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Abstract Purpose Electrical artefacts are frequent in implantable cardiac monitors (ICMs). We analyzed the subcutaneous electrogram (sECG) provided by an ICM with a long sensing vector and factors potentially affecting its quality. Methods Consecutive ICM recipients underwent a follow‐up where demographics, body mass index (BMI), implant location, and surface ECG were collected. The sECG was then analyzed in terms of R‐wave amplitude and P‐wave visibility. Results A total of 84 patients (43% female, median age 68 [58‐76] years) were enrolled at 3 sites. ICMs were positioned with intermediate inclination (n = 44, 52%), parallel (n = 35, 43%), or perpendicular (n = 5, 6%) to the sternum. The median R‐wave amplitude was 1.10 (0.72‐1.48) mV with P waves readily visible in 69.2% (95% confidence interval, CI: 57.8%‐79.2%), partially visible in 23.1% [95% CI: 14.3%‐34.0%], and never visible in 7.7% [95% CI: 2.9%‐16.0%] of patients. Men had higher R‐wave amplitudes compared to women (1.40 [0.96‐1.80] mV vs 1.00 [0.60‐1.20] mV, P = .001), while obese people tended to have lower values (0.80 [0.62‐1.28] mV vs 1.10 [0.90‐1.50] mV, P = .074). The P‐wave visibility reached 86.2% [95% CI: 68.3%‐96.1%] in patients with high‐voltage P waves (≥0.2 mV) at surface ECG. The sECG quality was not affected by implant site. Conclusion In ordinary clinical practice, ICMs with long sensing vector provided median R‐wave amplitude above 1 mV and reliable P‐wave visibility of nearly 70%, regardless of the position of the device. Women and obese patients showed lower but still very good signal quality.

O estudo floristico e fitossociológico dos compo­ nentes arbóreo e arbustivo da mata subtropical preser­vada no Parque Estadual do Turvo, RS (27 º a 27 º20'S e 53 °40' a 54° 10'W), está sendo feito pelo método de quadrantes, em três áreas com estruturas aparentemen­te distintas. O presente trabalho apresenta os resultados do estudo titossociológico da área 1, onde foram alocados 107 pontos, com amostragem de 428 indivíduos do componente arbóreo (DAP-z: 10 cm) e428 do componen­te arbustivo (DAP < 1O cm e h 2: 1 m). Foram estimadas densidade e freqüência absolutas e relativas, dominância relativa, índice de valor de importância e índice de valor de cobertura. Determinou-se ainda a distribuição dos indivíduos em classes de diâmetro e em classes de altura. A densidade total por área foi estimada em 546,59 indivíduos/ha para o componente arbóreo e 1499,25 indivíduos/ha para o arbustivo. Sorocea bonplandii apre­sentou o maior IVI para ambos os componentes. A estratificação dos indivíduos do componente arbóreo permite a delimitação de três estratos, apesar de não bem definidos.

o estudo florístico e fitossociológico dos componentes arbóreo e arbustivo da mata subtropical preservada no Parque Estadual do Turvo, RS (27° a 27°20'S e 53°40' a 54°10'W) está sendo feito pelo método de quadrantes em três áreas com estruturas aparentemente distintas. Este trabalho apresenta os resultados do levantamento florístico da área 1, onde foram alocados 107 pontos com amostragem de 428 indivíduos do componentearbóreo (DAP >10 cm) e 428 do componente arbustivo (DAP < 10 cm e H >1 m), num total de 37 famílias, 69 gêneros e 88 espécies. O levantamento do componente arbóreo pelo método de quadrantes, comparado com um levantamento de todas as árvores com DAP >10 cm feito em 1 ha, da mesma área em estudo demonstra a adequação do método de quadrantes para levantamentos desta natureza.

Migration is an important life-history strategy that is adopted by a significant proportion of bird species from temperate areas. Birds initiate migration after accumulating considerable energy reserves, primarily in the form of fat and muscle. Sustained exercise, such as during the crossing of ecological barriers, leads to the depletion of energy reservesand increased physiological stress. Stopover sites, where birds rest and restore energy, play a fundamental role in mitigating these challenges. The duration of resting at stopover sites is influenced by environmental and physiological conditions upon arrival, and the amount of body fat reserves plays an important role. While sleep is recognized as essential for all organisms, its importance is accentuated during migration, where energy management becomes a survival constraint. Previous research indicated that individuals with larger fat reserves tend to sleep less and favor an untucked sleep posture, influencing energy recovery and anti-predatory vigilance. We explored the relationship between sleep behavior and posture, metabolic state, and energy conservation strategies during migration in the common whitethroat (Curruca communis). We were able to confirm that sleeping in a tucked position results in metabolic energy savings, at the cost of reduced vigilance. However, whitethroats did not show alterations of their sleep patterns as a response to the amount of stored reserves. This suggests that they may not be taking full advantage of the metabolic gains of sleeping in a tucked posture, at least at this stage of their migratory journey. We suggest that, to achieve optimal fuel accumulation and maximize stopover efficiency, whitethroats prioritize increased foraging over modulating their sleep patterns., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

Behavioural flexibility plays a major role in the way animals cope with novel situations, and physiological stress responses are adaptive and highly efficient mechanisms to cope with unpredictable events. Previous studies investigating the role of stress responses in mediating behavioural flexibility were mostly done in laboratory rodents using stressors and cognitive challenges unrelated to the ecology of the species. To better understand how stress mediates behavioural flexibility in a natural context, direct manipulations of the stress response and cognitive tests in ecologically relevant contexts are needed. To this aim, we pharmacologically blocked glucocorticoid receptors (GR) in adult Neolamprologus pulcher using a minimally invasive application of a GR antagonist. GR blockade prevents the recovery after a stressful event, which we predicted to impair behavioural flexibility. After the application of the GR antagonist, we repeatedly exposed fish to a predator and tested their behavioural flexibility using a detour task, i.e. fish had to find a new, longer route to the shelter when the shortest route was blocked. While the latencies to find the shelter were not different between treatments, GR blocked fish showed more failed attempts during the detour tasks than control fish. Furthermore, weak performance during the detour tasks was accompanied by an increase of fear related behaviours. This suggests that blocking GR changed the perception of fear and resulted in an impaired behavioural flexibility. Therefore, our results support a potential link between the capacity to recover from stressors and behavioural flexibility in N. pulcher with potential consequences for an effective and adaptive coping with changing environments., Competing Interests: Declaration of competing interest We declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Understanding sexual communication requires assessing the behaviour of both the sender and the receiver. Receiver responses to sexual displays carry relevant information, but such signals or cues may be subtle and therefore technically challenging to investigate. Here, we focus on receiver body movements in response to high-intensity courtship in spotted bowerbirds ( Ptilonorhynchus maculatus ). Male bowerbirds perform a vigorous courtship choreography on dedicated display structures-bowers. Bower owners tolerate other non-territorial males at their bowers, yet the courtship displays of these so-called 'subordinate' males rarely result in successful copulations. Males that display at high intensity are preferred by females in this species, yet excessively aggressive displays may be threatening, hence scaring prospective mates away. In this study, we hypothesized that bower owners are better able to exhibit high-intensity movements without startling their audience compared with subordinate males. To address this question, we used a combination of behavioural coding and AI-based tracking of body movements, which allows precise spatial and temporal resolution for the study of subtle behavioural responses. Contrary to our predictions, we found that bower owners evoked stronger startle responses than subordinate males. We discuss these unexpected results and suggest further experimental approaches for future investigations., Competing Interests: We declare we have no competing interests., (© 2024 The Author(s).)

Migration is one of the most extreme and energy demanding life history strategies to have evolved in the animal kingdom. In birds, champions of long-distance migrations, the seasonal emergence of the migratory phenotype is characterised by rapid physiological and metabolic remodelling, including substantial accumulation of fat stores and increases in nocturnality. The molecular underpinnings and brain adaptations to seasonal migrations remain poorly understood. Here, we exposed Common quails (Coturnix coturnix) to controlled changes in day length to simulate southward autumn migration, and then blocked the photoperiod until birds entered the non-migratory wintering phase. We first performed de novo RNA-Sequencing from selected brain samples (hypothalamus) collected from birds at a standardised time at night, either in a migratory state (when restlessness was highest and at their body mass peak), or in a non-migratory state and conducted differential gene expression and functional pathways analyses. We found that the migratory state was associated with up-regulation of a few, yet functionally well defined, gene expression networks implicated in fat trafficking, protein and carbohydrate metabolism. Further analyses that focused on candidate genes (apolipoprotein H or APOH, lysosomal associated membrane protein-2 or LAMP2) from samples collected during the day or night across the entire study population suggested differences in the expression of these genes depending on the time of the day with the largest expression levels being found in the migratory birds sampled at night. We also found that expression of APOH was positively associated with levels of nocturnal activity in the migratory birds; such an association was absent within the non-migratory birds. Our results provide novel experimental evidence revealing that hypothalamic changes in expression of apolipoprotein pathways, which regulate the circulatory transport of lipids, are likely key regulatory activators of nocturnal migratory movements. Our study paves the way for performing deeper functional investigations on seasonal molecular remodelling underlying the development of the migratory phenotype., (© 2024. The Author(s).)

Background: Female mice are more resistant to obesogenic effects of a high-fat diet (HFD), compared to male mice. Although the underlying mechanisms are poorly understood, sex hormones seem to play an important role. Interestingly, the activity of the oestrogen receptor-α (ERα) is affected by the calcium-sensing-receptor (CaSR). Therefore, we investigated sex-differences upon diet-induced obesity and the role of adipocyte-specific CaSR herein., Methods: Adipocyte-specific Casr deficient mice (AdipoqCre + Casr flox ) and control mice (Casr flox ) were injected with AAV8-PCSK9 to make them prone to develop atherosclerosis and fed an obesity-inducing diet for 12 weeks., Findings: Female mice have lower visceral white adipose tissue (vWAT) mass compared to male mice, while this sex-difference is abolished upon adipocyte-specific Casr deficiency. Furthermore, while females showed elevated levels of inflammatory cytokines and CD3 + CD8 + T cell accumulation in vWAT, compared to males, adipocyte-specific Casr deficiency abrogated this sex-phenotype and demonstrated an inhibition of inflammatory signalling pathways. The expression of Erα, as well as associated genes involved in adipocyte differentiation, was increased in female mice in a mostly adipocyte-specific Casr dependent manner. Interestingly, circulating lipid levels were reduced in female compared to male mice, which correlated with decreased atherosclerotic plaque formation. These systemic effects were abrogated upon adipocyte-specific Casr deficiency., Interpretation: Our findings indicate that female mice show a more pronounced vWAT dysfunction compared to males upon obesity. This sex effect is abolished upon adipocyte-specific Casr deficiency. In contrast, females show diminished atherosclerotic plaque formation compared to males, an effect that was abrogated by adipocyte-specific Casr deficiency., Funding: This work was supported by a grant from the Interdisciplinary Center for Clinical Research within the faculty of Medicine at the RWTH Aachen University, by the Corona Foundation, by the Deutsche Forschungsgemeinschaft (DFG), the BMBF and Free State of Bavaria and the DZHK., Competing Interests: Declaration of interests None., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The ERLIN1 p.Ile291Val single-nucleotide polymorphism (rs2862954) is associated with protection from steatotic liver disease (SLD), but effects of this variant on metabolic phenotypes remain uncertain., Methods: Metabolic phenotypes and outcomes associated with ERLIN1 p.Ile291Val were analyzed by using a genome-first approach in the UK Biobank (UKB), Penn Medicine BioBank (PMBB), and All of Us cohort., Findings: ERLIN1 p.Ile291Val carriers exhibited significantly lower serum levels of alanine aminotransferase and aspartate aminotransferase as well as higher levels of triglycerides, low-density lipoprotein cholesterol, Apolipoprotein B, high-density lipoprotein cholesterol, and Apolipoprotein A1 in UKB, and these values were affected by ERLIN1 p.Ile291Val in an allele-dose-dependent manner. Homozygous ERLIN1 p.Ile291Val carriers had a significantly reduced risk of developing metabolic dysfunction-associated SLD (MASLD, adjusted odds ratio [aOR] = 0.92, 95% confidence interval [CI], 0.88-0.96). The protective effect of this variant was enhanced in patients with alcoholic liver disease. Our results were replicated in PMBB and the All of Us cohort. Strikingly, the protective effects of ERLIN1 p.Ile291Val were not apparent in individuals carrying the TM6SF2 p.Glu167Lys variant associated with increased risk of SLD. We analyzed the effects of predicted loss-of-function ERLIN1 variants and found that they had opposite effects, namely reduced plasma lipids, suggesting that ERLIN1 p.Ile291Val may be a gain-of-function variant., Conclusion: Our study contributes to a better understanding of ERLIN1 by investigating a coding variant that has emerged as a potential gain-of-function mutation with protective effects against MASLD development., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

A multitude of animal species undergo prolonged fasting events at regularly occurring life history stages. During such periods of food deprivation, individuals need to suppress their appetite. The satiety signalling gut hormone ghrelin has received much attention in this context in studies looking at mammalian systems. In wild birds, however, knowledge on the ghrelin system and its role during extended fasts is still scarce. In this study, we collected plasma samples for measurements of circulating ghrelin concentrations from adult southern rockhopper penguins (Eudyptes chrysocome chrysocome) during the three to four week-long moult-fast that they repeat annually to replace their feathers. We further sampled chicks before and after feeding bouts and non-moulting adults. Circulating ghrelin levels did not differ significantly between fed and unfed chicks but chicks had significantly lower plasma ghrelin levels compared to adults. Furthermore, penguins in late moult (i.e. individuals at the end of the prolonged fasting bout) had higher ghrelin levels compared to non-moulting adults. Our results show elevated levels of circulating ghrelin during moult and generally lower levels of ghrelin in chicks than in adults regardless of feeding state. Given the scarcity or absence of knowledge on the function of ghrelin in seabirds and in fasting birds in general, our results add greatly to our understanding of the avian ghrelin system., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The ability of individual animals to defend a territory as well as various phenotypic and behavioral traits may be targets of sexual selection used by males to evaluate their competitors or by females to choose males. A frequent question in animal behavior is whether male traits and characteristics of their territory are correlated and what are the mechanisms that may mediate such associations when they exist. Because hormones link phenotype to behavior, by studying the role of testosterone in territoriality one may come closer to understanding the mechanisms mediating correlations or lack thereof between characteristics of territories and of males. We evaluated whether variation in characteristics of territories (size and quality) are correlated with variation in morphology, coloration, testosterone, heterozygosity, and calls in two species of poison frogs. The Amazonian frog Allobates aff. trilineatus exhibits male care and defends territories only during the breeding season, while the endangered frog Oophaga lehmanni displays maternal care and defends territories throughout the year. We found that morphological traits (body length, weight, thigh size), call activity, and testosterone levels correlated with size and various indicators of quality of the territory. However, the direction of these correlations (whether positive or negative) and which specific morphological, acoustic traits or testosterone level variables covaried depended on the species. Our findings highlight an endocrine pathway as part of the physiological machinery that may underlie the interplay between male traits and territorial behavior. We were able to identify some male traits related to territory attributes, but whether females choose males based on these traits requires further research., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Common variants of the max-like protein X (MLX)-interacting protein-like (MLXIPL) gene, encoding the transcription factor carbohydrate-responsive element-binding protein, have been shown to be associated with plasma triglyceride levels. However, the role of these variants in steatotic liver disease (SLD) is unclear., Methods: We used a genome-first approach to analyze a variety of metabolic phenotypes and clinical outcomes associated with a common missense variant in MLXIPL, Gln241His, in 2 large biobanks: the UK Biobank and the Penn Medicine Biobank., Results: Carriers of MLXIPL Gln241His were associated with significantly lower serum levels of triglycerides, apolipoprotein-B, gamma-glutamyl transferase, and alkaline phosphatase. Additionally, MLXIPL Gln241His carriers were associated with significantly higher serum levels of HDL cholesterol and alanine aminotransferase. Carriers homozygous for MLXIPL Gln241His showed a higher risk of SLD in 2 unrelated cohorts. Carriers of MLXIPL Gln241His were especially more likely to be diagnosed with SLD if they were female, obese, and/or also carried the PNPLA3 I148M variant. Furthermore, the heterozygous carriage of MLXIPL Gln241His was associated with significantly higher all-cause, liver-related, and cardiovascular mortality rates. Nuclear magnetic resonance metabolomics data indicated that carriage of MLXIPL Gln241His was significantly associated with lower serum levels of VLDL and increased serum levels of HDL cholesterol., Conclusions: Analyses of the MLXIPL Gln241His polymorphism showed a significant association with a higher risk of SLD diagnosis and elevated serum alanine aminotransferase as well as significantly lower serum triglycerides and apolipoprotein-B levels. MLXIPL might, therefore, be a potential pharmacological target for the treatment of SLD and hyperlipidemia, notably for patients at risk. More mechanistic studies are needed to better understand the role of MLXIPL Gln241His on lipid metabolism and steatosis development., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Social perception relies on different sensory channels, including vision and audition, which are specifically important for judgements of appearance. Therefore, to understand multimodal integration in person perception, it is important to study both face and voice in a synchronized form. We introduce the Vienna Talking Faces (ViTaFa) database, a high-quality audiovisual database focused on multimodal research of social perception. ViTaFa includes different stimulus modalities: audiovisual dynamic, visual dynamic, visual static, and auditory dynamic. Stimuli were recorded and edited under highly standardized conditions and were collected from 40 real individuals, and the sample matches typical student samples in psychological research (young individuals aged 18 to 45). Stimuli include sequences of various types of spoken content from each person, including German sentences, words, reading passages, vowels, and language-unrelated pseudo-words. Recordings were made with different emotional expressions (neutral, happy, angry, sad, and flirtatious). ViTaFa is freely accessible for academic non-profit research after signing a confidentiality agreement form via https://osf.io/9jtzx/ and stands out from other databases due to its multimodal format, high quality, and comprehensive quantification of stimulus features and human judgements related to attractiveness. Additionally, over 200 human raters validated emotion expression of the stimuli. In summary, ViTaFa provides a valuable resource for investigating audiovisual signals of social perception., (© 2023. The Author(s).)

The bewildering courtship phenotypes of male birds of paradise ( Paradisaedae ) represent a classic example of sexual selection through mate choice. While the majority of sexual selection studies have focused on either mate choice or intrasexual competition, males across a variety of taxa adopt alternative mating tactics as additional means of obtaining fertilization when they are otherwise unable to. For example, across various polygynous birds, subordinate males engage in sneak copulations, which may offset the fitness costs of prolonged subordinate periods. Despite exhibiting strong mating skews and male delayed plumage maturation, reports of sneak copulation in the birds of paradise are exceedingly rare. After reviewing an extensive video collection of courtship interactions, we found examples of mountings by female-plumaged birds in three birds of paradise species: the Western parotia Parotia sefilata , Carola's parotia Parotia carolae , and the magnificent bird of paradise Cicinnurus magnificus . While homosexual mountings by females have been documented previously in Lawes' parotia P. lawesii , adult males in the magnificent bird of paradise violently attacked intruding female-plumaged birds attempting to mount receivers, suggesting that they may be immature males engaging in alternative mating tactics. Overall, the rare video footage described here is suggestive of two fascinating, yet unexplored phenomena in polygynous birds: alternative mating tactics and female homosexual behaviour., Competing Interests: Conflict of Interest Statement The authors are not aware of any conflicts of interest that may have influenced the present article.

Trivalent chromium (Cr(III)) is a contaminant with toxic activity. Its presence in waters and soils is usually related to industrial activities such as tanneries. The aim of this study was to compare the removal of Cr(III) in hydroponic solutions and tannery effluents using two floating macrophytes: Salvinia auriculata and Eichhornia crassipes . First, to determine the chromium removal capacity in solution and the bioaccumulation factor (BAF) in tissues of each plant, experiments were set up with contaminated solutions with Cr(III) concentrations of 2, 5, 10, 20, and 40 mg/L. Subsequently, both plant species were exposed to a primary tannery effluent contaminated with 12 mg/L of Cr(III) in order to study the removal capacity of organic and inorganic matter, as well as the acute toxicity in the water flea ( Daphnia magna ) and genotoxicity in zebrafish ( Danio rerio ). Tests carried out on nutrient solutions revealed that both plants have a high capacity for removing Cr(III) in solution. The BAF in tissues was higher in E. crassipes compared to S. auriculata . In the experiments with a tannery effluent, both species presented low nutrient and organic matter removal efficiency, but they showed good Cr(III) removal capacity, with average reduction values of 57% for S. auriculata and 54% for E. crassipes after 72 h of exposure. E. crassipes contributed most to the reduction in acute toxicity in D. magna , while S. auriculata did not show a similar effect. However, both plant species managed to reduce the genotoxicity marker in D. rerio when compared with the initial effluent and the control.

While immunity is frequently dampened when birds engage in strenuous migratory flights, whether and how immunity changes during the rapid accumulation of energy stores in preparation for migration remains largely unknown. Here we induced pre-migratory fattening through controlled changes of daylight in common quails (Coturnix coturnix) and regularly assessed changes in three markers of constitutive innate immunity (leukocyte coping capacity or LCC, hemagglutination and hemolysis titres) and measures of body composition (lean and fat mass). All the three markers showed similar changes over the pre-migratory fattening process. LCC responses, hemagglutination titres, and hemolysis titres, were on average higher in the mid-fattening phase compared to the peak-fattening phase, when values were similar to those observed prior the start of pre-migratory fattening. At mid-fattening, we found that the birds that showed a larger accumulation of fat mass (as % of body mass) had lower LCC peak responses and hemolysis titres. Reversibly, at mid-fattening, we also found that the birds that kept a higher proportion of lean mass (as % of body mass) had the highest LCC peaks. Our results indicate that migratory birds undergo changes in immune indices (over 8 weeks) as they accumulate energy stores for migration and propose that this could be due to competing or trade-off processes between metabolic remodelling and innate immune system function., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

During long-distance migrations, some bird species make use of in-wake flying, which should allow them to profit from the upwash produced by another bird. While indirect evidence supports energy saving as the primary benefit of in-wake flying, measurements are still missing. We equipped migrating northern bald ibises ( Geronticus eremita ) with high-precision global navigation satellite system data loggers to track their position in the flock. We estimated birds' energy expenditure through different proxies, namely dynamic body acceleration (DBA), heart rate and effective wingbeat frequency. During active flapping flight, DBA estimates dropped off when in-wake compared with when not-in-wake. In addition, effective wingbeat frequency decreased, suggesting an increased use of intermittent gliding flight during in-wake periods. Heart rate varied greatly among individuals, with a clear decrease during gliding-corroborating its energy-saving function. Furthermore, we found consistent proof for decreased heart rate during in-wake flying, by up to 4.2%. Hence, we have shown that flying in the wake of another individual reduces birds' DBA, heart rate and effective wingbeat frequency, which could reflect reduced energy requirement.

Few studies have offered detailed descriptions of copulatory behaviours in the birds of paradise (family Paradisaeidae) and systematic investigations of their sexual behaviours are rare. We recorded courtship behaviours of Victoria's Riflebird Ptiloris victoriae in the Atherton Tablelands in Queensland, Australia using motion triggered cameras and report a rare case of three sequential mountings by an adult-plumaged male. While the recipient of these mountings performed female-typical sexual behaviours, it also briefly performed a male courtship display behaviour, suggesting that it may be an immature male. This observation raises several questions about the courtship behaviour of this species. Females may, for instance, occasionally solicit multiple copulations from preferred males to maximize the amount of transferred sperm. Another intriguing possibility is that immature males tolerate being mounted and potentially even mimic female sexual behaviours when learning from the displays of adult males. We also describe a novel adult male sexual behaviour, namely 'nape-pecking'., Competing Interests: Conflicts of interest/Competing interests: The authors are not aware of any conflicts of interest that may have influenced the material presented in this article.

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Traditionally, xenobiotic receptors are known for their role in chemical sensing and detoxification, as receptor activation regulates the expression of various key enzymes and receptors. However, recent studies have highlighted that xenobiotic receptors also play a key role in the regulation of lipid metabolism and therefore function also as metabolic sensors. Since dyslipidemia is a major risk factor for various cardiometabolic diseases, like atherosclerosis and non-alcoholic fatty liver disease, it is of major importance to understand the molecular mechanisms that are regulated by xenobiotic receptors. In this review, three major xenobiotic receptors will be discussed, being the aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR) and the constitutive androstane receptor (CAR). Specifically, this review will focus on recent insights into the metabolic functions of these receptors, especially in the field of lipid metabolism and the associated dyslipidemia.

To tackle the COVID-19 infodemic, we analysed 58,625 articles from 460 unverified sources, that is, sources that were indicated by fact checkers and other mis/disinformation experts as frequently spreading mis/disinformation, covering the period from 1 January 2020 to 31 December 2022. Our aim was to identify the main narratives of COVID-19 mis/disinformation, develop a codebook, automate the process of narrative classification by training an automatic classifier, and analyse the spread of narratives over time and across countries. Articles were retrieved with a customised version of the Europe Media Monitor (EMM) processing chain providing a stream of text items. Machine translation was employed to automatically translate non-English text to English and clustering was carried out to group similar articles. A multi-level codebook of COVID-19 mis/disinformation narratives was developed following an inductive approach; a transformer-based model was developed to classify all text items according to the codebook. Using the transformer-based model, we identified 12 supernarratives that evolved over the three years studied. The analysis shows that there are often real events behind mis/disinformation trends, which unverified sources misrepresent or take out of context. We established a process that allows for near real-time monitoring of COVID-19 mis/disinformation. This experience will be useful to analyse mis/disinformation about other topics, such as climate change, migration, and geopolitical developments., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kotseva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Sexual selection research has been dominated by the notion that mate choice selects for the most vigorous displays that best reflect the quality of the courter. However, courtship displays are often temporally structured, containing different elements with varying degrees of intensity and conspicuousness. For example, highly intense movements are often coupled with more subtle components such as static postures or hiding displays. Here, we refer to such subtle display traits as 'coy', as they involve the withholding of information about maximal display capabilities. We examine the role of intensity variation within temporally dynamic displays, and discuss three hypotheses for the evolution of coy courtship behaviours. We first review the threat reduction hypothesis, which points to sexual coercion and sexual autonomy as important facets of sexual selection. We then suggest that variation in display magnitude exploits pre-existing perceptual biases for temporal contrast. Lastly, we propose that information withholding may leverage receivers' predispositions for filling gaps in information-the 'curiosity bias'. Overall, our goal is to draw attention to temporal variation in display magnitude, and to advocate possible scenarios for the evolution of courtship traits that regularly occur below performance maxima. Throughout, we highlight novel directions for empirical and theoretical investigations.

Urbanisation is one of the biggest environmental challenges of our time, yet we still lack an integrative understanding of how cities affect behaviour, physiology and parasite susceptibility of free-living organisms. In this study, we focus on carotenoids, strictly dietary micronutrients that can either be used as yellow-red pigments, for integument colouration (signalling function), or as antioxidants, to strengthen the immune system (physiological function) in an urban predator, the Eurasian kestrel (Falco tinnunculus). Kestrels are specialised vole hunters but shift to avian prey in cities where diurnal rodents are not sufficiently available. This different foraging strategy might determine the quantity of carotenoids available. We measured integument colouration, circulating carotenoids in the blood and ectoparasite burden in kestrels along an urban gradient. Our results showed that nestlings that were raised in more urbanised areas displayed, unrelated to their ectoparasite burden, a paler integument colouration. Paler colours were furthermore associated with a lower concentration of circulating carotenoids. These findings support the hypothesis that the entire urban food web is carotenoid deprived and only prey of low quality with low carotenoid content is available (e.g. fewer carotenoids in urban trees, insects, small birds and finally kestrels). The alternative hypothesis that nestlings allocate carotenoids to reduce physiological stress and/or to cope with parasites rather than invest into colouration could not be supported. Our study adds to existing evidence that urban stressors negatively affect carotenoid production in urban areas, a deficiency that dissipate into higher trophic levels., (© 2023. The Author(s).)

Background: The hepatoprotective effects of aspirin have been observed in individuals with viral hepatitis; however, its impact on the general population remains uncertain. Understanding the association between aspirin use and the development of liver diseases is crucial for optimizing preventive strategies., Methods: We identified individuals with aspirin use in the UK Biobank and the Penn Medicine Biobank, as well as propensity-score-matched controls. Outcome measures included new liver disease development, diagnosed by MRI or "International Classification of Diseases and Related Health Problems" coding, and incidences of gastrointestinal bleeding and ulcers., Results: In the UK Biobank cohort, regular aspirin use was associated with an 11.2% reduction in the risk of developing new liver diseases during the average 11.84 ± 2.01-year follow-up period (HR=0.888, 95% CI = 0.819-0.963; p = 4.1 × 10-3). Notably, the risk of metabolic dysfunction-associated steatotic liver disease (ICD-10 K76.0) and MRI-diagnosed steatosis was significantly lower among aspirin users (HR = 0.882-0.911), whereas no increased risk of gastrointestinal bleeding or ulcers was observed. These findings were replicated in the Penn Medicine Biobank cohort, in which the protective effect of aspirin appeared to be dependent on the duration of intake. The greatest risk reduction for new liver disease development was observed after at least 1 year of aspirin use (HR = 0.569, 95% CI = 0.425-0.762; p = 1.6 × 10-4). Intriguingly, when considering general risk factors, only men exhibited a lower risk of MRI-confirmed or ICD-coded steatosis with aspirin use (HRs = 0.806-0.906), while no significant protective effect of aspirin was observed in females., Conclusion: This cohort study demonstrated that regular aspirin use was associated with a reduced risk of liver disease in men without an elevated risk of gastrointestinal bleeding or ulcers. Further investigation is warranted to elucidate potential sex-related differences in the effects of aspirin and to inform tailored preventive strategies for liver diseases., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Migratory species are changing their timing of departure from wintering areas and arrival to breeding sites (i.e. migration phenology) in response to climate change to exploit maximum food availability at higher latitudes and improve their fitness. Despite the impact of changing migration phenology at population and community level, the extent to which individual and species-specific response affects associations among co-migrating species has been seldom explored. By applying temporal co-occurrence network models on 15 years of standardized bird ringing data at a spring stopover site, we show that African-European migratory landbirds tend to migrate in well-defined groups of species with high temporal overlap. Such 'co-migration fidelity' significantly increased over the years and was higher in long-distance (trans-Saharan) than in short-distance (North African) migrants. Our findings suggest non-random patterns of associations in co-migrating species, possibly related to the existence of regulatory mechanisms associated with changing climate conditions and different uses of stopover sites, ultimately influencing the global economy of migration of landbirds in the Palearctic-African migration system., Competing Interests: We declare we have no competing interests., (© 2023 The Authors.)

Background: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity in people with and without diabetes, but it is underdiagnosed, posing challenges for research and clinical management. Here, we determine if natural language processing (NLP) of data in the electronic health record (EHR) could identify undiagnosed patients with hepatic steatosis based on pathology and radiology reports., Methods: A rule-based NLP algorithm was built using a Linguamatics literature text mining tool to search 2.15 million pathology report and 2.7 million imaging reports in the Penn Medicine EHR from November 2014, through December 2020, for evidence of hepatic steatosis. For quality control, two independent physicians manually reviewed randomly chosen biopsy and imaging reports (n = 353, PPV 99.7%)., Findings: After exclusion of individuals with other causes of hepatic steatosis, 3007 patients with biopsy-proven NAFLD and 42,083 patients with imaging-proven NAFLD were identified. Interestingly, elevated ALT was not a sensitive predictor of the presence of steatosis, and only half of the biopsied patients with steatosis ever received an ICD diagnosis code for the presence of NAFLD/NASH. There was a robust association for PNPLA3 and TM6SF2 risk alleles and steatosis identified by NLP. We identified 234 disorders that were significantly over- or underrepresented in all subjects with steatosis and identified changes in serum markers (e.g., GGT) associated with presence of steatosis., Interpretation: This study demonstrates clear feasibility of NLP-based approaches to identify patients whose steatosis was indicated in imaging and pathology reports within a large healthcare system and uncovers undercoding of NAFLD in the general population. Identification of patients at risk could link them to improved care and outcomes., Funding: The study was funded by US and German funding sources that did provide financial support only and had no influence or control over the research process., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

The Stroke-Heart syndrome is a major chapter in neurocardiology. Both brain-heart and stroke-heart correlations are based on neurophysiological studies that define and describe the relation between the central autonomic system and cardiac function and it will be presented in this narrative review. The Stroke-Heart syndrome groups the entire spectrum of cardiac changes - clinical, ECG, echocardiographic, biological, morphological - that occur in the first 30 days from the onset of stroke, especially in the first days. Their presence significantly marks the evolution and prognosis of stroke. The damage resulted from hypothalamus-pituitary-adrenal axis activation and high catecholamine release (adrenergic storm) targets mainly the myocyte and the microcirculation.The Takotsubo syndrome and Stunned myocardium are distinct forms of neurogenic myocardial ischemia - with changes in ECG, parietal motility, and biological markers - usually reversible although evolution towards cardiac dysfunction is also possible. The concept of Stroke-Heart syndrome and the brain-heart correlation brought new scientific information regarding stress cardiomyopathy or neurogenic myocardial injury., (© 2023 Ileana Raluca Nistor et al., published by Sciendo.)

Background: Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease are among the most common liver diseases worldwide, and there are currently no Food and Drug Administration (FDA)-approved treatments. Recent studies have focused on lifestyle changes to prevent and treat NAFLD. Omega-3 supplementation is associated with improved outcomes in patients with chronic liver disease. However, it is unclear whether Omega-3 supplementation can prevent the development of liver disease, particularly in individuals at an increased (genetic) risk., Methods: In this UK Biobank cohort study, we established a multivariate cox proportional hazards model for the risk of incident liver disease during an 11 year follow up time. We adjusted the model for diabetes, prevalent cardiovascular disorders, socioeconomic status, diet, alcohol consumption, physical activity, medication intake (insulin, biguanides, statins and aspirin), and baseline characteristics., Results: Omega-3 supplementation reduced the risk of incident liver disease (HR = 0.716; 95% CI: 0.639, 0.802; p = 7.6 × 10 -9 ). This protective association was particularly evident for alcoholic liver disease (HR = 0.559; 95% CI: 0.347, 0.833; p = 4.3 × 10 -3 ), liver failure (HR = 0.548; 95% CI: 0.343, 0.875; p = 1.2 × 10 -2 ), and non-alcoholic liver disease (HR = 0.784; 95% CI: 0.650, 0.944; p = 1.0 × 10 -2 ). Interestingly, we were able to replicate the association with reduced risk of NAFLD in a subset with liver MRIs (HR = 0.846; 95% CI: 0.777, 0.921; p = 1.1 × 10 -4 ). In particular, women benefited from Omega-3 supplementation as well as heterozygous allele carriers of the liver-damaging variant PNPLA3 rs738409., Conclusions: Omega-3 supplementation may reduce the incidence of liver disease. Our study highlights the potential of personalized treatment strategies for individuals at risk of metabolic liver disease. Further evaluation in clinical trials is warranted before Omega-3 can be recommended for the prevention of liver disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vell, Creasy, Scorletti, Seeling, Hehl, Rendel, Schneider and Schneider.)

Background: Genetic inactivation and pharmacologic inhibition of the microsomal triglyceride transfer protein (MTP; gene name MTTP) inhibits hepatic secretion of VLDL, thereby reducing serum lipids and apoB at the expense of increasing hepatic steatosis., Aim: To examine the effects of missense variants in MTTP on hepatic and circulating lipids., Methods: We analysed the association of MTTP missense variants with metabolic, hepatic and clinical phenotypes in the Penn Medicine Biobank (PMBB; n = 37,960) and the UKBiobank (UKB; n = 451,444)., Results: We analysed 24 missense variants in MTTP in PMBB for association with biopsy-proven hepatic steatosis and found that an isoleucine 128 to threonine variant (I128T: rs3816873-A, frequency 26%) was associated with reduced steatosis (p < 0.001). PMBB subjects with imaging-proven steatosis also revealed significantly fewer carriers of MTTP I128T compared to controls. Analysis in UKB also showed that MTTP I128T was associated with reduced risk of hepatic steatosis. Unexpectedly, MTTP I128T was found to be associated with reduced plasma levels of LDL-cholesterol and apoB (all p < 0.001). Functional studies indicated that MTTP I128T is neither a classic loss nor gain of function allele., Conclusions: MTTP I128T is associated with reduced hepatic steatosis as well as reduced plasma lipids and apoB. This paradoxical profile is not consistent with a simple gain or loss of function in MTP activity and suggests a more complex effect on MTP function. Further investigation of MTTP I128T will provide insight into the structure-function of MTP and potentially new approaches to modulate MTP activity that could both reduce hepatic and circulating lipids., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Some multimodal signals-that is, occurring in more than one sensory modality-appear to carry additional information which is not present when component signals are presented separately. To understand the function of male ring dove's (Streptopelia risoria) multimodal courtship, we used audiovisual playback of male displays to investigate female response to stimuli differing in their audiovisual timing. From natural courtship recordings, we created a shifted stimulus where audio was shifted relative to video by a fixed value and a jittered stimulus, where each call was moved randomly along the visual channel. We presented 3 groups of females with the same stimulus type, that is, control, shifted, and jittered, for 7 days. We recorded their behavior and assessed pre- and post-test blood estradiol concentration. We found that playback exposure increased estradiol levels, confirming that this technique can be efficiently used to study doves' sexual communication. Additionally, chasing behavior (indicating sexual stimulation) increased over experimental days only in the control condition, suggesting a role of multimodal timing on female response. This stresses the importance of signal configuration in multimodal communication, as additional information is likely to be contained in the temporal association between modalities., (© 2022 The Authors. Integrative Zoology published by International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Background: Irritable bowel syndrome (IBS) is one of the most common functional digestive disorders. Our understanding about its comorbidities, biomarkers, or long-term risks is still incomplete., Objective: To characterize comorbidities and biomarkers for IBS and establish the effect of IBS on overall- and cause specific mortality., Methods: We analyzed data from the population-based cohort of the UK Biobank (UKB) with 493,974 participants, including self-reported physician-diagnosed (n = 20,603) and ICD-10 diagnosed (n = 7656) IBS patients, with a mean follow-up of 11 years. We performed a phenome-wide association study (PheWAS) and competing risk analysis to characterize common clinical features in IBS patients., Results: In PheWAS analyses, 260 PheCodes were significantly overrepresented in self-reported physician-diagnosed IBS patients, 633 in patients with ICD-10 diagnosed IBS (ICD-10-IBS), with 221 (40%) overlapping. In addition to gastrointestinal diseases, psychiatric, musculoskeletal, and endocrine/metabolic disorders represented the most strongly associated PheCodes in IBS patients. Self-reported physician-diagnosed IBS was not associated with increased overall mortality and the risk of death from cancer was decreased (hazard ratio [HR] = 0.78 [95% CI = 0.7-0.9]). Lastly, we evaluated changes in serum metabolites in IBS patients and identified glycoprotein acetyls (GlycA) as a potential biomarker in IBS. One standard deviation increase in GlycA raised the risk of self-reported IBS/ICD-10 coded by 9%-20% (odds ratio [OR] = 1.09 [95% CI = 1.1-1.1]/OR = 1.20 [95% CI = 1.1-1.3]) and the risk of overall mortality in ICD-10-IBS patients by 28% (HR = 1.28 [95% CI = 1.1-1.5])., Conclusion: Our large-scale association study determined IBS patients having an increased risk of several different comorbidities and that GlycA was increased in IBS patients., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Importance: Given the burden of chronic liver disease on the health care system, more information on the hepatoprotective association of statins in the general population is needed., Objective: To examine whether regular statin use is associated with a reduction in liver disease, particularly hepatocellular carcinoma (HCC) and liver-related deaths, in the general population., Design, Setting, and Participants: This cohort study used data from the UK Biobank (UKB) (individuals aged 37-73 years) collected from baseline (2006-2010) to the end of follow-up in May 2021, from the TriNetX cohort (individuals aged 18-90 years) enrolled from baseline (2011-2020) until end of follow-up in September 2022, and from the Penn Medicine Biobank (PMBB) (individuals aged 18-102 years) with ongoing enrollment starting in 2013 to the end of follow-up in December 2020. Individuals were matched using propensity score matching according to the following criteria: age, sex, body mass index, ethnicity, diabetes with or without insulin or biguanide use, hypertension, ischemic heart disease, dyslipidemia, aspirin use, and number of medications taken (UKB only). Data analysis was performed from April 2021 to April 2023., Exposure: Regular statin use., Main Outcomes and Measures: Primary outcomes were liver disease and HCC development as well as liver-associated death., Results: A total of 1 785 491 individuals were evaluated after matching (aged 55 to 61 years on average, up to 56% men, and up to 49% women). A total of 581 cases of liver-associated death, 472 cases of incident HCC, and 98 497 new liver diseases were registered during the follow-up period. Individuals were aged 55-61 years on average, with a slightly higher proportion of men (up to 56%). In UKB individuals (n = 205 057) without previously diagnosed liver disease, statin users (n = 56 109) had a 15% lower hazard ratio (HR) for the association of developing a new liver disease (HR, 0.85; 95% CI, 0.78-0.92; P < .001). In addition, statin users demonstrated a 28% lower HR for the association with liver-related death (HR, 0.72; 95% CI, 0.59-0.88; P = .001) and a 42% lower HR for the development of HCC (HR, 0.58; 95% CI, 0.35-0.96; P = .04). In TriNetX individuals (n = 1 568 794), the HR for the association of HCC was reduced even further for statin users (HR, 0.26; 95% CI, 0.22-0.31; P = .003). The hepatoprotective association of statins was time and dose dependent, with a significant association in PMBB individuals (n = 11 640) for incident liver diseases after 1 year of statin use (HR, 0.76; 95% CI, 0.59-0.98; P = .03). Taking statins was particularly beneficial in men, individuals with diabetes, and individuals with a high Fibrosis-4 index at baseline. Carriers of the heterozygous minor allele of PNPLA3 rs738409 benefited from statin use and had a 69% lower HR for the association with HCC (UKB HR, 0.31; 95% CI, 0.11-0.85; P = .02)., Conclusions and Relevance: This cohort study indicates substantial preventive associations of statins against liver disease, with an association with duration and dose of intake.

Organismal behavior, with its tremendous complexity and diversity, is generated by numerous physiological systems acting in coordination. Understanding how these systems evolve to support differences in behavior within and among species is a longstanding goal in biology that has captured the imagination of researchers who work on a multitude of taxa, including humans. Of particular importance are the physiological determinants of behavioral evolution, which are sometimes overlooked because we lack a robust conceptual framework to study mechanisms underlying adaptation and diversification of behavior. Here, we discuss a framework for such an analysis that applies a "systems view" to our understanding of behavioral control. This approach involves linking separate models that consider behavior and physiology as their own networks into a singular vertically integrated behavioral control system. In doing so, hormones commonly stand out as the links, or edges, among nodes within this system. To ground our discussion, we focus on studies of manakins (Pipridae), a family of Neotropical birds. These species have numerous physiological and endocrine specializations that support their elaborate reproductive displays. As a result, manakins provide a useful example to help imagine and visualize the way systems concepts can inform our appreciation of behavioral evolution. In particular, manakins help clarify how connectedness among physiological systems-which is maintained through endocrine signaling-potentiate and/or constrain the evolution of complex behavior to yield behavioral differences across taxa. Ultimately, we hope this review will continue to stimulate thought, discussion, and the emergence of research focused on integrated phenotypes in behavioral ecology and endocrinology., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cardiac resynchronization therapy (CRT) via biventricular pacing (BVP) is a well-established therapy for patients with heart failure with reduced ejection fraction and left bundle branch block, who remain symptomatic despite optimal medical therapy. Despite the long-standing clinical evidence, as well as the familiarity of cardiac electrophysiologists with the implantation technique, CRT via BVP cannot be achieved or may result ineffective in up to one-third of the patients. Therefore, new alternative techniques, such as conduction system pacing and left ventricular pacing, are emerging as potential alternatives to this technique, not only in case of BVP failure, but also as a stand-alone first choice due to several potential advantages over traditional CRT. Specifically, due to its procedural characteristics, left bundle branch area pacing appears to be the most convincing technique, showing comparable efficacy outcomes when compared with traditional CRT, not increasing short-term device-related complications, as well as improving procedural times. However, transvenous leads remain a major limitation of all these pacing modalities. To overcome this limit, a leadless left ventricular endocardial pacing has been developed as an additional tool to achieve a left endocardial activation, although being still associated with non-negligible pitfalls, limiting its current use in clinical practice. This article focuses on the current state and latest progresses in cardiac resynchronization therapy., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Tropical species are considered to be more threatened by climate change than those of other world regions. This increased sensitivity to warming is thought to stem from the assumptions of low physiological capacity to withstand temperature fluctuations and already living near their limits of heat tolerance under current climatic conditions. For birds, despite thorough documentation of community-level rearrangements, such as biotic attrition and elevational shifts, there is no consistent evidence of direct physiological sensitivity to warming. In this review, we provide an integrative outlook into the physiological response of tropical birds to thermal variation and their capacity to cope with warming. In short, evidence from the literature suggests that the assumed physiological sensitivity to warming attributed to tropical biotas does not seem to be a fundamental characteristic of tropical birds. Tropical birds do possess the physiological capacities to deal with fluctuating temperatures, including high-elevation species, and are prepared to withstand elevated levels of heat, even those living in hot and arid environments. However, there are still many unaddressed points that hinder a more complete understanding of the response of tropical birds to warming, such as cooling capacities when exposed to combined gradients of heat and humidity, the response of montane species to heat, and thermoregulation under increased levels of microclimatic stress in disturbed ecosystems. Further research into how populations and species from different ecological contexts handle warming will increase our understanding of current and future community rearrangements in tropical birds., Competing Interests: None declared., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Cross-scale studies combining information on policy instruments and on drivers of deforestation and forest degradation are key to design and implement effective forest protection measures. We investigated the scale and country dependency of stakeholder perceptions about future threats to tropical forests (e.g. agriculture, logging, woodfuel) and preferred policy instruments (e.g. reforestation, protected areas, combat illegal logging), by interviewing 224 representatives of forest-related institutions. We conducted analysis of variance and principal component analysis for eighteen variables across three countries (Zambia, Ecuador and the Philippines) and four spatial levels (from international to local). We found that the overall alertness about commercial drivers and the confidence in policy instruments are significantly lower at subnational levels and also in Zambia. Stakeholder expectations about the most important drivers and the most effective policies in the coming decade follow regional narratives, suggesting that there are no one-size-fits-all solutions in international forest policy. However, we found an unexpected consensus across scales, indicating potential for collaboration between institutions operating at different geographical levels. Overall, agriculture remains the driver with the highest expected influence (43%), while a strong favoritism for reforestation and forest restoration (38%) suggests a paradigm shift from protected areas to a stronger focus on integrative approaches., (© 2023. The Author(s).)