bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of COVID-19 cases during Tokyo’s Olympic and Paralympic Games
Authors: Tokuda Yasuharu , Kuniya Toshikazu 
Published: April 2021

ABSTRACTTokyo’s Olympic and Paralympic Games set to begin in late July 2021 without spectators from abroad, but vaccine rollout has been slow in Japan compared to other developed countries. In this study, COVID-19 epidemic curve in Tokyo is developed based on weekly reported data from January 23, 2020 until April 16, 2021. The maximum daily number of the infected cases in Tokyo in August 2021 would be 7,991 if the current pace of vaccinations (1/1,000 per day). This daily number is greater than the highest daily cases (2,447) recorded on January 7, 2021. However, if the rollout pace could be doubled (1/500 per day), the peak daily new cases would be 4,470 in August. If it could be quadrupled (1/250 per day), the peak would be noted at 2,128 in July and the highest number in August would be 1,977. If vaccine rollout could not be enhanced, the cancellation might be an acceptable decision, since health is the most precious to our Olympians.
REST/NRSF drives homeostatic plasticity of inhibitory synapses in a target-dependent fashion
Authors: Prestigio Cosimo , Ferrante Daniele , Marte Antonella , Romei Alessandra , Lignani Gabriele , Onofri Franco , Valente Pierluigi , Benfenati Fabio , Baldelli P Pietro 
Published: April 2021

ABSTRACTThe repressor-element 1-silencing transcription/neuron-restrictive silencer factor (REST/NRSF) controls hundreds of neuron specific genes. We showed that REST/NRSF downregulates glutamatergic transmission in response to hyperactivity, thus contributing to neuronal homeostasis. However, whether GABAergic transmission is also implicated in the homeostatic action of REST/NRSF is unknown. Here, we show that hyperactivity-induced REST/NRSF activation triggers a homeostatic enhancement of GABAergic inhibition, with increased frequency of miniature inhibitory postsynaptic currents (IPSCs) and amplitude of evoked IPSCs. Notably, this effect was only observed at inhibitory-onto-excitatory neuron synapses, whose density increased at perisomatic sites, demonstrating a strict target-selectivity. These effects were occluded by TrkB receptor inhibition and resulted from a coordinated and sequential activation of the Npas4 and BDNF gene programs. The findings highlight the central role of REST/NRSF in the complex transcriptional responses aimed at preserving physiological levels of neuronal activity in front of the ever-changing environment.Impact StatementThis work elucidates the mechanisms by which the transcriptional regulator REST/NRSF selectively upregulates GABAergic transmission onto excitatory neurons in response to hyperactivity to rescue neuronal homeostasis.
Deep time course proteomics of SARS-CoV- and SARS-CoV-2-infected human lung epithelial cells (Calu-3) reveals strong induction of interferon-stimulated gene (ISG) expression by SARS-CoV-2 in contrast to SARS-CoV
Authors: Grossegesse Marica , Bourquain Daniel , Neumann Markus , Schaade Lars , Nitsche Andreas , Doellinger Joerg 
Published: April 2021

AbstractSARS-CoV and SARS-CoV-2 infections are characterized by remarkable differences, including contagiosity and case fatality rate. The underlying mechanisms are not well understood, illustrating major knowledge gaps of coronavirus biology. In this study, protein expression of SARS-CoV- and SARS-CoV-2-infected human lung epithelial cell line Calu-3 was analysed using data-independent acquisition mass spectrometry (DIA-MS). This resulted in the so far most comprehensive map of infection-related proteome-wide expression changes in human cells covering the quantification of 7478 proteins across 4 time points. Most notably, the activation of interferon type-I response was observed, which surprisingly is absent in other recent proteome studies, but is known to occur in SARS-CoV-2-infected patients. The data reveal that SARS-CoV-2 triggers interferon-stimulated gene (ISG) expression much stronger than SARS-CoV, which reflects the already described differences in interferon sensitivity. Potentially, this may be caused by the enhanced expression of viral M protein of SARS-CoV in comparison to SARS-CoV-2, which is a known inhibitor of type I interferon expression. This study expands the knowledge on the host response to SARS-CoV-2 infections on a global scale using an infection model, which seems to be well suited to analyse innate immunity.
Comparative Analysis of Emerging B.1.1.7+E484K SARS-CoV-2 isolates from Pennsylvania
Authors: Moustafa Ahmed M. , Bianco Colleen , Denu Lidiya , Ahmed Azad , Neide Brandy , Everett John , Reddy Shantan , Rabut Emilie , Deseignora Jasmine , Feldman Michael D. , Rodino Kyle G. , Bushman Frederic , Harris Rebecca M. , Mell Josh Chang , Planet Paul J. 
Published: April 2021

AbstractRapid whole genome sequencing of SARS-CoV-2 has presented the ability to detect new emerging variants of concern in near real time. Here we report the genome of a virus isolated in Pennsylvania in March 2021 that was identified as lineage B.1.1.7 (VOC-202012/01) that also harbors the E484K spike mutation, which has been shown to promote “escape” from neutralizing antibodiesin vitro. We compare this sequence to the only 5 other B.1.1.7+E484K genomes from Pennsylvania, all of which were isolated in mid March. Beginning in February 2021, only a small number (n=60) of isolates with this profile have been detected in the US, and only a total of 253 have been reported globally (first in the UK in December 2020). Comparative genomics of all currently available high coverage B.1.1.7+E484K genomes (n=235) available on GISAID suggested the existence of 7 distinct groups or clonal complexes (CC; as defined by GNUVID) bearing the E484K mutation raising the possibility of 7 independent acquisitions of the E484K spike mutation in each background. Phylogenetic analysis suggested the presence of at least 3 distinct clades of B.1.1.7+E484K circulating in the US, with the Pennsylvanian isolates belonging to two distinct clades. Increased genomic surveillance will be crucial for detection of emerging variants of concern that can escape natural and vaccine induced immunity.
Is a nudge all we need to promote deliberate clinical inertia and thoughtful clinical decision making?
Authors: Foster Mieke , Egerton‐Warburton Diana , Cullen Louise , Fatovich Daniel M , Keijzers Gerben 
Published: April 2021

AbstractDeliberate clinical inertia is the art of doing nothing as a positive response. Individual clinicians can promote deliberate clinical inertia through teaching, re‐framing the act of ‘doing nothing’ as ‘doing something’ and engaging in shared decision making. Behaviour change on a larger scale requires a systematic approach. Nudging is a subtle change to the decision‐making context to prompt specific choices. A nudge unit is a team of relevant professionals who engage with various multidisciplinary teams within a health service who help test and implement nudge interventions in a clinical environment. A nudge unit could be used to design environments to prompt clinicians to re‐think before ordering unnecessary tests or treatments. Nudge units could improve knowledge translation, support continuous quality improvement and help build a learning health system. They could also boost collaboration and empower staff to evaluate their workplace decision‐making frameworks.
International student mobilities in a contagion: (Im)mobilising higher education?
Authors: Sidhu Ravinder , Cheng Yi' En , Collins Francis , Ho Kong Chong , Yeoh Brenda 
Published: April 2021

AbstractThis article reflects on the possible effects of the COVID‐19 pandemic on international student mobilities and higher education systems. Celebrated as a ‘success’ story of a mutually beneficial globalisation, international higher education as we have known it is unravelling and reassembling. We offer an overview of the material changes and public discourses that are reframing student mobilities and higher education from three Anglophone positions involving Australia, Singapore, and New Zealand. The authors interrogate the amplified role of digital infrastructures in remaking international higher education, through border management practices and digital learning strategies. We outline changes at the urban scale that are starting to take hold from the stasis in student mobilities. We also speculate on emerging modalities of international higher education and their accompanying economies of opportunities and vulnerabilities. Our reflections take seriously calls to understand the wide‐reaching implications of an invisible, border‐crossing microbe, and interrupt the impulse to resurrect what came before the pandemic. It is in this spirit of thoughtful reflection to stop rebuilding ‘more of the same’ that we interrogate novel border rationalities and market making, which are being called on in work to govern space–time and subjects in a fragile post‐COVID world.
Morphological and scanning electron microscopic study of the gonadal arterioles in the Tibetan sheep
Authors: Guo Yajun , Yang Yanan , Wang Biao , Liu Chengze , Li Mingna , Wang Xinrong 
Published: April 2021

AbstractThis research aimed at revealing the structural features of Tibetan sheep's testicular and ovarian vasculature and providing theoretical basis for Tibetan sheep's physiological adaptability in plateau and low‐oxygen environments. Through scanning electron microscopy, corrosion casts of the feature of the gonad arterioles were observed and analysed. The results of this study found that centrifugal arteries, centrifugal and centripetal arterioles were distributed in a ‘dendritic’ fashion in the testis lobule, the ovarian arteries and arterioles, which had a spiral shape. Testicular Tibetan Sheep knot‐like artery had a denser spiral structure, and there were more branches in the microarteries. On the testis lobule and arteriole of caput epididymidis, the arteriole surface shows the ‘fusiform’ indentation to be more shallower. The ovarian artery had a higher degree of helix; its surface was distributed like a ‘bark‐like’ indentation; and the ring was narrower and denser. Nevertheless, the arteriole network had a high concentration and a wide number of branches, as that of the ovarian arteriole network which had more end branches, the surface of the arterioles of ovaries and testicles was scarred and denser. The studies indicate that the structural features of testicular lobule, epididymal arterioles and ovarian arterioles are more conducive to increase the oxygen supply to the gonads tissue and controlling blood flow velocity and metabolism to respond to high altitudes and low‐oxygen environments.
Neurofibromatosis type 1: Expanded variant spectrum with multiplex ligation‐dependent probe amplification and genotype–phenotype correlation in 138 Turkish patients
Authors: Güneş Nilay , Yeşil Gözde , Geyik Filiz , Kasap Büşra , Celkan Tiraje , Kebudi Rejin , Tüysüz Beyhan 
Published: April 2021

AbstractObjectiveTo investigate the variant spectrum and genotype–phenotype correlations in a Turkish cohort with Neurofibromatosis Type‐1 (NF1).Materials and methods We retrospectively investigated the clinical and molecular data of 138 NF1 patients from 129 families who had been followed‐up for a median of 3.9 (1.25–18.5) years.ResultsNF1 sequencing revealed 73 different intragenic variants, 19 of which were novel. Seven large deletions were detected by multiplex ligation‐dependent probe amplification (MLPA) analyses. The total detection rate of pathogenic NF1 variants was found to be 87.1%. Comparing age groups, cutaneous neurofibromas, freckling, and Lisch nodules were more prevalent in patients older than 12 years (p > .05). Optic glioma detected in 17.3% of the patients and was significantly more common before the age of 6 (p > .001). Other solid tumors developed in 5% of the patients. There was no genotype–phenotype correlation between patients with truncating and nontruncating variants. However, six out of seven patients with large deletions had significant developmental delay, one patient with the c.2970_2972delAAT (p.Met992del) variant had only typical pigmentary features, and another patient with the c.4267A > G (p.Lys1423Glu) variant had CALMs, freckling, neurofibromas, and Noonan‐like phenotype.ConclusionsWe described 19 novel variants and seven large deletions in NF1. Applying MLPA assay in NF1 is useful in expanding the molecular diagnosis. Although very limited genotype–phenotype correlation has been reported in NF1, the fact that specific phenotypic findings were observed in our patients with large deletions and two intragenic variants supports the studies published recently.
Visualising and understanding cGMP signals in the cardiovascular system
Authors: Feil Robert , Lehners Moritz , Stehle Daniel , Feil Susanne 
Published: April 2021

cGMP is an important signalling molecule in humans. Fluorescent cGMP biosensors have emerged as powerful tools for the sensitive analysis of cGMP pathways at the single‐cell level. Here, we briefly outline cGMP's multifaceted role in (patho)physiology and pharmacotherapy. Then we summarise what new insights cGMP imaging has provided into endogenous cGMP signalling and drug action, with a focus on the cardiovascular system. Indeed, the use of cGMP biosensors has led to several conceptual advances, such as the discovery of local, intercellular and mechanosensitive cGMP signals. Importantly, single‐cell imaging can provide valuable information about the heterogeneity of cGMP signals within and between individual cells of an isolated cell population or tissue. We also discuss current challenges and future directions of cGMP imaging, such as the direct visualisation of cGMP microdomains, simultaneous monitoring of cGMP and other signalling molecules and, ultimately, cGMP imaging in tissues and animals under close‐to‐native conditions.LINKED ARTICLESThis article is part of a themed issue on cGMP Signalling in Cell Growth and Survival. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.11/issuetoc
L‐NAME, a nitric oxide synthase inhibitor, increases the protein expression of both executioner and inhibitor of apoptosis in the placental bed of mid‐to‐late pregnant rats
Authors: Ishikawa Wataru , Kazama Shugo , Suzuki Takehito , Yamana Rei , Miyazaki Yoko , Tanaka Kazuaki , Usami Makoto , Takizawa Tatsuya 
Published: April 2021

AbstractThe involvement of nitric oxide (NO) signaling in apoptosis was examined in the placental bed of mid‐to‐late pregnant rats. Pregnant rats were treated with l‐NAME, a nitric oxide synthase inhibitor, by subcutaneous infusion for 48 hours before the examination at day 13.5, 17.5, or 21.5. l‐NAME induced apoptosis in the placental bed to a limited extent at days 13.5 and 17.5, but not at day 21.5. When the placental bed was examined at day 17.5, the protein expression of both executioner (C‐Cas3) and inhibitor (XIAP) of apoptosis was increased by l‐NAME, but they did not co‐localized with apoptosis. It was presumed that placental bed apoptosis induced by l‐NAME is regulated through the expression of both executioner and inhibitor, possibly involving protein S‐nitrosylation.
Nickel and tattoos: Where are we?
Authors: Kluger Nicolas 
Published: April 2021

AbstractTattoos are not mentioned as a source of exposure to nickel. Traces of nickel are, however, almost inevitably found in tattoo inks as impurities and sometimes in tattooed skin. Whether nickel in tattoos has any health consequence is debated. We performed a narrative review of what is currently known about this topic. Today, nickel is frequently detected in inks, but at highly variable levels. It appears to be at higher concentrations in green, blue, and sometimes brown and violet inks. Only nickel allergy in tattooed individuals and nickel‐associated tattoo ink allergy are addressed in the literature. Reports of tattoo ink allergy related to nickel are rare and heterogenous. Authors often neglect possible implications of other metals or dyes. A positive patch test is not enough to confirm the role of nickel in a reaction observed after tattooing. We found no report of any systemic complication attributed to nickel from tattoos. The Council of Europe bans the presence of nickel at high levels in tattoo inks, which is a safety net for individuals with nickel allergy. Large epidemiologic case–control studies with systematic biopsies on normal and inflamed tattoos and patch testing would help to understand the role of nickel in tattoo ink allergies.
Detecting a copycat effect in school shootings using spatio‐temporal panel count models
Authors: Schweikert Karsten , Huth Manuel , Gius Mark 
Published: April 2021

AbstractSchool shootings are often motivated by the perpetrators' desire for media attention and notoriety. As school shootings receive intense regional and national media coverage, a high likelihood for copycat attacks can be expected. We investigate whether a copycat effect can be detected in US state‐level school shooting data from 1990 to 2017. We do so by estimating spatio‐temporal panel count models and control for socio‐economic characteristics, as well as state and Federal gun control laws. Positive spatial and temporal dependence indicate that the risk for additional school shootings in the same and neighboring states increases after the initial attack.
How Children Process Reduced Forms: A Computational Cognitive Modeling Approach to Pronoun Processing in Discourse
Authors: Vogelzang Margreet , Guasti Maria Teresa , van Rijn Hedderik , Hendriks Petra 
Published: April 2021

AbstractReduced forms such as the pronoun he provide little information about their intended meaning compared to more elaborate descriptions such as the lead singer of Coldplay. Listeners must therefore use contextual information to recover their meaning. Across languages, there appears to be a trade‐off between the informativity of a form and the prominence of its referent. For example, Italian adults generally interpret informationally empty null pronouns as in the sentence Corre (meaning “He/She/It runs”) as referring to the most prominent referent in the discourse, and more informative overt pronouns (e.g., lui in Lui corre, “He runs”) as referring to less prominent referents. Although children acquiring Italian are known to experience difficulties interpreting pronouns, it is unclear how they acquire this division of pragmatic labor between null and overt subject pronouns, and how this relates to the development of their cognitive capacities. Here we show that cognitive development can account for the general interpretation patterns displayed by Italian‐speaking children and adults. Using experimental studies and computational simulations in a framework modeling bounded‐rational behavior, we argue that null pronoun interpretation is influenced by working memory capacity and thus appears to depend on discourse context, whereas overt pronoun interpretation is influenced by processing speed, suggesting that listeners must reason about the speaker's choices. Our results demonstrate that cognitive capacities may constrain the acquisition of linguistic forms and their meanings in various ways. The novel predictions generated by the computational simulations point out several directions for future research.
Direct Versus Indirect Causation as a Semantic Linguistic Universal: Using a Computational Model of English, Hebrew, Hindi, Japanese, and K'iche’ Mayan to Predict Grammaticality Judgments in Balinese
Authors: Aryawibawa I Nyoman , Qomariana Yana , Artawa Ketut , Ambridge Ben 
Published: April 2021

AbstractThe aim of this study was to test the claim that languages universally employ morphosyntactic marking to differentiate events of more‐ versus less‐direct causation, preferring to mark them with less‐ and more‐ overt marking, respectively (e.g., Somebody broke the window vs. Somebody MADE the window break; *Somebody cried the boy vs. Somebody MADE the boy cry). To this end, we investigated whether a recent computational model which learns to predict speakers’ by‐verb relative preference for the two causatives in English, Hebrew, Hindi, Japanese, and K'iche’ Mayan is able to generalize to a sixth language on which it has never been trained: Balinese. Judgments of the relative acceptability of the less‐ and more‐transparent causative forms of 60 verbs were collected from 48 native‐speaking Balinese adults. The composite crosslinguistic computational model was able to predict these judgments, not only for verbs that it had seen, but also––in a split‐half validation test––to verbs that it had never seen in any language. A “random‐semantics” model showed only a relatively small decrement in performance with seen verbs, whose behavior can be learned on a verb‐by‐verb basis, but achieved zero correlation with human judgments when generalizing to unseen verbs. Together, these findings suggest that Balinese conceptualizes directness of causation in a similar way to these unrelated languages, and therefore constitute support for the view that the distinction between more‐ versus less‐distinct causation constitutes a morphosyntactic universal.
How Reliably Do Eye Parameters Indicate Internal Versus External Attentional Focus?
Authors: Annerer‐Walcher Sonja , Ceh Simon M. , Putze Felix , Kampen Marvin , Körner Christof , Benedek Mathias 
Published: April 2021

AbstractEye behavior is increasingly used as an indicator of internal versus external focus of attention both in research and application. However, available findings are partly inconsistent, which might be attributed to the different nature of the employed types of internal and external cognition tasks. The present study, therefore, investigated how consistently different eye parameters respond to internal versus external attentional focus across three task modalities: numerical, verbal, and visuo‐spatial. Three eye parameters robustly differentiated between internal and external attentional focus across all tasks. Blinks, pupil diameter variance, and fixation disparity variance were consistently increased during internally directed attention. We also observed substantial attentional focus effects on other parameters (pupil diameter, fixation disparity, saccades, and microsaccades), but they were moderated by task type. Single‐trial analysis of our data using machine learning techniques further confirmed our results: Classifying the focus of attention by means of eye tracking works well across participants, but generalizing across tasks proves to be challenging. Based on the effects of task type on eye parameters, we discuss what eye parameters are best suited as indicators of internal versus external attentional focus in different settings.
Is Aristotelian friendship disinterested?: Aristotle on loving the other for himself and wishing goods for the other's sake
Authors: Kim Bradford Jean‐Hyuk 
Published: April 2021

AbstractIt has been not atypical for commentators to argue that Aristotelian friendship features disinterested concern for others, that is, concern for others that is completely independent of one's own happiness. Often, the relevant commentators point to some normative features of Aristotelian friendship, wishing goods for the other's sake and loving the other for herself, where these are assumed to be disinterested. While the disinterested interpretations may be correct overall, I argue that wishing goods for the other's sake and loving the other for herself constitute a dubious foundation for disinterested interpretations. For wishing goods for the other's sake does not involve a reason for action on the other's behalf, and the primary point of loving the other for herself is the role of the other in facilitating one's own happiness, specifically conceived of by Aristotle in terms of one's own virtuous activity.