bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of a child with primary ciliary dyskinesia
Authors: Kumar Aneeta , Walker Woolf T 
Published: February 2020

Abstract
Primary ciliary dyskinesia (PCD) is an autosomal recessive condition characterized by dysmotile cilia. Typically associated with defects in the cilia structure, it results in impaired mucociliary clearance of pathogens from the lungs and sinuses. Consequently, patients suffer from recurrent sinopulmonary and middle ear infections. We report on the management of a 5-year-old boy who presented with increased work of breathing, fever and crepitations, with an existing diagnosis of PCD with situs inversus totalis. Chest X-ray imaging revealed right lower lobe collapse. He was managed with intensive physiotherapy, nebulized mucolytic agents and antibiotics. However, due to a poor response, he underwent flexible bronchoscopy, which allowed removal of a mucus plug and subsequent re-expansion of his collapsed lobe. Although there is limited evidence for the management of PCD, here we discuss the accepted strategies for its management, based on expert opinion and guidelines for other suppurative lung diseases.
The Longitudinal Effects of Comorbid Health Burden on Functional Outcomes for Adults With Moderate to Severe Traumatic Brain Injury
Authors: Kumar Raj G. , Ketchum Jessica M. , Corrigan John D. , Hammond Flora M. , Sevigny Mitch , Dams-O'Connor Kristen 
Published: February 2020

Objective:
To evaluate the impact of physical, mental, and total health condition burden on functional outcome and life satisfaction up to 10 years after moderate to severe traumatic brain injury (TBI).

Setting:
Six TBI Model Systems centers.

Participants:
Three hundred ninety-three participants in the TBI Model Systems National Database.

Design:
Retrospective cohort study.

Main Measures:
Self-reported physical and mental health conditions at 10 years postinjury. Functional Independence Measure Motor and Cognitive subscales and the Satisfaction With Life Scale measured at 1, 2, 5, and 10 years.

Results:
In 10-year longitudinal individual growth curve models adjusted for covariates and inverse probability weighted to account for selection bias, greater physical and mental health comorbidity burden was negatively associated with functional cognition and life satisfaction trajectories. Physical, but not mental, comorbidity burden was negatively associated with functional motor trajectories. Higher total health burden was associated with poorer functional motor and cognitive trajectories and lower life satisfaction.

Conclusions:
This study offers evidence that comorbidity burden negatively impacts longitudinal functional and life satisfaction outcomes after TBI. The findings suggest that better identification and treatment of comorbidities may benefit life satisfaction, functional outcome, reduce healthcare costs, and decrease reinjury. Specific guidelines are needed for the management of comorbidities in TBI populations.
Visual Field Plots: A Comparison Study Between Standard Automated Perimetry and Eye Movement Perimetry
Authors: Mazumdar Deepmala , Pel Johan J.M. , Kadavath Meethal Najiya S. , Asokan Rashima , Panday Manish , Steen Johannes v.d. , George Ronnie 
Published: February 2020

Précis:
This eye movement perimetry (EMP) study describes the development of saccadic reaction time (SRT)-based visual field plots, which could effectively display the presence, location, and extent of glaucomatous defects and support clinical decision-making.

Purpose:
EMP is capable of discriminating normal from glaucomatous visual field defects on the basis of average delays in SRTs. To classify the presence and extent of age-corrected visual field defects, it is required to create SRT-based probability maps.

Aim:
The aim of this study was to create visual field probability plots based on SRTs and to evaluate their clinical applicability by 2 glaucoma specialists.

Materials and Methods:
The development phase included 95 controls segregated into 5 age-bins to estimate normative limits of SRT. Next, for the testing phase, a set of 28 healthy subjects and 24 glaucoma patients were recruited who underwent standard automated perimetry (SAP) and EMP visual field testing. Fifty-two SAP and EMP plots were presented to 2 glaucoma specialists to classify them as normal or abnormal and to identify the defect location and pattern as 1 or more of 7 predefined categories.

Results:
The glaucoma specialists showed a sensitivity of 100% and a specificity of 93% and 96% for identifying normal versus abnormal visual field. For specialists 1 and 2, 85% and 92%, respectively, of EMP reports were assigned to the same category as SAP. The reports that did not agree with SAP were graded to a higher defect pattern. The intermethod agreement for specialists 1 and 2 was κ 0.92 and 0.96, respectively.

Conclusion:
SRT-based visual field probability plots provided a comprehensive summary of an individual’s visual field status and showed comparable clinical applicability to that of SAP plots.
Podosomes in endothelial cell--microenvironment interactions
Authors: Alonso Florian , Spuul Pirjo , Génot Elisabeth 
Published: February 2020

Purpose of reviewThe discovery of podosomes in endothelial cells during the process of angiogenesisin vivoopens a new era in vascular biology. Podosomes are actin-based microdomains located at the plasma membrane that have been extensively described butin vitroand in other cells. This review focuses on podosomes in endothelial cells and aims to rise hypotheses about when and how these structures mediate cell--microenvironment interactions.Recent findingsA wealth of new information regarding podosome organization and functioning has been collected in simple 2D models. Characterization of their modular architecture has unravelled their mechanics. However, context matters and podosome characteristics and functioning are shaped by the microenvironment. Although matrix degradation was seen as the typical function of podosomes, mechanosensing now appears equally prominent and involved in setting of the proteolytic machinery. Endothelial podosomes breach the basement membrane, and are thus, involved in vascular remodelling.SummaryIn endothelial cells, podosomes are involved in breaking up the basement membrane, giving the cells the opportunity to invade adjacent tissues and to engage in new cell--cell interactions. Such functions are particularly relevant to vascular biology and the exploration of podosomes inin vivosettings should bring clues to many unanswered questions.
Are Pain and Fatigue in Multiple Myeloma Related to Psychosocial Factors?
Authors: Wilson Rogers Luke P. , Rennoldson Mike 
Published: February 2020

Background
Fatigue, pain, and psychological distress have been found to be among the most significant quality of life concerns for patients with multiple myeloma. Strong links between these variables have been found in other cancer populations.

Objective
The aim of this study was to systematically review the research literature on the associations between psychosocial factors and pain and/or fatigue in patients with multiple myeloma.

Interventions/Methods
The review followed PRISMA guidelines. A systematic search of 3 databases was conducted. Included studies were appraised for risk of bias. Data were extracted and combined in a narrative synthesis.

Results:
The review identified 11 studies for inclusion, reporting data from a total of 2432 participants. It found consistent evidence of a medium-sized relationship between both global distress and depression on the one hand and pain and fatigue on the other. The included studies were highly varied in the psychosocial factors they investigated.

Conclusions:
There is good evidence that pain and fatigue are related to global distress and depression in patients with multiple myeloma. The evidence on relationships with other psychosocial factors is inconclusive. Research investigating the role of more specific psychosocial processes is called for.

Implications for Practice:
Assessment of pain and fatigue in patients with multiple myeloma should routinely include screening for psychological distress. Interventions for psychological distress may be considered as adjuvant intervention strategies for pain and fatigue in patients with multiple myeloma.
Tau Imaging in the 4-Repeat-Tauopathies Progressive Supranuclear Palsy and Corticobasal Syndrome
Authors: Schröter Nils , Blazhenets Ganna , Frings Lars , Barkhausen Christoph , Jost Wolfgang H. , Weiller Cornelius , Rijntjes Michel , Meyer Philipp T. 
Published: February 2020

Background and Objectives
To evaluate tau PET using 11C-pyridinyl-butadienyl-benzothiazole 3 (11C-PBB3) in the 4-repeat (4R)-tauopathies progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS).

Methods
Retrospective analysis of 11C-PBB3 PET in 2, 7, and 2 patients with CBS, PSP, and Alzheimer dementia (AD), respectively. Normalized 11C-PBB3 uptake in clusters with significant hypometabolism on 18F-FDG-PET and corresponding atlas-based volumes of interest was compared between diagnostic groups.

Results
In accordance with visually appreciable group differences, 11C-PBB3 uptake was significantly higher in dorsolateral frontal and motor cortex in CBS patients and frontal and temporal cortices in AD patients as compared with PSP patients. Patients with PSP showed mildly but significantly higher uptake in midbrain compared with AD patients.

Conclusions
In line with known neuropathological changes, the spatial pattern and magnitude of 11C-PBB3 tau binding differ between CBS, PSP, and AD, which may be of diagnostic utility. Thus, 11C-PBB3 offers a promising lead structure for development of ligands for tau imaging, including 4R-tauopathies.
Case Report 18F-FDG PET/CT of Pseudomyogenic Hemangioendothelioma
Authors: Plouznikoff Nicolas , Mourad Stephanie A. , Turpin Sophie , Turcotte Robert E. , Mitchell David A. , Lambert Raymond 
Published: February 2020

Abstract
Hemangioendotheliomas are a heterogeneous group of vascular neoplasm that may affect the liver, bone, and soft tissues. Among its variants, pseudomyogenic hemangioendothelioma is rarely encountered. Pseudomyogenic hemangioendothelioma is usually characterized by multiple soft tissue lesions, with occasional bone lesions. Fewer than 20 cases with exclusive involvement of bone structures have been reported. We describe a case of pseudomyogenic hemangioendothelioma involving multiple bony structures but without soft tissue involvement in a 7-year-old girl, imaged with 18F-FDG PET/CT at diagnosis and during treatment with mammalian target of rapamycin inhibitors.
Toxic stress-specific cytoprotective responses regulate learned behavioral decisions inC. elegans
Authors: Hajdú Gábor , Gecse Eszter , Taisz István , Móra István , Sőti Csaba 
Published: February 2020

AbstractBackgroundProtection of organismal integrity involve physiological stress responses and behavioral defenses. Recent studies in the roundwormCaenorhabditis eleganshave shown that pathogen and toxin exposure simultaneously stimulate cellular stress and detoxification responses and aversive behavior. However, whether a coordinate regulation exists between cellular and neurobehavioral defenses remains unclear.ResultsHere we show that exposure ofC. elegansto high concentrations of naturally attractive food-derived odors, benzaldehyde and diacetyl, induces toxicity and aversive behavior. Benzaldehyde preconditioning activates systemic cytoprotective stress responses involving DAF-16/FOXO, SKN-1/Nrf and Hsp90 in somatic cells, which confer behavioral tolerance to benzaldehyde and cross-tolerance to the structurally similar methyl-salicylate, but not to the structurally unrelated diacetyl. In contrast, diacetyl preconditioning augments diacetyl avoidance and does not induce apparent molecular defenses. Reinforcement of the experiences using massed training forms relevant associative memories. Memory retrieval by the odor olfactory cues leads to avoidance of food contaminated by diacetyl and context-dependent behavioral decision to avoid benzaldehyde only if there is an alternative, food-indicative odor.ConclusionsOur findings reveal a regulatory link between physiological stress responses and learned behavior which facilitates self-protection in real and anticipated stresses. The potential conservation of this somato-neuronal connection might have relevance in maladaptive avoidant human behaviors.
Interferon-induced Protein-44 and Interferon-induced Protein 44-like restrict replication of Respiratory Syncytial Virus
Authors: Busse D. C. , Habgood-Coote D. , Clare S. , Brandt C. , Bassano I. , Kaforou M. , Herberg J. , Levin M. , Eleouet Jean-Francois , Kellam P. , Tregoning J. S. 
Published: February 2020

AbstractCellular intrinsic immunity, mediated by the expression of an array of interferon-stimulated antiviral genes, is a vital part of host defence. We have previously used a bioinformatic screen to identify two interferon stimulated genes (ISG) with poorly characterised function, Interferon-induced protein 44 (IFI44) and interferon-induced protein 44-like (IFI44L), as potentially being important in Respiratory Syncytial Virus (RSV) infection. Using overexpression systems, CRISPR-Cas9-mediated knockout, and a knockout mouse model we investigated the antiviral capability of these genes in the control of RSV replication. Over-expression of IFI44 or IFI44L was sufficient to restrict RSV infection at an early time post infection. Knocking out these genes in mammalian airway epithelial cells increased levels of infection. Both genes express antiproliferative factors that have no effect on RSV attachment but reduce RSV replication in a minigenome assay. The loss ofIfi44was associated with a more severe infection phenotypein vivo. These studies demonstrate a function for IFI44 and IFI44L in controlling RSV infection.ImportanceRSV infects all children under two years of age, but only a subset of children get severe disease. We hypothesize that susceptibility to severe RSV necessitating hospitalization in children without pre-defined risk factors is in part mediated at the anti-viral gene level. But there is a large array of anti-viral genes, particularly in the ISG family about which the mechanism is poorly understood. Having observed significantly lower levels of IFI44 and IFI44L gene expression in hospitalized children with a confirmed diagnosis of RSV, we dissected the function of these two genes. Through a range of over-expression and knockout studies we show that the genes are anti-viral and anti-proliferative. This study is important because IFI44 and IFI44L are upregulated after a wide range of viral infections and IFI44L can serve as a diagnostic bio-marker of viral infection.
An Effective CTL Peptide Vaccine for Ebola Zaire Based on Survivors’ CD8+ Targeting of a Particular Nucleocapsid Protein Epitope with Potential Implications for COVID-19 Vaccine Design
Authors: Herst CV , Burkholz S , Sidney J , Sette A , Harris PE , Massey S , Brasel T , Cunha-Neto E , Rosa DS , Chao WCH , Carback R , Hodge T , Wang L , Ciotlos S , Lloyd P , Rubsamen R 
Published: February 2020

AbstractThe 2013-2016 West Africa EBOV epidemic was the biggest EBOV outbreak to date. An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. The dominant response (25/26 subjects) was specific to the EBOV nucleocapsid protein (NP). It has been suggested that epitopes on the EBOV NP could form an important part of an effective T-cell vaccine for Ebola Zaire. We show that a 9-amino-acid peptide NP44-52 (YQVNNLEEI) located in a conserved region of EBOV NP provides protection against morbidity and mortality after mouse adapted EBOV challenge. A single vaccination in a C57BL/6 mouse using an adjuvanted microsphere peptide vaccine formulation containing NP44-52 is enough to confer immunity in mice. Our work suggests that a peptide vaccine based on CD8+ T-cell immunity in EBOV survivors is conceptually sound and feasible. Nucleocapsid proteins within SARS-CoV-2 contain multiple class I epitopes with predicted HLA restrictions consistent with broad population coverage. A similar approach to a CTL vaccine design may be possible for that virus.
Epitope-based peptide vaccine design and target site characterization against novel coronavirus disease caused by SARS-CoV-2
Authors: Li Lin , Sun Ting , He Yufei , Li Wendong , Fan Yubo , Zhang Jing 
Published: February 2020

AbstractThe outbreak of the 2019 novel coronavirus (SARS-CoV-2) has infected thousands of people with a large number of deaths across 26 countries. The sudden appearance of the virus leads to the limited existing therapies for SARS-CoV-2. Therefore, vaccines and antiviral medicines are in desperate need. This study took immune-informatics approaches to identify B- and T-cell epitopes for surface glycoprotein (S) of SARS-CoV-2, followed by estimating their antigenicity and interactions with the human leukocyte antigen (HLA) alleles. We identified four B cell epitopes, two MHC class-I and nine MHC class-II binding T-cell epitopes, which showed highly antigenic features. Allergenicity, toxicity and physiochemical properties analysis confirmed the specificity and selectivity of epitopes. The stability and safety of epitopes were confirmed by digestion analysis. No mutations were observed in all the selected B- and T-cell epitopes across all isolates from different locations worldwide. Epitopes were thus identified and some of them can be potential candidates for vaccine development.
Genome editing human primary T cells with microfluidic vortex shedding & CRISPR Cas9
Authors: Jarrell Justin A. , Sytsma Brandon J. , Wilson Leah H. , Pan Fong L. , Lau Katherine H.W.J. , Kirby Giles T. S. , Lievano Adrian A. , Pawell Ryan S. 
Published: February 2020

AbstractMicrofluidic vortex shedding (μVS) can rapidly deliver mRNA to T cells with high yield. The mechanistic underpinning ofμVSintracellular delivery remains undefined andμVS-Cas9 genome editing requires further studies. Herein, we evaluated a series ofμVSdevices containing splitter plates to attenuate vortex shedding and understand the contribution of computed force and frequency on efficiency and viability. We then selected aμVSdesign to knockout the expression of the endogenous T cell receptor in primary human T cells via delivery of CRISPR-Cas9 ribonucleoprotein (RNP) with and without brief exposure to an electric field (eμVS).μVSalone resulted in an equivalent yield of genome-edited T cells relative to electroporation with improved cell quality. A 1.8-fold increase in editing efficiency was demonstrated witheμVSwith negligible impact on cell viability. Cumulatively, these results demonstrate the utility ofμVSandeμVSfor genome editing human primary T cells with Cas9 RNPs.
Using karyotyping and achene morphology to accurately identifySonchus oleraceus(Asteraceae) in the context of its biological control
Authors: Ollivier M. , Gauthier P. , Lesieur V. , Thomann T. , Jourdan M. , Bon M. C. , Sheppard A. , Raghu S. , Tixier M. S. , Martin J.-F. 
Published: February 2020

AbstractIn weed biocontrol, accurate identification of the target weed is essential to select effective and host-specific biocontrol agents. This study focuses on the biocontrol of an invasive weed species in Australia, native from Europe, the common sowthistle,Sonchus oleraceusL. (Asteraceae). During field surveys, the distinction betweenS. oleraceusand a morphologically related species (S. asperL.) was difficult because of specimens bearing intermediate morphological features. These observations raised questions about the reliability the morphological characters used for distinguishing between these species and the identity of the intermediate phenotypes. First, cytological analyses coupled with morphological comparisons were carried out on specimens collected in Europe and Australia. Results showed that specimens morphologically described asS. oleraceusandS. asperpossessed, in accordance with literature 32 and 18 chromosomes, respectively. Specimens with intermediate morphotypes had 32 chromosomes, showing that they belong toS. oleraceusspecies. The variability of characters used for diagnosis is discussed and for a particular feature, achene ornamentation, an inquiry among 30 people was carried out to determine how this character might be relevant for distinguishing the two species herein considered. The successful identification rate was 92.2% (SE ± 0.77) showing the practical interest of this feature for diagnosis.
Single cell transcriptomics reveals lineage trajectory of the retinal ganglion cells in wild-type andAtoh7-null retinas
Authors: Wu Fuguo , Bard Jonathan E. , Kann Julien , Yergeau Donald , Sapkota Darshan , Ge Yichen , Hu Zihua , Wang Jie , Liu Tao , Mu Xiuqian 
Published: February 2020

AbstractPast studies concluded that Atoh7 is critical for the emergence of the retinal ganglion cell (RGC) lineage in the developing retina, whereas Pou4f2 and Isl1 function in RGC differentiation. Atoh7 is expressed in a subset of retinal progenitor cells (RPCs) and is considered a competence factor for the RGC fate, but the molecular properties of these RPCs have not been well characterized. In this study, we first used conventional RNA-seq to investigate transcriptomic changes inAtoh7-,Pou4f2-, andIsl1-null retinas at embryonic (E) day 14.5 and identified the differentially expressed genes (DEGs), which expanded our understanding of the scope of downstream events. We then performed single cell RNA-seq (scRNA-seq) on E13.5 and E17.5 wild-type andAtoh7-null retinal cells. Clustering analysis not only correctly identified known cell types at these developmental stages but also revealed a transitional cell state which was marked byAtoh7and genes for other lineages in a highly overlapping fashion and shared by all early developmental trajectories. Further, analysis of theAtoh7-null retina revealed that, unlike previously believed, the RGC lineage still progressed considerably and a substantial amount of RGC-specific gene expression still occurred. Thus, Atoh7 likely collaborates with other factors to shepherd the transitional RPCs to the RGC lineage by competing with other lineage factors and activating RGC-specific genes. This study thus provides significant insights into the nature of RPC competence for different retinal cell fates and revises our current view on the emergence of the RGC lineage.