bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness and acceptability of an opt-out nudge to promote influenza vaccination among medical residents in Nice, France: a randomized controlled trial
Authors: Barbaroux Adriaan , Serati Ilaria 
Published: September 2022

ABSTRACTBackgroundNudges have been proposed as an effective tool to promote influenza vaccination of healthcare workers. To be successful, nudges must match the needs of the target healthcare workers population and be acceptable.ObjectiveTo evaluate the effectiveness and the acceptability of an opt-out nudge promoting influenza vaccination among medical residents.MethodsThe hypothesis were that an opt-out nudge would be effective, better accepted when applied to patients than to residents, and that prior exposure to a nudge and being vaccinated increase its acceptability and residents’ sense of autonomy (the feeling of being in control of their choice about whether to get vaccinated). Residents were randomly divided into two parallel experimental arms: a nudge group and a control group. The nudge consisted in offering participants an appointment for a flu shot, while leaving them the choice to refuse or to reschedule it.ResultsThe analysis included 260 residents. Residents in nudge group were more likely to be vaccinated than residents in control group. There was a strong consensus among the residents that it is very acceptable to nudge their peers and patients. Acceptability for residents and patients did not differ. Acceptability was better among residents exposed to the nudge and residents who were vaccinated. Residents considered that the nudge does not reduce their control over whether to get a flu shot. The sense of autonomy was associated with nudge’s acceptability.ConclusionAn opt-out nudge to promote influenza vaccination among medical residents can be effective and very well accepted. These data suggest that this approach can complement other vaccination promoting interventions and be eventually extended to other healthcare workers’ categories and to general population, but should consider its ethical implications. More studies are needed to assess the nudge’s effectiveness and acceptability on other populations.Key messagesNudging is one of the most efficient techniques to improve vaccination coverage.Changing defaults may be effective in promoting vaccination and well accepted.Changing defaults does not lower the feeling of control over choices.The sense of autonomy related to a nudge is correlated to its acceptability.Behavior adoption increases the sense of autonomy related to a nudge.Using defaults for nudge should take into account the ethical implications.
Teacher- and Parent-Reported Trajectories of Challenging Behavior Among Individuals with Autism
Authors: Rosen Nicole E. , Schiltz Hillary K. , Lord Catherine 
Published: September 2022

AbstractPeople with autism spectrum disorder (ASD) frequently exhibit challenging behaviors throughout the lifespan, which can have pervasive effects on quality of life. Challenging behaviors have been shown to change over time as a function of various individual-level factors (e.g., cognitive ability), yet research is primarily limited to parent-reported measures. To expand upon this work, the present study aimed to examine trajectories of teacher- and parent-reported challenging behaviors (i.e., hyperactivity, irritability, social withdrawal) and to test whether predictors including ASD features, verbal intelligence quotient, and consistency in reporter impact these trajectories among individuals with ASD or non-spectrum delays from ages 9 to 18. Multilevel models revealed that, according to both teacher and parent report, participants showed the greatest improvement in hyperactivity, less but still notable improvement in irritability, and stable levels of social withdrawal over time. Higher cognitive ability and fewer ASD features emerged as important individual differences related to fewer challenging behaviors. The multi-informant perspective and longitudinal design provide novel insight into the manifestations of these challenging behaviors across different contexts and across time. Findings highlight the importance of addressing challenging behaviors as these behaviors tend to persist throughout development in both home and school contexts, especially for children with particular diagnostic and cognitive profiles.Lay SummaryAccording to both teacher and parent report, youth with autism showed the greatest improvement in hyperactivity, less but still notable improvement in irritability, and stable levels of social withdrawal from school-age to adolescence. Fewer autism features and greater cognitive ability were related to fewer challenging behaviors. This study’s use of multiple reporters (e.g., teachers and parents) across time provided insight into the persistence of challenging behaviors in the home and school settings and across development.
Reactive Postural Responses Predict Risk For Acute Musculoskeletal Injury In Collegiate Athletes
Authors: Morris Amanda , Fino Nora F. , Pelo Ryan , Cushman Daniel M. , Monson Nicholas E. , Jameson Trevor , Dibble Leland E. , Fino Peter C. 
Published: September 2022

ABSTRACTIdentifying risk factors for musculoskeletal (MSK) injury is critical to maintain the health and safety of athletes. While current tests consider isolated assessments of function or subjective ratings, objective tests of reactive postural responses, especially when in cognitively demanding scenarios, may better identify risk of MSK injury than traditional tests alone.ObjectivesTo examine if objective assessments of reactive postural responses, quantified using wearable inertial measurement units, are associated with the risk for acute lower extremity MSK injuries in collegiate athletes.DesignProspective survival analysisMethods191 Division I NCAA athletes completed an instrumented version of a modified Push and Release (I-mP&R) test at the beginning of their competitive season. The I-mP&R was performed with eyes closed under single- and dual-task (concurrent cognitive task) conditions. Inertial measurement units recorded acceleration and angular velocity data that was used to calculate time to stability (TTS). Acute lower extremity MSK injuries were tracked from first team activity for six months. Cox proportional hazard models were used to determine if longer times to stability were associated with faster time to injury.ResultsLonger TTS was associated with increased risk of injury; every 250 ms increase in dual-task median TTS was associated with a 37% increased risk of acute, lower-extremity MSK injury.ConclusionTests of reactive balance, particularly under dual-task conditions, may be able to identify athletes at risk of acute lower extremity MSK injury. Clinically-feasible, instrumented tests of reactive should be considered in assessments for prediction and prevention of MSK injury in collegiate athletes.
Noninvasive diagnosis of secondary infections in COVID-19 by sequencing of plasma microbial cell-free DNA
Authors: Lisius Grace , Duttagupta Radha , Ahmed Asim A. , Hensley Matthew , Al-Yousif Nameer , Lu Michael , Bain William , Shah Faraaz , Schaefer Caitlin , Qin Shulin , Wang Xiaohong , Zhang Yingze , Mitchell Kevin J. , Hughes Ellen K. , Jacobs Jana L. , Naqvi Asma , Haidar Ghady , Mellors John W. , Methé Barbara , McVerry Bryan J. , Morris Alison , Kitsios Georgios D. 
Published: September 2022

AbstractBackgroundSecondary infection (SI) diagnosis in COVID-19 is challenging, due to overlapping clinical presentations, practical limitations in obtaining samples from the lower respiratory tract (LRT), and low sensitivity of microbiologic cultures.Research QuestionCan metagenomic sequencing of plasma microbial cell-free DNA (mcfDNA-Seq) help diagnose SIs complicating COVID-19?Study Design and MethodsWe enrolled 42 inpatients with COVID-19 classified as microbiologically-confirmed SI (Micro-SI, n=8), clinically-diagnosed SI (Clinical-SI, n=13, i.e. empiric antimicrobials), or no clinical suspicion for SI (No-Suspected-SI, n=21) at time of enrollment. From baseline and follow-up plasma samples (days 5 and 10 post-enrollment), we quantified mcfDNA for all detected microbes by mcfDNA sequencing and measured nine host-response biomarkers. From LRT samples among intubated subjects, we quantified bacterial burden with 16S rRNA gene quantitative PCR.ResultsWe performed mcfDNA-Seq in 82 plasma samples. Sequencing was successful in 60/82 (73.2%) samples, which had significantly lower levels of human cfDNA than failed samples (p<0.0001). McfDNA detection was significantly higher in Micro-SI (15/16 [94%]) compared to Clinical-SI samples (8/14 [57%], p=0.03), and unexpectedly common in No-Suspected-SI samples (25/30 [83%]), similar to detection rate in Micro-SI. We detected culture-concordant mcfDNA species in 13/16 Micro-SI samples (81%) and mcfDNA levels tracked with SI outcome (resolution or persistence) under antibiotic therapy. McfDNA levels correlated significantly with LRT bacterial burden (r=0.74, p=0.02) as well as plasma biomarkers of host response (white blood cell count, IL-6, IL-8, and SPD, all p<0.05). Baseline mcfDNA levels were predictive of worse 90-day survival (hazard ratio 1.30 [1.02-1.64] for each log10 mcfDNA, p=0.03).InterpretationHigh circulating levels of mcfDNA in a substantial proportion of patients with COVID-19 without clinical suspicion for SI suggest that SIs may often remain undiagnosed. McfDNA-Seq, when clinically available, can offer a non-invasive diagnostic tool for pathogen identification, with prognostic value on host inflammatory response and clinical outcomes.
How short decoding times, stimulus dimensionality and spontaneous activity constrain the shape of tuning curves: A speed-accuracy trade-off
Authors: Lenninger Movitz , Skoglund Mikael , Herman Pawel , Kumar Arvind 
Published: September 2022

AbstractAccording to the efficient coding hypothesis, sensory neurons are adapted to provide maximal information about the environment given some biophysical constraints. Early sensory neurons modulate their average firing rates in response to some features of the external stimulus, creating tuned responses. In early visual areas, these modulations (or tunings) are predominantly single-peaked. However, periodic tuning, as exhibited by grid cells, has been linked to a significant increase in decoding performance. Does this imply that the tuning curves in early visual areas are sub-optimal? We argue that the time scale at which neurons encode information is imperative to understanding the relative advantages of single-peaked and periodic tuning curves. Because, if decoding ability scales differently with time for the different shapes of tuning curves, the time scale at which the neurons operate becomes critical. Here, we show that the possibility of catastrophic (large) errors due to overlapping neural responses for distinct stimulus conditions creates a trade-off between decoding time and decoding ability. Unfortunately, standard theoretical measures such as Fisher information do not capture these errors. We investigate how (very) short decoding times and stimulus dimensionality affect the optimal shape of tuning curves for stimuli with finite domains. In particular, we focus on the spatial periods of the tuning curves (or the number of “peaks”) for a class of circular tuning curves. We show a general trend for minimal decoding time, i.e., the shortest decoding time required to produce a statistically reliable signal, to increase with increasing Fisher information implying a trade-off between accuracy and speed. This trade-off is reinforced whenever the stimulus dimensionality is high or there is ongoing activity. Thus, given constraints on processing speed, we present normative arguments for the existence of single-peaked, rather than a periodic, tuning organization observed in early visual areas.
G protein-coupled Receptor Contributions to Wing Growth and Morphogenesis inDrosophila melanogaster
Authors: Huizar Francisco J. , Kumar Nilay , Unger Maria , Velagala Vijay , Wu Qinfeng , Brodskiy Pavel A. , Zartman Jeremiah J. 
Published: September 2022

AbstractThe development of multicellular organisms relies on a symphony of spatiotemporally coordinated signals that regulate gene expression. G protein-coupled receptors (GPCRs) are the largest group of transmembrane receptors that play a pivotal role in transducing extracellular signals into physiological outcomes. Emerging research has implicated neurotransmitter GPCRs, classically associated with communication in neuronal tissues, as regulators of pattern formation and morphogenesis. However, how these receptors interact amongst themselves and signaling pathways to regulate organogenesis is still poorly understood. To address this gap, we performed a systematic RNA interference (RNAi)-based screening of 111 GPCRs along with 8 Gα, 3 Gβ, and 2 Gγprotein subunits inDrosophila melanogaster. We performed a coupled, machine learning-based quantitative and qualitative analysis to identify both severe and more subtle phenotypes. Of the genes screened, 25 demonstrated at least 60% penetrance of severe phenotypes with several of the most severe phenotypes resulting from the knockdown of neuropeptide and neurotransmitter GPCRs that were not known previously to regulate epithelial morphogenesis. Phenotypes observed in positive hits mimic phenotypic manifestations of diseases caused by dysregulation of orthologous human genes. Quantitative reverse transcription polymerase chain reaction and meta-analysis of RNA expression validated positive hits. Overall, the combined qualitative and quantitative characterization of GPCRs and G proteins identifies an extensive set of GPCRs involved in regulating epithelial morphogenesis and relevant to the study of a broad range of human diseases.
Individual differences in neural event segmentation of continuous experiences
Authors: Sava-Segal Clara , Richards Chandler , Leung Megan , Finn Emily S. 
Published: September 2022

AbstractEvent segmentation is a spontaneous part of perception, important for processing continuous information and organizing it into memory. While neural and behavioral event segmentation show a degree of inter-subject consistency, meaningful individual variability exists atop these shared patterns. Here we characterized individual differences in the location of neural event boundaries across four short movies that evoked variable interpretations. Event boundary alignment across subjects followed a posterior-to-anterior gradient that was tightly correlated with the rate of segmentation: slower-segmenting regions that integrate information over longer time periods showed more individual variability in boundary locations. This relationship held irrespective of the stimulus, but the degree to which boundaries in particular regions were shared versus idiosyncratic depended on certain aspects of movie content. Furthermore, this variability was behaviorally significant in that similarity of neural boundary locations during movie-watching predicted similarity in how the movie was ultimately remembered and appraised. In particular, we identified a subset of regions in which neural boundary locations are both aligned with behavioral boundaries during encoding and predictive of stimulus interpretation, suggesting that event segmentation may be a mechanism by which narratives generate variable memories and appraisals of stimuli.
Characterizing the differential distribution and targets of Sumo paralogs in the mouse brain
Authors: Suk Terry R. , Nguyen Trina T. , Fisk Zoe A. , Mitkovski Miso , Geertsma Haley M. , Parmasad Jean-Louis A. , Heer Meghan M. , Callaghan Steve M. , Brose Nils , Tirard Marilyn , Rousseaux Maxime W.C. 
Published: September 2022

ABSTRACTSUMOylation is an evolutionarily conserved and essential mechanism whereby Small Ubiquitin Like Modifiers, or SUMO proteins (Sumo in mice), are covalently bound to protein substrates in a highly dynamic and reversible manner. SUMOylation is involved in a variety of basic neurological processes including learning and memory, and central nervous system development, but is also linked with neurological disorders. However, studying SUMOylation in vivo remains challenging due to limited tools to study Sumo proteins and their targets in their native context. More complexity arises from the fact that Sumo1 and Sumo2 are ∼50% homologous, whereas Sumo2 and Sumo3 are nearly identical and indistinguishable with antibodies. While Sumo paralogues can compensate for one another’s loss, Sumo2 is highest expressed and only paralog essential for embryonic development making it critical to uncover roles specific to Sumo2 in vivo. To further examine the roles of Sumo2, and to begin to tease apart the redundancy and similarity between key Sumo paralogs, we generated (His6-)HA epitope-tagged Sumo2 knock-in mouse alleles, expanding the current Sumo knock-in mouse tool-kit comprising of the previously generated His6-HA-Sumo1 knock-in model. Using these HA-Sumo mouse lines, we performed whole brain imaging and mapping to the Allen Brain Atlas to analyze the relative distribution of the Sumo1 and Sumo2 paralogues in the adult mouse brain. We observed differential staining patterns between Sumo1 and Sumo2, including a partial localization of Sumo2 in nerve cell synapses of the hippocampus. Combining immunoprecipitation with mass spectrometry, we identified native substrates targeted by Sumo1 or Sumo2 in the mouse brain. We validated select hits using proximity ligation assays, further providing insight into the subcellular distribution of neuronal Sumo2-conjugates. These mouse models thus serve as valuable tools to study the cellular and biochemical roles of SUMOylation in the central nervous system.
Local and long-distance inputs dynamically regulate striatal acetylcholine during decision making
Authors: Chantranupong Lynne , Beron Celia C. , Zimmer Joshua A. , Wen Michelle J. , Wang Wengang , Sabatini Bernardo L. 
Published: September 2022

AbstractWithin the basal ganglia, striatal dopamine (DA) and acetylcholine (Ach) are essential for the selection and reinforcement of motor actions and decision making. In vitro studies have revealed a circuit local to the striatum by which each of these two neurotransmitters directly regulates release of the other. Ach, released by a unique population of cholinergic interneurons (CINs), drives DA release via direct axonal depolarization. In turn, DA inhibits CIN activity via dopamine D2 receptors (D2R). Whether and how this circuit contributes to striatal function in vivo remains unknown. To define the in vivo role of this circuit, we monitored Ach and DA signals in the ventrolateral striatum of mice performing a reward-based decision-making task. We establish that DA and Ach exhibit multiphasic and anticorrelated transients that are modulated by decision history and reward outcome. However, CIN perturbations reveal that DA dynamics and reward-prediction error encoding do not require Ach release by CINs. On the other hand, CIN-specific deletion of D2Rs shows that DA inhibits Ach levels in a D2R-dependent manner, and loss of this regulation impairs decision-making. To determine how other inputs to striatum shape Ach signals, we assessed the contribution of projections from cortex and thalamus and found that glutamate release from both sources is required for Ach release. Altogether, we uncover a dynamic relationship between DA and Ach during decision making and reveal modes of CIN regulation by local DA signals and long-range cortical and thalamic inputs. These findings deepen our understanding of the neurochemical basis of decision making and behavior.
Stu2 has an essential kinetochore role independent of regulating microtubule dynamics
Authors: Abouelghar Ahmed , Carrier Joseph S. , Torvi Julia R. , Jenson Erin , Jones Chloe , Gangadharan Binnu , Geyer Elisabeth A. , Rice Luke M. , Lagesse Brent , Barnes Georjana , Miller Matthew P. 
Published: September 2022

ABSTRACTch-TOG family proteins, including the budding yeast Stu2, are essential for spindle formation and chromosome segregation. Such functions depend on an array of activities ranging from microtubule nucleation, polymerization and depolymerization, to conferring tension sensitivity to kinetochores. This functional diversity makes it challenging to dissect these various functions and understand their relative importance. Here, we developed separation-of-function mutants and used artificial tethering tools to elucidate several important mechanistic insights into Stu2’s essential role. We show that Stu2’s microtubule polymerization activity depends on its basic linker region but is surprisingly dispensable for viability; that in fact, Stu2 carries out an essential kinetochore-associated function; and finally, that Stu2’s precise location within the kinetochore is critical for its function, suggesting a spatial separation mode of action may underlie its ability to confer tension sensitivity. Our findings highlight the significance of Stu2’s kinetochore role and provide insights into the molecular mechanisms by which it performs its various functions.
How enhancers regulate wavelike gene expression patterns: Novel enhancer prediction and live reporter systems identify an enhancer associated with the arrest of pair-rule waves in the short-germ beetleTribolium
Authors: Mau Christine , Rudolf Heike , Strobl Frederic , Schmid Benjamin , Regensburger Timo , Palmisano Ralf , Stelzer Ernst , Taher Leila , El-Sherif Ezzat 
Published: September 2022

AbstractA key problem in development is to understand how genes turn on or off at the right place and right time during embryogenesis. Such decisions are made by non-coding sequences called ‘enhancers’. Much of our models of how enhancers work rely on the assumption that genes are activatedde novoas stable domains across embryonic tissues. Such view has been strengthened by the intensive landmark studies of the early patterning of the anterior-posterior (AP) axis of theDrosophilaembryo, where indeed gene expression domains seem to arise more or less stably. However, careful analysis of gene expressions in other model systems (including the AP patterning in vertebrates and short-germ insects like the beetleTribolium castaneum) painted a different, very dynamic view of gene regulation, where genes are oftentimes expressed in a wavelike fashion. How such gene expression waves are mediated at the enhancer level is so far unclear. Here we establish the AP patterning of the short-germ beetleTriboliumas a model system to study dynamic and temporal pattern formation at the enhancer level. To that end, we established an enhancer prediction system inTriboliumbased on time- and tissue-specific ATAC-seq and an enhancer live reporter system based on MS2 tagging. Using this experimental framework, we discovered severalTriboliumenhancers, and assessed the spatiotemporal activities of some of them in live embryos. We found our data consistent with a model in which the timing of gene expression during embryonic pattern formation is mediated by a balancing act between enhancers that induce rapid changes in gene expressions (that we call ‘dynamic enhancers’) and enhancers that stabilizes gene expressions (that we call ‘static enhancers’).