rudyvdbrink/CitationDatabase huggingface dataset:
Pericyte-secreted IGF2 promotes breast cancer brain metastasis formation.
Molecular oncology, 2020

Brain metastases are life-threatening complications of triple-negative breast cancer, melanoma, and a few other tumor types. Poor outcome of cerebral secondary tumors largely depends on the microenvironment formed by cells of the neurovascular unit, among which pericytes are the least characterized. By using in vivo and in vitro techniques and human samples, here we show that pericytes play crucial role in the development of metastatic brain tumors by directly influencing key steps of the development of the disease. Brain pericytes had a prompt chemoattractant effect on breast cancer cells and established direct contacts with them. By secreting high amounts of extracellular matrix proteins, pericytes enhanced adhesion of both melanoma and triple-negative cancer cells, which might be particularly important in the exclusive perivascular growth of these tumor cells. In addition, pericytes secreted insulin-like growth factor 2 (IGF2), which had a very significant pro-proliferative effect on mammary carcinoma, but not on melanoma cells. By inhibiting IGF2 signaling using silencing or picropodophyllin (PPP), we could block the proliferation-increasing effect of pericytes on breast cancer cells. Administration of PPP (a blood-brain barrier-permeable substance) significantly decreased the size of brain tumors in mice inoculated with triple-negative breast cancer cells. Taken together, our results indicate that brain pericytes have significant pro-metastatic features, especially in breast cancer. Our study underlines the importance of targeting pericytes and the IGF axis as potential strategies in brain metastatic diseases.
Ethical considerations on the complicity of psychologists and scientists in torture.
Journal of the Royal Army Medical Corps, 2019

The long-standing debate on medical complicity in torture has overlooked the complicity of cognitive scientists-psychologists, psychiatrists and neuroscientists-in the practice of torture as a distinct phenomenon. In this paper, we identify the risk of the re-emergence of torture as a practice in the USA, and the complicity of cognitive scientists in these practices.
Outer Hair Cell Glutamate Signaling through Type II Spiral Ganglion Afferents Activates Neurons in the Cochlear Nucleus in Response to Nondamaging Sounds.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2021

Cochlear outer hair cells (OHCs) are known to uniquely participate in auditory processing through their electromotility, and like inner hair cells, are also capable of releasing vesicular glutamate onto spiral ganglion (SG) neurons: in this case, onto the sparse Type II SG neurons. However, unlike glutamate signaling at the inner hair cell-Type I SG neuron synapse, which is robust across a wide spectrum of sound intensities, glutamate signaling at the OHC-Type II SG neuron synapse is weaker and has been hypothesized to occur only at intense, possibly damaging sound levels. Here, we tested the ability of the OHC-Type II SG pathway to signal to the brain in response to moderate, nondamaging sound (80 dB SPL) as well as to intense sound (115 dB SPL). First, we determined the VGluTs associated with OHC signaling and then confirmed the loss of glutamatergic synaptic transmission from OHCs to Type II SG neurons in KO mice using dendritic patch-clamp recordings. Next, we generated genetic mouse lines in which vesicular glutamate release occurs selectively from OHCs, and then assessed c-Fos expression in the cochlear nucleus in response to sound. From these analyses, we show, for the first time, that glutamatergic signaling at the OHC-Type II SG neuron synapse is capable of activating cochlear nucleus neurons, even at moderate sound levels.
Region-by-region analysis of PET, MRI, and histology in en bloc-resected oligodendrogliomas reveals intra-tumoral heterogeneity.
European journal of nuclear medicine and molecular imaging, 2019

Oligodendrogliomas are heterogeneous tumors in terms of imaging appearance, and a deeper understanding of the histopathological tumor characteristics in correlation to imaging parameters is needed. We used PET-to-MRI-to-histology co-registration with the aim of studying intra-tumoral
Lifetime analysis of mdx skeletal muscle reveals a progressive pathology that leads to myofiber loss.
Scientific reports, 2020

The muscular dystrophy X-linked mouse (mdx) is the most commonly used preclinical model for Duchenne muscular dystrophy. Although disease progression in the mouse does not perfectly model the human disease, it shares many pathological features. Early characterizations of the model reported severe pathology through early adulthood followed by disease stabilization. As a result, research in the mdx mouse has largely focused on early adulthood. The overarching goal of this study is to improve the understanding of the mdx mouse model by tracking pathological features of the disease throughout life. We performed a thorough characterization of myofiber pathology in mdx mice from 2 weeks to 2 years of age. We report that individual mdx muscle fibers undergo progressive hypertrophy that continues through the lifespan. Despite massive hypertrophy on the myofiber level, we report no hypertrophy on the muscle level. These seemingly contradictory findings are explained by previously underappreciated myofiber loss in mdx mice. We conclude that due to myofiber loss, in combination with the progressive nature of other pathological features, aged mdx muscle tissue provides reliable benchmarks for disease progression that may be valuable in testing the efficacy of therapeutics for Duchenne muscular dystrophy.
Neural mechanisms of self-affirmation's stress buffering effects.
Social cognitive and affective neuroscience, 2020

Self-affirmation can buffer stress responses across different contexts, yet the neural mechanisms for these effects are unknown. Self-affirmation has been shown to increase activity in reward-related neural regions, including the ventral striatum and ventromedial prefrontal cortex (VMPFC). Given that reward-related prefrontal cortical regions such as the VMPFC are involved in reducing neurobiological and behavioral responses to stress, we hypothesized that self-affirmation would activate VMPFC and also reduce neural responses to stress in key neural threat system regions such as the dorsal anterior cingulate cortex (dACC) and anterior insula (AI). We explored this hypothesis using self-affirmation and evaluative stress tasks following a within-subjects design in the fMRI scanner. Consistent with prior work, self-affirmation blocks led to lower self-reported stress and improved performance. With respect to neural activity, compared to control blocks, self-affirmation blocks led to greater VMPFC activity, and subsequently less left AI (but not dACC) activity during stress task blocks. Functional connectivity analyses revealed greater connectivity between the VMPFC and left and right AI during self-affirmation compared to control. These findings begin to articulate the neural circuits involved in self-affirmation's effects during exposure to stressors, and more broadly specify neural reward-based responses to stressful situations.
Controlling the behaviour of Drosophila melanogaster via smartphone optogenetics.
Scientific reports, 2020

Invertebrates such as Drosophila melanogaster have proven to be a valuable model organism for studies of the nervous system. In order to control neuronal activity, optogenetics has evolved as a powerful technique enabling non-invasive stimulation using light. This requires light sources that can deliver patterns of light with high temporal and spatial precision. Currently employed light sources for stimulation of small invertebrates, however, are either limited in spatial resolution or require sophisticated and bulky equipment. In this work, we used smartphone displays for optogenetic control of Drosophila melanogaster. We developed an open-source smartphone app that allows time-dependent display of light patterns and used this to activate and inhibit different neuronal populations in both larvae and adult flies. Characteristic behavioural responses were observed depending on the displayed colour and brightness and in agreement with the activation spectra and light sensitivity of the used channelrhodopsins. By displaying patterns of light, we constrained larval movement and were able to guide larvae on the display. Our method serves as a low-cost high-resolution testbench for optogenetic experiments using small invertebrate species and is particularly appealing to application in neuroscience teaching labs.
Direct Reprogramming of Human Fetal- and Stem Cell-Derived Glial Progenitor Cells into Midbrain Dopaminergic Neurons.
Stem cell reports, 2020

Human glial progenitor cells (hGPCs) are promising cellular substrates to explore for the in situ production of new neurons for brain repair. Proof of concept for direct neuronal reprogramming of glial progenitors has been obtained in mouse models in vivo, but conversion using human cells has not yet been demonstrated. Such studies have been difficult to perform since hGPCs are born late during human fetal development, with limited accessibility for in vitro culture. In this study, we show proof of concept of hGPC conversion using fetal cells and also establish a renewable and reproducible stem cell-based hGPC system for direct neural conversion in vitro. Using this system, we have identified optimal combinations of fate determinants for the efficient dopaminergic (DA) conversion of hGPCs, thereby yielding a therapeutically relevant cell type that selectively degenerates in Parkinson's disease. The induced DA neurons show a progressive, subtype-specific phenotypic maturation and acquire functional electrophysiological properties indicative of DA phenotype.
Pharmacokinetics, safety, and tolerability of olaparib and temozolomide for recurrent glioblastoma: results of the phase I OPARATIC trial.
Neuro-oncology, 2020

The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib potentiated radiation and temozolomide (TMZ) chemotherapy in preclinical glioblastoma models but brain penetration was poor. Clinically, PARP inhibitors exacerbate the hematological side effects of TMZ. The OPARATIC trial was conducted to measure penetration of recurrent glioblastoma by olaparib and assess the safety and tolerability of its combination with TMZ.
Aberrant computational mechanisms of social learning and decision-making in schizophrenia and borderline personality disorder.
PLoS computational biology, 2020

Psychiatric disorders are ubiquitously characterized by debilitating social impairments. These difficulties are thought to emerge from aberrant social inference. In order to elucidate the underlying computational mechanisms, patients diagnosed with major depressive disorder (N = 29), schizophrenia (N = 31), and borderline personality disorder (N = 31) as well as healthy controls (N = 34) performed a probabilistic reward learning task in which participants could learn from social and non-social information. Patients with schizophrenia and borderline personality disorder performed more poorly on the task than healthy controls and patients with major depressive disorder. Broken down by domain, borderline personality disorder patients performed better in the social compared to the non-social domain. In contrast, controls and major depressive disorder patients showed the opposite pattern and schizophrenia patients showed no difference between domains. In effect, borderline personality disorder patients gave up a possible overall performance advantage by concentrating their learning in the social at the expense of the non-social domain. We used computational modeling to assess learning and decision-making parameters estimated for each participant from their behavior. This enabled additional insights into the underlying learning and decision-making mechanisms. Patients with borderline personality disorder showed slower learning from social and non-social information and an exaggerated sensitivity to changes in environmental volatility, both in the non-social and the social domain, but more so in the latter. Regarding decision-making the modeling revealed that compared to controls and major depression patients, patients with borderline personality disorder and schizophrenia showed a stronger reliance on social relative to non-social information when making choices. Depressed patients did not differ significantly from controls in this respect. Overall, our results are consistent with the notion of a general interpersonal hypersensitivity in borderline personality disorder and schizophrenia based on a shared computational mechanism characterized by an over-reliance on beliefs about others in making decisions and by an exaggerated need to make sense of others during learning specifically in borderline personality disorder.
An "all-wheel drive" proposal to accelerate clinical research in common and rare neurological diseases.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2020

The complex biology of neurological diseases calls for collaborative efforts that may increase the success rate of clinical research. Models have been proposed, but concrete actions remain insufficient. Based on recent considerations from basic science, from science of patient input and from an analysis of scientific resources in Italy, we here explain why our country may represent an appropriate environment for such actions. Furthermore, we sketch operational framework and business model to be applied in order to accelerate, in parallel, the development of therapies in common and rare diseases.
Sialic Acid and Sialylated Oligosaccharide Supplementation during Lactation Improves Learning and Memory in Rats.
Nutrients, 2018

Sialic acids (Sia) are postulated to improve cognitive abilities. This study evaluated Sia effects on rat behavior when administered in a free form as N-acetylneuraminic acid (Neu5Ac) or conjugated as 6'-sialyllactose (6'-SL). Rat milk contains Sia, which peaks at Postnatal Day 9 and drops to a minimum by Day 15. To bypass this Sia peak, a cohort of foster mothers was used to raise the experimental pups. A group of pups received a daily oral supplementation of Neu5Ac to mimic the amount naturally present in rat milk, and another group received the same molar amount of Sia as 6'-SL. The control group received water. After weaning, rats were submitted to behavioral evaluation. One year later, behavior was re-evaluated, and in vivo long-term potentiation (LTP) was performed. Brain samples were collected and analyzed at both ages. Adult rats who received Sia performed significantly better in the behavioral assessment and showed an enhanced LTP compared to controls. Within Sia groups, 6'-SL rats showed better scores in some cognitive outcomes compared to Neu5Ac rats. At weaning, an effect on polysialylated-neural cell adhesion molecule (PSA-NCAM) levels in the frontal cortex was only observed in 6'-SL fed rats. Providing Sia during lactation, especially as 6'-SL, improves memory and LTP in adult rats.
[Episodic foresight in normal cognitive and pathological aging].
Geriatrie et psychologie neuropsychiatrie du vieillissement, 2016

The ability to project the self forward in time to pre-experience personal events is referred to as episodic future thinking. Different theories have been proposed to try to explain the neurocognitive mechanisms underlying episodic future thinking. In this paper we focus on studies concerning the episodic prospection capacity in cognitive aging and in neurodegenerative diseases such as Alzheimer's disease and semantic dementia. Older adults usually produce fewer episodic details than young adults when recalling past events and when imagining future events. Patients with early to moderate Alzheimer's disease have impaired capacity in the generation of episodic details for retrieved past events and imagined future events. Similarly patients with early to moderate semantic dementia have difficulties in episodic future thinking whereas they succeed to retrieve episodic past events. These patterns are discussed with regard to the respective role of the episodic and personal semantic representations in future personal thoughts as a function of temporal distance by purposing a new neurocognitive model (TEDIFT).
Jail-Based Competency Restoration.
The journal of the American Academy of Psychiatry and the Law, 2018

One of the most traditional, longstanding, and essential methods of providing the proper level of psychiatric treatment for severely disturbed jail inmates with serious mental illness has been hospital transfer. Transfer does not necessarily imply diversion from trial, but diversion from jail, at least while the detainee is in need of higher level care. Unfortunately, hospital transfer has become increasingly unavailable. Two responses to the unavailability of hospital care for pretrial detainees have been used as justification for maintaining this deficiency: the development of jail-based competency restoration programs and the acceptance of enforced medication of pretrial detainees in jail. The authors analyze each of these practices as inadequate responses to the state's failure to provide timely pretrial hospitalization to detainees who have a serious mental illness and are in need of this level of service.
Machine Learning of Spatiotemporal Bursting Behavior in Developing Neural Networks.
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference, 2018

As with other modern sciences (and their computational counterparts), neuroscience experiments can now produce data that, in terms of both quantity and complexity, challenge our interpretative abilities. It is relatively common to be faced with datasets containing many millions of neural spikes collected from tens of thousands of neurons. Traditional data analysis methods can, in a relatively straightforward manner, identify large-scale features in such data (e.g., on the scale of entire networks). What these approaches often cannot do is to connect macroscopic activity to the relevant small-scale behaviors of individual cells, especially in the face of ongoing background activity that is not relevant. This communication presents an application of machine learning techniques to bridge the gap between microscopic and macroscopic behaviors and identify the small-scale activity that leads to large-scale behavior, reducing data complexity to a level that can be amenable to further analysis. A small number of spatiotemporal spikes (among many millions) were found to provide reliable information about if and where a burst will occur.
Analysis of three-dimensional facet joint displacement during two passive upper cervical mobilizations.
Musculoskeletal science & practice, 2020

Understanding the 3D-kinematics of the upper cervical spine during manual mobilization is essential for clinical examination and therapy. Some information about rotational motion is available in literature but translational components are often ignored, complicating the understanding of the complex inter-segmental motions.
Hyperkeratotic acral melanoma mimicking a common wart.
Plastic and reconstructive surgery. Global open, 2015

Acral melanoma is a great pretender; anything but i nfrequently, it adopts clinical faces, simulating skin conditions that make the healthcare provider diagnose it as a benign disease of the palms, soles, and ungual regions. We present a case of a hyperkeratotic acral melanoma that has been misdiagnosed and that has led to an amputation of the thumb.
Prevalence of osteoporosis in schizophrenia patients using the osteoporosis self-assessment tool for Asians.
Journal of mental health (Abingdon, England), 2018

The aims of the current study were to investigate the prevalence and socio-demographic correlates of risk of osteoporosis in Singapore among patients with schizophrenia using the osteoporosis self-assessment tool for Asians (OSTA).
Smaller caudate gray matter volume is associated with greater implicit suicidal ideation in depressed adolescents.
Journal of affective disorders, 2021

Objective biomarkers of cognitive vulnerabilities related to suicidal ideation (SI) may assist in early prevention in adolescents. Previously, we found that smaller gray matter volumes (GMVs) of the dorsal striatum prospectively predicted implicit SI, measured using a computerized implicit association test (IAT) assessing associations between "self" and "death," in a community sample of adolescents. Here, we sought to replicate these findings in an independent sample of depressed adolescents.
Dissociating gait from static appearance: A virtual reality study of the role of dynamic identity signatures in person recognition.
Cognition, 2020

Studies on person recognition have primarily examined recognition of static faces, presented on a computer screen at a close distance. Nevertheless, in naturalistic situations we typically see the whole dynamic person, often approaching from a distance. In such cases, facial information may be less clear, and the motion pattern of an individual, their dynamic identity signature (DIS), may be used for person recognition. Studies that examined the role of motion in person recognition, presented videos of people in motion. However, such stimuli do not allow for the dissociation of gait from face and body form, as different identities differ both in their gait and static appearance. To examine the contribution of gait in person recognition, independently from static appearance, we used a virtual environment, and presented across participants, the same face and body form with different gaits. The virtual environment also enabled us to assess the distance at which a person is recognized as a continuous variable. Using this setting, we assessed the accuracy and distance at which identities are recognized based on their gait, as a function of gait distinctiveness. We find that the accuracy and distance at which people were recognized increased with gait distinctiveness. Importantly, these effects were found when recognizing identities in motion but not from static displays, indicating that DIS rather than attention, enabled more accurate person recognition. Overall these findings highlight that gait contributes to person recognition beyond the face and body and stress an important role for gait in real-life person recognition.
Fused placentas: Till birth do us part.
Placenta, 2021

Twinning and placental fusion occur at a low frequency in species like humans and mice. They are linked to reduced birth weight and intertwin growth discrepancy with important consequences for perinatal survival. Despite this, little is known about the histological characteristics of the twin or fused placenta and how these relate to fetal growth. In this case report, we characterise the histological changes of a fused mouse placenta showing intertwin growth discrepancy. Our study demonstrates that morphological changes in the placental exchange and endocrine regions and elevated calcification levels may contribute to the intertwin growth discrepancy observed in mouse pregnancy.