bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human platelet lysate biotherapy for traumatic brain injury: preclinical assessment
Authors: Nebie Ouada , Carvalho Kevin , Barro Lassina , Delila Liling , Faivre Emilie , Renn Ting-Yi , Chou Ming-Li , Wu Yu-Wen , Nyam-Erdene Ariunjargal , Chou Szu-Yi , Buée Luc , Hu Chaur-Jong , Peng Chih-Wei , Devos David , Blum David , Burnouf Thierry 
Published: May 2021

Abstract
Traumatic brain injury (TBI) leads to major brain anatomopathological damages underlined by neuroinflammation, oxidative stress and progressive neurodegeneration, ultimately leading to motor and cognitive deterioration. The multiple pathological events resulting from TBI can be addressed not by a single therapeutic approach, but rather by a synergistic biotherapy capable of activating a complementary set of signalling pathways and providing synergistic neuroprotective, anti-inflammatory, antioxidative, and neurorestorative activities. Human platelet lysate might fulfil these requirements as it is composed of a plethora of biomolecules readily accessible as a TBI biotherapy.
In the present study, we tested the therapeutic potential of human platelet lysate using in vitro and in vivo models of TBI. We first prepared and characterized platelet lysate from clinical-grade human platelet concentrates. Platelets were pelletized, lysed by three freeze-thaw cycles, and centrifuged. The supernatant was purified by 56°C 30 min heat treatment and spun to obtain the heat-treated platelet pellet lysate that was characterized by ELISA and proteomic analyses. Two mouse models were used to investigate platelet lysate neuroprotective potential. The injury was induced by an in-house manual controlled scratching of the animals’ cortex or by controlled cortical impact injury. The platelet lysate treatment was performed by topical application of 60 µl in the lesioned area, followed by daily 60 µl intranasal administration from Day 1 to 6 post-injury.
Platelet lysate proteomics identified over 1000 proteins including growth factors, neurotrophins, and antioxidants. ELISA detected several neurotrophic and angiogenic factors at ∼1–50 ng/ml levels. We demonstrate, using two mouse models of TBI, that topical application and intranasal platelet lysate consistently improved mouse motor function in the beam and rotarod tests, mitigated cortical neuroinflammation, and oxidative stress in the injury area, as revealed by downregulation of pro-inflammatory genes and the reduction in reactive oxygen species levels. Moreover, platelet lysate treatment reduced the loss of cortical synaptic proteins. Unbiased proteomic analyses revealed that heat-treated platelet pellet lysate reversed several pathways promoted by both controlled cortical impact and cortical brain scratch and related to transport, postsynaptic density, mitochondria or lipid metabolism.
The present data strongly support, for the first time, that human platelet lysate is a reliable and effective therapeutic source of neurorestorative factors. Therefore, brain administration of platelet lysate is a therapeutical strategy that deserves serious and urgent consideration for universal brain trauma treatment.
Common molecular mechanisms ofSLC6A1variant-mediated neurodevelopmental disorders in astrocytes and neurons
Authors: Mermer Felicia , Poliquin Sarah , Rigsby Kathryn , Rastogi Anuj , Shen Wangzhen , Romero-Morales Alejandra , Nwosu Gerald , McGrath Patrick , Demerast Scott , Aoto Jason , Bilousova Ganna , Lal Dennis , Gama Vivian , Kang Jing-Qiong 
Published: May 2021

AbstractSolute carrier family 6 member 1 (SLC6A1) is abundantly expressed in the developing brain even before the CNS is formed. Its encoded GABA transporter 1 (GAT-1) is responsible for the reuptake of GABA into presynaptic neurons and glia, thereby modulating neurotransmission. GAT-1 is expressed globally in the brain, in both astrocytes and neurons. The GABA uptake function of GAT-1 in neurons cannot be compensated for by other GABA transporters, while the function in glia can be partially replaced by GABA transporter 3. Recently, many variants in SLC6A1 have been associated with a spectrum of epilepsy syndromes and neurodevelopmental disorders, including myoclonic atonic epilepsy, childhood absence epilepsy, autism, and intellectual disability, but the pathomechanisms associated with these phenotypes remain unclear. The presence of GAT-1 in both neurons and astrocytes further obscures the role of abnormal GAT-1 in the heterogeneous disease phenotype manifestations. Here we examine the impact on transporter trafficking and function of 22 SLC6A1 variants identified in patients with a broad spectrum of phenotypes. We also evaluate changes in protein expression and subcellular localization of the variant GAT-1 in various cell types, including neurons and astrocytes derived from human patient induced pluripotent stem cells. We found that a partial or complete loss-of-function represents a common disease mechanism, although the extent of GABA uptake reduction is variable. The reduced GABA uptake appears to be due to reduced cell surface expression of the variant transporter caused by variant protein misfolding, endoplasmic reticulum retention, and subsequent degradation. Although the extent of reduction of the total protein, surface protein, and the GABA uptake level of the variant transporters is variable, the loss of GABA uptake function and endoplasmic reticulum retention is consistent across induced pluripotent stem cell-derived cell types, including astrocytes and neurons, for the surveyed variants. Interestingly, we did not find a clear correlation of GABA uptake function and the disease phenotypes, such as myoclonic atonic epilepsy versus developmental delay, in this study. Together, our study suggests that impaired transporter protein trafficking and surface expression are the major disease-associated mechanisms associated with pathogenic SLC6A1 variants. Our results resemble findings from pathogenic variants in other genes affecting the GABA pathway, such as GABAA receptors. This study provides critical insight into therapeutic developments for SLC6A1 variant-mediated disorders and implicates that boosting transporter function by either genetic or pharmacological approaches would be beneficial.
Expression of IGF-2 Receptor in the Auditory Cortex Improves the Precision of Recent Fear Memories and Maintains Detailed Remote Fear Memories Over Time
Authors: Concina Giulia , Renna Annamaria , Milano Luisella , Manassero Eugenio , Stabile Francesca , Sacchetti Benedetto 
Published: May 2021

Abstract
Traumatic memories may become less precise over time and lead to the development of fear responses to novel stimuli, a process referred to as time-dependent fear generalization. The conditions that cause the growth of fear generalization over time are poorly understood. Here, we found that, in male rats, the level of discrimination at the early time point contributes to determining whether fear generalization will develop with the passage of time or not, suggesting a link between the precision of recent memory and the stability of remote engrams. We also found that the expression of insulin-like growth factor 2 receptor in layer 2/3 of the auditory cortex is linked to the precision of recent memories and to the stability of remote engrams and the development of fear generalization over time. These findings provide new insights on the neural mechanisms that underlie the time-dependent development of fear generalization that may occur over time after a traumatic event.
Gut Resistome of Preschool Children After Prolonged Mass Azithromycin Distribution: A Cluster-randomized Trial
Authors: Arzika Ahmed M , Maliki Ramatou , Abdou Amza , Mankara Alio K , Harouna Abdoul N , Cook Catherine , Hinterwirth Armin , Worden Lee , Zhong Lina , Chen Cindi , Ruder Kevin , Zhou Zhaoxia , Lebas Elodie , O’Brien Kieran S , Oldenburg Catherine E , Le Victoria , Arnold Benjamin F , Porco Travis C , Keenan Jeremy D , Lietman Thomas M , Doan Thuy 
Published: May 2021

Abstract

We evaluated the gut resistome of children from communities treated with 10 twice-yearly azithromycin distributions. Although the macrolide resistance remained higher in the azithromycin arm, the selection of non-macrolide resistance observed at earlier time points did not persist. Longitudinal resistance monitoring should be a critical component of mass distribution programs.

Clinical trials registration
NCT02047981
The distance backbone of complex networks
Authors: Simas Tiago , Correia Rion Brattig , Rocha Luis M 
Published: May 2021

AbstractRedundancy needs more precise characterization as it is a major factor in the evolution and robustness of networks of multivariate interactions. We investigate the complexity of such interactions by inferring a connection transitivity that includes all possible measures of path length for weighted graphs. The result, without breaking the graph into smaller components, is a distance backbone subgraph sufficient to compute all shortest paths. This is important for understanding the dynamics of spread and communication phenomena in real-world networks. The general methodology we formally derive yields a principled graph reduction technique and provides a finer characterization of the triangular geometry of all edges—those that contribute to shortest paths and those that do not but are involved in other network phenomena. We demonstrate that the distance backbone is very small in large networks across domains ranging from air traffic to the human brain connectome, revealing that network robustness to attacks and failures seems to stem from surprisingly vast amounts of redundancy.
Effects of elevated temperature andpCO2 on the respiration, biomineralization and photophysiology of the giant clamTridacna maxima
Authors: Brahmi Chloé , Chapron Leila , Le Moullac Gilles , Soyez Claude , Beliaeff Benoît , Lazareth Claire E , Gaertner-Mazouni Nabila , Vidal-Dupiol Jeremie 
Published: May 2021

AbstractMany reef organisms, such as the giant clams, are confronted with global change effects. Abnormally high seawater temperatures can lead to mass bleaching events and subsequent mortality, while ocean acidification may impact biomineralization processes. Despite its strong ecological and socio-economic importance, its responses to these threats still need to be explored. We investigated physiological responses of 4-year-old Tridacna maxima to realistic levels of temperature (+1.5°C) and partial pressure of carbon dioxide (pCO2) (+800 μatm of CO2) predicted for 2100 in French Polynesian lagoons during the warmer season. During a 65-day crossed-factorial experiment, individuals were exposed to two temperatures (29.2°C, 30.7°C) and two pCO2 (430 μatm, 1212 μatm) conditions. The impact of each environmental parameter and their potential synergetic effect were evaluated based on respiration, biomineralization and photophysiology. Kinetics of thermal and/or acidification stress were evaluated by performing measurements at different times of exposure (29, 41, 53, 65 days). At 30.7°C, the holobiont O2 production, symbiont photosynthetic yield and density were negatively impacted. High pCO2 had a significant negative effect on shell growth rate, symbiont photosynthetic yield and density. No significant differences of the shell microstructure were observed between control and experimental conditions in the first 29 days; however, modifications (i.e. less-cohesive lamellae) appeared from 41 days in all temperature and pCO2 conditions. No significant synergetic effect was found. Present thermal conditions (29.2°C) appeared to be sufficiently stressful to induce a host acclimatization response. All these observations indicate that temperature and pCO2 are both forcing variables affecting T. maxima’s physiology and jeopardize its survival under environmental conditions predicted for the end of this century.
Treatment of atrial fibrillation with doxapram: TASK-1 potassium channel inhibition as a novel pharmacological strategy
Authors: Wiedmann Felix , Beyersdorf Christoph , Zhou Xiao Bo , Kraft Manuel , Paasche Amelie , Jávorszky Natasa , Rinné Susanne , Sutanto Henry , Büscher Antonius , Foerster Kathrin I , Blank Antje , El-Battrawy Ibrahim , Li Xin , Lang Siegfried , Tochtermann Ursula , Kremer Jamila , Arif Rawa , Karck Matthias , Decher Niels , van Loon Gunther , Akin Ibrahim , Borggrefe Martin , Kallenberger Stefan , Heijman Jordi , Haefeli Walter E , Katus Hugo A , Schmidt Constanze 
Published: May 2021

Abstract

Aims
TASK-1 (K2P3.1) two-pore-domain potassium channels are atrial-specific and significantly up-regulated in atrial fibrillation (AF) patients, contributing to AF-related electrical remodelling. Inhibition of TASK-1 in cardiomyocytes of AF patients was shown to counteract AF-related action potential duration shortening. Doxapram was identified as a potent inhibitor of the TASK-1 channel. In this study, we investigated the antiarrhythmic efficacy of doxapram in a porcine model of AF.

Methods and results
Doxapram successfully cardioverted pigs with artificially induced episodes of AF. We established a porcine model of persistent AF in domestic pigs via intermittent atrial burst stimulation using implanted pacemakers. All pigs underwent catheter-based electrophysiological investigations prior to and after 14 days of doxapram treatment. Pigs in the treatment group received intravenous administration of doxapram once per day. In doxapram-treated AF pigs, the AF burden was significantly reduced. After 14 days of treatment with doxapram, TASK-1 currents were still similar to values of sinus rhythm animals. Doxapram significantly suppressed AF episodes and normalized cellular electrophysiology by inhibition of the TASK-1 channel. Patch-clamp experiments on human atrial cardiomyocytes, isolated from patients with and without AF could reproduce the TASK-1 inhibitory effect of doxapram.

Conclusion
Repurposing doxapram might yield a promising new antiarrhythmic drug to treat AF in patients.
Prediction of right heart failure after left ventricular assist implantation: external validation of the EUROMACS right-sided heart failure risk score
Authors: Rivas-Lasarte Mercedes , Kumar Salil , Derbala Mohamed H , Ferrall Joel , Cefalu Matthew , Rashid Syed Muhammad Ibrahim , Joseph Denny T , Goldstein Daniel J , Jorde Ulrich P , Guha Ashrith , Bhimaraj Arvind , Suarez Erik E , Smith Sakima A , Sims Daniel B 
Published: May 2021

Abstract

Aims
Prediction of right heart failure (RHF) after left ventricular assist device (LVAD) implant remains a challenge. The EUROMACS right-sided heart failure (EUROMACS-RHF) risk score was proposed as a prediction tool for post-LVAD RHF but lacks from large external validation. The aim of our study was to externally validate the score.

Methods and results
From January 2007 to December 2017, 878 continuous-flow LVADs were implanted at three tertiary centres. We calculated the EUROMACS-RHF score in 662 patients with complete data. We evaluated its predictive performance for early RHF defined as either (i) need for short- or long-term right-sided circulatory support, (ii) continuous inotropic support for ≥14 days, or (iii) nitric oxide for ≥48 h post-operatively. Right heart failure occurred in 211 patients (32%). When compared with non-RHF patients, pre-operatively they had higher creatinine, bilirubin, right atrial pressure, and lower INTERMACS class (P &lt; 0.05); length of stay and in-hospital mortality were higher. Area under the ROC curve for RHF prediction of the EUROMACS-RHF score was 0.64 [95% confidence interval (CI) 0.60–0.68]. Reclassification of patients with RHF was significantly better when applying the EUROMACS-RHF risk score on top of previous published scores. Patients in the high-risk category had significantly higher in-hospital and 2-year mortality [hazard ratio: 1.64 (95% CI 1.16–2.32) P = 0.005].

Conclusion
In an external cohort, the EUROMACS-RHF had limited discrimination predicting RHF. The clinical utility of this score remains to be determined.
Left atrial appendage perforation during appendage angiography treated by percutaneous left atrial appendage closure: a case report
Authors: Champagne Catherine , Dognin Nicolas , Rodés-Cabau Josep , Champagne Jean 
Published: May 2021

Abstract

Background
Pericardial effusion is a common complication of percutaneous left atrial appendage (LAA) closure. Acute management is the cornerstone of pericardial effusion treatment and interrupting the intervention is often required.

Case summary
A 65-year-old man presented an acute 10 mm pericardial effusion following pigtail contrast appendage injection. A rapid Watchman Flex 24 mm (Boston Scientific) deployment permitted bleeding interruption. A needle pericardiocentesis was achieved in order to prevent any haemodynamical instability.

Discussion
This case report describes an atypical cause of pericardial effusion and a technique for bleeding control with LAA closure device deployment.
Epidemiology of cardiac implantable electronic device infections: incidence and risk factors
Authors: Han Hui-Chen , Hawkins Nathaniel M , Pearman Charles M , Birnie David H , Krahn Andrew D 
Published: May 2021

AbstractCardiac implantable electronic device (CIED) infection is a potentially devastating complication of CIED procedures, causing significant morbidity and mortality for patients. Of all CIED complications, infection has the greatest impact on mortality, requirement for re-intervention and additional hospital treatment days. Based on large prospective studies, the infection rate at 12-months after a CIED procedure is approximately 1%. The risk of CIED infection may be related to several factors which should be considered with regards to risk minimization. These include technical factors, patient factors, and periprocedural factors. Technical factors include the number of leads and size of generator, the absolute number of interventions which have been performed for the patient, and the operative approach. Patient factors include various non-modifiable underlying comorbidities and potentially modifiable transient conditions. Procedural factors include both peri-operative and post-operative factors. The contemporary PADIT score, derived from a large cohort of CIED patients, is useful for the prediction of infection risk. In this review, we summarize the key information regarding epidemiology, incidence and risk factors for CIED infection.
Chromosome-scale assembly of the Sparassis latifolia genome obtained using long-read and Hi-C sequencing
Authors: Yang Chi , Ma Lu , Xiao Donglai , Liu Xiaoyu , Jiang Xiaoling , Ying Zhenghe , Lin Yanquan 
Published: May 2021

Abstract
Sparassis latifolia is a valuable edible mushroom cultivated in China. In 2018, our research group reported an incomplete and low-quality genome of S. latifolia obtained by Illumina HiSeq 2500 sequencing. These limitations in the available genome have constrained genetic and genomic studies in this mushroom resource. Herein, an updated draft genome sequence of S. latifolia was generated by Oxford Nanopore sequencing and the high-through chromosome conformation capture (Hi-C) technique. A total of 8.24 Gb of Oxford Nanopore long reads representing ∼198.08X coverage of the S. latifolia genome were generated. Subsequently, a high-quality genome of 41.41 Mb, with scaffold and contig N50 sizes of 3.31 and 1.51 Mb, respectively, was assembled. Hi-C scaffolding of the genome resulted in 12 pseudochromosomes containing 93.56% of the bases in the assembled genome. Genome annotation further revealed that 17.47% of the genome was composed of repetitive sequences. In addition, 13,103 protein-coding genes were predicted, among which 98.72% were functionally annotated. BUSCO assay results further revealed that there were 92.07% complete BUSCOs. The improved chromosome-scale assembly and genome features described here will aid further molecular elucidation of various traits, breeding of S. latifolia, and evolutionary studies with related taxa.
Comparative Population Genetics in the Human Gut Microbiome
Authors: Shoemaker William R , Chen Daisy , Garud Nandita R 
Published: May 2021

Abstract
Genetic variation in the human gut microbiome is responsible for conferring a number of crucial phenotypes like the ability to digest food and metabolize drugs. Yet, our understanding of how this variation arises and is maintained remains relatively poor. Thus, the microbiome remains a largely untapped resource, as the large number of coexisting species in the microbiome presents a unique opportunity to compare and contrast evolutionary processes across species to identify universal trends and deviations. Here we outline features of the human gut microbiome that, while not unique in isolation, as an assemblage make it a system with unparalleled potential for comparative population genomics studies. We consciously take a broad view of comparative population genetics, emphasizing how sampling a large number of species allows researchers to identify universal evolutionary dynamics in addition to new genes, which can then be leveraged to identify exceptional species that deviate from general patterns. To highlight the potential power of comparative population genetics in the microbiome, we reanalyze patterns of purifying selection across ∼40 prevalent species in the human gut microbiome to identify intriguing trends which highlight functional categories in the microbiome that may be under more or less constraint.
Sociohistorical Change in Urban Older Adults’ Perceived Speed of Time and Time Pressure
Authors: Löckenhoff Corinna E , Drewelies Johanna , Duezel Sandra , Steinhagen-Thiessen Elisabeth , Demuth Ilja , Freund Alexandra M , Staudinger Ursula M , Lindenberger Ulman , Wagner Gert G , Ram Nilam , Gerstorf Denis 
Published: May 2021

Abstract

Objectives
Perceptions of time are shaped by sociohistorical factors. Specifically, economic growth and modernization often engender a sense of acceleration. Research has primarily focused on one time perception dimension (perceived time pressure) in one subpopulation (working-age adults), but it is not clear whether historical changes extend to other dimensions (e.g., perceived speed of time) and other subpopulations, such as older adults who are no longer in the workforce and experience age-related shifts in time perception. We therefore examined sociohistorical and age-related trends in two dimensions of time perception in two cohorts of urban older adults.

Method
Using propensity score matching for age and education, samples were drawn from the Berlin Aging Study (1990–1993, n = 256, Mage = 77.49) and the Berlin Aging Study-II (2009–2014, n = 248, Mage = 77.49). Cohort differences in means, variances, covariance, and correlates of perceived speed of time and time pressure were examined using multigroup SEM.

Results
There were no cohort differences in the perceived speed of time, but later-born cohorts reported more time pressure than earlier-born cohorts. There were no significant age differences, but perceptions of speed of time were more heterogeneous in the 1990s than in the 2010s. Cohorts did not differ in how time perceptions were associated with sociodemographic, health, cognitive, and psychosocial correlates.

Discussion
These findings document sociohistorical trends toward greater perceived time pressure and reduced heterogeneity in perceived speed of time among later-born urban adults. Conceptualizations of social acceleration should thus consider the whole adult life span.