR. The findings suggest that LOR may be an alternative, to APDs, for controlling agitation without compromising spontaneous recovery and perhaps could afford a dual benefit by also promoting therapeutic efficacy.	Behavioural brain research	2,018	2
32,619,029	Zebrafish models of impulsivity and impulse control disorders.	Impulse control disorders (ICDs) are characterized by generalized difficulty controlling emotions and behaviors. ICDs are a broad group of the central nervous system (CNS) disorders including conduct disorder, intermittent explosive, oppositional-defiant disorder, antisocial personality disorder, kleptomania, pyromania and other illnesses. Although they all share a common feature (aberrant impulsivity), their pathobiology is complex and poorly understood. There are also currently no ICD-specific therapies to treat these illnesses. Animal models are a valuable tool for studying ICD pathobiology and potential therapies. The zebrafish (Danio rerio) has become a useful model organism to study CNS disorders due to high genetic and physiological homology to mammals, and sensitivity to various pharmacological and genetic manipulations. Here, we summarize experimental models of impulsivity and ICD in zebrafish and highlight their growing translational significance. We also emphasize the need for further development of zebrafish ICD models to improve our understanding of their pathogenesis and to search for novel therapeutic treatments.	The European journal of neuroscience	2,020	11
31,853,879	Time-conjunctive representations of future events.	It is widely accepted that people can predict the relative imminence of future events. However, it is unknown whether the timing of future events is represented using only a "strength-like" estimate or if future events are represented conjunctively with their position on a mental timeline. We examined how people judge temporal relationships among anticipated future events using the novel Judgment of Anticipated Co-Occurrence (JACO) task. Participants were initially trained on a stream of letters sampled from a probabilistically repeating sequence. During test trials, the stream was interrupted with pairs of probe letters and the participants' task was to choose the probe letter they expected to appear in the stream during a lagged target window 4-6 items (4.3-8.5 s) in the future. Participants performed above chance as they gained experience with the task. Because the correct item was sometimes the more imminent probe letter and other times the less imminent probe letter, these results rule out the possibility that participants relied solely on thresholding a strength-like estimate of temporal imminence. Rather, these results suggest that participants held (1) temporally organized predictions of the future letters in the stream, (2) a temporal estimate of the lagged target window, and (3) some means to compare the two and evaluate their temporal alignment. Response time increased with the lag to the more imminent probe letter, suggesting that participants accessed the future sequentially in a manner that mirrors scanning processes previously proposed to operate on memory representations in the short-term judgment of recency task.	Memory & cognition	2,020	5
32,711,067	Optical imaging reveals functional domains in primate sensorimotor cortex.	Motor cortex (M1) and somatosensory cortex (S1) are central to arm and hand control. Efforts to understand encoding in M1 and S1 have focused on temporal relationships between neural activity and movement features. However, it remains unclear how the neural activity is spatially organized within M1 and S1. Optical imaging methods are well-suited for revealing the spatio-temporal organization of cortical activity, but their application is sparse in monkey sensorimotor cortex. Here, we investigate the effectiveness of intrinsic signal optical imaging (ISOI) for measuring cortical activity that supports arm and hand control in a macaque monkey. ISOI revealed spatial domains that were active in M1 and S1 in response to instructed reaching and grasping. The lateral M1 domains overlapped the hand representation and contained a population of neurons with peak firing during grasping. In contrast, the medial M1 domain overlapped the arm representation and a population of neurons with peak firing during reaching. The S1 domain overlapped the hand representations of areas 1 and 2 and a population of neurons with peak firing upon hand contact with the target. Our single unit recordings indicate that ISOI domains report the locations of spatial clusters of functionally related neurons. ISOI is therefore an effective tool for surveilling the neocortex for "hot zones" of activity that supports movement. Combining the strengths of ISOI with other imaging modalities (e.g., fMRI, 2-photon) and with electrophysiological methods can open new frontiers in understanding the spatio-temporal organization of cortical signals involved in movement control.	NeuroImage	2,020	11
32,805,265	Role of radially aligned scleral collagen fibers in optic nerve head biomechanics.	Collagen fibers organized circumferentially around the canal in the peripapillary sclera are thought to provide biomechanical support to the sensitive tissues within the optic nerve head (ONH). Recent studies have demonstrated the existence of a family of fibers in the innermost sclera organized radially from the scleral canal. Our goal was to determine the role of these radial fibers in the sensitivity of scleral canal biomechanics to acute increases in intraocular pressure (IOP). Following the same general approach of previous parametric sensitivity studies, we created nonlinear generic finite element models of a posterior pole with various combinations of radial and circumferential fibers at an IOP of 0 mmHg. We then simulated the effects of normal and elevated IOP levels (15 and 30 mmHg). We monitored four IOP-induced geometric changes: peripapillary sclera stretch, scleral canal displacement, lamina cribrosa displacement, and scleral canal expansion. In addition, we examined the radial (maximum tension) and through-thickness (maximum compression) strains within the ONH tissues. Our models predicted that: 1) radial fibers reduced the posterior displacement of the lamina, especially at elevated IOP; 2) radial fibers reduced IOP-induced radial strain within the peripapillary sclera and retinal tissue; and 3) a combination of radial and circumferential fibers maintained strains within the ONH at a level similar to those conferred by circumferential fibers alone. In conclusion, radial fibers provide support for the posterior globe, additional to that provided by circumferential fibers. Most importantly, a combination of both fiber families can better protect ONH tissues from excessive IOP-induced deformation than either alone.	Experimental eye research	2,020	10
31,038,734	From red vegetables to sexuality: Resymbolizing the meaning of concrete thought in eating disorders.	This paper introduces and describes the theory and practice of a novel treatment approach to eating disorders-internal language enhancement therapy (ILET)-illustrated with a case study. This treatment approach is informed by the neurobiology of emotional processing integrated with elements of psychoanalytic theory and practice, early maternal preoccupation, development of the self, early right hemisphere language development, and techniques from cognitive behavioral therapy. ILET is based on the Discontinuous Model of Neural Emotional Processing, which means that emotions are processed in the brain either symbolically or concretely. The aim of ILET is to open up and reinforce the underused brain pathway to the symbolic functions by forensically working back to and accurately identifying the emotional material that triggers the concrete state. When the emotional trigger is identified it is explored using symbolic and metaphoric language that reconnects the patient to the symbolic state. ILET posits that eating disorders only appear in the concrete state.	Journal of clinical psychology	2,019	8

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