bluuebunny/crossref_metadata_2025 huggingface dataset:
The Audible Contrast Threshold (ACT™) test: a clinical spectro-temporal modulation detection test
Authors: Zaar Johannes , Simonsen Lisbeth Birkelund , Sanchez-Lopez Raul , Laugesen Søren
Published: October 2023

Over the last decade, multiple studies have shown that hearing-impaired listeners’ speech-in-noise reception ability, measured with audibility compensation, is closely associated with performance in spectro-temporal modulation (STM) detection tests. STM tests thus have the potential to provide highly relevant beyond-the-audiogram information in the clinic, but the available STM tests have not been optimized for clinical use in terms of test duration, required equipment, and procedural standardization. The present study introduces a quick-and-simple clinically viable STM test, named the Audible Contrast Threshold (ACT) test. First, an experimenter-controlled STM measurement paradigm was developed, in which the patient is presented binaurally with a continuous audibility-corrected noise via headphones and asked to press a pushbutton whenever they hear an STM target sound in the noise. The patient’s threshold is established using a Hughson-Westlake tracking procedure with a three-out-of-five criterion and then refined by post-processing the collected data using a logistic function. Different stimulation paradigms were tested in 28 hearing-impaired participants and compared to data previously measured in the same participants with an established STM test paradigm. The best stimulation paradigm showed excellent test-retest reliability and good agreement with the established laboratory version. Second, the best stimulation paradigm with 1-second noise “waves” (windowed noise) was chosen, further optimized with respect to step size and logistic-function fitting, and tested in a population of 25 young normal-hearing participants using various types of transducers to obtain normative data. Based on these normative data, the “normalized Contrast Level” (in dB nCL) scale was defined, where 0±4 dB nCL corresponds to normal performance and the greater the positive value of dB nCL, the greater the audible contrast loss. Overall, the results of the present study indicate that the ACT test may be considered a reliable, quick-and-simple (and thus clinically viable) test of STM sensitivity. The ACT can be measured directly after the audiogram using the same set up, adding only a few minutes to the process.

CITE AS

1) In text: Zaar/Simonsen et al. (2023)

2) In reference list: Zaar, J./Simonsen L. B., Sanchez-Lopez, R., and Laugesen, S. (2023): “The Audible Contrast Threshold (ACT™) test: a clinical spectro-temporal modulation detection test,” medRxiv.
Partial suppression of BCAA catabolism as a potential therapy for BCKDK deficiency
Authors: Ohl Laura , Kuhs Amanda , Pluck Ryan , Durham Emily , Noji Michael , Philip Nathan D , Arany Zoltan , Ahrens-Nicklas Rebecca C
Published: October 2023

Branched chain ketoacid dehydrogenase kinase (BCKDK) deficiency is a recently described inherited neurometabolic disorder of branched chain amino acid (BCAA) metabolism implying increased BCAA catabolism. It has been hypothesized that a severe reduction in systemic BCAA levels underlies the disease pathophysiology, and that BCAA supplementation may ameliorate disease phenotypes. To test this hypothesis, we characterized a recent mouse model of BCKDK deficiency and evaluated the efficacy of enteral BCAA supplementation in this model. Surprisingly, BCAA supplementation exacerbated neurodevelopmental deficits and did not correct biochemical abnormalities despite increasing systemic BCAA levels. These data suggest that aberrant flux through the BCAA catabolic pathway, not just BCAA insufficiency, may contribute to disease pathology. In support of this conclusion, genetic re-regulation of BCAA catabolism, throughDbthaploinsufficiency, partially rescued biochemical and behavioral phenotypes in BCKDK deficient mice. Collectively, these data raise into question assumptions widely made about the pathophysiology of BCKDK insufficiency and suggest a novel approach to develop potential therapies for this disease.
Restriction of Arginine Induces Antibiotic Tolerance inStaphylococcus aureus
Authors: Freiberg Jeffrey A. , Ruiz Valeria M. Reyes , Green Erin R. , Skaar Eric P.
Published: October 2023

Staphylococcus aureusis responsible for a substantial number of invasive infections globally each year. These infections are problematic because they are frequently recalcitrant to antibiotic treatment, particularly when they are caused by Methicillin-ResistantStaphylococcus aureus(MRSA). Antibiotic tolerance, the ability for bacteria to persist despite normally lethal doses of antibiotics, is responsible for most antibiotic treatment failure in MRSA infections. To understand how antibiotic tolerance is induced,S. aureusbiofilms exposed to multiple anti-MRSA antibiotics (vancomycin, ceftaroline, delafloxacin, and linezolid) were examined using both quantitative proteomics and transposon sequencing. These screens indicated that arginine metabolism is involved in antibiotic tolerance within a biofilm and led to the hypothesis that depletion of arginine withinS. aureuscommunities can induce antibiotic tolerance. Consistent with this hypothesis, inactivation ofargH,the final gene in the arginine synthesis pathway, induces antibiotic tolerance under conditions in which the parental strain is susceptible to antibiotics. Arginine restriction was found to induce antibiotic tolerance via inhibition of protein synthesis. Finally, althoughS. aureusfitness in a mouse skin infection model is decreased in anargHmutant, its ability to survivein vivoduring antibiotic treatment with vancomycin is enhanced, highlighting the relationship between arginine metabolism and antibiotic tolerance duringS. aureusinfection. Uncovering this link between arginine metabolism and antibiotic tolerance has the potential to open new therapeutic avenues targeting previously recalcitrantS. aureusinfections.

Significance Statement

Methicillin-ResistantStaphylococcus aureus(MRSA) is a leading bacterial cause of morbidity and mortality worldwide. Despite the availability of numerous antibiotics within vitroefficacy against MRSA, there are still high rates of antibiotic treatment failure inS. aureusinfections, suggesting antibiotic tolerance is common during human infections. Here, we report a direct connection between the metabolism of arginine, an essential amino acid inS. aureus, and tolerance to multiple classes of antibiotics. This represents a key pathway towards broad antibiotic tolerance inS. aureusand therefore an attractive target to help repotentiate current antibiotics and potentially reduce treatment failure.
Bacterial pore-forming toxin pneumolysin drives pathogenicity through shed toxin-loaded host extracellular vesicles
Authors: Parveen Saba , Bhat Chinmayi V , Aziz Shaheena , Arya J , Dutta Asmita , Dutta Somit , Show Sautan , Sharma Kuldeep , Johnson John Bernet , Nongthomba Upendra , Banerjee Anirban , Subramanian Karthik
Published: October 2023

Streptococcus pneumoniaeis a global priority respiratory pathogen that kills over a million people annually and produces the pore-forming cytotoxin, pneumolysin (PLY). Host cells expel membrane assembled toxin by shedding microvesicles, but the composition and pathophysiological sequelae of the toxin-induced host extracellular vesicles (EVs) are unknown. Here, we found that EVs shed from PLY-challenged monocytes (PLY-EVs) harbor membrane-bound toxin that induced cytotoxicity upon fusion with recipient cells. EVs from human monocytes challenged with recombinant PLY as well as PLY-expressing pneumococcal strains, but not the isogenic PLY mutant, primed dendritic cells and evoked higher pro-inflammatory cytokines upon infection. Proteomic analysis revealed that PLY-EVs are enriched for key antimicrobial and inflammatory host proteins such as IFI16, NLRC4, PTX3 and MMP9.In vivo, zebrafish and mice administered with PLY-EVs showed mortality, pericardial edema, tissue damage and inflammation. Our findings show that host EVs bearing the cytotoxin PLY constitute a previously unexplored mechanism of pneumococcal pathogenesis.
Receptor cavity-based screening reveals potential allosteric modulators of gonadotropin receptors in carp (Cyprinus carpio)
Authors: Atre Ishwar , Hollander-Cohen Lian , Lankry Hodaya , Levavi-Sivan Berta
Published: October 2023

The gonadotropins follicle stimulating hormone (FSH) and luteinizing hormone (LH) are key regulators of sexual development and the reproductive cycle in vertebrates. Unlike most G protein-coupled receptors (GPCR), the FSHR and LHR have large extracellular domains containing multiple leucine-rich repeats, which leads to an elaborate mechanism of receptor activation via orthosteric sites that is difficult to manipulate synthetically. To bypass the orthosteric mechanism, in this study using carp as a model organism we identified allosteric sites capable of receptor activation on the transmembrane domain, which are spatially separated from the orthosteric sites. We have further generated pharmacophore hypothesis based on the structural motifs and exposed residues of these cavities. Using available online small compound libraries consisting of >70000 small molecules, we have thereon used receptor cavity-based hypothesis and other screening stages to identify potential modulators of the allosteric binding site on the carp FSHR and LHRin-silico. We then examined byin vitrotransactivation assay the effect of four candidate compounds on FSHR and LHR, as compared to the activity of native ligands. Our results reveal both specific and dual effective allosteric modulators for FSHR and LHR, demonstrating the potential of our approach for efficient pharmacophore-based screening.
Evaluation of purine-nucleoside degrading ability andin vivouric acid lowering ofStreptococcus thermophilus(ID-PDP3), a novel antiuricemia strain
Authors: Kim Dayoung , Moon Jin Seok , Kim Ji Eun , Jang Ye-Ji , Choi Han Sol , Oh Ikhoon
Published: October 2023

This study evaluated 15 lactic acid bacteria in terms of their ability to degrade inosine and hypoxanthine—which are the intermediates in purine metabolism—for the management of hyperuricemia and gout. After a preliminary screening based on HPLC, CR1 (Lactiplantibacillus plantarum) and GZ1 (Lactiplantibacillus pentosus) showed the highest nucleoside degrading rates and were therefore selected for further characterization. IDCC 2201 (S. thermophilus), which possessed thehptgene encoding hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and exhibited purine degradation, was also selected. These three selected strains were examined in terms of the effect of probiotics on lowering serum uric acid in a rat model of potassium oxonate (PO)-induced hyperuricemia. Among them, the level of serum uric acid was most reduced by IDCC 2201 (p < 0.05). Further, analysis of the microbiome showed that administration of IDCC 2201 recovered the ratio of Bacteroidetes/Firmicutes in the intestinal microbial composition unbalanced by hyperuricemia and showed a difference in the intestinal microbial composition compared to the group administered with allopurinol. Moreover, intestinal short-chain fatty acids (SCFAs) were significantly increased. Ultimately, the findings show that IDCC 2201 lowers uric acid levels by degrading purine-nucleosides and restores intestinal flora and SCFAs, ultimately suggesting that IDCC 2201 is a promising candidate for use as an adjuvant treatment in patients with hyperuricemia.
Serum-deprivation response of ARPE-19 cells; expression patterns relevant to age-related macular degeneration
Authors: Peterson Katherine M. , Mishra Sanghamitra , Asaki Esther , Powell John I. , He Yiwen , Berger Alan E. , Rajapakse Dinusha , Wistow Graeme
Published: October 2023

ARPE-19 cells are derived from adult human retinal pigment epithelium (RPE). The response of these cells to the stress of serum deprivation mimics some important processes relevant to age-related macular degeneration (AMD). Here we extend the characterization of this response using RNASeq and EGSEA gene set analysis of ARPE-19 cells over nine days of serum deprivation. This experiment confirmed the up-regulation of cholesterol and lipid-associated pathways that increase cholesterol levels in these cells. The gene expression analysis also identified other pathways relevant to AMD progression. There were significant changes in extracellular matrix gene expression, notably a switch from expression of collagen IV, a key component of Bruch’s membrane (part of the blood-retina barrier), to expression of a fibrosis-like collagen type I matrix. Changes in the expression profile of the extracellular matrix led to the discovery that amelotin is induced in AMD and is associated with the development of the calcium deposits seen in late-stage geographic atrophy. The transcriptional profiles of other pathways, including inflammation, complement, and coagulation, were also modified, consistent with immune response patterns seen in AMD. As previously noted, the cells resist apoptosis and autophagy but instead initiate a gene expression pattern characteristic of senescence, consistent with the maintenance of barrier function even as other aspects of RPE function are compromised. Other differentially regulated genes were identified that open new avenues for investigation. Our results suggest that ARPE-19 cells maintain significant stress responses characteristic of native RPE that are informative for AMD. As such, they provide a convenient system for discovery and for testing potential therapeutic interventions.
Distinct functions for the paralogous RBM41 and U11/U12-65K proteins in the minor spliceosome
Authors: Norppa Antto J. , Chowdhury Iftekhar , van Rooijen Laura E. , Ravantti Janne J. , Snel Berend , Varjosalo Markku , Frilander Mikko J.
Published: October 2023

In this work, we identify RBM41 as a novel unique protein component of the minor spliceosome. RBM41 has no previously recognized cellular function but has been identified as a paralog of the U11/U12-65K protein, a known unique component of the minor spliceosome that functions during the early steps of minor intron recognition as a component of the U11/U12 di-snRNP. We show that both proteins use their highly similar C-terminal RRMs to bind to 3’-terminal stem-loops in U12 and U6atac snRNAs with comparable affinity. Our BioID data indicate that the unique N-terminal domain of RBM41 is necessary for its association with complexes containing DHX8, an RNA helicase, which in the major spliceosome drives the release of mature mRNA from the spliceosome. Consistently, we show that RBM41 associates with excised U12-type intron lariats, is present in the U12 mono-snRNP, and is enriched in Cajal bodies, together suggesting that RBM41 functions in the post-splicing steps of the minor spliceosome assembly/disassembly cycle. This contrasts with the U11/U12-65K protein, which uses the N-terminal region to interact with U11 snRNP during the intron recognition step. Finally, we show that while RBM41 knockout cells are viable, they show alterations in the splicing of U12-type introns, particularly differential U12-type 3’ splice site usage. Together, our results highlight the role 3’-terminal stem-loop of U12 snRNA as a dynamic binding platform for the paralogous U11/U12-65K and RBM41 proteins, which function at distinct stages of minor spliceosome assembly/disassembly cycle.
Fitness landscape of substrate-adaptive mutations in evolved APC transporters
Authors: Karapanagioti Foteini , Atlason Úlfur Á. , Slotboom Dirk J. , Poolman Bert , Obermaier Sebastian
Published: October 2023

The emergence of new protein functions is crucial for the evolution of organisms. This process has been extensively researched for soluble enzymes, but it is largely unexplored for membrane transporters, even though the ability to acquire new nutrients from a changing environment requires evolvability of transport functions. Here, we demonstrate the importance of environmental pressure in obtaining a new activity or altering a promiscuous activity in members of the Amino acid-Polyamine-organoCation (APC)-type yeast amino acid transporters family. We identify APC members that have broader substrate spectra than previously described. Usingin vivoexperimental evolution, we evolve two of these transporter genes,AGP1andPUT4, towards new substrate specificities. Single mutations on these transporters are found to be sufficient for expanding the substrate range of the proteins, while retaining the capacity to transport all original substrates. Nonetheless, each adaptive mutation comes with a distinct effect on the fitness for each of the original substrates, illustrating a trade-off between the ancestral and evolved functions. Collectively, our findings reveal how substrate-adaptive mutations in membrane transporters contribute to fitness and provide insights into how organisms can use transporter evolution to explore new ecological niches.
Lipid discovery enabled by sequence statistics and machine learning
Authors: Christensen Priya M. , Martin Jonathan , Uppuluri Aparna , Joyce Luke R. , Wei Yahan , Guan Ziqiang , Morcos Faruck , Palmer Kelli L.
Published: October 2023

Bacterial membranes are complex and dynamic, arising from an array of evolutionary pressures. One enzyme that alters membrane compositions through covalent lipid modification is MprF. We recently identified thatStreptococcus agalactiaeMprF synthesizes lysyl-phosphatidylglycerol (Lys-PG) from anionic PG, and a novel cationic lipid, lysyl-glucosyl-diacylglycerol (Lys-Glc-DAG), from neutral glycolipid Glc-DAG. This unexpected result prompted us to investigate whether Lys-Glc-DAG occurs in other MprF-containing bacteria, and whether other novel MprF products exist. Here, we studied protein sequence features determining MprF substrate specificity. First, pairwise analyses identified several streptococ-cal MprFs synthesizing Lys-Glc-DAG. Second, a restricted Boltzmann machine-guided approach led us to discover an entirely new substrate for MprF inEnterococcus, diglucosyl-diacylglycerol (Glc2-DAG), and an expanded set of organisms that modify glycolipid substrates using MprF. Overall, we combined the wealth of available sequence data with machine learning to model evolutionary constraints on MprF sequences across the bacterial domain, thereby identifying a novel cationic lipid.
Initiation of a ZAKα-dependent Ribotoxic Stress Response by the Innate Immunity Endoribonuclease RNase L
Authors: Xi Jiajia , Snieckute Goda , Asthana Abhishek , Gaughan Christina , Bekker-Jensen Simon , Silverman Robert H.
Published: October 2023

RNase L is a regulated endoribonuclease in higher vertebrates that functions in antiviral innate immunity. Interferons induce OAS enzymes that sense double-stranded RNA of viral origin leading to synthesis of 2’,5’-oligoadenylate (2-5A) activators of RNase L. However, it is unknown precisely how RNase L inhibits viral infections. To isolate effects of RNase L from other effects of double-stranded RNA or virus, 2-5A was directly introduced into cells. Here we report that RNase L activation by 2-5A causes a ribotoxic stress response that requires the ribosome-associated MAP3K, ZAKα. Subsequently, the stress-activated protein kinases (SAPK) JNK and p38α are phosphorylated. RNase L activation profoundly altered the transcriptome by widespread depletion of mRNAs associated with different cellular functions, but also by SAPK-dependent induction of inflammatory genes. Our findings show that 2-5A is a ribotoxic stressor that causes RNA damage through RNase L triggering a ZAKα kinase cascade leading to proinflammatory signaling and apoptosis.

Highlights

RNase L signals antiviral innate immunity from the ribosome

The ribotoxic stress response requires the MAP3K ZAKα

RNA cleavage leads to transcription of proinflammatory genes

ZAKα contributes to apoptosis downstream of RNase L activity
Polarity-dependent expression and localization of secretory glucoamylase mRNA in filamentous fungal cells
Authors: Morita Yuki , Takegawa Kaoru , Collins Brett M. , Higuchi Yujiro
Published: October 2023

In multinuclear and multicellular filamentous fungi little is known about how mRNAs encoding secreted enzymes are transcribed and localized spatiotemporally. To better understand this process we visualized mRNA encoding GlaA, a glucoamylase secreted in large amounts by the industrial filamentous fungusAspergillus oryzae, in living cells by the MS2 system. We found thatglaAmRNA was significantly transcribed and localized near the hyphal tip and septum, which are the sites of protein secretion. We also revealed thatglaAmRNA exhibits long-range dynamics in the vicinity of the endoplasmic reticulum (ER) in a manner that is dependent on the microtubule motor proteins kinesin-1 and kinesin-3, but independent of early endosomes. Moreover, we elucidated that the regulatory mechanisms ofglaAmRNA by stress granules and processing bodies were different under high temperature and ER stress. Collectively, this study uncovers a dynamic regulatory mechanism of mRNA encoding a secretory enzyme in filamentous fungi.
Parkinsonism Sac domain mutation in Synaptojanin-1 affects ciliary properties in iPSC-derived dopaminergic neurons
Authors: Rafiq Nisha Mohd , Fujise Kenshiro , Rosenfeld Martin Shaun , Xu Peng , Wu Yumei , De Camilli Pietro
Published: October 2023

Synaptojanin-1 (SJ1) is a major neuronal-enriched PI(4,5)P24- and 5-phosphatase implicated in the shedding of endocytic factors during endocytosis. A mutation (R258Q) that impairs selectively its 4-phosphatase activity causes Parkinsonism in humans and neurological defects in mice (SJ1RQKI mice). Studies of these mice showed, besides an abnormal assembly state of endocytic factors at synapses, the presence of dystrophic nerve terminals selectively in a subset of nigro-striatal dopamine (DA)-ergic axons, suggesting a special lability of DA neurons to the impairment of SJ1 function. Here we have further investigated the impact of SJ1 on DA neurons using iPSC-derived SJ1 KO and SJ1RQKI DA neurons and their isogenic controls. In addition to the expected enhanced clustering of endocytic factors in nerve terminals, we observed in both SJ1 mutant neuronal lines increased cilia length. Further analysis of cilia of SJ1RQDA neurons revealed abnormal accumulation of the Ca2+channel Cav1.3 and of ubiquitin chains, suggesting an impaired clearing of proteins from cilia which may result from an endocytic defect at the ciliary base, where a focal concentration of SJ1 was observed. We suggest that SJ1 may contribute to the control of ciliary protein dynamics in DA neurons, with implications on cilia-mediated signaling.
Design and selection of drug properties to increase the public health impact of next-generation seasonal malaria chemoprevention: a modelling study
Authors: Braunack-Mayer Lydia , Malinga Josephine , Masserey Thiery , Nekkab Narimane , Sen Swapnoleena , Schellenberg David , Tchouatieu André-Marie , Kelly Sherrie L , Penny Melissa A
Published: October 2023

Background

Seasonal malaria chemoprevention (SMC) is recommended for disease control in settings with moderate to highPlasmodium falciparumtransmission and currently depends on administration of sulfadoxine-pyrimethamine with amodiaquine. However, poor regimenadherence and the increasedfrequencyof sulfadoxine-pyrimethamine resistant parasite mutations may threaten SMC’s effectiveness. We need guidance to de-risk the development of drug compounds for malaria prevention.

Methods

We combined an individual-based malaria transmission model that has explicit parasite growth with drug pharmacokinetic/pharmacodynamic models. We modelled SMC drug attributes for several possible modes-of-action, linked to their potential public health impact. Global sensitivity analyses identified trade-offs between drug elimination half-life, maximum killing effect, and SMC coverage, and optimisation identified minimum requirements to maximise malaria burden reductions.

Findings

Model predictions show that preventing infection for the entire period between SMC cycles is more important than drug curative efficacy for clinical disease effectiveness outcomes, but similarly important for impact on prevalence. When four SMC cycles are deployed to children under five years with high levels of coverage (69% of children receiving all cycles), drug candidates require a duration of protection half-life of >23 days (elimination half-life >10 days) to achieve >75% clinical incidence and severe disease reductions (measured over the intervention period in the target population, compared with no intervention across a range of modelled scenarios). High coverage is critical to achieve these targets, requiring >60% of children received all SMC cycles and >90% of children at least one cycle regardless of the drug’s duration.

Interpretation

While efficacy is crucial for malaria prevalence reductions, chemoprevention development should select drug candidates for their duration of protection to maximise burden reductions, with the duration half-life determiningcycle timing. Explicitlydesigning or selectingdrug properties to increase communityuptake is paramount.

Funding

Bill & Melinda Gates Foundation and the Swiss National Science Foundation.
Deletion of CD44 promotes adipogenesis by regulating PPARɣ and cell cycle-related pathways
Authors: Weng Xiong , Jiang Hao , Zhou Houjiang , Lin De , Wang Jing , Kang Li
Published: October 2023

CD44, a cell surface adhesion receptor and stem cell biomarker, is recently implicated in chronic metabolic diseases. Ablation of CD44 ameliorates adipose tissue inflammation and insulin resistance in obesity. Here, we investigated cell type specific CD44 expression in human and mouse adipose tissue and further studied how CD44 in preadipocytes regulates adipocyte function. Using Crispr Cas9-mdediated gene deletion and lentivirus-mediated gene re-expression, we discovered that deletion of CD44 promotes adipocyte differentiation and adipogenesis, whereas re-expression of CD44 abolishes this effect and decreases insulin responsiveness and adiponectin secretion in 3T3-L1 cells. Mechanistically, CD44 does so via suppressingPpargexpression. Using quantitative proteomics analysis, we further discovered that cell cycle-regulated pathways were mostly decreased by deletion of CD44. Indeed, re-expression of CD44 moderately restored expression of proteins involved in all phases of the cell cycle. Our data suggest that CD44 plays a crucial role in regulating adipogenesis and adipocyte function possibly through regulating PPAR☐ and cell cycle-related pathways. This study provides evidence for the first time that CD44 expressed in preadipocytes plays key roles in regulating adipocyte function outside immune cells where CD44 is primarily expressed. Therefore, targeting CD44 in (pre)adipocytes may provide therapeutic potential to treat obesity-associated metabolic complications.
Influence of consumption experience on the behavior of craft beer consumers: beginner and experienced consumers
Authors: Haddad Felipe Furtini , Vieira Kelly Carvalho , Carneiro João de Deus Souza
Published: October 2023

Purpose

This paper aims to identify the profiles of beginner and experienced consumers (BCs and ECs) of craft beer and evaluate their perception, knowledge and purchase intention.

Design/methodology/approach

A total of 291 craft beer consumers including 148 BCs and 143 ECs participated in the study, which was divided into 2 stages: quantitative research through a questionnaire and conjoint analysis.

Findings

BCs are mostly female, with a lower age, income and consumption frequency, presented a shallower understanding of International Bitterness Units (IBU) and considered 7.0% alcohol by volume (ABV) as a high-relative value in craft beers. Otherwise, ECs are mostly men with a higher age and consumption frequency, and they don't consider 50 IBU as high bitterness. The results of conjoint analysis indicate that both groups of consumers attribute greater relative importance to ABV and nonalcoholic beers had lower purchase intentions. Finally, the authors show that beer with 30 IBU and 4.5% ABV is preferred by both BCs and ECs.

Originality/value

The authors' identification about the distinct behaviors of different groups of consumers, based on their consumption time of craft beer, as managerial implications for industries producing craft beer and, as a theoretical contribution, the authors have defined “BCs” and “ECs” based on the experiences with and durations of craft beer consumption.
A cross-national study of the emotional intelligence of young adults in the Middle East
Authors: Nassar Yahya Hayati , Alharballeh Siham , Dodeen Hamzeh Mohd
Published: October 2023

Purpose

This study aimed to assess emotional intelligence (EI) among young adults across three Arab countries: Egypt, Jordan and the United Arab Emirates.

Design/methodology/approach

A total of 1884 university students participated from the three countries and completed the Schutte Self Report Emotional Intelligence Test (SSEIT). Data were validated by confirmatory factor analysis using SPSS AMOS version 29. Path analysis, t-tests and analyses of variance were performed to understand the influence of background variables on the EI of the study participants.

Findings

The results provide theoretical support for the SSEIT and the hypothesized relationship between managing personal and others' emotions. Although significant differences were found between participants in terms of gender and grade point average (GPA), no difference was found between participants based on nationality. The results of this study indicate the need to prioritize EI in young adults and other implications.

Originality/value

The importance of EI in individuals' daily lives cannot be overemphasized. However, scholarly insights into the state of EI in the Arab context are scarce.
How popular is a topic on social media? A multi-criteria decision-making framework based on user engagement
Authors: Güner Samet , Cebeci Halil Ibrahim , Aydemir Emrah
Published: October 2023

Purpose

Social media is widely used to capture citizens' opinions and topics deemed important. The importance or interest social media users attribute to a topic is traditionally measured by tweet frequency. This approach is practical but overlooks other user engagement tools such as retweets, likes, quotes, and replies. As a result, it may lead to a misinterpretation of social media signals. This paper aims to propose a method that considers all user engagement indicators and ranks the topics based on the interest attributed by social media users.

Design/methodology/approach

A multi-criteria decision-making framework was proposed, which calculates the relative importance of user engagement tools using objective (information entropy) and subjective (Bayesian Best-Worst Method) methods. The results of the two methods are aggregated with a combinative method. Then, topics are ranked based on their user engagement levels using Multi-Objective Optimization by Ratio Analysis.

Findings

The proposed approach was used to determine citizens' priorities in transport policy, and the findings are compared with those obtained solely based on tweet frequency. The results revealed that the proposed multi-criteria decision-making framework generated more comprehensive and robust results.

Practical implications

The proposed method provides a systematic way to interpret social media signals and guide institutions in making better policies, hence ensuring that the demands of users/society are properly addressed.

Originality/value

This study presents a systematic method to prioritize user preferences in social media. It is the first in the literature to discuss the necessity of considering all user engagement indicators and proposes a reliable method that calculates their relative importance.
Pilot effectiveness trial of Mood Lifters for individuals who self-report bipolar disorder
Authors: Pokowitz Elena Lauren , Menzies Cassandra , Votta Cecilia , Ye Haonan , O’Donnell Lisa , Deldin Patricia
Published: October 2023

Purpose

Bipolar disorder is associated with poor mental and physical health outcomes, and therefore, it is crucial to research and develop effective interventions for this population (Grande et al., 2016). Unfortunately, research on the efficacy of current interventions shows only small improvements in symptoms and quality of life (Oud et al., 2016). Additionally, individuals with bipolar disorder face barriers to accessing care like social stigma, isolation and financial constraints (Blixen et al., 2016). This paper aims to introduce and examine the effectiveness of an accessible, peer-led group program, Mood Lifters (Votta and Deldin, 2022), in those who completed the program and also self-reported a diagnosis of bipolar disorder.

Design/methodology/approach

Mood Lifters is a 15-week, peer-led group program that approaches mental wellness from a biopsychosocial framework using strategies from a variety of evidence-based treatment methods (e.g. cognitive-behavioral therapy, dialectical behavior therapy, interpersonal psychotherapy, etc.). Participants meet once a week for 1 hour to review various mental health topics, including behavioral changes and insight into mood patterns. Individuals who participated in nonacademic groups in a company setting and self-reported a bipolar diagnosis were surveyed at the beginning and end of their program to measure various aspects of psychological functioning.

Findings

Results suggest that these individuals experienced significant improvements in depression, anxiety, social functioning and perceived stress, along with flourishing and positive and negative affect.

Originality/value

These findings are promising, given that bipolar disorder is historically difficult to treat (Grande et al., 2016). Based on this preliminary evidence, the authors have developed a Mood Lifters program specifically for individuals with bipolar disorder and are launching a randomized control clinical trial.
Automation in public sector jobs and services: a framework to analyze public digital transformation’s impact in a data-constrained environment
Authors: Bonomi Savignon Andrea , Zecchinelli Riccardo , Costumato Lorenzo , Scalabrini Fabiana
Published: October 2023

Purpose

This study aims to estimate the value of the impact from digital transformation (DX) focusing on its automation effect, looking at the time and cost savings coming from the substitution effect with an adoption of digital technologies. For example, cloud and artificial intelligence technologies such as ChatGPT have the potential to change ways of working, substituting and replacing several of the tasks that are currently carried out by public administration (PA) employees and labor processes underpinning PA services.

Design/methodology/approach

The paper outlines a new framework to estimate the potential impact of DX on the public sector. The authors apply this framework to estimate the value of the impact of DX on the Italian PA, defining the latter by the collection of the value of its labor (i.e. PA workforce salaries) and by the collection of the value of its outputs (i.e. public services’ costs).

Findings

This study ultimately maps out the magnitude and trends of how likely the PA occupations and services could be substituted in a wider process of DX. To do this, the authors apply their framework to the Italian PA, and they triangulate secondary data collection, from official accounts of the Italian Ministry of Economics and the National Statistical Institute, with methodological antecedents from the UK Office for National Statistics and experts’ insights. Results provide a snapshot on the type and magnitude of PA jobs and services projected to be affected by automation over the next 10 years.

Originality/value

To the best of the authors’ knowledge, this paper provides for the first time an approach to estimate the value of the impact of DX on the public sector in a data-constrained environment – or in the lack of the required primary data. Once applied to the Italian PA, this approach provides a granular map of the automatability of each of the PA occupations and of the PA services. Finally, this paper mentions preliminary insights on potential challenges related to equity in public sector jobs and implications on recruitment processes.
Rethinking tourism: why and who?
Authors: Butler Richard
Published: October 2023

Purpose

This study aims to discuss the idea of a rethinking of tourism, as proposed in the academic literature, in the wake of the coronavirus disease 2019 (COVID-19) pandemic, to evaluate the rationale for such a process and to consider by and for whom such a rethink should be undertaken.

Design/methodology/approach

This is a viewpoint paper, interpreting the literature on the topic of refocusing and rethinking tourism in general and identifying issues arising from such arguments – in particular, the impact of such a process on tourists and their destinations.

Findings

Whilst a rethink of tourism is appropriate and necessary in many respects, the rationale and goals of such a process need to be made specific and focussed rather than general and based on interest groups' preferences and beliefs.

Originality/value

Much of the discussion about rethinking tourism has focussed on what is perceived to be wrong with tourism by the various interest groups rather than what the goal and value of a refocus might be. This paper questions that approach and argues for change at local and specific levels rather than a sweeping and generalised approach.
Rethinking tourism: where is it going and how will it impact people and planet? A personal perspective
Authors: Tarlow Peter
Published: October 2023

Purpose

This paper aims to discuss the complexity of predicting the future and of making tourism futuristic predictions. It argues that tourism cannot be separated from the world context in which it operates and explores the various impacts of tourism on people and planet both in a near and more distant future.

Design/methodology/approach

This paper revises several reports and research by world economic and tourism authorities as they provide arguments for the study of trends and the complexity of the evolution of the travel and tourism industry.

Findings

There is no certain way to know what the future will bring to the tourism industry or how it will interact with society and the physical environment. What the author does know is that from the beginning of time, events do not occur in isolation and that travel and tourism will impact everything that it touches. It is impossible to make exact predictions as to what tourism will be like in the near and distant future, what the author does know is that humans will want to travel, to explore and to learn, and this desire will interact not only with tourism but with the course of history.

Originality/value

By exploring the evolution of tourism in the context of science, the author cannot even be certain where tourism will occur, if only on the same planet, within the other planets of the solar system or in the vastness of space. Science fiction predicts the latter, but only the unfolding of history will teach of the accuracy of future predictions and how the future of travel will be.
Risk factors of rituximab‐induced thrombocytopenia in patients with autoimmune bullous diseases
Authors: Lee Sang Gyun , Kim Soo‐Chan , Kim Jong Hoon
Published: October 2023

Rituximab has been the mainstay treatment for autoimmune bullous diseases (AIBDs). Among the side effects of rituximab, rituximab‐induced thrombocytopenia (RIT) is a rare but critical complication. However, there have been no reports or identification of risk factors for RIT in patients with AIBD. In our retrospective study, we compared rituximab‐treated AIBD in patients with and without thrombocytopenia to explore the risk factors. In addition, we compared two different rituximab protocols (rheumatoid arthritis [RA] and lymphoma) in terms of the incidence and severity of thrombocytopenia. A total of 222 patients were enrolled, and 46 patients (20.7%) developed RIT. Multivariate logistic regression analysis identified age and chronic kidney disease (CKD) as significant factors for RIT. We also found that patients treated with the lymphoma protocol demonstrated a significantly higher mean post‐rituximab platelet count compared with those on the RA protocol. This was the first analysis, to our knowledge, of risk factors for RIT in patients with AIBD. Individuals aged 70 or older and those with multiple comorbidities, particularly CKD, should be closely monitored for thrombocytopenia. For patients with CKD, it may be safer to use the lymphoma protocol for rituximab administration as it results in a lesser reduction in post‐rituximab platelet count.
Root litter decomposition is suppressed in species mixtures and in the presence of living roots
Authors: Heredia‐Acuña Cristina , Semchenko Marina , De Vries Franciska T.
Published: October 2023

Plant species diversity and identity can significantly modify litter decomposition, but the underlying mechanisms remain elusive, particularly for root litter. Here, we aimed to disentangle the mechanisms by which plant species diversity alters root litter decomposition. We hypothesised that (1) interactions between species in mixed communities result in litter that decomposes faster than litter produced in monocultures; (2) litter decomposition is accelerated in the presence of living plants, especially when the litter and living plant identities are matched (known as home‐field advantage).

Monocultures and a mixture of four common grassland species were established to obtain individual litter and a ‘natural’ root litter mixture. An ‘artificial’ mixed litter was created using litter from monocultures, mixed in the same proportions as the species composition in the natural litter mixtures based on qPCR measurements. These six root litter types were incubated in four monocultures, a four‐species mixture and an unplanted soil.

Root decomposition was strongly affected by root litter identity and the presence, but not diversity, of living roots. Mixed‐species litter decomposed slower than expected based on the decomposition of single‐species litters. In addition, the presence of living roots suppressed decomposition independent of the match between litter and living plant identities. Decomposition was not significantly different between the ‘natural’ and ‘artificial’ root litter mixtures, indicating that root‐root interactions in species mixtures did not affect root chemical quality.

Synthesis. Suppressed decomposition in the presence of living roots indicates that interactions between microbial communities associated with living roots and root litter control root litter decomposition. As we found no support for the importance of home‐field advantage or interspecific root interactions in modifying decomposition, suppressed decomposition of mixed‐species litter seems to be primarily driven by chemical rather than biotic interactions.
Carnitine acetyltransferase deficiency mediates mitochondrial dysfunction‐induced cellular senescence in dermal fibroblasts
Authors: Song Min Ji , Park Chi‐Hyun , Kim Haesoo , Han Sangbum , Lee Si Hyung , Lee Dong Hun , Chung Jin Ho
Published: October 2023

Aging is accompanied by impaired mitochondrial function and accumulation of senescent cells. Mitochondrial dysfunction contributes to senescence by increasing the levels of reactive oxygen species and compromising energy metabolism. Senescent cells secrete a senescence‐associated secretory phenotype (SASP) and stimulate chronic low‐grade inflammation, ultimately inducing inflammaging. Mitochondrial dysfunction and cellular senescence are two closely related hallmarks of aging; however, the key driver genes that link mitochondrial dysfunction and cellular senescence remain unclear. Here, we aimed to elucidate a novel role of carnitine acetyltransferase (CRAT) in the development of mitochondrial dysfunction and cellular senescence in dermal fibroblasts. Transcriptomic analysis of skin tissues from young and aged participants showed significantly decreased CRAT expression in intrinsically aged skin. CRAT downregulation in human dermal fibroblasts recapitulated mitochondrial changes in senescent cells and induced SASP secretion. Specifically, CRAT knockdown caused mitochondrial dysfunction, as indicated by increased oxidative stress, disruption of mitochondrial morphology, and a metabolic shift from oxidative phosphorylation to glycolysis. Mitochondrial damage induced the release of mitochondrial DNA into the cytosol, which activated the cyclic GMP‐AMP synthase (cGAS)‐stimulator of interferon genes (STING) and NF‐ĸB pathways to induce SASPs. Consistently, fibroblast‐specific CRAT‐knockout mice showed increased skin aging phenotypes in vivo, including decreased cell proliferation, increased SASP expression, increased inflammation, and decreased collagen density. Our results suggest that CRAT deficiency contributes to aging by mediating mitochondrial dysfunction‐induced senescence.
Impaired mitophagosome–lysosome fusion mediates olanzapine‐induced aging
Authors: Chen Xi , Wang Zhizhen , Zheng Peng , Dongol Anjila , Xie Yuanyi , Ge Xing , Zheng Mingxuan , Dang Xuemei , Seyhan Zehra Boz , Nagaratnam Nathan , Yu Yinghua , Huang Xu‐Feng
Published: October 2023

The lifespan of schizophrenia patients is significantly shorter than the general population. Olanzapine is one of the most commonly used antipsychotic drugs (APDs) for treating patients with psychosis, including schizophrenia and bipolar disorder. Despite their effectiveness in treating positive and negative symptoms, prolonged exposure to APDs may lead to accelerated aging and cognitive decline, among other side effects. Here we report that dysfunctional mitophagy is a fundamental mechanism underlying accelerated aging induced by olanzapine, using in vitro and in vivo (Caenorhabditis elegans) models. We showed that the aberrant mitophagy caused by olanzapine was via blocking mitophagosome–lysosome fusion. Furthermore, olanzapine can induce mitochondrial damage and hyperfragmentation of the mitochondrial network. The mitophagosome–lysosome fusion in olanzapine‐induced aging models can be restored by a mitophagy inducer, urolithin A, which alleviates defective mitophagy, mitochondrial damage, and fragmentation of the mitochondrial network. Moreover, the mitophagy inducer ameliorated behavioral changes induced by olanzapine, including shortened lifespan, and impaired health span, learning, and memory. These data indicate that olanzapine impairs mitophagy, leading to the shortened lifespan, impaired health span, and cognitive deficits. Furthermore, this study suggests the potential application of mitophagy inducers as therapeutic strategies to reverse APD‐induced adverse effects associated with accelerated aging.
National and subnational regulation of farm practices for consumer products sold within a jurisdiction: California's Proposition 12
Authors: Lee Hanbin , Sexton Richard J. , Sumner Daniel A.
Published: October 2023

This article studies the economic effects of regulations that restrict farm practices used to produce products sold within a regulating jurisdiction, regardless of where the product was produced. We apply this analysis to the impact of California's law on sow housing and the North American hog/pork supply chain. California's Proposition 12 requires that specified pork products sold in California come from hogs whose mothers were housed according to California requirements. Such regulations, whether imposed by national or subnational authorities, have unique impacts on production, demand, prices, and economic welfare both within and outside the regulating jurisdiction. Our model identifies these effects and quantifies their impacts within a calibrated equilibrium framework. Results show that California consumers will buy less pork under Proposition 12 because retail prices of regulated cuts of pork will rise by about 7%. Compliant hog producers will, on average, earn greater profits, while impacts on prices and quantities of products sold outside of California are minimal. Regulations like Proposition 12 are especially costly ways to affect farm animal treatment because they impose costs throughout the supply chain. We consider a simple alternative policy that would achieve far more change in animal housing at lower cost.