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33,489,296	Virtual body ownership and its consequences for implicit racial bias are dependent on social context.	When people hold implicit biases against a group they typically engage in discriminatory behaviour against group members. In the context of the implicit racial bias of 'White' against 'Black' people, it has been shown several times that implicit bias is reduced after a short exposure of embodiment in a dark-skinned body in virtual reality. Embodiment usually leads to the illusion of ownership over the virtual body, irrespective of its skin colour. Previous studies have been carried out in virtual scenarios that are affectively neutral or positive. Here, we show that when the scenario is affectively negative the illusion of body ownership of White participants over a White body is lessened, and implicit bias is higher for White participants in a Black virtual body. The study was carried out with 92 White female participants, in a between-groups design with two factors: BodyType (their virtual body was White or Black) and a surrounding Crowd was Negative, Neutral or Positive towards the participant. We argue that negative affect prevents the formation of new positive associations with Black and distress leads to disownership of the virtual body. Although virtual reality is often thought of as an 'empathy machine' our results suggest caution, that this may not be universally the case.	Royal Society open science	2,020	12
32,667,097	Identifying and managing care for children with autism spectrum disorders in general practice: A systematic review and narrative synthesis.	Many healthcare systems are organised such that General Practitioners (GPs) often have a key role in identifying autism spectrum disorders (hereafter collectively referred to as autism) in children. In this review, we explored what GPs know about autism and the factors that influence their ability to identify and manage care for their patients with autism in practice. We conducted a systematic narrative review using eight electronic databases. These included Embase and MEDLINE via Ovid, Web of Knowledge, PsycINFO via Ebscohost, PubMed, Scopus, ProQuest Dissertations and Thesis, and Applied Social Sciences Index and Abstracts (ASSIA) via ProQuest. Our search yielded 2,743 citations. Primary research studies were included, and we did not impose any geographical, language or date restrictions. We identified 17 studies that met our inclusion criteria. Studies included in the review were conducted between 2003 and 2019. We thematically synthesised the material and identified the following themes: the prototypical image of a child with autism; experience, sources of information, and managing care; barriers to identification; strategies to aid in identification; and characteristics that facilitate expertise. Together, the findings from this review present a mixed picture of GP knowledge and experiences in identifying autism and managing care for children with the condition. At one end of the continuum, there were GPs who had not heard of autism or endorsed outmoded aetiological theories. Others, however, demonstrated a sound knowledge of the conditions but had limited confidence in their ability to identify the condition. Many GPs and researchers alike called for more training and this might be effective. However, framing the problem as one of a lack of training risks silences the array of organisational factors that impact on a GP's ability to provide care for these patients.	Health & social care in the community	2,020	11
33,169,030	Modeling behaviorally relevant neural dynamics enabled by preferential subspace identification.	Neural activity exhibits complex dynamics related to various brain functions, internal states and behaviors. Understanding how neural dynamics explain specific measured behaviors requires dissociating behaviorally relevant and irrelevant dynamics, which is not achieved with current neural dynamic models as they are learned without considering behavior. We develop preferential subspace identification (PSID), which is an algorithm that models neural activity while dissociating and prioritizing its behaviorally relevant dynamics. Modeling data in two monkeys performing three-dimensional reach and grasp tasks, PSID revealed that the behaviorally relevant dynamics are significantly lower-dimensional than otherwise implied. Moreover, PSID discovered distinct rotational dynamics that were more predictive of behavior. Furthermore, PSID more accurately learned behaviorally relevant dynamics for each joint and recording channel. Finally, modeling data in two monkeys performing saccades demonstrated the generalization of PSID across behaviors, brain regions and neural signal types. PSID provides a general new tool to reveal behaviorally relevant neural dynamics that can otherwise go unnoticed.	Nature neuroscience	2,021	1
30,940,234	Special, radical, failure of reduction in psychiatry.	Use of network models to identify causal structure typically blocks reduction across the sciences. Entanglement of mental processes with environmental and intentional relationships, as Borsboom et al. argue, makes reduction of psychology to neuroscience particularly implausible. However, in psychiatry, a mental disorder can involve no brain disorder at all, even when the former crucially depends on aspects of brain structure. Gambling addiction constitutes an example.	The Behavioral and brain sciences	2,019	1
32,803,279	A New Treatment for Local Adiposity with Ascorbic Acid and Ascorbyl-Palmitate Solution: Clinical and Histological Study.	Localized adiposity (AL) is the accumulation of subcutaneous adipose tissue, placed in definite anatomic areas, building up an alteration of the body silhouette. The aim of the present clinical and histological study is to assess the effectiveness of an injectable solution containing sodium salt of ascorbic acid 0.24% and surfactant agent at 0.020% ascorbyl-palmitate (SAP) for treating local adiposity.	Aesthetic plastic surgery	2,020	10
32,249,318	Altered Signaling in CB1R-5-HT2AR Heteromers in Olfactory Neuroepithelium Cells of Schizophrenia Patients is Modulated by Cannabis Use.	Schizophrenia (SCZ) has been associated with serotonergic and endocannabinoid systems dysregulation, but difficulty in obtaining in vivo neurological tissue has limited its exploration. We investigated CB1R-5-HT2AR heteromer expression and functionality via intracellular pERK and cAMP quantification in olfactory neuroepithelium (ON) cells of SCZ patients non-cannabis users (SCZ/nc), and evaluated whether cannabis modulated these parameters in patients using cannabis (SCZ/c). Results were compared vs healthy controls non-cannabis users (HC/nc) and healthy controls cannabis users (HC/c). Further, antipsychotic effects on heteromer signaling were tested in vitro in HC/nc and HC/c. Results indicated that heteromer expression was enhanced in both SCZ groups vs HC/nc. Additionally, pooling all 4 groups together, heteromer expression correlated with worse attentional performance and more neurological soft signs (NSS), indicating that these changes may be useful markers for neurocognitive impairment. Remarkably, the previously reported signaling properties of CB1R-5-HT2AR heteromers in ON cells were absent, specifically in SCZ/nc treated with clozapine. These findings were mimicked in cells from HC/nc exposed to clozapine, suggesting a major role of this antipsychotic in altering the quaternary structure of the CB1R-5-HT2AR heteromer in SCZ/nc patients. In contrast, cells from SCZ/c showed enhanced heteromer functionality similar to HC/c. Our data highlight a molecular marker of the interaction between antipsychotic medication and cannabis use in SCZ with relevance for future studies evaluating its association with specific neuropsychiatric alterations.	Schizophrenia bulletin	2,020	12
33,124,220	Dynamic evolution of transposable elements, demographic history, and gene content of paleognathous birds.	Palaeognathae includes ratite and tinamou species that are important for understanding early avian evolution. Here, we analyzed the whole-genome sequences of 15 paleognathous species to infer their demographic histories, which are presently unknown. We found that most species showed a reduction of population size since the beginning of the last glacial period, except for those species distributed in Australasia and in the far south of South America. Different degrees of contraction and expansion of transposable elements (TE) have shaped the paleognathous genome architecture, with a higher transposon removal rate in tinamous than in ratites. One repeat family, AviRTE, likely underwent horizontal transfer from tropical parasites to the ancestor of little and undulated tinamous about 30 million years ago. Our analysis of gene families identified rapid turnover of immune and reproduction-related genes but found no evidence of gene family changes underlying the convergent evolution of flightlessness among ratites. We also found that mitochondrial genes have experienced a faster evolutionary rate in tinamous than in ratites, with the former also showing more degenerated W chromosomes. This result can be explained by the Hill-Robertson interference affecting genetically linked W chromosomes and mitochondria. Overall, we reconstructed the evolutionary history of the Palaeognathae populations, genes, and TEs. Our findings of co-evolution between mitochondria and W chromosomes highlight the key difference in genome evolution between species with ZW sex chromosomes and those with XY sex chromosomes.	Zoological research	2,021	1
28,537,943	Reinforcing effectiveness of midazolam, ethanol, and sucrose: behavioral economic comparison of a mixture relative to its component solutions.	Benzodiazepines (BZs) are relatively safe when administered alone. However, these drugs can produce severe side effects when coadministered with ethanol. Despite these adverse consequences, rates of concurrent BZ and ethanol misuse are increasing, and it is unclear whether this behavior is maintained by an enhanced reinforcing effect of the mixture. To address this issue, the current study compared the reinforcing effectiveness of sucrose solutions mixed with midazolam, ethanol, or both. Eight male rats were trained to orally self-administer solutions of either sucrose (S), sucrose+midazolam (SM), sucrose+ethanol (SE), or sucrose+midazolam+ethanol (SME). The response requirement was increased between sessions until the number of reinforcers earned was zero and the relationship between response requirement and reinforcers earned was analyzed using the exponential model of demand. Although baseline intake was similar across drug conditions, consumption of SM was least affected by increases in cost, indicating that it possessed the highest reinforcing effectiveness (i.e. least elastic). The reinforcing effectiveness of S, SE, and SME did not differ significantly. The finding that the reinforcing effectiveness of the SME was less than that of SM does not support the supposition that BZ and ethanol coadministration is maintained by a higher reinforcing effectiveness of the mixture.	Behavioural pharmacology	2,017	8
33,532,150	The Relationship of Rapid Eye Movement Sleep Behavior Disorder and Freezing of Gait in Parkinson's Disease.	Rapid eye movement sleep behavior disorder (RBD) contributes to injury due to the alteration of the expected atonia during rapid eye movement (REM) sleep. It occurs before the overt signs of Parkinson's disease (PD). The co-expression of PD and RBD is characterized by non-tremor predominant subtype and higher incidence of freezing. Freezing of gait (FOG) is a debilitating symptom seen in PD patients that lead to falls. While this phenomenon is understood poorly, the involvement of the pedunculopontine nucleus (PPN) and the neural circuits that control locomotion and gait have been examined. This network has also the same control for REM sleep and arousal. The close relationship between PD and RBD and FOG's consequences has led us to explore the relationship between RBD and PD with FOG. This review provides an overview of the neural connections that control gait, locomotion, and REM sleep. The neural changes were seen in PD with FOG and RBD, and sensory and motor changes observed in these two diseases. The functional neuroanatomy that controls REM sleep, arousal, and locomotion overlap significantly with multiple neural circuits affected in RBD and PD with FOG. Visual perception dysfunction and motor symptoms that primarily affect gait initiation are common to both patients with RBD and FOG in PD, leading to freezing episodes. Prospective studies should be conducted to elucidate the relationship of RBD and PD with FOG subtype and find innovative treatment approaches and diagnostic tools for PD with FOG.	Cureus	2,020	12
32,447,274	Feasibility of Real Time Internet-Based Teleconsultation in Patients With Multiple Sclerosis: Interventional Pilot Study.	Telemedicine (TM) is currently flourishing in rural and emergency settings, but its implementation in the routine management of chronic neurological disorders has developed with more hesitation. Limited access to specialized care facilities and expanding patient populations, combined with unprecedented mobility restrictions imposed by the coronavirus disease pandemic, are currently stressing the need for remote solutions in this field. Studies in patients with multiple sclerosis (MS) have been heterogeneous in objectives and methodology but generally support the concept that TM interventions produce clinical benefits, cost-effectiveness, and user satisfaction. Nonetheless, data on live interaction between patients and health care providers for MS teleconsultation purposes remain scarce.	Journal of medical Internet research	2,020	8
28,268,946	Designing a hands-on brain computer interface laboratory course.	Devices and systems that interact with the brain have become a growing field of research and development in recent years. Engineering students are well positioned to contribute to both hardware development and signal analysis techniques in this field. However, this area has been left out of most engineering curricula. We developed an electroencephalography (EEG) based brain computer interface (BCI) laboratory course to educate students through hands-on experiments. The course is offered jointly by the Biomedical Engineering, Electrical Engineering, and Computer Science Departments of Columbia University in the City of New York and is open to senior undergraduate and graduate students. The course provides an effective introduction to the experimental design, neuroscience concepts, data analysis techniques, and technical skills required in the field of BCI.	Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference	2,016	8
18,300,006	Motor neuron disease associated with multiple myeloma.	The association between Amyotrophic Lateral Sclerosis or other Motor Neuron Diseases (MNDs) with Lymphoproliferative Disorders (LPDs) and plasma cell neoplasias (such as Hodgkin's or non-Hodgkin's lymphoma, Waldenstrom's macroglobulinemia, multiple myeloma, chronic lymphocytic leukemia) has been described. It is not clear whether LPDs play a role in the pathogenesis of MND; however it is possible that patients might have antibodies against motor neurons. An association between motor neuron disease and Multiple myeloma (MM) is rarely reported in the literature. This article reports a case of a 75-year-old male with MM and MND. Interestingly, the patient was in complete remission for MM when he was diagnosed as MND and he died due to progressive MND.	The International journal of neuroscience	2,008	3
33,691,240	The clinical significance of histone deacetylase-8 in human breast cancer.	Recent studies have shown that the histone deacetylase-8 (HDAC8), as one of the HDACs, regulates the expression and activity of various genes involved in cancer initiation and progression. The HDAC8 plays an epigenetic role to dysregulate expressions or to interact with transcription factors. Most researchers had focused on the HDAC 1-3 and 6, but today the HDAC8 isotype is a promising target in cancer therapy. Different studies, on breast cancer (BC) cells, have recently shown the HDAC8 overexpression and suggested its oncogenic potential. It seems that the HDAC8 could be a novel and promising target in breast cancer treatment. Some studies on BC demonstrated therapeutic properties of the inhibitors of HDAC8 such as suberoylanilide hydroxamic acid (SAHA), Trichostatin A, valproic acid, sodium butyrate, 1,3,4 oxadiazole with alanine hybrid [(R)-2-amino-N-((5-phenyl-1,3,4-oxadiazol-2-yl) methyl) propanamide (10b)], N-(2-Hydroxyphenyl)-2propylpentanamide (compound 2) and PCI-34051. In this review, we highlight the role and existing inhibitors of HDAC8 in BC pathogenesis and therapy.	Pathology, research and practice	2,021	4
28,237,802	RETRACTED: Early hyperbaric oxygen therapy may improve the long term neurological consequences of diabetic patients suffering from hemorrhagic stroke.	This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of Neuroscience Letters has learned that text throughout this paper duplicates, or nearly duplicates, text in an earlier paper by others (Rusyniak DE, Kirk MA, May JD, Kao LW, Brizendine EJ, Welch JL, Cordell WH, Alonso RJ; Hyperbaric Oxygen in Acute Ischemic Stroke Trial Pilot Study, Stroke. 2003 Feb;34(2):571-4).	Neuroscience letters	2,017	3
33,051,377	Reduced Independence in Daily Living Is Associated with the Gut Microbiome in People with HIV and HCV.	Alterations in the gut microbiome are associated with neurocognition and related disorders, including in the context of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. However, the connection between the gut microbiome and cognitive decline, gauged by increased dependence in instrumental activities of daily living (IADL), remains largely unexplored in the context of these diseases. Here we characterized the gut microbiome using 16S rRNA amplicon sequencing and untargeted metabolomics with liquid chromatography-mass spectrometry from 347 people with HIV, HIV and HCV, or neither, all of whom underwent a comprehensive neuropsychiatric assessment. We observed that IADL-dependent and -independent HIV-monoinfected (HIV-positive [HIV+]/HCV-negative [HCV-]) and coinfected (HIV+/HCV+) individuals have distinct gut microbiomes. Moreover, we found that dependent individuals with HIV or HIV and HCV were enriched in	mSystems	2,020	10
24,339,572	Hemorrhage and ischemia in different hemispheres in a child with moyamoya disease: Case report and review of literature.	Hemorrhagic type of moyamoya disease (MMD) is extremely rare in children. Ischemia following hemorrhage is very rare in MMD. There are only 11 reports of mixed-type of MMD, with the patient having both hemorrhage and ischemia in the same hemisphere at the time of presentation, or at different time periods. The ischemia is usually secondary to a precipitating cause. However, there are no reports of a child presenting with both ischemia and hemorrhage in different hemispheres. We present a previously unreported phenomenon of MMD, presenting as hemorrhage and ischemia in opposite hemispheres and review the relevant literature.	Annals of Indian Academy of Neurology	2,013	10
32,820,392	New neurophysiological human thermal model based on thermoreceptor responses.	A new neurophysiological human thermal model based on thermoreceptor responses, the NHTM model, has been developed to predict regulatory responses and physiological variables in asymmetric transient environments. The passive system is based on Wissler's model, which is more complex and refined. Wissler's model segments the human body into 21 cylindrical parts. Each part is divided into 21 layers, 15 for the tissues and 6 for clothes, and each layer is divided into 12 angular sectors. Thus, we have 3780 nodes for the tissues and 1512 for clothes. The passive system simulates heat exchange within the body and between the body and the surroundings. The active system is composed of the thermoregulatory mechanisms, i.e., skin blood flow, shivering thermogenesis, and sweating. The skin blood flow model and the shivering model are based on thermoreceptor responses. The sweating model is that of Fiala et al. and is based on error signals. The NHTM model was compared with Wissler's model, and the results showed that a calculation based on neurophysiology can improve the performance of the thermoregulation model. The NHTM model was more accurate in the prediction of mean skin temperature, with a mean absolute error of 0.27 °C versus 0.80 °C for the original Wissler model. The prediction accuracy of the NHTM model for local skin temperatures and core temperature could be improved via an optimization method to prove the ability of the new thermoregulation model to fit with the physiological characteristics of different populations.	International journal of biometeorology	2,020	12
32,592,806	Overexpression of HDAC6, but not HDAC3 and HDAC4 in the penumbra after photothrombotic stroke in the rat cerebral cortex and the neuroprotective effects of α-phenyl tropolone, HPOB, and sodium valproate.	Epigenetic processes play important roles in brain responses to ischemic injury. We studied effects of photothrombotic stroke (PTS, a model of ischemic stroke) on the intracellular level and cellular localization of histone deacetylases HDAC3, HDAC4 and HDAC6 in the rat brain cortex, and tested the potential neuroprotector ability of their inhibitors. The background level of HDAC3, HDAC4 and HDAC6 in the rat cerebral cortex was relatively low. HDAC3 localized in the nuclei of some neurons and few astrocytes. HDAC4 was found in the neuronal cytoplasm. After PTS, their levels in penumbra did not change, but HDAC4 appeared in the nuclei of some cells. Its level in the cytoplasmic, but not nuclear fraction of penumbra decreased at 24, but not 4 h after PTS. HDAC6 was upregulated in neurons and astrocytes in the PTS-induced penumbra, especially in the nuclear fraction. Unlike HDAC3 and HDAC4, HDAC6 co-localized with TUNEL-positive apoptotic cells. Inhibitory analysis confirmed the involvement of HDAC6, but not HDAC3 and HDAC4 in neurodegeneration. HDAC6 inhibitor HPOB, HDAC2/8 inhibitor α-phenyl tropolone, and non-specific histone deacetylase inhibitor sodium valproate, but not HDAC3 inhibitor BRD3308, or HDAC4 inhibitor LMK235, decreased PTS-induced infarction volume in the mouse brain, reduced apoptosis, and recovered the motor behavior. HPOB also restored PTS-impaired acetylation of α-tubulin. α-phenyl tropolone restored acetylation of histone H4 in penumbra cells. These results suggest that histone deacetylases HDAC6 and HDAC2 are the possible molecular targets for anti-ischemic therapy, and their inhibitors α-phenyl tropolone, HBOP and sodium valproate can be considered as promising neuroprotectors.	Brain research bulletin	2,020	9
31,351,097	Optimizing techniques for injecting DiI into the brain nuclei of neonatal mice P6 - C57Bl6/CBA.	DiI (1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate) is a lipophilic dye used to research the intracerebral connections of neonatal animals. This dye is most frequently used in the form of dry crystals, but injections of the marker in this state into the mouse brain nuclei, such as MHb (2 cases), LHbM (2 cases), LPA (3 cases) and TS (1 case), clearly revealed excessive lateral diffusion marker into the tissue. Eventually, all the investigated cases except the LPA gave a false positive result. To find the optimal method of marker injection,DiI-kerosene liquid films (3 cases in the MHb); DiI-kerosene gelatinous paste (3 cases in the MHb); injections of insoluble DiI crystals from a solution of 99% dmso (3 cases in the MHb) and 70% ethanol (3 cases in the MHb, 2 cases in the LHbM, 4 cases in the TS) were tested. Injections of DiI in the form of undissolved crystals from a 70% ethanol solution gave a minimal level of side diffusion in all the studied cases. This method of injection is optimal and recommended for use.	Journal of neuroscience methods	2,019	10
32,985,503	CLR01 protects dopaminergic neurons in vitro and in mouse models of Parkinson's disease.	Parkinson's disease (PD) affects millions of patients worldwide and is characterized by alpha-synuclein aggregation in dopamine neurons. Molecular tweezers have shown high potential as anti-aggregation agents targeting positively charged residues of proteins undergoing amyloidogenic processes. Here we report that the molecular tweezer CLR01 decreased aggregation and toxicity in induced pluripotent stem cell-derived dopaminergic cultures treated with PD brain protein extracts. In microfluidic devices CLR01 reduced alpha-synuclein aggregation in cell somas when axonal terminals were exposed to alpha-synuclein oligomers. We then tested CLR01 in vivo in a humanized alpha-synuclein overexpressing mouse model; mice treated at 12 months of age when motor defects are mild exhibited an improvement in motor defects and a decreased oligomeric alpha-synuclein burden. Finally, CLR01 reduced alpha-synuclein-associated pathology in mice injected with alpha-synuclein aggregates into the striatum or substantia nigra. Taken together, these results highlight CLR01 as a disease-modifying therapy for PD and support further clinical investigation.	Nature communications	2,020	9
36,151,621	[A virologist visits the Papuan anthropophagists].	In the 1950's, the American Carleton Gajdusek (1923-2008) was able to find the cause for kuru, a systematically fatal neurological disease, observed mainly on the Western Highlands of New Guinea. While living for a long period with the local indigenous population and studying their customs, he evidenced the infectious origin of this pathology and its transmission mechanism, cannibalism. He also demonstrated the transmissible nature of the agent of Creutzfeldt-Jakob. His works opened an important prospective field of research in neuroscience. A Nobel prize rewarded this outstanding scientific and human adventure.	Virologie (Montrouge, France)	2,009	10
32,607,636	Effects of C-Peptide Replacement Therapy on Bone Microarchitecture Parameters in Streptozotocin-Diabetic Rats.	C-peptide therapy protects against diabetic micro- and macrovascular damages and neuropatic complications. However, to date, the role of C-peptide in preventing diabetes-related bone loss has not been investigated. Our aim was to evaluate if C-peptide infusion improves bone quality in diabetic rats. Twenty-three male Wistar rats were randomly divided into three groups: normal control group; sham diabetic control group; diabetic plus C-peptide group. Diabetes was induced by streptozotocin injection and C-peptide was delivered subcutaneously for 6 weeks. We performed micro-CT and histological testing to assess several trabecular microarchitectural parameters. At the end, diabetic plus C-peptide rats had a higher serum C-peptide (p = 0.02) and calcium (p = 0.04) levels and tibia weight (p = 0.02) than the diabetic control group. The diabetic plus C-peptide group showed a higher trabecular thickness and cross-sectional thickness than the diabetic control group (p = 0.01 and p = 0.03). Both the normal control and diabetic plus C-peptide groups had more Runx-2 and PLIN1 positive cells in comparison with the diabetic control group (p = 0.045 and p = 0.034). Diabetic rats receiving C-peptide had higher quality of trabecular bone than diabetic rats not receiving this treatment. If confirmed, C-peptide could have a role in improving bone quality in diabetes.	Calcified tissue international	2,020	9
32,989,152	Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer's disease.	Alzheimer's disease (AD) is the most common form of dementia but has no effective treatment. A comprehensive investigation of cell type-specific responses and cellular heterogeneity in AD is required to provide precise molecular and cellular targets for therapeutic development. Accordingly, we perform single-nucleus transcriptome analysis of 169,496 nuclei from the prefrontal cortical samples of AD patients and normal control (NC) subjects. Differential analysis shows that the cell type-specific transcriptomic changes in AD are associated with the disruption of biological processes including angiogenesis, immune activation, synaptic signaling, and myelination. Subcluster analysis reveals that compared to NC brains, AD brains contain fewer neuroprotective astrocytes and oligodendrocytes. Importantly, our findings show that a subpopulation of angiogenic endothelial cells is induced in the brain in patients with AD. These angiogenic endothelial cells exhibit increased expression of angiogenic growth factors and their receptors (i.e.,	Proceedings of the National Academy of Sciences of the United States of America	2,020	10
33,067,520	HARDI-ZOOMit protocol improves specificity to microstructural changes in presymptomatic myelopathy.	Diffusion magnetic resonance imaging (dMRI) proved promising in patients with non-myelopathic degenerative cervical cord compression (NMDCCC), i.e., without clinically manifested myelopathy. Aim of the study is to present a fast multi-shell HARDI-ZOOMit dMRI protocol and validate its usability to detect microstructural myelopathy in NMDCCC patients. In 7 young healthy volunteers, 13 age-comparable healthy controls, 18 patients with mild NMDCCC and 15 patients with severe NMDCCC, the protocol provided higher signal-to-noise ratio, enhanced visualization of white/gray matter structures in microstructural maps, improved dMRI metric reproducibility, preserved sensitivity (SE = 87.88%) and increased specificity (SP = 92.31%) of control-patient group differences when compared to DTI-RESOLVE protocol (SE = 87.88%, SP = 76.92%). Of the 56 tested microstructural parameters, HARDI-ZOOMit yielded significant patient-control differences in 19 parameters, whereas in DTI-RESOLVE data, differences were observed in 10 parameters, with mostly lower robustness. Novel marker the white-gray matter diffusivity gradient demonstrated the highest separation. HARDI-ZOOMit protocol detected larger number of crossing fibers (5-15% of voxels) with physiologically plausible orientations than DTI-RESOLVE protocol (0-8% of voxels). Crossings were detected in areas of dorsal horns and anterior white commissure. HARDI-ZOOMit protocol proved to be a sensitive and practical tool for clinical quantitative spinal cord imaging.	Scientific reports	2,020	10
34,589,904	Microbial metabolites and immune regulation: New targets for major depressive disorder.	Treatments for depression and mood disorders have been singularly targeted at the brain without consideration for the context of the rest of the body. As evidence mounts for a role of autoimmunity and inflammation as risk factors and contributors to mood disorders, attention has shifted to one of the primary immunoregulatory organs in the body--the gut. Gut-brain interactions have been established and correlative links between the microbiome and mood have been examined, but with novel tools and a base of understanding, focus shifts to the mechanisms of these communications. In this review, we examine how the small molecules produced by metabolic processes of bacteria in the gut influence the host immune system. The gaps in knowledge discussed here include the under characterized diversity of small molecules crossing the gut walls, as well as the need to close the logical loop connecting the microbiome to the immune system, and the immune system to behavior and mood. As we move past the dawn of this field, more precise understanding using novel tools and techniques will help move toward a more informed and systematic process for clinically evaluating the efficacy of probiotics and bacterially derived compounds as antidepressants and mood regulators.	Brain, behavior, & immunity - health	2,020	12
34,277,802	Evaluation of the reporting quality of clinical practice guidelines on gliomas using the RIGHT checklist.	The reporting quality of clinical practice guidelines (CPGs) for gliomas has not yet been thoroughly assessed. The International Reporting Items for Practice Guidelines in Healthcare (RIGHT) statement developed in 2016 provides a reporting framework to improve the quality of CPGs. We aimed to estimate the reporting quality of glioma guidelines using the RIGHT checklist and investigate how the reporting quality differs by selected characteristics.	Annals of translational medicine	2,021	6
33,212,335	Developing a New Set of ACGME Milestones for Child Neurology Residency.	The Educational Milestones developed by the Accreditation Council for Graduate Medical Education (ACGME) are a construct used to evaluate the development of core competencies during residency and fellowship training. The milestones were developed to create a framework for professional development during graduate medical education. The first iteration of milestones for the child neurology residency was implemented in 2015. In the years that followed, the ACGME received and reviewed feedback about the milestones and set out to revise them.	Pediatric neurology	2,021	1
32,877,742	Sleep and its regulation: An emerging pathogenic and treatment frontier in Alzheimer's disease.	A majority of patients with Alzheimer's disease (AD) experience some form of sleep disruption, including nocturnal sleep fragmentation, increased daytime napping, decreased slow-wave sleep (SWS, stage N3), and decreased rapid-eye-movement sleep (REM). Clinical studies are investigating whether such sleep disturbances are a consequence of the underlying disease, and whether they also contribute to the clinical and pathological manifestations of AD. Emerging research has provided a direct link between several of these sleep disruptions and AD pathophysiology, suggesting that treating sleep disorders in this population may target basic mechanisms of the disease. Here, we provide a comprehensive review of sleep disturbances associated with the spectrum of AD, ranging from the preclinical stages through dementia. We discuss how sleep interacts with AD pathophysiology and, critically, whether sleep impairments can be targeted to modify the disease course in a subgroup of affected AD patients. Ultimately, larger studies that fully utilize new diagnostic and experimental tools will be required to better define the most relevant sleep disturbance to target in AD, the interventions that best modulate this target symptom, and whether successful early intervention can modify AD risk and prevent dementia.	Progress in neurobiology	2,021	2
30,802,076	Independent recollection/familiarity ratings can dissociate: Evidence from the effects of test context on recognition of event details.	Bodner and Richardson-Champion (2007) found a dissociative effect of test context on binary remember/know judgments about a critical set of details from a film sequence. Details of medium difficulty were more likely to be judged "recollected" when preceded by a set of difficult details than a set of easy details, but were similarly likely to be judged "familiar." Using the same paradigm, we replicated this dissociation when participants independently rated recollection and familiarity. Our finding represents the first evidence that independent recollection/familiarity ratings can be dissociated. In contrast, previous studies using independent ratings have yielded parallel effects of variables that produce dissociative effects with binary judgments. Our discussion considers potential causes of this dissociation, whether test context influenced discrimination or response bias, and implications for interpreting subjective recognition experiences. Demonstrations that test context can affect recollection reports also have implications for designing and conducting eyewitness interviews. (PsycINFO Database Record (c) 2019 APA, all rights reserved).	Canadian journal of experimental psychology = Revue canadienne de psychologie experimentale	2,019	6
31,189,912	Duets recorded in the wild reveal that interindividually coordinated motor control enables cooperative behavior.	Many organisms coordinate rhythmic motor actions with those of a partner to generate cooperative social behavior such as duet singing. The neural mechanisms that enable rhythmic interindividual coordination of motor actions are unknown. Here we investigate the neural basis of vocal duetting behavior by using an approach that enables simultaneous recordings of individual vocalizations and multiunit vocal premotor activity in songbird pairs ranging freely in their natural habitat. We find that in the duet-initiating bird, the onset of the partner's contribution to the duet triggers a change in rhythm in the periodic neural discharges that are exclusively locked to the initiating bird's own vocalizations. The resulting interindividually synchronized neural activity pattern elicits vocalizations that perfectly alternate between partners in the ongoing song. We suggest that rhythmic cooperative behavior requires exact interindividual coordination of premotor neural activity, which might be achieved by integration of sensory information originating from the interacting partner.	Nature communications	2,019	6
33,140,877	Martial arts training is related to implicit intermanual transfer of visuomotor adaptation.	Recent work identified an explicit and implicit transfer of sensorimotor adaptation with one limb to the other, untrained limb. Here, we pursue the idea that different individual factors contribute differently to the amount of explicit and implicit intermanual transfer. In particular, we tested a group of judo athletes who show enhanced right-hemispheric involvement in motor control and a group of equally trained athletes. After adaptation to a 60° visual rotation, we estimated awareness of the perturbation and transfer to the untrained, non-dominant left hand in two experiments. We measured the total amount of intermanual transfer (explicit plus implicit) by telling the participants to repeat what was learned during adaptation, and the amount of implicit transfer by instructing the participants to refrain from using what was learned and to perform movements as during baseline instead. We found no difference between the total intermanual transfer of judokas and running experts, with mean absolute transfer values of 42.4° and 47.0°. Implicit intermanual transfer was very limited, but larger in judokas than in general sports athletes, with mean values of 5.2° and 1.6°. A multiple linear regression analysis further revealed that total intermanual transfer, which mainly represents the explicit transfer, is related to awareness of the perturbation, while implicit intermanual transfer can be predicted by judo training, amount of total training, speed of adaptation, and handedness scores. The findings suggest that neuronal mechanisms such as hemispheric interactions and functional specialization underlying intermanual transfer of motor learning may be applied according to individual predisposition.	The European journal of neuroscience	2,021	2
33,432,098	Development of phenotypic assays for identifying novel blockers of L-type calcium channels in neurons.	L-type calcium channels (LTCCs) are highly expressed in the heart and brain and are critical for cardiac and neuronal functions. LTCC-blocking drugs have a long and successful record in the clinic for treating cardiovascular disorders. In contrast, establishment of their efficacy for indications of the central nervous system remains challenging given the tendency of existing LTCC drugs being functionally and mechanistically more selective for peripheral tissues. LTCCs in vivo are large macromolecular complexes consisting of a pore-forming subunit and other modulatory proteins, some of which may be neuro-specific and potentially harbor mechanisms for neuronal selectivity. To exploit the possibility of identifying mechanistically novel and/or neuro-selective blockers, we developed two phenotypic assays-a calcium flux-based primary screening assay and a patch clamp secondary assay, using rat primary cortical cultures. We screened a library comprised of 1278 known bioactive agents and successfully identified a majority of the potent LTCC-blocking drugs in the library. Significantly, we identified a previously unrecognized LTCC blocker with a novel mechanism, which was corroborated by patch clamp and binding studies. As such, these phenotypic assays are robust and represent an important step towards identifying mechanistically novel and neuro-selective LTCC blockers.	Scientific reports	2,021	1
32,808,721	Gesture's body orientation modulates the N400 for visual sentences primed by gestures.	Body orientation of gesture entails social-communicative intention, and may thus influence how gestures are perceived and comprehended together with auditory speech during face-to-face communication. To date, despite the emergence of neuroscientific literature on the role of body orientation on hand action perception, limited studies have directly investigated the role of body orientation in the interaction between gesture and language. To address this research question, we carried out an electroencephalography (EEG) experiment presenting to participants (n = 21) videos of frontal and lateral communicative hand gestures of 5 s (e.g., raising a hand), followed by visually presented sentences that are either congruent or incongruent with the gesture (e.g., "the mountain is high/low…"). Participants underwent a semantic probe task, judging whether a target word is related or unrelated to the gesture-sentence event. EEG results suggest that, during the perception phase of handgestures, while both frontal and lateral gestures elicited a power decrease in both the alpha (8-12 Hz) and the beta (16-24 Hz) bands, lateral versus frontal gestures elicited reduced power decrease in the beta band, source-located to the medial prefrontal cortex. For sentence comprehension, at the critical word whose meaning is congruent/incongruent with the gesture prime, frontal gestures elicited an N400 effect for gesture-sentence incongruency. More importantly, this incongruency effect was significantly reduced for lateral gestures. These findings suggest that body orientation plays an important role in gesture perception, and that its inferred social-communicative intention may influence gesture-language interaction at semantic level.	Human brain mapping	2,020	12
31,839,913	Effectiveness of Religious-Spiritual Group Therapy on Spiritual Health and Quality of Life in Methadone-treated Patients: A Randomized Clinical Trial.	Spirituality is one of the most important factors that can contribute to the recovery of substance use disorder (SUD). The objective of this study is to evaluate the efficacy of the religious-spiritual group therapy on the spiritual health and the quality of life in methadone-treated patients.	Addiction & health	2,019	7
33,344,730	Social isolation alters behavior, the gut-immune-brain axis, and neurochemical circuits in male and female prairie voles.	The absence of social support, or social isolation, can be stressful, leading to a suite of physical and psychological health issues. Growing evidence suggests that disruption of the gut-immune-brain axis plays a crucial role in the negative outcomes seen from social isolation stress. However, the mechanisms remain largely unknown. The socially monogamous prairie vole (	Neurobiology of stress	2,020	11
31,355,751	Coronary stent implantation for acute basilar artery occlusion with underlying stenosis.	Our aim was to study the effectiveness of coronary stent implantation during the endovascular treatment (EVT) of acute basilar artery occlusion (BAO) with occlusion-underlying intracranial atherosclerotic stenosis (ICAS).	EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology	2,020	12
31,587,291	The role of dark-side of motivation and intention to continue in exercise: A self-determination theory approach.	Motivation plays an important role when it comes to regular physical exercise. Hence, low levels of intentions to continue exercising in the future may ultimately lead to higher rates of exercise dropout. The first objective of the present research was to test a theoretical model considering the dark side of motivational determinants on intentions towards exercising in the future. The second objective consisted in comparing groups with different characteristics, as a way to identify individuals with weaker intention, which is believed to be an indicator of a higher dropout risk. In total, 544 (294 female; 250 male) gym exercisers aged between 18 and 58 years (M = 35.00; SD = 11.57) partook in the present research. Participants were engaged in fitness group classes (n = 273) or in cardio/resistance workouts (n = 271), and their exercise experience ranged from 3 to 120 months (M = 47.41; SD = 7.54). Results showed that the measurement and the structural model had an excellent fit. In addition, the structural model was invariant between gender, fitness activities, and exercise experience. Each group displayed different explained variance in intention to continue exercising. Overall, male, young adults and more experienced exercisers had stronger intentions towards exercising. Fitness instructors should be aware of their own thwarting behaviors, especially when interacting with female, young and less experienced exercisers, since they have weaker intentions to exercise in the future, possibly representing an increased risk of withdrawal.	Scandinavian journal of psychology	2,019	12
32,759,370	Sex Differences in the Inflammatory Consequences of Stress: Implications for Pharmacotherapy.	Women are at significantly greater risk of developing stress-related disorders such as depression. The increased risk begins during puberty and continues throughout life until menopause, suggesting a role for ovarian hormones in this increased susceptibility. Importantly, inflammation has been gaining momentum in its role in the pathogenesis of depression. Herein, clinical and preclinical studies have been reviewed to better understand how sex differences within the immune system may contribute to exaggerated risk of depression in females. First, studies that investigate the ability of psychologic stress episodes to engage the inflammatory systems both in the brain and periphery are reviewed with a special focus on sex-specific effects. Moreover, studies are discussed that identify whether imbalanced inflammatory milieu contributes to the development of depression in males versus females and whether these effects are regulated by estradiol. Importantly, we propose a locus coeruleus-norepinephrine-cytokine circuit as a conduit through which stress could increase stress susceptibly in females. Finally, the anti-inflammatory capacity of traditional and nontraditional antidepressants is investigated, with the goal of providing a better understanding of pharmacotherapeutics to enhance strategies to personalize antidepressant treatments between the sexes. The studies reviewed herein strongly support the need for further studies to elucidate whether females are especially sensitive to anti-inflammatory compounds as adjuvants to traditional therapies. SIGNIFICANCE STATEMENT: Women have hve an increased risk of developing stress-related disorders such as depression. In this review, literature from clinical and preclinical studies are integrated to define sex differences in stress-induced inflammatory responses as a potential source for the etiology of sex differences in depressive disorders. Moreover, the anti-inflammatory capacity of traditional and nontraditional antidepressants is reviewed to inform on potential pharmacotherapeutic strategies to personalize antidepressant therapy in a sex-dependent manner.	The Journal of pharmacology and experimental therapeutics	2,020	10
33,183,323	Touchscreen-based location discrimination and paired associate learning tasks detect cognitive impairment at an early stage in an App knock-in mouse model of Alzheimer's disease.	Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline with accumulation of amyloid beta (Aβ) and neurofibrillary tangles that usually begins 15-30 years before clinical diagnosis. Rodent models that recapitulate aggressive Aβ and/or the pathology of neurofibrillary tangles are essential for AD research. Accordingly, non-invasive early detection systems in these animal models are required to evaluate the phenotypic changes, elucidate the mechanism of disease progression, and facilitate development of novel therapeutic approaches. Although many behavioral tests efficiently reveal cognitive impairments at the later stage of the disease in AD models, it has been challenging to detect such impairments at the early stage. To address this issue, we subjected 4-6-month-old male App	Molecular brain	2,020	11
32,916,286	Cross-species functional alignment reveals evolutionary hierarchy within the connectome.	Evolution provides an important window into how cortical organization shapes function and vice versa. The complex mosaic of changes in brain morphology and functional organization that have shaped the mammalian cortex during evolution, complicates attempts to chart cortical differences across species. It limits our ability to fully appreciate how evolution has shaped our brain, especially in systems associated with unique human cognitive capabilities that lack anatomical homologues in other species. Here, we develop a function-based method for cross-species alignment that enables the quantification of homologous regions between humans and rhesus macaques, even when their location is decoupled from anatomical landmarks. Critically, we find cross-species similarity in functional organization reflects a gradient of evolutionary change that decreases from unimodal systems and culminates with the most pronounced changes in posterior regions of the default mode network (angular gyrus, posterior cingulate and middle temporal cortices). Our findings suggest that the establishment of the default mode network, as the apex of a cognitive hierarchy, has changed in a complex manner during human evolution - even within subnetworks.	NeuroImage	2,020	12
32,563,776	Cannabis use the week before admission to psychiatric in-patient service as a marker of severity.	To evaluate if cannabis dose recorded as standard joint unit (SJU) consumed before admission and other related factors have an influence on psychiatric inpatient's symptom severity and clinical outcomes.	Journal of psychiatric research	2,020	10
21,708,256	The golden years: a tribute to Erminio Costa.	In June of 1968 the NIMH established the Laboratory of Preclinical Pharmacology (LPP) under the leadership of Erminio Costa at St. Elizabeths Hospital in Washington, DC. From its inception until 1985 more than 170 scientists produced over 800 scientific publications that largely influenced the direction of neuroscience research. Under Dr. Costa's scientific guidance LPP made numerous discoveries that contributed to the understanding of neuronal function and push the fledging field of neuroscience forward. Methods were developed to measure the turnover rate of catecholamines, serotonin, acetylcholine and GABA, and to assess the dynamic state of neuronal stores of peptides; the regulation of tyrosine hydroxylase activity was revealed; the molecular mechanisms underlying neurotransmitter receptor signaling and regulation were explored; the concept that opioid peptides function as neuromodulators in structures that are not involved in pain threshold regulation was proposed; the role of GABAergic transmission for the action of benzodiazepines was pioneered; the endogenous mechanisms operative in opiate tolerance were elucidated; and approaches to measure mRNA and evaluate its regulation were introduced. As a tribute to Dr. Costa, this article presents the initial journey and the many contributions to teaching and research that he made from 1963 to 1985, a period that I worked with him and call it "the golden years".	Pharmacological research	2,011	10
29,358,565	Microglia activation mediated by toll-like receptor-4 impairs brain white matter tracts in rats.	Microglia activation and white matter injury coexist after repeated episodes of mild brain trauma and ischemic stroke. Axon degeneration and demyelination can activate microglia; however, it is unclear whether early microglia activation can impair the function of white matter tracts and lead to injury. Rat corpus callosum (CC) slices were treated with lipopolysaccharide (LPS) or LPS +	Journal of biomedical research	2,018	3
31,178,032	[Improve the benefit/risk balance of methadone by respecting its pharmacological specificities].	Recent data on methadone from 2008 to 2017 by the French addictovigilance network warms on the increase of methadone use, its diversion, its increase of overdose risk factors (opioids associated, occasional use) and deaths. Whereas methadone is an essential drug for opioid addiction, its use remains complex because of its pharmacology leading to increase the awareness of health professionals.	Therapie	2,019	6
33,548,389	Exosome-based liquid biopsies in cancer: opportunities and challenges.	Liquid biopsy in cancer has gained momentum in clinical research and is experiencing a boom for a variety of applications. There are significant efforts to utilize liquid biopsies in cancer for early detection and treatment stratification, as well as residual disease and recurrence monitoring. Although most efforts have used circulating tumor cells and circulating tumor DNA for this purpose, exosomes and other extracellular vesicles have emerged as a platform with potentially broader and complementary applications. Exosomes/extracellular vesicles are small vesicles released by cells, including cancer cells, into the surrounding biofluids. These exosomes contain tumor-derived materials such as DNA, RNA, protein, lipid, sugar structures, and metabolites. In addition, exosomes carry molecules on their surface that provides clues regarding their origin, making it possible to sort vesicle types and enrich signatures from tissue-specific origins. Exosomes are part of the intercellular communication system and cancer cells frequently use them as biological messengers to benefit their growth. Since exosomes are part of the disease process, they have become of tremendous interest in biomarker research. Exosomes are remarkably stable in biofluids, such as plasma and urine, and can be isolated for clinical evaluation even in the early stages of the disease. Exosome-based biomarkers have quickly become adopted in the clinical arena and the first exosome RNA-based prostate cancer test has already helped >50 000 patients in their decision process and is now included in the National Comprehensive Cancer Network guidelines for early prostate cancer detection. This review will discuss the advantages and challenges of exosome-based liquid biopsies for tumor biomarkers and clinical implementation in the context of circulating tumor DNA and circulating tumor cells.	Annals of oncology : official journal of the European Society for Medical Oncology	2,021	4
32,844,323	Evaluation of a screening program for iron overload and HFE mutations in 50,493 blood donors.	Early detection of individuals with hereditary hemochromatosis (HH) is important to manage iron levels and prevent future organ damage. Although the HFE mutations that cause most cases of HH have been identified, their geographic distribution is highly variable, and their contribution to iron overload is not fully understood. All new registered blood donors at the Sahlgrenska University hospital between 1998 and 2015 were included in the study. Donors with signs of iron overload at baseline and subsequent follow-up testing were recommended genotyping of the HFE gene. Of the 50,493 donors that were included in the study, 950 (1.9%) had signs of iron overload on both test occasions. Of the 840 donors with iron overload that performed HFE genotyping, 117 were homozygous for C282Y, and 97 were compound heterozygotes. The prevalence of C282Y homozygosity was 0.23%. Iron overload screening effectively detects individuals at risk of carrying the C282Y mutation of the HFE gene and enables early treatment to prevent HH complications.	Annals of hematology	2,020	10
32,543,455	Exploring the phytochemical and nutraceutical potentials of dasapatrachurnam.	BackgroundDasapatrachurnam (DPC), a multicurative powder prepared from the leaves of 10 green leafy vegetables, was developed recently with known ethnobotanical and ethnopharmacological significance. However, its functional role in curing a disease is not yet scientifically proven. The present study aims at performing the phytochemical screening of DPC and exploring its possible activity as bacteriostatic, antineoplastic and anti-inflammatory. MethodsWe performed qualitative and Fourier transform infrared spectroscopy (FTIR) to find out the presence of active compounds and tested the bacteriostatic activity in four bacterial strains namely Bacillus subtilis, Escherichia coli, Streptococcus pyogenes and Staphylococcus aureus by agar well diffusion method. We further explored the antineoplastic activity in vitro in C6 and HEK293 cell lines by cell viability assay and the anti-inflammatory activity in the ovalbumin-induced inflammation in male Wistar rats. ResultsDPC showed 60% solubility in PBS and showed the presence of flavonoids and glycosides. FTIR results indicated the presence of alkyl, ketone and aldehyde groups. The bacteriostatic activity of DPC was higher (60%) in E.coli and lower (8%) in S.aureus, when compared to streptomycin. The anti-cancerous activity of DPC in C6 and HEK293 cancer cells was similar to their respective positive controls, curcumin and camptothecin. The anti-inflammatory activity of DPC was more evident with local administration in all the parameters studied in brain hippocampus, kidney, liver and spleen in ovalbumin-induced rats. ConclusionOur results, for the first time, suggest the potentiality of the DPC in treating bacterial diseases, cancer and also inflammation. Our results also suggest the possible therapeutic role of DPC in treating chronic kidney disease.	Journal of complementary & integrative medicine	2,020	9
19,007,704	The American Association of Critical Care Nurse's Beacon Award: a framework for quality.	The Beacon Award for Critical Care Excellence recognizes individual critical care units that have met rigid criteria for excellence, exhibiting high-quality standards and exceptional care of patients and their families. Used as a framework for quality, the award criteria focus on structure, process, and outcomes that enable quality to emerge in the critical care environment. The journey toward meeting Beacon Award criteria can produce long-lasting changes that transform unit-based culture and lead to sustained excellence.	Critical care nursing clinics of North America	2,008	12
32,209,283	Role of neurokinin B in ovine puberty.	Puberty is the process whereby an individual acquires the ability to reproduce, and the attainment of puberty in a timely manner is critical for both humans and livestock. For livestock, the initiation of puberty at the appropriate time aids in increasing lifetime productivity, thus maximizing profitability for producers. For humans, particularly females, early or late puberty is associated with several adverse health outcomes, including polycystic ovary syndrome, obesity, metabolic syndrome, osteoporosis, and psychosocial distress. Therefore, characterizing the mechanisms responsible for puberty onset would have a significant impact on human and animal health. It has been postulated that a group of neurons in the arcuate nucleus of the hypothalamus may play a role in puberty onset. These neurons contain kisspeptin, neurokinin B (NKB), and dynorphin and are often called KNDy neurons. Although the role of kisspeptin in puberty onset has been heavily researched, the involvement of NKB and dynorphin is not well defined. This mini-review focuses on the role of NKB in the initiation of puberty in female sheep. Stimulation of the receptor for NKB, NK3R, elicits LH secretion in a GnRH-dependent manner in prepubertal ewes, and both functional and neuroanatomical changes to the NKB system, particularly within the preoptic area, appear to occur as female sheep transition from a prepubertal to an adult state. Thus, NKB is likely an important component of puberty onset in sheep, although its integration with other systems that impact the pubertal process, such as photoperiod and nutrition, remains to be elucidated.	Domestic animal endocrinology	2,020	10
30,102,594	Diagnosing and treating bipolar disorder in primary care.	Major depression often presents in patients with a history of both depression and mania, although patients may not have the insight to report manic symptoms as problematic. Distinguishing pure (unipolar) depression from bipolar depression is important for prognostic and treatment reasons. Once identified, bipolar depression can be adequately and safely treated.	Cleveland Clinic journal of medicine	2,018	8
32,723,705	Clinical predictors of adverse events during continuous video-EEG monitoring in an epilepsy unit.	Patients admitted to epilepsy monitoring units (EMUs) for diagnostic and presurgical evaluation have an increased risk of seizure-related injury, particularly in the many cases in which medication is withdrawn. The purpose of this study was to assess the prevalence of adverse events (AEs) in this setting and to analyse associated clinical factors and costs. We evaluated consecutive patients admitted to an EMU at a tertiary care hospital over a 10-year period based on a descriptive, longitudinal study. We analysed the occurrence of AEs (traumatic injury, psychiatric complications, status epilepticus, cardiorespiratory disturbances, and death), investigated potential risk factors using univariate and multivariate logistic regression analysis, and compared admission costs between patients with and without AEs. In total, 411 EMU admissions were studied corresponding to 352 patients (55% women; mean [SD] age: 41.7 [12.1] years). Twenty-five patients (6%) experienced an AE. The most common event was traumatic injury (n=9), followed by status epilepticus (n=8), psychiatric complications (n=7), and cardiorespiratory disturbances (n=1). On comparing patients with and without AEs, we observed that the former were more likely to experience generalized seizures (OR: 7.81; 95% CI: 3.51-12.23; p<0.001) or have more seizures overall during admission (OR: 3.2; 95% CI: 1.42-6.8; p=0.002). Patients with AEs also had longer EMU stays (6.91 [2.64] vs 5.08 [1.1]; p=0.004), longer hospital stays (8.45 [3.6] vs 5.18 [1.2]; p<0.001), and higher costs (€7277.71 [€2743.9] vs €5175.7 [€1182.5]; p<0.001). Patients with generalized seizures and more seizures during admission were at greater risk of AEs, which were associated with higher admission costs.	Epileptic disorders : international epilepsy journal with videotape	2,020	8
22,230,889	Bolus injection of hypertonic solutions for cerebral edema in rats: challenge of homeostasis of healthy brain.	Hypertonic solutions are mainstay of osmotherapy to cerebral edema. How hypertonic solutions affect healthy brain homeostasis, however, is not fully understood. Using rat model of cerebral edema induced by local cryoinjury, we found with immunohistochemistry that less microglial activation in healthy hemishere 24 h after hypertonic saline (HS, 3% NaCl) administration, compared to mannitol (20%, the same osmotic concentration of 3% NaCl) while dehydrating the brain tissue. To see whether blood-brain barrier (BBB) or aquaporin-4 (AQP4) contribute to this difference, HS or mannitol was intra-arterially injected to normal rats, and BBB opening, ultrastructure and AQP4 immunoreactivity were examined. Evans blue extravasation indicated that BBB was opened much lighter in HS group than mannitol group at the same time points. Electron microscopy also showed edema around the capillaries slightly lighter in HS than mannitol group 24 h after injection. Meanwhile, HS injection led to AQP4 down regulation in expression similarly as mannitol, compared with NS group. These data suggested that bolus injection of hypertonic agents may lead to microglia activation in healthy brain in different extent, due to BBB compromise, instead of water movement or AQP4 expression. Hence in clinical application, BBB of healthy brain should be considered in perspective to maintain the brain homeostasis.	Neuroscience letters	2,012	2
32,912,931	Chromonomer: A Tool Set for Repairing and Enhancing Assembled Genomes Through Integration of Genetic Maps and Conserved Synteny.	The pace of the sequencing and computational assembly of novel reference genomes is accelerating. Though DNA sequencing technologies and assembly software tools continue to improve, biological features of genomes such as repetitive sequence as well as molecular artifacts that often accompany sequencing library preparation can lead to fragmented or chimeric assemblies. If left uncorrected, defects like these trammel progress on understanding genome structure and function, or worse, positively mislead this research. Fortunately, integration of additional, independent streams of information, such as a marker-dense genetic map and conserved orthologous gene order from related taxa, can be used to scaffold together unlinked, disordered fragments and to restructure a reference genome where it is incorrectly joined. We present a tool set for automating these processes, one that additionally tracks any changes to the assembly and to the genetic map, and which allows the user to scrutinize these changes with the help of web-based, graphical visualizations. Chromonomer takes a user-defined reference genome, a map of genetic markers, and, optionally, conserved synteny information to construct an improved reference genome of chromosome models: a "chromonome". We demonstrate Chromonomer's performance on genome assemblies and genetic maps that have disparate characteristics and levels of quality.	G3 (Bethesda, Md.)	2,020	11
26,282,694	Hospital-treated suicide attempts among Finnish fire setters: a follow-up study.	High rates of attempted and completed suicide have been reported among offenders, but there has been little attention in this respect to fire setters specifically. Aim Our aim was to investigate hospital-treated suicide attempts among male fire setters.	Criminal behaviour and mental health : CBMH	2,016	12
32,446,880	Changes in parental feeding practices and preschoolers' food intake following a randomized controlled childhood obesity trial.	Childhood obesity treatment involving parents is most effective during the preschool age. However, the mechanisms of change are not known. The present study reports on secondary outcomes (changes in parental feeding practices and child food intake) of early obesity treatment. The More and Less study is a randomized controlled trial conducted in Stockholm County, Sweden. Children with obesity (n = 174, mean BMI SDS 3.0, mean age 5 years, 56% girls) and their parents (60% with foreign background, 40% with a university degree) were randomized to: 1) standard treatment focusing on lifestyle recommendations (ST), 2) a parent support program with boosters (PGB), and 3) a parent support program without boosters (PGNB). The Child Feeding Questionnaire (CFQ) was used to measure parental feeding practices. Child food intake was assessed with a Food Frequency Questionnaire (FFQ). We calculated the monthly changes in CFQ practices and FFQ items based on four measurements. We did not find any significant between-group differences in parental feeding practices and child food intake over time. However, general linear models showed that changes in certain feeding practices predicted changes in child food intake. When ST was compared to the parent support groups, some associations moved in opposite directions. For example, increasing maternal restriction predicted increased consumption of cookies/buns in PGNB (b = 2.3, p < 0.05) and decreased consumption of cookies/buns in ST (b = -2.1, p < 0.05). This is among the few studies to examine the effect of parental feeding practices on child food intake and weight status after obesity treatment among preschoolers. We found no evidence that changes in feeding practices or changes in child food intake mediated child weight loss. Future studies should consider other intermediary processes related to general parenting practices and parent-child interactions.	Appetite	2,020	11
32,546,654	Early postmortem brain MRI findings in COVID-19 non-survivors.	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered to have potential neuroinvasiveness that might lead to acute brain disorders or contribute to respiratory distress in patients with coronavirus disease 2019 (COVID-19). This study investigates the occurrence of structural brain abnormalities in non-survivors of COVID-19 in a virtopsy framework.	Neurology	2,020	10
33,169,017	Rapid pathogen detection by metagenomic next-generation sequencing of infected body fluids.	We developed a metagenomic next-generation sequencing (mNGS) test using cell-free DNA from body fluids to identify pathogens. The performance of mNGS testing of 182 body fluids from 160 patients with acute illness was evaluated using two sequencing platforms in comparison to microbiological testing using culture, 16S bacterial PCR and/or 28S-internal transcribed ribosomal gene spacer (28S-ITS) fungal PCR. Test sensitivity and specificity of detection were 79 and 91% for bacteria and 91 and 89% for fungi, respectively, by Illumina sequencing; and 75 and 81% for bacteria and 91 and 100% for fungi, respectively, by nanopore sequencing. In a case series of 12 patients with culture/PCR-negative body fluids but for whom an infectious diagnosis was ultimately established, seven (58%) were mNGS positive. Real-time computational analysis enabled pathogen identification by nanopore sequencing in a median 50-min sequencing and 6-h sample-to-answer time. Rapid mNGS testing is a promising tool for diagnosis of unknown infections from body fluids.	Nature medicine	2,021	1
33,536,199	Neuronal Activity in the Posterior Cingulate Cortex Signals Environmental Information and Predicts Behavioral Variability during Trapline Foraging.	Animals engage in routine behavior to efficiently navigate their environments. This routine behavior may be influenced by the state of the environment, such as the location and size of rewards. The neural circuits tracking environmental information and how that information impacts decisions to deviate from routines remain unexplored. To investigate the representation of environmental information during routine foraging, we recorded the activity of single neurons in posterior cingulate cortex (PCC) in 2 male monkeys searching through an array of targets in which the location of rewards was unknown. Outside the laboratory, people and animals solve such traveling salesman problems by following routine traplines that connect nearest-neighbor locations. In our task, monkeys also deployed traplining routines; but as the environment became better known, they deviate from them despite the reduction in foraging efficiency. While foraging, PCC neurons tracked environmental information but not reward and predicted variability in the pattern of choices. Together, these findings suggest that PCC may mediate the influence of information on variability in choice behavior.	The Journal of neuroscience : the official journal of the Society for Neuroscience	2,021	3
34,589,902	Memantine can protect against inflammation-based cognitive decline in geriatric depression.	Geriatric depression is frequently accompanied by cognitive complaints and inflammation that increase risk for treatment-resistant depression and dementia. Memantine, a neuroprotective drug, can improve depression, inflammation, and help prevent cognitive decline. In our six-month clinical trial, escitalopram/memantine (ESC/MEM) improved mood and cognition compared to escitalopram/placebo treatment (ESC/PBO; NCT01902004). In this report, we examined the impact of baseline inflammation on mood and cognitive outcomes.	Brain, behavior, & immunity - health	2,020	12
32,495,318	Possibilities and the parallel meanings of factual and counterfactual conditionals.	The mental model theory postulates that the meanings of conditionals are based on possibilities. Indicative conditionals-such as "If he is injured tomorrow, then he will take some leave"-have a factual interpretation that can be paraphrased as It is possible, and remains so, that he is injured tomorrow, and in that case certain that he takes some leave. Subjunctive conditionals, such as, "If he were injured tomorrow, then he would take some leave," have a prefactual interpretation that has the same paraphrase. But when context makes clear that his injury will not occur, the subjunctive has a counterfactual paraphrase, with the first clause: It was once possible, but does not remain so, that he will be injured tomorrow. Three experiments corroborated these predictions for participants' selections of paraphrases in their native Spanish, for epistemic and deontic conditionals, for those referring to past and to future events, and for those with then clauses referring to what may or must happen. These results are contrary to normal modal logics. They are also contrary to theories based on probabilities, which are inapplicable to deontic conditionals, such as, "If you have a ticket, then you must enter the show."	Memory & cognition	2,020	10
32,986,715	Restriction on self-renewing asymmetric division is coupled to terminal asymmetric division in the Drosophila CNS.	Neuronal precursor cells undergo self-renewing and non-self-renewing asymmetric divisions to generate a large number of neurons of distinct identities. In Drosophila, primary precursor neuroblasts undergo a varying number of self-renewing asymmetric divisions, with one known exception, the MP2 lineage, which undergoes just one terminal asymmetric division similar to the secondary precursor cells. The mechanism and the genes that regulate the transition from self-renewing to non-self-renewing asymmetric division or the number of times a precursor divides is unknown. Here, we show that the T-box transcription factor, Midline (Mid), couples these events. We find that in mid loss of function mutants, MP2 undergoes additional self-renewing asymmetric divisions, the identity of progeny neurons generated dependent upon Numb localization in the parent MP2. MP2 expresses Mid transiently and an over-expression of mid in MP2 can block its division. The mechanism which directs the self-renewing asymmetric division of MP2 in mid involves an upregulation of Cyclin E. Our results indicate that Mid inhibits cyclin E gene expression by binding to a variant Mid-binding site in the cyclin E promoter and represses its expression without entirely abolishing it. Consistent with this, over-expression of cyclin E in MP2 causes its multiple self-renewing asymmetric division. These results reveal a Mid-regulated pathway that restricts the self-renewing asymmetric division potential of cells via inhibiting cyclin E and facilitating their exit from cell cycle.	PLoS genetics	2,020	9
32,821,956	In vitro evaluation of potential benefits of a silica-rich thermal water (Monfortinho Thermal Water) in hyperkeratotic skin conditions.	Thermal therapy has gained popularity over the years, and Portugal is one of the richest European countries in mineral therapeutic waters. The interest in the use of these natural mineral waters (NMW) for dermatologic purposes is continuously growing but there is a lack of scientific studies supporting its health benefits. The study aims to investigate the effect of a silica-rich NMW in skin cell homeostasis using two representative cell lines of the epidermis and dermis, keratinocytes and fibroblasts, respectively, in addition to a macrophage cell line. Mouse skin fibroblasts, macrophages and human keratinocytes were exposed to culture medium prepared with NMW. Cell metabolism (MTT or resazurin assays) and cell proliferation (trypan blue exclusion dye assay) were investigated. Migration (scratch-wound assay) and senescence (β-galactosidase activity assay) of fibroblasts were also studied. Exposure to NMW compromised the cell metabolic state of all the cell lines tested. This impairment was more pronounced in skin keratinocytes (60% reduction) relatively to skin fibroblasts (45% reduction) or macrophages (25% reduction). Proliferation of macrophages was reduced threefold upon exposure to thermal water, compared to controls. No differences were observed in migration between fibroblasts exposed to NMW and controls, while a potentiation of senescence of these cells was observed. Our results shed light in the bioactive effects of a silica-rich NMW supporting its therapeutic use. A reduction in both cell metabolism and proliferation of keratinocytes and macrophages supports the empirical clinical benefits of this NMW in hyperkeratotic conditions, such as psoriasis and atopic dermatitis.	International journal of biometeorology	2,020	11
33,055,425	Fgr contributes to hemorrhage-induced thalamic pain by activating NF-κB/ERK1/2 pathways.	Thalamic pain, a type of central poststroke pain, frequently occurs following ischemia/hemorrhage in the thalamus. Current treatment of this disorder is often ineffective, at least in part due to largely unknown mechanisms that underlie thalamic pain genesis. Here, we report that hemorrhage caused by microinjection of type IV collagenase or autologous whole blood into unilateral ventral posterior lateral nucleus and ventral posterior medial nucleus of the thalamus increased the expression of Fgr, a member of the Src family nonreceptor tyrosine kinases, at both mRNA and protein levels in thalamic microglia. Pharmacological inhibition or genetic knockdown of thalamic Fgr attenuated the hemorrhage-induced thalamic injury on the ipsilateral side and the development and maintenance of mechanical, heat, and cold pain hypersensitivities on the contralateral side. Mechanistically, the increased Fgr participated in hemorrhage-induced microglial activation and subsequent production of TNF-α likely through activation of both NF-κB and ERK1/2 pathways in thalamic microglia. Our findings suggest that Fgr is a key player in thalamic pain and a potential target for the therapeutic management of this disorder.	JCI insight	2,020	10
33,181,887	Development and validation of a screening questionnaire for psychogenic nonepileptic seizures.	Epilepsy and psychogenic nonepileptic seizures (PNES) are serious conditions, associated with substantial morbidity and mortality. Although prompt diagnosis is essential, these conditions are frequently misdiagnosed, delaying appropriate treatment. We developed and validated the Anxiety, Abuse, and Somatization Questionnaire (AASQ), a quick and clinically practical tool to differentiate PNES from epilepsy.	Epilepsy & behavior : E&B	2,020	11
33,087,832	Automated video-based heart rate tracking for the anesthetized and behaving monkey.	Heart rate (HR) is extremely valuable in the study of complex behaviours and their physiological correlates in non-human primates. However, collecting this information is often challenging, involving either invasive implants or tedious behavioural training. In the present study, we implement a Eulerian video magnification (EVM) heart tracking method in the macaque monkey combined with wavelet transform. This is based on a measure of image to image fluctuations in skin reflectance due to changes in blood influx. We show a strong temporal coherence and amplitude match between EVM-based heart tracking and ground truth ECG, from both color (RGB) and infrared (IR) videos, in anesthetized macaques, to a level comparable to what can be achieved in humans. We further show that this method allows to identify consistent HR changes following the presentation of conspecific emotional voices or faces. EVM is used to extract HR in humans but has never been applied to non-human primates. Video photoplethysmography allows to extract awake macaques HR from RGB videos. In contrast, our method allows to extract awake macaques HR from both RGB and IR videos and is particularly resilient to the head motion that can be observed in awake behaving monkeys. Overall, we believe that this method can be generalized as a tool to track HR of the awake behaving monkey, for ethological, behavioural, neuroscience or welfare purposes.	Scientific reports	2,020	10
32,531,456	Lamotrigine induced Brugada-pattern in a patient with genetic epilepsy associated with a novel variant in SCN9A.	A 30-year-old man presented with intellectual disability associated with epilepsy. The epilepsy was initially treated with sodium valproate and since he was 28 years-old with lamotrigine. With the addition of lamotrigine, a pattern of Brugada syndrome appeared on the electrocardiogram. The family history was positive for epilepsy from the motheŕs side, who had never been treated with lamotrigine.	Gene	2,020	9
27,966,545	The novel homozygous KCNJ10 c.986T>C (p.(Leu329Pro)) variant is pathogenic for the SeSAME/EAST homologue in Malinois dogs.	SeSAME/EAST syndrome is a multisystemic disorder in humans, characterised by seizures, sensorineural deafness, ataxia, developmental delay and electrolyte imbalance. It is exclusively caused by homozygous or compound heterozygous variations in the KCNJ10 gene. Here we describe a similar syndrome in two families belonging to the Malinois dog breed, based on clinical, neurological, electrodiagnostic and histopathological examination. Genetic analysis detected a novel pathogenic KCNJ10 c.986T>C (p.(Leu329Pro)) variant that is inherited in an autosomal recessive way. This variant has an allele frequency of 2.9% in the Belgian Malinois population, but is not found in closely related dog breeds or in dog breeds where similar symptoms have been already described. The canine phenotype is remarkably similar to humans, including ataxia and seizures. In addition, in half of the dogs clinical and electrophysiological signs of neuromyotonia were observed. Because there is currently no cure and treatment is nonspecific and unsatisfactory, this canine translational model could be used for further elucidating the genotype/phenotype correlation of this monogenic multisystem disorder and as an excellent intermediate step for drug safety testing and efficacy evaluations before initiating human studies.	European journal of human genetics : EJHG	2,017	2
33,587,295	MPEP Lowers Binge Drinking in Male and Female C57BL/6 Mice: Relationship with mGlu5/Homer2/Erk2 Signaling.	Metabotropic glutamate receptor 5 (mGlu5) plays an important role in excessive alcohol use and the mGlu5/Homer2/Erk2 signaling pathway has been implicated in binge drinking. The mGlu5 negative allosteric modulator (NAM) 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP) has been shown to reduce binge drinking in male mice, but less is known about its effect on female mice. Here, we sought to determine whether sex differences exists in the effects of MPEP on binge drinking and whether they relate to changes in the MPEP mGlu5/Homer2/Erk2 signaling.	Alcoholism, clinical and experimental research	2,021	4
31,188,707	Fall Prevention Exercises With or Without Behavior Change Support for Community-Dwelling Older Adults: A Two-Year Follow-Up of a Randomized Controlled Trial.	This study investigates the effectiveness of two fall prevention exercise interventions targeting physical performance, activity level, fall-related self-efficacy, health-related quality of life, and falls: the Otago Exercise Programme (OEP) with and the OEP without behavior change support. In this randomized controlled trial (RCT), 175 participants were randomised into two intervention groups and one control group. A total of 124 community-dwelling older adults over the age of 75 who needed walking aids or home support participated in the two-year follow-up. The OEP with and the OEP without support for behavior change displayed no long-term benefits on physical performance, fall-related self-efficacy, health-related quality of life, and falls compared to a control group. Although no significant differences were detected between the groups, the results implied the control group's physical activity level decreased compared to the intervention groups at two-year follow up.	Journal of aging and physical activity	2,019	6
35,548,258	Creating online animated videos to reach and engage youth: Lessons learned from pain science education and a call to action.	Engaging youth in evidence-based health education has the capacity to positively impact their experiences of health and illness across the lifespan. In particular, pain science education is now an established part of the treatment arsenal for persistent pain conditions in adults, and there are calls to build educational resources for youth with pain. In this paper, we argue that high-quality online animated videos are a potentially excellent medium to engage youth at a mass level in pain science education. We present and compare two collaborations between clinician-scientists and industry to create and disseminate online animated videos for pain science education ("Mysterious Science of Pain" and "Tame the Beast"). We discuss the advantages, disadvantages, and methods of evaluation for each approach, as well as summarizing overall lessons learned. We provide this information as a guiding framework for clinician-scientists to collaborate with industry in building engaging and impactful health education resources for young people.	Paediatric & neonatal pain	2,020	12
21,103,947	Neuroimmune pharmacology: an elective course for molecular and cellular bioscience graduate programs.	Neuroimmune pharmacology is an interdisciplinary field which integrates neuroscience, immunology, and pharmacology. This new discipline has developed over the last two decades in order to study the etiology and treatment of disorders involving both the immune and nervous systems. The proposed Neuroimmune Pharmacology course is a semester-long elective course for students in molecular and cellular biology graduate programs. It is designed to introduce these students to basic principles and practices of neuroimmune pharmacology as well as to the application of molecular and cellular biological techniques in the study of neuroimmune disorders. The goal of this elective course is to help prepare future molecular and cellular biologists to undertake research initiatives in the field of neuroimmunity in health and disease.	Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology	2,011	3
33,513,455	Novelty seeking is associated with increased body weight and orbitofrontal grey matter volume reduction.	Novelty seeking (NS) has previously been identified as a personality trait that is associated with elevated body mass index (BMI) and obesity. Of note, both obesity and reduced impulse control - a core feature of NS - have previously been associated with grey matter volume (GMV) reductions in the orbitofrontal cortex (OFC). Yet, it remains unknown, if body weight-related grey matter decline in the OFC might be explained by higher levels of NS. To address this question, we studied associations between NS, BMI and brain structure in 355 healthy subjects. Brain images were pre-processed using voxel-based morphometry (VBM). BMI was calculated from self-reported height and weight. The Tridimensional Personality Questionnaire (TPQ) was used to assess NS. NS and BMI were associated positively (r = .137, p = .01) with NS being a significant predictor of BMI (B = 0.172; SE B = 0.05; ß = 0.184; p = 0.001). Significant associations between BMI and GMV specifically in the OFC (x = -44, y = 56, z = -2, t(350) = 4.34, k = 5, p	Psychoneuroendocrinology	2,021	4
29,519,964	[Pharmacologic Therapies for Different Types of Dementia].	We provide a general overview of pharmacologic treatments for different types of dementia in light of the Guidelines on the Clinical Management of Dementia in Japan 2017, clinical data not addressed in those guidelines, and the results of observational studies, focusing mainly on the treatment of Alzheimer-type dementia. In everyday clinical practice, patients must be provided with personalized treatment that strikes a balance between evidence-based treatment, as described in the guidelines and actual clinical circumstances.	Brain and nerve = Shinkei kenkyu no shinpo	2,018	3
33,113,378	DWnt4 and DWnt10 Regulate Morphogenesis and Arrangement of Columnar Units via Fz2/PCP Signaling in the Drosophila Brain.	Columns are structural and functional units of the brain. However, the mechanism of column formation remains unclear. The medulla of the fly visual center shares features with the mammalian cerebral cortex, such as columnar and layered structures, and provides a good opportunity to study the mechanisms of column formation. Column formation is initiated by three core neurons in the medulla, namely, Mi1, R8, and R7. The proper orientation of neurons is required for the orientation and arrangement of multiple columns. Their orientations may be under the control of planar cell polarity (PCP) signaling, because it is known to regulate the orientation of cells in two-dimensional tissue structures. In this study, we demonstrate that the ligands DWnt4 and DWnt10 expressed specifically in the ventral medulla and dorsal medulla, respectively, globally regulate the columnar arrangement and orientation of Mi1 and R8 terminals through Fz2/PCP signaling in a three-dimensional space.	Cell reports	2,020	10
33,052,409	Pupillary response to representations of light in paintings.	It is known that, although the level of light is the primary determinant of pupil size, cognitive factors can also affect pupil diameter. It has been demonstrated that photographs of the sun produce pupil constriction independently of their luminance and other low-level features, suggesting that high-level visual processing may also modulate pupil response. Here, we measure pupil response to artistic paintings of the sun, moon, or containing a uniform lighting, that, being mediated by the artist's interpretation of reality and his technical rendering, require an even higher level of interpretation compared with photographs. We also study how chromatic content and spatial layout affect the results by presenting grey-scale and inverted versions of each painting. Finally, we assess directly with a categorization test how subjective image interpretation affects pupil response. We find that paintings with the sun elicit a smaller pupil size than paintings with the moon, or paintings containing no visible light source. The effect produced by sun paintings is reduced by disrupting contextual information, such as by removing color or manipulating the relations between paintings features that make more difficult to identify the source of light. Finally, and more importantly, pupil diameter changes according to observers' interpretation of the scene represented in the same stimulus. In conclusion, results show that the subcortical pupillary response to light is modulated by subjective interpretation of luminous objects, suggesting the involvement of cortical systems in charge of cognitive processes, such as attention, object recognition, familiarity, memory, and imagination.	Journal of vision	2,020	10
31,170,744	[Artificial Intelligence in Endoscopy: Deep Neural Nets for Endoscopic Computer Vision - Methods & Perspectives].	Artificial neural networks, as a specific approach towards artificial intelligence (AI), can open up a variety of new perspectives for endoscopy, such as automated lesion detection and the precise prediction of a lesion's histology by its endoscopic appearance. Whilst early experiments do suggest an enormous potential for these methods, public expectations on their application in various fields of medicine sometimes appear to be grounded on general fascination rather than detailed understanding of their inner workings. Based on a selective review of the literature, this article shall convey an intuitive understanding of the underlying methods in order to help close the gap between functioning and fascination and allow for a realistic discussion of their perspectives and limitations in endoscopy.After decades of research, the success of deep neuronal networks in image classification has provoked rising interest for AI during recent years. We quickly touch upon the developments surrounding this breakthrough and the reasons for their impact on various disciplines much beyond computer science. Through a comparison with the functioning of the human vision system, we aim to understand the mechanisms of these techniques and their success in computer vision tasks in detail. Based on these considerations, we analyse the functioning of some important AI applications in endoscopy, deduce specific limitations and perspectives, discuss the current state of their evaluation in practical endoscopy and make a plea for the need for additional and realistic tests. Moreover, we seek to give an impression of some further specific applications that can currently be foreseen and how these can shape the role that AI might finally acquire in the routine clinical practice of GI endoscopy.	Zeitschrift fur Gastroenterologie	2,019	6
32,810,776	Smart phone assisted quinoline-hemicyanine based fluorescent probe for the selective detection of glutathione and the application in living cells.	Quinoline appended hemicyanine 6MIM with strong ICT character was successfully synthesized through simple condensation reaction of 6-methoxy-2-chloro-3-formyl quinoline with 2-benzothiazolinium iodide. The photophysical characteristics of synthesized probe revealed that it would selectively detect glutathione (GSH) when it compared with different amino acids including biothiols and the detection limit is found to be 100 nM. The turn off sensor is due to thiol-halogen S	Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy	2,020	12
33,152,338	The role of dopamine signaling in prairie vole peer relationships.	Dopamine signaling mediates the formation of some types of social relationships, including reproductive pair bonds in the socially monogamous prairie vole (Microtus ochrogaster). In addition to these pair bonds with mates, prairie voles demonstrate selective preferences for familiar same-sex peers. The dependence of peer relationships on dopamine signaling has not been tested, and the mechanisms supporting these relationships may differ from those underlying pair bonds. We examined the effects of pharmacological manipulations of dopamine signaling on peer partner preference and socially conditioned place preference in female prairie voles. Haloperidol blockade of dopamine receptors at multiple doses did not alter selective preferences for familiar same-sex partners, suggesting that dopamine neurotransmission is not necessary for the formation of prairie vole peer relationships, unlike mate relationships. Dopamine receptor agonist apomorphine facilitated peer partner preferences under conditions normally insufficient for partner preference formation; however, in the absence of effects from blockade, it is difficult to distinguish between a role for dopamine in partner preference formation and the generally rewarding properties of a dopamine agonist. Prairie voles exhibited socially conditioned place preferences for new but not long-term same-sex peers, and these preferences were not blocked by haloperidol. These results suggest that prairie vole peer relationships are less dependent on dopamine signaling than pair bonds, while still being rewarding. The data support distinct roles of dopamine and motivation in prairie vole peer relationships relative to mate relationships, suggesting that reproductive bonds are mediated differently from non-reproductive ones.	Hormones and behavior	2,021	1
31,173,799	The expression of allocentric object-place recognition memory during development.	The allocentric representation of space is a fundamental pillar of episodic experience. In infant rats, the neural circuitry underlying the formation of allocentric spatial representations is functioning from early on when eyes are opening, i.e., before postnatal day (PD) 15. However, it remains unclear when and how during early development rats use these representations to regulate spatial behavior. Here, we studied indicators of memory-based spatial navigation using a classical object-place recognition (OPR) task set-up in infant (PD15), pre-weanling (PD18), juvenile (PD25), peri-adolescent (PD31), adolescent (PD38, PD48), and young adult rats (PD84). On the task, rats explored an arena with two identical objects, and memory was tested in a recall phase 3 h later in the same arena with, one object displaced from its original location. Only at adolescence (PD38), rats showed the typical adult-like expression of allocentric spatial memory with a preferential exploration of the object at the novel location. However, the first expression of allocentric spatial memory was revealed already in PD18 rats, which contrasting with PD84 rats, showed a preference to explore the object at the familiar location. At PD31, rats showed a null preference between the object-locations. Nevertheless, spatial memory at this age expressed in a preference for the zone including the familiar object-location. In PD15 rats, we found no evidence for a memory-based organization of spatial behavior. In conclusion, although rats might be able to form allocentric neuronal representations of space already earlier, only from PD18 on, such representations are used to organize spatial behavior, with a motivational shift from familiarity to novelty-driven navigation occurring during adolescence.	Behavioural brain research	2,019	10
20,477,143	Quantification of antineural antibodies in autoimmune neurological disorders.	More than 50 different neurological pathologies have a confirmed or suspected autoimmune etiology affecting an estimated number of 75 million people worldwide. Autoantibodies are a useful diagnostic marker for most autoimmune diseases even though their pathological role is not evident, and several tests for their detection are commercially available. However, for autoimmune diseases involving the nervous system, lack of clear information on the identity of antineural antibody targets and the presence of many rare diseases have hampered the development of specific diagnostic assays. This review focuses on the actual knowledge on confirmed and suspected autoimmune diseases that target the CNS and the diagnostic relevance of corresponding antineural autoantibodies.	Expert review of clinical immunology	2,007	11
33,238,123	An IL-27-Driven Transcriptional Network Identifies Regulators of IL-10 Expression across T Helper Cell Subsets.	Interleukin-27 (IL-27) is an immunoregulatory cytokine that suppresses inflammation through multiple mechanisms, including induction of IL-10, but the transcriptional network mediating its diverse functions remains unclear. Combining temporal RNA profiling with computational algorithms, we predict 79 transcription factors induced by IL-27 in T cells. We validate 11 known and discover 5 positive (Cebpb, Fosl2, Tbx21, Hlx, and Atf3) and 2 negative (Irf9 and Irf8) Il10 regulators, generating an experimentally refined regulatory network for Il10. We report two central regulators, Prdm1 and Maf, that cooperatively drive the expression of signature genes induced by IL-27 in type 1 regulatory T cells, mediate IL-10 expression in all T helper cells, and determine the regulatory phenotype of colonic Foxp3	Cell reports	2,020	11
32,162,607	Assessment of bioavailability of Mg from Mg citrate and Mg oxide by measuring urinary excretion in Mg-saturated subjects.	Low magnesium (Mg) levels are linked to many diseases. Studies suggest that organic salts of Mg are more readily bioavailable than its oxide or inorganic salts used for supplements production. Unfortunately, the plethora of variables in the previous study designs complicates the making of any clear and reliable conclusions.	Magnesium research	2,019	8
32,574,803	Modulatory effects of dynamic fMRI-based neurofeedback on emotion regulation networks in adolescent females.	Research has shown that difficulties with emotion regulation abilities in childhood and adolescence increase the risk for developing symptoms of mental disorders, e.g anxiety. We investigated whether functional magnetic resonance imaging (fMRI)-based neurofeedback (NF) can modulate brain networks supporting emotion regulation abilities in adolescent females. We performed three experiments (Experiment 1: N = 18; Experiment 2: N = 30; Experiment 3: N = 20). We first compared different NF implementations regarding their effectiveness of modulating prefrontal cortex (PFC)-amygdala functional connectivity (fc). Further we assessed the effects of fc-NF on neural measures, emotional/metacognitive measures and their associations. Finally, we probed the mechanism underlying fc-NF by examining concentrations of inhibitory and excitatory neurotransmitters. Results showed that NF implementations differentially modulate PFC-amygdala fc. Using the most effective NF implementation we observed important relationships between neural and emotional/metacognitive measures, such as practice-related change in fc was related with change in thought control ability. Further, we found that the relationship between state anxiety prior to the MRI session and the effect of fc-NF was moderated by GABA concentrations in the PFC and anterior cingulate cortex. To conclude, we were able to show that fc-NF can be used in adolescent females to shape neural and emotional/metacognitive measures underlying emotion regulation. We further show that neurotransmitter concentrations moderate fc-NF-effects.	NeuroImage	2,020	10
33,410,627	Pandemic of the aging society - sporadic cerebral small vessel disease.	Age-related sporadic cerebral small vessel disease (CSVD) has gained increasing attention over the past decades because of its increasing prevalence associated with an aging population. The widespread application of and advances in brain magnetic resonance imaging in recent decades have significantly increased researchers' understanding in the in vivo evolution of CSVD, its impact upon the brain, its risk factors, and the mechanisms that explain the various clinical manifestation associated with sporadic CSVD. In this review, we aimed to provide an update on the pathophysiology, risk factors, biomarkers, and the determinants and spectrum of the clinical manifestation of sporadic CSVD.	Chinese medical journal	2,021	1
30,538,240	Publisher Correction: Tracing the transitions from pluripotency to germ cell fate with CRISPR screening.	Ufuk Günesdogan was incorrectly associated with Center for Genetic Analysis of Behaviour, National Institute for Physiological Sciences, 5-1 Higashiyama Myodaiji, Okazaki, Aichi 444-8787, Japan and Toshihiro Kobayashi was incorrectly associated with Department of Developmental Biology, University of Göttingen, Göttingen Center for Molecular Biosciences, Justus-von-Liebig Weg 11, 37077 Göttingen, Germany. This has now been corrected in both the PDF and HTML versions of the Article.	Nature communications	2,018	12
19,837,052	David de Wied: Eminent scientist and academic leader: A personal note.	David de Wied was a natural leader with many a talent. He was the director of the Rudolf Magnus Institute at Utrecht University and president of the Royal Netherlands Academy of Arts and Sciences. He coached over 75 Ph.D. students and hosted some 200 foreign scientists who joined him in his multidisciplinary neuropeptide research. Many of them became lifelong friends, frequenting the home of Liedje and David de Wied. Born in Deventer (The Netherlands) on January 12th, 1925, David de Wied's early boyhood first in Deventer and later in Leeuwarden appears to have been no different from that of any other provincial Dutch boys in pre-war Holland. After the war David enrolled at Groningen University to study medicine. Subsequently he specialized in experimental pharmacology. To understand the determination of David de Wied is to understand the drive of a Jewish young man, who during the war, had been forced to go underground and unable to develop in a free and independent manner. Therefore, later in life, time became very precious to him and everything that came across his path had to be taken seriously. In this short sketch of David de Wied I will try to highlight his outstanding scientific accomplishments as well as his personality as both have inspired a generation of young scientists. It is a great honour and a pleasure to be part of this meeting in memory of David de Wied.	European journal of pharmacology	2,010	1
33,011,817	Transient serotonin depletion at adolescence, but not at early infancy, reduced subsequent anxiety-like behavior and alcohol intake in female mice.	Serotonin (5-HT) plays an important role in the organization of the central nervous system and in the development of social interaction deficits and psychiatric disorders, including anxiety, depression, and addiction disorders. Notably, disruption of the 5-HT system during sensitive periods of development exerts long-term consequences, including altered anxiety response and problematic use of alcohol.	Psychopharmacology	2,021	1
31,377,538	Age-related differences in the structural and effective connectivity of cognitive control: a combined fMRI and DTI study of mental arithmetic.	Cognitive changes with aging are highly variable across individuals. This study investigated whether cognitive control performance might depend on preservation of structural and effective connectivity in older individuals. Specifically, we tested inhibition following working memory (WM) updating and maintenance. We analyzed diffusion tensor imaging and functional magnetic resonance imaging data in thirty-four young adults and thirty-four older adults, who performed an arithmetic verification task during functional magnetic resonance imaging. Results revealed larger arithmetic interference in older adults relative to young adults after WM updating, whereas both groups showed similar interference after WM maintenance. In both groups, arithmetic interference was associated with larger activations and stronger effective connectivity among bilateral anterior cingulate, bilateral inferior frontal gyrus, and left angular gyrus, with larger activations of frontal regions in older adults than in younger adults. In older adults, preservation of frontoparietal structural microstructure, especially involving the inferior frontaloccipital fasciculus, was associated with reduced interference, and stronger task-related effective connectivity. These results highlight how both structural and functional changes in the cognitive control network contribute to individual variability in performance during aging.	Neurobiology of aging	2,019	10
32,497,293	N-terminal heterogeneity of parenchymal and vascular amyloid-β deposits in Alzheimer's disease.	The deposition of amyloid-β (Aβ) peptides in the form of extracellular plaques in the brain represents one of the classical hallmarks of Alzheimer's disease (AD). In addition to 'full-length' Aβ starting with aspartic acid (Asp-1), considerable amounts of various shorter, N-terminally truncated Aβ peptides have been identified by mass spectrometry in autopsy samples from individuals with AD.	Neuropathology and applied neurobiology	2,020	12
32,973,115	Remote platelet function testing using P-selectin expression in patients with recent cerebral ischaemia on clopidogrel.	Antiplatelet agents reduce recurrence after cerebral ischaemia but are not effective in all patients, in part because of treatment resistance. The primary aim was to assess the proportion of patients who are insensitive to clopidogrel. The secondary aim was to assess the association between insensitivity to clopidogrel and recurrent cerebrovascular events.	Stroke and vascular neurology	2,021	3
32,552,571	Role of Feedback Connections in Central Visual Processing.	The physiological response properties of neurons in the visual system are inherited mainly from feedforward inputs. Interestingly, feedback inputs often outnumber feedforward inputs. Although they are numerous, feedback connections are weaker, slower, and considered to be modulatory, in contrast to fast, high-efficacy feedforward connections. Accordingly, the functional role of feedback in visual processing has remained a fundamental mystery in vision science. At the core of this mystery are questions about whether feedback circuits regulate spatial receptive field properties versus temporal responses among target neurons, or whether feedback serves a more global role in arousal or attention. These proposed functions are not mutually exclusive, and there is compelling evidence to support multiple functional roles for feedback. In this review, the role of feedback in vision will be explored mainly from the perspective of corticothalamic feedback. Further generalized principles of feedback applicable to corticocortical connections will also be considered.	Annual review of vision science	2,020	9
32,779,865	Substrate reduction therapy with Miglustat in pediatric patients with GM1 type 2 gangliosidosis delays neurological involvement: A multicenter experience.	In GM1 gangliosidosis the lack of function of β-galactosidase results in an accumulation of GM1 ganglioside and related glycoconjugates in visceral organs, and particularly in the central nervous system, leading to severe disability and premature death. In the type 2 form of the disease, early intervention would be important to avoid precocious complications. To date, there are no effective therapeutic options in preventing progressive neurological deterioration. Substrate reduction therapy with Miglustat, a N-alkylated sugar that inhibits the enzyme glucosylceramide synthase, has been proposed for the treatment of several lysosomal storage disorders such as Gaucher type 1 and Niemann Pick Type C diseases. However, data on Miglustat therapy in patients with GM1 gangliosidosis are still scarce.	Molecular genetics & genomic medicine	2,020	10
32,172,457	Growth-Promoting Treatment Screening for Corticospinal Neurons in Mouse and Man.	Neurons of the central nervous system (CNS) that project long axons into the spinal cord have a poor axon regenerative capacity compared to neurons of the peripheral nervous system. The corticospinal tract (CST) is particularly notorious for its poor regeneration. Because of this, traumatic spinal cord injury (SCI) is a devastating condition that remains as yet uncured. Based on our recent observations that direct neuronal interleukin-4 (IL-4) signaling leads to repair of axonal swellings and beneficial effects in neuroinflammation, we hypothesized that IL-4 acts directly on the CST. Here, we developed a tissue culture model for CST regeneration and found that IL-4 promoted new growth cone formation after axon transection. Most importantly, IL-4 directly increased the regenerative capacity of both murine and human CST axons, which corroborates its regenerative effects in CNS damage. Overall, these findings serve as proof-of-concept that our CST regeneration model is suitable for fast screening of new treatments for SCI.	Cellular and molecular neurobiology	2,020	11
22,742,874	N-Methyl-D-aspartate (NMDA) receptor involvement in central nervous system prostaglandin production during the relapse phase of chronic relapsing experimental autoimmune encephalomyelitis (CR EAE).	Our previous studies have established that major changes in central nervous system (CNS) prostaglandin (PG) levels occur during the relapse phase of chronic relapsing experimental autoimmune encephalomyelitis (CR EAE), an animal model of the human demyelinating disease multiple sclerosis. PG production is controlled through a series of enzymic pathways that, in EAE, are influenced by neuroantigen-driven autoimmune events. In non-immune-based models of CNS disease, endogenous glucocorticoids have been proposed as instigators of PG synthesis via activation of the N-methyl-D-aspartate (NMDA) receptor. Glucocorticoids have an important regulatory role in the pathogenesis EAE and the NMDA receptor is intimately involved in many of the characteristic neuroinflammatory processes that govern the disease. Therefore, the alterations in prostanoid concentrations during the relapse stage of CR EAE may ultimately be governed by glucocorticoid-induced NMDA receptor activation. The current investigation has examined the proposed glucocorticoid-NMDA receptor link by determining the effects of the receptor antagonist, (+) MK-801, on CNS PGE 2 and PGD 2 levels in Biozzi mice with relapse symptoms of CR EAE. Prostanoid concentrations in the cerebral cortex were not altered by drug administration, and in cerebellar tissues, a vehicle effect negated any drug-induced changes. However, the level of PGD 2 in spinal cords from (+) MK-801-dosed mice was significantly lower, compared to controls, but PGE 2 concentrations remained unchanged. The results suggest that glucocorticoid-NMDA receptor-linked events are not primarily responsible for PG generation in the brain but may influence prostanoid production in discrete areas of the CNS.	Fundamental & clinical pharmacology	2,013	10
30,788,408	Health and criminal justice system involvement among African American siblings.	Health disparities between African Americans and Whites have persisted in the United States. Researchers have recently hypothesized that the relatively poor health of African Americans may be caused, in part, by African American overrepresentation in the criminal justice system.	SSM - population health	2,019	4
19,345,109	Use of spontaneous ventilation to monitor the effects of posterior fossa surgery in the sitting position.	We describe the successful excision, guided by spontaneous ventilation, of a cervico-medullary hemangioblastoma in a 22-year-old female in the sitting position. A balanced anesthesia technique comprising an oxygen, nitrous oxide, sevoflurane, fentanyl and vecuronium mixture was used. Apart from routine monitors, electroencephalographic spectral entropy monitoring was used to determine the depth of anesthesia and transesophageal echocardiography for detection of venous air embolism. The patient remained in spontaneous ventilation for 235min during tumor excision. The intraoperative and postoperative course were uneventful. The patient recovered without any major neurological deficit.	Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia	2,009	7
33,150,102	The Application of Digital Platforms in Supporting UK International Medical Graduates.	Although international medical graduates (IMGs) constitute considerable percentage of doctors in the National Health Service (NHS), they face several challenges in acclimatizing to the NHS health system. Communication skills, language subtleties, and career progression difficulties are among the most important challenges that overseas doctors face. Some resources are already available to support these doctors and several trusts across the UK have developed local interventions and educational programs to help their doctors bridge the gaps in their knowledge. However, there is no proof of the external validity of these programs and none are identified as effective on a national level. Senior IMGs are leading very popular and inspiring projects using digital platforms, especially social media. We identified several social media pages, groups, and websites subscribed to by hundreds of thousands of doctors in the UK and around the world, including doctors who are planning a future career in the UK. These platforms provide information, resources, support, and answers to questions posed by junior IMGs. Inspired by these projects and also by an Australian project that transformed a local IMG education program, we studied whether using digital platforms and transforming evidence-based local programs to national ones would be the best way forward to support IMGs.	Cureus	2,020	10
32,470,180	A Regions of Interest Voxel-Based Morphometry Study of the Human Brain During High-Frequency Spinal Cord Stimulation in Patients With Failed Back Surgery Syndrome.	The effectiveness of spinal cord stimulation (SCS) as pain-relieving treatment for failed back surgery syndrome (FBSS) has already been demonstrated. However, potential structural and functional brain alterations resulting from subsensory SCS are less clear. The aim of this study was to test structural volumetric changes in a priori chosen regions of interest related to chronic pain after 1 month and 3 months of high-frequency SCS in patients with FBSS.	Pain practice : the official journal of World Institute of Pain	2,020	11
33,187,098	An Accurate and Robust Method for Spike Sorting Based on Convolutional Neural Networks.	In the fields of neuroscience and biomedical signal processing, spike sorting is a crucial step to extract the information of single neurons from extracellular recordings. In this paper, we propose a novel deep learning approach based on one-dimensional convolutional neural networks (1D-CNNs) to implement accurate and robust spike sorting. The results of the simulated data demonstrated that the clustering accuracy in most datasets was greater than 99%, despite the multiple levels of noise and various degrees of overlapped spikes. Moreover, the proposed method performed significantly better than the state-of-the-art method named "WMsorting" and a deep-learning-based multilayer perceptron (MLP) model. In addition, the experimental data recorded from the primary visual cortex of a macaque monkey were used to evaluate the proposed method in a practical application. It was shown that the method could successfully isolate most spikes of different neurons (ranging from two to five) by training the 1D-CNN model with a small number of manually labeled spikes. Considering the above, the deep learning method proposed in this paper is of great advantage for spike sorting with high accuracy and strong robustness. It lays the foundation for application in more challenging works, such as distinguishing overlapped spikes and the simultaneous sorting of multichannel recordings.	Brain sciences	2,020	11
33,752,777	The effect of anaesthetic dose on response and remission in electroconvulsive therapy for major depressive disorder: nationwide register-based cohort study.	Electroconvulsive therapy (ECT) is a safe and effective treatment for major depressive disorder (MDD). ECT treatment effect relies on induced generalised seizures. Most anaesthetics raise the seizure threshold and shorten seizure duration. There are no conclusive studies on the effect of anaesthetic dose on response and remission rates with ECT for MDD.	BJPsych open	2,021	3

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