rudyvdbrink/CitationDatabase huggingface dataset:
Meet Your Stress Management Professionals: The Endocannabinoids.
Trends in molecular medicine, 2020

The endocannabinoid signaling system (ECSS) is altered by exposure to stress and mediates and modulates the effects of stress on the brain. Considerable preclinical data support critical roles for the endocannabinoids and their target, the CB1 cannabinoid receptor, in the adaptation of the brain to repeated stress exposure. Chronic stress exposure increases vulnerability to mental illness, so the ECSS has attracted attention as a potential therapeutic target for the prevention and treatment of stress-related psychopathology. We discuss human genetic studies indicating that the ECSS contributes to risk for mental illness in those exposed to severe stress and trauma early in life, and we explore the potential difficulties in pharmacological manipulation of the ECSS.
Bayesian models of mentalizing.
Brain topography, 2008

Surprisingly effortless is the human capacity known as "mentalizing", i.e., the ability to explain and predict the behavior of others by attributing to them independent mental states, such as beliefs, desires, emotions or intentions. This capacity is, among other factors, dependent on the correct anticipation of the dynamics of facially expressed emotions based on our beliefs and experience. Important information about the neural processes involved in mentalizing can be derived from dynamic recordings of neural activity such as the EEG. We here exemplify how the so-called Bayesian probabilistic models can help us to model the neural dynamic involved in the perception of clips that evolve from neutral to emotionally laden faces. Contrasting with conventional models, in Bayesian models, probabilities can be used to dynamically update beliefs based on new incoming information. Our results show that a reproducible model of the neural dynamic involved in the appraisal of facial expression can be derived from the grand mean ERP over five subjects. One of the two models used to predict the individual subject dynamic yield correct estimates for four of the five subjects analyzed. These results encourage the future use of Bayesian formalism to build more detailed models able to describe the single trial dynamic.
BRAF inhibition protects against hearing loss in mice.
Science advances, 2020

Hearing loss caused by noise, aging, antibiotics, and chemotherapy affects 10% of the world population, yet there are no Food and Drug Administration (FDA)-approved drugs to prevent it. Here, we screened 162 small-molecule kinase-specific inhibitors for reduction of cisplatin toxicity in an inner ear cell line and identified dabrafenib (TAFINLAR), a BRAF kinase inhibitor FDA-approved for cancer treatment. Dabrafenib and six additional kinase inhibitors in the BRAF/MEK/ERK cellular pathway mitigated cisplatin-induced hair cell death in the cell line and mouse cochlear explants. In adult mice, oral delivery of dabrafenib repressed ERK phosphorylation in cochlear cells, and protected from cisplatin- and noise-induced hearing loss. Full protection was achieved in mice with co-treatment with oral AZD5438, a CDK2 kinase inhibitor. Our study explores a previously unidentified cellular pathway and molecular target BRAF kinase for otoprotection and may advance dabrafenib into clinics to benefit patients with cisplatin- and noise-induced ototoxicity.
A Mendelian randomization study of the causal association between anxiety phenotypes and schizophrenia.
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 2020

Schizophrenia shows a genetic correlation with both anxiety disorder and neuroticism, a trait strongly associated with anxiety. However, genetic correlations do not discern causality from genetic confounding. We therefore aimed to investigate whether anxiety-related phenotypes lie on the causal pathway to schizophrenia using Mendelian randomization (MR). Four MR methods, each with different assumptions regarding instrument validity, were used to investigate casual associations of anxiety and neuroticism related phenotypes on schizophrenia, and vice versa: inverse variance weighted (IVW), weighted median, weighted mode, and, when appropriate, MR Egger regression. MR provided evidence of a causal effect of neuroticism on schizophrenia (IVW odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.12-1.59), but only weak evidence of a causal effect of anxiety on schizophrenia (IVW OR: 1.10, 95% CI: 1.01-1.19). There was also evidence of a causal association from schizophrenia liability to anxiety disorder (IVW OR: 1.28, 95% CI: 1.18-1.39) and worry (IVW beta: 0.05, 95% CI: 0.03-0.07), but effect estimates from schizophrenia to neuroticism were inconsistent in the main analysis. The evidence of neuroticism increasing schizophrenia risk provided by our results supports future efforts to evaluate neuroticism- or anxiety-based therapies to prevent onset of psychotic disorders.
Wearable Transdermal Alcohol Monitors: A Systematic Review of Detection Validity, and Relationship Between Transdermal and Breath Alcohol Concentration and Influencing Factors.
Alcoholism, clinical and experimental research, 2020

Research on alcohol consumption mostly relies on self-reported data, which are subject to recall bias. Wearable transdermal alcohol concentration (TAC) monitors address this limitation by continuously measuring the ethanol excreted via the skin. This systematic review aims to provide an overview of TAC monitors' reliability to detect alcohol consumption and methods to estimate breath alcohol concentration (BrAC) and number of standard drinks consumed in a given time frame.
High-Spatial-Resolution Three-dimensional Imaging of Human Spinal Cord and Column Anatomy with Postmortem X-ray Phase-Contrast Micro-CT.
Radiology, 2021

Background Modern high-spatial-resolution radiologic methods enable increasingly detailed volumetric postmortem investigations of human neuroanatomy for diagnostic, research, and educational purposes. Purpose To evaluate the viability of postmortem x-ray phase-contrast micro-CT to provide tissue-conserving, high-spatial-resolution, three-dimensional neuroimaging of the human spinal cord and column by comparing quality of x-ray phase-contrast micro-CT images of nondissected Thiel-embalmed human spines with images of extracted formalin-fixed human spinal cords. Specific focus was placed on assessing the detection of micrometric spinal cord soft-tissue structure and vasculature. Materials and Methods In this study from August 2015 to August 2019, three Thiel-embalmed human spinal column samples, unilaterally perfused with an iodinated vascular contrast agent, and three extracted formalin-fixed spinal cord samples were imaged postmortem at a synchrotron radiation facility. Propagation-based x-ray phase-contrast micro-CT was used with monochromatic 60-keV x-rays and a detector with either 46-µm or 8-µm pixel sizes. A single-distance phase-retrieval algorithm was applied to the acquired CT projection images in advance of filtered back projection CT reconstruction. The influence on image quality of Thiel versus formalin embalming was examined, and images were qualitatively evaluated in terms of the value of their anatomic representations. Results The x-ray phase-contrast micro-CT of Thiel-embalmed samples resulted in soft-tissue contrast within the vertebral canal, despite evident nervous tissue deterioration after Thiel embalming. Gross spinal cord anatomy, spinal meninges, contrast agent-enhanced spinal vasculature, and spinal nerves were all well rendered alongside surrounding vertebral bone structure. The x-ray phase-contrast micro-CT of formalin-fixed boneless cords led to much higher gray versus white matter contrast and to microscale visualization of deep medullary vasculature and neuronal perikarya. Conclusion This work demonstrated the use of x-ray phase-contrast micro-CT for detailed volumetric anatomic visualization of embalmed human spines. The method provided three-dimensional display of bone, nervous tissue, and vasculature at microscale resolutions without exogenous contrast agents. © RSNA, 2020
Thirst recruits phasic dopamine signaling through subfornical organ neurons.
Proceedings of the National Academy of Sciences of the United States of America, 2020

Thirst is a highly potent drive that motivates organisms to seek out and consume balance-restoring stimuli. The detection of dehydration is well understood and involves signals of peripheral origin and the sampling of internal milieu by first order homeostatic neurons within the lamina terminalis-particularly glutamatergic neurons of the subfornical organ expressing CaMKIIa (SFO
Perioperative COX2 and β-adrenergic blockade improves biomarkers of tumor metastasis, immunity, and inflammation in colorectal cancer: A randomized controlled trial.
Cancer, 2020

Preclinical studies have implicated excess release of catecholamines and prostaglandins in the mediation of prometastatic processes during surgical treatment of cancer. In this study, we tested the combined perioperative blockade of these pathways in patients with colorectal cancer (CRC).
Pinin protects astrocytes from cell death after acute ischemic stroke via maintenance of mitochondrial anti-apoptotic and bioenergetics functions.
Journal of biomedical science, 2019

Stroke is the second most common cause of deaths worldwide. After an ischemic stroke, the proliferated reactive astrocytes in the peri-infarct areas play a beneficial role in neuronal survival. As such, astrocytes have gradually become a target for neuroprotection in stroke. The present study assessed the hypothesis that Pinin (Pnn), originally identified as a nuclear and desmosome-associated protein and is now known to possess anti-apoptotic capacity, protects astrocytes from cell death after ischemic stroke and delineated the underlying mechanisms.
Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera.
Cell, 2021

SARS-CoV-2 has caused over 2 million deaths in little over a year. Vaccines are being deployed at scale, aiming to generate responses against the virus spike. The scale of the pandemic and error-prone virus replication is leading to the appearance of mutant viruses and potentially escape from antibody responses. Variant B.1.1.7, now dominant in the UK, with increased transmission, harbors 9 amino acid changes in the spike, including N501Y in the ACE2 interacting surface. We examine the ability of B.1.1.7 to evade antibody responses elicited by natural SARS-CoV-2 infection or vaccination. We map the impact of N501Y by structure/function analysis of a large panel of well-characterized monoclonal antibodies. B.1.1.7 is harder to neutralize than parental virus, compromising neutralization by some members of a major class of public antibodies through light-chain contacts with residue 501. However, widespread escape from monoclonal antibodies or antibody responses generated by natural infection or vaccination was not observed.
Brain oscillatory activity associated with switch and mixing costs during reactive control.
Psychophysiology, 2020

Task-switching paradigms, which involve task repetitions and between-task switches, have long been used as a benchmark of cognitive control processes. When mixed and single-task blocks are presented, two types of costs usually occur: the switch cost, measured by contrasting performance on switch and repeat trials during the mixed-task blocks, and the mixing cost, calculated as the performance difference between the all-repeat trials from the single-task blocks and the repeat trials from the mixed-task blocks. Both costs can be mitigated by informational cues that signal the upcoming task switch beforehand. Recent electroencephalographic studies have started unveiling the brain oscillatory activity underlying the switch cost during the preparatory cue-target interval, thus, targeting proactive control processes. Less attention has instead been paid to the mixing cost and, importantly, to the oscillatory dynamics involved in switch and mixing costs during reactive control. To fill this gap, here, we analyzed the time-frequency data obtained during a task-switching paradigm wherein the simultaneous presentation of task cues and targets increased the need for reactive control. Results showed that while alpha and beta bands were modulated by switch and mixing costs in a similar gradual fashion, with greater suppression going from switch to repeat and all-repeat trials, theta power was sensitive to the switch cost with increased power for switch than repeat trials. Together, our findings join previous studies underlining the importance of theta, alpha and beta oscillations in task-switching and extend them by depicting the oscillations involved in switch and mixing costs during reactive control processes.
The Insula Cortex Contacts Distinct Output Streams of the Central Amygdala.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020

The emergence of genetic tools has provided new means of mapping functionality in central amygdala (CeA) neuron populations based on their molecular profiles, response properties, and importantly, connectivity patterns. While abundant evidence indicates that neuronal signals arrive in the CeA eliciting both aversive and appetitive behaviors, our understanding of the anatomy of the underlying long-range CeA network remains fragmentary. In this study, we combine viral tracings, electrophysiological, and optogenetic approaches to establish in male mice, a wiring chart between the insula cortex (IC), a major sensory input region of the lateral and capsular part of the CeA (CeL/C), and four principal output streams of this nucleus. We found that retrogradely labeled output neurons occupy discrete and likely strategic locations in the CeL/C, and that they are disproportionally controlled by the IC. We identified a direct line of connection between the IC and the lateral hypothalamus (LH), which engages numerous LH-projecting CeL/C cells whose activity can be strongly upregulated on firing of IC neurons. In comparison, CeL/C neurons projecting to the bed nucleus of the stria terminalis (BNST) are also frequently contacted by incoming IC axons, but the strength of this connection is weak. Our results provide a link between long-range inputs and outputs of the CeA and pave the way to a better understanding of how internal, external, and experience dependent information may impinge on action selection by the CeA.
On the cortical connectivity in the macaque brain: A comparison of diffusion tractography and histological tracing data.
NeuroImage, 2020

Diffusion-weighted magnetic resonance imaging (DW-MRI) tractography is a non-invasive tool to probe neural connections and the structure of the white matter. It has been applied successfully in studies of neurological disorders and normal connectivity. Recent work has revealed that tractography produces a high incidence of false-positive connections, often from "bottleneck" white matter configurations. The rich literature in histological connectivity analysis studies in the macaque monkey enables quantitative evaluation of the performance of tractography algorithms. In this study, we use the intricate connections of frontal, cingulate, and parietal areas, well established by the anatomical literature, to derive a symmetrical histological connectivity matrix composed of 59 cortical areas. We evaluate the performance of fifteen diffusion tractography algorithms, including global, deterministic, and probabilistic state-of-the-art methods for the connectivity predictions of 1711 distinct pairs of areas, among which 680 are reported connected by the literature. The diffusion connectivity analysis was performed on a different ex-vivo macaque brain, acquired using multi-shell DW-MRI protocol, at high spatial and angular resolutions. Across all tested algorithms, the true-positive and true-negative connections were dominant over false-positive and false-negative connections, respectively. Moreover, three-quarters of streamlines had endpoints location in agreement with histological data, on average. Furthermore, probabilistic streamline tractography algorithms show the best performances in predicting which areas are connected. Altogether, we propose a method for quantitative evaluation of tractography algorithms, which aims at improving the sensitivity and the specificity of diffusion-based connectivity analysis. Overall, those results confirm the usefulness of tractography in predicting connectivity, although errors are produced. Many of the errors result from bottleneck white matter configurations near the cortical grey matter and should be the target of future implementation of methods.
Are adult stressful life events associated with psychotic relapse? A systematic review of 23 studies.
Psychological medicine, 2020

Relapse rates among individuals with psychotic disorders are high. In addition to the financial burden placed on clinical services, relapse is associated with worse long-term prognosis and poorer quality of life. Robust evidence indicates that stressful life events commonly precede the onset of the first psychotic episode; however, the extent to which they are associated with relapse remains unclear. The aim of this systematic review is to summarize available research investigating the association between recent stressful life events and psychotic relapse or relapse of bipolar disorder if the diagnosis included psychotic symptoms. PsycINFO, Medline and EMBASE were searched for cross-sectional, retrospective and prospective studies published between 01/01/1970 and 08/01/2020 that investigated the association between adult stressful life events and relapse of psychosis. Study quality was assessed using the Effective Public Health Practice Project guidelines. Twenty-three studies met eligibility criteria (prospective studies: 14; retrospective studies: 6; cross-sectional: 3) providing data on 2046 participants in total (sample size range: 14-240 participants). Relapse was defined as a return of psychotic symptoms (n = 20), a return of symptoms requiring hospitalization (n = 2) and a return of symptoms or hospitalization (n = 1). Adult stressful life events were defined as life events occurring after the onset of psychosis. Stressful life events included but were not limited to adult trauma, bereavement, financial problems and conflict. Eighteen studies found a significant positive association between adult stressful life events and psychotic relapse and five studies found a non-significant association. We conclude that adult stressful life events, occurring after psychosis onset, appear to be associated with psychotic relapse.
Multi-scale segmentation in GBM treatment using diffusion tensor imaging.
Computers in biology and medicine, 2020

Glioblastoma (GBM) is the commonest primary malignant brain tumor in adults, and despite advances in multi-modality therapy, the outlook for patients has changed little in the last 10 years. Local recurrence is the predominant pattern of treatment failure, hence improved local therapies (surgery and radiotherapy) are needed to improve patient outcomes. Currently segmentation of GBM for surgery or radiotherapy (RT) planning is labor intensive, especially for high-dimensional MR imaging methods that may provide more sensitive indicators of tumor phenotype. Automating processing and segmentation of these images will aid treatment planning. Diffusion tensor magnetic resonance imaging is a recently developed technique (DTI) that is exquisitely sensitive to the ordered diffusion of water in white matter tracts. Our group has shown that decomposition of the tensor information into the isotropic component (p - shown to represent tumor invasion) and the anisotropic component (q - shown to represent the tumor bulk) can provide valuable prognostic information regarding tumor infiltration and patient survival. However, tensor decomposition of DTI data is not commonly used for neurosurgery or radiotherapy treatment planning due to difficulties in segmenting the resultant image maps. For this reason, automated techniques for segmentation of tensor decomposition maps would have significant clinical utility. In this paper, we modified a well-established convolutional neural network architecture (CNN) for medical image segmentation and used it as an automatic multi-sequence GBM segmentation based on both DTI image maps (p and q maps) and conventional MRI sequences (T2-FLAIR and T1 weighted post contrast (T1c)). In this proof-of-concept work, we have used multiple MRI sequences, each with individually defined ground truths for better understanding of the contribution of each image sequence to the segmentation performance. The high accuracy and efficiency of our proposed model demonstrates the potential of utilizing diffusion MR images for target definition in precision radiation treatment planning and surgery in routine clinical practice.
Perspectives on transcriptomics in animal physiology studies.
Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology, 2020

Reductionist approaches in physiology and biochemistry are essential for understanding how animals cope and adapt to their environments. Transcriptomics is no longer restricted to a select few, and accessibility and affordability continue to facilitate its rapid growth as a science. More than 6000 publications (a conservative estimate) over the past decade quantify the response of the transcriptome to a wide breadth of questions in animal physiology. Transcriptomes have been quantified under conditions of hypoxia, climate change, salinity, drought, environmental pollution, and ultraviolet radiation among others; these studies have greatly improved understanding of the molecular machinery required for organismal adaptation. These "snapshots in time" however are never complete as the transcriptome is exquisitely sensitive to an individual's current physiologic state. Animal physiologists new to the field must recognize limitations of transcriptome technologies and consider experimental designs that strengthen physiologic interpretation. Current estimates suggest that a sample size of 6 or more are required for RNA-seq experiments in order to capture the majority of differentially expressed genes confidently. "Outside-the-box" approaches for statistical analyses of data derived from RNA-seq should be explored, as studies continue to point out that high false discoveries rates are pervasive with RNA-seq studies, reminiscent of the early days of microarrays. Incorporating biological variability, rather than reducing it (i.e. pooling strategies), into experimental designs is essential. Moreover, real-time PCR must not be viewed as a "validation step" to justify low samples sizes, but rather an orthogonal method to strengthen biological interpretation. The use of proper experimental controls in transcriptomics studies (i.e. spike-in controls and technical replication) are recommended and there is a pressing need for inter-laboratory tests (round robin experiments) to quantify repeatability and to identify sources of transcriptome variation within the context of animal physiology. Testing the reproducibility of transcriptome experiments in light of physiology in non-model organisms would be a significant contribution to the community. Single cell transcriptomics and multiplexing barcoding strategies such as decode-seq are poised to further advance the reductionist view of animal physiology; researchers are encouraged to consult literature herein and elsewhere for guidance on best practices and limitations of transcriptome technologies when studying the physiology of animals.
Building neuromuscular junctions 
Development (Cambridge, England), 2020

The neuromuscular junction (NMJ) has been the model of choice to understand the principles of communication at chemical synapses. Following groundbreaking experiments carried out over 60 years ago, many studies have focused on the molecular mechanisms underlying the development and physiology of these synapses. This Review summarizes the progress made to date towards obtaining faithful models of NMJs