bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attentional modulation of neural dynamics in tactile perception of complex regional pain syndrome patients
Authors: Defina Serena , Niedernhuber Maria , Shenker Nicholas , Brown Christopher A. , Bekinschtein Tristan A. 
Published: July 2021

AbstractBody perceptual disturbances are an increasingly acknowledged set of symptoms and possible clinical markers of complex regional pain syndrome (CRPS), but the neurophysiological and neurocognitive changes that underlie them are still far from being clear. We adopted a multivariate and neurodynamical approach to the analysis of EEG modulations evoked by touch to highlight differences between patients and healthy controls, between affected and unaffected side of the body, and between “passive” (i.e., no task demands and equiprobable digit stimulation) and “active” tactile processing (i.e., where a digit discrimination task was administered and spatial probability manipulated). When correct identifications are considered, an early reduction in cortical decodability (28–56 ms) distinguishes CRPS patients from healthy volunteers. However, when error trials are included in the classifier's training, there is an unexpected increased decodability in the CRPS group compared with healthy volunteers (280–320 ms). These group differences in neural processing seemed to be driven by the affected rather than the unaffected side. We corroborated these findings with several exploratory analyses of neural representation dynamics and behavioural modelling, highlighting the need for single participant analyses. Although several limitations impacted the robustness and generalizability of these comparisons, the proposed analytical approach yielded promising insights (as well as possible biomarkers based on neural dynamics) into the relatively unexplored alterations of tactile decision‐making and attentional control mechanisms in chronic CRPS.
Pre‐stimulus alpha oscillation and post‐stimulus cortical activity differ in localization between consciously perceived and missed near‐threshold somatosensory stimuli
Authors: Uemura Jun‐ichi , Hoshino Aiko , Igarashi Go , Matsui Yusuke , Chishima Makoto , Hoshiyama Minoru 
Published: July 2021

AbstractConscious perception of a near‐threshold (NT) stimulus is characterized by the pre‐ and post‐stimulus brain state. However, the power of pre‐stimulus neural oscillations and strength of post‐stimulus cortical activity that lead to conscious perception have rarely been examined in individual cortical areas. This is because most previous electro‐ and magnetoencephalography (EEG and MEG, respectively) studies involved scalp‐ and sensor‐level analyses. Therefore, we recorded MEG during a continuous NT somatosensory stimulus detection task and applied the reconstructed source data in order to identify cortical areas where the post‐stimulus cortical activity and pre‐stimulus alpha oscillation predict the conscious perception of NT somatosensory stimuli. We found that the somatosensory hierarchical processing areas, prefrontal areas and cortical areas belonging to the default mode network showed stronger cortical activity for consciously perceived trials in the post‐stimulus period, but the cortical activity in primary somatosensory area (SI) is independent of conscious perception during the early stage of NT stimulus processing. In addition, we revealed that the pre‐stimulus alpha oscillation only in SI is predictive of conscious perception. These findings suggest that the bottom‐up stream of somatosensory information flow following SI and pre‐stimulus alpha activity fluctuation in SI as a top‐down modulation are crucial constituents of conscious perception.
T cell composition and polygenic multiple sclerosis risk: A population‐based study in children
Authors: de Mol Casper L. , Looman Kirsten I. M. , van Luijn Marvin M. , Kreft Karim L. , Jansen Philip R. , van Zelm Menno C. , Smolders Joost J. F. M. , White Tonya J. H. , Moll Henriette A. , Neuteboom Rinze F. 
Published: July 2021

AbstractBackground and purposePatients with multiple sclerosis (MS) have altered T cell function and composition. Common genetic risk variants for MS affect proteins that function in the immune system. It is currently unclear to what extent T cell composition is affected by genetic risk factors for MS, and how this may precede a possible disease onset. Here, we aim to assess whether an MS polygenic risk score (PRS) is associated with an altered T cell composition in a large cohort of children from the general population.MethodsWe included genotyped participants from the population‐based Generation R study in whom immunophenotyping of blood T cells was performed at the age of 6 years. Analyses of variance were used to determine the impact of MS‐PRSs on total T cell numbers (n = 1261), CD4+and CD8+lineages, and subsets therein (n= 675). In addition, T‐cell‐specific PRSs were constructed based on functional pathway data.ResultsThe MS‐PRS negatively correlated with CD8+T cell frequencies (p = 2.92 × 10−3), which resulted in a positive association with CD4+/CD8+T cell ratios (p = 8.27 × 10−9). These associations were mainly driven by two of 195 genome‐wide significant MS risk variants: the main genetic risk variant for MS,HLA‐DRB1*15:01and anHLA‐Brisk variant. We observed no significant associations for the T‐cell‐specific PRSs.ConclusionsOur results suggest that MS‐associated genetic variants affect T cell composition during childhood in the general population.
Atrial fibrosis in embolic stroke of undetermined source: A multicenter study
Authors: Kühnlein Peter , Mahnkopf Christian , Majersik Jennifer J. , Wilson Brent D. , Mitlacher Marcel , Tirschwell David , Longstreth W. T. , Akoum Nazem 
Published: July 2021

AbstractBackground and purposeLeft atrial (LA) cardiac disease is a suspected cause of embolic stroke of undetermined source (ESUS). We tested the hypothesis that LA fibrosis, quantified using late‐gadolinium‐enhancement magnetic resonance imaging (LGE‐MRI), predicts recurrent stroke or atrial fibrillation (AF) in patients with ESUS.MethodsWe compared atrial fibrosis in healthy controls and patients with lacunar stroke, ESUS, and known AF with or without prior stroke. We followed patients with ESUS prospectively for the primary outcome of recurrent ischemic stroke, incident AF, or both.ResultsWe enrolled 203 patients from three centers: 103 patients without AF (35 healthy controls, 15 with lacunar strokes, 53 with ESUS) and 100 patients with AF (50 with and 50 without prior stroke). Patients with ESUS had significantly higher atrial fibrosis (15.0 ± 6.2%) compared to healthy controls (8.1 ± 7.9%; <0.0001) and compared to lacunar stroke patients (10.8 ± 8.4; p = 0.02), but had comparable fibrosis to patients with AF with (17.9 ± 11.4%) or without prior stroke (16.6 ± 9.2%; p = NS for both). Over a mean follow‐up of 19 months, nine of 53 patients (16.9%) with ESUS experienced the combined primary outcome, which included six patients (11.3%) with recurrent ischemic stroke and five patients with incident AF (9.4%). Patients with ESUS with fibrosis ≥12% had a higher proportion of the combined outcome: 25.0% vs. 4.8%; p = 0.039.ConclusionsPatients with ESUS demonstrate atrial fibrosis comparable to that seen in AF. Atrial fibrosis ≥12% was associated with recurrent stroke, incident AF or both. This subgroup of ESUS patients may benefit from anticoagulation for secondary prevention of ischemic stroke.
Novel mechanisms of microbial crosstalk with skin innate immunity
Authors: Chinnappan Mahendran , Harris‐Tryon Tamia A. 
Published: July 2021

AbstractSkin is an organ with a dynamic ecosystem that harbours pathogenic and commensal microbes, which constantly communicate amongst each other and with the host immune system. Evolutionarily, skin and its microbiota have evolved to remain in homeostasis. However, frequently this homeostatic relationship is disturbed by a variety of factors such as environmental stress, diet, genetic mutations, and the microbiome itself. Commensal microbes also play a major role in the maintenance of microbial homeostasis. In addition to their ability to limit pathogens, many skin commensals such as Staphylococcus epidermidis and Cutibacterium acnes have recently been implicated in disease pathogenesis either by directly modulating the host immune components or by supporting the expansion of other pathogenic microbes. Likewise, opportunistic skin pathogens such as Staphylococcus aureus and Staphylococcus lugdunensis are able to breach the skin and cause disease. Though much has been established about the microbiota's function in skin immunity, we are in a time where newer mechanistic insights rapidly redefine our understanding of the host/microbial interface in the skin. In this review, we provide a concise summary of recent advances in our understanding of the interplay between host defense strategies and the skin microbiota.
Sampling units derived from geopolitical boundaries bias biodiversity analyses
Authors: Murphy Stephen J. 
Published: July 2021

AbstractAimSampling decisions are known to influence the estimation and interpretation of biodiversity. The use of geopolitical and administrative boundaries (GABs) for mapping biodiversity variables and identifying hotspots has a long history in biogeography and conservation biology. However, potential biases associated with these units and their effects on conservation decisions has not been adequately explored.LocationGlobal.Time period21,000 years ago to present day.Major taxa studiedAmphibians, birds, mammals and reptiles.MethodsI calculated biodiversity metrics for four major taxa at eight different spatial resolutions to understand scale‐dependencies. I then compared these estimates to those using GABs (e.g., countries and other large units) as sampling units. I also used both grid‐ and GAB‐based sampling designs to model the relationship between biodiversity patterns and relevant climate variables.ResultsLarger sampling units led to higher estimates of species richness and phylogenetic diversity. Taxonomic and phylogenetic endemism remained relatively stable across scales due to competing biases related to grain size and estimation of range size. Using GABs led to both under‐ and overestimation of endemism when compared to fine‐resolution grid‐based estimates, with differences varying across space and taxonomic groups. Importantly, using GABs resulted in different locations being identified as biodiversity hotspots when compared to grid‐based analyses. Likewise, different climate drivers of species richness and endemism were identified when using a GAB‐ versus grid‐based sampling design.Main conclusionsUsing GABs will remain an important method for mapping variation in biodiversity metrics across the globe. However, appropriate understanding of the biases associated with these and other ad‐hoc sampling designs should be better understood and accounted for in macroecology analyses, including for understanding environmental drivers of biodiversity patterns and identifying local and regional diversity hotspots. This is especially true for measures of diversity that incorporate species range size, such as taxonomic and phylogenetic endemism.
MONEY METRICS IN APPLIED WELFARE ANALYSIS: A SADDLEPOINT REHABILITATION
Authors: Schlee Edward E. , Khan M. Ali 
Published: July 2021

AbstractOnce a popular tool to estimate welfare changes, the money metric of McKenzie‐Samuelson gradually faded from use after welfare theorists and practitioners argued that it led to inegalitarian recommendations. We prove that, at a competitive equilibrium price, any associated competitive allocation maximizes the money‐metric sum; and, as is well understood, competitive allocations can be egalitarian or inegalitarian. The result applies to economies in which individual demand is not rationalizable by any binary relation, let alone a binary relation representable by a utility function, a behavioral setting considered, for example, in Bernheim–Rangel.
Breakpoint characterization of a rare alpha0‐thalassemia deletion using targeted locus amplification on genomic DNA
Authors: Hottentot Quint P. , de Meijer Emile , Buermans Henk P. J. , White Stefan J. , Harteveld Cornelis L. 
Published: July 2021

AbstractIntroductionThe high‐sequence homology of the α‐globin‐gene cluster is responsible for microhomology‐mediated recombination events during meiosis, resulting in a high density of deletion breakpoints within a 10 kb region. Commonly used deletion detection methods, such as multiplex ligation‐dependent probe amplification (MLPA) and Southern blot, cannot exactly define the breakpoints. This typically requires long‐range PCR, which is not always successful. Targeted locus amplification (TLA) is a targeted enrichment method that can be used to sequence up to 70 kb of neighboring DNA sequences without prior knowledge about the target site.MethodsGenomic DNA (gDNA) TLA is a technique that folds isolated DNA, ensuring that adjacent loci are in a close spatial proximity. Subsequent digestion and religation form DNA circles that are amplified using fragment‐specific inverse primers, creating a library that is suitable for Illumina sequencing.ResultsHere, we describe the characterization of a rare 16 771 bp deletion, utilizing gDNA TLA with a single inverse PCR primer set on one end of the breakpoint. Primers for breakpoint PCR were designed to confirm the deletion breakpoints and were consequently used to characterize the same deletion in 10 additional carriers sharing comparable hematologic data and similar MLPA results.ConclusionsThe gDNA TLA technology was successfully used to identify deletion breakpoints within the alpha‐globin cluster. The deletion was described only once in an earlier study as the ‐‐gb, but as it was not registered correctly in the available databases, it was not initially recognized as such.
Impact of centrifugation on thrombin generation in healthy subjects and in patients treated with direct oral anticoagulants
Authors: Hardy Michael , Dellanoce Claudia , Douxfils Jonathan , Carlo Audrey , Lessire Sarah , Bouvy Céline , Testa Sophie , Mullier François 
Published: July 2021

AbstractIntroductionDouble centrifugation before freezing is recommended before thrombin generation assays (TGA). However, this procedure is not mandatory for routine hemostasis tests, precluding the use of these samples for TGA. The aim of this study is to assess the impact of single and double centrifugation on TGA performed on frozen samples from healthy volunteers (HVs) and patients receiving direct oral anticoagulants (DOACs).MethodsForty HVs and 57 patients receiving a DOAC (dabigatran, rivaroxaban, apixaban, or edoxaban) were included in this prospective double‐center observational study. Blood was collected into 109 mmol/L citrated tubes and frozen at −70°C before TGA using ST Genesia with STG‐DrugScreen reagent. Four pre‐analytical conditions were studied: (A) single centrifugation (2000 g, 15 minutes) before freezing; (B) one centrifugation before freezing and another after thawing (2000 g, 15 minutes for both); (C) one centrifugation before freezing(2000 g, 15 minutes) and another after thawing (2000 g, 10 minutes); (D) double centrifugation (2000 g, 15 minutes) before freezing (reference). Centrifugation conditions (A), (B), and (C) were compared with the reference condition (D). Acceptable relative differences were defined at 6%, 8%, and 10% for normalized lag time, endogenous thrombin potential, and peak height, respectively.ResultsCentrifugation conditions had a small but acceptable impact on HVs samples, but single centrifugation always resulted in unacceptable reductions in normalized lag times for DOAC samples. A second centrifugation after thawing permitted the recovery of acceptable differences for the three TGA parameters for edoxaban but not for apixaban, rivaroxaban, nor dabigatran.ConclusionDouble centrifugation before freezing should remain the recommended pre‐analytical condition before TGA.
Influenza virus infection selectively triggers the accumulation and persistence of more potent Helios‐expressing Foxp3+ regulatory T cells in the lungs
Authors: Lu Chunni , Chen Weisan 
Published: July 2021

AbstractFoxp3+ regulatory T cells (Tregs) represent a special lineage of CD4+ T cells. Analysis of Treg response during primary and secondary influenza virus infection clearly demonstrates a robust accumulation of Tregs into the infected lungs and the existence of a population of long‐lived antigen‐specific memory Tregs in the same tissues after resolution of the infection. However, it remains unknown whether these Tregs co‐express Helios, a member of the Ikaros transcription factor family. In this study, Foxp3+Helios+ and Foxp3+Helios‐ Tregs in the lungs, mLNs and spleens of influenza virus‐infected and uninfected control mice were tracked. The data show that while there is a co‐existence of Foxp3+Helios+ and Foxp3+Helios‐ Tregs in the tissues, the accumulated Tregs in the lungs and lung‐draining mediastinal lymph nodes (mLNs) of the infected mice are highly enriched for Foxp3+Helios+ cells. It was further demonstrated that, after the clearance of primary infection, Foxp3+Helios+ cells have the ability to persist in the tissues over their Helios‐ counterparts. More importantly, Foxp3+Helios+ Tregs accumulated in an accelerated kinetics during recall response to reinfection. In vitro analysis of Treg suppressive function revealed that Foxp3+Helios+ Tregs are more capable of suppressing influenza virus‐specific CD8+ T cell activation, cytokine production and proliferation. Together, the data provide new insights into Treg responses during primary and secondary influenza virus infection and suggest that Foxp3+Helios+ Tregs predominantly drive the Treg responses.
Symptom trajectories for palliative care inpatients with and without hyperactive delirium in the last week of life
Authors: Dai Yunyun , Walpole Grace , Ding Jinfeng , Scanlon Cian , Ho Luke , Khoo Ru Hui , Huang Chongmei , Cook Angus , William Leeroy , Johnson Claire E. 
Published: July 2021

AbstractAimsHyperactive delirium (HD) is a common and distressing symptom among palliative care patients. This study aimed to describe the characteristics of HD and associated symptoms among palliative care inpatients and evaluate relationships between HD development and symptom trajectories in this population.DesignA retrospective study was conducted.MethodsA retrospective review of medical records was conducted for all patients who died in a large Australian specialist palliative care unit between 1 January and 31 December 2019. Patients were assessed daily using the Symptoms Assessment Scale (SAS) and Palliative Care Problem Severity Scale (PCPSS). Multilevel models were used to estimate the differences in symptoms trajectories in the last 7 days of life between the two groups.ResultsOf the 501 included patients, 64.5% (323) had an episode of HD. For 30% (95) of patients, HD occurred prior to admission. Compared with patients without HD, those with HD had significantly higher odds ratios (ORs) for four of the seven SAS symptoms (sleep problems, appetite, fatigue and pain; OR range: 1.94–4.48, p < .05), and all four PCPSS items (OR range: 2.00–3.00, p < .05) in the last week of life.ConclusionsPalliative care inpatients commonly experience HD in their last week of life. There are higher levels of symptom distress, complexity, psychological concerns and family/carer concerns among patients with HD compared with those without HD.ImpactThe high prevalence of HD, and its association with higher levels of symptom distress, highlights the importance of routine screening and optimal management for HD among palliative care patients. Given the widely recognized challenges facing palliative care professionals in assessment and management of delirium, provision of relevant training among these professionals is recommended.
Procedural efficacy and safety of standardized, ablation index guided fixed 50 W high‐power short‐duration pulmonary vein isolation and substrate modification using the CLOSE protocol
Authors: Francke Alexander , Taha Nadja S. , Scharfe Frank , Schoen Steffen , Wunderlich Carsten , Christoph Marian 
Published: July 2021

AbstractIntroductionAblation index (AI)‐guided ablation according to the CLOSE protocol is very effective in terms of chronic pulmonary vein isolation (PVI). However, the optimal radiofrequency (RF) power remains controversial. Here, we thought to investigate the efficiency and safety of an AI‐guided fixed circumferential 50 W high‐power short‐duration (HPSD) PVI using the CLOSE protocol.Methods and ResultsIn a single‐center trial, 40 patients underwent randomized PVI using AI‐guided ablation without esophageal temperature monitoring. In 20 patients a CLOSE protocol guided fixed 50 W HPSD was followed irrespective of the anatomical localization. Twenty subjects were treated according to the CLOSE protocol with standard power settings (20 W posterior and 40 W roof and anterior wall). In addition, 80 consecutive patients were treated according to the HPSD protocol to gather additional safety data. All patients underwent postprocedural esophagogastroduodenoscopy to reveal esophageal lesions (EDELs). The mean total procedural time was 80.3 ± 22.5 in HPSD compared to control 109.1 ± 27.4 min (p < .001). The total RF‐time was significantly lower in HPSD with 1379 ± 505 s versus control 2374 ± 619 s (p < .001). There were no differences in periprocedural complications. EDEL occurred in 13% in the HPSD and 10% in the control group. EDEL occurring in the 50 W HSDP patients were smaller, more superficial, and had a faster healing tendency.ConclusionA fixed 50 W HPSD circumferential PVI relying on the AI and CLOSE protocol reduce the total procedure time and the total RF time, without increasing the complication rates. The incidence of EDELs was similar using 50 W at the posterior atrial wall.
Safety and efficacy of cell‐free and concentrated ascites reinfusion therapy against cirrhotic ascites in comparison with malignancy‐related ascites
Authors: Ito Tetsuya , Hanafusa Norio , Soneda Noriko , Isoai Ayako , Kobayashi Ryosuke , Torii Naoko , Kato Michio 
Published: July 2021

AbstractBackground and AimCell‐free and concentrated ascites reinfusion therapy (CART) has been performed against cirrhotic ascites, one of the most common complications seen in patients with decompensated cirrhosis. The aim of this study is to investigate its safety and efficacy, and differences in clinical profiles from CART against malignancy‐related ascites with different pathological background.MethodsThe present investigation involved a sub‐analysis of data obtained from a prospective observational study of CART performed at 22 centers. The condition of each procedure, therapeutic options, laboratory data, performance status, dietary intake, and abdominal circumference of participants were analyzed. Clinical parameters were compared between before and after CART, with or without albumin infusion, and also primary diseases including cirrhosis and malignant disease.ResultsBetween January 2014 and January 2015, a total of 48 and 275 CART procedures were performed in patients with cirrhosis and malignancies. In cirrhotic patients, serum albumin concentration increased significantly in groups both with and without concomitant albumin infusion (P = 0.002 and P = 0.023), and no significant difference in CART interval was seen between these groups (P = 0.393). CART interval was not significantly different between cirrhosis and malignancy groups (P = 0.334). Dietary intake significantly improved after CART in both groups (P = 0.043 and P < 0.001). Adverse events were with no clinical significance as observed in patients with malignancies.ConclusionsCell‐free and concentrated ascites reinfusion therapy was performed safely and effectively in patients with ascites related to decompensated cirrhosis and offers the potential efficacy to maintain plasma colloid osmotic pressure after paracentesis as well as in patients with malignancy.