bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of trust, risk perception, and health behavior on COVID-19 disease burden: Evidence from a multi-state US survey
Authors: Ridenhour Benjamin J. , Sarathchandra Dilshani , Seamon Erich , Brown Helen , Leung Fok-Yan , Johnson-Leon Maureen , Megheib Mohamed , Miller Craig R. , Johnson-Leung Jennifer 
Published: November 2021

AbstractEarly public health strategies to prevent the spread of COVID-19 in the United States relied on non-pharmaceutical interventions (NPIs) as vaccines and therapeutic treatments were not yet available. Implementation of NPIs, primarily social distancing and mask wearing, varied widely between communities within the US due to variable government mandates, as well as differences in attitudes and opinions. To understand the interplay of trust, risk perception, behavioral intention, and disease burden, we developed a survey instrument to study attitudes concerning COVID-19 and pandemic behavioral change in three states: Idaho, Texas, and Vermont. We designed our survey (n= 1034) to detect whether these relationships were significantly different in rural populations. The best fitting structural equation models show that trust indirectly affects protective pandemic behaviors via health and economic risk perception. We explore two different variations of this social cognitive model: the first assumes behavioral intention affects future disease burden while the second assumes that observed disease burden affects behavioral intention. In our models we include several exogenous variables to control for demographic and geographic effects. Notably, political ideology is the only exogenous variable which significantly affects all aspects of the social cognitive model (trust, risk perception, and behavioral intention). While there is a direct negative effect associated with rurality on disease burden, likely due to the protective effect of low population density in the early pandemic waves, we found a marginally significant, positive, indirect effect of rurality on disease burden via decreased trust (p= 0.095). This trust deficit creates additional vulnerabilities to COVID-19 in rural communities which also have reduced healthcare capacity. Increasing trust by methods such as in-group messaging could potentially remove some of the disparities inferred by our models and increase NPI effectiveness.
Broadly-neutralizing antibodies that bind to the influenza hemagglutinin stalk domain enhance the effectiveness of neuraminidase inhibitors via Fc-mediated effector functions
Authors: Zhang Ali , Chaudhari Hanu , Agung Yonathan , D’Agostino Michael R. , Ang Jann C. , Miller Matthew S. 
Published: November 2021

SummaryThe conserved hemagglutinin stalk domain is an attractive target for broadly effective antibody-based therapeutics and next generation universal influenza vaccines. Protection provided by hemagglutinin stalk binding antibodies is principally mediated through activation of immune effector cells. Titers of stalk-binding antibodies are highly variable on an individual level, and tend to increase with age as a result of increasing exposures to influenza virus. In our study, we show that stalk-binding antibodies cooperate with neuraminidase inhibitors to protect against influenza virus infection in an Fc-dependent manner. These data suggest that the effectiveness of neuraminidase inhibitors is likely influenced by an individual’s titers of stalk-binding antibodies, and that neuraminidase inhibitors may enhance the effectiveness of future stalk-binding monoclonal antibody-based treatments.
DeepProjection: Rapid and structure-specific projections of tissue sheets embedded in 3D microscopy stacks using deep learning
Authors: Haertter Daniel , Wang Xiaolei , Fogerson Stephanie M. , Ramkumar Nitya , Crawford Janice M. , Poss Kenneth D. , Di Talia Stefano , Kiehart Daniel P. , Schmidt Christoph F. 
Published: November 2021

AbstractThe efficient extraction of local high-resolution content from massive amounts of imaging data remains a serious and unsolved problem in studies of complex biological tissues. Here we present DeepProjection, a trainable projection algorithm based on deep learning. This algorithm rapidly and robustly extracts image content contained in curved manifolds from time-lapse recorded 3D image stacks by binary masking of background content, stack by stack. The masks calculated for a given movie, when predicted, e.g., on fluorescent cell boundaries on one channel, can subsequently be applied to project other fluorescent channels from the same manifold. We apply DeepProjection to follow the dynamic movements of 2D-tissue sheets in embryonic development. We show that we can selectively project the amnioserosa cell sheet during dorsal closure in Drosophila melanogaster embryos and the periderm layer in the elongating zebrafish embryo while masking highly fluorescent out-of-plane artifacts.
The influence of somatosensory and auditory evoked potentials on concurrent transcranial-magnetic stimulation – electroencephalography recordings
Authors: Chowdhury Nahian S , Rogasch Nigel C , Chiang Alan , Millard Samantha K , Skippen Patrick , Chang Wei-Ju , Bilska Katarzyna , Si E. , Seminowicz David A , Schabrun Siobhan M 
Published: November 2021

AbstractBackgroundTranscranial magnetic stimulation (TMS) evoked potentials (TEPs) can be used to index cortical excitability. However, it remains unclear to what extent TEPs reflect somatosensory and auditory-evoked potentials which arise from the scalp sensation and click of the TMS coil, as opposed to transcranial stimulation of cortical circuits.ObjectivesThe present study had two aims; a) to determine the extent to which sensory potentials contaminate TEPs using a spatially matched sham condition, and b) to determine whether sensory potentials reflect auditory or somatosensory potentials alone, or a combination of the two.MethodsTwenty healthy participants received active or sham stimulation, with the latter consisting of the click of a sham coil combined with scalp electrical stimulation. Earplugs/headphones were used to suppress the TMS click noise. Two additional control conditions i) electrical stimulation alone and ii) auditory stimulation alone were included in a subset of 13 participants.ResultsSignals from active and sham stimulation were correlated in spatial and temporal domains, especially >70ms post-stimulation. Relative to auditory or electrical stimulation alone, combined (sham) stimulation resulted in a) larger evoked responses b) stronger correlations with active stimulation and c) a signal that could not be explained by the linear sum of electrical and auditory stimulation alone.ConclusionsSensory potentials can confound data interpretations of TEPs at timepoints >70ms post-TMS, while earlier timepoints appear reflective of cortical excitability. Furthermore, contamination of TEPs cannot be explained by auditory or somatosensory potentials alone, but instead reflects a non-linear interaction between both sources. Future studies may benefit from controlling for sensory contamination using sham conditions that are spatially matched to active TMS, and which consist of combined auditory and somatosensory stimulation.
BOXR1030, an anti-GPC3 CAR with exogenous GOT2 expression, shows enhanced T cell metabolism and improved antitumor activity
Authors: Hickman Taylor L. , Choi Eugene , Whiteman Kathleen R. , Muralidharan Sujatha , Pai Tapasya , Johnson Tyler , Parikh Avani , Friedman Taylor , Gilbert Madaline , Shen Binzhang , Barron Luke , McGinness Kathleen E. , Ettenberg Seth A. , Motz Greg T. , Weiss Glen J. , Jensen-Smith Amy 
Published: November 2021

AbstractPurposeThe solid tumor microenvironment (TME) drives T cell dysfunction and inhibits the effectiveness of immunotherapies such as chimeric antigen receptor-based T cell (CAR T) cells. Early data has shown that modulation of T cell metabolism can improve intratumoral T cell function in preclinical models.Experimental DesignWe evaluated GPC3 expression in human normal and tumor tissue specimens. We developed and evaluated BOXR1030, a novel CAR T therapeutic co-expressing glypican-3 (GPC3)-targeted CAR and exogenous glutamic-oxaloacetic transaminase 2 (GOT2) in terms of CAR T cell function both in vitro and in vivo.ResultsExpression of tumor antigen GPC3 was observed by immunohistochemical staining in tumor biopsies from hepatocellular carcinoma, liposarcoma, squamous lung cancer, and Merkel cell carcinoma patients. Compared to control GPC3 CAR alone, BOXR1030 (GPC3-targeted CAR T cell that co-expressed GOT2) demonstrated superior in vivo efficacy in aggressive solid tumor xenograft models, and showed favorable attributes in vitro including an enhanced cytokine production profile, a less-differentiated T cell phenotype with lower expression of stress and exhaustion markers, an enhanced metabolic profile and increased proliferation in TME-like conditions.ConclusionsTogether, these results demonstrated that co-expression of GOT2 can substantially improve the overall antitumor activity of CAR T cells by inducing broad changes in cellular function and phenotype. These data show that BOXR1030 is an attractive approach to targeting select solid tumors. To this end, BOXR1030 will be explored in the clinic to assess safety, dose- finding, and preliminary efficacy (NCT05120271).
Clinical impact of the rapid molecular detection of RSV and influenza A and B viruses in the emergency department
Authors: Yin Nicolas , Van Nuffelen Marc , Bartiaux Magali , Préseau Thierry , Roggen Inge , Delaunoy Sabrina , Mahadeb Bhavna , Dahma Hafid , Busson Laurent , Vandenberg Olivier , Hallin Marie 
Published: November 2021

AbstractIntroductionUsing respiratory viruses’ rapid diagnostic tests in the emergency department could allow better and faster clinical management. Point-of-care PCR instruments now provide results in less than 30 minutes. The objective of this study was to assess the impact of the use of a rapid molecular diagnostic test, the cobas® Influenza A/B & RSV Assay for use on Roche’s cobas® Liat® instrument, during the clinical management of emergency department patients.MethodsPatients (adults and children) requiring admission or suffering from an underlying condition at risk of respiratory complication were prospectively recruited in the emergency department of four hospitals in the Brussels region. Physician’s intentions regarding admission, isolation, antibiotic, and antiviral use were collected before and after performing the rapid molecular test. Additionally, a comparison of the analytical performance of this test against antigen rapid tests and viral culture was performed as well as a time-to-result evaluation.ResultsAmong 293 patients recruited, 90 had a positive PCR whereas 44 had a positive antigen test. PCR yielded a sensitivity of 100% for all targets. Antigen tests yielded sensitivities ranging from 66.7% for influenza B to 83.3% for the respiratory syncytial virus (RSV). The use of PCR allowed a decrease in the overall need for isolation and treatment by limiting the isolation of negative patients and the antibiotic use for positive patients. Meanwhile, antiviral treatments better targeted patients with a positive influenza PCR.ConclusionThe use of a rapid influenza and RSV molecular test improves the clinical management of patients admitted to the emergency department by providing a fast and reliable result. Their additional cost compared to antigen tests should be balanced with the benefit of their analytical performance, leading to efficient reductions in the need of isolation and antibiotic use.
Modeling COVID-19 care capacity in a major health system
Authors: Erlendsdottir Margret , Eshghi Soheil , Crawford Forrest 
Published: November 2021

AbstractHospital resources, especially critical care beds and ventilators, have been strained by additional demand throughout the COVID-19 pandemic. Rationing of scarce critical care resources may occur when available resource limits are exceeded. However, the dynamic nature of the COVID-19 pandemic and variability in projections of the future burden of COVID-19 infection pose challenges for optimizing resource allocation to critical care units in hospitals. Connecticut experienced a spike in the number of COVID-19 cases between March and June 2020. Uncertainty about future incidence made it difficult to predict the magnitude and duration of the increased COVID-19 burden on the healthcare system. In this paper, we describe a model of COVID-19 hospital capacity and occupancy that generates estimates of the resources necessary to accommodate COVID-19 patients under infection scenarios of varying severity. We present the model structure and dynamics, procedure for parameter estimation, and publicly available web application where we implemented the tool. We then describe calibration using data from over 3,000 COVID-19 patients seen at the Yale-New Haven Health System between March and July 2020. We conclude with recommendations for modeling tools to inform decision-making using incomplete information during future crises.
Parental control: ecology drives plasticity in parental response to offspring signals
Authors: Caro S.M. , Velasco A.C. , van Mastrigt T. , van Oers K. , Griffin A.S. , West S.A. , Hinde C.A. 
Published: November 2021

AbstractDifferent bird species have completely different parent-offspring interactions. When food is plentiful, the chicks that are begging the loudest are fed the most. When food is scarce, bird species instead feed the largest offspring. While this variation could be due to parents responding to signalling differently based on food availability, it could equally be due to offspring adjusting their behaviour, or to variation in information availability. We tested between these competing explanations experimentally, by manipulating food availability in a population of wild great tits,Parus major, while standardising offspring behaviour and size. We found that when food was more plentiful, parents were: (1) more likely to preferentially feed the chicks that were begging the most; and (2) less likely to preferentially feed larger chicks. In addition, we consistently found these same patterns, in a meta-analysis across 57 bird species. Overall, our results suggest that parents have more control over food distribution than offspring do, and that they flexibly adjust how they respond to both offspring signals and cues of offspring quality in response to food availability. Consequently, depending upon environmental conditions, predictably different signalling systems are favoured.
High diversity of pimpline parasitoid wasps (Hymenoptera, Ichneumonidae, Pimplinae) from the lowermost Eocene Fur Formation
Authors: Klopfstein Seraina 
Published: November 2021

AbstractWith an estimated 100,000 extant species, Darwin wasps (Ichneumonidae) are more specious than all vertebrates together. However, only 288 fossil species have been described to date, with hundreds more awaiting formal description in palaeontological collections. One of the largest gaps in our knowledge concerns the ~12 million years between the K-PG mass extinction and the late Ypresian, from which only two species have been formally described, including Pimpla stigmatica Henriksen from the Danish Fur Formation (~55 Ma). Ie here redescribe and reclassify this species in the genus Epitheronia Gupta, n. comb., and describe nine new species from this fossil locality that are consistent with a placement in Pimplinae: Crusopimpla collina n. sp., C. elongata n. sp., C. minuta n. sp., C. rettigi n. sp., C. violina n. sp., Theronia? furensis n. sp., T. nigriscutum n. sp., Xanthopimpla ciboisae n. sp., and X. crescendae n. sp. The diagnosis of the genus Crusopimpla Kopylov, Spasojevic & Klopfstein is amend in the light of the new species. By comparing the preserved colouration between and within specimens of different species, we draw conclusions about the taxonomic usefulness of colour patterns observed in Fur Formation ichneumonids. The number of described species of pimpline parasitoid wasps from Fur is very high when compared to any other fossil deposit, but low with respect to numbers of extant species. Further study and excavation of Fur ichneumonids will certainly reveal an even higher diversity.
Validity of freehand three-dimensional ultrasound system in measurement of three-dimensional surface shape of shoulder muscles
Authors: Umehara Jun , Fukuda Norio , Konda Shoji , Hirashima Masaya 
Published: November 2021

AbstractFreehand three-dimensional ultrasound (3DUS) system is a promising technique for accurately assessing muscle morphology. However, its accuracy has been validated mainly in terms of volume by examining lower limb muscles. This study aimed to validate 3DUS in the measurements of 3D surface shape and volume by comparing them with MRI measurements while ensuring the reproducibility of participant posture by focusing on the shoulder muscles. The supraspinatus, infraspinatus, and posterior deltoid muscles of 10 healthy males were scanned using 3DUS and MRI while secured by an immobilization support customized for each participant. A 3D surface model of each muscle was created from the 3DUS and MRI methods, and the agreement between them was assessed. For the muscle volume, the mean difference between the two models was within −0.51 cm3. For the 3D surface shape, the distances between the closest points of the two models and Dice similarity coefficient were calculated. The results showed that the median surface distance was less than 1.21 mm and Dice similarity coefficient was larger than 0.85. These results suggest that, given the above error is permitted, 3DUS can be used as an alternative to MRI in measuring volume and surface shape, even for the shoulder muscles.
Deciphering a hexameric protein complex with Angstrom optical resolution
Authors: Mazal Hisham , Wieser Franz-Ferdinand , Sandoghdar Vahid 
Published: November 2021

AbstractCryogenic optical localization in three dimensions (COLD) was recently shown to resolve up to four binding sites on a single protein. However, because COLD relies on intensity fluctuations that result from the blinking behavior of fluorophores, it is limited to cases, where individual emitters show different brightness. This significantly lowers the measurement yield. To extend the number of resolved sites as well as the measurement yield, we employ partial labeling and combine it with polarization encoding in order to identify single fluorophores during their stochastic blinking. We then use a particle classification scheme to identify and resolve heterogenous subsets and combine them to reconstruct the three-dimensional arrangement of large molecular complexes. We showcase this method (polarCOLD) by resolving the trimer arrangement of proliferating cell nuclear antigen (PCNA) and the hexamer geometry of Caseinolytic Peptidase B (ClpB) ofThermus thermophilusin its quaternary structure, both with Angstrom resolution. The combination of polarCOLD and single-particle cryogenic electron microscopy (cryoEM) promises to provide crucial insight into intrinsic, environmental and dynamic heterogeneities of biomolecular structures. Furthermore, our approach is fully compatible with fluorescent protein labeling and can, thus, be used in a wide range of studies in cell and membrane biology.Significance statementFluorescence super-resolution microscopy has witnessed many clever innovations in the last two decades. Here, we advance the frontiers of this field of research by combining partial labeling and 2D image classification schemes with polarization-encoded single-molecule localization at liquid helium temperature to reach Angstrom resolution in three dimensions. We demonstrate the performance of the method by applying it to trimer and hexamer protein complexes. Our approach holds great promise for examining membrane protein structural assemblies and conformations in challenging native environments. The methodology closes the gap between electron and optical microscopy and offers an ideal ground for correlating the two modalities at the single-particle level. Indeed, correlative light and electron microscopy is an emerging technique that will provide new insight into cell biology.
Differential replay for reward and punishment paths predicts approach and avoidance
Authors: McFadyen Jessica , Liu Yunzhe , Dolan Raymond J 
Published: November 2021

AbstractPlanning is thought to involve neural replay, where states relevant to a task goal are rapidly reactivated in sequence. It remains unclear if, during planning, replay of a path relates to an actual prospective choice. Here, using magnetoencephalography (MEG), we studied participants while they planned to either approach or avoid an uncertain environment that contained paths leading to reward and to punishment. We show significant planning-related forward sequential replay with state-to-state transitions in the range of 20 to 90 ms. Replay of rewarding paths was boosted prior to a decision to avoid, and attenuated prior to a decision to approach. Crucially, a trial-by-trial bias in replaying punishing paths predicted an irrational choice to approach when a prospective environment was more risky, an effect that was particularly marked in more anxious participants. The findings reveal a coupling between the content of forwards replay and rational choice behaviour, such that replay prioritises an online representation of potential reward.
A human kinase yeast array for the identification of kinases modulating phosphorylation-dependent protein-protein interactions
Authors: Jehle Stefanie , Kunowska Natalia , Benlasfer Nouhad , Woodsmith Jonathan , Weber Gert , Wahl Markus C. , Stelzl Ulrich 
Published: November 2021

AbstractProtein kinases play an important role in cellular signaling pathways and their dysregulation leads to multiple diseases, making kinases prime drug targets. While more than 500 human protein kinases are known to collectively mediate phosphorylation of over 290,000 S/T/Y sites, the activities have been characterized only for a minor, intensively studied subset. To systematically address this discrepancy, we developed a human kinase array in Saccharomyces cerevisiae as a simple readout tool to systematically assess kinase activities. For this array, we expressed 266 human kinases in four different Saccharomyces cerevisiae strains and profiled ectopic growth as a proxy for kinase activity across 33 conditions. More than half of the kinases showed an activity-dependent phenotype across many conditions and in more than one strain. We then employed the kinase array to identify the kinase(s) that can modulate protein-protein-interactions (PPIs). Two characterized, phosphorylation-dependent PPIs with unknown kinase-substrate relationships were analyzed in a phospho-yeast two-hybrid assay. CK2α1 and SGK2 kinases can abrogate the interaction between the spliceosomal proteins AAR2 and PRPF8 and NEK6 kinase was found to mediate the estrogen receptor (ERα) interaction with 14-3-3 proteins. The human kinase yeast array can thus be used for a variety of kinase activity-dependent readouts.