bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dexmedetomidine Clearance Decreases with Increasing Drug Exposure: Implications for Current Dosing Regimens and Target-controlled Infusion Models Assuming Linear Pharmacokinetics
Authors: Alvarez-Jimenez Ricardo , Weerink Maud A. S. , Hannivoort Laura N. , Su Hong , Struys Michel M. R. F. , Loer Stephan A. , Colin Pieter J. 
Published: December 2021

Background
Numerous pharmacokinetic models have been published aiming at more accurate and safer dosing of dexmedetomidine. The vast majority of the developed models underpredict the measured plasma concentrations with respect to the target concentration, especially at plasma concentrations higher than those used in the original studies. The aim of this article was to develop a dexmedetomidine pharmacokinetic model in healthy adults emphasizing linear versus nonlinear kinetics.

Methods
The data of two previously published clinical trials with stepwise increasing dexmedetomidine target-controlled infusion were pooled to build a pharmacokinetic model using the NONMEM software package (ICON Development Solutions, USA). Data from 48 healthy subjects, included in a stratified manner, were utilized to build the model.

Results
A three-compartment mamillary model with nonlinear elimination from the central compartment was superior to a model assuming linear pharmacokinetics. Covariates included in the final model were age, sex, and total body weight. Cardiac output did not explain between-subject or within-subject variability in dexmedetomidine clearance. The results of a simulation study based on the final model showed that at concentrations up to 2 ng · ml–1, the predicted dexmedetomidine plasma concentrations were similar between the currently available Hannivoort model assuming linear pharmacokinetics and the nonlinear model developed in this study. At higher simulated plasma concentrations, exposure increased nonlinearly with target concentration due to the decreasing dexmedetomidine clearance with increasing plasma concentrations. Simulations also show that currently approved dosing regimens in the intensive care unit may potentially lead to higher-than-expected dexmedetomidine plasma concentrations.

Conclusions
This study developed a nonlinear three-compartment pharmacokinetic model that accurately described dexmedetomidine plasma concentrations. Dexmedetomidine may be safely administered up to target-controlled infusion targets under 2 ng · ml–1 using the Hannivoort model, which assumed linear pharmacokinetics. Consideration should be taken during long-term administration and during an initial loading dose when following the dosing strategies of the current guidelines.

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Preoperative Point-of-Care Ultrasound to Identify Frailty and Predict Postoperative Outcomes: A Diagnostic Accuracy Study
Authors: Canales Cecilia , Mazor Einat , Coy Heidi , Grogan Tristan R. , Duval Victor , Raman Steven , Cannesson Maxime , Singh Sumit P. 
Published: December 2021

Background
Frailty is increasingly being recognized as a public health issue, straining healthcare resources and increasing costs to care for these patients. Frailty is the decline in physical and cognitive reserves leading to increased vulnerability to stressors such as surgery or disease states. The goal of this pilot diagnostic accuracy study was to identify whether point-of-care ultrasound measurements of the quadriceps and rectus femoris muscles can be used to discriminate between frail and not-frail patients and predict postoperative outcomes. This study hypothesized that ultrasound could discriminate between frail and not-frail patients before surgery.

Methods
Preoperative ultrasound measurements of the quadriceps and rectus femoris were obtained in patients with previous computed tomography scans. Using the computed tomography scans, psoas muscle area was measured in all patients for comparative purposes. Frailty was identified using the Fried phenotype assessment. Postoperative outcomes included unplanned intensive care unit admission, delirium, intensive care unit length of stay, hospital length of stay, unplanned skilled nursing facility admission, rehospitalization, falls within 30 days, and all-cause 30-day and 1-yr mortality.

Results
A total of 32 patients and 20 healthy volunteers were included. Frailty was identified in 18 of the 32 patients. Receiver operating characteristic curve analysis showed that quadriceps depth and psoas muscle area are able to identify frailty (area under the curve–receiver operating characteristic, 0.80 [95% CI, 0.64 to 0.97] and 0.88 [95% CI, 0.76 to 1.00], respectively), whereas the cross-sectional area of the rectus femoris is less promising (area under the curve–receiver operating characteristic, 0.70 [95% CI, 0.49 to 0.91]). Quadriceps depth was also associated with unplanned postoperative skilled nursing facility discharge disposition (area under the curve 0.81 [95% CI, 0.61 to 1.00]) and delirium (area under the curve 0.89 [95% CI, 0.77 to 1.00]).

Conclusions
Similar to computed tomography measurements of psoas muscle area, preoperative ultrasound measurements of quadriceps depth shows promise in discriminating between frail and not-frail patients before surgery. It was also associated with skilled nursing facility admission and postoperative delirium.

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Evaluation of Vaccination Strategies for the metropolitan area of Madrid
Authors: Singh David E. , Lucerón Carmen Olmedo , Sánchez Aurora Limia , Guzman-Merino Miguel , Duran Christian , Delgado-Sanz Concepción , Gomez-Barroso Diana , Carretero Jesus , Marinescu Maria-Cristina 
Published: December 2021

AbstractBackgroundThis work analyses the impact of different vaccination strategies on the propagation of COVID-19 within the Madrid metropolitan area starting the 27th of December 2020 and ending in the Summer of 2021. The predictions are based on simulation using EpiGraph, an agent-based COVID-19 simulator.MethodsWe briefly summarize the different interconnected models of EpiGraph and then we provide a comprehensive description of the vaccination model. We evaluate different vaccination strategies, and we validate the simulator by comparing the simulation results with real data from the metropolitan area of Madrid during the third wave.ResultsWe consider the different COVID-19 propagation scenarios on a social environment consisting of the ten largest cities in the Madrid metropolitan area, with 5 million individuals. The results show that the strategy that fares best is to vaccinate the elderly first with the two doses spaced 56 days apart; this approach reduces the final infection rate and the number of deaths by an additional 6% and 3% with respect to vaccinating the elderly first at the interval between doses recommended by the vaccine producer.ConclusionResults show that prioritizing the vaccination of young individuals would significantly increase the number of deaths. On the other hand, spacing out the first and second dose by 56 days would result in a slight reduction in the number of infections and deaths. The reason is the increase in the number of vaccinated individuals at any time during the simulation.
Students Attitudes Surrounding STEM: A Social Cognitive Career Theory Instrument for High School
Authors: McDonough EmilyKate , Sawyer Kayle S. , Wilks Jessica , Jacque Berri 
Published: December 2021

AbstractTo broaden participation in science, technology, engineering, and math (STEM), we must understand the factors that shape perspectives and beliefs around career selection. Good measurement of these factors is crucial to quantify how effectively educational interventions impact student attitudes towards STEM. Adolescents are particularly suited for quantifying intervention efficacy because students build their identities during these formative years and make important career choices. To better quantify intervention efficacy at the high school level, we developed an instrument entitled Student Attitudes Surrounding STEM (SASS), which builds upon the social cognitive career theory (SCCT) framework for understanding career selection. Questionnaire responses were collected from 932 high school students and split into samples of 400 for exploratory factor analysis and 532 for confirmatory factor analysis. The 37 questions clustered into six factors: Self-Efficacy-Experience, Self-Efficacy-Academic, Outcome Expectations, Interests, Negative Perceptions of Scientists, and Career Awareness. Adequate construct validity for the factors indicated in the SASS model was suggested by the fit indices and theoretical considerations. Furthermore, the analyses supported criterion validity, internal consistency, and test-retest reliability. This tool represents a novel integration of three latent variables into SCCT: Negative Perceptions of Scientists, Career Awareness, and an experience factor for Self-Efficacy.
Neural synchronization is strongest to the spectral flux of slow music and depends on familiarity and beat salience
Authors: Weineck Kristin , Wen Olivia Xin , Henry Molly J. 
Published: December 2021

AbstractNeural activity in the auditory system synchronizes to sound rhythms, and brain–environment synchronization is thought to be fundamental to successful auditory perception. Sound rhythms are often operationalized in terms of the sound’s amplitude envelope. We hypothesized that – especially for music – the envelope might not best capture the complex spectro-temporal fluctuations that give rise to beat perception and synchronized neural activity. This study investigated 1) neural synchronization to different musical features, 2) tempo-dependence of neural synchronization, and 3) dependence of synchronization on familiarity, enjoyment, and ease of beat perception. In this electroencephalography study, 37 human participants listened to tempo-modulated music (1–4 Hz). Independent of whether the analysis approach was based on temporal response functions (TRFs) or reliable components analysis (RCA), the spectral flux of music – as opposed to the amplitude envelope – evoked strongest neural synchronization. Moreover, music with slower beat rates, high familiarity, and easy-to-perceive beats elicited the strongest neural response. Our results demonstrate the importance of spectro-temporal fluctuations in music for driving neural synchronization, and highlight its sensitivity to musical tempo, familiarity, and beat salience.
Dynamics of alpha suppression and enhancement may be related to resource competition in cross-modal cortical regions
Authors: Clements Grace M. , Gyurkovics Mate , Low Kathy A. , Beck Diane M. , Fabiani Monica , Gratton Gabriele 
Published: December 2021

AbstractIn the face of multiple sensory streams, there may be competition for processing resources in multimodal cortical area devoted to establishing representations. In such cases, alpha oscillations may serve to maintain the relevant representations and protect them from interference, whereas theta oscillations may facilitate their updating when needed. It can be hypothesized that these oscillations would differ in response to an auditory stimulus when the eyes are open or closed, as intermodal resource competition may be more prominent in the former than in the latter case. Across two studies we investigated the role of alpha and theta power in multimodal competition using an auditory task with the eyes open and closed, respectively enabling and disabling visual processing in parallel with the incoming auditory stream. In a passive listening task (Study 1a), we found alpha suppression following a pip tone with both eyes open and closed, but subsequent alpha enhancement only with closed eyes. We replicated this eyes-closed alpha enhancement in an independent sample (Study 1b). In an active auditory oddball task (Study 2), we again observed the eyes open/eyes closed alpha pattern found in Study 1 and also demonstrated that the more attentionally demanding oddball trials elicit the largest oscillatory effects. Theta power did not interact with eye status in either study. We propose a hypothesis to account for the findings in which alpha may be endemic to multimodal cortical areas in addition to visual ones.
A comparison of methodological approaches to the study of young sex chromosomes: A case study in Poecilia
Authors: Darolti Iulia , Almeida Pedro , Wright Alison E. , Mank Judith E. 
Published: December 2021

AbstractStudies of sex chromosome systems at early stages of divergence are key to understanding the initial process and underlying causes of recombination suppression. However, identifying signatures of divergence in homomorphic sex chromosomes can be challenging due to high levels of sequence similarity between the X and the Y. Variations in methodological precision and underlying data can make all the difference between detecting subtle divergence patterns or missing them entirely. Recent efforts to test for X-Y sequence differentiation in the guppy have led to contradictory results. Here we apply different analytical methodologies to the same dataset to test for the accuracy of different approaches in identifying patterns of sex chromosome divergence in the guppy. Our comparative analysis reveals that the most substantial source of variation in the results of the different analyses lies in the reference genome used. Analyses using custom-made de novo genome assemblies for the focal species successfully recover a signal of divergence across different methodological approaches. By contrast, using the distantly related Xiphophorus reference genome results in variable patterns, due to both sequence evolution and structural variations on the sex chromosomes between the guppy and Xiphophorus. Changes in mapping and filtering parameters can additionally introduce noise and obscure the signal. Our results illustrate how analytical differences can alter perceived results and we highlight best practices for the study of nascent sex chromosomes.
Bee communities in canola are affected by landscape context and farm management
Authors: Olsson Rachel L. , Pfeiffer Vera W. , Lee Benjamin W. , Crowder David W. 
Published: December 2021

AbstractBees are key pollinators that promote greater yield and seed quality of oilseed crops such as canola. Canola acreage has increased over 1,000% in the past decade in the Pacific Northwest USA, providing a major pulse of sugar-rich nectar and pollen resources that may affect bee health and community structure. However, because canola does not require insect pollination for seed production, few studies have examined the biodiversity of pollinators taking advantage of these resources, or the floral traits of canola that affect pollinators across variable landscapes. Here, we conducted pollinator surveys at canola farms across the inland Northwest region of the USA. We surveyed bee biodiversity and abundance, and assessed how these metrics correlated with landscape context, canola production practices, and floral traits of various canola varieties. We found that bee communities differed between sites and across growing seasons, with sweat bees more abundant later in the season, and mining bees more abundant earlier in the season. We also found that bees were more abundant overall on farms with less floral nectar and with less developed landscape surrounding the sampling area. Bee diversity was greater in spring canola than winter canola, and floral traits were also correlated with differing bee community diversity. This research provides important information for canola growers and land managers and offers a framework for future research in pollinator management in the inland Northwest.
Hunchback activates Bicoid in post-mitotic Pair1 neurons to regulate synapse number
Authors: Lee Kristen M , Linskens Amanda M , Doe Chris Q 
Published: December 2021

AbstractThe proper formation and function of neural circuits is crucial for cognition, sensation, and behavior. Neural circuits are highly-specific, and this specificity is dependent on neurons developing key features of their individual identities: morphology, anatomical location, molecular expression and biophysiological properties. Previous research has demonstrated that a neurons identity is, in part, generated by the temporal transcription window the neuron is born in, and the homeodomain transcription factors expressed in the mature neuron. However, whether temporal transcription factors and homeodomain transcription factors regulate neural circuit formation, maintenance and function remains unknown. Here, we utilize a well-characterized neural circuit in the Drosophila larvae, the Pair1 neuron. We determined that in the Pair1 neuron, the temporal transcription factor Hunchback activates the homeodomain transcription factor Bicoid (Bcd). Both Hunchback and Bcd are expressed in Pair1 throughout larval development. Interestingly, Hunchback and Bcd were not required in Pair1 for neurotransmitter identity or axonal morphology, but were required for synapse density. We found that these transcription factors were functioning post-mitotically in Pair1 to regulate synapse density. Additionally, knocking down Hunchback and Bcd in Pair1 neurons disrupted the behavioral output of the circuit. We utilized the genetic tool TransTango to determine that Hunchback function in Pair1 is to repress forming synapses with erroneous neurons. To our knowledge, these data are the first to show Hunchback activating Bcd expression, as well as the first to demonstrate a role for Hunchback and Bcd post-mitotically.
The Atypical Antipsychotic Quetiapine Induces Multiple Antibiotic Resistance in Escherichia coli
Authors: Kyono Yasuhiro , Ellezian Lori , Hu YueYue , Eliadis Kanella , Moy Junlone , Hirsch Elizabeth B. , Federle Michael J. , Flowers Stephanie A. 
Published: December 2021

ABSTRACTAtypical antipsychotic (AAP) medication is a critical tool for treating symptoms of psychiatric disorders. While AAPs primarily target dopamine (D2) and serotonin (5HT2A and 5HT1A) receptors, they also exhibit intrinsic antimicrobial activity as an off-target effect. Because AAPs are often prescribed to patients for many years, a potential risk associated with long-term AAP use is the unintended emergence of bacteria with antimicrobial resistance (AMR). Here, we show that exposure to the AAP quetiapine at estimated gut concentrations promotes AMR in Escherichia coli after six weeks. Quetiapine-exposed isolates exhibited an increase in minimal inhibitory concentrations (MICs) for ampicillin, tetracycline, ceftriaxone, and levofloxacin. By whole genome sequencing analysis, we identified mutations in genes that confer AMR, including the repressor for the multiple antibiotic resistance mar operon (marR), and real-time RT-qPCR analysis showed increased levels of marA, acrA, and tolC mRNAs and a reduced level of ompF mRNA in the isolates carrying marR mutations. To determine the contribution of each marR mutation to AMR, we constructed isogenic strains carrying individual mutant marR alleles in the parent background and re-evaluated their resistant phenotypes using MIC and RT-qPCR assays. While marR mutations induced a robust activity of the mar operon, they resulted in only a modest increase in MICs. Interestingly, although these marR mutations did not fully recapitulate the AMR phenotype of the quetiapine-exposed isolates, we show that marR mutations promote growth fitness in the presence of quetiapine. Our findings revealed an important link between the use of AAPs and AMR development in E. coli.
The impact of music on health-related quality of life, as quantified by the SF-36: A systematic review and meta-analysis
Authors: McCrary J. Matt , Altenmüller Eckart , Kretschmer Clara , Scholz Daniel S. 
Published: December 2021

AbstractBackground/ObjectivesIncreasing evidence supports the ability of music to broadly promote wellbeing and health-related quality of life (HRQOL). However, the magnitude of music’s effects on HRQOL is still unclear, particularly relative to established interventions, limiting inclusion of music interventions in health policy and care. The SF-36 is the most widely used instrument to evaluate HRQOL, with broad validity in evaluating the effects of a range of interventions. This study aims to synthesize and contextualize the impact of music interventions on HRQOL, as assessed by the SF-36.MethodsMEDLINE; EMBASE; Web of Science; PsycINFO, clinicaltrials.gov, and ICTRP databases were searched on 30 July 2021. Randomized and single-group studies of music interventions which reported SF-36 data at pre- and post-intervention timepoints were included. Observational studies were excluded. The quality and certainty of evidence provided by included articles and meta-analysis results was appraised using GRADE. Inverse variance random effects meta-analyses quantified changes in SF-36 mental and physical component summary scores (respectively, ‘MCS’ and ‘PCS’) pre- to post-intervention and vs. common control groups.ResultsAnalyses included 764 participants from 25 studies. Music interventions (music listening – 10 studies; music therapy – 7 studies; singing – 7 studies; gospel music – 1 study) significantly improved MCS (Mean difference (MD) [95% confidence interval]=3.0 [1.4, 4.6]; p<.001) and PCS (MD=1.0 [0.1, 2.0; p<.04) scores. In a subgroup (8 studies; music group – N=254; control – N=257) addition of music to standard treatment for a range of conditions significantly improved MCS scores vs. standard treatment alone (MD=3.7 [0.4, 7.1; p<.03). Effects did not vary between music listening, therapy and singing intervention types or doses (p≥.12); no evidence of small study or publication biases was present in any analysis (p≥.31). Music’s impact on MCS scores meets SF-36 minimum important difference thresholds (MD≥3) and is within the range of established interventions.ConclusionsThis study provides Moderate quality evidence that music interventions can generally be used to provide clinically meaningful improvements in HRQOL. Further study is needed to determine optimal music interventions and doses for distinct clinical and public health scenarios.FundingAlexander von Humboldt FoundationRegistrationPROSPERO (ID: CRD42021276204)
Simulation of Pedigree vs. fully-informative marker based relationships matrices in a Loblolly Pine breeding population
Authors: Festa Adam R , Whetten Ross 
Published: December 2021

AbstractComputer simulations of breeding strategies are an essential resource for tree breeders because they allow exploratory analyses into potential long-term impacts on genetic gain and inbreeding consequences without bearing the cost, time, or resource requirements of field experiments. Previous work has modeled the potential long-term implications on inbreeding and genetic gain using random mating and phenotypic selection. Reduction in sequencing costs has enabled the use of DNA marker-based relationship matrices in addition to or in place of pedigree-based allele sharing estimates; this has been shown to provide a significant increase in the accuracy of progeny breeding value prediction. A potential pitfall of genomic selection using genetic relationship matrices is increased coancestry among selections, leading to the accumulation of deleterious alleles and inbreeding depression. We used simulation to compare the relative genetic gain and risk of inbreeding depression within a breeding program similar to loblolly pine, utilizing pedigree-based or marker-based relationships over ten generations. We saw a faster rate of purging deleterious alleles when using a genomic relationship matrix based on markers that track identity-by-descent of segments of the genome. Additionally, we observed an increase in the rate of genetic gain when using a genomic relationship matrix instead of a pedigree-based relationship matrix. While the genetic variance of populations decreased more rapidly when using genomic-based relationship matrices as opposed to pedigree-based, there appeared to be no long-term consequences on the accumulation of deleterious alleles within the simulated breeding strategy.