rudyvdbrink/CitationDatabase huggingface dataset:
Bipolar disorders.
Lancet (London, England), 2020

Bipolar disorders are a complex group of severe and chronic disorders that includes bipolar I disorder, defined by the presence of a syndromal, manic episode, and bipolar II disorder, defined by the presence of a syndromal, hypomanic episode and a major depressive episode. Bipolar disorders substantially reduce psychosocial functioning and are associated with a loss of approximately 10-20 potential years of life. The mortality gap between populations with bipolar disorders and the general population is principally a result of excess deaths from cardiovascular disease and suicide. Bipolar disorder has a high heritability (approximately 70%). Bipolar disorders share genetic risk alleles with other mental and medical disorders. Bipolar I has a closer genetic association with schizophrenia relative to bipolar II, which has a closer genetic association with major depressive disorder. Although the pathogenesis of bipolar disorders is unknown, implicated processes include disturbances in neuronal-glial plasticity, monoaminergic signalling, inflammatory homoeostasis, cellular metabolic pathways, and mitochondrial function. The high prevalence of childhood maltreatment in people with bipolar disorders and the association between childhood maltreatment and a more complex presentation of bipolar disorder (eg, one including suicidality) highlight the role of adverse environmental exposures on the presentation of bipolar disorders. Although mania defines bipolar I disorder, depressive episodes and symptoms dominate the longitudinal course of, and disproportionately account for morbidity and mortality in, bipolar disorders. Lithium is the gold standard mood-stabilising agent for the treatment of people with bipolar disorders, and has antimanic, antidepressant, and anti-suicide effects. Although antipsychotics are effective in treating mania, few antipsychotics have proven to be effective in bipolar depression. Divalproex and carbamazepine are effective in the treatment of acute mania and lamotrigine is effective at treating and preventing bipolar depression. Antidepressants are widely prescribed for bipolar disorders despite a paucity of compelling evidence for their short-term or long-term efficacy. Moreover, antidepressant prescription in bipolar disorder is associated, in many cases, with mood destabilisation, especially during maintenance treatment. Unfortunately, effective pharmacological treatments for bipolar disorders are not universally available, particularly in low-income and middle-income countries. Targeting medical and psychiatric comorbidity, integrating adjunctive psychosocial treatments, and involving caregivers have been shown to improve health outcomes for people with bipolar disorders. The aim of this Seminar, which is intended mainly for primary care physicians, is to provide an overview of diagnostic, pathogenetic, and treatment considerations in bipolar disorders. Towards the foregoing aim, we review and synthesise evidence on the epidemiology, mechanisms, screening, and treatment of bipolar disorders.
Sleep and Circadian Rhythm Disturbance in Remitted Schizophrenia and Bipolar Disorder: A Systematic Review and Meta-analysis.
Schizophrenia bulletin, 2020

Sleep and circadian rhythm disturbances in schizophrenia are common, but incompletely characterized. We aimed to describe and compare the magnitude and heterogeneity of sleep-circadian alterations in remitted schizophrenia and compare them with those in interepisode bipolar disorder.
A Supported Employment linkage intervention for people with schizophrenia who want to work: a survey of patients' views.
Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists, 2015

Take into account patient views in developing a linkage intervention to the evidence-based Individual Placement and Support approach to Supported Employment (SE) for patients with schizophrenia on a mental health unit (MHU) who want to work in competitive employment.
Coronavirus Disease 2019 and Stroke: Clinical Manifestations and Pathophysiological Insights.
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association, 2020

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health threat. Some COVID-19 patients have exhibited widespread neurological manifestations including stroke. Acute ischemic stroke, intracerebral hemorrhage, and cerebral venous sinus thrombosis have been reported in patients with COVID-19. COVID-19-associated coagulopathy is increasingly recognized as a result of acute infection and is likely caused by inflammation, including inflammatory cytokine storm. Recent studies suggest that axonal transport of SARS-CoV-2 to the brain can occur via the cribriform plate adjacent to the olfactory bulb that may lead to symptomatic anosmia. The internalization of SARS-CoV-2 is mediated by the binding of the spike glycoprotein of the virus to the angiotensin-converting enzyme 2 (ACE2) on cellular membranes. ACE2 is expressed in several tissues including lung alveolar cells, gastrointestinal tissue, and brain. The aim of this review is to provide insights into the clinical manifestations and pathophysiological mechanisms of stroke in COVID-19 patients. SARS-CoV-2 can down-regulate ACE2 and, in turn, overactivate the classical renin-angiotensin system (RAS) axis and decrease the activation of the alternative RAS pathway in the brain. The consequent imbalance in vasodilation, neuroinflammation, oxidative stress, and thrombotic response may contribute to the pathophysiology of stroke during SARS-CoV-2 infection.
Neural stem cell-specific ITPA deficiency causes neural depolarization and epilepsy.
JCI insight, 2020

Inosine triphosphate pyrophosphatase (ITPA) hydrolyzes inosine triphosphate (ITP) and other deaminated purine nucleotides to the corresponding nucleoside monophosphates. In humans, ITPA deficiency causes severe encephalopathy with epileptic seizure, microcephaly, and developmental retardation. In this study, we established neural stem cell-specific Itpa-conditional KO mice (Itpa-cKO mice) to clarify the effects of ITPA deficiency on the neural system. The Itpa-cKO mice showed growth retardation and died within 3 weeks of birth. We did not observe any microcephaly in the Itpa-cKO mice, although the female Itpa-cKO mice did show adrenal hypoplasia. The Itpa-cKO mice showed limb-clasping upon tail suspension and spontaneous and/or audiogenic seizure. Whole-cell patch-clamp recordings from entorhinal cortex neurons in brain slices revealed a depolarized resting membrane potential, increased firing, and frequent spontaneous miniature excitatory postsynaptic current and miniature inhibitory postsynaptic current in the Itpa-cKO mice compared with ITPA-proficient controls. Accumulated ITP or its metabolites, such as cyclic inosine monophosphates, or RNA containing inosines may cause membrane depolarization and hyperexcitability in neurons and induce the phenotype of ITPA-deficient mice, including seizure.
[The role of dynamic electromyography in the follow-up of chronic immune polyneuropathies].
Revue neurologique, 2013

Nerve conduction studies providing insight into demyelinating process are essential for the diagnostic of chronic inflammatory demyelinating polyradiculoneuropathy. For the diagnostic, several sets of electrophysiologic criteria have been established. To assess the response to treatment, nerve conduction studies are often used in trials and in clinical practice. Nevertheless, the useful of these classical electrophysiologic techniques is debated because of their lack of sensibility and specificity. In the last 20 years, several works have showed that dysfunction of channels and pump of the axonal membrane at the site and around the site of the conduction block can precipitate conduction failure and produce weakness. These important features explaining clinical status are not correctly assessed by conventional nerve conduction studies. New nerve conduction examinations in dynamic conditions can explore these hyperexcitability modifications.
TGF-β1-induced miR-424 promotes pulmonary myofibroblast differentiation by targeting Slit2 protein expression.
Biochemical pharmacology, 2020

Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease with irreversible loss of lung tissue and function. Myofibroblasts in the lung are key cellular mediators of IPF progression. Transforming growth factor (TGF)-β1, a major profibrogenic cytokine, induces pulmonary myofibroblast differentiation, and emerging evidence has established the importance of microRNAs (miRs) in the development of IPF. The objective of this study was to define the pro-fibrotic roles and mechanisms of miRs in TGF-β1-induced pulmonary myofibroblast differentiation. Using RNA sequencing, we identified miR-424 as an important TGF-β1-induced miR in human lung fibroblasts (HLFs). Quantitative RT-PCR confirmed that miR-424 expression was increased by 2.6-fold in HLFs in response to TGF-β1 and was 1.7-fold higher in human fibrotic lung tissues as compared to non-fibrotic lung tissues. TGF-β1-induced upregulation of miR-424 was blocked by the Smad3 inhibitor SIS3, suggesting the involvement of this canonical TGF-β1 signaling pathway. Transfection of a miR-424 hairpin inhibitor into HLFs reduced TGF-β1-induced expression of classic myofibroblast differentiation markers including ɑ-smooth muscle actin (ɑ-SMA) and connective tissue growth factor (CTGF), whereas a miR-424 mimic significantly enhanced TGF-β1-induced myofibroblast differentiation. In addition, TGF-β1 induced Smad3 phosphorylation in HLFs, and this response was reduced by the miR-424 inhibitor. In silico analysis identified Slit2, a protein that inhibits TGF-β1 profibrogenic signaling, as a putative target of regulation by miR-424. Slit2 is less highly expressed in human fibrotic lung tissues than in non-fibrotic lung tissues, and knockdown of Slit2 by its siRNA enhanced TGF-β1-induced HLF differentiation. Overexpression of a miR-424 mimic down-regulated expression of Slit2 but not the Slit2 major receptor ROBO1 in HLFs. Luciferase reporter assays showed that the miR-424 mimic represses Slit2 3' untranslated region (3'-UTR) reporter activity, and mutations at the seeding regions in the 3'-UTR of Slit2 abolish this inhibition. Together, these data demonstrate a pro-fibrotic role of miR-424 in TGF-β1-induced HLF differentiation. It functions as a positive feed-back regulator of the TGF-β1 signaling pathway by reducing expression of the negative regulator Slit2. Thus, targeting miR-424 may provide a new therapeutic strategy to prevent myofibroblast differentiation and IPF progression.
Mass cytometry detects H3.3K27M-specific vaccine responses in diffuse midline glioma.
The Journal of clinical investigation, 2020

BACKGROUNDPatients with diffuse midline gliomas (DMGs), including diffuse intrinsic pontine glioma (DIPG), have dismal outcomes. We previously described the H3.3K27M mutation as a shared neoantigen in HLA-A*02.01+, H3.3K27M+ DMGs. Within the Pacific Pediatric Neuro-Oncology Consortium, we assessed the safety and efficacy of an H3.3K27M-targeted peptide vaccine.METHODSNewly diagnosed patients, aged 3-21 years, with HLA-A*02.01+ and H3.3K27M+ status were enrolled in stratum A (DIPG) or stratum B (nonpontine DMG). Vaccine was administered in combination with polyinosinic-polycytidylic acid-poly-I-lysine carboxymethylcellulose (poly-ICLC) every 3 weeks for 8 cycles, followed by once every 6 weeks. Immunomonitoring and imaging were performed every 3 months. Imaging was centrally reviewed. Immunological responses were assessed in PBMCs using mass cytometry.RESULTSA total of 19 patients were enrolled in stratum A (median age,11 years) and 10 in stratum B (median age, 13 years). There were no grade-4 treatment-related adverse events (TRAEs). Injection site reaction was the most commonly reported TRAE. Overall survival (OS) at 12 months was 40% (95% CI, 22%-73%) for patients in stratum A and 39% (95% CI, 16%-93%) for patients in stratum B. The median OS was 16.1 months for patients who had an expansion of H3.3K27M-reactive CD8+ T cells compared with 9.8 months for their counterparts (P = 0.05). Patients with DIPG with below-median baseline levels of myeloid-derived suppressor cells had prolonged OS compared with their counterparts (P < 0.01). Immediate pretreatment dexamethasone administration was inversely associated with H3.3K27M-reactive CD8+ T cell responses.CONCLUSIONAdministration of the H3.3K27M-specific vaccine was well tolerated. Patients with H3.3K27M-specific CD8+ immunological responses demonstrated prolonged OS compared with nonresponders.TRIAL REGISTRATIONClinicalTrials.gov NCT02960230.FUNDINGThe V Foundation, the Pacific Pediatric Neuro-Oncology Consortium Foundation, the Pediatric Brain Tumor Foundation, the Mithil Prasad Foundation, the MCJ Amelior Foundation, the Anne and Jason Farber Foundation, Will Power Research Fund Inc., the Isabella Kerr Molina Foundation, the Parker Institute for Cancer Immunotherapy, and the National Institute of Neurological Disorders and Stroke (NINDS), NIH (R35NS105068).
"If I Am Straight You Are Askew": Labelling Heterosexuals as Straight Worsen Gay Men's Perception.
Journal of sex research, 2021

A robust stream of research has shown the detrimental influence of slurs and derogatory epithets on attitudes toward minority groups. Extending prior work, we explored the influence of positive labels ascribed to the majority group on the evaluation of the minority group. Specifically, three studies tested the possibility that the label "straight," generally linked with the concept of morality, would promote a negative evaluation of gay men. Study 1 exposed English speakers to an individual person described as straight (vs. heterosexual) while Study 2 exposed English speakers to a target person described as straight (vs. heterosexual vs. no label). Study 3 considered a non-English sample (i.e., Italian adults) and experimentally induced the association between the straight label and the concept of heterosexuality. In each study, participants were asked to express their attitudes toward a gay target after the manipulation. Results showed that heterosexual participants exposed to the label "straight" reported more negative attitudes toward gay men than heterosexual participants exposed to the label "heterosexual" (or when they were not exposed to any label). Critically, such an effect emerged only among highly religious participants. Implications for policies and prejudice reduction are discussed.
Conversion of clinically isolated syndrome to multiple sclerosis: a prospective study.
Multiple sclerosis and related disorders, 2020

Multiple sclerosis (MS) begins with an acute clinical attack (clinically isolated syndrome) in approximately 85% of patients. The conversion rate from clinically isolated syndrome to multiple sclerosis has been documented at 30% to 82% in previous studies. When an individual presents for evaluation after a single episode of inflammation of the CNS, several decisions regarding follow-up in subsequent years need to be made, including that of whether or not to start a therapy. There is, therefore, an emerging need to identify the predictive factors that anticipate conversion from CIS to MS.
Cannabis use, cognitive performance, and symptoms of attention deficit/hyperactivity disorder in community adults.
Experimental and clinical psychopharmacology, 2020

There is some evidence that cannabis use is associated with lower cognitive performance and symptoms of attention-deficit/hyperactivity disorder (ADHD), but the existing literature is relatively inconsistent, potentially due to small samples in previous studies. Using a dimensional design, the current study examined cannabis use severity and age of first cannabis use in relation to neurocognitive performance and ADHD symptoms in a large sample of community adults (
Shared alterations in resting-state brain connectivity in adults with attention-deficit/hyperactivity disorder and their unaffected first-degree relatives.
Psychological medicine, 2021

Attention-deficit/hyperactivity disorder (ADHD) is a developmental condition that often persists into adulthood with extensive negative consequences on quality of life. Despite emerging evidence indicating the genetic basis of ADHD, investigations into the familial expression of latent neurocognitive traits remain limited.
Combining information on nocturnal rapid eye movement sleep latency and atonia to facilitate diagnosis of pediatric narcolepsy type 1.
Sleep, 2021

The diagnosis of narcolepsy type 1 (NT1) at its onset in children and adolescents is often difficult, with substantial diagnostic delay. We aimed to test and validate the effectiveness of rapid eye movement (REM) sleep latency (REML), the REM sleep atonia index (RAI), and their combination for the automatic identification of pediatric patients with NT1 based on the standard scoring of nocturnal polysomnograms.
Surgical outcomes of Supra- Infra Tentorial Extradural Hematoma (SIEDH): A retrospective study from a single institution.
Clinical neurology and neurosurgery, 2021

Bicompartmental Supra plus Infratentorial Extra Dural Hematoma (SIEDH) is an uncommon yet important category of Extradural Hematoma (EDH) straddling the transverse sinus. It requires quick decision making and proper surgical evacuation.
Efficient eddy current characterization using a 2D image-based sampling scheme and a model-based fitting approach.
Magnetic resonance in medicine, 2021

To propose two innovations to existing eddy current characterization techniques, which include (1) an efficient spatio-temporal sampling scheme and (2) a model-based fitting of spherical harmonic eddy current components.
How single neuron properties shape chaotic dynamics and signal transmission in random neural networks.
PLoS computational biology, 2019

While most models of randomly connected neural networks assume single-neuron models with simple dynamics, neurons in the brain exhibit complex intrinsic dynamics over multiple timescales. We analyze how the dynamical properties of single neurons and recurrent connections interact to shape the effective dynamics in large randomly connected networks. A novel dynamical mean-field theory for strongly connected networks of multi-dimensional rate neurons shows that the power spectrum of the network activity in the chaotic phase emerges from a nonlinear sharpening of the frequency response function of single neurons. For the case of two-dimensional rate neurons with strong adaptation, we find that the network exhibits a state of "resonant chaos", characterized by robust, narrow-band stochastic oscillations. The coherence of stochastic oscillations is maximal at the onset of chaos and their correlation time scales with the adaptation timescale of single units. Surprisingly, the resonance frequency can be predicted from the properties of isolated neurons, even in the presence of heterogeneity in the adaptation parameters. In the presence of these internally-generated chaotic fluctuations, the transmission of weak, low-frequency signals is strongly enhanced by adaptation, whereas signal transmission is not influenced by adaptation in the non-chaotic regime. Our theoretical framework can be applied to other mechanisms at the level of single neurons, such as synaptic filtering, refractoriness or spike synchronization. These results advance our understanding of the interaction between the dynamics of single units and recurrent connectivity, which is a fundamental step toward the description of biologically realistic neural networks.
Clinical reasoning: exploring its characteristics and enhancing its learning.
British journal of hospital medicine (London, England : 2005), 2020

Clinical reasoning is an extensive and intricate field, dealing with the process of thinking and decision making in practice. Its study can be quite challenging because it is context and task dependent. Educational frameworks such as the conscious competence model and the dual process reasoning model have been developed to help its understanding. To enhance the learning of clinical reasoning, there are significant areas that can be targeted through learning processes. These include knowledge adequacy; ability to gather appropriate patient data; use of proper reasoning strategies to address specific clinical questions; and the ability to reflect and evaluate on decisions taken, together with the role of the wider practice community and the activity of professional socialisation. This article explores the characteristics of clinical reasoning and delves deeper into the various strategies that prove useful for learning.
How childhood trauma and recent adverse events are related to hair cortisol levels in a large adult cohort.
Psychoneuroendocrinology, 2021

Exposure to adversity is a risk factor for many mental and somatic health problems. Hypothalamic-pituitary-adrenal (HPA) axis dysregulation is a potential mechanism linking adversity exposure and negative health outcomes. However, associations between adversity exposure and HPA-axis activity have been inconsistent. To understand the impact of adversity on the HPA-axis, we examined associations between early-life and recent adversity with hair cortisol concentration, an indicator of long-term systemic cortisol levels.
TPEN exerts selective anti-leukemic efficacy in ex vivo drug-resistant childhood acute leukemia.
Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, 2021

Despite some advances in the treatment of acute lymphoblastic (ALL) and myeloid leukemia (AML) in recent years, there is still a prominent percentage of pediatric patients with a reduced overall prognosis. Therefore, other therapeutic approaches are needed to treat those patients. In the present study, we report that the metal chelator TPEN affected ΔΨ
Two Neural Networks for Laughter: A Tractography Study.
Cerebral cortex (New York, N.Y. : 1991), 2021

Laughter is a complex motor behavior occurring in both emotional and nonemotional contexts. Here, we investigated whether the different functions of laughter are mediated by distinct networks and, if this is the case, which are the white matter tracts sustaining them. We performed a multifiber tractography investigation placing seeds in regions involved in laughter production, as identified by previous intracerebral electrical stimulation studies in humans: the pregenual anterior cingulate (pACC), ventral temporal pole (TPv), frontal operculum (FO), presupplementary motor cortex, and ventral striatum/nucleus accumbens (VS/NAcc). The primary motor cortex (M1) and two subcortical territories were also studied to trace the descending projections. Results provided evidence for the existence of two relatively distinct networks. A first network, including pACC, TPv, and VS/NAcc, is interconnected through the anterior cingulate bundle, the accumbofrontal tract, and the uncinate fasciculus, reaching the brainstem throughout the mamillo-tegmental tract. This network is likely involved in the production of emotional laughter. A second network, anchored to FO and M1, projects to the brainstem motor nuclei through the internal capsule. It is most likely the neural basis of nonemotional and conversational laughter. The two networks interact throughout the pre-SMA that is connected to both pACC and FO.
Patients' Views About the Disclosure of Collateral Findings in Pragmatic Clinical Trials: a Focus Group Study.
Journal of general internal medicine, 2020

Pragmatic clinical trials (PCTs) are increasingly being conducted to efficiently generate evidence to inform healthcare decision-making. Despite their growing acceptance, PCTs may involve a variety of ethical issues, including the management of pragmatic clinical trial-collateral findings (PCT-CFs), that is, information that emerges in PCTs that is unrelated to the primary research questions but may have implications for patients, clinicians, and health systems.