bluuebunny/crossref_metadata_2025 huggingface dataset:
Eco-evolutionary dynamics in two-species mutualistic systems: One-sided population decline triggers joint interaction disinvestment
Authors: Weyerer Franz , Weinbach Avril , Zarfl Christiane , Allhoff Korinna T.
Published: February 2023

The interplay between ecological and evolutionary dynamics can create feedback that reinforces external disturbances and potentially threatens species’ coexistence. For example, plants might invest less into attracting insect pollinators (decreased flower or nectar production) and more into independence (increased selfing or vegetative reproduction) when faced with pollinator decline. This adaptive response saves plant resources at the cost of further threatening the pollinator population. We ask under which conditions such self-reinforcing feedback occurs in two-species mutualistic systems when considering one-sided population decline and whether it can be counteracted by self-dampening feedback if co-evolution of both interaction partners is considered. Based on a mathematical model and in line with previous studies, we find that the described pattern of accelerated population decline occurs for a wide range of parameter values if a concave allocation trade-off between independent growth and interaction investment is assumed. The undisturbed population typically disinvests first, which then forces the declining population to also disinvest, in favour of other energy sources. However, a decelerated population decline can occur if the adaptation of the undisturbed partner is relatively slow compared to environmental decay, reducing the speed of its disinvestment, or if the initial investment into the interaction was very high. Our results suggest that if actions are taken to save endangered populations, not only the evolution of the target species but also of their interaction partner, as well as the interaction between them should be considered.
Protease-Activated Receptor 2 (PAR2) expressed in sensory neurons contributes to signs of pain and neuropathy in paclitaxel treated mice
Authors: Kume Moeno , Ahmad Ayesha , DeFea Kathryn A. , Vagner Josef , Dussor Gregory , Boitano Scott , Price Theodore J.
Published: February 2023

Background and Purpose

Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a common, dose-limiting side effect of cancer therapy. Protease-activated receptor 2 (PAR2) is implicated in a variety of pathologies, including CIPN. In this study, we demonstrate the role of PAR2 expressed in sensory neurons in a paclitaxel (PTX)-induced model of CIPN in mice.

Experimental Approach

CIPN was induced in both PAR2 knockout/WT mice and mice with PAR2 ablated in sensory neurons via the intraperitoneal injection of paclitaxel.In vivobehavioral studies were done in mice using von Frey filaments and the Mouse Grimace Scale. We then examined immunohistochemical staining of dorsal root ganglion (DRG) and hind paw skin samples from CIPN mice to measure satellite cell gliosis and intra-epidermal nerve fiber (IENF) density. Pharmacological reversal of CIPN pain was tested with the PAR2 antagonist C781

Key Results

Mechanical allodynia caused by paclitaxel treatment was alleviated in PAR2 knockout mice of both sexes. In the PAR2 sensory neuronal conditional knockout (cKO) mice, both mechanical allodynia and facial grimacing were attenuated in mice of both sexes. In the dorsal root ganglion of the paclitaxel-treated PAR2 cKO mice, satellite glial cell activation was reduced compared to control mice. IENF density analysis of the skin showed that the paclitaxel-treated control mice have a reduction in nerve fiber density while the PAR2 cKO mice had a comparable skin innervation as the vehicle-treated animals. Similar results were seen with satellite cell gliosis in the DRG where gliosis induced by PTX was absent in PAR cKO mice. Finally, C781 was able to transiently reverse established PTX-evoked mechanical allodynia.

Conclusions and Implications

Our work demonstrates that PAR2 expressed in sensory neurons plays a key role in paclitaxel-induced mechanical allodynia, spontaneous pain and signs of neuropathy, suggesting PAR2 as a possible therapeutic target in multiple aspects of paclitaxel CIPN.
Efficient generation of transgene-free canker-resistantCitrus sinensisusing Cas12a/crRNA ribonucleoprotein
Authors: Su Hang , Wang Yuanchun , Xu Jin , Omar Ahmad A. , Grosser Jude W. , Calovic Milica , Zhang Liyang , Vakulskas Christopher A. , Wang Nian
Published: February 2023

Citrus is one of the top three tree crops in the world and its production faces many devastating disease challenges such as citrus canker caused byXanthomonas citrisubsp. citri (Xcc). Genetic improvement of citrus via traditional approaches is a lengthy (approximately 20 years) and laborious process. Biotechnological approaches including CRISPR genome editing technologies have shown promise. However, none of the citrus plants generated by biotechnological approaches have been commercialized, which primarily resulted from the transgenic nature of the genetically modified plants. Here, we successfully developed transgene-free canker-resistantCitrus sinensislines in the T0 generation within 10 months through transformation of embryogenic citrus protoplasts with Cas12a/crRNA ribonucleoprotein (RNP) to edit the canker susceptibility geneCsLOB1. Among the 39 regenerated lines, 38 are biallelic/homozygous mutants based on Sanger sequencing analysis of targeting sites and whole genome sequencing, demonstrating a 97.4% biallelic/homozygous mutation rate. The edited lines do not contain off-target mutations. TheCsLOB1editedC. sinensislines demonstrate no differences from wild type plants except canker resistance. Importantly, the transgene-free canker-resistantC. sinensislines have received regulatory approval by USDA APHIS. This study presents an efficient genome editing approach for citrus using Cas12a/crRNA RNP, which has a broad impact on genetic improvement of elite citrus varieties and potentially other tree crops and their genetic study. This study represents a breakthrough by generating the first transgene-free canker-resistantC. sinensislines that provide a sustainable and efficient solution to control citrus canker.
Predicting the evolution of adaptation and plasticity from temporal environmental change
Authors: Gallegos Cristóbal , Hodgins Kathryn A. , Monro Keyne
Published: February 2023

Environmental change drives evolutionary adaptation, which determines geographic patterns of biodiversity. At a time of rapid environmental change, however, our ability to predict its evolutionary impacts is far from complete. Temporal environmental change, in particular, often involves joint changes in major components such as mean, trend, cyclic change, and noise. While theoretical predictions exist for adaptation to temporal change in isolated components, knowledge gaps remain. To identify those gaps, we review the relevant theoretical literature, finding that studies rarely assess the relative effects of components changing simultaneously, or attempt to translate theoretical predictions to field conditions. To address those gaps, we draw on classic evolutionary theory to develop a model for the evolution of environmental tolerance, determined by an evolving phenotypically plastic trait, in response to major components of temporal environmental change. We assess the effects of different components on the evolution of tolerance, including rates of adaptation towards new environmental optima, and the evolution of plasticity. We retrieve and synthesize earlier predictions of responses to components changing in isolation, while also generating new predictions of responses to components changing simultaneously. Notably, we show how different forms of environmental predictability emerging from the interplay of cyclic change, stochastic change (noise), and generation time shape predicted outcomes. We then parameterise our model using temperature time series from global marine hotspot in southern Australia, illustrating its utility for predicting testable geographic patterns in evolved thermal tolerance. Our framework provides new insights into the evolution of adaptation and plasticity under temporal environmental change, while offering a path to improving predictions of biological responses to climate change.
A novelWFS1variant associated with isolated congenital cataracts
Authors: Krutish Angela , Elmore James , Ilse Werner , Johnston Janine L. , Hittel Dustin , Kerr Marina , Khan Aneal , Rockman-Greenberg Cheryl , Mhanni Aizeddin A. ,   on behalf of the Canadian Prairie Metabolic Network (CPMN)
Published: February 2023

Biallelic variants in theWFS1gene are associated with Wolfram syndrome. However, recent publications document that heterozygous variants can lead to a variety of phenotypes, such as Wolfram-like syndrome or isolated features of Wolfram syndrome. In this case report, we present a male patient with a history of congenital cataracts and subjective complaints of muscle weakness. Clinical assessment demonstrated normal muscle strength, and genomic, biochemical, electrophysiologic, and muscle biopsy studies did not identify a potential cause of the proband's perceived muscle weakness. Whole-exome sequencing identified a novel de novo variant in theWFS1gene (c.1243G > T), representing one of only several patients in the published literature with isolated congenital cataracts and a heterozygousWFS1variant. The variety of phenotypes associated with heterozygous variants inWFS1suggests that this gene should be considered as a cause of both dominant and biallelic/recessive forms of disease. Future research should focus on elucidating the mechanism(s) of disease and variable expressivity inWFS1in order to improve our ability to provide patients and families with anticipatory guidance about the disease, including appropriate screening and medical interventions.
The effects of campaign-based logo changes on consumers’ attitude and behavior: a case of social distancing messages during the COVID-19 pandemic
Authors: Madadi Rozbeh , Torres Ivonne M. , Fazli-Salehi Reza , Zúñiga Miguel Ángel
Published: February 2023

Purpose

This research study examines how changing the logo to one that depicts social distancing impacts consumers’ attitude toward the brand, attitude toward social distancing guidelines, intention to follow social distancing guidelines, purchase intention, logo evaluation and word of mouth (WOM).

Design/methodology/approach

A 2 (logo type: conventional vs. novel) X 2 (product involvement: high vs. low) between-subjects experimental design was employed. A multivariate analysis of covariance (MANCOVA) was run on the dependent variables (i.e. attitude toward the brand, attitude toward social distancing guidelines, intention to follow social distancing guidelines, purchase intention, logo evaluation and WOM).

Findings

The results indicate a significant moderating effect of product involvement. Individuals who were exposed to a novel logo for a low-involvement product demonstrated improved purchase intentions, attitudes towards the brand, WOM and intentions to follow social distancing guidelines.

Practical implications

From a practical perspective, the results suggest that managers at global brands should consider their brand’s response to the COVID-19 crisis. For example, Nike chose to frame its consumers’ athletic habits as a lifesaving call to action with a new advertising copy that proposed, “If you ever dreamed of playing for millions around the world, now is your chance: play inside, play for the world,” to stress the necessity for people to stay at home.

Social implications

From a theoretical perspective, the results of this study add to the emerging literature on CSR and logo changing, and particularly on following social distancing guidelines introduced in response to COVID-19, by exploring the link between COVID-19 advertising in promotional materials (logo changing) and outcomes such as attitude toward the brand, attitude toward social distancing guidelines, intention to follow social distancing guidelines, purchase intention, logo evaluation and WOM.

Originality/value

This research study adds to the literature on CSR and logo changing, primarily the contribution is based on the understanding of the impact of social distancing guidelines introduced in response to COVID-19. More specifically, this research study contributes toward the understanding of the link between COVID-19 advertising in promotional materials (e.g. logo changing) and outcomes such as attitude toward the brand, attitude toward social distancing guidelines, intention to follow social distancing guidelines, purchase intention, logo evaluation and WOM.
Surface acting and work–family conflict: the roles of exhaustion, anxiety and education
Authors: Nauman Shazia , Imam Hassan , Basit Ameer A.
Published: February 2023

Purpose

This study examines how and under what conditions jobs involving surface acting as key employee performance requirements induce work–family conflict (WFC) and thus negatively impact employees' family lives. Drawing from stress theories, the authors modeled emotional exhaustion as a mediator and trait anxiety and education level as moderators in the surface acting–WFC relation.

Design/methodology/approach

Applying the time-lagged design, the authors collected data from 203 service sector employees whose jobs involved frequent interactions with customers. The authors assessed surface acting, trait anxiety and level of education at time 1, emotional exhaustion at time 2 and WFC at time 3 with a three-week time lag between each wave.

Findings

The study results confirmed that surface acting drained the emotional energies of the employees who on reaching homes were not able to attend to their family needs, thus experiencing WFC. The authors also found that employees who were high in trait anxiety and education level suffered most from emotional exhaustion and WFC.

Practical implications

To mitigate the harmful effects of surface acting, organizations should ensure that their employees who must perform surface acting have sufficient time off from their roles, such as regular breaks, free evenings and vacations to prevent emotional exhaustion. The authors further recommend hiring only those customer care candidates who have low tendencies to be anxious while interacting with customers.

Originality/value

This study integrates and extends both the emotional labor and WFC literature. This research answers the earlier calls for research on the effects of personality on WFC. Contrary to the expectation, the study reveals that a higher level of education does not buffer the impact of emotional exhaustion on WFC; it rather intensifies the harmful effect of emotional exhaustion on WFC.
The effect of E-commerce virtual live streamer socialness on consumers' experiential value: an empirical study based on Chinese E-commerce live streaming studios
Authors: Wu Ruijuan , Liu Jingjing , Chen Shuai , Tong Xing
Published: February 2023

Purpose

The objective of this study was to examine how high-social and low-social virtual live streamers affect consumers' experiential value (utilitarian value and hedonic value) and the mechanism and boundary conditions behind the effect.

Design/methodology/approach

The research consisted of four laboratory experiments.

Findings

The results showed that socialness has a positive significant effect on experiential value. Social presence mediated the effect of socialness on utilitarian value and hedonic value. In the relationship between socialness and experiential value, the moderating effects of communication style and situation were significant.

Practical implications

This study provides managerial implications for online stores about the use of virtual live streamers.

Originality/value

The finding of this paper extends the literature on virtual humans or avatars, enriches the literature on the characteristics of virtual humans and tests the explanatory power of social response theory.
A transformative and social marketing ecosystem investigation into drug use among young adults
Authors: Riedel Aimee , Beatson Amanda , Mulcahy Rory , Keating Byron
Published: February 2023

Purpose

The purpose of this study is to examine the underresearched transformative service research (TSR) and social marketing segment of young adults who use drugs and identify motivators that have been studied in previous literature, using a service ecosystem lens and provide direction for future research into this area. This research provides the evidence-based knowledge for transformative service and social marketing practitioners to design transformative services that target these motivators.

Design/methodology/approach

This systematic review, guided by the preferred reporting items for systematic reviews and meta-analysis framework, examines and analyses 207 articles published between 2015 and 2020.

Findings

This study identified that young adults are motivated to take drugs to enhance one’s experience, to cope, for social reasons, because of individual characteristics and for other reasons. Research has largely focused on microsystem and mesosystem motivators with data collected mainly using a microsystem approach.

Originality/value

This paper contributes to the TSR and social marketing literature by providing a holistic investigation into all motivators relevant to young adult drug use. An ecosystem classification and theoretical framework of the motivators is curated to help guide future TSR and social marketing research and interventions.
Chatting about ChatGPT: how may AI and GPT impact academia and libraries?
Authors: Lund Brady D. , Wang Ting
Published: February 2023

Purpose

This paper aims to provide an overview of key definitions related to ChatGPT, a public tool developed by OpenAI, and its underlying technology, Generative Pretrained Transformer (GPT).

Design/methodology/approach

This paper includes an interview with ChatGPT on its potential impact on academia and libraries. The interview discusses the benefits of ChatGPT such as improving search and discovery, reference and information services; cataloging and metadata generation; and content creation, as well as the ethical considerations that need to be taken into account, such as privacy and bias.

Findings

ChatGPT has considerable power to advance academia and librarianship in both anxiety-provoking and exciting new ways. However, it is important to consider how to use this technology responsibly and ethically, and to uncover how we, as professionals, can work alongside this technology to improve our work, rather than to abuse it or allow it to abuse us in the race to create new scholarly knowledge and educate future professionals.

Originality/value

This paper discusses the history and technology of GPT, including its generative pretrained transformer model, its ability to perform a wide range of language-based tasks and how ChatGPT uses this technology to function as a sophisticated chatbot.
Intraguild predation is increased in areas of low prey diversity in a generalist predator community
Authors: Uiterwaal Stella F. , Squires Amber J. , Grappone Bennett A. , Dillard Brian , Castaneda Ariadne , Kim Sora L. , DeLong John P.
Published: February 2023

Niche differentiation and intraguild predation (IGP) can allow ecologically similar species to coexist, although it is unclear which coexistence mechanism predominates in consumer communities. Until now, a limited ability to quantify diets from metabarcoding data has precluded the use of sequencing data to determine the relative importance of these mechanisms.

Here, we pair a recent metabarcoding quantification approach with stable isotope analysis to examine diet composition in a wolf spider community.

We compare the prevalence of resource partitioning and IGP in these spiders and test whether factors that influence foraging performance, including individual identity, morphology, prey community and environmental conditions, can explain variation in diet composition and IGP.

Extensive IGP is likely the primary coexistence mechanism in this community, and other factors to which foraging variation is often attributed do not explain diet composition and IGP here. Rather, IGP increases as prey diversity decreases.

Foragers are driven to IGP where resource niches are limited. We highlight the need to examine how drivers of predator–prey interaction strengths translate into foraging in natural systems.
Prevalence and risk factors of belching disorders: A cross‐sectional study among freshman college students
Authors: Shang Hai Tao , Ouyang Zhen , Chen Can , Duan Chao Fan , Bai Tao , Hou Xiao Hua
Published: February 2023

Objectives

Belching disorders seriously affect quality of life; however, their prevalences and risk factors remain unknown. The aim of our study was to determine the prevalence and risk factors, particularly lifestyle factors, of belching disorders among freshman college students in central China.

Methods

A cross‐sectional study was conducted in September 2019 in Huazhong University of Science and Technology (Wuhan, Hubei Province, China). The subjects were asked to complete a self‐administered questionnaire for data collection, including sociodemographic information, lifestyle factors, and gastrointestinal symptoms. Belching disorder was diagnosed based on the Rome IV criteria. Univariate and multivariate logistic regression analyses were performed to determine the risk factors for belching disorders.

Results

A total of 3335 subjects were enrolled, and 78.26% were men. Among them, 1.95% (65/3335) reported belching disorders. Significant differences in the Pittsburgh Sleep Quality Index (PSQI), Student‐Life Stress Inventory (SLSI) scores, and consumption of whole grains, black tea, coffee were found between the belching and non‐belching groups. Multivariate logistic regression analysis showed that coffee consumption at least once weekly and a high total SLSI score (over mean + standard deviation) were independent risk factors for belching disorders, while intake of whole grains at least once weekly was a protective factor.

Conclusions

Excessive belching is a common disorder among freshman college students in central China. Lifestyle factors, including consumption of whole grains and coffee, and stress, were associated with belching disorders. Therefore, dietary intervention may be a potential management for belching disorders.
Influence of protozoan grazing on magnetotactic bacteria on intracellular and extracellular iron content
Authors: Seki Yusuke , Eguchi Yukako , Taoka Azuma
Published: February 2023

Magnetotactic bacteria (MTB) ubiquitously inhabit the oxic–anoxic interface or anaerobic areas of aquatic environments. MTB biomineralize magnetite or greigite crystals and synthesize an organelle known as magnetosome. This intrinsic ability of MTB allows them to accumulate iron to levels 100–1000 times higher than those in non‐magnetotactic bacteria (non‐MTB). Therefore, MTB considerably contributes to the global iron cycle as primary iron suppliers in the aquatic environmental food chain. However, to the best of our knowledge, there have been no reports describing the effects of trophic interactions between MTB and their protist grazers on the iron distributions in MTB grazers and the extracellular milieu. Herein, we evaluated the effects of MTB grazing using a model species of protist (Tetrahymena pyriformis) and a model species of MTB (Magnetospirillum magneticum AMB‐1). MTB‐fed T. pyriformis exhibited a magnetic response and contained magnetite crystals in their vacuoles. Fluorescence imaging using a ferrous ion‐specific fluorescent dye revealed that the cellular ferrous ion content was five times higher in MTB‐fed T. pyriformis than in non‐MTB grazers. Moreover, soluble iron concentrations in the spent media increased with time during MTB predation. This study provides experimental evidence to delineate the importance of trophic interactions of MTB on iron distributions.
Individual level microbial communities in the digestive system of the freshwater isopod Asellus aquaticus: Complex, robust and prospective
Authors: Liao Aijuan , Hartikainen Hanna , Buser Claudia C.
Published: February 2023

The freshwater isopod Asellus aquaticus is an important decomposer of leaf detritus, and its diverse gut microbiome has been depicted as key contributors in lignocellulose degradation as of terrestrial isopods. However, it is not clear whether the individual‐level microbiome profiles in the isopod digestive system across different habitats match the implied robust digestion function of the microbiome. Here, we described the bacterial diversity and abundance in the digestive system (hindgut and caeca) of multiple A. aquaticus individuals from two contrasting freshwater habitats. Individuals from a lake and a stream harboured distinct microbiomes, indicating a strong link between the host‐associated microbiome and microbes inhabiting the environments. While faeces likely reflected the variations in environmental microbial communities included in the diet, the microbial communities also substantially differed in the hindgut and caeca. Microbes closely related to lignocellulose degradation are found consistently more enriched in the hindgut in each individual. Caeca often associated with taxa implicated in endosymbiotic/parasitic roles (Mycoplasmatales and Rickettsiales), highlighting a complex host–parasite–microbiome interaction. The results highlight the lability of the A. aquaticus microbiome supporting the different functions of the two digestive organs, which may confer particular advantages in freshwater environments characterized by seasonally fluctuating and spatially disparate resource availability.
Anaerobic methane‐oxidizing activity in a deep underground borehole dominantly colonized by Ca. Methanoperedenaceae
Authors: Nishimura Hiroki , Kouduka Mariko , Fukuda Akari , Ishimura Toyoho , Amano Yuki , Beppu Hikari , Miyakawa Kazuya , Suzuki Yohey
Published: February 2023

The family Ca. Methanoperedenaceae archaea mediates the anaerobic oxidation of methane (AOM) in different terrestrial environments. Using a newly developed high‐pressure laboratory incubation system, we investigated 214‐ and 249‐m deep groundwater samples at Horonobe Underground Research Laboratory, Japan, where the high and low abundances of Ca. Methanoperedenaceae archaea have been shown by genome‐resolved metagenomics, respectively. The groundwater samples amended with 13C‐labelled methane and amorphous Fe(III) were incubated at a pressure of 1.6 MPa. After 3–7 days of incubation, the AOM rate was 45.8 ± 19.8 nM/day in 214‐m groundwater. However, almost no activity was detected from 249‐m groundwater. Based on the results from 16S rRNA gene analysis, the abundance of Ca. Methanoperedenaceae archaea was high in the 214‐m deep groundwater sample, whereas Ca. Methanoperedenaceae archaea was undetected in the 249‐m deep groundwater sample. These results support the in situ AOM activity of Ca. Methanoperedenaceae archaea in the 214‐m deep subsurface borehole interval. Although the presence of Fe‐bearing phyllosilicates was demonstrated in the 214‐m deep groundwater, it needs to be determined whether Ca. Methanoperedenaceae archaea use the Fe‐bearing phyllosilicates as in situ electron acceptors by high‐pressure incubation amended with the Fe‐bearing phyllosilicates.
Optimizing insect metabarcoding using replicated mock communities
Authors: Iwaszkiewicz‐Eggebrecht Elzbieta , Granqvist Emma , Buczek Mateusz , Prus Monika , Kudlicka Jan , Roslin Tomas , Tack Ayco J. M. , Andersson Anders F. , Miraldo Andreia , Ronquist Fredrik , Łukasik Piotr
Published: February 2023

Metabarcoding (high‐throughput sequencing of marker gene amplicons) has emerged as a promising and cost‐effective method for characterizing insect community samples. Yet, the methodology varies greatly among studies and its performance has not been systematically evaluated to date. In particular, it is unclear how accurately metabarcoding can resolve species communities in terms of presence‐absence, abundance and biomass.

Here we use mock community experiments and a simple probabilistic model to evaluate the effect of different DNA extraction protocols on metabarcoding performance. Specifically, we ask four questions: (Q1) How consistent are the recovered community profiles across replicate mock communities?; (Q2) How does the choice of lysis buffer affect the recovery of the original community?; (Q3) How are community estimates affected by differing lysis times and homogenization? and (Q4) Is it possible to obtain adequate species abundance estimates through the use of biological spike‐ins?

We show that estimates are quite variable across community replicates. In general, a mild lysis protocol is better at reconstructing species lists and approximate counts, while homogenization is better at retrieving biomass composition. Small insects are more likely to be detected in lysates, while some tough species require homogenization to be detected. Results are less consistent across biological replicates for lysates than for homogenates. Some species are associated with strong PCR amplification bias, which complicates the reconstruction of species counts. Yet, with adequate spike‐in data, species abundance can be determined with roughly 40% standard error for homogenates, and with roughly 50% standard error for lysates, under ideal conditions. In the latter case, however, this often requires species‐specific reference data, while spike‐in data generalize better across species for homogenates.

We conclude that a non‐destructive, mild lysis approach shows the highest promise for the presence/absence description of the community, while also allowing future morphological or molecular work on the material. However, homogenization protocols perform better for characterizing community composition, in particular in terms of biomass.
Research and policy recommendations from the SOTA XVI: State of the Art Conference on VA Emergency Medicine
Authors: Ward Michael J. , Hwang Ula , Hastings S. Nicole , Timko Christine , Chen Jason I. , Vashi Anita A. , Mattocks Kristin , Abel Erica A. , Bravata Dawn M.
Published: February 2023

To better understand and prioritize research on emergency care for Veterans, the Department of Veteran Affairs (VA) Health Services Research and Development convened the 16th State of the Art Conference on VA Emergency Medicine (SAVE) in Winter 2022 with emergency clinicians, researchers, operational leaders, and additional stakeholders in attendance. Three specific areas of focus were identified including older Veterans, Veterans with mental health needs, and emergency care in the community (non‐VA) settings. Among older Veterans, identified priorities included examination of variation in care and its impact on patient outcomes, utilization, and costs; quality of emergency department (ED) care transitions and strategies to improve them; impact of geriatric ED care improvement initiatives; and use of geriatric assessment tools in the ED. For Veterans with mental health needs, priorities included enhancing the reach of effective, multicomponent suicide prevention interventions; development and evaluation of interventions to manage substance use disorders; and identifying and examining safety and effective acute psychosis practices. Community (non‐VA) emergency care priorities included examining changes in patterns of use and costs in VA and the community care settings as a result of recent policy and coverage changes (with an emphasis on modifiable factors); understanding quality, safety, and Veteran experience differences between VA and community settings; and better understanding follow‐up needs among Veterans who received emergency care (or urgent care) and how well those needs are being coordinated, communicated, and met. Beyond these three groups, cross‐cutting themes included the use of telehealth and implementation science to refine multicomponent interventions, care coordination, and data needs from both VA and non‐VA sources. Findings from this conference will be disseminated through multiple mechanisms and contribute to future funding applications focused on improving Veteran health.
How Can Local Policy Uncertainty Encourage Firm Innovation: A Competitive Advantage Channel*
Authors: Ni Xiaoran
Published: February 2023

Exploring the turnover of city heads in China, I find that state‐owned enterprises (SOEs), which possess competitive advantages (especially resource‐based) due to innate government connections, significantly increase innovation compared with non‐SOEs when local policy uncertainty heightens. In particular, when the turnover of city heads occurs, SOEs are able to obtain a larger amount of external financing at lower costs than non‐SOEs. Additionally, SOEs that file invention patents at the height of local policy uncertainty have better product market performances. My findings indicate that heightened local policy uncertainty enables firms with innate government connections to explore first‐mover advantages through innovation activities.
Immunohistochemical detection of double‐stranded RNA in formalin‐fixed paraffin‐embedded tissue
Authors: Thomsen Christian , Røge Rasmus , Fred Åsa , Wanders Alkwin
Published: February 2023

Double‐stranded RNA (dsRNA) is produced during most viral infections, and immunohistochemical detection of dsRNA has been proposed as a potential screening marker for viral replication. The anti‐dsRNA monoclonal antibody clone 9D5 is more sensitive than the established clone J2 but has not been validated in formalin‐fixed paraffin‐embedded (FFPE) tissue. This study aimed to test and compare the performance of the anti‐dsRNA monoclonal antibodies, 9D5 and J2, in FFPE tissue using an automated staining platform. Archived clinical tissue samples with viral infections (n = 34) and uninfected controls (n = 30) were examined. Immunohistochemical staining for dsRNA (9D5 and J2) and virus‐specific epitopes was performed. 9D5 provided a similar staining pattern but a higher signal‐to‐noise ratio than J2. The following proportions of virus‐infected tissue samples were dsRNA‐positive: SARS‐CoV‐2 (5/5), HPV (6/6), MCV (5/5), CMV (5/6), HSV (4/6), and EBV (0/6). Also, 18 of 30 uninfected samples were dsRNA positive, and an association between fixation time and intensity was observed. However, signals in all samples were markedly reduced by pretreatment with dsRNA‐specific RNAse‐III, indicating a specific reaction. In conclusion, dsRNA can be demonstrated in most viral infections with immunohistochemistry in FFPE tissue but with low clinical specificity. The antibody clone 9D5 performs better than clone J2.
Adjunctive lumateperone (ITI‐007) in the treatment of bipolar depression: Results from a randomized placebo‐controlled clinical trial
Authors: Suppes Trisha , Durgam Suresh , Kozauer Susan G. , Chen Richard , Lakkis Hassan D. , Davis Robert E. , Satlin Andrew , Vanover Kimberly E. , Mates Sharon , McIntyre Roger S. , Tohen Mauricio
Published: February 2023

Objective

This phase 3, randomized, double‐blind, placebo‐controlled study (NCT02600507) evaluated the efficacy and safety of lumateperone adjunctive therapy to lithium or valproate in patients with bipolar depression.

Methods

Patients (18–75 years) with bipolar I or bipolar II disorder experiencing a major depressive episode (MDE), with inadequate therapeutic response to lithium or valproate, were randomized 1:1:1 to 6 weeks adjunctive therapy with lumateperone 28 mg (n = 176), lumateperone 42 mg (n = 177), or placebo (n = 176). The primary and key secondary efficacy endpoints were change from baseline to Day 43 in Montgomery‐Åsberg Depression Rating Scale (MADRS) Total score and the Clinical Global Impression Scale‐Bipolar Version‐Severity Scale (CGI‐BP‐S) depression subscore. Safety assessments included adverse events, laboratory evaluations, vital signs, extrapyramidal symptoms (EPS), and suicidality.

Results

Patients treated with adjunctive lumateperone 42 mg showed significantly greater improvement compared with adjunctive placebo in MADRS Total score (LS mean difference vs placebo [LSMD], −2.4; p = 0.02) and CGI‐BP‐S depression subscore (LSMD, −0.3; p = 0.01), while adjunctive lumateperone 28 mg showed numerical improvement in MADRS Total score (LSMD, −1.7; p = 0.10) and improvement in the CGI‐BP‐S depression subscore (LSMD, −0.3; p = 0.04). Adjunctive lumateperone treatment was well tolerated; treatment‐emergent adverse events reported at rates >5% and twice placebo for lumateperone 42 mg were somnolence (11.3%), dizziness (10.7%), and nausea (8.5%), with minimal risk of EPS, metabolic abnormalities, or increased prolactin.

Conclusions

Lumateperone 42‐mg treatment adjunctive to lithium or valproate significantly improved depression symptoms and was generally well tolerated in patients with MDEs associated with either bipolar I or bipolar II disorder.
Procreative Justice and genetic selection for skin colour
Authors: Marway Herjeet Kaur
Published: February 2023

Should nonprejudiced reproducers genetically select embryos for light skin under background conditions of racism and colourism, given that darker skin will be disadvantageous for their child? Many intuit that there are strong moral reasons not to select light skin in these contexts. I argue that existing procreative principles cannot adequately account for this judgement. Instead, I argue that a more compelling rationale for this intuition is that such selection completes an instance of race or colour injustice. Given this, I propose a new, complementary principle—Procreative Justice—which holds that reproducers have strong pro tanto moral reasons to avoid completing race and colour injustices via their selection choices. While these reasons may be overridden by competing considerations, they nonetheless continue to exert normative force.
The importance of perceived quality of instruction, achievement motivation and difficulties in self‐regulation for students who drop out of university
Authors: Wild Steffen , Grassinger Robert
Published: February 2023

Background: Starting a study programme at an university, students are confronted with rising requirements regulating their learning processes and motivation. Both difficulties due to this regulation and the quality of instruction are associated with students dropping out from a study programme in the research.

Aims: The purpose of this research is to analyse the interplay and effect of difficulties in self‐regulated learning, achievement motivation (i.e. academic self‐concept, subject interest), and perceived quality of instruction in dropping out from an university study programme.

Sample: We sampled 2301 cooperative students in their first academic year. The average age was M = 22.12 (SD = 3.02), and 1167 were male (50.7%).

Method: This cross‐sectional study used structural equation models for hypothesis analysis. Three years after the survey, dropout information from the university administration was matched to the survey data.

Results: The results indicate associations between academic self‐concept, subject interest and difficulties in regulating one's motivation with dropout. An indirect effect was found between perceived quality of instruction and dropout via academic self‐concept, subject interest and difficulties in regulating one's motivation.

Conclusions: The relevance of perceived quality of instruction, self‐concept, subject interest and difficulties in motivational regulation and consequences for dropout is illustrated.
Development of a long‐acting relaxin analogue, LY3540378, for treatment of chronic heart failure
Authors: Verdino Petra , Lee Stacey L. , Cooper Fariba N. , Cottle Steven R. , Grealish Patrick F. , Hu Charlie C. , Meyer Catalina M. , Lin Joanne , Copeland Victoria , Porter Gina , Schroeder Richard L. , Thompson Tyran D. , Porras Leah L. , Dey Asim , Zhang Hong Y. , Beebe Emily C. , Matkovich Scot J. , Coskun Tamer , Balciunas Aldona M. , Ferrante Andrea , Siegel Robert , Malherbe Laurent , Bivi Nicoletta , Paavola Chad D. , Hansen Ryan J. , Abernathy Matthew M. , Nwosu Sylvia O. , Carr Molly C. , Heuer Josef G. , Wang Xiaojun
Published: February 2023

Background and Purpose

Chronic heart failure, a progressive disease with limited treatment options currently available, especially in heart failure with preserved ejection fraction (HFpEF), represents an unmet medical need as well as an economic burden. The development of a novel therapeutic to slow or reverse disease progression would be highly impactful to patients and society. Relaxin‐2 (relaxin) is a human hormone regulating cardiovascular, renal, and pulmonary adaptations during pregnancy. A short‐acting recombinant relaxin, Serelaxin, demonstrated short‐term heart failure symptom relief and biomarker improvement in acute heart failure trials. Here, we present the development of a long‐acting relaxin analogue to be tested in the treatment of chronic heart failure.

Experimental Approach

LY3540378 is a long‐acting protein therapeutic composed of a human relaxin analogue and a serum albumin‐binding VHH domain.

Key Results

LY3540378 is a potent agonist of the relaxin family peptide receptor 1 (RXFP1) and maintains selectivity against RXFP2/3/4 comparable to native relaxin. The half‐life of LY3540378 in preclinical species is extended through high affinity binding of the albumin‐binding VHH domain to serum albumin. When tested in a single dose administration, LY3540378 elicited relaxin‐mediated pharmacodynamic responses, such as reduced serum osmolality and increased renal blood flow in rats. In an isoproterenol‐induced cardiac hypertrophy mouse model, treatment with LY3540378 significantly reduced cardiac hypertrophy and improved isovolumetric relaxation time. In a monkey cardiovascular safety study, there were no adverse observations from administration of LY3540378.

Conclusion and Implications

LY3540378 demonstrated to be a suitable clinical development candidate, and is progressing in clinical trials.
Forest structure predicts species richness and functional diversity in Amazonian mixed‐species bird flocks
Authors: Coddington Charles P. J. , Cooper W. Justin , Mokross Karl , Luther David A.
Published: February 2023

Secondary forest has the potential to act as an important habitat for biodiversity and restoring ecological benefits. Functional diversity, which includes morphological and behavioral traits that mediate species interactions with the surrounding environment, relates to the resilience of ecosystems. To assess the relationship between habitat structural differences in primary and secondary forest and the resultant differences in functional diversity of avian species, we followed 11 mixed‐species flocks at the Biological Dynamics of Forest Fragments Project, near Manaus, Brazil. We used remote sensing LiDAR to assess which three‐dimensional forest structural features are most closely associated with variation in species richness and functional diversity in secondary and primary tropical forest flocks. The species richness of flocks in primary forest increased in areas with higher elevation and higher leaf area density in the understory and subcanopy but was not correlated with habitat structure in secondary forest. Functional diversity increased at lower elevations and with a denser subcanopy in both primary forest and secondary forest but only increased with greater understory leaf area density in primary forest. Together, these results indicate that a dense subcanopy and understory can be important for mixed‐species flocks and that flock richness and functional diversity can be predicted by vegetation structure.

Abstract in Portuguese is available with online material.
Medication management strategies by family caregivers of children with special healthcare needs
Authors: Min Elissa E. , Wheeler Holly , Hennessy Christine , Abebe Ephrem
Published: February 2023

Background

Little is known about the strategies utilized by family caregivers managing medications for their children with special healthcare needs (CSHCN), those who require higher than normal care due to their multifaceted healthcare needs. Medication management strategies are a set of methods or techniques developed or adapted by caregivers to overcome medication‐related barriers and ensure successful therapeutic outcomes. An in‐depth understanding of such strategies is a requisite first step toward developing interventions that support caregiver‐mediated medication management.

Methods

We conducted semi‐structured qualitative interviews with 20 family caregivers of CSHCN who were recruited as part of a community engaged research between Purdue University College of Pharmacy and Indiana Family to Family. Interviews were conducted through zoom and audio recorded. Each participant was provided with a $50 honorarium. Interviews were professionally transcribed and content analyzed to generate categories of medication management strategies.

Results

Five overarching categories of medication management strategies were identified. These included (1) medications, supplies and equipment inventory management; (2) organizing and tracking medications, supplies and equipment; (3) medication‐related communication, coordination and engagement; (4) medication administration and (5) researching and learning about medications. Within each category, caregivers developed or adapted specific strategies to overcome barriers in diverse care contexts (e.g., when interacting with healthcare systems, school staff or other members of their household).

Conclusion

These findings can inform current clinical practice through improved awareness of different strategies employed by caregivers and lay a foundation to develop interventions designed to support caregiver mediated medication management.
Reconciling multiple sources of influence: Longitudinal associations among perceived parent, closest friend, and popular peer injunctive norms and adolescent substance use
Authors: Field Nathan H. , Prinstein Mitchell J.
Published: February 2023

Prospective associations over a 5‐year period were examined among perceived parent, closest friend, and popular peer injunctive norms and the onset and frequency of adolescent substance use within a diverse (53% female, 45.5% White non‐Hispanic, 22.3% Hispanic, 21.5% Black, 1% Asian, and 6.4% another race) sample of 868 seventh‐ and eighth‐grade adolescents from 2012 to 2017. Analyses revealed adolescents' substance use norms were more lenient than perceptions of their parents' and stricter than perceptions of their closest friends'. Stricter perceptions of parent and closest friend norms, but not popular peer norms, were significantly associated with a later onset of alcohol, marijuana, and cigarette use, and the magnitude of the effect of each source' on later substance use varied across development.
Dragged kicking and screaming: Agency and violence for children entering secure accommodation
Authors: Lyttleton‐Smith Jen , Bayfield Hannah
Published: February 2023

Children entering secure accommodation, also known as ‘secure care’, are prevented from exercising free choice over most aspects of everyday life. This paper focuses on the relationship between agency and violence during transference to and early time in secure accommodation. Sharing interview extracts from 11 young people with experience of secure care as children, we explore how the routine processes of ‘suppressing’ children's agency supports the emergence of violence. We argue that the manner of transfer to secure accommodation creates a violent encounter that forces children's emotion and agency to redirect and intensify onto the self and others as further violence.