bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex-specific deubiquitylation drives immune-related neurodegeneration inDrosophila
Authors: Xia Jingnu , Pinto-Fernández Adán , Damianou Andreas , Lee Jeffery Y , Kessler Benedikt M , Davis Ilan , Elliott Paul , Ligoxygakis Petros
Published: December 2022

Risk of neurodegenerative disease such as late onset Alzheimer’s is linked to aberrant ubiquitinylation and accumulation of non-degraded proteins in brain cells. A glial network of innate immune genes modulates inflammatory responses to such protein deposition. However, vulnerability differs between the sexes. Here, we show that theDrosophilahomologue of the deubiquitylase Trabid can align the sex-specific aspects of neurodegenerative phenotypes with changes in ubiquitylation and inflammatory activity. An enzymatically null Trabid in flies, caused sex-specific changes in locomotion, sleep patterns, brain histology and ultimately, lifespan. These changes were underscored by altered ubiquitin and proteome enrichment profiles and the same enzymatic activity as its human counterpart. When the sex-determination genetransformerwas silenced in astrocytes or immunocompetent tissues, sex differences were significantly reduced. Our results indicate that Trabid underscores sex-specificity in disease neurology, by controlling the balance between ubiquitylation and inflammation.
A Very virulent infectious bursal disease virus closely related to New York strain isolated from vaccinated small-scale broiler poultry farm in Addis Ababa, Ethiopia
Authors: Almaw Gizat , Olani Abebe , Sombo Melaku , Yalew Bekele
Published: December 2022

Infectious bursal disease virus (IBDV) was initially identified in the USA. The first IBD case in Ethiopia was reported in 2002 and since then vaccination was employed to control the disease. However, IBD outbreaks continued to occur despite the routine vaccination. The present study investigated IBD outbreak that had occurred in a vaccinated small-scale broiler poultry farm. Eight samples (four Bursa and four spleen) were collected and all were confirmed to be IBDV positive using reverse transcription-polymerase chain reaction (RT-PCR) targeting the hypervariable region of virus protein 2 (hVP2). All the IBDV isolates of this study were identified to be very virulent IBDV (vvIBDV) strains. For the four IBDV isolates the nucleotide and deduced amino acid sequence for hVP2 was determined. The nucleotide sequence identity of the VP2 gene of the present outbreak isolates (which showed 100% homology among themselves) with the previous 19 vvIBDV characterized isolates from Ethiopia ranged from 90.8% to 96.9% but greater than 96% identity was recorded with only six isolates. The deduced amino acid (aa) sequence of the present outbreak isolates contained aa residues commonly found in vvIBDV strains: A222, I242, I256, I294 and S299 suggesting the strains belong to genogroup three (G3). The phylogenetic analysis of the isolates showed that all isolates clustered separately from classical virulent, vaccine and variant strains and also distantly related to UK661 (UK) and DV86 (Netherlands) very virulent strains but unexpectedly closely related to the New York, USA strain. In conclusion, the present study reported vvIBDV strains (G3) isolated from a vaccinated broiler flock. Further research is needed to characterize the molecular epidemiology and pathogenicity of the vvIBDV strains and evaluate protective efficacy of the current IBD vaccine used for routine vaccination.
Inhibition of translation termination by Drosocin, an antimicrobial peptide from fruit flies
Authors: Mangano Kyle , Klepacki Dorota , Ohanmu Irueosa , Baliga Chetana , Huang Weiping , Brakel Alexandra , Krizsan Andor , Polikanov Yury S. , Hoffmann Ralf , Vázquez-Laslop Nora , Mankin Alexander S.
Published: December 2022

A 19-amino acid longproline-richantimicrobialpeptide (PrAMP) Drosocin (Dro) is encoded in the fruit fly genome. Native Dro is glycosylated at a specific threonine residue, but the non-glycosylated peptide retains antibacterial activity. Dro shows sequence similarity to several other PrAMPs that bind in the ribosomal nascent peptide exit tunnel and inhibit protein synthesis by varying mechanisms. However, the target and mechanism of action of Dro remain unknown. Here we show that the primary mode of Dro action is inhibition of termination of protein synthesis. Our in vitro and in vivo experiments demonstrate that Dro stalls ribosomes at stop codons, likely sequestering class 1 release factors associated with the terminating ribosome. As the result, Dro strongly promotes readthrough of stop codons at subinhibitory concentrations. The elucidated mode of Dro action allows assigning it as the second member of the type II PrAMPs, of which only one representative, the antimicrobial peptide apidaecin (Api) produced by honeybees, was previously known. However, despite its functional similarity with Api, Dro interacts with the target in a markedly distinct way. The analysis of a comprehensive single-amino acid substitution library of endogenously expressed Dro variants shows that binding to the ribosome involves interactions of multiple amino acid residues distributed through the entire length of the PrAMP. Our data further show that the ribosome-targeting activity of non-glycosylated Dro can be significantly enhanced by single amino acid substitutions illuminating directions for improving its antibacterial properties.
Leadership and knowledge management practices for frugal innovation of firms in the emerging market: moderating role of collaborative culture
Authors: Le Phong Ba , Tran Dat Tho , Phung Thuy Minh Thu , Vu Khoa Dinh
Published: December 2022

Purpose

The purpose of this study is to explore the influence of transformational leadership (TL) on firm's frugal innovation. It also deepens understanding of appropriate mechanisms and conditions to improve specific aspects of frugal innovation namely frugal functionality, frugal cost and frugal ecosystem by examining the mediating role of knowledge management capability (KMC) and moderating mechanism of collaborative culture.

Design/methodology/approach

The paper utilized structural equation modeling and cross-sectional design to test hypotheses in the proposed research model using data collected from 351 participants in 112 Vietnamese firms.

Findings

The findings indicate that KMC significantly mediates TL's effects on aspects of firm's frugal innovation namely frugal functionality, frugal cost and frugal ecosystem. In addition, the influence of KMC on frugal functionality is different and depended on the extent of collaborative culture in an organization.

Research limitations/implications

The paper has significantly contributed to increasing the understanding of the link between TL and specific aspects of frugal innovation by highlighting the important role of KMC and positive effects of collaborative climate in an organization.

Originality/value

The paper is unique in the attempts to provide the valuable initiatives and integration view of leadership practices for improving specific dimensions of frugal innovation of firms in developing and emerging market.
Matchmaking under uncertainty: how hiring criteria and requirements in professional work are co-created
Authors: Tholen Gerbrand
Published: December 2022

Purpose

The aim of the study is to understand how the hiring process develops in cases where there are no explicit or formal requirements. How do implicit and informal criteria and requirements impact the process of selecting the right candidate?

Design/methodology/approach

A qualitative approach was employed through the use of semi-structured interviews with 47 external recruitment consultants in the south of England.

Findings

In contrast to what is assumed in mainstream Human Resource Management literature, employers do not rely on a comprehensive implicit understanding of what is needed in cases where there are no explicit criteria and requirements. Instead, high uncertainty makes the development of criteria and requirements incremental and negotiable but also problematic. The analysis shows that three mechanisms compensate for the lack of certainty in the hiring process. First, interviews with applicants shape how the hiring criteria develop. Second, market signals of what is available in the labour market help construct the criteria and requirements. Third, criteria and requirements are interpreted and negotiated during interactions with recruiters and others.

Originality/value

Hiring without explicit requirements and criteria is often understood as rather unproblematic and/or not fundamentally distinct from hiring with them. The study shows that in these cases the process becomes more unpredictable and more open to interpretation and negotiation.
Do commuters intend to avail electric street cars as public transport? Evidence from urban India
Authors: Dey Oindrila , Chakravarty Debalina
Published: December 2022

Purpose

Electric street car (ESC) is a globally popular clean and safe electric transport system for urban agglomeration. India envisions achieving “all-electric transport” by 2030, yet ESC as a modal transport alternative is not distinct in the policy discussion. The emerging market for electric transportation in urban spaces requires a detailed demand study at the service user level to remove behavioural barriers and design integrated energy planning in developing economies. This paper explores the probabilistic uptake intentions of the daily public transport commuters for ESCs over e-buses from the only Indian city with operational ESCs, Kolkata.

Design/methodology/approach

Using a random utility model on primary survey data from daily commuters, the authors identify demographic, psychometric and socio-economic factors influencing probabilistic uptake of ESC over e-buses.

Findings

It estimates that 38% of the commuters demand ESC over e-buses, given the alternatives' comparative details. Factors like frequent availability and technological upgradation would increase the uptake of ESCs.

Social implications

The study highlights that even though there are infrastructural challenges in the implementation of ESC, so does any other electric transport system; it is worth considering as a decarbonising transport alternative, given the high up-take intension of the users.

Originality/value

This is the first attempt to study the demand for ESC in developing economies, identifying the factors which may be considered in the sustainable urban transportation policy perspective.
The role of start-ups as knowledge brokers: a supply chain ecosystem perspective
Authors: Magliocca Pierpaolo , Herold David Martin M. , Canestrino Rossella , Temperini Valerio , Albino Vito
Published: December 2022

Purpose

Existing literature is limited in its ability to consider start-ups as a knowledge broker to trigger innovation in a supply chain ecosystem (SCE). In a traditional SCE, start-ups are relatively isolated, leading to structural holes that limit knowledge sharing among members. This paper aims to overcome that limitation and to build frameworks that help to illustrate the interaction between knowledge management and sharing, start-up innovation and an ecosystem from a supply chain perspective.

Design/methodology/approach

Following a qualitative approach, this study theorizes about the role of start-ups as knowledge brokers and the implications of knowledge management and sharing with members in an SCE concerning innovation. Conceptual analysis is used for examination, and this study uses a set of qualitative tactics to interpret and generate meaning from the existing literature.

Findings

This study develops two frameworks to provide insight into how start-ups can trigger innovation as knowledge brokers in an SCE. The first framework shows how start-ups, and their knowledge base, influence supply chain members and the overall ecosystem, highlighting the isolated function of start-ups and the issue of structural holes in a traditional SCE. The authors propose a model that illustrates how structural holes can be bridged within an SCE, thereby demonstrating how start-ups redefine the ecosystem architecture according to their knowledge broker position in the SCE.

Originality/value

By expanding insight into the concepts of how start-ups can trigger innovation as knowledge brokers in an SCE, this paper extends the so-far neglected area of start-ups and knowledge brokers. This study clarifies the conceptual and theoretical components and processes in an SCE and links the different roles of start-ups as knowledge brokers to the respective supply chain members to better understand the implications on the entire SCE.
Robots in tourism and Sustainable Development Goals: Tourism Agenda 2030 perspective article
Authors: Ivanov Stanislav , Duglio Stefano , Beltramo Riccardo
Published: December 2022

Purpose

The purpose of this perspective paper is to investigate the role of robots in tourism’s contribution to the achievement of the Sustainable Development Goals (SDGs).

Design/methodology/approach

With a deep analysis of the 17 SDGs and their 169 targets, the authors provide an interpretation on both the positive and negative impacts of robots in tourism towards the achievement of the SDG.

Findings

For several SDGs, the positive impact of robots in tourism is evident, whereas for others, it can be debated as the adoption of robots can lead to both positive and negative impacts, mostly dependent on how robots will be used. In particular, robots can provide a decent work environment for tourism and hospitality (TH) employees (SDG 8) who perform dangerous tasks while decreasing the consumption of resources (SDGs 2, 6, 7, 12, 13) due to their contribution to a company’s effectiveness and efficiency. In the meantime, robots have some impacts on the environment, both in terms of the use of resources (their manufacturing relies on rare Earth materials and robots are energy demanding) and output, especially for the management of toxic waste (e.g. batteries).

Research limitations/implications

The main limitation of this perspective paper is the lack of empirical measurement of the effects of robots in tourism on the achievement of the SDGs. However, it is a necessary exploration as a foundation for future research.

Practical implications

This perspective paper may be useful for robot manufacturers in identifying the positive and negative aspects of robots when designing sustainable robots (in terms of energy efficiency, management of the end-of-life of components, etc.) to conform to the expectations of the SDGs. It can be useful to TH companies when their managers evaluate whether to adopt robots in service operations or not.

Social implications

This contribution discusses the social implications in adopting robots in TH, specifically in terms of new opportunities for employment and in the substitution of humans in dirty, dull and dangerous tasks. It helps policymakers adopt the best policies for fostering the use of robots in TH with an eye to the environmental and social ramifications of robots.

Originality/value

To the best of the authors’ knowledge, this perspective paper is one of the first studies to investigate the role that robots can play in achieving the SDGs by TH companies.
Gender, Financial Literacy and Pension Savings*
Authors: Preston Alison , Wright Robert E.
Published: December 2022

The relationship between the gender gap in financial literacy and pension savings is examined in this paper. In Australia, individuals have considerable discretion with respect to how their pension savings are managed. We argue that financial literacy should have a positive impact on the profitability of these decisions. Analysis based on micro‐data from the Household, Income and Labour Dynamics in Australia (HILDA) Survey suggests that a sizable share of the gender gap in pension savings can be attributed to the gender gap in financial literacy. Therefore, policies aimed at improving the financial literacy of women should help improve the living standards of women in retirement.
Characteristics of pediatric continuous renal replacement therapies in hospitals with pediatric intensive care units in Japan
Authors: Haga Taiki , Ide Kentaro , Tani Masanori
Published: December 2022

Introduction

Information on the implementation of continuous renal replacement therapy (CRRT) in pediatric intensive care units (PICUs) is limited. We investigated the real‐world practice of this therapy in Japan.

Methods

We conducted a cross‐sectional survey of 26 hospitals with PICUs in Japan. One physician per hospital responded to the questionnaire.

Results

Fewer than half of the hospitals followed the CRRT practice guidelines; treatment options were often selected at a physician's discretion. PICUs varied widely in continuous renal replacement settings, circuit priming methods, frequency of circuit exchange, and policies for using CRRT in sepsis. Only two anticoagulants were used: nafamostat mesylate and unfractionated heparin. Most units did not change the nutritional dosage according to CRRT use. Many facilities were proactive concerning rehabilitation.

Conclusion

Nafamostat‐centered anticoagulation management was unique to Japan. Our results may help identify areas where additional clinical studies are needed to standardize CRRT practice.
Law and governance in the Anthropocene
Authors: Woolley Olivia , Harrington Cameron
Published: December 2022

This special issue on ‘Law and Governance in the Anthropocene’ brings together scholars from the disciplines of law and international relations to examine the ramifications of the Anthropocene for global governance and international law. The predominant focus of the literature to date has been understandably on defining the Anthropocene and on assessing what it means for the validity of longstanding viewpoints. However, more attention must be given to the specific changes needed in international relations and law in practice and as disciplines to adjust to the reality of human‐driven planetary change. Thus, it aims to build upon existing scholarship by developing specific governance responses to the challenges of the Anthropocene. This introductory article provides a brief outline of the larger workshop project which led to this special issue and offers a synopsis of the included articles. It concludes with some comments on the possible future directions for both scholarship and for legal and political practice.
Diverse gut microbiota pattern between mild and severe cancer‐related fatigue in lung cancer patients treated with first‐line chemotherapy: A pilot study
Authors: Wei Hao , Xie Lingling , Zhao Yihan , He Jun , Zhu Jiang , Li Mei , Sun Yu
Published: December 2022

Background

Cancer survivors perceive cancer‐related fatigue (CRF) as one of the most common symptoms. However, the potential relationship between CRF and gut microbiota has not been elucidated. Our study aimed to preliminary explore the diverse gut microbiota composition between mild and severe CRF in advanced lung cancer patients undergoing first‐line chemotherapy.

Methods

A total of 20 advanced lung patients treated with first‐line chemotherapy were enrolled, 10 with mild CRF and 10 with severe CRF. The self‐reported Piper Fatigue Scale and stool samples were collected from all eligible patients. The 16 S ribosomal ribonucleic acid gene was performed to analyze the intestinal microbiome.

Results

We identified the significantly diverse gut microbiota composition among patients with mild and severe CRF. The pattern was characterized by the increasing abundance in short‐chain fatty acid‐producing taxa for mild CRF patients (genus Lachnospiraceae‐UCG‐008 and family Lachnospiraceae, p < 0.05), whereas higher abundance in taxa related to inflammation (family Enterobacteriaceae and genus Escherichia‐Shigella, p < 0.05) for severe CRF patients. Significantly different Kyoto Encyclopedia of Genes and Genomes pathways between mild and severe CRF patients were evaluated concerning fatty acid metabolism, nucleotide metabolism, brain function, amino acid metabolism, and so on (p < 0.05).

Conclusions

Our study observed a plausible association between different levels of CRF and the diverse gut microbiota composition, with increasing proinflammation taxa in severe CRF patients and anti‐inflammation taxa growing in mild CRF patients. Further studies are warranted to evaluate whether CRF can be improved by modulating the gut microbiota composition.
Characteristics of xylazine‐related deaths in West Virginia—Xylazine‐related deaths
Authors: Sibbesen Julie , Abate Marie A. , Dai Zheng , Smith Gordon S. , Lundstrom Eric , Kraner James C. , Mock Allen R.
Published: December 2022

Background and Objectives

The involvement of xylazine, a veterinary drug, in West Virginia (WV) human drug‐related deaths was examined.

Methods

WV drug deaths from 2019 (when xylazine was first identified) to mid‐2021. Characteristics including toxicology findings were compared between xylazine and nonxylazine deaths.

Results

Of 3292 drug deaths, 117 involved xylazine, and the proportions of deaths with it have increased (1% [2019] to 5% [mid‐2021)]. Xylazine decedents had more cointoxicants, with fentanyl (98%) predominant followed by methamphetamine. Xylazine decedents had a significantly greater history of drug or alcohol misuse and hepatic disease.

Conclusions and Scientific Significance

In one of the largest analyses of xylazine‐involved deaths in a predominantly rural state, identification of xylazine was increasing with multiple cointoxicants (especially fentanyl), and was present in a few deaths with only one other substance involved. Health professionals should be aware of possible enhanced toxicity from xylazine ingestion especially since naloxone does not reverse xylazine's adverse effects.
An integrated interpreting service normalizes access to care for culturally and linguistically diverse (CALD) patients with colorectal cancer
Authors: Hodgson Russell , Albatat Batool , Tacey Mark , Zucchi Emiliano , Strugnell Neil , Lee Belinda
Published: December 2022

Aim

To compare access to the initial management and overall survival with colorectal cancer for limited English proficient (LEP) patients compared with patients from an English background.

Methods

All newly diagnosed patients from 2017 with colorectal cancer from a single health service with a highly multicultural catchment area and a well‐developed and integrated translation and language support (TALS) department were recruited. Time from referral to: biopsy, date seen by a surgeon, oncologist, discussion at a multidisciplinary meeting (MDM), and day of commencement of the first treatment modality, and overall survival were analyzed.

Results

One hundred sixty‐two patients were analyzed, including 57 LEP patients from 22 countries of birth. Interpreters were present at 687/782 appointments with LEP patients. There were no differences in demographics or cancer staging. There were no differences between English background and LEP patients with regard to times from referral to biopsy (1 vs. 0 days), specialist review (surgical: 4 vs. 6 days, oncological: 45 vs. 57 days), MDM discussion (23 vs. 15 days), or commencement of treatment (32 vs. 28.5 days). There were no differences in treatment for colorectal cancer, although a higher rate of stomas was noted in LEP patients. There was no difference in overall survival between groups.

Conclusion

Time to critical initial checkpoints and overall survival were similar in LEP and English background patients with colorectal cancer. An integrated TALS department may abrogate the language and cultural barriers that are known to disadvantage LEP patients and may contribute to normalizing care for the culturally and linguistically diverse community.
Effects of compound of hawthorn (Crataegus pinnatifida) and Chinese yam (Dioscorea opposita Thunb.) extracts on growth performance, intestinal health, and immune function in weaned pigs
Authors: Fu Linglong , Sun Mengning , Dong Wenxuan , Zhang Gang , Han Dandan , Zang Jianjun , Liu Hu
Published: December 2022

Plant extracts were considered as natural resources to alleviate weaning stress in pig production. A 28‐day study (Phase 1: d 0–14 and Phase 2: d 15–28) was conducted to investigate the effects of compound of hawthorn and yam extracts on growth performance, intestinal health, and immune function in weaned pigs. A total of 144 weaned pigs with average body weight (BW) of 7.89 ± 1.09 kg were assigned to three treatments with six replicates pens by BW and sex. Dietary treatments included negative control (NC), corn‐soybean meal basal diet; positive control (PC), NC + 0.08% enzyme preparations and 0.3% acidifiers; and CHY, NC + 0.3% compound of hawthorn and yam extracts. Compared with NC‐fed pigs, pigs fed CHY had greater (p < 0.05) growth performance in Phase 1. The CHY‐fed pigs had greater (p < 0.05) activities of duodenal lipase, trypsin, and greater (p < 0.05) serum concentrations of total antioxidant capacity and glutathione peroxidase. The CHY‐fed pigs had improved (p < 0.05) jejunal morphology and greater (p < 0.05) ileac valeric acid and colonic propionic acid, isobutyric acid concentrations than NC‐ and PC‐fed pigs. In conclusion, CHY can improve growth performance and is a promising additive in weaned pig diets.
Development of a chatbot for depression: adolescent perceptions and recommendations
Authors: Dosovitsky Gilly , Bunge Eduardo
Published: December 2022

Background

Chatbots are a relatively new technology that has shown promising outcomes for mental health symptoms in adults; however, few studies have been done with adolescents or reported adolescent user experiences and recommendations for chatbot development.

Methods

Twenty three participants ages 13–18 (Mage = 14.96) engaged in user testing of a chatbot developed to psychoeducate adolescents on depression, teach behavioral activation, and change negative thoughts. Thematic analysis was conducted of participants' responses to user experience questions, impressions, and recommendations.

Results

Over half (56.5%) of the sample completed the full intervention and provided user experience feedback online. The average NPS score was 6.04 (SD = 2.18), and 64.3% (n = 9) said they would use the chatbot in the future. Of all user experience responses, 54.5% were positive. The most common impressions were related to symptom improvement (61.1%) and availability (52.8%) The most frequent recommendations were related to solving technical problems (66%).

Conclusions

Chatbots for mental health are acceptable to some adolescents, a population that tends to be reluctant to engage with traditional mental health services. Most participants reported positive experiences with the chatbot, believing that it could help with symptom improvement and is highly available. Adolescents highlighted some technical and stylistic problems that developers should consider. More pilot and user testing is needed to develop mental health chatbots that are appealing and relevant to adolescents.
Efficacy of tezepelumab in patients with evidence of severe allergic asthma: Results from the phase 3 NAVIGATOR study
Authors: Corren Jonathan , Ambrose Christopher S. , Griffiths Janet M. , Hellqvist Åsa , Lindsley Andrew W. , Llanos Jean‐Pierre , Colice Gene , Menzies‐Gow Andrew
Published: December 2022

Background

Allergic asthma is the most common phenotype among patients with severe asthma. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab significantly reduced the annualized asthma exacerbation rate (AAER) versus placebo in patients with severe, uncontrolled asthma. This exploratory analysis evaluated the efficacy of tezepelumab in NAVIGATOR participants with evidence of severe allergic asthma.

Methods

Patients (12–80 years old) receiving medium‐ or high‐dose inhaled corticosteroids and ≥ 1 additional controller medication, with or without oral corticosteroids, were randomized to tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks in NAVIGATOR. In this analysis, the AAER, forced expiratory volume in 1 second (FEV1), patient‐reported outcomes (PROs), and type 2 biomarker levels were evaluated in patients grouped by sensitivity to perennial aeroallergens, confirmed symptomatic allergy, and eligibility for omalizumab treatment according to the United States (OMA‐US) and the European Union (OMA‐EU) prescribing information, including subgroups according to baseline blood eosinophil counts and fractional exhaled nitric oxide (FeNO) levels.

Results

Of 1059 patients who received treatment in NAVIGATOR, 680 (64%) had perennial aeroallergen sensitivity and 318 (30%) had confirmed symptomatic allergy; 379 (36%) and 359 (34%) patients were OMA‐US‐ and OMA‐EU‐eligible, respectively. Tezepelumab reduced the AAER over 52 weeks versus placebo by 58% (95% confidence interval [CI]: 47–67) to 68% (95% CI: 55–77) across these subgroups. Among omalizumab‐eligible patients, AAERs were reduced in patients across baseline blood eosinophil counts and FeNO levels. Tezepelumab improved FEV1 and PROs, and reduced type 2 biomarkers, versus placebo in patients with and without perennial allergy.

Conclusions

Tezepelumab was efficacious in patients with severe, uncontrolled asthma with evidence of allergic inflammation, defined by multiple clinically relevant definitions. These findings further support the benefits of tezepelumab in a broad population of patients with severe asthma, including those with severe allergic asthma.
Tirzepatide versus semaglutide for weight loss in patients with type 2 diabetes mellitus: A value for money analysis
Authors: Azuri Joseph , Hammerman Ariel , Aboalhasan Enis , Sluckis Ben , Arbel Ronen
Published: December 2022

Aims

Higher doses of the glucagon‐like peptide‐1 agonist semaglutide and, more recently, tirzepatide, a dual glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1 agonist showed a significant reduction in body weight in patients with type 2 diabetes mellitus. However, their comparative value for money for this indication is unclear. Therefore, we aimed to establish which provides better value for money.

Materials and Methods

We calculated the cost needed to treat to achieve a 1% reduction in body weight using high‐dose tirzepatide (15 mg) versus semaglutide (2.4 mg). The body weight reductions were extracted from published results of SURMOUNT‐1 and STEP 1 trials, respectively. In addition, we performed a scenario analysis to mitigate the primary differences between the two study populations. Drug costs were based on US GoodRx prices as of October 2022.

Results

Using tirzepatide resulted in a weight loss of 17.8% (95% CI: 16.3%‐19.3%) compared with 12.4% (95% CI: 11.5%‐13.4%) for semaglutide. The total cost of 72 weeks of tirzepatide was estimated at $17 527 compared with $22 878 for 68 weeks of semaglutide. Accordingly, the cost needed to treat per 1% of body weight reduction with tirzepatide is estimated at $985 (95% CI: $908‐$1075) compared with $1845 (95% CI: $1707‐$1989) with semaglutide. Scenario analysis confirmed these findings.

Conclusions

Tirzepatide provides better value for money than semaglutide for weight reduction.
Dorsal attention network activity during perceptual organization is distinct in schizophrenia and predictive of cognitive disorganization
Authors: Keane Brian P. , Krekelberg Bart , Mill Ravi D. , Silverstein Steven M. , Thompson Judy L. , Serody Megan R. , Barch Deanna M. , Cole Michael W.
Published: December 2022

Visual shape completion is a canonical perceptual organization process that integrates spatially distributed edge information into unified representations of objects. People with schizophrenia show difficulty in discriminating completed shapes, but the brain networks and functional connections underlying this perceptual difference remain poorly understood. Also unclear is whether brain network differences in schizophrenia occur in related illnesses or vary with illness features transdiagnostically. To address these topics, we scanned (functional magnetic resonance imaging, fMRI) people with schizophrenia, bipolar disorder, or no psychiatric illness during rest and during a task in which they discriminated configurations that formed or failed to form completed shapes (illusory and fragmented condition, respectively). Multivariate pattern differences were identified on the cortical surface using 360 predefined parcels and 12 functional networks composed of such parcels. Brain activity flow mapping was used to evaluate the likely involvement of resting‐state connections for shape completion. Illusory/fragmented task activation differences (‘modulations’) in the dorsal attention network (DAN) could distinguish people with schizophrenia from the other groups (AUCs > .85) and could transdiagnostically predict cognitive disorganization severity. Activity flow over functional connections from the DAN could predict secondary visual network modulations in each group, except in schizophrenia. The secondary visual network was strongly and similarly modulated in each group. Task modulations were dispersed over more networks in patients compared to controls. In summary, DAN activity during visual perceptual organization is distinct in schizophrenia, symptomatically relevant, and potentially related to improper attention‐related feedback into secondary visual areas.
Increased uptake of the P2X7 receptor radiotracer 18F‐JNJ‐64413739 in the brain and peripheral organs according to the severity of status epilepticus in male mice
Authors: Morgan James , Moreno Oscar , Alves Mariana , Baz Zuriñe , Menéndez Méndez Aida , Leister Hanna , Melia Ciara , Smith Jonathon , Visekruna Alexander , Nicke Annette , Bhattacharya Anindya , Ceusters Marc , Henshall David C. , Gómez‐Vallejo Vanessa , Llop Jordi , Engel Tobias
Published: December 2022

Objective

The P2X7 receptor (P2X7R) is an important contributor to neuroinflammation, responding to extracellularly released adenosine triphosphate. Expression of the P2X7R is increased in the brain in experimental and human epilepsy, and genetic or pharmacologic targeting of the receptor can reduce seizure frequency and severity in preclinical models. Experimentally induced seizures also increase levels of the P2X7R in blood. Here, we tested 18F‐JNJ‐64413739, a positron emission tomography (PET) P2X7R antagonist, as a potential noninvasive biomarker of seizure‐damage and epileptogenesis.

Methods

Status epilepticus was induced via an intra‐amygdala microinjection of kainic acid. Static PET studies (30 min duration, initiated 30 min after tracer administration) were conducted 48 h after status epilepticus via an intravenous injection of 18F‐JNJ‐64413739. PET images were coregistered with a brain magnetic resonance imaging atlas, tracer uptake was determined in the different brain regions and peripheral organs, and values were correlated to seizure severity during status epilepticus. 18F‐JNJ‐64413739 was also applied to ex vivo human brain slices obtained following surgical resection for intractable temporal lobe epilepsy.

Results

P2X7R radiotracer uptake correlated strongly with seizure severity during status epilepticus in brain structures including the cerebellum and ipsi‐ and contralateral cortex, hippocampus, striatum, and thalamus. In addition, a correlation between radiotracer uptake and seizure severity was also evident in peripheral organs such as the heart and the liver. Finally, P2X7R radiotracer uptake was found elevated in brain sections from patients with temporal lobe epilepsy when compared to control.

Significance

Taken together, our data suggest that P2X7R‐based PET imaging may help to identify seizure‐induced neuropathology and temporal lobe epilepsy patients with increased P2X7R levels possibly benefitting from P2X7R‐based treatments.
The cytosolic lncRNAdutA affects STATa signaling and developmental commitment in Dictyostelium
Authors: Saga Yukika , Shimoyama Yudai , Yamada Yoko , Morikawa Naoki , Kawata Takefumi
Published: December 2022

STATa is a pivotal transcription factor for Dictyostelium development. dutA is the most abundant RNA transcribed by RNA polymerase II in Dictyostelium, and its functional interplay with STATa has been suggested. This study demonstrates that dutA RNA molecules are distributed as spot‐like structures in the cytoplasm, and that its cell type‐specific expression changes dramatically during development. dutA RNA was exclusively detectable in the prespore region of slugs and then predominantly localized in prestalk cells, including the organizer region, at the Mexican hat stage before most dutA transcripts, excluding those in prestalk O cells, disappeared as culmination proceeded. dutA RNA was not translated into small peptides from any potential open reading frame, which confirmed that it is a cytoplasmic lncRNA. Ectopic expression of dutA RNA in the organizer region of slugs caused a prolonged slug migration period. In addition, buffered suspension‐cultured cells of the strain displayed reduced STATa nuclear translocation and phosphorylation on Tyr702. Analysis of gene expression in various dutA mutants revealed changes in the levels of several STATa‐regulated genes, such as the transcription factors mybC and gtaG, which might affect the phenotype. dutA RNA may regulate several mRNA species, thereby playing an indirect role in STATa activation.
Relaxation degree and defect dipoles‐controlled resistivity and leakage current in BF–BT‐based ceramics
Authors: Li Yang , Zheng Ting , Li Bing , Wu Jiagang
Published: December 2022

The low resistivity and high leakage current of bismuth ferrite–barium titanate‐based ceramics greatly limit its development. In this work, the resistivity and leakage current have been regulated by changing the relaxation degree and defect dipoles. With the introduction of Sb, the ceramics endure from weak relaxors with typically ferroelectric behavior to relaxor ferroelectrics and then to relaxors, where nearly 20 times improved resistivity can be obtained in relaxor ferroelectrics with chemical‐homogeneous grain structure and strip‐shaped/submicron‐sized coexisted domains, whereas deteriorated properties appear in relaxors with core–shell structure and tweed‐like ferroelectric domains. The decreased concentration of oxygen vacancies and Ti3+is responsible for the improved insulation in relaxor‐ferroelectrics, whereas the emergence of core–shell structure leads to electrical inhomogeneity and the conductive channels result in decreased resistivity. In addition, the leakage current mechanism is transformed from Ohmic conduction to space‐charge‐limited current as the electric field increases, which is induced by different domain switchings in ceramics with varied relaxation degrees.
Targeted gene panel analysis of Japanese patients with maturity‐onset diabetes of the young‐like diabetes mellitus: Roles of inactivating variants in the ABCC8 and insulin resistance genes
Authors: Yorifuji Tohru , Watanabe Yoh , Kitayama Kana , Yamada Yuki , Higuchi Shinji , Mori Jun , Kato Masaru , Takahashi Toru , Okuda Tokuko , Aoyama Takane
Published: December 2022

Aims/Introduction

To investigate the genetic background of Japanese patients with suspected maturity‐onset diabetes of the young (MODY).

Materials and Methods

On 340 proband patients referred from across Japan, genomic variants were analyzed using a targeted multigene panel analysis combined with the multiplex ligation probe amplification (MLPA) analysis, mitochondrial m.3243A > G analysis and methylation‐specific polymerase chain reaction of the imprinted 6q24 locus. Pathogenic/likely pathogenic variants were listed according to the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria. Additionally, variants with a population frequency <0.001 and Combined Annotation Dependent Depletion score >20 (CS >20) were listed as rare variants of uncertain significance‐CS >20.

Results

A total of 157 pathogenic/likely pathogenic variants and 44 rare variants of uncertain significance‐CS >20 were identified. In the pathogenic/likely pathogenic variants, alterations in the GCK gene were the most common (82, 52.2%) followed by HNF1A (29, 18.5%), HNF4A (13, 8.3%) and HNF1B (13, 8.3%). One patient was a 29.5% mosaic with a truncating INSR variant. In the rare variants of uncertain significance‐CS >20, 20 (45.5%) were in the genes coding for the adenosine triphosphate‐sensitive potassium channel, KCNJ11 or ABCC8, and four were in the genes of the insulin‐signaling pathway, INSR and PIK3R1. Four variants in ABCC8 were previously reported in patients with congenital hyperinsulinism, suggesting the inactivating nature of these variants, and at least two of our patients had a history of congenital hyperinsulinism evolving into diabetes. In two patients with INSR or PIK3R1 variants, insulin resistance was evident at diagnosis.

Conclusions

Causative genomic variants could be identified in at least 46.2% of clinically suspected MODY patients. ABCC8‐MODY with inactivating variants could represent a distinct category of MODY. Genes of insulin resistance should be included in the sequencing panel for MODY.
Neighborhood segregation, socioeconomic status, and cognitive function among older Chinese immigrants
Authors: Tang Fengyan , Li Ke , Rosso Andrea L. , Jiang Yanping , Li Mengting
Published: December 2022

Background

The fast‐growing population of older Chinese immigrants and their segregated residences highlight the importance of understanding the role of neighborhood context in cognitive health. The segregation‐cognition association is equivocal based on a limited number of studies among Hispanic and Asian Americans. To close the knowledge gap, this study examined the associations of neighborhood segregation and socioeconomic status (NSES) with cognitive functioning among older Chinese immigrants.

Methods

Four waves of cognitive performance tests were conducted in the Population Study of Chinese Elderly in Chicago (2011–2019) and linked to the 2010 to 2014 American Community Survey estimates of neighborhood contexts. NSES was a summary z‐score of six census variables of education, income/wealth, and occupation. Neighborhood segregation was measured by the Index of Concentrations at the Extremes (ICE), which simultaneously assesses Chinese and English language use within a given census tract. There were 170 census tracts in the present sample of 2044 participants. Latent growth curve models with adjusted cluster robust standard errors were estimated.

Results

On average, cognitive functioning declined over time (B = −0.07, p < 0.001). After adjusting for individual‐level predictors, living in high‐NSES neighborhoods was associated with slower cognitive decline (B = 0.003, p = 0.04). ICE was not associated with cognitive functioning, but boosted the protective effect of high NSES on cognitive decline (B = 0.006, p = 0.05).

Conclusions

Neighborhood socioeconomic advantage was related to slower cognitive decline among older Chinese immigrants, especially among those living in neighborhoods with more English speakers or less segregation. This finding suggests complex associations between neighborhood context and cognitive health among Chinese immigrants.
Life satisfaction among persons living with dementia and those without dementia
Authors: Gotanda Hiroshi , Tsugawa Yusuke , Xu Haiyong , Reuben David B.
Published: December 2022

Background

Despite possible major adverse cognitive, physical, social, and behavioral consequences, little is known about how persons living with dementia perceive satisfaction with life, a key component of well‐being. We sought to examine (i) whether persons living with dementia perceive a lower level of satisfaction compared to their peers without dementia and (ii) whether the associations between individual characteristics and life satisfaction are different between persons living with and without dementia.

Methods

Using a nationally representative sample of community‐dwelling older adults aged ≥70 years in the U.S. from the Health and Retirement Study, we compared scores on the Satisfaction with Life Scale (SWLS), a self‐reported 5‐item scale ranging from 1 to 7 (more satisfaction), between persons with probable dementia (n = 341) and those without (n = 5530), adjusting for individual characteristics. We also tested whether the associations between the individual characteristics and SWLS differ by dementia status.

Results

Scores on SWLS did not differ between persons with probable dementia and those without when adjusting for individual characteristics including limitations in activities of daily living (ADL) (adjusted difference, −0.09; 95% CI, −0.33 to +0.15; p‐value, 0.45). However, dementia status was associated with lower life satisfaction through the mediation of limitations in ADL (total effect, −0.29; bootstrapped 95% CI, −0.47 to −0.12). Most individual characteristics associated with lower life satisfaction were similar in the two groups, including younger age, more limitations in ADL, and depression. Less wealth was associated with lower satisfaction among persons without dementia but not among those with probable dementia.

Conclusions

Dementia status was only modestly associated with lower life satisfaction through the mediation of limitations in ADL among participants who were able to provide response. Future research is warranted to determine whether life satisfaction can be used as a meaningful outcome when evaluating well‐being among persons living with dementia.
Effectiveness of dietary interventions delivered by digital health to adults with chronic conditions: Systematic review and meta‐analysis
Authors: Barnett Amandine , Wright Charlene , Stone Christine , Ho Nok Yin , Adhyaru Pooja , Kostjasyn Sarah , Hickman Ingrid J. , Campbell Katrina L. , Mayr Hannah L. , Kelly Jaimon T.
Published: December 2022

Background

Digital health interventions may facilitate management of chronic conditions; however, no reviews have systematically assessed the effectiveness of dietary interventions delivered by digital health platforms for improving dietary intake and clinical outcomes for adults with diet‐related chronic conditions.

Methods

Databases CINAHL, CENTRAL, Embase and MEDLINE were searched from inception to April 2021 to identify controlled trials for dietary education delivered by digital health (mobile or electronic health) to adults with diet‐related chronic conditions. Random effects analysis was performed for diet quality, food groups, nutrients and clinical outcomes. Screening, data extraction and quality checking were completed in duplicate.

Results

Thirty‐nine studies were included involving 7333 participants. Significant changes were found for Mediterranean diet adherence score (standardised mean difference [SMD] = 0.79; 95% confidence interval [CI] = 0.18 to 1.40), overall fruit and vegetable intake (mean difference [MD]: 0.63 serves/day; 95% CI = 0.27–0.98), fruit intake alone (MD = 0.58 serves/day; 95% CI = 0.39 to 0.77) and sodium intake (SMD = −0.22; 95% CI = −0.44 to −0.01). Improvements were also found for waist circumference [MD = −2.24 centimetres; 95% CI = −4.14 to −0.33], body weight (MD = −1.94 kg; 95% CI = −2.63 to −1.24) and haemoglobin A1c (MD = −0.17%; 95% CI = −0.29 to −0.04). Validity of digital assessment tools to measure dietary intake were not reported. The quality of evidence was considered to have low to moderate certainty.

Conclusions

Modest improvements in diet and clinical outcomes may result from intervention via digital health for those with diet‐related chronic conditions. However, additional robust trials with better reporting of digital dietary assessment tools are needed to support implementation within clinical practice.