rudyvdbrink/CitationDatabase huggingface dataset:
Structural Insights into 5-HT1A/D4 Selectivity of WAY-100635 Analogues: Molecular Modeling, Synthesis, and in Vitro Binding.
Journal of chemical information and modeling, 2016

The resurgence of interest in 5-HT1A receptors as a therapeutic target requires the existence of highly selective 5-HT1A ligands. To date, WAY-100635 has been the prototypical antagonist of these receptors. However, this compound also has significant affinity for and activity at D4 dopamine receptors. In this context, this work was aimed at better understanding the 5-HT1A/D4 selectivity of WAY-100635 and analogues from a structural point of view. In silico investigations revealed two key interactions for the 5-HT1A/D4 selectivity of WAY-100635 and analogues. First, a hydrogen bond only found with the Ser 7.36 of D4 receptor appeared to be the key for a higher D4 affinity for newly synthesized aza analogues. The role of Ser 7.36 was confirmed as the affinity of aza analogues for the mutant D4 receptor S7.36A was reduced. Then, the formation of another hydrogen bond with the conserved Ser 5.42 residue appeared to be also critical for D4 binding.
Novel Notch signaling inhibitor NSI‑1 suppresses nuclear translocation of the Notch intracellular domain.
International journal of molecular medicine, 2019

The Notch receptor serves a fundamental role in the regulation of cell fate determination through intracellular signal transmission. Mutation of the Notch receptor results in abnormal active signaling, leading to the development of diseases involving abnormal cell growth, including malignant tumors. Therefore, the Notch signaling pathway is a useful pharmacological target for the treatment of cancer. In the present study, a compound screening system was designed to identify inhibitors of the Notch signaling targeting Notch intracellular domain (NICD). A total of 9,600 compounds were analyzed using the Michigan Cancer Foundation‑7 (MCF7) human breast adenocarcinoma cell line and the SH‑SY5Y human neuroblastoma cell line with the reporter assay system using an artificial protein encoding a partial Notch carboxyl‑terminal fragment fused to the Gal4 DNA‑binding domain. The molecular mechanism underlying the inhibition of Notch signaling by a hit compound was further validated using biochemical and cell biological approaches. Using the screening system, a potential candidate, Notch signaling inhibitor‑1 (NSI‑1), was isolated which showed 50% inhibition at 6.1 µM in an exogenous Notch signaling system. In addition, NSI‑1 suppressed the nuclear translocation of NICD and endogenous gene expression of hairy and enhancer of split‑1, indicating that NSI‑1 specifically targets Notch. Notably, NSI‑1 suppressed the cell viability of MCF7 cells and another human breast adenocarcinoma cell line, MDA‑MB‑231 exhibiting constitutive and high Notch signaling activity, whereas no significant effect was observed in the SH‑SY5Y cells bearing a lower Notch signaling activity. NSI‑1 significantly suppressed the viability of SH‑SY5Y cells expressing exogenous human Notch1. These results indicate that NSI‑1 is a novel Notch signaling inhibitor and suggest its potential as a useful drug for the treatment of diseases induced by constitutively active Notch signaling.
[¹⁸F]THK5351 PET Imaging in Patients with Mild Cognitive Impairment.
Journal of clinical neurology (Seoul, Korea), 2020

Mild cognitive impairment (MCI) is a condition with diverse clinical outcomes and subgroups. Here we investigated the topographic distribution of tau in vivo using the positron emission tomography (PET) tracer [¹⁸F]THK5351 in MCI subgroups.
Nanocomposite-Coated Silk-Based Artificial Conduits: The Influence of Structures on Regeneration of the Peripheral Nerve.
ACS applied bio materials, 2020

In this study, silk filaments are coated with different concentrations (5, 7.5, and 10% w/w) of carbon nanofibers (CNFs) dispersed in poly-ε-caprolactone. The nanocomposite-coated silk filaments are subjected to knitting, braiding, and twisting. The tubular structures are covered with a silk fibroin/polyvinyl film for the nerve conduit application. Physical characterization of the developed nerve conduits demonstrates suitable mechanical properties comparable to native nerve tissue. Cell proliferation is confirmed through in vitro cell culture studies using Neuro 2a and rat primary cortical neural progenitor cells, which show that the proliferation happens along the interconnected macrochannels of the internal structure of the nerve conduit. The knitted structure presents better biological properties than the nerve conduits with other internal structures. The in vivo sciatic nerve implantation is performed in a rabbit model using the best conduit, i.e., 10% CNF-based nanocomposite-coated silk with a knitted inner structure without any biomolecules or tube filling gels. Regeneration of a 2 cm gap excised sciatic nerve is investigated by immunohistochemistry and histology of implanted nerve conduits removed after 30 days. Results suggest that the CNF-based conducting nanocomposite coating in this well-defined architecture of the conduit helps in signal transmission and neural growth during the regeneration of the transected nerve.
Neurodevelopmental Trajectories and Psychiatric Morbidity: Lessons Learned From the 22q11.2 Deletion Syndrome.
Current psychiatry reports, 2021

The 22q11.2 deletion syndrome (22q11DS) is associated with a broad spectrum of neurodevelopmental phenotypes and is the strongest known single genetic risk factor for schizophrenia. Compared to other rare structural pathogenic genetic variants, 22q11DS is relatively common and one of the most extensively studied. This review provides a state-of-the-art overview of current insights regarding associated neurodevelopmental phenotypes and potential implications for 22q11DS and beyond.
Effect of organizational features on patient satisfaction with care in Italian multiple sclerosis centres.
European journal of neurology, 2017

Receiving clear, complete and up-to-date information and having a satisfying relationship with the health professional (HP) are of primary importance for MS patients. Healthcare organization plays a key role in promoting an effective relationship and communication between patients and HPs. The present study aims to explore which care organization and service characteristics provided by Italian MS centres best predict patients' satisfaction with healthcare.
Problematic Internet use in Parkinson's disease.
Parkinsonism & related disorders, 2014

Problematic Internet use (PIU) has been associated with impulse control disorders (ICDs), and postulated to share characteristics of a behavioral addiction with both impulsive and compulsive features. However, Internet use has not been previously systematically studied in Parkinson's disease.
Paediatric stroke: the need for interdisciplinary models of care.
Journal of paediatrics and child health, 2009

Stroke is an important cause of mortality and long-term morbidity in children. The aetiology of stroke in childhood differs from that of adults, with vasculopathies and congenital heart disease being the most commonly identified risk factors. Recognition and diagnosis are often delayed, limiting access to acute medical interventions such as thrombolysis. Optimal management of stroke in children is still not known and existing guidelines are at the level of expert consensus. Interdisciplinary childhood stroke programmes are required to meet the needs of this population and to contribute to the development of evidence-based therapies.
Seizure in cerebral venous and sinus thrombosis.
Epilepsia open, 2018

Many conflicting issues exist about seizure in the setting of cerebral venous and sinus thrombosis (CVST). In this article we aimed to address the existing data regarding incidence, characteristics, predictors, treatment, and prognosis of acute and late seizures in patients with CVST and to prepare more practical information for clinicians. PubMed, Embase, Web of science and Cochrane databases were searched within 1966-2016 using relevant keywords. A total of 63 papers met the inclusion criteria. Seizures are classified as acute symptomatic seizures (ASS; first 14 days) and post-CVST epilepsy (PCE; after 14 days). The incidence had been reported in a wide range of 6.9-76% for ASS and 4-16% for PCE. Focal and generalized seizures were observed with different predominance. ASS commonly occurred in patients with loss of consciousness, focal neurological deficits, supratentorial lesions and thrombosis in superior sagittal sinus, straight sinus, and cortical veins. PCE had been predisposed by occurrence of ASS, motor deficit, and supratentorial lesions, particularly hemorrhage. Most experts believe that primary prophylaxis with antiepileptic drugs in the acute phase is not indicated. However, the initiation of prophylaxis after the first seizure in patients with supratentorial lesions or focal neurological deficit should be recommended. The quality of current evidence is low and most conclusions are based on expert opinions. More accurate reports of seizure semiology, detailed antiepileptic treatment plans, and outcomes are necessary to answer the existing questions.
Bridging the gap: Mechanisms of plasticity and repair after pediatric TBI.
Experimental neurology, 2019

Traumatic brain injury is the leading cause of death and disability in the United States, and may be associated with long lasting impairments into adulthood. The multitude of ongoing neurobiological processes that occur during brain maturation confer both considerable vulnerability to TBI but may also provide adaptability and potential for recovery. This review will examine and synthesize our current understanding of developmental neurobiology in the context of pediatric TBI. Delineating this biology will facilitate more targeted initial care, mechanism-based therapeutic interventions and better long-term prognostication and follow-up.
Development of a test grid using Eye Movement Perimetry for screening glaucomatous visual field defects.
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 2018

Eye Movement Perimetry (EMP) uses Saccadic Eye Movement (SEM) responses for visual field evaluation. Previous studies have demonstrated significant delay in initiation of SEMs among glaucoma patients in comparison with healthy subjects. The aim of the current study was to develop an EMP-based screening grid to identify glaucomatous visual field defects.
Epigenomic landscapes of retinal rods and cones.
eLife, 2016

Rod and cone photoreceptors are highly similar in many respects but they have important functional and molecular differences. Here, we investigate genome-wide patterns of DNA methylation and chromatin accessibility in mouse rods and cones and correlate differences in these features with gene expression, histone marks, transcription factor binding, and DNA sequence motifs. Loss of NR2E3 in rods shifts their epigenomes to a more cone-like state. The data further reveal wide differences in DNA methylation between retinal photoreceptors and brain neurons. Surprisingly, we also find a substantial fraction of DNA hypo-methylated regions in adult rods that are not in active chromatin. Many of these regions exhibit hallmarks of regulatory regions that were active earlier in neuronal development, suggesting that these regions could remain undermethylated due to the highly compact chromatin in mature rods. This work defines the epigenomic landscapes of rods and cones, revealing features relevant to photoreceptor development and function.
Neuroplasticity in the mesolimbic dopamine system and cocaine addiction.
British journal of pharmacology, 2008

The main characteristics of cocaine addiction are compulsive drug use despite adverse consequences and high rates of relapse during periods of abstinence. A current popular hypothesis is that compulsive cocaine use and cocaine relapse is due to drug-induced neuroadaptations in reward-related learning and memory processes, which cause hypersensitivity to cocaine-associated cues, impulsive decision making and abnormal habit-like learned behaviours that are insensitive to adverse consequences. Here, we review results from studies on the effect of cocaine exposure on selected signalling cascades, growth factors and physiological processes previously implicated in neuroplasticity underlying normal learning and memory. These include the extracellular signal-regulated kinase (ERK) signalling pathway, brain-derived neurotrophic factor (BDNF), glutamate transmission, and synaptic plasticity (primarily in the form of long-term potentiation and depression, LTP and LTD). We also discuss the degree to which these cocaine-induced neuroplasticity changes in the mesolimbic dopamine system mediate cocaine psychomotor sensitization and cocaine-seeking behaviours, as assessed in animal models of drug addiction. Finally, we speculate on how these factors may interact to initiate and sustain cocaine psychomotor sensitization and cocaine seeking.
Comparing Alzheimer's and Parkinson's diseases networks using graph communities structure.
BMC systems biology, 2016

Recent advances in large datasets analysis offer new insights to modern biology allowing system-level investigation of pathologies. Here we describe a novel computational method that exploits the ever-growing amount of "omics" data to shed light on Alzheimer's and Parkinson's diseases. Neurological disorders exhibit a huge number of molecular alterations due to a complex interplay between genetic and environmental factors. Classical reductionist approaches are focused on a few elements, providing a narrow overview of the etiopathogenic complexity of multifactorial diseases. On the other hand, high-throughput technologies allow the evaluation of many components of biological systems and their behaviors. Analysis of Parkinson's Disease (PD) and Alzheimer's Disease (AD) from a network perspective can highlight proteins or pathways common but differently represented that can be discriminating between the two pathological conditions, thus highlight similarities and differences.
Relationship between anti-apoptotic proteins survivin and Bcl-2, and response to treatment in patients undergoing post-operative RT for laryngeal cancer: a pilot study.
Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology, 2013

Clinicopathological research has focused on identifying molecular and biological prognostic factors for laryngeal carcinoma (LSCC) treated with post-operative radiotherapy (RT). The aim of this study was to assess the prognostic importance of anti-apoptotic proteins survivin and B-cell lymphoma-2 (Bcl-2) in a series of patients with LSCC who had primary surgery followed by RT.
Activation of Preoptic GABAergic or Glutamatergic Neurons Modulates Sleep-Wake Architecture, but Not Anesthetic State Transitions.
Current biology : CB, 2020

The precise mechanism of general anesthesia remains unclear. In the last two decades, there has been considerable focus on the hypothesis that anesthetics co-opt the neural mechanisms regulating sleep. This hypothesis is supported by ample correlative evidence at the level of sleep-promoting nuclei, but causal investigations of potent inhaled anesthetics have not been conducted. Here, we tested the hypothesis that chemogenetic activation of discrete neuronal subpopulations within the median preoptic nucleus (MnPO) and ventrolateral preoptic nucleus (VLPO) of the hypothalamus would modulate sleep/wake states and alter the time to loss and resumption of consciousness associated with isoflurane, a potent halogenated ether in common clinical use. We show that activating MnPO/VLPO GABAergic or glutamatergic neurons does not alter anesthetic induction or recovery time. However, activation of these neuronal subpopulations did alter sleep-wake architecture. Notably, we report the novel finding that stimulation of VLPO glutamatergic neurons causes a strong increase in wakefulness. We conclude that activation of preoptic GABAergic or glutamatergic neurons that increase sleep or wakefulness does not substantively influence anesthetic state transitions. These data indicate that the correlative evidence for a mechanistic overlap of sleep and anesthesia at the level of an individual nucleus might not necessarily have strong causal significance.
Contrasting effects of selective lesions of nucleus accumbens core or shell on inhibitory control and amphetamine-induced impulsive behaviour.
The European journal of neuroscience, 2008

The core and shell subregions of the nucleus accumbens receive differential projections from areas of the medial prefrontal cortex that have dissociable effects on impulsive and perseverative responding. The contributions of these subregions to simple instrumental behaviour, inhibitory control and behavioural flexibility were investigated using a 'forced choice' task, various parameter manipulations and an omission schedule version of the task. Post-training, selective core lesions were achieved with microinjections of quinolinic acid and shell lesions with ibotenic acid. After a series of behavioural task manipulations, rats were re-stabilized on the standard version of the task and challenged with increasing doses of d-amphetamine (vehicle, 0.5 or 1.0 mg/kg i.p. 30 min prior to test). Neither core- nor shell-lesioned rats exhibited persistent deficits in simple instrumental behaviour or challenges to behavioural flexibility or inhibitory control. Significant differences between lesion groups were unmasked by d-amphetamine challenge in the standard version of the forced task. Core lesions potentiated and shell lesions attenuated the dose-dependent effect of d-amphetamine on increasing anticipatory responses seen in sham rats. These data imply that the accumbens core and shell subregions do not play major roles in highly-trained task performance or in challenges to behavioural control, but may have opposed effects following d-amphetamine treatment. Specifically, they suggest the shell subregion to be necessary for dopaminergic activation driving amphetamine-induced impulsive behaviour and the core subregion for the normal control of this behaviour via conditioned influences.
Quantitative demonstration of the efficacy of night-time apomorphine infusion to treat nocturnal hypokinesia in Parkinson's disease using wearable sensors.
Parkinsonism & related disorders, 2016

Nocturnal hypokinesia/akinesia is one of the common night-time symptoms in patients with Parkinson's disease (PD), negatively affecting quality of life of patients and caregivers. The recognition of this problem and treatment options are limited in clinical practice.
Rotenone-induced death of RGC-5 cells is caspase independent, involves the JNK and p38 pathways and is attenuated by specific green tea flavonoids.
Neurochemical research, 2012

The aim of the present studies was to characterise cell death following inhibition of mitochondrial complex I with rotenone in a transformed cell line (RGC-5 cells) and to examine the neuroprotective properties of the flavonoids genistein, epigallocatechin gallate (EGCG), epicatechin (EC) and baicalin. Rotenone-induced cell death of RGC-5 cells results in a generation of reactive oxygen species, a breakdown of DNA, the translocation of membrane phosphatidylserine, an up-regulation of haemoxygenase-1 and is unaffected by necrostatin-1 (inhibitor of necroptosis), z-VAD-fmk (pan caspase inhibitor) or NU1025 (PARP inhibitor) but attenuated with SP600125 (JNK inhibitor). Rotenone-induced toxicity of RGC-5 cells also caused an activation of mitogen-activated kinases indicated by an up-regulation and translocation into mitochondria of p-c-Jun, pJNK and pp38. Exposure of RGC-5 cells to rotenone does not affect apoptosis inducing factor or significantly stimulate caspase-3 activity. EGCG and EC both significantly blunt rotenone toxicity of RGC-5 cells at concentrations of 50 μM while genistein and baicalin were without effect. Significantly, genistein is approximately 20 times less efficacious than EGCG (IC(50) 2.5 μM) and EC (IC(50) 1.5 μM) at inhibiting sodium nitroprusside-induced lipid peroxidation. These studies show that rotenone toxicity of RGC-5 cells is neither necroptosis nor caspase-dependent apoptosis but involves the activation of mitogen-activated kinases and is inhibited by a JNK inhibitor, EGCG and EC. Genistein attenuates lipid peroxidation less efficaciously than EC and EGCG and does not affect rotenone toxicity of RGC-5 cells.
Emergency Physicians and Personal Narratives Improve the Perceived Effectiveness of COVID-19 Public Health Recommendations on Social Media: A Randomized Experiment.
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 2021

Containment of the coronavirus disease 2019 (COVID-19) pandemic requires the public to change behavior under social distancing mandates. Social media are important information dissemination platforms that can augment traditional channels communicating public health recommendations. The objective of the study was to assess the effectiveness of COVID-19 public health messaging on Twitter when delivered by emergency physicians and containing personal narratives.
Astrocyte uncoupling as a cause of human temporal lobe epilepsy.
Brain : a journal of neurology, 2015

Glial cells are now recognized as active communication partners in the central nervous system, and this new perspective has rekindled the question of their role in pathology. In the present study we analysed functional properties of astrocytes in hippocampal specimens from patients with mesial temporal lobe epilepsy without (n = 44) and with sclerosis (n = 75) combining patch clamp recording, K(+) concentration analysis, electroencephalography/video-monitoring, and fate mapping analysis. We found that the hippocampus of patients with mesial temporal lobe epilepsy with sclerosis is completely devoid of bona fide astrocytes and gap junction coupling, whereas coupled astrocytes were abundantly present in non-sclerotic specimens. To decide whether these glial changes represent cause or effect of mesial temporal lobe epilepsy with sclerosis, we developed a mouse model that reproduced key features of human mesial temporal lobe epilepsy with sclerosis. In this model, uncoupling impaired K(+) buffering and temporally preceded apoptotic neuronal death and the generation of spontaneous seizures. Uncoupling was induced through intraperitoneal injection of lipopolysaccharide, prevented in Toll-like receptor4 knockout mice and reproduced in situ through acute cytokine or lipopolysaccharide incubation. Fate mapping confirmed that in the course of mesial temporal lobe epilepsy with sclerosis, astrocytes acquire an atypical functional phenotype and lose coupling. These data suggest that astrocyte dysfunction might be a prime cause of mesial temporal lobe epilepsy with sclerosis and identify novel targets for anti-epileptogenic therapeutic intervention.