rudyvdbrink/CitationDatabase huggingface dataset:
Hubs of long-distance co-alteration characterize brain pathology.
Human brain mapping, 2020

It is becoming clearer that the impact of brain diseases is more convincingly represented in terms of co-alterations rather than in terms of localization of alterations. In this context, areas characterized by a long mean distance of co-alteration may be considered as hubs with a crucial role in the pathology. We calculated meta-analytic transdiagnostic networks of co-alteration for the gray matter decreases and increases, and we evaluated the mean Euclidean, fiber-length, and topological distance of its nodes. We also examined the proportion of co-alterations between canonical networks, and the transdiagnostic variance of the Euclidean distance. Furthermore, disease-specific analyses were conducted on schizophrenia and Alzheimer's disease. The anterodorsal prefrontal cortices appeared to be a transdiagnostic hub of long-distance co-alterations. Also, the disease-specific analyses showed that long-distance co-alterations are more able than classic meta-analyses to identify areas involved in pathology and symptomatology. Moreover, the distance maps were correlated with the normative connectivity. Our findings substantiate the network degeneration hypothesis in brain pathology. At the same time, they suggest that the concept of co-alteration might be a useful tool for clinical neuroscience.
Standard procedures for the diagnostic pathway of sleep-related epilepsies and comorbid sleep disorders: A European Academy of Neurology, European Sleep Research Society and International League against Epilepsy-Europe consensus review.
Journal of sleep research, 2020

Some epilepsy syndromes (sleep-related epilepsies [SRE]) have a strong link with sleep. Comorbid sleep disorders are common in patients with SRE and can exert a negative impact on seizure control and quality of life.
Gender identity better than sex explains individual differences in episodic and semantic components of autobiographical memory: An fMRI study.
NeuroImage, 2021

Advances in the literature of sex-related differences in autobiographical memory increasingly tend to highlight the importance of psychosocial factors such as gender identity, which may explain these differences better than sex as a biological factor. To date, however, none of these behavioral studies have investigated this hypothesis using neuroimaging. The purpose of this fMRI study is to examine for the first time sex and gender identity-related differences in episodic and semantic autobiographical memory in healthy participants (M=19, W=18). No sex-related differences were found; however, sex-related effects of masculine and feminine gender identity were identified in men and women independently. These results confirm the hypothesis that differences in episodic and semantic autobiographical memory are best explained by gender but are an interaction between biological sex and gender identity and extend these findings to the field of neuroimaging. We discuss the importance of hormonal factors to be taken into consideration in the future.
Acute targeting of pre-amyloid seeds in transgenic mice reduces Alzheimer-like pathology later in life.
Nature neuroscience, 2020

Amyloid-β (Aβ) deposits are a relatively late consequence of Aβ aggregation in Alzheimer's disease. When pathogenic Aβ seeds begin to form, propagate and spread is not known, nor are they biochemically defined. We tested various antibodies for their ability to neutralize Aβ seeds before Aβ deposition becomes detectable in Aβ precursor protein-transgenic mice. We also characterized the different antibody recognition profiles using immunoprecipitation of size-fractionated, native, mouse and human brain-derived Aβ assemblies. At least one antibody, aducanumab, after acute administration at the pre-amyloid stage, led to a significant reduction of Aβ deposition and downstream pathologies 6 months later. This demonstrates that therapeutically targetable pathogenic Aβ seeds already exist during the lag phase of protein aggregation in the brain. Thus, the preclinical phase of Alzheimer's disease-currently defined as Aβ deposition without clinical symptoms-may be a relatively late manifestation of a much earlier pathogenic seed formation and propagation that currently escapes detection in vivo.
Consumptive coagulopathy of severe yellow fever occurs independently of hepatocellular tropism and massive hepatic injury.
Proceedings of the National Academy of Sciences of the United States of America, 2020

Yellow fever (YF) is a mosquito-transmitted viral disease that causes tens of thousands of deaths each year despite the long-standing deployment of an effective vaccine. In its most severe form, YF manifests as a hemorrhagic fever that causes severe damage to visceral organs. Although coagulopathy is a defining feature of severe YF in humans, the mechanism by which it develops remains uncertain. Hepatocytes are a major target of yellow fever virus (YFV) infection, and the coagulopathy in severe YF has long been attributed to massive hepatocyte infection and destruction that results in a defect in clotting factor synthesis. However, when we analyzed blood from Brazilian patients with severe YF, we found high concentrations of plasma D-dimer, a fibrin split product, suggestive of a concurrent consumptive process. To define the relationship between coagulopathy and hepatocellular tropism, we compared infection and disease in
Maternal Programming of Social Dominance via Milk Cytokines.
iScience, 2020

Regular physical activity improves physical and mental health. Here we found that the effect of physical activity extends to the next generation. Voluntary wheel running of dams, from postpartum day 2 to weaning, increased the social dominance and reproductive success, but not the physical/metabolic health, of their otherwise sedentary offspring. The individual's own physical activity did not improve dominance status. Maternal exercise did not disrupt maternal care or the maternal and offspring microbiota. Rather, the development of dominance behavior in the offspring of running mothers could be explained by the reduction of LIF, CXCL1, and CXCL2 cytokines in breast milk. These data reveal a cytokine-mediated lactocrine pathway that responds to the mother's postpartum physical activity and programs offspring social dominance. As dominance behaviors are highly relevant to the individual's survival and reproduction, lactocrine programming could be an evolutionary mechanism by which a mother promotes the social rank of her offspring.
From loss to recovery: how to effectively assess chemosensory impairments during COVID-19 pandemic.
medRxiv : the preprint server for health sciences, 2021

Chemosensory impairments have been established as a specific indicator of COVID-19. They affect most patients and may persist long past the resolution of respiratory symptoms, representing an unprecedented medical challenge. Since the SARS-CoV-2 pandemic started, we now know much more about smell, taste, and chemesthesis loss associated with COVID-19. However, the temporal dynamics and characteristics of recovery are still unknown. Here, capitalizing on data from the Global Consortium for Chemosensory Research (GCCR) crowdsourced survey, we assessed chemosensory abilities after the resolution of respiratory symptoms in participants diagnosed with COVID-19 during the first wave of the pandemic in Italy. This analysis led to the identification of two patterns of chemosensory recovery, limited (partial) and substantial, which were found to be associated with differential age, degrees of chemosensory loss, and regional patterns. Uncovering the self-reported phenomenology of recovery from smell, taste, and chemesthetic disorders is the first, yet essential step, to provide healthcare professionals with the tools to take purposeful and targeted action to address chemosensory disorders and its severe discomfort.
A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer's disease with lecanemab, an anti-Aβ protofibril antibody.
Alzheimer's research & therapy, 2021

Lecanemab (BAN2401), an IgG1 monoclonal antibody, preferentially targets soluble aggregated amyloid beta (Aβ), with activity across oligomers, protofibrils, and insoluble fibrils. BAN2401-G000-201, a randomized double-blind clinical trial, utilized a Bayesian design with response-adaptive randomization to assess 3 doses across 2 regimens of lecanemab versus placebo in early Alzheimer's disease, mild cognitive impairment due to Alzheimer's disease (AD) and mild AD dementia.
Exploring autoantibody signatures in brain tissue from patients with severe mental illness.
Translational psychiatry, 2020

In recent years, studies have shown higher prevalence of autoantibodies in patients with schizophrenia compared to healthy individuals. This study applies an untargeted and a targeted affinity proteomics approach to explore and characterize the autoantibody repertoire in brain tissues from 73 subjects diagnosed with schizophrenia and 52 control subjects with no psychiatric or neurological disorders. Selected brain tissue lysates were first explored for IgG reactivity on planar microarrays composed of 11,520 protein fragments representing 10,820 unique proteins. Based on these results of ours and other previous studies of autoantibodies related to psychosis, we selected 226 fragments with an average length of 80 amino acids, representing 127 unique proteins. Tissue-based analysis of IgG reactivities using antigen suspension bead arrays was performed in a multiplex and parallel fashion for all 125 subjects. Among the detected autoantigens, higher IgG reactivity in subjects with schizophrenia, as compared to psychiatrically healthy subjects, was found against the glutamate ionotropic receptor NMDA type subunit 2D (anti-GluN2D). In a separate cohort with serum samples from 395 young adults with a wider spectrum of psychiatric disorders, higher levels of serum autoantibodies targeting GluN2D were found when compared to 102 control individuals. By further validating GluN2D and additional potential autoantigens, we will seek insights into how these are associated with severe mental illnesses.
Previous psychopathology predicted severe COVID-19 concern, anxiety, and PTSD symptoms in pregnant women during "lockdown" in Italy.
Archives of women's mental health, 2020

Italy was the first COVID-19 pandemic epicenter among European countries and established a period of full "lockdown", consisting of travel bans, mandatory staying at home, and temporary closure of nonessential businesses. Similar measures are known risk factors for psychological disturbances in the general population; still, little is known about their impact on pregnant women's mental health during COVID-19 pandemic. The cross-sectional, web-based, national survey "COVID-19 related Anxiety and StreSs in prEgnancy, poSt-partum and breaStfeeding" (COVID-ASSESS) was conducted during the first month of full "lockdown" in Italy. Participants were recruited via social networks with a snowball technique. The questionnaire was specifically developed to examine COVID-19 concerns and included the psychometric tests National Stressful Events Survey (NSESSS) for posttraumatic stress disorder (PTSD) and State-Trait Anxiety Inventory. A multivariable logistic regression model was fitted to explore the association of the concern, anxiety and PTSD symptoms with age, gestational weeks, parity, days of "lockdown", assisted reproductive technology use, psychopathological history, and previous perinatal losses. Out of 1015 pregnant women reached, 737 (72.6%) fully answered the questionnaire; no woman reported a COVID-19 infection. Median age was 34.4 years [quartiles 31.7, 37.2], median days in "lockdown" were 13.1 [11.0, 17.0], median gestational weeks were 27.8 [19.8, 34.0]. Clinically significant PTSD symptoms were present in 75 women (10.2%, NSESSS cutoff 24) and clinically significant anxiety symptoms were present in 160 women (21.7%, STAI-Y1 cutoff 50). Women were particularly worried about the health of their baby and of their elderly relatives, as well as of the possible impact of pandemic in the future of society. Previous anxiety predicted higher concern and PTSD symptoms; previous depression and anxiety were independently associated with current PTSD symptoms.
Expression of SARS-CoV-2 Entry Factors in the Pancreas of Normal Organ Donors and Individuals with COVID-19.
Cell metabolism, 2020

Diabetes is associated with increased mortality from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Given literature suggesting a potential association between SARS-CoV-2 infection and diabetes induction, we examined pancreatic expression of angiotensin-converting enzyme 2 (ACE2), the key entry factor for SARS-CoV-2 infection. Specifically, we analyzed five public scRNA-seq pancreas datasets and performed fluorescence in situ hybridization, western blotting, and immunolocalization for ACE2 with extensive reagent validation on normal human pancreatic tissues across the lifespan, as well as those from coronavirus disease 2019 (COVID-19) cases. These in silico and ex vivo analyses demonstrated prominent expression of ACE2 in pancreatic ductal epithelium and microvasculature, but we found rare endocrine cell expression at the mRNA level. Pancreata from individuals with COVID-19 demonstrated multiple thrombotic lesions with SARS-CoV-2 nucleocapsid protein expression that was primarily limited to ducts. These results suggest SARS-CoV-2 infection of pancreatic endocrine cells, via ACE2, is an unlikely central pathogenic feature of COVID-19-related diabetes.
Urinary metabolic phenotyping for Alzheimer's disease.
Scientific reports, 2020

Finding early disease markers using non-invasive and widely available methods is essential to develop a successful therapy for Alzheimer's Disease. Few studies to date have examined urine, the most readily available biofluid. Here we report the largest study to date using comprehensive metabolic phenotyping platforms (NMR spectroscopy and UHPLC-MS) to probe the urinary metabolome in-depth in people with Alzheimer's Disease and Mild Cognitive Impairment. Feature reduction was performed using metabolomic Quantitative Trait Loci, resulting in the list of metabolites associated with the genetic variants. This approach helps accuracy in identification of disease states and provides a route to a plausible mechanistic link to pathological processes. Using these mQTLs we built a Random Forests model, which not only correctly discriminates between people with Alzheimer's Disease and age-matched controls, but also between individuals with Mild Cognitive Impairment who were later diagnosed with Alzheimer's Disease and those who were not. Further annotation of top-ranking metabolic features nominated by the trained model revealed the involvement of cholesterol-derived metabolites and small-molecules that were linked to Alzheimer's pathology in previous studies.
Early life social experience and adulthood impulsivity - Implications of central serotonergic system during development.
Medical hypotheses, 2020

Developmental psychology highlights that early life experience is important in shaping later on mental manifestations, and it may apply to social development too. Impulsivity is a specific form of mental manifestation to reflect an impairment of individuals' ability to control their response. Increasing evidence reveals that disturbance of social development from early life, such as isolation rearing since weaning, could affect individuals' behavioral impulsivity. Its underlying mechanism remains unsolved, however manipulation of central 5-HT system provide effective therapeutic utility in both human and animal studies. We hypothesize that the pathophysiology of isolation rearing shares with the underlying mechanism of impulsivity in which a time-dependent change of central 5-HT is involved. The hypothesis can be tested by experiments to work out (i) early life social development serves as a factor in determining the function of central 5-HT in adulthood, and (ii) long term manipulation of central 5-HT can reverse the effects of isolation rearing on behavioral impulsivity and 5-HT related neurochemical profiles.
Robust estimation of quantitative perfusion from multi-phase pseudo-continuous arterial spin labeling.
Magnetic resonance in medicine, 2020

Multi-phase PCASL has been proposed as a means to achieve accurate perfusion quantification that is robust to imperfect shim in the labeling plane. However, there exists a bias in the estimation process that is a function of noise in the data. In this work, this bias is characterized and then addressed in animal and human data.
Unraveling neuroHIV in the Presence of Substance Use Disorders.
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2020

This special issue contains 10 invited review papers that highlighted and extended the presentations at the NIDA-sponsored workshop "Unraveling NeuroAIDS in the Presence of Substance Use Disorders" at the 25th Society on NeuroImmune Pharmacology conference in 2019. The topics covered by these papers focused on the interactive, additive or synergistic effects of substance use disorders (SUD) with HIV infection on the immune system and on neuropathogenesis. These papers reviewed four categories of substances of abuse (opioids, tobacco, stimulants, and cannabis) and how comorbid HIV infection (including models with HIV proteins, HIV transgenic rodent models and SIV) might further impact the dysregulated dopaminergic and immune systems, and the subsequent neuropathogenesis and behavioral disorders known as HIV-associated neurological disorders (HAND). These reviews provided detailed background knowledge regarding how each of these addictive substances and HIV individually or collectively affected the immune system at the cellular, molecular and system levels, and the subsequent clinical and behavioral outcomes. The authors also identified gaps, confounds or constraints in the current disease models and approaches, and proposed future research directions.
SARS-CoV-2 Receptors and Entry Genes Are Expressed in the Human Olfactory Neuroepithelium and Brain.
iScience, 2020

Reports indicate an association between COVID-19 and anosmia, as well as the presence of SARS-CoV-2 virions in the olfactory bulb. To test whether the olfactory neuroepithelium may represent a target of the virus, we generated RNA-seq libraries from human olfactory neuroepithelia, in which we found substantial expression of the genes coding for the virus receptor angiotensin-converting enzyme-2 (ACE2) and for the virus internalization enhancer TMPRSS2. We analyzed a human olfactory single-cell RNA-seq dataset and determined that sustentacular cells, which maintain the integrity of olfactory sensory neurons, express
Longitudinal trajectories of mood symptoms and global functioning in youth at high risk for bipolar disorder.
Journal of affective disorders, 2020

Little is known about the longitudinal course of mood symptoms and functioning in youth who are at high risk for bipolar disorder (BD). Identifying distinct course trajectories and predictors of those trajectories may help refine treatment approaches.
A New Method for Fibroblast-less Primary Skeletal Muscle Cell Culture by the Use of Hydroxyurea: (skeletal muscle cell culture/hydroxyurea/muscle cell differentiation/myosin heavy chain/dystrophin).
Development, growth & differentiation, 1994

A method was developed to suppress growth of fibroblasts in chicken and mouse primary skeletal muscle cell cultures. Addition of hydroxyurea to the culture medium at appropriate time and concentrations suppressed the proliferation of fibroblasts whereas leaving myotubes grow and differentiate. The most favorable time for the addition was soon after myotube formation. The optimal concentrations for our purpose ranged from 0.5 to 1.0 mM. In the presence of hydroxyurea at these concentrations, myotubes grew larger and well differentiated, whereas fibroblasts remained in the suppressed state. In chicken myotubes cultured with hydroxyurea, cross-striations, spontaneous twitching and myosin heavy chain appeared as in myotubes without hydroxyurea. In mouse myotubes cultured with hydroxyurea, myosin heavy chain and dystrophin appeared, as in control myotubes.
Potential application of endocannabinoid system agents in neuropsychiatric and neurodegenerative diseases-focusing on FAAH/MAGL inhibitors.
Acta pharmacologica Sinica, 2020

The endocannabinoid system (ECS) has received extensive attention for its neuroprotective effect on the brain. This system comprises endocannabinoids, endocannabinoid receptors, and the corresponding ligands and proteins. The molecular players involved in their regulation and metabolism are potential therapeutic targets for neuropsychiatric diseases including anxiety, depression and neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). The inhibitors of two endocannabinoid hydrolases, i.e., fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), have the capacity to increase the level of endocannabinoids indirectly, causing fewer side effects than those associated with direct supplementation of cannabinoids. Their antidepressant and anxiolytic mechanisms are considered to modulate the hypothalamic-pituitary-adrenal axis and regulate synaptic and neural plasticity. In terms of AD/PD, treatment with FAAH/MAGL inhibitors leads to reduction in amyloid β-protein deposition and inhibition of the death of dopamine neurons, which are commonly accepted to underlie the pathogenesis of AD and PD, respectively. Inflammation as the cause of depression/anxiety and PD/AD is also the target of FAAH/MAGL inhibitors. In this review, we summarize the application and involvement of FAAH/MAGL inhibitors in related neurological diseases. Focus on the latest research progress using FAAH/MAGL inhibitors is expected to facilitate the development of novel approaches with therapeutic potential.
Function of multiple sclerosis-protective HLA class I alleles revealed by genome-wide protein-quantitative trait loci mapping of interferon signalling.
PLoS genetics, 2020

Interferons (IFNs) are cytokines that are central to the host defence against viruses and other microorganisms. If not properly regulated, IFNs may contribute to the pathogenesis of inflammatory autoimmune, or infectious diseases. To identify genetic polymorphisms regulating the IFN system we performed an unbiased genome-wide protein-quantitative trait loci (pQTL) mapping of cell-type specific type I and type II IFN receptor levels and their responses in immune cells from 303 healthy individuals. Seven genome-wide significant (p < 5.0E-8) pQTLs were identified. Two independent SNPs that tagged the multiple sclerosis (MS)-protective HLA class I alleles A*02/A*68 and B*44, respectively, were associated with increased levels of IFNAR2 in B and T cells, with the most prominent effect in IgD-CD27+ memory B cells. The increased IFNAR2 levels in B cells were replicated in cells from an independent set of healthy individuals and in MS patients. Despite increased IFNAR2 levels, B and T cells carrying the MS-protective alleles displayed a reduced response to type I IFN stimulation. Expression and methylation-QTL analysis demonstrated increased mRNA expression of the pseudogene HLA-J in B cells carrying the MS-protective class I alleles, possibly driven via methylation-dependent transcriptional regulation. Together these data suggest that the MS-protective effects of HLA class I alleles are unrelated to their antigen-presenting function, and propose a previously unappreciated function of type I IFN signalling in B and T cells in MS immune-pathogenesis.
Leprosy in a prison population: A new active search strategy and a prospective clinical analysis.
PLoS neglected tropical diseases, 2020

This study evaluates an active search strategy for leprosy diagnosis based on responses to a Leprosy Suspicion Questionnaire (LSQ), and analyzing the clinical, immunoepidemiological and follow-up aspects for individuals living in a prison population.