bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated and semi-automated contact tracing: Protocol for a rapid review of available evidence and current challenges to inform the control of COVID-19
Authors: Braithwaite Isobel , Callender Tom , Bullock Miriam , Aldridge Robert W 
Published: April 2020

AbstractIntroductionTraditional approaches to case-finding, case isolation, and contact tracing methods have so far proved insufficient on their own to prevent the development of local epidemics of COVID-19 in many high-income countries despite relatively advanced public health systems. As a result, many governments have resorted to widespread social distancing measures and mass quarantines (‘lock-downs’) to reduce transmission and to prevent healthcare systems from being overwhelmed. However, such measures impose heavy human and societal costs. Automated or semi-automated digital contact tracing, in conjunction with scaled-up community testing, has been proposed as a key part of exit strategies from lockdowns. However, the effectiveness of these approaches to contact tracing is unclear, and to be effective, trusted, and widely adopted such technology must overcome several challenges.Methods and analysisWe will perform a rapid systematic review to assess the effectiveness of automated and semi-automated digital tools for contact tracing, and identify key considerations for successful implementation, to inform the control of COVID-19. We will search PubMed, EMBASE, EBSCO Medical COVID information portal, OVID Global Health, Cochrane Library, medRxiv, BioRxiv, and arXiv for peer-reviewed and pre-print papers on automated or semi-automated digital tools for contact tracing of COVID-19, another respiratory disease with pandemic potential (limited to SARS, MERS, or pandemic influenza), or Ebola, in human populations. Studies will be eligible if published in English between 1 January 2000 and 14 April 2020. We will synthesise study findings narratively and will consider meta-analysis if ≥ 3 suitable studies with comparable interventions and outcomes are available.Ethics and disseminationEthical approval is not required for this review. We plan to disseminate findings via pre-print, journal publication, through social media and web-based platforms and through direct stakeholder engagement.
Maternal Serum Concentrations of Selenium, Copper and Zinc during Pregnancy are associated with Risk of Spontaneous Preterm Birth: A case-control study from Malawi
Authors: Chiudzu Grace , Choko Augustine T. , Maluwa Alfred , Huber Sandra , Odland Jon 
Published: April 2020

AbstractPreterm birth is delivery before 37 completed weeks. A study was conducted to evaluate the association of maternal serum concentrations of selenium, copper, and zinc, and preterm birth. There were 181 women in this nested case-control study, 90/181 (49.7%) term and 91/181 (50.3%) preterm pregnant women. The overall mean serum concentration of selenium was 77.0; SD 19.4µg/L, copper was 2.50; SD 0.52 mg/L and zinc was 0.77; SD 0.20 mg/L with reference values of 47-142µg/L, 0.76-1.59mg/L and 0.59-1.11 mg/L, respectively. For preterm birth, mean serum concentrations for selenium was 79.7; SD 21.6µg/L, copper was 2.61; SD 0.57 mg/L, and zinc was 0.81; SD 0.20 mg/L compared to that of term births: selenium (74.2; SD 16.5µg/L; p=0.058), copper (2.39; SD 0.43 mg/L; p = 0.004), and zinc (0.73; SD 0.19 mg/L; p = 0.006) respectively. In adjusted analysis, every unit increase in maternal selenium concentrations gave increased odds of being a case OR 1.01 (95% CI: 0.99; 1.03), p=0.234, copper OR 1.62 (95% CI: 0.80; 3.32); p = 0.184, zinc OR 6.88 (95% CI: 1.25; 43.67); p=0.032. Results show that there was no deficiency of selenium, and zinc; and high serum concentrations of copper in pregnancy. Preterm birth was associated with higher maternal serum concentrations of copper and zinc.
Sequestration of TDP-43216-414aggregates by cytoplasmic expression of the proSAAS chaperone
Authors: Peinado Juan R. , Chaplot Kriti , Jarvela Timothy S. , Barbieri Edward M. , Shorter James , Lindberg Iris 
Published: April 2020

ABSTRACTAs neurons age, protein homeostasis becomes less efficient, resulting in misfolding and aggregation. Chaperone proteins perform vital functions in the maintenance of cellular proteostasis, and chaperone-based therapies that promote sequestration of toxic aggregates may prove useful in blocking the development of neurodegenerative disease. We previously demonstrated that proSAAS, a small secreted neuronal protein, exhibits potent chaperone activity against protein aggregationin vitro, and blocks the cytotoxic effects of amyloid and alpha synuclein oligomers in cell culture models. We now examine whether cytoplasmic expression of proSAAS results in interaction with protein aggregates in this cellular compartment. We used site-directed mutagenesis, confocal microscopy,in vitroaggregation assays, and functional assays to investigate the interaction of proSAAS with TDP-43 and other known aggregating proteins. We report that expression of proSAAS within the cytoplasm generates dense, membrane-less 2 μm proSAAS spheres which progressively fuse to form larger spheres, suggesting liquid droplet-like properties. ProSAAS spheres selectively accumulate a C-terminally truncated fluorescently-tagged form of TDP-43216-414, initiating its cellular redistribution by sequestration within the sphere core; these TDP-43216-414-containing spheres also exhibit dynamic fusion. Removal of either the predicted α-helix (37-70) composed of hydrophobic and charged amino acids or the stretch of amino acids encompassing the conserved hydrophobic region and the positively charged furin site (163-189) inhibits the ability of proSAAS both to form spheres and to encapsulate TDP-43 aggregates. As a functional output, we demonstrate that proSAAS expression results in cytoprotection against full-length TDP-43 toxicity in yeast. In summary, the normally secreted neuronal chaperone proSAAS, when expressed in the cytoplasm unexpectedly phase-separates to form spherical liquid-like condensates that undergo dynamic fusion. We conclude that cyto-proSAAS acts as a functional holdase for cytoplasmic TDP-43216-414molecules via this phase-separation property, representing a cytoprotectant whose unusual biochemical properties can potentially be exploited in the design of therapeutic molecules.
Inter-relationships between changes in stress, mindfulness, and dynamic functional connectivity in response to a social stressor
Authors: Teng James , Massar Stijn A.A. , Lim Julian 
Published: April 2020

AbstractWe conducted a study to understand how dynamic functional brain connectivity contributes to the moderating effect of trait mindfulness on the stress response. 40 participants provided subjective reports of stress, cortisol assays, and functional MRI before and after undergoing a social stressor. Self-reported trait mindfulness was also collected. Experiencing stress led to significant decreases in the prevalence of a connectivity state previously associated with mindfulness, but no changes in two connectivity states with prior links to arousal. Connectivity did not return to baseline 30 minutes after stress. Higher trait mindfulness was associated with attenuated affective and neuroendocrine stress response, and smaller decreases in the mindfulness-related connectivity state. In contrast, we found no association between affective response and functional connectivity. Taken together, these data allow us to construct a preliminary brain-behaviour model of how mindfulness dampens stress reactivity.
The macroecology and evolution of avian competence forBorrelia burgdorferi
Authors: Becker Daniel J. , Han Barbara A. 
Published: April 2020

AbstractAimPredicting novel reservoirs of zoonotic pathogens would be improved by identifying inter-specific drivers of host competence, the ability to transmit pathogens to new hosts or vectors. Tick-borne pathogens can provide a useful model system, as larvae become infected only when feeding on a competent host during their first bloodmeal. For tick-borne diseases, competence has been best studied forBorrelia burgdorferisensu lato (Bbsl), which causes Lyme borreliosis. Major reservoirs include several small mammal species, but birds may play an underrecognized role in human risk given their ability to disperse infected ticks across large spatial scales. Here, we provide a global synthesis of the ecological and evolutionary factors that determine the ability of bird species to infect larval ticks withBbsl.LocationGlobalTime period1983 to 2019Major taxa studiedBirdsMethodsWe compiled a dataset ofBbsl competence across 183 bird species and applied meta-analysis, phylogenetic factorization, and boosted regression trees to describe spatial and temporal patterns in competence, characterize its phylogenetic distribution across birds, reconstruct its evolution, and evaluate the trait profiles associated with competent avian species.ResultsHalf of sampled bird species show evidence of competence forBbsl. Competence displays moderate phylogenetic signal, has evolved multiple times across bird species, and is pronounced in the genusTurdus. Trait-based analyses distinguished competent birds with 80% accuracy and show that such species have low baseline corticosterone, exist on both ends of the pace-of-life continuum, breed and winter at high latitudes, and have broad migratory movements into their breeding range. We use these trait profiles to predict various likely but unsampled competent species, including novel concentrations of avian reservoirs within the Neotropics.Main conclusionOur results can generate new hypotheses for how birds contribute to the dynamics of tick-borne pathogens and help prioritize surveillance of likely but unsampled competent birds. Our findings further emphasize that birds display underrecognized variation in their contributions to enzootic cycles ofBbsl and the broader need to better consider competence in ecological and predictive studies of multi-host pathogens.
Turning the Stimulus On and Off Dynamically Changes the Direction of Alpha Traveling Waves
Authors: Pang Zhaoyang , Alamia Andrea , VanRullen Rufin 
Published: April 2020

AbstractTraveling waves have been studied to characterize the complex spatiotemporal dynamics of the brain. Several studies have suggested that the propagation direction of alpha traveling waves can be task-dependent. For example, a recent EEG study from our group found that forward waves (i.e. occipital to frontal, FW waves) were observed during visual processing, whereas backward waves (i.e. frontal to occipital, BW waves) mostly occurred in the absence of sensory input. These EEG recordings, however, were obtained from different experimental sessions and different groups of subjects. To further examine how the waves’ direction changes between task conditions, 13 participants were tested on a target detection task while EEG signals were recorded simultaneously. We alternated visual stimulation (5 s display of visual luminance sequences) and resting state (5 s of black screen) within each single trial, allowing us to monitor the moment-to-moment progression of traveling waves. As expected, the direction of alpha waves was closely linked with task conditions. First, FW waves from occipital to frontal regions, absent during rest, emerged as a result of visual processing, while BW waves in the opposite direction dominated in the absence of visual inputs, and were reduced (but not eliminated) by external visual inputs. Second, during visual stimulation (but not rest), both waves coexisted on average, but were negatively correlated. In summary, we conclude that the functional role of alpha traveling waves is closely related with their propagating direction, with stimulus-evoked FW waves supporting visual processing and spontaneous BW waves involved more in top-down control.
Novel non-transposable-element regulation patterns of KZFP family reveal new drivers of its rapid evolution
Authors: Shen Pan , Zheng Qijian , Xu Aishi , Liu Junhua , Hou Yushan , Gao Chao , Tian Chunyan , He Fuchu , Yang Dong 
Published: April 2020

AbstractOne striking feature of the large KRAB-containing zinc finger protein (KZFP) family is its rapid expansion and divergence since its formation about 400 million years ago. However, the evolutionary characteristics of KRAB domains, C2H2 zinc fingers and the full protein of KZFPs have not been fully analyzed. As for the drivers of the rapid evolution, it’s partly due to their coevolution with transposable elements (TEs). But their diverse functions besides inhibiting TEs suggest other reasons exist. Here we address these two issues by the systematic analysis of the divergence time and diversification pattern of KZFPs at three aspects and the functional analysis of the potential target genes besides TEs. We found that old-zinc-finger-containing KZFPs tend to have varied and disordered KRAB domains, indicating there are two ways of the evolution of KZFPs, including the variation of KRAB domains and the diversification of zinc fingers. Among them, the divergence of zinc fingers mainly contributes to the rapid evolution of KZFPs. Thus, we mainly focused on the functional requirements of the evolution of zinc fingers. Different from the classical regulation pattern of this family, we found and experimentally confirmed that KZFPs tend to bind to non-TE regions and can positively regulate target genes. Although most young genes tend to be with a low expression level, young-zinc-finger-containing KZFPs tend to be highly expressed in early embryonic development or early mesoderm differentiation, indicating their particular evolutionarily novel functional roles in these two processes. We further validated a young KZFP, ZNF611, can bind to non-TE region of STK38 gene and positively regulates its expression in ESCs. The emergence of new sequence in STK38 promoter may drive the evolution of zinc fingers in ZNF611. Finally, we proposed a ‘two-way evolution model’ of KZFP family.
Aquaporin mediating stomatal closure is associated with water conservation under mild water deficit
Authors: Ding Lei , Chaumont François 
Published: April 2020

SummaryContradictory results indicate that aquaporins might facilitate the diffusion of both water and H2O2during abscisic acid (ABA) triggered stomatal closure. Here, we tested whether maize plasma membrane PIP2;5 aquaporin regulates stomatal closure under water deficit or ABA treatment in intact plants, detached leaves, and peeled epidermis.Transpiration, stomatal conductance and aperture, as well as reactive oxygen species (ROS) in stomatal complexes were studied in maize lines deregulated inPIP2;5gene expression, under water deficit and/or ABA treatments.In well-watered conditions, the PIP2;5 overexpressing (OE) plants transpired more than the wild-type plants (WT), while no significant difference in transpiration was observed betweenpip2;5KO and WT plants. Upon mild-water deficit or low ABA concentration treatment, the transpiration and stomatal conductance decreased more in PIP2;5 OE, and less inpip2;5KO lines, in comparison with WT plants. Using isolated epidermis, ABA treatment induced faster stomatal closing in PIP2;5 OE lines compared to the WT, whilepip2;5KO stomata were ABA insensitive. These phenotypes were associated with guard cell ROS accumulation.Together, these data indicate that maize PIP2;5 regulates early stomatal closure for water conservation upon a water deficit environment.
Doxorubicin induces cardiotoxicity in a pluripotent stem cell model of aggressive B cell lymphoma cancer patients
Authors: Haupt Luis Peter , Maus Andreas , Tiburcy Malte , Köhne Steffen , Maurer Wiebke , Tappu Rewati , Haas Jan , Li Yun , Sasse Andre , Santos Celio C. X. , Dressel Ralf , Wojnowski L. , Bunt Gertrude , Shah Ajay M. , Meder Benjamin , Sossalla Samuel , Wollnik Bernd , Hasenfuß Gerd , Streckfuß-Bömeke Katrin 
Published: April 2020

AbstractCancer therapies have been shown to induce cardiovascular complications. The aims of this study were to establish anin vitroinduced pluripotent stem cell model (iPSC) of anthracycline-induced cardiotoxicity (ACT) from patients with an aggressive form of cancer.ACT-iPSC-CM generated from individuals with CD20+B-cell lymphoma cancer who had received high doses of DOX and suffered cardiac dysfunction were observed to be persistently more susceptible to DOX toxicity compared to control-iPSC-CM. ACT-iPSC-CM exhibited increased DOX-dependent disorganized myofilament structure and cell death, as well as higher reactive oxygen species (ROS) compared to controls. Importantly, analysis of engineered heart muscle (EHM) from ACT-iPSC-CM showed an impaired DOX-dependent mechanical functionality. Transcriptome profiles of EHM are in line with a disturbed adjustment to DOX-dependent alteration of Ca2+homeostasis in ACT-iPSC-CM. Furthermore, genetic variants in different cardiac key regulators were uncovered.In conclusion, we developed the first human iPSC-CM and EHM model of DOX-induced cardiac dysfunction in patients with B-cell lymphoma. Our results suggest that DOX-related stress resulted in decreased contractile activity and finally in heart failure in ACT patients.Brief summaryDevelopment of the first human iPSC-CM model of DOX-induced cardiac dysfunction in patients with aggressive B cell lymphoma and high-dose DOX treatment.
Pre-stimulus beta-band activity is a signature of statistical learning
Authors: Bogaerts Louisa , Richter Craig G. , Landau Ayelet N. , Frost Ram 
Published: April 2020

AbstractStatistical learning (SL) is taken to be the main mechanism by which cognitive systems discover the underlying regularities of the environment. We document, in the context of a classical visual SL task, divergent rhythmic EEG activity during the anticipation of stimuli within patterns versus pattern transitions. Our findings reveal differential pre-stimulus oscillatory activity in the beta band (∼20 Hz) that indexes learning: it emerges with increased pattern repetitions, and importantly, it is highly correlated with behavioral learning outcomes. These findings hold the promise of converging on an online measure of learning regularities and provide important theoretical insights regarding the mechanisms of SL and prediction.Significance StatementSL has become a major theoretical construct in cognitive science, providing the primary means by which organisms learn about regularities in the environment. As such it is a critical building block for basic and higher-order cognitive functions.Here we identify for the first time a spectral neural index in the time window prior to stimulus presentation, which evolves with increased pattern exposure, and is predictive of learning performance.The manifestation of learning that is revealed not in stimulus processing but in anticipatory moments of the learning episode, makes a direct link between the fields of statistical learning and predictive processing, and suggests a possible mechanistic account of visual SL.
Complement receptor 3 forms a compact high affinity complex with iC3b
Authors: Jensen Rasmus K. , Bajic Goran , Sen Mehmet , Springer Timothy A. , Vorup-Jensen Thomas , Andersen Gregers R. 
Published: April 2020

AbstractComplement receptor 3 (CR3, also known as Mac-1, integrin αMβ2, or CD11b/CD18) is expressed on a subset of myeloid and certain activated lymphoid cells. CR3 is essential for the phagocytosis of complement-opsonized particles such as pathogens and apoptotic or necrotic cells opsonized with the complement fragment iC3b and to a lesser extent C3dg. While the interaction between the iC3b thioester domain and the ligand binding CR3 αMI-domain is structurally and functionally well characterized, the nature of additional CR3-iC3b interactions required for phagocytosis of complement opsonized objects remain obscure. Here we analyzed the interaction between iC3b and the 150 kDa headpiece fragment of the CR3 ectodomain. Surface plasmon resonance experiments demonstrated a 30 nM affinity of CR3 for iC3b compared to 515 nM for the iC3b thioester domain. Small angle x-ray scattering analysis revealed that iC3b adopts an extended but preferred conformation in solution. Upon interaction with CR3, iC3b rearranges to form a compact receptor-ligand complex. Overall, the data suggest that the iC3b-CR3 interaction is of high affinity and relies on minor contacts formed between CR3 and regions outside the iC3b thioester domain. Our results rationalize the more efficient phagocytosis elicited by iC3b than by C3dg and pave the way for development of specific therapeutics for treatment of inflammatory and neurodegenerative diseases that do not interfere with recognition of non-complement CR3 ligands.
Electrical Automaticity and Intercellular Synchronization via Shared Extracellular Compartments
Authors: Poelzing St. , Keener J. P 
Published: April 2020

ABSTRACTElectrically excitable cells often spontaneously and synchronously depolarize in vitro and in vivo. It remains unknown how cells synchronize and autorhythmically activate above the intrinsic mean activation frequency of isolated cells without pacemaking mechanisms. Recent insights into ephaptic coupling (non-gap junction or synaptic coupling) suggest that cyclic ion accumulation and depletion in diffusion limited extracellular volumes densely expressing ion channels modifies action potentials. This report explores how potassium accumulation and depletion in a restricted extracellular domain promotes spontaneous oscillations in the Hodgkin Huxley action potential model, which does not spontaneously activate on its own without external stimulus. Simulations demonstrate cells sharing a diffusion limited extracellular compartment can become autorhythmic and synchronous despite intercellular electrical heterogeneity. Autorhythmic frequency can be determined by net potassium flux into the cleft and the cleft volume. Additionally, inexcitable cells can induce autorhythmic activity in an excitable cell via a shared cleft and sufficient potassium fluxes contributed by each cell. Importantly, the synchronization and autorhythmic activity conferred by shared cleft with reduced potassium efflux can occur in the absence of gap junctions. Lastly, not only can potassium oscillations in shared restricted clefts initiate, support, and suppress autorhythmic depolarizations, the same mechanism can homogenize repolarization. The work has implications for understanding how automaticity is coordinated among excitable cells and suggests a new role for non-excitable cells such as fibroblasts, macrophages, or astrocytes with sarcolemmal potassium handling proteins facing shared and restricted intercellular clefts.SIGNIFICANCEA mechanism of cyclic ion accumulation and depletion in diffusion limited extracellular compartments can suppress, initiate, and support autorhythmic activity. Additionally, autorhythmicity can emerge from electrophysiologically heterogeneous cell pairs sharing a diffusion limited extracellular compartment, even if the individual cells will not spontaneously depolarize on their own. Sustained and synchronous autorhythmic activity can occur in the absence of gap junction coupling. Lastly, the shared diffusion limited extracellular compartment can also reduce action potential duration gradients by synchronizing repolarization.