rudyvdbrink/CitationDatabase huggingface dataset:
Cx43 Present at the Leading Edge Membrane Governs Promigratory Effects of Osteoblast-Conditioned Medium on Human Prostate Cancer Cells in the Context of Bone Metastasis.
Cancers, 2020

Among the different interacting molecules implicated in bone metastases, connexin43 (Cx43) may increase sensitivity of prostate cancer (PCa) cells to bone microenvironment, as suggested by our in silico and human tissue samples analyses that revealed increased level of Cx43 expression with PCa progression and a Cx43 specific expression in bone secondary sites. The goal of the present study was to understand how Cx43 influences PCa cells sensitivity and aggressiveness to bone microenvironment. By means of Cx43-overexpressing PCa cell lines, we revealed a Cx43-dependent promigratory effect of osteoblastic conditioned media (ObCM). This effect on directional migration relied on the presence of Cx43 at the plasma membrane and not on gap junctional intercellular communication and hemichannel functions. ObCM stimulation induced Rac1 activation and Cx43 interaction with cortactin in protrusions of migrating PCa cells. Finally, by transfecting two different truncated forms of Cx43 in LNCaP cells, we determined that the carboxy terminal (CT) part of Cx43 is crucial for the responsiveness of PCa cells to ObCM. Our study demonstrates that Cx43 level and its membrane localization modulate the phenotypic response of PCa cells to osteoblastic microenvironment and that its CT domain plays a pivotal role.
Three-dimensional bioprinted glioblastoma microenvironments model cellular dependencies and immune interactions.
Cell research, 2020

Brain tumors are dynamic complex ecosystems with multiple cell types. To model the brain tumor microenvironment in a reproducible and scalable system, we developed a rapid three-dimensional (3D) bioprinting method to construct clinically relevant biomimetic tissue models. In recurrent glioblastoma, macrophages/microglia prominently contribute to the tumor mass. To parse the function of macrophages in 3D, we compared the growth of glioblastoma stem cells (GSCs) alone or with astrocytes and neural precursor cells in a hyaluronic acid-rich hydrogel, with or without macrophage. Bioprinted constructs integrating macrophage recapitulate patient-derived transcriptional profiles predictive of patient survival, maintenance of stemness, invasion, and drug resistance. Whole-genome CRISPR screening with bioprinted complex systems identified unique molecular dependencies in GSCs, relative to sphere culture. Multicellular bioprinted models serve as a scalable and physiologic platform to interrogate drug sensitivity, cellular crosstalk, invasion, context-specific functional dependencies, as well as immunologic interactions in a species-matched neural environment.
Neuron type-specific expression of a mutant KRAS impairs hippocampal-dependent learning and memory.
Scientific reports, 2020

KRAS mutations are associated with rare cases of neurodevelopmental disorders that can cause intellectual disabilities. Previous studies showed that mice expressing a mutant KRAS have impaired the development and function of GABAergic inhibitory neurons, which may contribute to behavioural deficits in the mutant mice. However, the underlying cellular mechanisms and the role of excitatory neurons in these behavioural deficits in adults are not fully understood. Herein, we report that neuron type-specific expression of a constitutively active mutant KRAS
Non-classical lipoid adrenal hyperplasia presenting as hypoglycemic seizures.
Journal of pediatric endocrinology & metabolism : JPEM, 2020

Introduction Primary adrenal insufficiency is a potentially life-threatening condition that can have many underlying causes. Mutations in the steroidogenic acute regulatory protein (StAR) gene produce lipoid congenital adrenal hyperplasia (LCAH) which usually presents in the infantile period with severe symptoms of adrenal insufficiency. Less commonly, a non-classical form is identified which may present at a later age in affected individuals. Till date, around 30 individuals with the non-classical form have been described. Case presentation We describe a 4-year-old 46, XX Indian girl who presented with hypoglycemic seizures and was subsequently diagnosed as non-classical LCAH on genetic analysis, with homozygous R188C mutation in the StAR gene. Conclusions StAR mutations may have a variety of clinical presentations and are likely under-diagnosed. Genetic diagnosis is important for treatment as well as monitoring of reproductive function.
The effects of depression on the treatment of OCD in a residential sample.
Bulletin of the Menninger Clinic, 2020

Studies investigating the impact of depressive symptoms on obsessive-compulsive disorder (OCD) treatment have yielded mixed findings. The purpose of the study is to extend previous research, which primarily used outpatient samples, to determine whether depression affects OCD treatment outcome among patients receiving intensive residential treatment. OCD patients receiving residential treatment based primarily on exposure and response prevention (ERP) provided data regarding symptoms of depression and OCD at admission and discharge. Patients reported large and significant reductions in OCD symptoms over the course of treatment. Change in OCD symptoms was not significantly affected by depressive symptoms, including patients with severe depressive symptoms. Change in depressive symptoms over the course of treatment was, however, robustly related to change in OCD symptoms, especially among patients who began treatment with severe symptoms of depression. These findings suggest that cognitive-behavior therapy delivered in a residential treatment setting drastically reduces OCD symptoms regardless of depressive symptoms.
Auditory perception is influenced by the orientation of the trunk relative to a sound source.
Experimental brain research, 2021

The study investigated how hearing depends on the whole body, head and trunk orientation relative to a sound source. In normal hearing humans we examined auditory thresholds and their ability to recognize logatomes (bi-syllabic non-sense words) at different whole body, head and trunk rotation relative to a sound source. We found that auditory threshold was increased and logatome recognition was impaired when the body or the trunk were rotated 40° away from a sound source compared to when the body or the trunk was oriented towards the sound source. Conversely, no effects were seen when only the head was rotated. Further, an increase of thresholds and impairment of logatome recognition were also observed after unilateral vibration of dorsal neck muscles that induces, per se, long-lasting illusory trunk displacement relative to the head. Thus, our findings support the idea that processing of acoustic signals depends on where a sound is located within a reference system defined by the subject's trunk coordinates.
CKLF1/CCR5 axis is involved in neutrophils migration of rats with transient cerebral ischemia.
International immunopharmacology, 2020

Chemokine-like factor 1 (CKLF1) is a chemokine increased significantly in ischemic brain poststroke. It shows chemotaxis effects on various immune cells, but the mechanisms of CKLF1 migrating neutrophils are poorly understood. Recent studies have provided evidence that CC chemokine receptor 5 (CCR5), a receptor of CKLF1, is involved in ischemic stroke.
Arterial lactate in traumatic brain injury - Relation to intracranial pressure dynamics, cerebral energy metabolism and clinical outcome.
Journal of critical care, 2020

High arterial lactate is associated with disturbed systemic physiology. Lactate can also be used as alternative cerebral fuel and it is involved in regulating cerebral blood flow. This study explored the relation of endogenous arterial lactate to systemic physiology, pressure autoregulation, cerebral energy metabolism, and clinical outcome in traumatic brain injury (TBI).
MRLocus: Identifying causal genes mediating a trait through Bayesian estimation of allelic heterogeneity.
PLoS genetics, 2021

Expression quantitative trait loci (eQTL) studies are used to understand the regulatory function of non-coding genome-wide association study (GWAS) risk loci, but colocalization alone does not demonstrate a causal relationship of gene expression affecting a trait. Evidence for mediation, that perturbation of gene expression in a given tissue or developmental context will induce a change in the downstream GWAS trait, can be provided by two-sample Mendelian Randomization (MR). Here, we introduce a new statistical method, MRLocus, for Bayesian estimation of the gene-to-trait effect from eQTL and GWAS summary data for loci with evidence of allelic heterogeneity, that is, containing multiple causal variants. MRLocus makes use of a colocalization step applied to each nearly-LD-independent eQTL, followed by an MR analysis step across eQTLs. Additionally, our method involves estimation of the extent of allelic heterogeneity through a dispersion parameter, indicating variable mediation effects from each individual eQTL on the downstream trait. Our method is evaluated against other state-of-the-art methods for estimation of the gene-to-trait mediation effect, using an existing simulation framework. In simulation, MRLocus often has the highest accuracy among competing methods, and in each case provides more accurate estimation of uncertainty as assessed through interval coverage. MRLocus is then applied to five candidate causal genes for mediation of particular GWAS traits, where gene-to-trait effects are concordant with those previously reported. We find that MRLocus's estimation of the causal effect across eQTLs within a locus provides useful information for determining how perturbation of gene expression or individual regulatory elements will affect downstream traits. The MRLocus method is implemented as an R package available at https://mikelove.github.io/mrlocus.
Regulatory landscape in brain development and disease.
Current opinion in genetics & development, 2020

Although many regulatory elements in the non-coding genome are linked to brain development and disease, deciphering their function has been challenging due to the lack of a genomic toolbox. However, recent advances in high throughput sequencing techniques have allowed us to begin decoding its function, enhancing our understanding of the regulatory landscape that underpins human traits and brain disorders. Here, we review how the regulatory landscape of the human brain undergoes dynamic changes across neurodevelopment, different cell types, and human evolution. We then discuss how regulatory landscapes shed light onto the molecular basis of neuropsychiatric disorders and guide the development of specifically targeted molecular therapies. Finally, we offer some thoughts on how these discoveries might impact the direction of future studies.
Moving on: How to switch young people with chronic intestinal failure from pediatric to adult care. a position statement by italian society of gastroenterology and hepatology and nutrition (SIGENP) and italian society of artificial nutrition and metabolism (SINPE).
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 2020

In 2019 the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) and the Italian Society of Artificial Nutrition and Metabolism (SINPE) created a joint panel of experts with the aim of preparing an official statement on transition in Chronic Intestinal Failure (CIF). The transition from pediatric to adult care has a key role in managing all chronic diseases and in optimizing the compliance to care. Thus SIGENP and SINPE, in light of the growing number of patients with IF who need long-term Parenteral Nutrition (PN) and multidisciplinary rehabilitation programs throughout adulthood, shared a common protocol to provide an accurate and timely process of transition from pediatric to adult centers for CIF. The main objectives of the transition process for CIF can be summarized as the so-called "acronym of the 5 M": 1)Motivate independent choices which are characteristics of the adult world; 2)Move towards adult goals (e.g. self-management of his pathology and sexual issues); 3)Maintain the habitual mode of care; 4) Minimize the difficulties involved in the transition process and 5)Modulate the length of the transition so as to fully share with the adult's team the children's peculiarities.
Prevalence, comorbidity and predictors of anxiety disorders among children and adolescents.
Asian journal of psychiatry, 2020

Childhood anxiety may lead to serious health consequences in later life. The present study provides the prevalence, comorbidity, and predictors of anxiety disorders among children and adolescents. This was a cross-sectional national project that was implemented on 28,698 children and adolescents in Iran. Participants entered the study by multistage cluster sampling with an equal number of each gender and three age groups (6-9, 10-14, and 15-18 years) within each cluster. The tools used in this research were the demographic questionnaire and K-SADS-PL. To analyze the data logistic regression and chi-square tests were used in SPSS (ver. 16). The prevalence of anxiety disorder in children and adolescents was 13.2 in boys and 15.1 in girls. Furthermore, gender, age, place of residence and history of psychiatric hospitalization of parents could predict anxiety disorders. Anxiety disorders had comorbidity with behavioral disorders, neurodevelopmental disorders, mood disorders, psychotic disorders, substance abuse disorders, and elimination disorders. According to our findings in this study, anxiety disorders affect the performance, health and life of children and adolescents, identifying the childhood anxiety, as well as finding diseases that are associated with anxiety disorders, can help in the prevention of the disorder.
Revisiting the Role of Health Care Proxies in Reproductive Choice.
Obstetrics and gynecology, 2021

In an effort to protect patients' reproductive rights, many states prohibit health care proxies from serving as surrogate decision makers for pregnancy termination in patients who lack capacity. We explore the case of a 24-year-old developmentally delayed woman with intractable seizures and complex psychosocial needs who was found to be pregnant. Her older sister was her health care proxy and declared that an abortion would be in her best interest, medically and socially; the patient herself lacked capacity to make this decision. Legally, her sister's judgment alone was insufficient to move forward with the procedure. Here we describe our multidisciplinary medical, ethical, and legal review of this case and how, despite agreeing with the patient's sister, legal barriers hindered our ability to obtain an abortion for this patient. Her situation illustrates the unintended consequences of our current approach to surrogate decision making in pregnancy termination. It highlights the need to reconsider the role of health care proxies in reproductive-choice decisions and emphasizes the value of a holistic evaluation of patients' social circumstances.
Guillain-Barré syndrome in SARS-CoV-2 infection: an instant systematic review of the first six months of pandemic.
Journal of neurology, neurosurgery, and psychiatry, 2020

A systematic review from 1 January to 30 June 2020 revealed 42 patients with Guillain-Barré syndrome (GBS) associated with SARS-CoV-2 infection. Single cases and small series were reported from 13 countries, the majority from Europe (79.4%) and especially from Italy (30.9%). SARS-CoV-2 infection was demonstrated by nasopharyngeal swab (85.7%) and serology (14.3%). Median time between COVID-19 and GBS onset in 36 patients was 11.5 days (IQR: 7.7-16). The most common clinical features were: limb weakness (76.2%), hypoareflexia (80.9 %), sensory disturbances (66.7 %) and facial palsy (38.1%). Dysautonomia occurred in 19%, respiratory failure in 33.3% and 40.5% of patients were admitted in intensive care unit. Most patients (71.4%) had the classical clinical presentation but virtually all GBS variants and subtypes were reported. Cerebrospinal fluid (CSF) albumin-cytological dissociation was found in 28/36 (77.8%) and PCR for SARS-CoV-2 was negative in 25/25 patients. Electrodiagnosis was demyelinating in 80.5% and levels 1 and 2 of Brighton criteria of diagnostic certainty, when applicable, were fulfilled in 94.5% patients. Antiganglioside antibodies were positive in only 1/22 patients. Treatments were intravenous immunoglobulin and/or plasma exchange (92.8%) with, at short-time follow-up, definite improvement or recovery in 62.1% of patients. One patient died. In conclusion, the most frequent phenotype of GBS in SARS-CoV-2 infection is the classical sensorimotor demyelinating GBS responding to the usual treatments. The time interval between infectious and neuropathic symptoms, absence of CSF pleocytosis and negative PCR support a postinfectious mechanism. The abundance of reports suggests a pathogenic link between SARS-CoV-2 infection and GBS but a case-control study is greatly needed.
Animal models of human mood.
Neuroscience and biobehavioral reviews, 2021

Humans' everyday experience of the world is influenced by our moods. Moods are consciously accessible affective states that extend over time that are characterized by their valence and arousal. They also likely have a long evolutionary heritage and serve as an important adaptive affective mechanism. When they become maladaptive or overly biased, pathological affective states such as depression can emerge. Despite the importance of moods for human experience, little is known about their causal neurobiological mechanisms. In humans, limitations related to methods and interpretations of the data prevent causal investigations into the origins of mood, highlighting the importance of animal models. Nonhuman primates that share key neuroanatomical, affective, and social features with humans will be essential to uncovering their foundation. Identifying and validating mood-like states in animals is, however, challenging not least because mood is a human construct requiring verbal communication. Here we outline a theoretical framework for animal models of human mood, drawing upon established psychological literature where it exists before reviewing the extant studies of non-human primate models of mood-like states.
Decision-dependent aftereffects for faces.
Vision research, 2014

Adaptation-related aftereffects (AEs) have been found in the perception of face identity, in that perception of an ambiguous face is typically biased away from the identity of a preceding unambiguous adaptor face. In previous studies, we could show that both perceptual ambiguity and physical similarity play a role in determining perceived face identity AEs, Cortex 49 (2013) 1963-1977, Plos One 8 (2013) e70525. Here, we tested further the role of ambiguity by manipulating participants' task such that the very same target stimuli were either ambiguous or unambiguous regarding stimulus classification. We created two partially overlapping continua spanning three unfamiliar face identities each, by morphing identity A via B to C, and B via C to D. In a first session, participants were familiarised with faces A and C and asked to classify faces of the A-B-C continuum as either identity A or C in an AE paradigm. Following adaptation to A or C, we observed contrastive AEs for the ambiguous identity B, but not for the unambiguous identities A or C. In a second session, the same participants were familiarised with faces B and D, followed by tests of AEs for the B-C-D continuum now involving a B-D classification task. We again observed contrastive AEs but only for target identity C (ambiguous for the decision) and not for B or D (unambiguous). Our results suggest that perceptual ambiguity, as given by the task-context, determines whether or not AEs are induced.
The Effect of Temporal Information on Placebo Analgesia and Nocebo Hyperalgesia.
Psychosomatic medicine, 2021

Expectations are known to be key determinants of placebo and nocebo phenomena. In previous studies, verbal suggestions to induce such expectations have mainly focused on the direction and magnitude of the effect, whereas little is known about the influence of temporal information.
Dietary cholesterol supplementation and inhibitory factor 1 serum levels in two dizygotic Smith-Lemli-Opitz syndrome twins: a case report.
Italian journal of pediatrics, 2020

Smith-Lemli-Opitz syndrome (SLOS) is a rare genetic neurodevelopmental disorder caused by the defect in the 7-dehydrocholesterol reductase. This defect leads to the deficiency of cholesterol biosynthesis with accumulation of 7-dehydrocholesterol. Inhibitory factor 1 (IF
Molecular exploration of paediatric intracranial germinomas from multi-ethnic Singapore.
BMC neurology, 2020

Germinomas (IG) account for up to 50% of all intracranial germ cell tumours. These tumours are reputed to be more prevalent in Oriental populations in comparison to Western cohorts. Biological characteristics of IG in other ethnic groups are unknown. Singapore is a multi-ethnic country with diverse cultures. Owing to inter-racial heterogeneity, the authors hypothesize there are molecular differences between paediatric IG patients in our local population. The aims of this study are exploratory: firstly, to identify molecular characteristics in this tumour type and circulating CSF unique to different racial cohorts; and next, to corroborate our findings with published literature.
ADHD-like behaviors caused by inactivation of a transcription factor controlling the balance of inhibitory and excitatory neuron development in the mouse anterior brainstem.
Translational psychiatry, 2020

The neural circuits regulating motivation and movement include midbrain dopaminergic neurons and associated inhibitory GABAergic and excitatory glutamatergic neurons in the anterior brainstem. Differentiation of specific subtypes of GABAergic and glutamatergic neurons in the mouse embryonic brainstem is controlled by a transcription factor Tal1. This study characterizes the behavioral and neurochemical changes caused by the absence of Tal1 function. The Tal1
A Mouse Primary Hepatocyte Culture Model for Studies of Circadian Oscillation.
Current protocols in mouse biology, 2015

Circadian rhythms regulate many aspects of behavior and physiological processes, and, through external signals, help an organism entrain to its environment. These rhythms are driven by circadian clocks in many cells and tissues within our bodies, and are synchronized by a central pacemaker in the brain, the suprachiasmatic nucleus. Peripheral oscillators include the liver, whose circadian clock controls persistent daily rhythms in gene expression and in liver-specific functions such as metabolic homeostasis and drug metabolism. Chronic circadian clock disruption, as in rotating shiftwork, has been linked to disorders including obesity, diabetes, and cardiovascular disease. The mouse primary hepatocyte culture model allows the examination of circadian rhythms in these cells. This article describes a transgenic mouse model that uses a bioluminescent reporter to examine the circadian properties of a core clock gene Period2. Hepatocytes are isolated using a modified collagenase perfusion technique and cultured in a sandwich configuration, then sealed in a buffered medium containing luciferin for detection of whole-culture or single-cell bioluminescence. After synchronization by a medium change, cultures demonstrate coherent circadian period and phase measures of bioluminescence from the PERIOD2::LUCIFERASE reporter.