bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urgent considerations for the neuro-oncologic treatment of patients with gliomas during the COVID-19 pandemic
Authors: Mohile Nimish A , Blakeley Jaishri O , Gatson Na Tosha N , Hottinger Andreas F , Lassman Andrew B , Ney Douglas E , Olar Adriana , Schiff David , Shih Helen A , Strowd Roy , van den Bent Martin J , Ziu Mateo 
Published: April 2020

Abstract
The COVID-19 outbreak is posing unprecedented risks and challenges for all communities and health care systems, worldwide. There are unique considerations for many adult patients with gliomas who are vulnerable to the novel coronavirus due to older age and immunosuppression. As patients with terminal illnesses, they present ethical challenges for centers that may need to ration access to ventilator care due to insufficient critical care capacity. It is urgent for the neuro-oncology community to develop a proactive and coordinated approach to the care of adults with gliomas in order to provide them with the best possible oncologic care while also reducing their risk of viral infection during times of potential health care system failure. In this article, we present an approach developed by an international multidisciplinary group to optimize the care of adults with gliomas during this pandemic. We recommend measures to promote strict physical distancing and minimize exposures for patients, address risk and benefit of all therapeutic interventions, proactively develop end-of-life plans, educate patients and caregivers, and ensure the health of the multidisciplinary neuro-oncology workforce. This pandemic is already changing neuro-oncologic care delivery around the globe. It is important to highlight opportunities to maximize the benefit and minimize the risk of glioma management during this pandemic and potentially, in the future.
Community transmission of rotavirus infection in a vaccinated population in Malawi: a prospective household cohort study
Authors: Bennett Aisleen , Pollock Louisa , Bar-Zeev Naor , Lewnard Joseph A. , Jere Khuzwayo C. , Lopman Benjamin , Iturriza-Gomara Miren , Pitzer Virginia E. , Cunliffe Nigel A. 
Published: April 2020

AbstractBackgroundRotavirus vaccine effectiveness (VE) is reduced among children in low-income countries (LICs). Indirect (transmission-mediated) effects of rotavirus vaccine may contribute to the total population impact of vaccination. We estimated the effectiveness of rotavirus vaccine in preventing transmission of rotavirus to household contacts in Blantyre, Malawi.MethodsWe recruited vaccine-age-eligible children with acute rotavirus gastroenteritis (case-children), together with their household contacts. Clinical data and stool samples were collected from case-children at presentation, and prospectively from household contacts over 14 days. A single stool sample was collected from control households containing asymptomatic children age-matched to case-children. Samples were tested for rotavirus using real-time PCR. Risk factors for household transmission of rotavirus infection and clinical rotavirus disease were identified using logistic regression. Vaccine effectiveness against transmission (VET) was estimated as one minus the ratio of secondary attack rates (SAR) in vaccinated and unvaccinated populations, using VE estimates from the associated diarrhoeal surveillance platform to estimate the counterfactual SAR without vaccination.FindingsA total of 196 case-households and 55 control-households were recruited. Household SAR for rotavirus infection was high (65%); SAR for clinical disease was much lower (5%). Asymptomatic infection in control households was common (28%). Increasing disease severity was associated with increased risk of transmission of both rotavirus infection and disease to household contacts. Estimated VET was 39% (95% confidence interval 16-57%).InterpretationRotavirus vaccine has the potential to substantially reduce household rotavirus transmission. This should be considered in clinical and health economic assessments of vaccine impact.FundingWellcome Trust and NIH/NIAID.
Transmembrane Stem Cell Factor Protein Therapeutics Enhance Revascularization in Ischemia without Mast Cell Activation
Authors: Takematsu Eri , Auster Jeff , Chen Po-Chih , Srinath Sanjana , Canga Sophia , Singh Aditya , Majid Marjan , Sherman Michael , Dunn Andrew , Graham Annette , Martin Patricia , Baker Aaron B. 
Published: April 2020

AbstractStem cell factor (SCF) is a cytokine that regulates hematopoiesis and other biological processes. While clinical treatments using SCF would be highly beneficial, these have been limited by toxicity related to mast cell activation. Transmembrane SCF (tmSCF) has differential activity from soluble SCF and has not been explored as a therapeutic agent. We created novel therapeutics using tmSCF embedded in proteoliposomes or lipid nanodiscs. Mouse models of anaphylaxis and ischemia revealed the tmSCF-based therapies did not activate mast cells and improved the revascularization in the ischemic hind limb. Proteoliposomal tmSCF preferentially acted on endothelial cells to induce angiogenesis while tmSCF nanodiscs had greater activity in inducing stem cell mobilization and recruitment to the site of injury. The type of lipid nanocarrier used altered the relative cellular uptake pathways and signaling in a cell type dependent manner. Overall, we found that tmSCF-based therapies can provide therapeutic benefits without off target effects.
Infection with novelBacteroides phage BV01alters host transcriptome and bile acid metabolism in a common human gut microbe
Authors: Campbell Danielle E. , Ly Lindsey K. , Ridlon Jason M. , Hsiao Ansel , Whitaker Rachel J. , Degnan Patrick H. 
Published: April 2020

ABSTRACTThe bacterial genusBacteroidesis among the most abundant and common taxa in the human gut, yet little is known about the phages infecting the group.Bacteroides phage BV01(BV01) was identified as a prophage integrated on the chromosome of its host,Bacteroides vulgatusATCC 8482. Phage BV01 is actively produced, and infects susceptibleB. vulgatushosts in the mouse gut. Infection with BV01 causes a generalized repression of theB. vulgatustranscriptome, downregulating 103 transcripts and upregulating only 12. Integration of BV01 disrupts the promoter sequence of a downstream gene encoding a putative tryptophan-rich sensory protein (tspO). Deletion oftspOand subsequent RNAseq analysis revealed that more than half of the differentially-regulated transcripts are shared with the BV01 lysogen, suggesting the transcriptomic response to BV01 is linked totspO. Among these differentially-regulated transcripts are two encoding bile salt hydrolases. Bile acid deconjugation assays show that BV01 represses its host’s ability to hydrolyze bile acids in atspO-dependent manner. Analysis of 256 published healthy human gut metagenomes suggests that phage integration adjacent toB. vulgatus-liketspOgenes is rare within an individual, but common among humans. Finally, this work proposes a novel phage family that includes BV01, theSalyersviridae, whose host range spans theBacteroidesand is detectable in human-associated samples. Together, these findings highlight the importance of phage-host interactions to our understanding of how gut microbes sense and interact with their environment.IMPORTANCEThe links between human disease and the gut microbiome are numerous. Most mechanisms by which most gut microbes and their activities change and impact human health remain elusive. Phages, viruses that infect bacteria, are hypothesized to play a central role in modulating both community dynamics and functional activities. Here we have characterized an active prophage, BV01, which infects a pervasive and abundant human gut-associated species. BV01 infection alters its host’s transcriptional profile including its metabolism of bile acids, molecules implicated in mediating health and disease states in the gut. This highlights that prophages and other components of the variable genome should not be overlooked in bacterial genomes because they may dramatically alter host phenotypes. Furthermore, BV01 represents a new family of phages infecting human gut symbionts, providing a foundation for future investigations of phage-host interactions in these clinically-relevant but underexplored hosts.
Comparison of thein vitroactivity of novel and established nitrification inhibitors applied in agriculture: challenging the effectiveness of the currently available compounds
Authors: Papadopoulou Evangelia S. , Bachtsevani Eleftheria , Lampronikou Eleni , Adamou Eleni , Katsaouni Afroditi , Thion Cécile , Vasileiadis Sotirios , Menkissoglu-Spiroudi Urania , Nicol Graeme W. , Karpouzas Dimitrios G. 
Published: April 2020

ABSTRACTNitrification inhibitors (NIs) applied to soil reduce nitrogen fertilizer losses from agricultural ecosystems. Currently available NIs appear to selectively inhibit ammonia-oxidizing bacteria (AOB), while their impact on other groups of nitrifiers is limited. Ethoxyquin (EQ), a preservative shown to inhibit ammonia-oxidizers (AO) in soil, is rapidly transformed to 2,6-dihydro-2,2,4-trimethyl-6-quinone imine (QI) and 2,4-dimethyl-6-ethoxy-quinoline (EQNL). We compared the inhibitory potential of EQ and its derivativesin vitrowith other established NIs that have been applied in an agricultural setting (dicyandiamide (DCD), nitrapyrin (NP), 3,4-dimethylpyrazole phosphate (DMPP)) by evaluating their impact on the activity and growth of five soil-derived strains (two AOB (Nitrosomonas europaea, Nitrosospira multiformis), two ammonia-oxidizing archaea (AOA) (“CandidatusNitrosocosmicus franklandus”, “CandidatusNitrosotalea sinensis”), and one nitrite-oxidizing bacterium (NOB) (Nitrobactersp.)). NIs degradation was also determined. AOA were more sensitive than AOB or NOB to EQ and its derivatives. Despite its transient character, QI was primarily responsible for AO inhibition by EQ, and the most potent NI against AOA. For AOB, QI was more potent than DCD but less than nitrapyrin and DMPP. AOA and NOB showed higher tolerance to the persistent compounds DCD and DMPP. Our findings benchmark the activity range of known and novel NIs with practical implications for their use, and the development of novel NIs with broad or complementary activity against all AO.
Distinct target-specific mechanisms homeostatically stabilize transmission at pre-and post-synaptic compartments
Authors: Goel Pragya , Nishimura Samantha , Chetlapalli Karthik , Li Xiling , Chen Catherine , Dickman Dion 
Published: April 2020

ABSTRACTNeurons must establish and stabilize connections made with diverse targets, each with distinct demands and functional characteristics. AtDrosophilaneuromuscular junctions, synaptic strength remains stable in a manipulation that simultaneously induces hypo-innervation on one target and hyper-innervation on the other. However, the expression mechanisms that achieve this exquisite target-specific homeostatic control remain enigmatic. Here, we identify the distinct target-specific homeostatic expression mechanisms. On the hypo-innervated target, an increase in postsynaptic glutamate receptor (GluR) abundance is sufficient to compensate for reduced innervation, without any apparent presynaptic adaptations. In contrast, a target-specific reduction in presynaptic neurotransmitter release probability is reflected by a decrease in active zone components restricted to terminals of hyper-innervated targets. Finally, loss of postsynaptic GluRs on one target induces a compartmentalized, homeostatic enhancement of presynaptic neurotransmitter release called presynaptic homeostatic potentiation that can be precisely balanced with the adaptations required for both hypo- and hyper-innervation to maintain stable synaptic strength. Thus, distinct anterograde and retrograde signaling systems operate at pre- and post-synaptic compartments to enable target-specific, homeostatic control of neurotransmission.
Impaired expression of chloroplast HSP90C chaperone activates plant defense responses leading to a disease symptom-like phenotype
Authors: Shaikhul Islam , Ashok Bhor Sachin , Keisuke Tanaka , Hikaru Sakamoto , Takashi Yaeno , Hidetaka Kaya , Kappei Kobayashi 
Published: April 2020

AbstractRNA-seq analysis of a transgenic tobacco plant, i-hpHSP90C, in which chloroplastHSP90Cgenes can be silenced in an artificially inducible manner resulting in the development of chlorosis, revealed the up- and down-regulation of 2746 and 3490 genes, respectively. Gene Ontology analysis of these differentially expressed genes indicated the upregulation of ROS-responsive genes, the activation of the innate immunity and cell death pathways, and the downregulation of genes involved in photosynthesis, plastid organization, and cell cycle. Cell death was confirmed by trypan blue staining and electrolyte leakage assay and the H2O2production by diaminobenzidine staining. The upregulation of ER stress-responsive genes suggested the interplay between ER protein quality control and chloroplast or immune response. The results collectively suggest that the reduced levels of HSP90C chaperone leads the plant to develop chlorosis primarily through the global downregulation of chloroplast and photosynthesis-related genes and additionally through the light-dependent production of ROS, followed by the activation of immune responses including the cell death.HighlightInduced silencing ofHSP90Cgene caused the upregulation of stress-responsive genes and the activation of innate immune response, which resulted in the chlorosis development accompanying cell death.
Cryo-EM structure of the fully-loaded asymmetric anthrax lethal toxin in its heptameric pre-pore state
Authors: Antoni Claudia , Quentin Dennis , Lang Alexander E. , Aktories Klaus , Gatsogiannis Christos , Raunser Stefan 
Published: April 2020

AbstractAnthrax toxin is the major virulence factor secreted byBacillus anthracis, causing high mortality in humans and other mammals. It consists of a membrane translocase, known as protective antigen (PA), that catalyzes the unfolding of its cytotoxic substrates lethal factor (LF) and edema factor (EF), followed by translocation into the host cell. Substrate recruitment to the heptameric PA pre-pore and subsequent translocation, however, are not well understood. Here, we report three high-resolution cryo-EM structures of the fully-loaded anthrax lethal toxin in its heptameric pre-pore state, which differ in the position and conformation of LFs. The structures reveal that three LFs interact with the heptameric PA and upon binding change their conformation to form a continuous chain of head-to-tail interactions. As a result of the underlying symmetry mismatch, one LF binding site in PA remains unoccupied. Whereas one LF directly interacts with a part of PA called α-clamp, the others do not interact with this region, indicating an intermediate state between toxin assembly and translocation. Interestingly, the interaction of the N-terminal domain with the α-clamp correlates with a higher flexibility in the C-terminal domain of the protein. Based on our data, we propose a model for toxin assembly, in which the order of LF binding determines which factor is translocated first.
Communicability distance reveals hidden patterns of Alzheimer disease
Authors: Lella Eufemia , Estrada Ernesto 
Published: April 2020

AbstractThe communicability distance between pairs of regions in human brain is used as a quantitative proxy for studying Alzheimer disease. Using this distance we obtain the shortest communicability path lengths between different regions of brain networks from Alzheimer diseased (AD) patients and healthy cohorts (HC). We show that the shortest communicability path length is significantly better than the shortest topological path length in distinguishing AD patients from HC. Based on this approach we identify 399 pairs of brain regions for which there are very significant changes in the shortest communicability path length after AD appears. We find that 42% of these regions interconnect both brain hemispheres, 28% connect regions inside the left hemisphere only and 20% affects vermis connection with brain hemispheres. These findings clearly agree with the disconnection syndrome hypothesis of Alzheimer disease. Finally, we show that in 76.9% damaged brain regions the shortest communicability path length drops in AD in relation to HC. This counterintuitive finding indicates that AD transforms the brain network into a more efficient system from the perspective of the transmission of the disease, because it drops the circulability of the disease factor around the brain regions in relation to its transmissibility to other regions.
The mRNA-binding protein HuR is a kinetically-privileged electrophile sensor
Authors: Poganik Jesse R. , Van Hall-Beauvais Alexandra K. , Long Marcus J. C. , Disare Michael T. , Zhao Yi , Aye Yimon 
Published: April 2020

AbstractThe key mRNA-binding proteins HuR and AUF1 are reported stress sensors in mammals. Intrigued by recent reports of sensitivity of these proteins to the electrophilic lipid prostaglandin A2 and other redox signals, we here examined their sensing abilities to a prototypical redox-linked lipid-derived electrophile, 4-hydroxynonenal (HNE). Leveraging our T-REX electrophile delivery platform, we found that only HuR, and not AUF1, is a kinetically-privileged sensor of HNE in HEK293T cells, and sensing functions through a specific cysteine, C13. Cells depleted of HuR, upon treatment with HNE, manifest unique alterations in cell viability and Nrf2-transcription-factor-driven antioxidant response (AR), which our recent work shows is regulated by HuR at the Nrf2-mRNA level. Mutagenesis studies showed that C13-specific sensing alone is not sufficient to explain HuR-dependent stress responsivities, further highlighting a complex context-dependent layer of Nrf2/AR regulation through HuR.
Physical and mental health characteristics of adults with subjective cognitive decline: A study of 3,407 people aged 18-81 years from an MTurk-based U.S. national sample
Authors: Van Patten Ryan , Nguyen Tanya T. , Mahmood Zanjbeel , Lee Ellen E. , Daly Rebecca E. , Palmer Barton W. , Wu Tsung-Chin , Tu Xin , Jeste Dilip V. , Twamley Elizabeth W. 
Published: April 2020

AbstractSubjective cognitive decline (SCD), or internal feelings of reduced mental capacity, is of increasing interest in the scientific, clinical, and lay community. Much of the extant literature is focused on SCD as a risk factor for Alzheimer’s disease in older adults, while less attention has been paid to non-cognitive health correlates of SCD across adulthood. Consequently, we investigated physical and mental health correlates of SCD in younger, middle-aged, and older adults. We recruited 3,407 U.S. residents through Amazon’s Mechanical Turk, an online labor market. Participants completed a 90-item self-report survey questionnaire assessing sociodemographic characteristics, physical health, sleep, depression, anxiety, loneliness, wisdom, self-efficacy, and happiness. Overall, 493/1930 (25.5%) of younger adults (18-49) and 278/1032 (26.9%) of older adults (50 or older) endorsed the SCD item. Multivariate analysis of variance and follow-upt-tests revealed worse physical and mental health characteristics in people endorsing SCD compared to those who did not, with effect sizes primarily in the medium to large range. Additionally, age did not moderate relationships between SCD and physical and mental health. Results suggest that SCD is associated with a diverse set of negative health characteristics such as poor sleep and high body mass index, and lower levels of positive factors including happiness and wisdom. Effect sizes of psychological correlates of SCD were as large as (or larger than) those of physical correlates, indicating that mental health and affective symptoms may be critical to consider when evaluating SCD. Overall, findings from this large, national U.S. sample suggest the presence of relationships between SCD and multiple psychological and perceived health factors; our results also show that SCD may be highly prevalent in both younger and older adults, suggesting that it be assessed across the adult lifespan.
Mechanics and energetics of walking and running up and downhill: A joint-level perspective to guide design of lower-limb exoskeletons
Authors: Nuckols Richard W. , Takahashi Kota Z. , Farris Dominic J. , Mizrachi Sarai , Riemer Raziel , Sawicki Gregory S. 
Published: April 2020

AbstractLower-limb wearable robotic devices can provide effective assistance to both clinical and healthy populations; however, how assistance should be applied in different gait conditions and environments is still unclear. We suggest a biologically-inspired approach derived from knowledge of human locomotion mechanics and energetics to establish a ‘roadmap’ for wearable robot design. In this study, we characterize the changes in joint mechanics during both walking and running across a range of incline/decline grades and then provide an analysis that informs the development of lower-limb exoskeletons capable of operating across a range of mechanical demands. Eight subjects (6M,2F) completed five walking (1.25 m-1) trials at −15%, −10%, 0%, 10%, and 15% grade and five running (2.25 m s-1) trials at −10%, −5%, 0%, 5%, and 10% grade on a treadmill. We calculated time-varying joint moment and power output for the ankle, knee, and hip. For each gait, we examined how individual limb-joints contributed to total limb positive, negative and net power across grades. For both walking and running, changes in grade caused a redistribution of joint mechanical power generation and absorption. From level to incline walking, the ankle’s contribution to limb positive power decreased from 44% on the level to 28% at 15% uphill grade (p< 0.0001) while the hip’s contribution increased from 27% to 52% (p< 0.0001). In running, regardless of the surface gradient, the ankle was consistently the dominant source of lower-limb positive mechanical power (47-55%). In the context of our results, we outline three distinct use-modes that could be emphasized in future lower-limb exoskeleton designs 1) Energy injection: adding positive work into the gait cycle, 2) Energy extraction: removing negative work from the gait cycle, and 3) Energy transfer: extracting energy in one gait phase and then injecting it in another phase (i.e., regenerative braking).