bluuebunny/crossref_metadata_2025 huggingface dataset:
Simple Models For Neuroscience Research Discoveries: How Often Are These Models Used In Africa
Authors: Hamidu S. K. , Ahmad U. , Abdulazeez R. , Muhammad Z. , Alkhamis A.I. , Umar M. , Ladan A. A. , Nasr F. E. , Ahmad A. , Musa S. , Ya’u J. , Hamman W. O. , Yoshimatsu T. , Issa S. R. , Maina M. B.
Published: December 2022

Simple animal model systems such asDrosophila, Zebrafish, andC. Eleganshave enabled numerous breakthroughs in understanding human health and disease. Their conserved biological processes, ever-expanding established procedures for handling, and amenability for molecular and genetic manipulation, in addition to the minimal ethical concerns, have made these models preferred choices in several life science disciplines globally. Owing to their cheap maintenance cost, adopting these model systems will help bridge the research gap between Africa and the Global North and contribute to advancing scientific knowledge in African universities through practical sessions. However, the extent to which these models are used across Africa is unknown. Here, we analysed the use ofDrosophila, Zebrafish, andC. elegansmodel systems in scientific publications from African laboratories from the year 2000 to 2021. Of 1851 PubMed-indexed publications in which at least one simple animal model was mentioned, 168 used at least one of these models for the actual investigation. With an average of 21 articles per country, South Africa, Nigeria, Kenya, Egypt, Morocco, and Tunisia contributed 75% of these studies. The remaining 25% were contributed by seven other countries at 2-7 articles per country. From here, we extracted and analysed information on funding and international collaboration. This revealed that 24.4 % of the studies were exclusively funded locally, 28.57 % exclusively funded internationally, 15.5% received both local and international funding, and the rest (31.5%) were unfunded, revealing that there is satisfactory access to funds for simple animal model studies, especially from external funders. By analysing the pattern of collaborations, we show that most of these studies had international collaborations, while very few collaborated within Africa. Our work provides data on the current state of research using simple model systems in African laboratories and argues that incorporating these models will advance biomedical science research in Africa.
How benthic sediment microbial communities respond to glyphosate and its metabolite: A microcosm experiment
Authors: Cornish Christine M , Bergholz Peter , Schmidt Kaycie , Sweetman Jon
Published: December 2022

Glyphosate is the most commonly used agricultural herbicide in the world. In aquatic ecosystems, glyphosate often adsorbs to benthic substrates or is metabolized and degraded by microorganisms. The effects of glyphosate on microbial communities varies widely as microorganisms respond differently to exposure. To help understand the impacts of glyphosate on the sediment microbiome we conducted a microcosm experiment examining the responses of benthic sediment microbial communities to herbicide treatments. Sediments from a prairie pothole wetland were collected and 16S rRNA gene sequencing was used to analyze community composition 2-hours and 14-days after a single treatment of low (0.07 ppm), medium (0.7 ppm), or high (7 ppm) glyphosate, aminomethylphosphonic acid (glyphosate metabolite), or a glyphosate-based commercial formula. We found no significant differences in microbial community composition between treatments, concentration levels, or time. These findings suggest that microbial species in the Prairie Pothole Region of North America may be tolerant to glyphosate exposure.
Ventral pallidal GABAergic neuron calcium activity encodes cue-driven reward-seeking and persists in the absence of reward delivery
Authors: Scott Alexandra , Palmer Dakota , Cayton Christelle A. , Lin Iris , Richard Jocelyn M.
Published: December 2022

Reward-seeking behavior is often initiated by environmental cues that signal reward availability. This is a necessary behavioral response; however, cue reactivity and reward-seeking behavior can become maladaptive. To better understand how cue elicited reward-seeking becomes maladaptive, it is important to understand the neural circuits involved in assigning appetitive value to rewarding cues and actions. Ventral pallidum (VP) neurons are known to contribute to cue elicited reward-seeking behavior and have heterogeneous responses in a discriminative stimulus (DS) task. The VP neuronal subtypes and output pathways that encode distinct aspects of the DS task remain unknown. Here, we used an intersectional viral approach with fiber photometry to record bulk calcium activity in VP GABAergic (VP GABA) neurons in male and female rats as they learned and performed the DS task. We found that VP GABA neurons are excited by reward-predictive cues but not neutral cues, and that this response develops over time. We also found that this cue-evoked response predicts reward-seeking behavior. Additionally, we found increased VP GABA calcium activity at the time of expected reward delivery, which occurred even on trials when reward was omitted. Together, these findings suggest that VP GABA neurons encode reward expectation and calcium activity in these neurons is predictive of the vigor of cue-elicited reward-seeking.
Expanded tRNA methyltransferase family member TRMT9B regulates synaptic growth and function
Authors: Hogan C.A. , Gratz S.J. , Dumouchel J.L. , Delgado A. , Lentini J.M. , Madhwani K.R. , Thakur R.S. , Fu D. , O’Connor-Giles Kate M.
Published: December 2022

Nervous system function relies on the formation and function of synaptic connections between neurons. Through a genetic screen inDrosophilafor new conserved synaptic genes, we identified CG42261/Fid/ TRMT9B as a negative regulator of synaptogenesis. TRMT9B has been studied for its role as a tumor suppressor in multiple carcinomas and is one of two metazoan homologs of yeast tRNA methyltransferase 9 (Trm9), which methylates tRNA wobble uridines. Members of the expanded family of tRNA methyltransferases are increasingly being associated with neurological disorders and new biochemical functions. Interestingly, whereas Trm9 homolog ALKBH8/CG17807 is ubiquitously expressed, we find that TRMT9B is enriched in the nervous system, including at synapses. However, in the absence of animal models the role of TRMT9B in the nervous system has remained unknown. Here, we generated null alleles ofTRMT9BandALKBH8, and through liquid chromatography-mass spectrometry find that ALKBH8 is responsible for canonical tRNA wobble uridine methylation under basal conditions. In the nervous system, we find that TRMT9B negatively regulates synaptogenesis through a methyltransferase-dependent mechanism in agreement with our modeling studies. Finally, we find that neurotransmitter release is impaired inTRMT9Bmutants. Our findings reveal a role for TRMT9B in regulating synapse formation and function, and highlight the importance of the expanded family of tRNA methyltransferases in the nervous system.
Androgen-mediated TGFβ expression suppresses anti-tumor neutrophil response in bone metastatic prostate cancer
Authors: Alsamraae Massar , Costanzo-Garvey Diane , Teply Benjamin A. , Boyle Shawna , Sommerville Gary , Herbert Zach , Morrissey Colm , Dafferner Alicia J. , Abdalla Maher Y. , Fallet Rachel W. , Kielian Tammy , Jensen-Smith Heather , deOliveira Edson I. , Chen Keqiang , Bettencourt Ian A. , Wang Ji Ming , McVicar Daniel W. , Keeley Tyler , Yu Fang , Cook Leah M.
Published: December 2022

Prostate Cancer (PCa) bone metastases are associated with spinal cord compression, fracture, bone pain and death. Despite advances in the medical therapy for localized disease, metastatic disease is incurable and osseous progression is largely dictated by tumor-stromal interactions in the bone microenvironment. We showed previously that tumor bone neutrophils are tumoricidal to PCa but lose their cytotoxic potential as the tumor progresses. However, there have been no studies to date to clinically define and characterize neutrophils throughout the prostate cancer disease spectrum to determine their biomarker potential. Using patient peripheral blood polymorphonuclear neutrophils (PMNs), we identify that PCa progression dictates PMN properties, including viability, cell surface markers and gene expression. However, the majority of PMNs elicited an anti-tumor responseex vivodemonstrating that PMN cytotoxicity is cell autonomous and independent of PCa disease stage. In fact, we identify a novel role for androgen regulation, i.e., androgen deprivation therapy (ADT), in suppressing PMN cytotoxicity via altered transforming growth factor beta receptor I (TβRI). Using preclinical models, we found that high dose testosterone/bipolar androgen therapy (BAT) and genetic or pharmacologic TβRI inhibition combined with standard ADT rescued the androgen-associated suppression and restored PMN anti-tumor immune response. This combination provided a therapeutic strategy more impactful than ADT alone, in bone metastatic prostate cancer (BM-PCa). These studies: 1) highlight a necessity for both molecular and functional characterization of PMNs per cancer type and 2) reveals the ability to program PMN immune response for successful targeting of BM-PCa.
Improving Therapeutic Protein Secretion in the Probiotic YeastSaccharomyces boulardiiusing a Multifactorial Engineering Approach
Authors: Durmusoglu Deniz , Al’Abri Ibrahim , Williams Taufika Islam , Collins Leonard B. , Martínez José L. , Crook Nathan
Published: December 2022

The probiotic yeastSaccharomyces boulardii(Sb) is a promising chassis to deliver therapeutic proteins to the gut due toSb’s innate therapeutic properties, resistance to phage and antibiotics, and high protein secretion capacity. To maintain therapeutic efficacy in the context of challenges such as washout, low rates of diffusion, weak target binding, and/or high rates of proteolysis, it is desirable to engineerSbstrains with enhanced levels of protein secretion. In this work, we explored genetic modifications in bothcis- (i.e., to the expression cassette of the secreted protein) andtrans- (i.e., to theSbgenome) that enhanceSb’s ability to secrete proteins, taking aClostridioides difficileToxin A neutralizing peptide (NPA) as our model therapeutic. First, by modulating the copy number of the NPA expression cassette, we found NPA concentrations in the supernatant could be varied by 6-fold (76-458 mg/L) in microbioreactor fermentations. In the context of high NPA copy number, we found a previously-developed collection of native and synthetic secretion signals could further tune NPA secretion between 121 - 463 mg/L. Then, guided by prior knowledge ofS. cerevisiae’s secretion mechanisms, we generated a library of homozygous single gene deletion strains, the most productive of which achieved 2297 mg/L secretory production of NPA. We then expanded on this library by performing combinatorial gene deletions, supplemented by proteomics experiments. We ultimately constructed a quadruple protease-deficientSbstrain that produces 5045 mg/L secretory NPA, an improvement of >10-fold over wild-typeSb. Overall, this work systematically explores a broad collection of engineering strategies to improve protein secretion inSband highlights the ability of proteomics to highlight under-explored mediators of this process. In doing so, we created a set of probiotic strains that are capable of delivering a wide range of protein titers and therefore furthers the ability ofSbto deliver therapeutics to the gut and other settings to which it is adapted.
Kinase-modulated bioluminescent indicators enable noninvasive imaging of drug activity in the brain
Authors: Wu Yan , Walker Joel R. , Westberg Michael , Ning Lin , Monje Michelle , Kirkland Thomas A. , Lin Michael Z. , Su Yichi
Published: December 2022

Aberrant kinase activity contributes to the pathogenesis of brain cancers, neurodegeneration, and neuropsychiatric diseases, but identifying kinase inhibitors that function in the brain is challenging. Drug levels in blood do not predict efficacy in the brain because the blood-brain barrier prevents entry of most compounds. Rather, assessing kinase inhibition in the brain requires tissue dissection and biochemical analysis, a time-consuming and resource-intensive process. Here, we report kinase-modulated bioluminescent indicators (KiMBIs) for non-invasive longitudinal imaging of drug activity in the brain based on a recently optimized luciferase-luciferin system. We develop an ERK KiMBI to report inhibitors of the Ras-Raf-MEK-ERK pathway, for which no bioluminescent indicators previously existed. ERK KiMBI discriminates between brain-penetrant and non-penetrant MEK inhibitors, reveals blood-tumor barrier leakiness in xenograft models, and reports MEK inhibitor pharmacodynamics in native brain tissues and intracranial xenografts. Finally, we use ERK KiMBI to screen ERK inhibitors for brain efficacy, identifying temuterkib as a promising brain-active ERK inhibitor, a result not predicted from chemical characteristics alone. Thus, KiMBIs enable the rapid identification and pharmacodynamic characterization of kinase inhibitors suitable for treating brain diseases.
Differential roles of positive and negative supercoiling in organizing theE. coligenome
Authors: Fu Ziqi , Guo Monica S. , Zhou Weiqiang , Xiao Jie
Published: December 2022

This study aims to explore whether and how positive and negative supercoiling contribute to the three-dimensional (3D) organization of the bacterial genome. We used recently publishedEscherichia coliGapR ChIP-seq and TopoI ChIP-seq (also called EcTopoI-seq) data, which marks positive and negative supercoiling sites, respectively, to study how positive and negative supercoiling correlates with the corresponding contact frequencies obtained from chromosome conformation capture sequencing (Hi-C and 5C). We found that supercoiled chromosomal loci have overall higher Hi-C contact frequencies than sites that are not supercoiled, with positive supercoiling surprisingly corresponding to higher spatial contacts than negative supercoiling. Additionally, Hi-C contact frequencies alone could identify positive, but not negative, supercoiling with high accuracy. The majority of positive and negative supercoils coincide with highly active transcription units, with a minor group likely associated with replication and other genomic processes. Our results suggest that both positive and negative supercoiling enhance chromosome interactions, but positive supercoils contribute more than negative supercoils to bring distant chromosomal loci closer in space. Based on these results, we propose new physical models of how theE. colichromosome is organized differentially by positive and negative supercoils.
Increased intracellular crowding during hyperosmotic stress
Authors: Kitamura Akira , Oasa Sho , Kawaguchi Haruka , Osaka Misato , Vukojević Vladana , Kinjo Masataka
Published: December 2022

Hyperosmotic stress activates in live cells numerous processes and also promotes intracellular protein/RNA aggregation and phase separation. However, the time course and the extent of these changes remain largely uncharacterized. To investigate dynamic changes in intracellular macromolecular crowding (MMC) induced by hyperosmotic stress in live cells, we used Fluorescence Lifetime Imaging Microscopy (FLIM) and Fluorescence Correlation Spectroscopy (FCS) to quantify changes in the local environment by measuring the fluorescence lifetime and the diffusion of the monomeric enhanced Green Fluorescent Protein (eGFP), respectively. Real-time monitoring of eGFP fluorescence lifetime showed that a faster response to environmental changes due to MMC is observed than when measuring the acceptor/donor emission ratio using the MMC-sensitive Förster Resonance Energy Transfer sensor (GimRET). This suggests that eGFP molecular electronic states and/or collision frequency are affected by changes in the immediate surroundings due to MMC without requiring conformational changes as is the case for the GimRET sensor. Furthermore, eGFP diffusion assessed by FCS indicated higher intracellular viscosity due to increased MMC during hyperosmotic stress. Our findings reveal that changes in eGFP fluorescence lifetime and diffusion are early indicators of elevated intracellular MMC. These variables can therefore be used for quantitative characterization of MMC in live cells.
A stochastic world model on gravity for stability inference
Authors: Huang Taicheng , Liu Jia
Published: December 2022

The fact that objects without proper support will fall to the ground is not only a natural phenomenon, but also common sense in mind. Previous studies suggest that humans may infer objects’ stability through a world model that performs mental simulations witha prioriknowledge of gravity acting upon the objects. Here we measured participants’ sensitivity to gravity to investigate how the world model works. We found that the world model on gravity was not a faithful replica of the physical laws, but instead encoded gravity’s vertical direction as a Gaussian distribution. The world model with this stochastic feature fit nicely with participants’ subjective sense of objects’ stability and explained the illusion that taller objects are perceived as more likely to fall. Furthermore, a computational model with reinforcement learning revealed that the stochastic characteristic likely originated from experience-dependent comparisons between predictions formed by internal simulations and the realities observed in the external world, which illustrated the ecological advantage of stochastic representation in balancing accuracy and speed for efficient stability inference. The stochastic world model on gravity provides an example of howa prioriknowledge of the physical world is implemented in mind that helps humans operate flexibly in open-ended environments.

Significance Statement

Humans possess an exceptional capacity for inferring the stability of objects, a skill that has been crucial to the survival of our predecessors and continues to facilitate our daily interactions with the natural world. The present study elucidates that our representation of gravitational direction adheres to a Gaussian distribution, with the vertical orientation as the maximum likelihood. This stochastic representation is likely to have originated from our interactions with the physical world, conferring an ecological advantage of balancing accuracy with speed. Therefore, the world model on gravity in the mind is a distorted replica of the natural world, enabling adaptive functionality in open-ended environments and thus shedding light on developing machines imbued with embodied intelligence.
Flexible and scalable control of T cell memory by a reversible epigenetic switch
Authors: Abadie Kathleen , Clark Elisa C. , Ukogu Obinna , Yang Wei , Daza Riza M. , Ng Kenneth K.H. , Fathima Jumana , Wang Allan L. , Bhandoola Avinash , Nourmohammad Armita , Shendure Jay , Cao Junyue , Kueh Hao Yuan
Published: December 2022

The immune system encodes information about the severity of a pathogenic threat in the quantity and type of memory cell populations formed in response. This encoding emerges from the decisions of lymphocytes to maintain or lose self-renewal and memory potential during a challenge. By tracking responding CD8 T cells at the single-cell and clonal lineage level using time-resolved transcriptomics and quantitative live imaging, we identify a remarkably flexible decision-making strategy, whereby T cells initially choose whether to maintain or lose memory potential early after antigen recognition, but following pathogen clearance may regain memory potential if initially lost. Mechanistically, this flexibility is implemented by acis-epigenetic switch that silences the memory regulator TCF1 in a stochastic and reversible manner in response to stimulatory inputs. Mathematical modeling shows how this strategy allows memory T cell numbers to scale robustly with pathogen virulence and immune response magnitudes. We propose that flexibility and stochasticity in cellular decision making ensures optimal immune responses against diverse threats.
Components of micro-evolutionary and phenotypic change in seasonal migration versus residence in a wild population
Authors: Acker Paul , Daunt Francis , Wanless Sarah , Burthe Sarah J. , Newell Mark A. , Harris Michael P. , Swann Robert L. , Gunn Carrie , Morley Tim I. , Reid Jane M.
Published: December 2022

Dissecting joint micro-evolutionary and plastic responses to environmental perturbations fundamentally requires quantifying interacting components of genetic and environmental variation underlying expression of key traits. This ambition is particularly challenging for phenotypically discrete traits where multiscale decompositions are required to handle non-linear transformations of underlying genetic and environmental variation into phenotypic variation, especially when effects have to be estimated from incomplete field observations. We devised a novel joint multistate capture-recapture and quantitative genetic animal model, and fitted this model to full-annual-cycle resighting data from partially migratory European shags (Gulosus aristotelis) to estimate key components of genetic, environmental and phenotypic variance in the ecologically critical discrete trait of seasonal migration versus residence. We demonstrate non-trivial additive genetic variance in latent liability for migration, resulting in estimated micro-evolutionary responses following two episodes of strong survival selection. Yet, underlying additive genetic effects interacted with substantial permanent individual and temporary environmental effects to generate complex non-additive effects, causing large intrinsic gene-by-environment interaction variance in phenotypic expression. Our findings reveal how temporal dynamics of seasonal migration result from combinations of instantaneous micro-evolution and within-individual phenotypic inertia, and highlight how plastic phenotypic variation could expose cryptic genetic variation underlying discrete traits to complex forms of selection.
A bubble in the making: symbolic boundaries in a Finnish expatriate community
Authors: Peltonen Tuomo , Huhtinen Sirkka-Liisa
Published: December 2022

Purpose

While there is anecdotal evidence that internationally mobile workers often form isolated nation-based communities or “expatriate bubbles,” previous academic scholarship on the expatriate communities and their subjective boundaries is limited. The primary purpose of this article is to advance the theoretical or conceptual understanding of expatriate communities as bubbles.

Design/methodology/approach

As developed by Lamont and Molnár (2002), the theory of symbolic boundaries is applied and set to scrutinize the production and maintenance of insulated expatriate communities. Empirically, an ethnographic study of a community of Finnish expatriates in a Southeast Asian country is undertaken to describe how symbolic boundaries are constructed.

Findings

The main theoretical implication of the paper is the recognition that expatriates themselves are involved in creating the “bubble.” The boundaries separating the national expatriate community are not externally imposed but can be viewed as consequences of the active boundary work of the expatriates. The empirical study demonstrates how the Finnish expatriates negotiated the symbolic boundaries of their community, drawing on cultural, moral and spatial modalities in different levels of boundary work.

Originality/value

There need to be more systematic attempts to develop a theoretically grounded understanding of insulated expatriate communities and their boundaries. This article contributes to the sociological conceptualization of expatriate bubbles by utilizing the symbolic boundary approach, which adds perspective to the embryonic theory of the subjective boundaries of expatriate communities. The multiplicity of different types of symbolic boundaries and their modalities suggests that an expatriate bubble is rarely a finished state or structure.
Rethinking Accounting, Accountability, and Accounting Regulation: Concerns about the Proposed Canadian Sustainability Standards Board*
Authors: Cooper David J. , Everett Jeff , Himick Darlene , Senkl Daniela
Published: December 2022

This paper expands on a letter recently submitted by a group of Canadian business academics to the Independent Review Committee on Standard Setting in Canada (IRCSSC) in response to the committee's proposed Canadian Sustainability Standards Board. We highlight sections of the IRCSSC's Consultation Paper that we find problematic and draw on accounting and other research to explain why it fails to live up to its potential. Chief among the problems we identify is that the IRCSSC appears to be wedded to the same narrow, investor‐based focus promoted by the International Sustainability Standard Board. We also draw attention to the rushed nature of the process, its exclusion of lay experts, the IRCSSC's ambiguous use of the term public interest, and its inattention to alternative understandings of value and the environment (including the people within it). Finally, we problematize the IRCSSC's sidestepping of the issues of power, culture, and conflict; its neglect of monitoring and enforcement; and its surprising disregard of the Global Reporting Initiative. Along with a number of suggestions for improving the process and its outcome, this paper also contributes to ongoing debates on standard setting and the question of whether accounting is currently equipped to provide the necessary tools for sustainability reporting.
Acute effects of lithium augmentation on the kidney in geriatric compared with non‐geriatric patients with treatment‐resistant depression
Authors: Osterland Sarah Luise , Adli Mazda , Saritas Turgay , Schlattmann Peter , Behr Joachim , Müller‐Mertel Ronja , Hoffmann Kai , Stamm Thomas J. , Bschor Tom , Richter Christoph , Steinacher Bruno , Jockers‐Scherübl Maria‐Christiane , Köhler Stephan , Heinz Andreas , Ricken Roland , Buspavanich Pichit
Published: December 2022

Introduction

Lithium augmentation (LA) of antidepressants is a first‐line therapy option for treatment‐resistant depression (TRD). Nevertheless, it is rarely used in geriatric patients mostly because of the fear of kidney toxicity. The purpose of this study is to investigate estimated glomerular filtration rate (eGFR) changes and number of acute kidney injuries (AKI) using LA in geriatric compared with non‐geriatric patients.

Methods

In a prospective multicenter cohort study, eGFR changes were measured in 201 patients with unipolar depression (nage≥65years = 29; nage<65years = 172) at baseline and over 2–6 weeks of LA. We used linear mixed models to investigate changes in eGFR upon LA and assessed the number of AKIs, according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines.

Results

Both age groups showed a significant eGFR decline over the course of treatment with lower eGFR in geriatric patients. The lithium serum level (interpretable as “effect of LA”) had a significant effect on eGFR decline. Both effects (age group and lithium serum level) on eGFR decline did not influence each other, meaning the effect of LA on eGFR decline did not differ between age groups. Two AKIs were observed in the geriatric age group when serum lithium levels exceeded the therapeutic range of >0.8 mmol/L.

Conclusion

This is the first study investigating eGFR change and AKI upon LA for TRD in geriatric compared with non‐geriatric patients. Our data suggest that LA, as an effective treatment option in geriatric patients, should be closely monitored to avoid AKIs.
Systematic review with network meta‐analysis: Risk of Herpes zoster with biological therapies and small molecules in inflammatory bowel disease
Authors: Din Shahida , Selinger Christian P. , Black Christopher J. , Ford Alexander C.
Published: December 2022

Background

Biologics and small molecules for inflammatory bowel disease (IBD) may increase infection risk. Herpes zoster causes acute and long‐term symptoms, but vaccination is not recommended in patients with IBD, unless >50 years of age.

Aims

To examine risk of Herpes zoster infection with all licensed biologics and small molecules for IBD using network meta‐analysis.

Methods

We searched the literature to 4th October 2022, for randomised controlled trials of these drugs in luminal Crohn's disease or ulcerative colitis reporting data on occurrence of Herpes zoster infection during follow‐up. We used a frequentist approach and a random effects model, pooling data as relative risks (RRs) with 95% confidence intervals (CIs).

Results

We identified 25 trials (9935 patients). Only tofacitinib 10 mg b.d. (RR = 6.90; 95% CI 1.56–30.63, number needed to harm (NNH) = 97; 95% CI 19–1022) and upadacitinib 45 mg o.d. (RR = 7.89; 95% CI 1.04–59.59, NNH = 83; 95% CI 10–14,305) were significantly more likely to increase risk of Herpes zoster infection. Janus kinase inhibitors were the most likely drug class to increase risk of infection, and risk increased with higher doses (RR with lowest dose = 3.16; 95% CI 1.02–9.84, NNH = 265; 95% CI 65–28,610, RR with higher dose = 5.91; 95% CI 2.21–15.82, NNH = 117; 95% CI 39–473).

Conclusions

In a network meta‐analysis, the janus kinase inhibitor tofacitinib, and all janus kinase inhibitors considered as a class, were most likely to increase risk of Herpes zoster infection. Risk increased with higher doses.
Association between use of febuxostat and muscle injury: A disproportionality analysis and meta‐analysis of randomized controlled trials
Authors: Mitsuboshi Satoru , Kotake Kazumasa
Published: December 2022

Aims

Several reports have suggested an association between febuxostat and muscle injury. The purpose of this study was to determine whether febuxostat increases the risk of muscle injury. This study included an analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS) database and a systematic review/meta‐analysis of randomized controlled trials.

Methods

First, evaluation of the FAERS data included a disproportionality analysis that compared patients with and without rhabdomyolysis according to whether they were receiving febuxostat or allopurinol. Second, a systematic review/meta‐analysis was performed to assess the risk of rhabdomyolysis and muscle injury in patients who used febuxostat or allopurinol.

Results

Analysis of the FAERS data revealed disproportionality for increasing rhabdomyolysis in patients who received febuxostat (reporting odds ratio 4.49, 95% confidence interval [CI] 3.72–5.38, P < .01) and allopurinol (reporting odds ratio 2.49, 95% CI 2.25–2.75, P < .01). Nineteen studies were eligible for inclusion in the systematic review/meta‐analysis. Rhabdomyolysis was reported in only 1 study. The risk of any type of muscle damage was not significantly increased with febuxostat compared with placebo (risk ratio 0.92, 95% CI 0.73–1.17, P = .52, I2 = 0%; 8 studies including 2597 participants, high‐certainty evidence) or allopurinol (risk ratio 1.03, 95% CI 0.94–1.11, P = .56, I2 = 0%; 9 studies including 17 644 participants, moderate‐certainty evidence).

Conclusion

Febuxostat does not seem to affect the risk of muscle injury. However, the findings of this meta‐analysis indicate a need for further high‐quality observational studies with long‐term follow‐up.
Endogenous testosterone concentrations and muscle mass, strength and performance in women, a systematic review of observational studies
Authors: Taylor Sasha , Islam Rakibul M. , Bell Robin J. , Hemachandra Chandima , Davis Susan R.
Published: December 2022

Objective

To explore the associations between endogenous testosterone blood concentrations and muscle mass, strength and performance in community dwelling women.

Design, Patients and Measurements

Online databases, including Ovid MEDLINE, EMBASE and Web of Science, were searched for observational studies, with at least 100 female participants, reporting associations between endogenous testosterone blood concentrations and muscle mass, strength and performance. The findings were synthesized in a narrative review. Heterogeneity in study design and analysis precluded a meta‐analysis.

Results

Of the 36 articles retrieved for full‐text review, 10 met the inclusion criteria. Eight studies were cross‐sectional, 1 longitudinal and 1 provided both cross‐sectional and longitudinal data. Testosterone was measured by liquid chromatography‐tandem mass spectrometry in two studies and by immunoassay in 8. An association between total testosterone and muscle mass, strength or performance in women was not found. The studies of calculated free or bioavailable testosterone and lean muscle mass reported a positive association, but no association was reported for muscle strength or performance. Each included study was limited by a high risk of bias in at least one assessed domain.

Conclusions

This review does not support an association between testosterone and muscle mass, strength or performance in women. This, together with the reported associations between free or bioavailable testosterone and muscle mass should be interpreted cautiously due to the predominant use of immunoassay and the inaccuracy of calculated variables. Additionally, biological significance of nonprotein bound testosterone has not been established. Further studies examining the relationship between precisely measured testosterone and muscle mass and function in women are required.
Decoding the contributions of gut microbiota and cerebral metabolism in acute liver injury mice with and without cognitive dysfunction
Authors: Sun Tianning , Du Hongying , Li Zhen , Xiong Jun , Liu Yanbo , Li Yujuan , Zhang Wencui , Liang Fangyuan , He Jingang , Liu Xiaodong , Xiang Hongbing
Published: December 2022

Aims

Patients with acute liver injury (ALI) can develop cognitive dysfunction (CD). The study investigated the role of gut microbiota and cerebral metabolism in ALI mice with and without CD.

Methods

Male C57BL/6 mice that received thioacetamide were classified into ALI mice with (susceptible) or without (unsusceptible) CD‐like phenotypes by hierarchical cluster analysis of behavior. The role of gut microbiota was investigated by 16S ribosomal RNA gene sequencing and feces microbiota transplantation (FMT). 1H‐[13C] NMR and electrophysiology were used to detect the changes in cerebral neurotransmitter metabolic and synaptic transition in neurons or astrocytes.

Results

Apromixlay 55% (11/20) of mice developed CD and FMT from the susceptible group transmitted CD to gut microbiota‐depleted mice. Alloprevotella was enriched in the susceptible group. GABA production was decreased in the frontal cortex, while hippocampal glutamine was increased in the susceptible group. Altered Escherichia. Shigella and Alloprevotella were correlated with behaviors and cerebral metabolic kinetics and identified as good predictors of ALI‐induced CD. The frequencies of both miniature inhibitory and excitatory postsynaptic currents in hippocampal CA1 and prefrontal cortex were decreased in the susceptible group.

Conclusion

Altered transmitter metabolism and synaptic transmission in the hippocampus and prefrontal cortex and gut microbiota disturbance may lead to ALI‐induced CD.
Descriptive analysis evaluating the use of direct oral anticoagulation therapy in heart and lung transplant recipients
Authors: Rubido Eric D. , Cooper Megan H. , Donahue Kevin R. , Krisl Jill
Published: December 2022

Background

Direct oral anticoagulants (DOACs) are widely utilized following cardiothoracic transplantation with limited guidance regarding drug–drug interactions (DDIs), periprocedural management, and DOAC‐specific monitoring.

Methods

We performed a single‐center, retrospective, descriptive analysis of adult cardiothoracic transplant recipients initiated on DOAC therapy between May 2016 and July 2021. The primary endpoint for this analysis was the percentage of patients dosed per package labeling. Secondary endpoints included DOAC prescribing in the context of DDIs, renal dysfunction, and periprocedural management, as well as thromboembolism and major bleeding at 12 months.

Results

A total of 125 patients were included in this analysis with a median age of 62 years. At initiation, 63.2% of patients were dosed according to package labeling. The most common reason for non‐labeled dosing was concomitant azole antifungal therapy. DOAC therapy was held for 82 procedures with no reported thrombotic events and one major bleed in the setting of AKI. Hemodialysis‐dependence was associated with a reduced risk of thrombosis (0 vs. 10 events per 100 PY, p = .002) and an increased risk of major bleeding (23 vs. 8 events per 100 PY, p = .006). Additionally, DOAC‐specific anti‐xa guided dosing was associated with a reduced risk of major bleeding (0 vs. 13 events per 100 PY, p < .001).

Conclusion

Our findings show that deviation from package labeling is common following cardiothoracic transplantation and its association with clinical outcomes warrants further study.
Musical coordination affects children's perspective‐taking, but musical synchrony does not
Authors: Wan Yingjia , Wei Yipu , Xu Baorui , Zhu Liqi , Tanenhaus Michael K.
Published: December 2022

Perspective‐taking, which is important for communication and social activities, can be cultivated through joint actions, including musical activities in children. We examined how rhythmic activities requiring coordination affect perspective‐taking in a referential communication task with 100 Chinese 4‐ to 6‐year‐old children. In Study 1, 5‐ to 6‐year‐old children played an instrument with a virtual partner in one of three coordination conditions: synchrony, asynchrony, and antiphase synchrony. Eye movements were then monitored with the partner giving instructions to identify a shape referent which included a pre‐nominal scalar adjective (e.g., big cubic block). When the target contrast (a small cubic block) was in the shared ground and a competitor contrast was occluded for the partner, participants who used perspective differences could, in principle, identify the intended referent before the shape was named. We hypothesized that asynchronous and antiphase synchronous musical activities, which require self‐other distinction, might have stronger effects on perspective‐taking than synchronous activity. Children in the asynchrony and antiphase synchrony conditions, but not the synchrony condition, showed anticipatory looks at the target, demonstrating real‐time use of the partner's perspective. Study 2 was conducted to determine if asynchrony and antiphase asynchrony resulted in perspective‐taking that otherwise would not have been observed, or if synchronous coordination inhibited perspective‐taking that would otherwise have occurred. We found no evidence for online perspective‐taking in 4‐ to 6‐year‐old children without music manipulation. Therefore, playing instruments asynchronously or in alternation, but not synchronously, increases perspective‐taking in children of this age, likely by training self‐other distinction and control. A video abstract of this article can be viewed at https://youtu.be/TM9h_GpFlsA.

Research Highlights

This study is the first to show that rhythmic coordination, a form of non‐linguistic interaction, can affect children's performance in a subsequent linguistic task.

Eye‐movement data revealed that children's perspective‐taking in language processing was facilitated by prior asynchronous and antiphase synchronous musical interactions, but not by synchronous coordination.

The results challenge the common “similar is better” view, suggesting that maintaining self‐other distinction may benefit social interactions that involve representing individual differences.
Respiratory function in uncomplicated type 1 diabetes: Blunted during exercise even though normal at rest!
Authors: Jlali Islem , Heyman Elsa , Matran Régis , Marais Gaelle , Descatoire Aurélien , Rabasa‐Lhoret Rémi , Touil Imen , Pawlak‐Chaouch Mehdi , Mucci Patrick , Fontaine Pierre , Baquet Georges , Tagougui Sémah
Published: December 2022

Aims

Type 1 diabetes is associated with a substantially increased risk of impaired lung function, which may impair aerobic fitness. We therefore aimed to examine the ventilatory response during maximal exercise and the pulmonary diffusion capacity function at rest in individuals with uncomplicated type 1 diabetes.

Methods

In all, 17 adults with type 1 diabetes free from micro–macrovascular complications (glycated haemoglobin: 8.0 ± 1.3%), and 17 non‐diabetic adults, carefully matched to the type 1 diabetes group according to gender, age, level of physical activity and body composition, participated in our study. Lung function was assessed by spirometry and measurements of the combined diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO) at rest. Subjects performed a maximal exercise test during which the respiratory parameters were measured.

Results

At rest, DLCO (30.4 ± 6.1 ml min−1 mmHg−1 vs. 31.4 ± 5.7 ml min−1 mmHg−1, respectively, p = 0.2), its determinants Dm (membrane diffusion capacity) and Vc (pulmonary capillary volume) were comparable among type 1 diabetes and control groups, respectively. Nevertheless, spirometry parameters (forced vital capacity = 4.9 ± 1.0 L vs. 5.5 ± 1.0 L, p < 0.05; forced expiratory volume 1 = 4.0 ± 0.7 L vs. 4.3 ± 0.7 L, p < 0.05) were lower in individuals with type 1 diabetes, although in the predicted normal range. During exercise, ventilatory response to exercise was different between the two groups: tidal volume was lower in type 1 diabetes vs. individuals without diabetes (p < 0.05). Type 1 diabetes showed a reduced VO2max (34.7 ± 6.8 vs. 37.9 ± 6.3, respectively, p = 0.04) in comparison to healthy subjects.

Conclusions

Individuals with uncomplicated type 1 diabetes display normal alveolar‐capillary diffusion capacity and at rest, while their forced vital capacity, tidal volumes and VO2 are reduced during maximal exercise.
Microbial adhesion and viability on novel CAD/CAM framework materials for implant‐supported hybrid prostheses
Authors: Vulović Stefan , Popovac Aleksandra , Radunović Milena , Petrović Sanja , Todorović Miloš , Milić‐Lemić Aleksandra
Published: December 2022

The aim of the study was to investigate the adhesion and viability of Streptococcus oralis and Candida albicans under in vitro conditions on CAD/CAM framework materials for implant‐supported hybrid prostheses. Twenty‐nine specimens were prepared from each of three different materials: ZR (zirconia), PEEK (polyether ether ketone) and CoCr4 (CoCr4 alloy). The experimental part included surface roughness (SR) and contact angle of water (CAW) measurements, followed by colony forming unit (CFU), cell viability assay and scanning electron microscopy (SEM) analyses of Strep. oralis and C. albicans biofilms on the materials’ surfaces. Kruskal‐Wallis and one‐way analysis of variance (ANOVA) tests were used for differences between materials, and the correlation between measurements was estimated using Spearman's correlation coefficient. PEEK specimens revealed higher SR, CAW and CFU mean values, than ZR and CoCr4 specimens. Strong positive correlation was found between SR and CFU and between CAW and CFU for both microbial species. Cell viability assay revealed similar values for both species across materials. Higher numbers of Strep. oralis and C. albicans on PEEK specimens confirm the impact of the higher surface roughness and contact angle values on the microbial adhesion and describes PEEK as less desirable than ZR and CoCr4 from microbiological aspect.
Masstige marketing: Addressing short‐term and long‐term happiness
Authors: Burhanudin Burhanudin
Published: December 2022

Consumers must manage their experiences to achieve their goals. It is currently unclear how masstige products are involved in these experiences. This study experimentally examines the relationships between self‐control, self‐indulgence, intention to purchase a masstige product, and both short‐ and long‐term happiness. In total, 319 consumers participated in this experiment. This study compared four models addressing these relationships and concluded that a higher level of self‐control leads to a lower level of self‐indulgence and a weaker intention to purchase a masstige product. Additionally, a higher level of self‐indulgence leads to a stronger intention to purchase a masstige product. Finally, a higher level of short‐term happiness leads to a greater level of long‐term happiness and stronger intention to purchase a masstige product.
Effect of tea extract on starch gelatinisation, gluten aggregation and quality characteristics of dry yellow alkaline noodle
Authors: Xu Min , Du Jingjing , Hou Gary G. , Du Xianfeng
Published: December 2022

Three kinds of tea extracts (green tea extract, black tea extract and oolong tea extract) were incorporated into a dry yellow alkaline noodle (YAN) at a concentration of 0.5%–2.0% to investigate their effects on starch gelatinisation, gluten aggregation and noodle quality characteristics. Due to the starch–polyphenol interaction, the temperature and enthalpy required for starch gelatinisation were decreased by 0.90–1.10 °C and 2.85–3.31 J/g, respectively, when 2.0% tea extract was added compared with the control. Furthermore, the dry noodles showed lower starch pasting viscosities (reduced by 28.35%–55.20%) and increased resistance to breakdown and retrogradation. Through the hydrogen bonding between gliadins and tea polyphenols, the conformation of gluten was modified (15.41%–24.62% and 15.19%–22.95% increases in α‐helix and β‐sheet contents, respectively) and its structure was strengthened. The combined effect of tea extracts on starch gelatinisation and gluten formation behaviour resulted in the restricted water permeability and mobility in the structure of cooked noodles, which was associated with increased hardness (13.15–16.34 N), cohesiveness (0.63–0.69), chewiness (7.47–10.88) and resilience (0.34–0.42). It also decreased the absolute adhesiveness (0.11–0.13 N.sec) of cooked YANs. In the alkaline noodle system, three kinds of tea extracts exhibited similar effects on the quality characteristics of YAN. The results suggest that tea extracts are capable of improving YAN texture.
Consistent pressure ulcer prevention practice: The effect on PU prevalence and PU stages, and impact on PU prevention—A quasi‐experimental intervention study
Authors: Mäki‐Turja‐Rostedt Sirpa , Leino‐Kilpi Helena , Koivunen Marita , Vahlberg Tero , Haavisto Elina
Published: December 2022

This study evaluates the effect of nursing staff's renewed consistent pressure ulcer (PU) prevention practice on PU prevalence and the PU prevention implemented for residents. A quasi‐experimental intervention study was conducted. The data were collected from 232 residents (n = 115 in intervention and 117 in comparison group) in two public long‐term older people care (LOPC) facilities in Finland using the Pressure Ulcer Patient instrument (PUP‐Instrument). The facilities were chosen with convenience sampling, after which they were randomly allocated as either intervention or comparison facility. Based on international guidelines for PU prevention, the renewed, consistent PU prevention practice with six areas was developed and implemented using the operational model for evidence‐based practices (OMEBP). After the intervention, a significant difference between the intervention and the comparison facility was seen in the prevalence of PUs and in the residents’ highest stage of PUs in the sacrum, buttock and hip areas, and heels. Between the facilities, a significant difference was seen in the use of PU and nutrition risk assessment instruments and nutritional supplements, time used for repositioning in the daytime and at night‐time, lifting belt use, and avoiding shearing or stretching residents’ skin. The successful intervention improved skin integrity in LOPC facilities.