bluuebunny/crossref_metadata_2025 huggingface dataset:
Thromboxane A2/thromboxane A2 receptor axis facilitates hepatic insulin resistance and steatosis through endoplasmic reticulum stress in non‐alcoholic fatty liver disease
Authors: Dai Yufeng , Xu Ruijie , Chen Jinxiang , Fang Jialong , Zhang Hao , Li Haitao , Chen Wei
Published: September 2023

Background and Purpose

Defective insulin signalling and dysfunction of the endoplasmic reticulum (ER), driven by excessive lipid accumulation in the liver, is a characteristic feature in the pathogenesis of non‐alcoholic fatty liver disease (NAFLD). Thromboxane A2 (TXA2), an arachidonic acid metabolite, is significantly elevated in obesity and plays a crucial role in hepatic gluconeogenesis and adipose tissue macrophage polarization. However, the role of liver TXA2/TP receptors in insulin resistance and lipid metabolism is largely unknown.

Experimental Approach

TP receptor knockout (TP−/−) mice were generated and fed a high‐fat diet for 16 weeks. Insulin sensitivity, ER stress responses and hepatic lipid accumulation were assessed. Furthermore, we used primary hepatocytes to dissect the mechanisms by which the TXA2/TP receptor axis regulates insulin signalling and hepatocyte lipogenesis.

Key Results

TXA2 was increased in diet‐induced obese mice, and depletion of TP receptors in adult mice improved systemic insulin resistance and hepatic steatosis. Mechanistically, we found that the TXA2/TP receptor axis disrupts insulin signalling by activating the Ca2+/calcium calmodulin‐dependent kinase II γ (CaMKIIγ)–protein kinase RNA‐like endoplasmic reticulum kinase (PERK)–C/EBP homologous protein (Chop)–tribbles‐like protein 3 (TRB3) axis in hepatocytes. In addition, our results revealed that the TXA2/TP receptor axis directly promoted lipogenesis in primary hepatocytes and contributed to Kupffer cell inflammation.

Conclusions and Implications

The TXA2/TP receptor axis facilitates insulin resistance through Ca2+/CaMKIIγ to activate PERK–Chop–TRB3 signalling. Inhibition of hepatocyte TP receptors improved hepatic steatosis and inflammation. The TP receptor is a new therapeutic target for NAFLD and metabolic syndrome.
Dual action of macrophage miR‐204 confines cyclosporine A‐induced atherosclerosis
Authors: Su Jia‐Hui , Hong Yu , Han Cong‐Cong , Yu Jie , Guan Xin , Zhu Ya‐Mei , Wang Cheng , Ma Ming‐Ming , Pang Rui‐Ping , Ou Jing‐Song , Zhou Jia‐Guo , Zhang Zi‐Yi , Ban Tao , Liang Si‐Jia
Published: September 2023

Background and Purpose

Atherosclerosis induced by cyclosporine A (CsA), an inhibitor of the calcineurin/nuclear factor of activated T cells (NFAT) pathway, is a major concern after organ transplantation. However, the atherosclerotic mechanisms of CsA remain obscure. We previously demonstrated that calcineurin/NFAT signalling inhibition contributes to atherogenesis via suppressing microRNA‐204 (miR‐204) transcription. We therefore hypothesised that miR‐204 is involved in the development of CsA‐induced atherosclerosis.

Experimental Approach

ApoE−/− mice with macrophage‐miR‐204 overexpression were generated to determine the effects of miR‐204 on CsA‐induced atherosclerosis. Luciferase reporter assays and chromatin immunoprecipitation sequencing were performed to explore the targets mediating miR‐204 effects.

Key Results

CsA alone did not significantly affect atherosclerotic lesions or serum lipid levels. However, it exacerbated high‐fat diet‐induced atherosclerosis and hyperlipidemia in C57BL/6J and ApoE−/− mice, respectively. miR‐204 levels decreased in circulating monocytes and plaque lesions during CsA‐induced atherosclerosis. The upregulation of miR‐204 in macrophages inhibited CsA‐induced atherosclerotic plaque formation but did not affect serum lipid levels. miR‐204 limited the CsA‐induced foam cell formation by reducing the expression of the scavenger receptors SR‐BII and CD36. SR‐BII was post‐transcriptionally regulated by mature miR‐204‐5p via 3′‐UTR targeting. Additionally, nuclear‐localised miR‐204‐3p prevented the CsA‐induced binding of Ago2 to the CD36 promoter, suppressing CD36 transcription. SR‐BII or CD36 expression restoration dampened the beneficial effects of miR‐204 on CsA‐induced atherosclerosis.

Conclusion and Implications

Macrophage miR‐204 ameliorates CsA‐induced atherosclerosis, suggesting that miR‐204 may be a potential target for the prevention and treatment of CsA‐related atherosclerotic side effects.
Combination of PARP inhibitor and CDK4/6 inhibitor modulates cGAS/STING‐dependent therapy‐induced senescence and provides “one‐two punch” opportunity with anti‐PD‐L1 therapy in colorectal cancer
Authors: Wang Tao , Liu Weizhen , Shen Qian , Tao Ruikang , Li Chengguo , Shen Qian , Lin Yao , Huang Yongzhou , Yang Lei , Xie Gengchen , Bai Jie , Li Ruidong , Wang Lulu , Tao Kaixiong , Yin Yuping
Published: September 2023

Although PARP inhibitor (PARPi) has been proven to be a promising anticancer drug in cancer patients harboring BRCA1/2 mutation, it provides limited clinical benefit in colorectal cancer patients with a low prevalence of BRCA1/2 mutations. In our study, we found PARPi talazoparib significantly induced cellular senescence via inhibiting p53 ubiquitination and activating p21. Furthermore, CDK4/6i palbociclib amplified this therapy‐induced senescence (TIS) in vitro and in vivo. Mechanistically, talazoparib and palbociclib combination induced senescence‐associated secretory phenotype (SASP), and characterization of SASP components revealed type I interferon (IFN)‐related mediators, which were amplified by cGAS/STING signaling. More importantly, RNA sequencing data indicated that combination therapy activated T cell signatures and combination treatment transformed the tumor microenvironment (TME) into a more antitumor state with increased CD8 T cells and natural killer (NK) cells and decreased macrophages and granulocytic myeloid‐derived suppressor cells (G‐MDSCs). Moreover, clearance of the TIS cells by αPD‐L1 promoted survival in immunocompetent mouse colorectal cancer models. Collectively, we elucidated the synergistic antitumor and immunomodulatory mechanisms of the talazoparib–palbociclib combination. Further combination with PD‐L1 antibody might be a promising “one‐two punch” therapeutic strategy for colorectal cancer patients.
Developmental trajectories of achievement emotions in mathematics during adolescence
Authors: Sakaki Michiko , Murayama Kou , Frenzel Anne C. , Goetz Thomas , Marsh Herbert W. , Lichtenfeld Stephanie , Pekrun Reinhard
Published: September 2023

This study examined how adolescents' emotions in mathematics develop over time. Growth curve modeling was applied to longitudinal data collected annually from 2002 to 2006 (Grades 5–9; N = 3425 German adolescents; Mage = 11.7, 15.6 years at the first and last waves, respectively; 50.0% female). Results indicated that enjoyment and pride decreased over time (Glass's Δs = −.86, −.71). In contrast, negative emotions exhibited more complex patterns: Anger, boredom, and hopelessness increased (Δs = .52, .79, .26), shame decreased (Δ = −.12), and anxiety remained stable (Δ = .00). These change trajectories of emotions were associated with change trajectories of perceived control, intrinsic value, achievement value, and achievement in mathematics. Implications and future directions are discussed.
Usage and coordination of governance principles to address proximate and distal drivers of conflicts in fisheries commons
Authors: McClanahan Tim R.
Published: September 2023

Commons’ problems and solutions have the elements of local, proximate, and large‐scale distal processes. Solutions, therefore, require accessing, implementing, and coordinating information and actions at multiple scales. Restoring commons, such as fisheries, will require a better understanding of how stakeholders access and use information at various scales to resolve governance and restrictions problems. In 179 household interviews, perceptions of fisheries conflicts and their causes were identified, and 16 management committee key informants described their methods for mediating hypothetical small‐scale fisheries problems in Kenya. The 6 studied sites varied in human development and demographic contexts but had notable similarities that reflected a respondent's focus on localized, direct, and proximate fishing conflicts. The most cited problems included limited space, disagreement about gears, poor resource conditions, and locally inadequate benefits. The most cited sources of information were local households and the community, and there was considerably less acknowledgment of distal problems and solutions. Key informants selected a limited number of local community‐focused solutions. For example, informants chose to mediate conflicts between neighbors with local community meetings rather than through formal national institutions. Therefore, distal solutions were likely to be perceived as ineffectual, possibly due to the challenges of polycentric governance coordination. However, widespread overfishing arises from overarching distal processes not fully amenable to local solutions. Therefore, a focus on local action is expected to limit the ability to address distal problems. These include conflicting values, demographic changes, supportive governance frameworks, emerging technologies, resolving conflicting local rules, fair between‐group enforcement, responding to temporary shortages of fish, and intercommunity border and rule disputes. Improved coordination and integration of information and institutions to simultaneously address both proximate and distal common's problems are recommended.
Impact on species' online attention when named after celebrities
Authors: Blake Katie , Anderson Sean C. , Gleave Adam , Veríssimo Diogo
Published: September 2023

Celebrities can generate substantial attention and influence public interest in species. Using a large‐scale examination of publicly available data, we assessed whether species across 6 taxonomic groups received more page views on Wikipedia when the species was named after a celebrity than when it was not. We conducted our analysis for 4 increasingly strict thresholds of how many average daily Wikipedia page views a celebrity had (1, 10, 100, or 1000 views). Overall, we found a high probability (0.96–0.98) that species named after celebrities had more page views than their closest relatives that were not named after celebrities, irrespective of the celebrity threshold. The multiplicative effect on species’ page views was larger but more uncertain as celebrity page‐view thresholds increased. The range for thresholds of 1 to 1000 was 1.08 (95% credible interval [CI] 1.00–1.18) to 1.76 (95% CI 0.96–2.80), respectively. The hierarchical estimates for the taxa tended to be positive. The strongest effects were for invertebrates, followed by amphibians, reptiles, fish, and mammals, whereas the weakest effect was for birds at lower page‐view thresholds. Our results suggest that naming species after celebrities could be particularly significant for those belonging to taxonomic groups that are generally less popular than others (e.g., invertebrates). Celebrities may further influence the effectiveness of this marketing strategy, depending on their likability and connection to the species named after them. Eponyms may serve as a reminder of the disproportionate power dynamics between populations and some namesakes’ untenable actions. However, they also provide an opportunity to recognize remarkable individuals and promote equity, inclusivity, and diversity in taxonomic practice. We encourage taxonomists to examine whether naming threatened species after celebrities could affect conservation support, especially for species that are otherwise typically overlooked by the public.
Chief executive officer private firm experience and idiosyncratic risk
Authors: Mishra Dev R.
Published: September 2023

Research Question/Issue

We examine chief executive officers' (CEOs) lifetime work experience in private firms and its potential influence in shaping managers' style in public firms and their corporate policies and thus the market's perception of a firm's risk.

Research Findings/Insights

We find that the idiosyncratic risk of public firms increases with the extent of CEO work experience in privately owned firms (CEO private experience). While there is no evidence of higher investment risk taking by private CEOs, the proportion of private‐firm work experience has a positive association with disclosure deficiency, decrease in manager‐owner agency conflicts, and an increase in political risk revelations at earnings conference calls, which, in turn, are associated with the elevation of idiosyncratic risk.

Theoretical/Academic Implications

The findings of this study underscore arguments in the upper echelons theory, imprinting theory, and behavioral agency theory. The study also has implications for literature related to corporate disclosure, governance, and political risk.

Practitioner/Policy Implications

Idiosyncratic risk is important for firms, as the literature suggests it hurts a firm's ability to finance future capital investments; therefore, it is optimal for corporate boards to have strategies in place to monitor and offer orientation packages targeted at alleviating CEO style heterogeneities presented by their prior work experience in private firms.
Electrochromic materials: Scope for the cyclic decay mechanisms and performance stability optimisation strategies
Authors: Wu Yue , Mishra Yogendra Kumar , Xiong Jian
Published: September 2023

Electrochromic materials (ECMs) have important potential applications in the field of intelligent optoelectronic displays. However, ECMs and its devices cannot be truly applied on a large scale until the problem of their long‐period performance degradation is really solved. This article focuses on summarising the attenuation mechanism of common ECMs, which is mainly divided into three types: structural damage, irreversible reaction and ion capture, and summarises four optimisation strategies for the cyclic stability of ECMs at the present stage: doping is used to change the internal structure of the material in order to achieve the purpose of improving the cyclic stability; composite means to allow a variety of materials to interact with each other in order that the original material has no excellent performance; improve the cyclic stability of ECMs by the special characteristics of nanostructures; and enhance the performance by optimising the preparation process and regulating the parameters in the preparation process. Finally, the article discusses the potential for optimising the long‐term stability of ECMs in the future, based on the earlier‐mentioned research.
Opportunities and challenges of 5G network technology toward precision medicine
Authors: Kang Chia Chao , Lee Tze Yan , Lim Wai Feng , Yeo Wendy Wai Yeng
Published: September 2023

Moving away from traditional “one‐size‐fits‐all” treatment to precision‐based medicine has tremendously improved disease prognosis, accuracy of diagnosis, disease progression prediction, and targeted‐treatment. The current cutting‐edge of 5G network technology is enabling a growing trend in precision medicine to extend its utility and value to the smart healthcare system. The 5G network technology will bring together big data, artificial intelligence, and machine learning to provide essential levels of connectivity to enable a new health ecosystem toward precision medicine. In the 5G‐enabled health ecosystem, its applications involve predictive and preventative measurements which enable advances in patient personalization. This review aims to discuss the opportunities, challenges, and prospects posed to 5G network technology in moving forward to deliver personalized treatments and patient‐centric care via a precision medicine approach.
Reconsideration of the current models of estimated kidney function‐based drug dose adjustment in older adults: The role of biological age
Authors: Alikhani Radin , Pai Manjunath P.
Published: September 2023

Human lifespan has increased from a median of 46.5 years in 1950 to 71.7 years in 2022. As people age, one of the inevitable consequences is a decline in kidney function and glomerular filtration rate (GFR) which can have direct or indirect effects on the pharmacokinetic and pharmacodynamic profiles of many drugs. Numerous equations have been developed to generate estimated GFR (eGFR) using the two principal biomarkers: serum creatinine and serum cystatin C. However, the trajectory of changes with aging is dissimilar in these equations. In addition, there is recognition that chronological age (lifespan) often does not reflect biological age (healthspan) as an essential parameter in kidney function equations. In the past decade, there has been an increasing interest in quantifying biological age and new commercially available assays have entered the marketplace. In this narrative review, we illustrate how dominant equations of eGFR model the fractional change in this parameter very differently across chronological age. In addition, we review various biological age indicators (aging clocks) and challenges to their application in clinical practice. Importantly, by comparing vancomycin's mean clearance as a drug with limited metabolism and unchanged elimination between two age milestones in some recent population pharmacokinetic models, we show how efforts to quantify kidney function in older adults optimally remain under‐explored, particularly those at the upper end of their lifespan. We also propose considering new models that integrate biological age as a new pathway to improve precision drug dosing in older adults.
Forschung für die Praxis: Ernährung und Mikrobiom bei Autoimmunkrankheiten
Authors: Vorobyev Artem , Ludwig Ralf J.
Published: September 2023

Die Häufigkeit von Autoimmunerkrankungen in Industrieländern hat während der letzten Jahrzehnte ständig zugenommen. Diese Erkrankungen führen zu erhöhter Sterblichkeit sowie anhaltender Beeinträchtigung der Lebensqualität der Patienten und bedeuten eine große medizinische Belastung. Die Behandlung von Autoimmunkrankheiten beruht häufig auf unspezifischer Immunsuppression, was das Risiko von Infektionskrankheiten und Krebsmanifestationen erhöht. Die Pathogenese von Autoimmunerkrankungen ist komplex und umfasst nicht nur genetische Faktoren, sondern auch Umwelteinflüsse, die als Grund für die Zunahme von Autoimmunerkrankungen angesehen werden. Zahlreiche Umweltfaktoren wie Infektionen, Rauchen, Medikamente oder Ernährung können das Auftreten von Autoimmunität entweder fördern oder verhindern. Die Mechanismen der Beeinflussung durch Umwelteinflüsse sind jedoch komplex und derzeit noch nicht eindeutig geklärt. Die Entschlüsselung dieser Wechselwirkungen könnte unser Verständnis der Autoimmunität verbessern und neue Behandlungsmöglichkeiten für die Patienten eröffnen.
Kompressionstherapie in der Dermatologie
Authors: Dissemond Joachim , Protz Kerstin , Stücker Markus
Published: September 2023

Die Kompressionstherapie ist eine konservative Therapie, die bei vielen Patienten mit dermatologischen Krankheiten durchgeführt werden kann, insbesondere wenn diese mit Ödemen assoziiert sind. Neben den wissenschaftlich sehr gut belegten Indikationen bei venösen und lymphatischen Erkrankungen, gibt es auch zunehmend wissenschaftliche Hinweise, dass durch die Kompressionstherapie die Abheilung entzündlicher Dermatosen unterstützt wird. Wenn Ödeme vorliegen, handelt es sich, unabhängig von deren Genese, um einen Einsatz im Rahmen der Zulassung der Kompressionstherapie.

Für die Kompressionstherapie stehen heute verschiedene Materialien und Versorgungsoptionen mit systemspezifischen Vor‐ und Nachteilen zur Verfügung. Oft ist eine Kompressionstherapie mit niedrigen Ruhedruckwerten für einen Therapieerfolg ausreichend und wird von den Patienten besser toleriert. Als wichtigste Kontraindikationen der Kompressionstherapie sind die fortgeschrittene periphere arterielle Verschlusskrankheit und die dekompensierte Herzinsuffizienz zu beachten.

Bei der gemeinsam mit dem Patienten getroffenen Entscheidung für eine Kompressionstherapie, sollten individuelle Faktoren und wirtschaftliche Aspekte berücksichtigt werden. Wann immer möglich, ist ein Selbstmanagement des Patienten zu unterstützen. Hierfür sind Edukation und Hilfsmittel erforderlich.
S2k guideline diagnosis, prevention, and therapy of hand eczema
Authors: Bauer Andrea , Brans Richard , Brehler Randolf , Büttner Marion , Dickel Heinrich , Elsner Peter , Fartasch Manigé , Herzog Claudia , John Swen‐Malte , Köllner Arno , Maul Julia‐Tatjana , Merk Hans , Molin Sonja , Nast Alexander , Nikolakis Georgios D. , Schliemann Sybille , Skudlik Christoph , Weisshaar Elke , Werfel Thomas , Zidane Miriam , Worm Margitta
Published: September 2023

The consensus‐based guideline “Diagnosis, prevention, and treatment of hand eczema (HE)” provides concrete instructions and recommendations for diagnosis, prevention, and therapy of HE based on an evidence‐ and consensus‐based approach. The guideline was created based on the German guideline “Management von Handekzemen” from 2009 and the current guideline of the European Society of Contact Dermatitis (ESCD) “Guidelines for diagnosis, prevention, and treatment of hand eczema” from 2022. The general goal of the guideline is to provide dermatologists and allergologists in practice and clinics with an accepted, evidence‐based decision‐making tool for selecting and conducting suitable and sufficient therapy for patients with hand eczema. The guideline is based on two Cochrane reviews of therapeutic and preventive interventions for HE. The remaining chapters were mainly developed and consented based on non‐systematic literature research by the expert group. The expert group consisted of members of allergological and occupational dermatological professional associations and working groups, a patient representative, and methodologists. The proposals for recommendations and key statements were consented by using a nominal group process during a consensus conference on September 15, 2022. The structured consensus‐building process was professionally moderated. This guideline is valid until February 22, 2028.
The real‐world observational prospective study of health outcomes with dulaglutide and liraglutide in patients with type 2 diabetes (TROPHIES): Final, 24‐month analysis of time to first significant treatment change, treatment persistence and clinical outcomes
Authors: Giorgino Francesco , Guerci Bruno , Füchtenbusch Martin , Lebrec Jérémie , Boye Kristina , Orsini Federici Marco , Heitmann Elke , Dib Anne , Yu Maria , Sapin Hélène , García‐Pérez Luis‐Emilio
Published: September 2023

Aims

To present the final results of the TROPHIES study (The real‐world observational prospective study of health outcomes with dulaglutide and liraglutide in patients with type 2 diabetes).

Materials and Methods

The prospective, real‐world TROPHIES study included patients with type 2 diabetes initiating their first injectable glucose‐lowering medication (GLM), dulaglutide or liraglutide, in France, Germany and Italy. The primary endpoint was the time spent on dulaglutide or liraglutide until a significant treatment change over 24 months. Other endpoints measured persistence with treatment, clinical outcomes (glycated haemoglobin [HbA1c] and weight) and treatment patterns. Kaplan‐Meier estimates of time to first significant treatment change and persistence with treatment were generated. Propensity‐score‐based inverse probability of treatment weighting (IPTW) was used to adjust for baseline imbalances in the comparison between cohorts.

Results

The 286 of 1014 patients (28.2%) in the dulaglutide cohort and 448 of 991 patients (45.2%) in the liraglutide cohort had a significant treatment change over 24 months. By IPTW analysis, dulaglutide‐initiating patients were less likely to have a significant treatment change (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.46‐0.63) and more likely to be persistent with treatment (HR 0.69, 95% CI 0.56‐0.86) over 24 months than liraglutide‐initiating patients. Dulaglutide and liraglutide yielded similar HbA1c (−11.80 mmol/mol [1.08%] and −11.91 mmol/mol [1.09%]) and weight (−3.5 kg and −3.3 kg) reductions from baseline to 24 months. Few changes in patterns of treatment with other GLMs were observed in the two cohorts.

Conclusions

Dulaglutide‐initiating patients had a longer time spent without any significant treatment change and higher persistence than those initiating liraglutide. Treatment with either glucagon‐like peptide‐1 receptor agonist yielded similar and clinically meaningful reductions in HbA1c and body weight.
Metacommunity organisation of Amazonian stream fish assemblages: The importance of spatial and environmental factors
Authors: Martins André Ribeiro , Bastos Douglas Aviz , Sousa Leandro Melo , Giarrizzo Tommaso , Vieira Thiago Bernardi , Hepp Luiz Ubiratan
Published: September 2023

Metacommunity theory seeks to explain how local and regional processes contribute to the organisation of biological communities. Recent conceptual frameworks of this theory indicate that the dynamics of populations and communities are jointly established by dispersal, species responses to environmental conditions and biotic interactions dependent on species density. Here, we use hierarchical joint species distribution modelling to verify the effects of environmental factors (at multiple spatial scales), drainage network configuration, spatial autocorrelation and interspecific interactions on the structure of fish assemblages in terra‐firme streams in the Eastern Brazilian Amazon. Thirty streams were sampled in two field surveys, and 89 species were collected in total. Our results confirm the effects of limited dispersal, environmental conditions (at multiple scales) and the configuration of the drainage network on the dynamics of these assemblages. Furthermore, our results suggest that interspecific interactions are less relevant for the structuring of fish metacommunities in small Amazonian headwater streams. Abiotic factors like drainage networks and environmental heterogeneity were better predictors of species distributions than co‐occurrence patterns with potential competitors or predators.
RNA therapeutics for epilepsy: An emerging modality for drug discovery
Authors: Hansen Stine N. , Holm Anja , Kauppinen Sakari , Klitgaard Henrik
Published: September 2023

Drug discovery in epilepsy began with the finding of potassium bromide by Sir Charles Locock in 1857. The following century witnessed the introduction of phenotypic screening tests for discovering antiseizure medications (ASMs). Despite the high success rate of developing ASMs, they have so far failed in eliminating drug resistance and in delivering disease‐modifying treatments. This emphasizes the need for new drug discovery strategies in epilepsy. RNA‐based drugs have recently shown promise as a new modality with the potential of providing disease modification and counteracting drug resistance in epilepsy. RNA therapeutics can be directed either toward noncoding RNAs, such as microRNAs, long noncoding RNAs (ncRNAs), and circular RNAs, or toward messenger RNAs. The former show promise in sporadic, nongenetic epilepsies, as interference with ncRNAs allows for modulation of entire disease pathways, whereas the latter seem more promising in monogenic childhood epilepsies. Here, we describe therapeutic strategies for modulating disease‐associated RNA molecules and highlight the potential of RNA therapeutics for the treatment of different patient populations such as sporadic, drug‐resistant epilepsy, and childhood monogenic epilepsies.
Detection of equine herpesvirus‐1 (EHV‐1) in urine samples during outbreaks of equine herpesvirus myeloencephalopathy
Authors: Velloso Alvarez Ana , Jose‐Cunilleras E. , Dorrego‐Rodriguez Abel , Santiago‐Llorente Isabel , de la Cuesta‐Torrado Maria , Troya‐Portillo Lucas , Rivera Belen , Vitale Valentina , de Juan Lucia , Cruz‐Lopez Fatima
Published: September 2023

Background

Real‐time PCR is the diagnostic technique of choice for the diagnosis and control of equine herpesvirus‐1 (EHV‐1) in an outbreak setting. The presence of EHV‐1 in nasal swabs (NS), whole blood, brain and spinal cord samples has been extensively described; however, there are no reports on the excretion of EHV‐1 in urine, its DNA detection patterns, and the role of urine in viral spread during an outbreak.

Objectives

To determine the presence of EHV‐1 DNA in urine during natural infection and to compare the DNA detection patterns of EHV‐1 in urine, buffy coat (BC) and NS.

Study design

Descriptive study of natural infection.

Methods

Urine and whole blood/NS samples were collected at different time points during the hospitalisation of 21 horses involved in two EHV‐1 myeloencephalopathy outbreaks in 2021 and 2023 in Spain. Quantitative real‐time PCR was performed to compare the viral DNA load between BC‐urine samples in 2021 and NS‐urine samples in 2023. Sex, age, breed, presence of neurological signs, EHV‐1 vaccination status and treatment data were recorded for all horses.

Results

A total of 18 hospitalised horses during the 2021 and 2023 outbreaks were positive for EHV‐1, and viral DNA was detected in urine samples from a total of 11 horses in both outbreaks. Compared with BC samples, DNA presence was detected in urine samples for longer duration and with slightly higher concentration; however, compared with NS, detection of EHV‐1 in urine was similar in duration with lower DNA concentrations.

Main limitations

Limited sample size, different sampling times and protocols (BC vs. NS) in two natural infection outbreak settings.

Conclusions

EHV‐1 was detected in the urine from naturally infected horses. Urine should be considered as complimentary to blood and NS in diagnosis of EHV‐1 infection.
The state of astragaloside IV research: A bibliometric and visualized analysis
Authors: Liu Ning , Ji Yansu , Liu Rui , Jin Xin
Published: September 2023

Background

Astragaloside IV has emerged as a pharmaceutical monomer with great medical applications and potential. Astragaloside IV has many effects such as improving myocardial ischemia, cerebral ischemia–reperfusion injury, anti‐inflammatory, analgesic, antiviral, promoting lymphocyte proliferation, and antitumor effects. However, there are few bibliometric studies on astragaloside IV.

Objectives

We aim to visualize the hotspots and trends in astragaloside IV research through bibliometric analysis to further understand the future development of basic and clinical research.

Methods The articles and reviews on astragaloside IV were screened from the Web of Science Core Collection, and knowledge maps were generated using CiteSpace software. Bibliometric analysis was performed on 971 articles published from 1998 to 2022.

Results

The number of articles on astragaloside IV increased yearly. These publications came from 42 countries/regions, with China being the largest. The primary research institutions were Shanghai University of Traditional Chinese Medicine and Guangzhou University of Traditional Chinese Medicine. Journal of Ethnopharmacology was the most studied journal and co‐cited journal. A total of 473 authors were included, among which Hongxin Wang had the highest number of publications and Zhang Wd had the highest total citation frequency. After analysis, the most common keywords are astragaloside IV, expression, and oxidative stress. Cardiovascular disease, cerebral ischemia, cancer, and kidney disease are current and developing research fields.

Conclusion

This study used bibliometrics and visualization methods to analyze the research hotspots and trends of astragaloside IV. Astragaloside IV on ischemia–reperfusion injury, cancer, and tumor may become the focus of future research.
Novel tetrahydrofolate‐dependent d‐serine dehydratase activity of serine hydroxymethyltransferases
Authors: Miyamoto Tetsuya , Fushinobu Shinya , Saitoh Yasuaki , Sekine Masae , Katane Masumi , Sakai‐Kato Kumiko , Homma Hiroshi
Published: September 2023

d‐Serine plays vital physiological roles in the functional regulation of the mammalian brain, where it is produced from l‐serine by serine racemase and degraded by d‐amino acid oxidase. In the present study, we identified a new d‐serine metabolizing activity of serine hydroxymethyltransferase (SHMT) in bacteria as well as mammals. SHMT is known to catalyze the conversion of l‐serine and tetrahydrofolate (THF) to glycine and 5,10‐methylenetetrahydrofolate, respectively. In addition, we found that human and Escherichia coli SHMTs have d‐serine dehydratase activity, which degrades d‐serine to pyruvate and ammonia. We characterized this enzymatic activity along with canonical SHMT activity. Intriguingly, SHMT required THF to catalyze d‐serine dehydration and did not exhibit dehydratase activity toward l‐serine. Furthermore, SHMT did not use d‐serine as a substrate in the canonical hydroxymethyltransferase reaction. The d‐serine dehydratase activities of two isozymes of human SHMT were inhibited in the presence of a high concentration of THF, whereas that of E. coli SHMT was increased. The pH and temperature profiles of d‐serine dehydratase and serine hydroxymethyltransferase activities of these three SHMTs were partially distinct. The catalytic efficiency (kcat/Km) of dehydratase activity was lower than that of hydroxymethyltransferase activity. Nevertheless, the d‐serine dehydratase activity of SHMT was physiologically important because d‐serine inhibited the growth of an SHMT deletion mutant of E. coli, ∆glyA, more than that of the wild‐type strain. Collectively, these results suggest that SHMT is involved not only in l‐ but also in d‐serine metabolism through the degradation of d‐serine.
A Miner's rule based fatigue life prediction model for combined high and low cycle fatigue considering loading interaction effect
Authors: Wang Xiaowei , Hou Jun , Guo Hui , Wang Yansong , Sun Yujuan , Teng Bing
Published: September 2023

The key components in service, such as aero‐engine turbine blades, are generally bearing complex interactions of high and low cycle fatigue loading. It is essential to make accurate fatigue life predictions for these components. In this paper, based on experimental analysis and the Miner's rule, a combined cycle fatigue life prediction model is proposed. The effect of the loading interaction of the high and low cycle fatigue is considered through the coupled damage, which is proposed based on the investigation of the fatigue test results and does not require additional material constants except for the S‐N curve parameters. The applicability of the proposed model is validated by the experimental data of three materials and the turbine blade. Compared with the T‐K model and Miner's rule, the results demonstrate that the proposed model provides high precision accuracy.
Increasing winter temperatures explain body size decrease in wintering bird populations of Northern Europe—But response patterns vary along the spatioclimatic gradient
Authors: Bosco Laura , Otterbeck Andreas , Fransson Thord , Lindén Andreas , Piha Markus , Lehikoinen Aleksi
Published: September 2023

Aim

Recent evidence has shown changes in body size and shape of individuals, which are suggested to be a result of global warming caused by climate change. Here, we explored the spatiotemporal changes in wing length and body mass of 24 wintering bird species in Northern Europe and how these relate to temperature anomaly.

Location

Finland and Sweden, Europe.

Time Period

50 years, 1970 to 2020.

Major Taxa Studied

Birds, 24 species.

Methods

We used site‐specific, long‐term winter ringing data containing wing length and body mass measurements from across Sweden and Finland for 24 bird species. We modelled wing length and body mass change over time, in relation to the spatioclimatic gradient and as response to temperature anomalies (of [i] the same winter as the ringing took place, [ii] the previous winter and [iii] the previous spring) by accounting for phylogenetic relatedness between species and their species‐specific responses to each predictor of interest.

Results

We show that across all species, body size has decreased since the 1970s, with a negative relationship between wing length and temperature anomalies of previous winters, suggesting carry‐over effects likely linked to body size‐related survival or dispersal. Body mass was negatively related to the temperature anomaly of the same winter, indicating more immediate effects related to reduced fat reserves during mild winters.

Main Conclusions

Our results highlight a climate‐driven decrease in body size across several species and its association with positive anomalies in winter temperature in the high latitudes. However, the responses are not spatially uniform and there is considerable species‐specific variation, emphasizing the importance of conducting multispecies studies when investigating responses to climate change. The mechanisms of decreasing wing length and body mass seem to differ and underline the immediate and carry‐over effects of temperature warming during the nonbreeding season.
Nutrient use by tropical ant communities varies among three extensive elevational gradients: A cross‐continental comparison
Authors: Moses Jimmy , Peters Marcell K. , Tiede Yvonne , Mottl Ondrej , Donoso David A. , Farwig Nina , Fayle Tom M. , Novotny Vojtech , Sanders Nathan J. , Klimes Petr
Published: September 2023

Aim

Many studies demonstrate that climate limits invertebrates along tropical elevational gradients, but we have only a rudimentary understanding of the role of nutrient limitation and climatic seasonality. Here we examined the relationships between ant community structure, nutrient use and season along three undisturbed elevational gradients, each from a different continent.

Location

Ecuador (South America), Papua New Guinea (PNG: Oceania), Tanzania (Africa).

Time period

2011–2014.

Major taxa studied

Ants.

Methods

Along each of the three gradients, we placed six distinct nutrient types (amino acid, sucrose, sucrose + amino acid, lipid, NaCl, H2O). In total, we distributed 2370 baits at 38 sites from 203 m to 3972 m. We used generalized linear models to test for the effects of elevation and season on ant species richness and activity and relative nutrient use. We also tested if changes in ant trophic guilds corresponded to changes in the use of particular nutrients.

Results

Both species richness and activity decreased with elevation along each gradient. However, there were significant interaction effects among elevation, region and season, as ant activity in the dry season was higher in Ecuador and Tanzania but lower in PNG. Relative nutrient use varied among regions: ant preference for some nutrients changed with increasing elevation in Ecuador (decrease in lipid use) and Tanzania (decrease in amino acid and H2O use), while season affected nutrient use in PNG. There were common trends in trophic guilds along the three elevational gradients (e.g. proportional increase of predators), but these did not explain most of the nutrient use patterns.

Main conclusion

While the structure of ant communities changed similarly with elevation, both the seasonal and elevational effects on nutrient use by ants differed between continents. We argue that regional differences in climate and nutrient availability rather than ant functional composition shape nutrient use by ants.
Re‐centring class‐making across borders at various durées: Translocational optic, coloniality of class theory and multi‐scalar capitalist dynamics
Authors: Amelina Anna , Schäfer Jana
Published: September 2023

Sociological research on cross‐border class‐making often centres on contemporary dynamics of social inequality in the context of migration and mobility. Relying on the cultural–sociological and processual understanding of 'class', the article integrates three bodies of literature to study complexities of global and transnational class‐making to overcome the 'presentist' bias. Building on the accounts of the Annales School, and specifically on Fernand Braudel's famous distinction between courte durée, moyenne durée and longue durée of historic time periods, the article brings together three different bodies of research: (i) transnational and intersectional approaches; (ii) conceptual history of class theory and (iii) theories of racial and multi‐scalar capitalist dynamics to develop a flexible and relational, but historic‐sensitive toolkit for the analysis of global and transnational class‐making. One of the greatest advantages of this multi‐temporal outlook is that it allows to avoid over‐generalizing accounts on the logics of class‐making and to unpick potentially heterogeneous dynamics of class (re)production.
Populism and administrative dysfunction: The impact of U. S. government shutdowns on personnel and policy implementation
Authors: Resh William , Ahn Yongjin , Moynihan Donald
Published: September 2023

We examine the implications of anti‐statist populist leaders' inattention to competence and service delivery, and their embrace of a particular form of dysfunctional politics: government shutdowns. This paper explores the effects of US government shutdowns on agency policy implementation and personnel and using survey data from several hundred thousand federal employees. The first study gauges the effect of the 2018–2019 shutdown on specific elements of agency policy implementation. The results suggest that shutdowns, as a type of shock associated with anti‐statist politics, undermine the quality of government in the eyes of those closest to the work. The second and third studies consider the effect of shutdowns on employee morale, using the 2013, and 2018–2019 shutdown. While our findings indicate that the 2013 shutdown wrought durable negative impacts on the morale of shutdown agency personnel, that event appears to have prepared agencies to absorb any negative morale impacts in the 2018–2019 shutdown. Our study shows both the immediate and long‐term dynamics of government shutdowns on policy implementation and the administrative workforce.
Comprehensive analyses of the clinicopathological features and genomic mutations of combined hepatocellular‐cholangiocarcinoma
Authors: Ito Takashi , Ishii Takamichi , Takeda Haruhiko , Sumiyoshi Shinji , Tomofuji Katsuhiro , Wakama Satoshi , Makino Kenta , Horie Hiroshi , Kumagai Ken , Takai Atsushi , Uebayashi Elena Yukie , Ogiso Satoshi , Fukumitsu Ken , Haga Hironori , Seno Hiroshi , Hatano Etsuro
Published: September 2023

Aim

Combined hepatocellular‐cholangiocarcinoma (cHCC‐CCA) is a rare primary liver cancer that has two different tumor phenotypes in a single tumor nodule. The relationship between genetic mutations and clinicopathological features of cHCC‐CCA remains to be elucidated.

Methods

Whole‐exome sequencing analyses were carried out in 13 primary and 2 recurrent cHCC‐CCAs. The whole‐exome analyses and clinicopathological information were integrated.

Results

TP53 was the most frequently mutated gene in this cohort, followed by BAP1, IDH1/2, and NFE2L2 mutations in multiple cases. All tumors with diameters <3 cm had TP53 mutations. In contrast, six of seven tumors with diameters ≥3 cm did not have TP53 mutations, but all seven tumors had mutations in genes associated with various pathways, including Wnt, RAS/PI3K, and epigenetic modulators. In the signature analysis, the pattern of mutations shown in the TP53 mutation group tended to be more similar to HCC than the TP53 nonmutation group. Mutations in recurrent cHCC‐CCA tumors were frequently identical to those in the primary tumor, suggesting that those tumors originated from identical clones of the primary cHCC‐CCA tumors. Recurrent and co‐occurrent HCC tumors in the same patients with cHCC‐CCA had either common or different mutation patterns from the primary cHCC‐CCA tumors in each case.

Conclusions

The study suggested that there were two subtypes of cHCC‐CCA, one involving TP53 mutations in the early stage of the carcinogenic process and the other not involving such mutations. The comparison of the variants between primary and recurrent tumors suggested that cHCC‐CCA was derived from an identical clone.
Horizontal prey distribution determines the foraging performance of short‐ and long‐billed waders in virtual resource landscapes
Authors: Deboelpaep Evelien , Pint Steven , Koedam Nico , Van der Stocken Tom , Vanschoenwinkel Bram
Published: September 2023

When waders gather in mixed‐species flocks to feed on benthic prey, differences in morphological traits, foraging strategies and prey selection may allow different species to optimize their energy intake while reducing competition. As the effect of the fine‐scale spatial distribution of resources on energy intake is unknown, we simulated the foraging performance of two types of waders with contrasting body plans and foraging strategies in a variety of virtual mudflats with different horizontal and vertical prey distribution patterns. Although larger, longer‐billed individuals had higher energy intake rates, smaller individuals with shorter bills maintained higher prey capture rates by relocating if prey was insufficiently available. Shorter‐billed individuals struggled more to meet their energetic demands because they selected smaller prey items and had a more limited capacity to metabolize energy from food. Being able to catch larger, high‐quality prey offered a competitive advantage for longer‐billed individuals, which could be a driving force for the evolutionary lengthening of bills in waders. Interestingly, their performance was more affected by the horizontal than by the vertical prey distribution. Quantifying prey distributions may help explain how some wader species can co‐occur in the field and why some wetland areas are unattractive as foraging areas. The work confirms that the foraging performance of larger, longer‐billed birds is not limited by bill size per se, but by the energetic trade‐offs associated with the ability to catch larger prey items more efficiently, increased handling times and higher absolute energy costs. These trade‐offs may become particularly important in landscapes where prey is scarce and spatially patchy.
Effects of 1,3‐propanediol associated, or not, with butylene glycol and/or glycerol on skin hydration and skin barrier function
Authors: Pinto Juliana Rodrigues , Monteiro e Silva Silas Arandas , Leonardi Gislaine Ricci
Published: September 2023

Objective

This study aimed to assess the effect of 1,3‐propanediol at different concentrations (5%, 10%, or 15%), either applied alone or in combination with butylene glycol (BG) (5%) and/or glycerol (5%), on skin hydration and skin barrier function. The measurements were conducted using capacitance to determine skin hydration and trans epidermal water loss (TEWL) rates to evaluate skin barrier function.

Methods

A total of 30 healthy female subjects participated in the study. Capacitance and TEWL measurements were conducted at multiple time points, including before application and at 15 min, 2 and 8 h after the humectants were applied to the forearms of the subjects. All the subjects provided written informed consent.

Results

The 1,3‐propanediol in all concentrations and in all combinations (with BG and/or glycerol) increased skin hydration and improved skin barrier function 15 min, 2 and 8 h after application. Glycerol increased the hydration performance of 1,3‐propanediol. The application of 1,3‐propanediol at a concentration of 15%, either alone or in combination with other humectants, reduced the TEWL to a greater extent than lower concentrations of 1,3‐propanediol. Furthermore, the addition of glycerol to 1,3‐propanediol 15% improved the skin barrier and reduced TEWL when compared with 1,3‐propanediol alone and with the combination of 1,3‐propanediol + BG.

Conclusion

The humectants significantly improved skin hydration and reduced TEWL throughout the 8‐h time course. The increase in 1,3‐propanediol concentration, as well as its combination with glycerol, provided a greater benefit to the skin, improving both hydration and the skin barrier function.