bluuebunny/crossref_metadata_2025 huggingface dataset:
Is categorization in visual working memory a way to reduce mental effort? A pupillometry study
Authors: Zhou Cherie , Lorist Monicque M. , Mathôt Sebastiaan
Published: November 2021

Recent studies on visual working memory (VWM) have shown that visual information can be stored in VWM as continuous (e.g., a specific shade of red) as well as categorical representations (e.g., the general category red). It has been widely assumed, yet never directly tested, that continuous representations require more VWM mental effort than categorical representations; given limited VWM capacity, this would mean that fewer continuous, as compared to categorical, representations can be maintained simultaneously. We tested this assumption by measuring pupil size, as a proxy for mental effort, in a delayed estimation task. Participants memorized one to four ambiguous (boundaries between adjacent color categories) or prototypical colors to encourage continuous or categorical representations, respectively; after a delay, a probe indicated the location of the to-be-reported color. We found that, for set size 1, pupil size was larger while maintaining ambiguous as compared to prototypical colors, but without any difference in memory precision; this suggests that participants relied on an effortful continuous representation to maintain a single ambiguous color, thus resulting in pupil dilation while preserving precision. In contrast, for set size 2 and higher, pupil size was equally large while maintaining ambiguous and prototypical colors, but memory precision was now substantially reduced for ambiguous colors; this suggests that participants now also relied on categorical representations for ambiguous colors (which are by definition a poor fit to any category), thus reducing memory precision but not resulting in pupil dilation. Taken together, our results suggest that continuous representations are more effortful than categorical representations, and that very few continuous representations (perhaps only one) can be maintained simultaneously.

Significance statement

Visual working memory (VWM) can store visual information in two more-or-less distinct formats: continuous and categorical representations. It is widely assumed that VWM capacity for continuous representations is more limited than for categorical representations, yet this assumption has never been explicitly tested. Here we address this crucial question of whether continuous representations cost more resources, and as a consequence limits VWM capacity, as compared to categorical representations. To do so, we measured pupil size (as a proxy for mental effort) and memory performance in a delayed estimation task. Crucially, our results suggest that continuous representations are more effortful than categorical representations, and that only one continuous representation can be maintained in VWM at one time.
Global Structure of the Intrinsically Disordered Protein Tau Emerges from its Local Structure
Authors: Stelzl Lukas S. , Pietrek Lisa M. , Holla Andrea , Oroz Javier , Sikora Mateusz , Köfinger Jürgen , Schuler Benjamin , Zweckstetter Markus , Hummer Gerhard
Published: November 2021

The paradigmatic disordered protein tau plays an important role in neuronal function and neurodegenerative diseases. To disentangle the factors controlling the balance between functional and disease-associated conformational states, we build a structural ensemble of the tau K18 fragment containing the four pseudorepeat domains involved in both microtubule binding and amyloid fibril formation. We assemble 129-residue-long tau K18 chains at atomic resolution from an extensive fragment library constructed with molecular dynamics simulations. We introduce a reweighted hierarchical chain growth (RHCG) algorithm that integrates experimental data reporting on the local structure into the assembly process in a systematic manner. By combining Bayesian ensemble refinement with importance sampling, we obtain well-defined ensembles and overcome the problem of exponentially varying weights in the integrative modeling of long-chain polymeric molecules. The resulting tau K18 ensembles capture nuclear magnetic resonance (NMR) chemical shift and J-coupling measurements. Without further fitting, we achieve excellent agreement with measurements of NMR residual dipolar couplings. The good agreement with experimental measures of global structures such as singlemolecule Förster resonance energy transfer (FRET) efficiencies is improved further by ensemble refinement. By comparing wild-type and mutant ensembles, we show that pathogenic single-point P301 mutations shift the population from the turn-like conformations of the functional microtubule-bound state to the extended conformations of disease-associated tau fibrils. RHCG thus provides us with an atomically resolved view of the population equilibrium between functional and aggregation-prone states of tau K18, and demonstrates that global structural characteristics of this intrinsically disordered protein emerge from its local structure.
Zika virus-specific IgM elicited during pregnancy exhibits ultrapotent neutralization
Authors: Singh Tulika , Hwang Kwan-Ki , Miller Andrew S. , Jones Rebecca L. , Lopez Cesar A. , Giuberti Camila , Gladden Morgan A. , Miller Itzayana , Webster Helen S. , Eudailey Joshua A. , Luo Kan , Holle Tarra Von , Edwards Robert J. , Valencia Sarah , Burgomaster Katherine E. , Zhang Summer , Mangold Jesse F. , Tu Joshua J. , Dennis Maria , Alam S. Munir , Premkumar Lakshmanane , Dietze Reynaldo , Pierson Theodore C. , Ooi Eng Eong , Lazear Helen M. , Kuhn Richard J. , Permar Sallie R. , Bonsignori Mattia
Published: November 2021

Congenital Zika virus (ZIKV) infection results in neurodevelopmental deficits in up to 14% of infants born to ZIKV-infected mothers. Neutralizing antibodies are a critical component of protective immunity. Here, we demonstrate that plasma IgM responses contribute to ZIKV immunity in pregnancy, mediating neutralization up to three months post symptoms. From a ZIKV-infected pregnant woman, we established a B cell line secreting a pentameric ZIKV-specific IgM (DH1017.IgM) that exhibited ultrapotent ZIKV neutralization dependent on the IgM isotype. DH1017.IgM targets a novel envelope dimer epitope within Domain II. The arrangement of this epitope on the virion is compatible with concurrent engagement of all ten antigen-binding sites of DH1017.IgM, a solution not achievable by IgG antibodies. DH1017.IgM protected against lethal ZIKV challenge in mice. Our findings identify a unique role of antibodies of the IgM isotype in protection against ZIKV and posit DH1017.IgM as a safe and effective candidate immunoprophylactic, particularly during pregnancy.

Key points

Plasma IgM contributes to early ZIKV neutralization during pregnancy

Ultrapotent neutralization by pentameric DH1017.IgM mAb depends on isotype

DH1017.IgM can engage all binding sites concurrently through different angles of approach

DH1017.IgM protects mice against lethal ZIKV challenge
High-quality reference genome for an arid-adapted mammal, the banner-tailed kangaroo rat (Dipodomys spectabilis)
Authors: Harder Avril M. , Walden Kimberly K.O. , Marra Nicholas J. , Willoughby Janna R.
Published: November 2021

Kangaroo rats in the genus Dipodomys are found in a variety of habitat types in western North America, including deserts, arid and semi-arid grasslands, and scrublands. Many Dipodomys species are experiencing strong population declines due to increasing habitat fragmentation, with two species listed as federally endangered. The precarious state of many Dipodomys populations, including those occupying extreme environments, make species of this genus valuable subjects for studying the impacts of habitat degradation and fragmentation on population genomic patterns and for characterizing the genomic bases of adaptation to harsh conditions. To facilitate exploration of such questions, we assembled and annotated a reference genome for the banner-tailed kangaroo rat (D. spectabilis) using PacBio HiFi sequencing reads, providing a more contiguous genomic resource than two previously assembled Dipodomys genomes. Using the HiFi data for D. spectabilis and publicly available sequencing data for two other Dipodomys species (D. ordii and D. stephensi), we demonstrate the utility of this new assembly for studies of congeners by conducting inference of historic effective population sizes (Ne) and linking these patterns to the species’ current extinction risk statuses. The genome assembly presented here will serve as a valuable resource for population and conservation genomic studies of Dipodomys species, comparative genomic research within mammals and rodents, and investigations into genomic adaptation to extreme environments and changing landscapes.

Significance statement

Kangaroo rats in the genus Dipodomys occur in a wide variety of habitat types, ranging from scrublands to arid deserts, and are increasingly impacted by habitat fragmentation with populations of many species in strong decline. To facilitate population and conservation genomic studies of Dipodomys species, we generated the first reference genome assembly for the extensively studied banner-tailed kangaroo rat (D. spectabilis) from long read PacBio sequencing data. The genome assembly presented here will serve as a valuable resource for studies of Dipodomys species—which have long served as ecological and physiological models for the study of osmoregulation—comparative genomic surveys of mammals and rodents, and investigations into genomic adaptation to extreme environments and changing landscapes.
The Flowering Repressor SVP recruits the TOPLESS co-repressor to control flowering in chrysanthemum and Arabidopsis
Authors: Zhang Zixin , Hu Qian , Zhu Yuqing , Gao Zheng , Shang Erlei , Liu Gaofeng , Liu Weixin , Hu Rongqian , Chong Xinran , Guan Zhiyong , Fang Weimin , Chen Sumei , Sun Bo , He Yuehui , Jiang Jiafu , Chen Fadi
Published: November 2021

Plant flowering time is a consequence of the perception of environmental and endogenous signals. The MCM1-AGAMOUSDEFICIENS-SRF-box (MADS-box) gene SHORT VEGETATIVE PHASE (SVP) is a pivotal repressor that negatively regulates the floral transition during the vegetative phase. The transcriptional corepressor TOPLESS (TPL) plays critical roles in many aspects of plant life. An interaction first identified between the second LXLXLX motif (LRLGLP) of CmSVP with CmTPL1-2, which can repress the expression of a key flowering factor CmFTL3 by binding its promotor CArG element in chrysanthemum. Genetic analysis suggested that the CmSVP-CmTPL1-2 transcriptional complex is a prerequisite for SVP to act as a floral repressor, which reduces CmFTL3 transcriptional activity. CmSVP rescued the phenotype of the svp-31 mutant in Arabidopsis, and overexpression of AtSVP or CmSVP in the Arabidopsis dominant negative mutation tpl-1 led to a loss-of-function in late flowering, which confirmed the highly conserved function of SVP in the two completely different species. Thus, we have validated a conserved machinery wherein SVP relies on TPL to inhibit flowering through the direct regulation of FT, which is more meaningful for the evolution of species and could be translated to high-quality cultivation and breeding of crops.
Demyelination induces transcriptional reprograming in proprioceptive and Aβ rapidly adapting low-threshold-mechanoreceptor neurons
Authors: Elbaz Benayahu , Yang Lite , Rader Braesen Lee , Kawaguchi Riki , Traka Maria , Woolf Clifford J , Renthal William , Popko Brian
Published: November 2021

Schwann cells, the main glial cell in the peripheral nervous system (PNS), ensheath bundles of small unmyelinated axons or form myelin on larger axons. PNS injuries initiate transcriptional reprograming in both Schwann cells and sensory neurons that promotes regeneration. While the factors that initiate the transcriptional reprograming in Schwann cells are well characterized, the full range of stimuli that initiate this reprograming in sensory neurons remain elusive. Here, using a genetic model of Schwann cell ablation, we find that Schwann cell loss results in transient PNS demyelination without overt axonal loss. By profiling sensory ganglia at single-cell resolution we show that this demyelination induces transcriptional reprogramming preferably in proprioceptive and Aβ RA-LTMR neurons. Transcriptional reprograming is assumed to be a cell autonomous response of sensory neurons to mechanical axonal injury. By identifying similar reprograming in non-injured, demyelinated neurons, our study suggests that this reprograming represents a non-cell autonomous transcriptional response of sensory neurons to the loss of axon-Schwann cell interactions.

Highlights

Ablation of Schwann cells results in transient PNS demyelination, without overt axonal loss.

Schwann cell loss results in transcriptional reprograming in specific sensory neurons.

Spinal nerve transection (mechanical injury of axons) and demyelination (intact axons) induces similar transcriptional responses in DRG neurons.

The transcriptional response to demyelination among DRG neurons is specific to the large myelinated proprioceptive and Aβ RA-LTMR neurons.
Aquaglyceroporin AQP7’s affinity for its substrate glycerol
Authors: Falato Michael , Chan Ruth , Chen Liao Y.
Published: November 2021

AQP7 is one of the four human aquaglyceroporins that facilitate glycerol transport across the cell membrane, a biophysical process that is essential in human physiology. Therefore, it is interesting to compute AQP7’s affinity for its substrate (glycerol) with reasonable certainty to compare with the experimental data suggesting high affinity in contrast with most computational studies predicting low affinity. In this study aimed at computing the AQP7-glycerol affinity with high confidence, we implemented a direct computation of the affinity from unbiased equilibrium molecular dynamics (MD) simulations of three all-atom systems constituted with 0.16M, 4.32M, and 10.23M atoms, respectively. These three sets of simulations manifested a fundamental physics law that the intrinsic fluctuations of pressure in a system are inversely proportional to the system size (the number of atoms in it). These simulations showed that the computed values of glycerol-AQP7 affinity are dependent upon the system size (the inverse affinity estimations were, respectively, 47.3 mM, 1.6 mM, and 0.92 mM for the three model systems). In this, we obtained a lower bound for the AQP7-glycerol affinity (an upper bound for the dissociation constant). Namely, the AQP7-glycerol affinity is stronger than 1087/M (the dissociation constant is less than 0.92 mM). Additionally, we conducted hyper steered MD (hSMD) simulations to map out the Gibbs free-energy profile. From the free-energy profile, we produced an independent computation of the AQP7-glycerol dissociation constant being approximately 0.18 mM.

Table of contents entry
How increased cognitive load affects the dual-task cost in healthy young adults? A randomized, double-blind sham-controlled study
Authors: Behrangrad Shabnam , Zoghi Maryam , Mansouri Farshad , Jaberzadeh Shapour
Published: November 2021

Our ability to interact flexibly with the surrounding environment and achieve an adaptive goal-directed response is one of the necessities of balance control. This study aimed to examine the interaction between cognitive demand and the necessity for keeping balance in unstable conditions. We examined the effects of performing two cognitive tasks, namely the Stroop test and Wisconsin Card Sorting Test (WCST), on postural balance in healthy young adults. Stroop and the WCST test assess selective attention and cognitive flexibility in shifting between rules, respectively. Thirty-two healthy adults were included in two experimental conditions (control and treatment) in random order, separated by at least seven days. Standing balance was evaluated by the Sway Medical Mobile application in eyes open (EO) and eyes closed (EC) in different stance positions: feet apart, feet together, semi-tandem, tandem, and single-leg stance (SLS). Balance was evaluated before and after the cognitive test in each experimental condition. Our findings indicate that performing cognitively demanding tasks adversely affected the balance ability in more demanding balance tests such as the SLS with EC (P □ 0.05). However, no significant changes were seen in other balance tests (P □ 0.05). Additionally, no significant changes were seen in balance ability after the Stroop or Wisconsin card sorting test alone. These results confirm that performing cognitively demanding tasks significantly reduced the ability to keep balance in less stable conditions. These findings have significant implications in understanding and preventing falls and incidents resulting from an impaired balance in complex and cognitively demanding conditions.
Rare alternative second line injectable drug resistance markers identified by gene-wise genome wide association in M. tuberculosis with unexplained resistance
Authors: Conkle-Gutierrez Derek , Kim Calvin , Ramirez-Busby Sarah M. , Modlin Samuel J. , Mansjö Mikael , Werngren Jim , Rigouts Leen , Hoffner Sven E. , Valafar Faramarz
Published: November 2021

Point mutations in the rrs gene and eis promoter are known to confer resistance to second-line injectable drugs (SLIDs) amikacin (AMK), capreomycin (CAP), and kanamycin (KAN). While mutations in these canonical genes confer a majority of SLID-resistance, alternative mechanisms of resistance are not uncommon and threaten effective treatment decisions when using conventional molecular diagnostics. In total, 1184 clinical M. tuberculosis isolates from 7 countries were studied for genomic markers associated with phenotypic resistance. The markers rrs:A1401G and rrs:G1484T were associated with resistance to all three SLIDs, and three known markers in the eis promoter (eis:G-10A, eis:C-12T, and eis:C-14T) were similarly associated with kanamycin resistance (KAN-R). Among 325, 324, 270 AMK-R, CAP-R, and KAN-R isolates, 264 (81.2%), 250 (77.2%), and 249 (92.3%) harbored canonical mutations, respectively. Thirteen isolates harbored more than one canonical mutation. Canonical mutations did not account for 111 of the phenotypically resistant isolates. A gene-wise method identified three genes and promoters with mutations that, on aggregate, associated with unexplained resistance to at least one SLID. Our analysis associated whiB7 promoter mutations with KAN resistance, supporting clinical relevance for the previously demonstrated role of whiB7 overexpression in KAN resistance. We also provide evidence for the novel association of ppe51 (a gene previously associated with various antimicrobial compounds) with AMK resistance, and for the novel association of thrB with AMK and CAP resistance. The use of gene-wise association can provide additional insight, and therefore is recommended for identification of rare mechanisms of resistance when individual mutations carry insufficient statistical power.
TBX2 controls a proproliferative gene expression program in melanoma
Authors: Lu Sizhu , Louphrasitthiphol Pakavarin , Goradia Nishit , Lambert Jean-Philippe , Schmidt Johannes , Chauhan Jagat , Rughani Milap G. , Larue Lionel , Wilmanns Matthias , Goding Colin R.
Published: November 2021

Senescence shapes embryonic development, plays a key role in aging, and is a critical barrier to cancer initiation, yet how senescence is regulated remains incompletely understood. TBX2 is an antisenescence T-box family transcription repressor implicated in embryonic development and cancer. However, the repertoire of TBX2 target genes, its cooperating partners, and how TBX2 promotes proliferation and senescence bypass are poorly understood. Here, using melanoma as a model, we show that TBX2 lies downstream from PI3K signaling and that TBX2 binds and is required for expression of E2F1, a key antisenescence cell cycle regulator. Remarkably, TBX2 binding in vivo is associated with CACGTG E-boxes, present in genes down-regulated by TBX2 depletion, more frequently than the consensus T-element DNA binding motif that is restricted to Tbx2 repressed genes. TBX2 is revealed to interact with a wide range of transcription factors and cofactors, including key components of the BCOR/PRC1.1 complex that are recruited by TBX2 to theE2F1locus. Our results provide key insights into how PI3K signaling modulates TBX2 function in cancer to drive proliferation.
Widespread microRNA degradation elements in target mRNAs can assist the encoded proteins
Authors: Li Lu , Sheng Peike , Li Tianqi , Fields Christopher J. , Hiers Nicholas M. , Wang Yuzhi , Li Jianping , Guardia Casey M. , Licht Jonathan D. , Xie Mingyi
Published: November 2021

Binding of microRNAs (miRNAs) to mRNAs normally results in post-transcriptional repression of gene expression. However, extensive base-pairing between miRNAs and target RNAs can trigger miRNA degradation, a phenomenon called target RNA-directed miRNA degradation (TDMD). Here, we systematically analyzed Argonaute-CLASH (cross-linking, ligation, and sequencing of miRNA–target RNA hybrids) data and identified numerous candidate TDMD triggers, focusing on their ability to induce nontemplated nucleotide addition at the miRNA 3′ end. When exogenously expressed in various cell lines, eight triggers induce degradation of corresponding miRNAs. Both the TDMD base-pairing and surrounding sequences are essential for TDMD. CRISPR knockout of endogenous trigger or ZSWIM8, a ubiquitin ligase essential for TDMD, reduced miRNA degradation. Furthermore, degradation of miR-221 and miR-222 by a trigger in BCL2L11, which encodes a proapoptotic protein, enhances apoptosis. Therefore, we uncovered widespread TDMD triggers in target RNAs and demonstrated an example that could functionally cooperate with the encoded protein.
Government data governance framework based on a data middle platform
Authors: Mao Zijun , Wu Jingyi , Qiao Yali , Yao Hong
Published: November 2021

Purpose

The present paper constructed a new framework for government data governance based on the concept of a data middle platform to elicit the detailed requirements and functionalities of a government data governance framework.

Design/methodology/approach

Following a three-cycle activity, the design science research (DSR) paradigm was used to develop design propositions. The design propositions are obtained based on a systematic literature review of government data governance and data governance frameworks. Cases and experts further assessed the effectiveness of the implementation of the artifacts.

Findings

The study developed an effective framework for government data governance that supported the digital service needs of the government. The results demonstrated the advantages of the framework in adapting to organizational operations and data, realized the value of data assets, improved data auditing and oversight and facilitated communication. From the collection of data to the output of government services, the framework adapted to the new characteristics of digital government.

Originality/value

Knowledge of the “data middle platforms” generated in this study provides new knowledge to the design of government data governance frameworks and helps translate design propositions into concrete capabilities. By reviewing earlier literature, the article identified the core needs and challenges of government data governance to help practitioners approach government data governance in a structured manner.
Value co-creation for developing cultural and creative virtual brand communities
Authors: Chen Longshan , Yuan Leping , Zhu Zhangxiang
Published: November 2021

Purpose

This study aims to explore the value co-creation for developing cultural and creative virtual brand communities (CCVBCs) by developing a conceptual framework based on the stimulus-organism-response framework, social cognition theory (SCT) and social exchange theory (SET).

Design/methodology/approach

The proposed conceptual framework was developed from a comprehensive review of the related literature. This study tested and validated the proposed framework using partial least square structural equation model based on the data collected through a survey.

Findings

First, perceived hedonic benefit was positively affected by content personalization, user interaction design and technological innovation. Perceived social benefit and perceived self-achievement benefit were positively affected by user interaction design and technological innovation. Second, user content creation behavior was affected by perceived social benefit and perceived self-achievement benefit; user browsing behavior was significantly affected only by perceived hedonic benefit, and interaction behavior was significantly affected by perceived hedonic benefit, perceived social benefit and perceived self-achievement benefit. Third, perceived social benefit and perceived self-achievement benefit partially mediated the relationship between user interaction design and interaction behavior. As for the influence of technological innovation on interaction behavior, however, and the influence of user interaction design and technological innovation on content creation behavior, both perceived social benefit and perceived self-achievement benefit had complete mediation.

Originality/value

This study found that the characteristics of developing CCVBCs affected perceived benefit in participating in the value co-creation process. The results contributed to the value creation research by enriching the understanding of user value co-creation in developing CCVBCs.
Designing inclusive environments for people living with dementia: how much do we really know?
Authors: Evans Simon Chester , Waller Sarah , Bray Jennifer
Published: November 2021

Purpose

Recent years have seen a growing interest in and awareness of the importance of environmental design to the well-being of people living with dementia, in terms of both policy and practice. This trend has been accompanied by a plethora of advice, guidance and tools that aim to encourage and promote the development of inclusive environments. Not all of these are evidence-based, and even those that claim to be so are limited by a paucity of good quality, comprehensive research studies. This paper aims to consider the current state of knowledge in the field of dementia-friendly design and describes a project that refreshed and updated the suite of Environmental Assessment Tools originally developed by The Kings Fund and now managed by the Association for Dementia Studies.

Design/methodology/approach

The mixed methods project reported on in this paper comprised a review of the literature, a survey of people who have used the five design assessment tools and an iterative process of updating the tools to make them as evidence-based and user-friendly as possible.

Findings

The suite of five assessment tools was refreshed and updated to reflect the latest evidence and the views of professionals and others who use the tools. The authors conclude that while a focus on dementia-friendly design is to be welcomed, there remains a need for relevant high-quality evidence to inform such work. In particular, there is a lack of research within people’s own homes and studies that include the perspectives of people living with dementia.

Originality/value

Few assessment tools and guidelines for dementia-friendly environments are truly evidence-based. This paper reports on a project that combined a comprehensive literature review with the views of practitioners to update a widely used suite of tools that aim to make a range of settings more suitable for people living with dementia.
Phthalate hydrolase: distribution, diversity and molecular evolution
Authors: Bhattacharyya Mousumi , Basu Suman , Dhar Rinita , Dutta Tapan K.
Published: November 2021

The alpha/beta‐fold superfamily of hydrolases is rapidly becoming one of the largest groups of structurally related enzymes with diverse catalytic functions. In this superfamily of enzymes, esterase deserves special attention because of their wide distribution in biological systems and importance towards environmental and industrial applications. Among various esterases, phthalate hydrolases are the key alpha/beta enzymes involved in the metabolism of structurally diverse estrogenic phthalic acid esters, ubiquitously distributed synthetic chemicals, used as plasticizer in plastic manufacturing processes. Although they vary both at the sequence and functional levels, these hydrolases use a similar acid–base‐nucleophile catalytic mechanism to catalyse reactions on structurally different substrates. The current review attempts to present insights on phthalate hydrolases, describing their sources, structural diversities, phylogenetic affiliations and catalytically different types or classes of enzymes, categorized as diesterase, monoesterase and diesterase–monoesterase, capable of hydrolysing phthalate diester, phthalate monoester and both respectively. Furthermore, available information on in silico analyses and site‐directed mutagenesis studies revealing structure–function integrity and altered enzyme kinetics have been highlighted along with the possible scenario of their evolution at the molecular level.
Glucagon‐like peptide‐1 receptor agonist, liraglutide, reduces heroin self‐administration and drug‐induced reinstatement of heroin‐seeking behaviour in rats
Authors: Douton Joaquin E. , Horvath Nelli , Mills‐Huffnagle Sara , Nyland Jennifer E. , Hajnal Andras , Grigson Patricia S.
Published: November 2021

Drug addiction is a chronic brain disease characterized by the uncontrolled use of a substance. Due to its relapsing nature, addiction is difficult to treat, as individuals can relapse following even long periods of abstinence and, it is during this time, that they are most vulnerable to overdose. In America, opioid overdose has been increasing for decades, making finding new treatments to help patients remain abstinent and prevent overdose deaths imperative. Recently, glucagon‐like peptide‐1 (GLP‐1) receptor agonists have shown promise in reducing motivated behaviours for drugs of abuse. In this study, we test the effectiveness of the GLP‐1 analogue, liraglutide (LIR), in reducing heroin addiction‐like behaviour, and the potential side effects associated with the treatment. We show that daily treatment with LIR (0.1 mg/kg sc) increases the latency to take heroin, reduces heroin self‐administration, prevents escalation of heroin self‐administration and reduces drug‐induced reinstatement of heroin‐seeking behaviour in rats. A 1‐h pretreatment time, however, was too short to reduce cue‐induced seeking in our study. Moreover, we showed that, while LIR (0.1, 0.3, 0.6 and 1.0 mg/kg sc) supported conditioned taste avoidance of a LIR‐paired saccharin cue, it did not elicit intake of the antiemetic kaolin in heroin‐naïve or heroin‐experienced rats. Further, 0.1 mg/kg LIR did not produce great disruptions in food intake or body weight. Overall, the data show that LIR is effective in reducing heroin taking and heroin seeking at doses that do not cause malaise and have a modest effect on food intake and body weight gain.
The association between involuntary alcohol treatment and subsequent emergency department visits and hospitalizations: a Bayesian analysis of treated patients and matched controls
Authors: Vuong Thu , Gillies Malcolm , Larney Sarah , Montebello Mark , Ritter Alison
Published: November 2021

Background and aims

Many nations have provisions for involuntary treatment of alcohol dependence where the person is at serious risk of harm to themselves. To date, there has been little thorough evaluation of its effectiveness. This study aimed to determine if there were differences between involuntary and voluntary treatment for alcohol dependence on subsequent emergency and hospital care.

Design

A retrospective cohort design using linked routinely collected administrative data on health‐care utilization.

Setting

Hospital and community‐based alcohol treatment, New South Wales, Australia.

Participants

A total of 231 patients who were involuntarily treated for alcohol dependence and 231 matched controls who received treatment as usual within the period May 2012 to April 2018.

Intervention and comparator

Involuntary treatment comprised a 28‐day mandated hospital admission which included supervised withdrawal, comprehensive assessment, rehabilitation and support followed by voluntary aftercare support for up to 6 months. Treatment as usual comprised three not mutually exclusive forms of intensive voluntary alcohol treatment: withdrawal management, rehabilitation and pharmacotherapies for alcohol dependence.

Measurements

Outcome measures: changes in the number of emergency department (ED) visits and number of unplanned hospital admissions 12 months before and 12 months after completion of index treatment.

Findings

Both groups showed a reduction in ED visits (incidence rate ratio (IRR) = 0.56, 95% credible intervals (CrI) = 0.39–0.78) and unplanned hospital admissions (IRR = 0.49, 95% CrI = 0.37–0.65). There was no statistically significant difference between the two groups (IRR = 0.77, 95% CrI = 0.58–1.03 for ED visits and IRR = 0.79, 95% CrI = 0.62–1.01 for hospital admissions). The Bayes factors were 0.925 and 0.936 for ED visits and unplanned hospital admissions, respectively, interpreted as weak evidence in support of the null hypothesis of no difference between the interventions.

Conclusions

Involuntary treatment of alcohol dependence was associated with reduced health service utilization in the year following treatment, and the outcomes did not differ from those of a matched control group.
Smoking trajectories from adolescence to early adulthood as a longitudinal predictor of mental health in adulthood: evidence from 21 years of a nationally representative cohort
Authors: Lee Boram , Levy Douglas E. , Macy Jonathan T. , Elam Kit K. , Bidulescu Aurelian , Seo Dong‐Chul
Published: November 2021

Aims

To measure the prospective relationship between smoking trajectories from adolescence to young adulthood and mental health in later adulthood and test whether this relationship was mediated by concurrent co‐use of alcohol and marijuana.

Design

Longitudinal study using data drawn from rounds 1 to 18 of the National Longitudinal Survey of Youth 1997 (NLSY97), a nationally representative cohort study spanning 21 years.

Setting

United States.

Participants

The analytical sample included those who completed survey items about smoking behaviors on at least half the data collection opportunities in adolescence and young adulthood (n = 8570, 48.9% female, 66.2% white).

Measurements

Mental health in adulthood was measured using the five‐item Mental Health Inventory (MHI‐5; range = 0–100) at round 18. Seven trajectories of smoking from adolescence to young adulthood were identified by group‐based multi‐trajectory modeling, using data over 11 years from rounds 1 to 11.

Findings

Late‐onset moderate smokers [β = −1.95, 95% confidence interval (CI) = −3.61 to −0.29], late‐onset accelerated smokers (β = −2.53, 95% CI = −4.28 to −0.78), early‐onset heavy smokers (β = −3.72, 95% CI = −5.59 to −1.85) and early‐onset moderate smokers (β = −2.66, 95% CI = −4.48 to −0.84) showed poorer regression‐adjusted mean MHI‐5 scores in later adulthood than stable abstainers, even after controlling for baseline mental health and covariates. Whether or not a difference in MHI‐5 scores was present between quitters and stable abstainers was inconclusive. The concurrent co‐use of alcohol and marijuana in young adulthood significantly mediated the relationship between smoking trajectory and mental health.

Conclusions

Continued smoking, especially early‐onset and heavy smoking from adolescence to young adulthood, appears to increase the risk of poor mental health later in mid‐adulthood, and quitting smoking in young adulthood may mitigate such risk even among early‐onset smokers. Mediation analyses underscore the role of using multiple substances in this pathway.
Altered cardiac autonomic function after recovery from COVID‐19
Authors: Kurtoğlu Ertuğrul , Afsin Abdulmecit , Aktaş İbrahim , Aktürk Erdal , Kutlusoy Ergün , Çağaşar Özlem
Published: November 2021

Background

Autonomic dysfunction may occur during the acute phase of COVID‐19. Heart rate variability (HRV) is a useful tool for the assessment of cardiac sympathetic and parasympathetic balance. We aimed to evaluate cardiac autonomic function by using HRV in subjects after recovery from COVID‐19 who had previously symptomatic and were followed outpatiently.

Methods

The study group composed of 50 subjects with a confirmed history of COVID‐19 and the control group composed of 50 healthy subjects without a history of COVID‐19 and vaccination. All the study participants underwent 2‐dimensional, pulsed‐ and tissue‐Doppler echocardiographic examinations and 24‐hour Holter monitoring for HRV analysis.

Results

Time domain parameters of SDNN, SDANN, SDNNi, RMSSD, pNN50, and HRV triangular index were all decreased in the study group when compared with the control group. Frequency domain parameters of TP, VLF, LF, HF, and HFnu were also decreased in the study group in comparison with the control group. LFnu was similar between groups. Nonlinear parameters of HRV including α1and α2decreased in the study group. By contrast, Lmax, Lmean, DET, REC, and Shannon entropy increased in the study population. Approximate and sample entropies also enhanced in the study group.

Conclusions

The present study showed that all three domain HRV significantly altered in patients after recovery from COVID‐19 indicating some degree of dysfunction in cardiac autonomic nervous system. HRV may be a useful tool for the detection of preclinical autonomic dysfunction in this group of patients.
Rules versus principles for ethical market behaviour
Authors: Honohan Patrick
Published: November 2021

In designing regulation, as has long been recognized in the academic literature, there is a tension between reliance on fixed mechanical “bright line” rules and the flexibility offered by granting a degree of discretion to the regulator subject to guiding principles. The failure of principles‐based financial regulation a decade ago reinforced a trend towards mechanical rules. This essay, drawing on practical experience gleaned in the years following the Global Financial Crisis, argues that both are needed; indeed, in many cases, the regulatory policymaker needs some discretion if it is to be sufficiently intrusive. Although regulatory discretion brings its own risks, the growing complexity of products and markets suggests a tilt towards granting greater discretion to the regulator in preference to over‐complicating mechanical rules.
Reproductive justice for the haunted Nordic welfare state: Race, racism, and queer bioethics in Finland
Authors: Sudenkaarne Tiia , Blell Mwenza
Published: November 2021

The Nordic welfare state aims to offer universal healthcare and achieve good health, bar none. We discuss past and present moral blind spots in welfare state bioethics through reproductive justice and queer bioethics, particularly focusing on race and racism, based on ethnographic data from Finland. Globally portrayed as aspirational and mostly uninterrogated, it is crucial to have a thorough bioethical evaluation of a Nordic model informed by Black and queer perspectives. We have come to conceptualize the Finnish welfare state as haunted. We fear that the seemingly non‐racial racial hygiene continues to haunt bioethics of the welfare state as structural racism. A key cause for this concern is the lack of racial awareness in public politics and the reluctance in discussing racism due to the national agenda of color‐blindness. This crucially compounds to our findings that medical professionals prefer to think they operate on “purely medical” reasoning as opposed to nuanced ethical contemplation, the latter associated with “social issues” that allegedly cannot be resolved and are outside medical interest. We discuss how the bioethical aftermath of eugenics remains unresolved. Racist, classist, sexist, ableist, and cis‐ and heteronormative stratification of reproduction requires a nuanced moral compass for Nordic welfare state bioethics, not “strictly medical practice.” We suggest queer bioethics as a moral theory for recalibrating this compass, joining forces with other justice movements to tackle racism in healthcare and further to interrogate racism, sexism, ableism and cis‐ and heteronormativity in bioethics.
Using the in vitro drug sensitivity test to identify candidate treatments for transient abnormal myelopoiesis
Authors: Yokosuka Tomoko , Ito Mieko , Yoshino Yuki , Hirose Ayana , Nakamura Wataru , Sakurai Yukari , Hayashi Akiko , Fujita Sachio , Miyagawa Naoyuki , Keino Dai , Iwasaki Fuminori , Hamanoue Satoshi , Yanagimachi Masakatsu , Goto Shoko , Nagai Jun‐ichi , Ueno Hiroo , Takita Junko , Tanaka Yukichi , Taga Takashi , Goto Hiroaki
Published: November 2021

Approximately 20% of patients with transient abnormal myelopoiesis (TAM) die due to hepatic or multiorgan failure. To identify potential new treatments for TAM, we performed in vitro drug sensitivity testing (DST) using the peripheral blood samples of eight patients with TAM. DST screened 41 agents for cytotoxic properties against TAM blasts. Compared with the reference samples of healthy subjects, TAM blasts were more sensitive to glucocorticoids, the mitogen‐activated protein kinase kinase (MAP2K) inhibitor trametinib, and cytarabine. Our present results support the therapeutic potential of glucocorticoids and the role of the RAS/MAP2K signalling pathway in TAM pathogenesis.
Role of the Andean uplift as an asymmetrical barrier to gene flow in the neotropical leaf‐cutting ant Atta cephalotes
Authors: Muñoz‐Valencia Vanessa , Vélez‐Martínez Glever Alexander , Montoya‐Lerma James , Díaz Fernando
Published: November 2021

Neotropical diversification by the Andean uplift is typically addressed on a large evolutionary scale (e.g., speciation), even though many species are still distributed in both sides of the mountains. The three parallel mountain ranges in the northern Andes (Colombia) impose a major geographical barrier to species’ migration from South to Central America. How important these barriers are for conspecific diversification of cross‐Andean species such as the leaf‐cutting ants remains largely unknown. To answer this question, we studied the mtCOI gene of Atta cephalotes, the most widely distributed leaf‐cutting ant species. Our hierarchical analyses evidenced substantial genetic structure among regions and populations, suggesting a more complex biogeographical history of Andean populations than previously thought. These mountains seem to isolate Central American and Western Colombian populations from the rest of A. cephalotes in South America. Population and migration modeling are consistent with the origin of this species in South America and a major role of the Eastern cordillera as a geographical barrier to historical gene flow, restricting dispersion from north to south. These findings provide insights into the role of the Andean uplift as barrier to gene flow in species of leaf‐cutting ants.

Abstract in Spanish is available with online material.
Atraumatic restorative treatments and oral health‐related quality of life and dental anxiety in Australian Aboriginal children: A cluster‐randomized trial
Authors: Arrow Peter , Piggott Susan , Carter Sheryl , McPhee Rob , Atkinson David , Brennan David Simon , Kularatna Sanjeewa , Tonmukayakul Utsana , Nanda Soniya , Mackean Tamara , Jamieson Lisa
Published: November 2021

Objectives

The management of early childhood caries is challenging and the impacts of its treatment on child oral health‐related quality of life (COHRQoL) and dental anxiety among Australian Aboriginal children is relatively unknown. The aim of the study was to compare the impact on COHRQoL and dental anxiety after approximately 12 months among Aboriginal children treated for early childhood caries (ECC) using the Atraumatic Restorative Treatment and the Hall Technique (ART/HT: test) or standard care (control).

Methods

Consenting Aboriginal communities in the North‐West of Western Australia were randomized into early (test) or delayed (control) intervention for the management of ECC. Children and parents/carers completed a questionnaire at baseline and at follow‐up. The questionnaire sought information on COHRQoL using the proxy‐reported Early Childhood Oral Health Impact Scale (ECOHIS) and the self‐reported Caries Impacts and Experiences Questionnaire for Children (CARIES‐QC). The test group was provided with the ART/HT care at baseline while the control group was advised to seek care through the usual care options available within the community. At follow‐up, both groups were offered care using the ART/HT approach. Changes in the mean scores from baseline to follow‐up within groups were evaluated using appropriate paired (t‐test, Wilcoxon paired test), and between groups with unpaired tests (t‐test). Multivariate regression analysis after multiple imputations of missing data used generalized estimating equation (GEE) controlling for clustering within communities.

Results

Twenty‐five communities and 338 children (mean age = 3.6 years, sd 1.7) participated in the study (test = 177). One child was excluded from the analysis because of a missing questionnaire and clinical data at baseline and follow‐up. At baseline, test group children were older (test = 3.8 years, 95% CI 3.6–4.1;control = 3.3 years, 95% CI 3.1–3.6) and had higher caries experience (test dmft = 4.4, 95% CI 3.8–5.0;control dmft = 3.1, 95% CI 2.5–3.7), but there was no significant difference in COHRQoL or anxiety levels between the groups. At follow‐up, parents in the delayed intervention reported worsening of COHRQoL (70% worsening of the family impact section of the ECOHIS and 37% worsening of the total ECOHIS scale), and there was an 8% reduction in child dental anxiety among the early treatment group.

Conclusions

The application of the ART/HT approaches was feasible, effective, and impacted positively on child oral health‐related quality of life and child dental anxiety among Aboriginal children in remote communities. The model of care as tested in this study should be further developed for inclusion in main‐stream service delivery programmes.
Menstrual cycle regularity as a predictor for heart disease and diabetes: Findings from a large population‐based longitudinal cohort study
Authors: Kiconco Sylvia , Teede Helena J. , Earnest Arul , Loxton Deborah , Joham Anju E.
Published: November 2021

Objective

Menstrual cycle regularity underpins the diagnosis of polycystic ovary syndrome (PCOS), which is linked to adverse cardio‐metabolic profile. However, links between menstrual disorders and metabolic conditions are often under‐appreciated and not considered when assessing cardio‐metabolic risk in women. We aimed to assess the risk of diabetes and heart disease in women with irregular menstrual cycles and those whose cycles were regular.

Methods

This was a community based longitudinal cohort study. We utilized the 1946 to 1951 birth cohort database (N = 13,714) of the Australian Longitudinal Study on Women's Health (ALSWH) over a 20‐year follow‐up period. Data were analysed using Cox regression models.

Results

Women with irregular menstrual cycles had 20% higher risk of developing heart disease [adjusted hazard ratio [HR]: 1.20, 95% confidence interval [CI]: 1.01–1.43) compared with those with regular menstrual cycles. We also observed 17% higher risk of diabetes (HR: 1.17, 95% CI: 1.00–1.38) in women who had irregular menstrual cycles than in women who had regular menstrual cycles. The diabetes risk was 30% higher (HR: 1.30, 95% CI: 1.09–1.55) if women had irregular cycles and did not use hormone replacement therapy, but this was not significant on adjustment for all covariates.

Conclusion

Having irregular menstrual cycles appears to be an early indicator for heart disease and diabetes. These findings suggest that irregular cycles among women in their forties may be linked to adverse cardio‐metabolic outcomes. These women may benefit from screening and prevention strategies as recommended by related guidelines such as the international evidence‐based guideline for the assessment and management of PCOS.