bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simulation-Based Inference for Whole-Brain Network Modeling of Epilepsy using Deep Neural Density Estimators
Authors: Hashemi Meysam , Vattikonda Anirudh N. , Jha Jayant , Sip Viktor , Woodman Marmaduke M. , Bartolomei Fabrice , Jirsa Viktor K. 
Published: June 2022

AbstractWhole-brain network modeling of epilepsy is a data-driven approach that combines personalized anatomical information with dynamical models of abnormal brain activity to generate spatio-temporal seizure patterns as observed in brain imaging signals. Such a parametric simulator is equipped with a stochastic generative process, which itself provides the basis for inference and prediction of the local and global brain dynamics affected by disorders. However, the calculation of likelihood function at whole-brain scale is often intractable. Thus, likelihood-free inference algorithms are required to efficiently estimate the parameters pertaining to the hypothetical areas in the brain, ideally including the uncertainty. In this detailed study, we present simulation-based inference for the virtual epileptic patient (SBI-VEP) model, which only requires forward simulations, enabling us to amortize posterior inference on parameters from low-dimensional data features representing whole-brain epileptic patterns. We use state-of-the-art deep learning algorithms for conditional density estimation to retrieve the statistical relationships between parameters and observations through a sequence of invertible transformations. This approach enables us to readily predict seizure dynamics from new input data. We show that the SBI-VEP is able to accurately estimate the posterior distribution of parameters linked to the extent of the epileptogenic and propagation zones in the brain from the sparse observations of intracranial EEG signals. The presented Bayesian methodology can deal with non-linear latent dynamics and parameter degeneracy, paving the way for reliable prediction of neurological disorders from neuroimaging modalities, which can be crucial for planning intervention strategies.
Long COVID is associated with extensive in-vivo neuroinflammation on [18F]DPA-714 PET
Authors: Visser Denise , Golla Sandeep S.V. , Verfaillie Sander C.J. , Coomans Emma M. , Rikken Roos M. , van de Giessen Elsmarieke M. , den Hollander Marijke E. , Verveen Anouk , Yaqub Maqsood , Barkhof Frederik , Horn Janneke , Koopman Bart , Schober Patrick , Koch Dook W. , Schuit Robert C. , Windhorst Albert D. , Kassiou Michael , Boellaard Ronald , van Vugt Michele , Knoop Hans , Tolboom Nelleke , van Berckel Bart N.M. 
Published: June 2022

SummaryA significant number of COVID-19 patients develop ‘long COVID’, a condition defined by long-lasting debilitating, often neurological, symptoms. The pathophysiology of long COVID is unknown. Here we present in-vivo evidence of widespread neuroinflammation in long COVID, using a quantitative assessment, [18F]DPA-714 PET, in two long COVID patients. We reanalyzed historical data from three matched healthy control subjects, for comparison purposes. Both patients with long COVID had widespread increases in [18F]DPA-714 binding throughout the brain. Quantitative measures of binding (BPND values) were increased on average by 121% and 76%, respectively. This implicates profound neuroinflammation in the pathophysiology of long COVID.
Real-world evidence on levodopa dose escalation in patients with Parkinson’s disease treated with istradefylline
Authors: Hattori Nobutaka , Kabata Daijiro , Asada Shinji , Kanda Tomoyuki , Nomura Takanobu , Shintani Ayumi , Mori Akihisa 
Published: June 2022

AbstractObjectiveIstradefylline, a selective adenosine A2A receptor antagonist, is indicated in the US and Japan as adjunctive treatment to levodopa/decarboxylase inhibitors in adults with Parkinson’s disease (PD) experiencing OFF time. This study aimed to observe patterns of dose escalation of levodopa over time in patients initiated on istradefylline.MethodsUsing Japanese electronic health record data, interrupted time series analyses were used to compare levodopa daily dose (LDD, mg/day) gradients in patients before and after initiation of istradefylline. Data were analyzed by period relative to istradefylline initiation (Month 1): pre-istradefylline (Months -72 to 0), early istradefylline (Months 1 to 24), and late istradefylline (Months 25 to 72). Subgroup analyses included LDD before istradefylline initiation (<400, ≥400 to <600, ≥600 mg/day) and treatment with or without monoamine oxidase-B inhibitors (MAO-BIs), catechol-O-methyltransferase inhibitors (COMTIs), or dopamine agonists before istradefylline initiation.ResultsThe analysis included 4026 patients; mean (SD) baseline LDD was 419.27 mg (174.19). Patients receiving ≥600 mg/day levodopa or not receiving MAO-BIs or COMTIs demonstrated a significant reduction in LDD increase gradient for pre-istradefylline vs late-phase istradefylline (≥600 mg/day levodopa, -6.259 mg/day each month, p<0.001; no MAO-BIs, -1.819 mg/day each month, p=0.004; no COMTIs, -1.412 mg/day each month, p=0.027).ConclusionsThis real-world analysis of Japanese prescription data indicated that slowing of LDD escalation was observed in patients initiated on istradefylline, particularly in those receiving ≥600 mg/day levodopa, suggesting istradefylline may slow progressive LDD increases. These findings suggest that initiating istradefylline before other levodopa-adjunctive therapies may mitigate LDD increases, potentially reducing occurrence or severity of levodopa-induced complications in long-term istradefylline treatment.
Distinct smell and taste disorder phenotype of post-acute COVID-19 sequelae
Authors: Rass Verena , Tymoszuk Piotr , Sahanic Sabina , Heim Beatrice , Ausserhofer Dietmar , Lindner Anna , Kofler Mario , Mahlknecht Philipp , Boehm Anna , Hüfner Katharina , Pizzini Alex , Sonnweber Thomas , Kurz Katharina , Pfeifer Bernhard , Kiechl Stefan , Peball Marina , Kindl Philipp , Putnina Lauma , Fava Elena , Djamshidian Atbin , Huber Andreas , Wiedermann Christian J. , Sperner-Unterweger Barbara , Wöll Ewald , Beer Ronny , Schiefecker Alois Josef , Bellmann-Weiler Rosa , Bachler Herbert , Tancevski Ivan , Pfausler Bettina , Piccoliori Giuliano , Seppi Klaus , Weiss Günter , Löffler-Ragg Judith , Helbok Raimund 
Published: June 2022

AbstractBackgroundOlfactory dysfunction (OD) often accompanies acute coronavirus disease 2019 (COVID-19) and its sequelae. Herein, we investigated OD during COVID-19 recovery in the context of other symptoms, quality of life, physical and mental health.MethodsSymptom recovery patterns were analyzed in a bi-national, ambulatory COVID-19 survey (n = 906, ≥ 90 days follow-up) and a multi-center observational cross-sectional cohort of ambulatory and hospitalized individuals (n = 108, 360 days follow-up) with multi-dimensional scaling, association rule mining and partitioning around medoids clustering.ResultsBoth in the ambulatory collective (72%, n = 655/906) and the cross-sectional ambulatory and hospitalized cohort (41%, n = 44/108) self-reported OD was frequent during acute COVID-19, displayed a slow recovery pace (ambulatory: 28 days, cross-sectional: 90 days median recovery time) and commonly co-occurred with taste disorders. In the ambulatory collective, a predominantly young, female, comorbidity-free group of convalescents with persistent OD and taste disorder (>90 days) was identified. This post-acute smell and taste disorder phenotype was characterized by a low frequency of other leading post-acute symptoms including fatigue, respiratory and neurocognitive complaints. Despite a protracted smell and taste dysfunction, this subset had high ratings of physical performance, mental health, and quality of life.ConclusionOur results underline the clinical heterogeneity of post-acute COVID-19 sequelae calling for tailored management strategies. The persistent smell and taste disorder phenotype may represent a distinct COVID-19 recovery pathway characterized by a good recovery of other COVID-19 related symptoms.Study registrationClinicalTrials.gov: NCT04661462 (ambulatory collective), NCT04416100 (cross-sectional cohort).
Polygenic Risk Score Improves the Accuracy of a Clinical Risk Score for Coronary Artery Disease
Authors: King Austin , Wu Lang , Deng Hong-Wen , Shen Hui , Wu Chong 
Published: June 2022

AbstractBackgroundThe value of polygenic risk scores (PRS) towards improving guideline-recommended clinical risk models for coronary artery disease (CAD) prediction is controversial. Here we examine whether an integrated polygenic risk score improves prediction of CAD beyond pooled cohort equations.MethodsAn observation study of 291,305 unrelated White British UK Biobank participants enrolled from 2006 to 2010 was conducted. A case-control sample of 9,499 prevalent CAD cases and an equal number of randomly selected controls was used for tuning and integrating of the polygenic risk scores. A separate cohort of 272,307 individuals (with follow-up to 2020) was used to examine the risk prediction performance of pooled cohort equations, integrated polygenic risk score, and PRS-enhanced pooled cohort equation for incident CAD cases. Performance of each model was analyzed by discrimination and risk reclassification using a 7.5% threshold.ResultsIn the cohort of 272,307 individuals (mean age, 56.7 years) used to analyze predictive accuracy, there were 7,036 incident CAD cases over a 12-year follow-up period. Model discrimination was tested for integrated polygenic risk score, pooled cohort equation, and PRS-enhanced pooled cohort equation with reported C-statistics of 0.640 (95% CI, 0.634-0.646), 0.718 (95% CI, 0.713-0.723), and 0.753 (95% CI, 0.748-0.758), respectively. Risk reclassification for the addition of the integrated polygenic risk score to the pooled cohort equation at a 7.5% risk threshold resulted in a net reclassification improvement of 0.117 (95% CI, 0.102 to 0.129) for cases and -0.023 (95% CI, -0.025 to -0.022) for noncases [overall: 0.093 (95% CI, 0.08 to 0.104)]. For incident CAD cases, this represented 14.2% correctly reclassified to the higher-risk category and 2.6% incorrectly reclassified to the lower-risk category.Conclusions and RelevanceAddition of the integrated polygenic risk score for CAD to the pooled cohort questions improves the predictive accuracy for incident CAD and clinical risk classification in the White British from the UK biobank. These findings suggest that an integrated polygenic risk score may enhance CAD risk prediction and screening in the White British population.
Increase of scabies infestations during the COVID-19 pandemic in Catalonia
Authors: Medina Manuel , Mora Núria , Ramos Francisca , Méndez-Boo Leonardo , Guiriguet Carolina , Hermosilla Eduardo , Fàbregas Mireia , Mas Ariadna , Rodoreda Sara , Coma Ermengol , Fina Francesc 
Published: June 2022

AbstractDuring the COVID-19 pandemic, several clinicians in Spain reported an increase in scabies diagnoses. We performed a time-series analysis with data from 2014 to 2022 to quantify this increase. We found an increasing trend during late 2020 and 2021, peaking in March 2022 with an almost 4.5-fold incidence than expected, especially in those aged between 16 and 30 years. Although scabies is more frequent in most socioeconomic deprived areas, the observed rise occurs in all the areas. We recommend increasing surveillance among other countries to detect unexpected increases in scabies outbreaks.
Globalisation and Maternal Health Care Utilisation in sub-Saharan Africa: A Bayesian Multilevel Analysis
Authors: Simona Simona 
Published: June 2022

AbstractBackgroundGlobalization is considered a major structural determinant of health and health care outcomes across the world. This study examines the influence of globalisation on maternal healthcare utilisation in sub-Saharan Africa.MethodsCross-sectional pooled survey data from 34 Demographic and Health Surveys (DHS) with 22559 randomly selected women of reproductive age group with a recent birth were combined with country-level globalisation indices from the KOF Swiss Economic Institute. Bayesian multilevel models were applied on maternal health care utilisation indicators (antenatal care visits, institutional delivery, and postnatal care check-ups) in relation to three dimensions of globalisation indices (economic, social, and political) and selected covariates.ResultsThe results from the study demonstrate that the influence of globalisation on maternal healthcare depends on the dimension of globalisation. After controlling for selected individual and community-level factors, social globalisation is significantly associated with all the indicators of maternal healthcare utilisation while economic globalisation is significantly associated with antenatal care and postnatal check-ups for mothers and new-born babies.ConclusionMore consideration in terms of public policy and further research, should be given to dimensions of globalisation which are more likely to influence maternal healthcare utilisation in sub-Saharan Africa.
Crosshair, semi-automated targeting for electron microscopy with a motorised ultramicrotome
Authors: Meechan Kimberly , Guan Wei , Riedinger Alfons , Stankova Vera , Yoshimura Azumi , Pipitone Rosa , Milberger Arthur , Schaar Helmuth , Romero-Brey Inés , Templin Rachel , Peddie Christopher J , Schieber Nicole L , Jones Martin L , Collinson Lucy , Schwab Yannick 
Published: June 2022

AbstractVolume electron microscopy (EM) is a time consuming process - often requiring weeks or months of continuous acquisition for large samples. In order to compare the ultrastructure of a number of individuals or conditions, acquisition times must therefore be reduced. For resin-embedded samples, one solution is to selectively target smaller regions of interest by trimming with an ultramicrotome. This is a difficult and labour-intensive process, requiring manual positioning of the diamond knife and sample, and much time and training to master. Here, we have developed a semi-automated workflow for targeting with a modified ultramicrotome. We adapted two recent commercial systems to add motors for each rotational axis (and also each translational axis for one system), allowing precise and automated movement. We also developed a user-friendly software to convert X-ray images of resin-embedded samples into angles and cutting depths for the ultramicrotome. This is provided as an open-source Fiji plugin called Crosshair. This workflow is demonstrated by targeting regions of interest in a series of Platynereis dumerilii samples.
Distinct antibody responses to endemic coronaviruses pre- and post-SARS-CoV-2 infection in Kenyan infants and mothers
Authors: Stoddard Caitlin I. , Sung Kevin , Ojee Ednah , Adhiambo Judith , Begnel Emily R. , Slyker Jennifer , Gantt Soren , Matsen Frederick A. , Kinuthia John , Wamalwa Dalton , Overbaugh Julie , Lehman Dara A. 
Published: June 2022

AbstractPre-existing antibodies that bind endemic human coronaviruses (eHCoVs) can cross-react with SARS-CoV-2, the betacoronavirus that causes COVID-19, but whether these responses influence SARS-CoV-2 infection is still under investigation and is particularly understudied in infants. In this study, we measured eHCoV and SARS-CoV-1 IgG antibody titers before and after SARS-CoV-2 seroconversion in a cohort of Kenyan women and their infants. Pre-existing eHCoV antibody binding titers were not consistently associated with SARS-CoV-2 seroconversion in infants or mothers, though we observed a very modest association between pre-existing HCoV-229E antibody levels and lack of SARS-CoV-2 seroconversion in infants. After seroconversion to SARS-CoV-2, antibody binding titers to endemic betacoronaviruses HCoV-OC43 and HCoV-HKU1, and the highly pathogenic betacoronavirus SARS-CoV-1, but not endemic alphacoronaviruses HCoV-229E and HCoV-NL63, increased in mothers. However, eHCoV antibody levels did not increase following SARS-CoV-2 seroconversion in infants, suggesting the increase seen in mothers was not simply due to cross-reactivity to naively generated SARS-CoV-2 antibodies. In contrast, the levels of antibodies that could bind SARS-CoV-1 increased after SARS-CoV-2 seroconversion in both mothers and infants, both of whom are unlikely to have had a prior SARS-CoV-1 infection, supporting prior findings that SARS-CoV-2 responses cross-react with SARS-CoV-1. In summary, we find evidence for increased eHCoV antibody levels following SARS-CoV-2 seroconversion in mothers but not infants, suggesting eHCoV responses can be boosted by SARS-CoV-2 infection when a prior memory response has been established, and that pre-existing cross-reactive antibodies are not strongly associated with SARS-CoV-2 infection risk in mothers or infants.
An Accelerometer Based Heart Monitor to Measure Changes of the Autonomic Nervous System
Authors: Babenko Viktoriya , Dundon Neil M. , Macy Alan , Stump Alexandra , Turbow Macey , Cieslak Matthew , Grafton Scott T. 
Published: June 2022

AbstractThe electrocardiogram (ECG) and impedance cardiography (ICG) are typically combined to estimate electromechanical features such as the pre-ejection period (PEP) and left ventricular ejection time (LVET); indicators of changes in the cardiac specific drive of the autonomic nervous system (ANS). Current methods of ICG are time intensive in subject preparation and the measurements are vulnerable to non-reproducible subject-specific electrode configuration. Furthermore, analysis of impedance waveforms can be time consuming and labeling of key time points can suffer from experimenter bias. Here we present a wearable heart monitor that includes ECG, but replaces the commonly used 8 ICG electrodes with a single accelerometer (ACC) placed at the suprasternal notch. The ACC indirectly measures movement of the arterial pulse wave as blood is ejected into the aorta and great vessels. The resulting ACC waveform is processed into two smooth and readily identified waves, corresponding to the timing of the opening and closing of the aortic valve. We tested the ACC’s utility and reliability for tracking cardiac ANS tone by comparing PEP and LVET measurements obtained simultaneously with conventional ICG and the ACC. Participants were recorded in the sitting and supine position with ECG, ICG, and ACC. While seated, they engaged in a classic physical stress task known to modulate ANS activity. There were obvious and significant associations between ICG and ACC estimates of PEP and LVET derivatives with respect to time. These findings support ACC as a complementary method for tracking ANS that is robust, time efficient, and readily accessible to researchers.
The histone demethylase KDM3 prevents auto-immune piRNAs production in Drosophila
Authors: Casier Karine , Autaa Julie , Gueguen Nathalie , Delmarre Valérie , Pauline Marie P. , Ronsseray Stéphane , Carré Clément , Brasset Emilie , Teysset Laure , Boivin Antoine 
Published: June 2022

SUMMARYIn animals, genome integrity of the germ line is protected from transposable element (TE) activity by small, non-coding, dedicated RNAs acting as an immune system against TEs, and called PIWI-interacting RNAs (piRNAs) 1,2. In Drosophila, the production of piRNAs is initiated from heterochromatic loci containing remnants of TEs and enriched in histone H3 trimethylated on lysine 9 (H3K9me3) 3–5. These loci, called piRNA clusters, constitute a memory of past TE invasions. Little is known about how piRNA clusters are genetically defined. Using a genetic screen combined with a bimodal epigenetic state piRNA cluster (BX2), we identified the splicing factor Half pint (Hfp) and the histone demethylase KDM3 as being able to prevent BX2 piRNA production. Furthermore, we showed that Hfp is needed to splice Kdm3 transcripts. Germline expression of Kdm3 coding sequence (splicing-independent) rescued the hfp germline knock-down (GLKD) effect demonstrating that Kdm3 is sufficient to prevent BX2 piRNA production. Our data revealed that in the absence of Kdm3, dozens of gene-containing regions become bona fide germinal dual strand piRNA clusters. Indeed, they produce piRNAs originating from both DNA strands, become transcribed in a Moonshiner-dependent manner and enriched in di-and tri-methylation of lysine 9 of histone H3 (H3K9me2/3) and in Rhino, an HP1-like protein. Eggs laid by Kdm3 GLKD females do not hatch and show developmental defects phenocopying loss of function of genes included into the new piRNA clusters, suggesting an inheritance of functional ovarian “auto-immune” piRNAs. Our results demonstrate that some gene-containing regions are actively prevented for piRNA production by proteins that counteract piRNA cluster emergence. Hence, a non-piRNA-producing state is therefore not a “by default” state but rather a cellular lock that is actively controlled for some genomic loci.KEY FACTSHfp regulates the expression of Kdm3 via its splicingKdm3 prevents genomic regions containing coding genes from becoming piRNA clustersEmbryos from Kdm3 mutant females show developmental phenotypes suggesting that auto-immune piRNAs are functional and alter the expression of genes embedded in newly established piRNA clusters
Differential vulnerability of neuronal subpopulations of the subiculum in a mouse model for mesial temporal lobe epilepsy
Authors: Franz Julia , Barheier Nicole , Tulke Susanne , Haas Carola A. , Häussler Ute 
Published: June 2022

AbstractSelective loss of inhibitory interneurons (INs) that promotes a shift toward an excitatory predominance may have a critical impact on the generation of epileptic activity. While research on mesial temporal lobe epilepsy (MTLE) has mostly focused on hippocampal changes, including IN loss, the subiculum as the major output region of the hippocampal formation has received comparatively little attention. Although it has been shown to occupy a key position in the epileptic network, data on cellular changes in the subiculum are controversial. Using the intrahippocampal kainate (KA) mouse model for MTLE, which recapitulates main features of human MTLE such as hippocampal sclerosis and granule cell dispersion followingstatus epilepticus(SE), we identified cell loss in the subiculum and quantified changes in specific IN subpopulations along its dorsoventral axis.We performed intrahippocampal recordings, FluoroJade C-staining for degenerating neurons shortly after SE and immunohistochemistry for neuronal nuclei (NeuN), parvalbumin (PV), neuropeptide Y (NPY), calretinin (CR) and calbindin (CB), andin situhybridization for glutamic acid decarboxylase(Gad) 67mRNA at 21 days after KA.We observed remarkable cell loss in the ipsilateral subiculum shortly after SE which was reflected in lowered density of NeuN+ cells in the chronic stage when epileptic activity could be measured in the subiculum concomitant with the hippocampus. We show a position-dependent reduction ofGad67-expressing INs by ~50% which particularly affected the PV- and to a lesser extent CR-expressing INs, whereas CB-expressing cells were unchanged.Interestingly, the density of NPY-positive neurons was increased, but double-labeling forGad67mRNA expression revealed that rather ade novoexpression of NPY in non-GABAergic cells instead of IN changes underlay this increase.Our data reveal a position- and cell type-specific vulnerability of subicular INs in MTLE which might contribute to hyperexcitability of the subiculum, as reflected in the occurrence of epileptic activity.Keypoints (3-5)The subiculum develops epileptic activity after intrahippocampal kainate injection in miceGad67-mRNA expressing interneurons are reduced in the subiculum in the intrahippocampal kainate model for mesial temporal lobe epilepsyParvalbumin- and calretinin-expressing interneurons are particularly vulnerable in epilepsyNeuropeptide Y upregulation in non-GABAergic cells in the subiculum indicates compensatory processes