bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-ejaculatory Inhibition of Female Sexual Drive via Heterogeneous Neuronal Ensembles in the Medial Preoptic Area
Authors: Ishii Kentaro K , Hashikawa Koichi , Chea Jane , Yin Shihan , Fox Rebecca Erin , Kan Suyang , Shah Meha , Zhou Charles , Navarrete Jovana , Murry Alexandria D. , Szelenyi Eric R , Golden Sam A. , Stuber Garret D.
Published: September 2023

Male ejaculation acutely suppresses sexual motivation in male mice. In contrast, relatively little is known about how male ejaculation affects sexual motivation and sexual behavior in female mice. How the brain responds to completion of mating is also unclear. Here, by using self-paced mating assay, we first demonstrate that female mice show decreased sexual motivation acutely after experiencing male ejaculation. By using brain-wide analysis of activity-dependent labeling, we next pinpointed the medial preoptic area as a brain region strongly activated during the post-ejaculatory period. Furthermore, using freely movingin vivocalcium imaging to compare neural activity of inhibitory and excitatory neurons in the medial preoptic area, we revealed that a subset of the neurons in this region respond significantly and specifically to male ejaculation but not to female-to-male sniffing or to male mounting. While there were excitatory and inhibitory neurons that showed increased response to male ejaculation, the response magnitude as well as the proportion of neurons responding to the event was significantly larger in the inhibitory neuron population. Next, by unbiased classification of their responses, we also found a subpopulation of neurons that increase their activity late after the onset of male ejaculation. These neurons were all inhibitory indicating that male ejaculation induces a prolonged inhibitory activity in the medial preoptic area. Lastly, we found that chemogenetic activation of medial preoptic area neurons that were active during post-ejaculatory period, but not during appetitive or consummatory periods, were sufficient to suppress female sexual motivation. Together, our data illuminate the importance of medial preoptic area as a brain node which encodes a negative signal that sustains low sexual motivation state after the female mice experience ejaculation.

Highlights

Female mice show decreased sexual motivation in the post-ejaculatory period.

A subset of MPOA neurons in female respond specifically to male ejaculation.

Male-ejaculation evokes persistent activity in MPOA inhibitory neurons in females.

Activation of a subset of MPOA neurons is sufficient to suppress female sexual motivation.
SARS-CoV-2 ORF8 modulates lung inflammation and clinical disease progression
Authors: McGrath Marisa E. , Xue Yong , Taylor Louis , Dillen Carly , Ardanuy Jeremy , Gonzalez-Juarbe Norberto , Baracco Lauren , Kim Raymond , Hart Rebecca , Assad-Garcia Nacyra , Vashee Sanjay , Frieman Matthew B.
Published: September 2023

The virus severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, is the causative agent of the current COVID-19 pandemic. It possesses a large 30 kilobase (kb) genome that encodes structural, non-structural, and accessory proteins. Although not necessary to cause disease, these accessory proteins are known to influence viral replication and pathogenesis. Through the synthesis of novel infectious clones of SARS-CoV-2 that lack one or more of the accessory proteins of the virus, we have found that one of these accessory proteins, ORF8, is critical for the modulation of the host inflammatory response. Mice infected with a SARS-CoV-2 virus lacking ORF8 exhibit increased weight loss and exacerbated macrophage infiltration into the lungs. Additionally, infection of mice with recombinant SARS-CoV-2 viruses encoding ORF8 mutations found in variants of concern reveal that naturally occurring mutations in this protein influence disease severity. Our studies with a virus lacking this ORF8 protein and viruses possessing naturally occurring point mutations in this protein demonstrate that this protein impacts pathogenesis.

Significance

Since its emergence in 2019, SARS-CoV-2 has accrued mutations throughout its 30kb genome. Of particular interest are the mutations present in the ORF8 protein, which occur in every major variant. The precise function and impact of this protein on disease severity and pathogenesis remains understudies. Our studies reveal that the ORF8 protein modulates the immune response by impacting macrophage infiltration into the lungs. Additionally, we have shown that the ORF8 protein of SARS-CoV-2 has accrued mutations throughout its evolution that lead to a loss of function phenotype in this protein. Our work reveals that the ORF8 protein of SARS-CoV-2 contributes significantly to disease progression through modulation of the inflammatory response.
Proteome-scale prediction of molecular mechanisms underlying dominant genetic diseases
Authors: Badonyi Mihaly , Marsh Joseph A
Published: September 2023

Many dominant genetic disorders result from protein-altering mutations, acting primarily through dominant-negative (DN), gain-of-function (GOF), and loss-of-function (LOF) mechanisms. Deciphering the mechanisms by which dominant diseases exert their effects is often experimentally challenging and resource intensive, but is essential for developing appropriate therapeutic approaches. Diseases that arise via a LOF mechanism are more amenable to be treated by conventional gene therapy, whereas DN and GOF mechanisms may require gene editing or targeting by small molecules. Moreover, pathogenic missense mutations that act via DN and GOF mechanisms are more difficult to identify than those that act via LOF using nearly all currently available variant effect predictors. Here, we introduce a tripartite statistical model made up of support vector machine binary classifiers trained to predict whether human protein-coding genes are likely to be associated with DN, GOF, or LOF molecular disease mechanisms. We test the utility of the predictions by examining biologically and clinically meaningful properties known to be associated with the mechanisms. Our results strongly support that the models are able to generalise on unseen data and offer insight into the functional attributes of proteins associated with different mechanisms. We hope that our predictions will serve as a springboard for researchers studying novel variants and those of uncertain clinical significance, guiding variant interpretation strategies and experimental characterisation. Predictions for the human UniProt reference proteome are available athttps://osf.io/z4dcp/.
Olfactory-to-visual facilitation in the infant brain declines gradually from 4 to 12 months
Authors: Rekow Diane , Baudouin Jean-Yves , Kiseleva Anna , Rossion Bruno , Durand Karine , Schaal Benoist , Leleu Arnaud
Published: September 2023

During infant development, intersensory facilitation declines gradually as unisensory perception improves. However, this developmental trade-off has been mainly investigated using audiovisual stimulations. Here, fifty 4- to 12-month-old infants were tested to determine whether the facilitating effect of their mother’s body odor on neural face categorization, as previously observed at 4 months, decreases with age. In a baseline odor context, results revealed a face-selective electroencephalographic (EEG) response that increases and changes qualitatively between 4 and 12 months, marking improved face categorization. At the same time, the benefit of adding maternal odor fades gradually with age, indicating an inverse relation with the strength of the sole visual response, and generalizing to olfactory-visual interactions previous evidence from the audiovisual domain.
Hippocampal connectivity patterns echo macroscale cortical evolution in the primate brain
Authors: Eichert Nicole , DeKraker Jordan , Howard Amy F.D. , Huszar Istvan N. , Zhu Silei , Sallet Jérôme , Miller Karla L. , Mars Rogier B. , Jbabdi Saad , Bernhardt Boris C.
Published: September 2023

The hippocampus is involved in numerous cognitive functions, some of which have uniquely human aspects, such as autobiographical memory. Hippocampal anatomy, however, is typically considered conserved across primates and its evolutionary diversification is rarely studied. Comparing hippocampal structure and function is, therefore, critical for understanding human brain architecture. Here, we developed a novel comparative framework to study the hippocampus across species characterising its geometry, microstructure, and functional network embedding. In humans and macaques, we generated a new comparative space that represents the hippocampus as an unfolded surface, which respects its sheet-like anatomy. We mapped histological and MRI-derived markers of microstructure to the hippocampal surface and integrated it with low-dimensional embedding of resting-state MRI connectivity data. Our results demonstrate that the micro– and macro-structural organisation of the hippocampus are overall conserved in both species, showing consistent anterior-posterior and subfield-to-subfield differentiation. Furthermore, while hippocampal functional organisation also follows anterior-posterior trends in both species, hippocampal functional connectivity markedly reflected evolutionary reconfiguration of transmodal networks, in particular the default-mode network. Specifically, the inferior parietal lobe in the macaque mirrors an incomplete integration of the default mode network in non-human primates. By combining fine-grained anatomical investigation with large-scale functional imaging, we showed that microstructurally preserved regions like the hippocampus may still undergo functional reconfiguration, due to their embedding in higher-order association networks.

While the hippocampus is key for uniquely human cognitive abilities, it is also a phylogenetically old cortex and paradoxically considered evolutionarily preserved. Here, we introduce a comparative framework to quantify preservation and reconfiguration of hippocampal organisation in primate evolution, by analysing the hippocampus as an unfolded cortical surface that is geometrically matched across species. Our findings revealed an overall conservation of hippocampal macro– and micro-structure, showing anterior-posterior and, perpendicularly, subfield-related organisational axes in both humans and macaques. However, while functional organisation in both species also followed an anterior-posterior axis, the latter showed a marked evolutionary reconfiguration, which mirrors a rudimentary integration of the default-mode-network in non-human primates. Our findings suggest that microstructurally preserved regions like the hippocampus may still undergo functional reconfiguration in primate evolution, due to their embedding in heteromodal association networks.
How does V1 population activity inform perceptual certainty?
Authors: Boundy-Singer Zoe M. , Ziemba Corey M. , Hénaff Olivier J. , Goris Robbe L. T.
Published: September 2023

Neural population activity in sensory cortex informs our perceptual interpretation of the environment. Oftentimes, this population activity will support multiple alternative interpretations. The larger the set of plausible alternatives, the more uncertain the selected perceptual interpretation. We test the hypothesis that the reliability of perceptual interpretations can be revealed through simple transformations of sensory population activity. We recorded V1 population activity in fixating macaques while presenting oriented stimuli under different levels of nuisance variability and signal strength. We developed a decoding procedure to infer from V1 activity the most likely stimulus orientation as well as the certainty of this estimate. Our analysis shows that response magnitude, response dispersion, and variability in response gain all offer useful proxies for orientation certainty. Of these three metrics, the last one has the strongest association with the decoder’s uncertainty estimates. These results clarify that the nature of neural population activity in sensory cortex provides downstream circuits with multiple options to assess the reliability of perceptual interpretations.
Studies of zinc content reduction using flake zinc powder in epoxy zinc-rich coatings
Authors: Liu Yang , Wang Jialing , Cai Huayang , Shao Yawei , Xu Zhengyi , Wang Yanqiu , Wang Junyi
Published: September 2023

Purpose

Epoxy zinc-rich coatings are widely used in harsh environments because of the long-lasting cathodic protection of steel surfaces. The purpose of this paper is to use flake zinc powder instead of the commonly used spherical zinc powder to reduce the zinc powder content.

Design/methodology/approach

In this paper, the authors have prepared an anticorrosive zinc-rich coating using a flake zinc powder instead of the conventional spherical zinc powder. The optimal dispersion of scaly zinc powder in zinc-rich coatings has been explored by looking at the surface and cross-sectional morphology and studying the cathodic protection time of the coating.

Findings

The final epoxy zinc-rich coating with 35 Wt.% flake zinc powder content was prepared using sand-milling dispersions. It has a similar cathodic protection time and salt spray resistance as the 60 Wt.% spherical zinc-rich coating, with a higher low-frequency impedance modulus value.

Originality/value

This study uses flake zinc powder instead of the traditional spherical zinc powder. This reduces the amount of zinc powder in the coating and improves the corrosion resistance of the coating.
The effect of corporate reputation on customer loyalty in the Ghanaian banking industry: the role of country-of-origin
Authors: Gli Deli Dotse , Tweneboah-Koduah Ernest Yaw , Odoom Raphael , Kodua Prince
Published: September 2023

Purpose

Customer loyalty is of growing interest to many service firms due to the many tangible and intangible benefits it offers them. However, building customer loyalty is challenging for many service firms. This study aims to examine the impact of corporate reputation on customer loyalty. It also assesses the moderating role of the firm's country of origin in this relationship.

Design/methodology/approach

Survey research design was used to collect data from 367 universal banks' customers. Data were analysed using structural equation modelling.

Findings

The findings shed light on several crucial aspects of corporate reputation that influence customer loyalty. Specifically, signals of corporate social responsibility, corporate credibility, product attributes and relationship marketing were found to have a substantial impact on customer loyalty. Additionally, the study uncovers a noteworthy insight that the firm's country of origin plays a moderating role in the relationship between corporate reputation and customer loyalty, particularly in the context of the banking sector.

Originality/value

This research stands out due to its utilisation of signalling theory, making it one of the pioneering works in the bank brand management literature. It presents a comprehensive corporate reputation framework and its profound implications for customer loyalty. Furthermore, the study underscores the significance of considering the strength of the country-of-origin effect in shaping customer loyalty relationships.
Foreign institutional investors and the value of excess cash holdings: international evidence
Authors: Ilyas Muhammad , Mian Rehman Uddin , Mian Affan
Published: September 2023

Purpose

Using a comprehensive sample from developed and emerging economies, this study aims to examine whether foreign institutional investors (FIIs) enhance the value of excess cash by constraining the potential self-appropriating managerial propensity related to its inefficient utilization.

Design/methodology/approach

This study uses a large panel data set of firms from 32 non-US countries from 2007 to 2018. Using data from COMPUSTAT Global and S&P Capital IQ, this study uses ordinary least squares regression with year- and firm-fixed effects for the baseline analysis. In addition, two-stage least squares with instrumental variable regression and propensity score matching approaches were used to address the potential endogeneity.

Findings

This study shows that FIIs significantly increase the value of excess cash holdings. The authors also found that the positive impact of FIIs is more significant when investors come from common-law countries with better governance and investor protection. Furthermore, in countries and firms with weaker governance controls, the relationship between FIIs and the value of excess cash is stronger, consistent with the institutional monitoring hypothesis. Collectively, the findings imply that FIIs are advantageous to investees because they effectively promote the efficient deployment of corporate resources.

Practical implications

Collectively, the findings of this study imply that FIIs are advantageous to investees because they effectively promote the efficient deployment of corporate resources.

Originality/value

This study offers new evidence on how FIIs impact the value of excess cash in an international setting. In addition, it highlights the significance of the legal origin of institutional investors’ home country and the governance quality of host countries and investee firms in influencing the effect of foreign institutional monitoring on the value of excess cash.
Non-criminalised fire use and self-concept: a preliminary grounded theory study
Authors: Lee Robyn , Horsley Faye , McKeown Annette
Published: September 2023

Purpose

Previous qualitative research by Horsley (2020) and Lee (2019) highlighted the importance of self-concept (SC) in understanding fire use. This study, therefore, aims to further investigate the relevance of SC in non-criminalised fire use, with a view towards informing early interventions for firesetting prevention.

Design/methodology/approach

In this preliminary study, ten participants engaging in extensive, non-criminalised fire use were interviewed about their fire-related experiences and how this relates to SC. This was analysed using techniques informed by the grounded theory.

Findings

Three core categories were identified: control, identity and self-esteem, which provide a preliminary framework for understanding how SC and non-criminalised fire use are inter-related. The core categories relate to the study aim because they are conceptualised as three elements of SC, which are strengthened through interactions with fire. The mechanisms through which the categories relate to fire use and SC are discussed.

Practical implications

Forensic implications are discussed regarding early intervention and prevention. The authors argue that knowledge of non-criminalised fire use could provide a valuable blueprint for healthy fire use and, thus, feed into treatment and intervention. Given that previous research has highlighted the importance of SC in relation to how and why people interact with fire, the authors suggest that it should be given greater emphasis in clinical work with those thought to be at risk of firesetting.

Originality/value

To date, firesetting research has focused primarily on criminalised acts, i.e. arson. This paper adopts a different approach and explores how and why people engage with fire in healthy and adaptive ways.
Achieving circularity is a distant dream: entrepreneurial barriers to circular business models in SMEs of emerging economies
Authors: Saharan Akash , Samadhiya Ashutosh , Kumar Anil , Pandey Krishan Kumar , Luthra Sunil , Garza-Reyes Jose Arturo
Published: September 2023

Purpose

Circularity has acted as an essential phenomenon for small and medium enterprises (SMEs) in emerging economies, pressuring entrepreneurs to its adoption in their businesses. During the adoption and implementation of circularity, entrepreneurs or circular entrepreneurs (to be precise) are facing various challenges to its effective functioning. However, the scholarly literature has offered limited research into this phenomenon. Thus, the purpose of this research is to identify the various barriers and sub-barriers for circular entrepreneurs to adopt circularity in SMEs of emerging economies.

Design/methodology/approach

A combined qualitative and quantitative approach was employed to achieve the objectives of the study. In the first stage, through an extensive literature review, a list of barriers was identified and in the second stage, a deductive approach was employed to finalize the barriers. Finally, Best-Worst Method (BWM), a multi-criteria decision-making (MCDM) method, was used to analyse the significant importance of the barriers.

Findings

The findings of the study suggested the “financial barrier” as the first-ranked barrier in the adoption of Circular Business Models (CBMs), followed by the “regulatory and operational barrier” as the top second and third barriers. In terms of sub-barriers, “lack of access to funding and capital” has been identified as the top sub-barrier in the adoption of CBM, followed by “excessive regulations and red tape” and “challenges due to ambiguity of the concept”.

Practical implications

To transition from a circular to a linear business approach considerably quicker and smoother, entrepreneurs may utilize the findings of this study as a blueprint for the steps to overcome the barriers in a linear to a circular transition.

Originality/value

This research differentiates from other studies due to solicited input directly from the people who are most familiar with the challenges of making the transition from linear to CBM, i.e. the entrepreneurs themselves.
Identification and analysis of enterprise risks in the open product innovation: the case of Volkswagen Brazil
Authors: Santos Ricardo Fernandes , Oliva Fábio Lotti , Grisi Celso Claudio de Hildebrand e , Kotabe Masaaki , Del Giudice Manlio , Papa Armando
Published: September 2023

Purpose

The problem statement is how to identify and analyze the corporate risks involved in the relationships with external agents involved in the open product innovation process (OPIP)? Seeking to extend this investigation, the purpose of this paper is to analyze the enterprise risks identified in corporate relations with external agents of the OPIP. This study proposes the systematization of the process of identification and analysis of the enterprise risks involved in the process of open product innovation.

Design/methodology/approach

The case explored in this study is the OPIP of Volkswagen do Brasil (VWB), one of the most important subsidiaries of the Volkswagen Group. Criteria were selected to both assessing corporate relations with external agents of the open innovation of VWB and analyzing the enterprise risks identified in these relations. Data collection included interviews with management-level professionals engaged in the OPIP activities and technical visits to a VWB’s industrial plant.

Findings

Results demonstrate that the enterprise risks mostly affecting the OPIP have a critical impact on the manufacturing process and initial sales of the new product.

Originality/value

The originality of the study focuses on the proposal of a systematization of how to identify and analyze the corporate risks involved in the process of open product innovation. The study focuses on the theoretical frontier on the open innovation and enterprise risk management (ERM) in the open innovation process.
Arriving late and lean at a stopover site is selected against in a declining migratory bird population
Authors: Peng He‐Bo , Ma Zhijun , Rakhimberdiev Eldar , van Gils Jan A. , Battley Phil F. , Rogers Danny I. , Choi Chi‐Yeung , Wu Wei , Feng Xuesong , Ma Qiang , Hua Ning , Minton Clive , Hassell Chris J. , Piersma Theunis
Published: September 2023

Loss and/or deterioration of refuelling habitats have caused population declines in many migratory bird species but whether this results from unequal mortality among individuals varying in migration traits remains to be shown.

Based on 13 years of body mass and size data of great knots (Calidris tenuirostris) at a stopover site of the Yellow Sea, combined with resightings of individuals marked at this stopover site along the East Asian‐Australasian Flyway, we assessed year to year changes in annual apparent survival rates, and how apparent survival differed between migration phenotypes (i.e. migration timing and fuel stores). The measurements occurred over a period of habitat loss and/or deterioration in this flyway.

We found that the annual apparent survival rates of great knots rapidly declined from 2006 to 2018, late‐arriving individuals with small fuel stores exhibiting the lowest apparent survival rate. There was an advancement in mean arrival date and an increase in the mean fuel load of stopping birds over the study period.

Our results suggest that late‐arriving individuals with small fuel loads were selected against. Thus, habitat loss and/or deterioration at staging sites may cause changes in the composition of migratory phenotypes at the population‐level.
Effects of arbuscular mycorrhizal fungi on plant invasion success driven by nitrogen fluctuations
Authors: Zhang Xue , Zhang Tao , Liu Yanjie
Published: September 2023

Both enemies and mutualists play crucial roles in shaping plant invasion processes. Recent studies have suggested that resource fluctuations could indirectly promote plant invasion through higher trophic levels, such as enemies. However, the influence of mutualists like arbuscular mycorrhizal fungi (AMF) on plant invasion under nitrogen fluctuations remains untested.

We conducted a pot mesocosm experiment using a three‐factorial experimental design to assess the individual and interactive effects of nitrogen availability, nitrogen fluctuation and AMF on invasive success of alien plants. We grew nine invasive alien species alongside five different native communities in pot mesocosms. These were then subjected to varied nitrogen availabilities (low vs. high), nitrogen fluctuations (constant vs. pulsed) and AMF presence or absence within a sterile substrate.

We found that pulsed nitrogen supply increased the dominance of invasive alien species in low nitrogen availability, regardless of the presence or absence of AMF inoculation. However, in high nitrogen availability, pulsed nitrogen supply only enhanced this dominance in pots without AMF inoculation. This was tentatively evidenced by the three‐way interaction among nitrogen‐availability, nitrogen‐fluctuation and AMF‐inoculation treatments. Furthermore, the dominance promotion by nitrogen addition was greater than that by AMF inoculation.

Synthesis and applications. Our findings present, for the first time, evidence that AMF may play a crucial role in mediating the promotion effects of nitrogen fluctuations on alien plant invasion. To better understand the invasion process of alien plants and evaluate their impact on native communities, future research should integrate abiotic and biotic drivers into a single framework. Furthermore, our findings underscore the importance of prioritizing habitats with higher nutrient availability and variability for protection against alien plant invasions.
Exotic success following disturbance explained by weak native resilience and ruderal exotic bias
Authors: Pearson Dean E. , Ortega Yvette K. , Eren Özkan , Villarreal Diego , Lekberg Ylva , Hierro José
Published: September 2023

Disturbance is a primary driver of exotic plant invasions, but why disturbance commonly favours exotics over natives is unresolved.

To address this question, we conducted the first biogeographic study of disturbance across multiple plant species. We experimentally disturbed grasslands and added seeds of 34 plant species to plots in their native range and in two introduced ranges that differed in invasibility (susceptibility to invasion) to evaluate recruitment while examining potential influences of resource availability, native community recovery from disturbance (resilience) and life‐history traits in local species pools.

Species pools in the native (donor) range were more strongly skewed towards ruderal taxa than species pools in the introduced ranges. This bias in the donor pool was exacerbated by introduction filters that further selected for ruderal traits, strongly skewing exotic species pools in the introduced ranges towards ruderals. Sown species, which reflected these trait patterns, benefited from disturbance universally, but their disturbance response was 10‐fold greater in the more invasible introduced range. This result was not explained by nutrient availability, which responded similar to disturbance across ranges. Nor was it driven by background propagule pressure, which was minimal. Rather, the exaggerated disturbance effect in the more invasible introduced range appeared to be driven by weak recovery of the native plant community that allowed ruderal‐biased exotics to proliferate.

Overall, disturbance appeared to favoured exotics because they were much more likely than natives to be ruderal. However, this trait bias only corresponded with an invader advantage in the more invasible range where weak community resilience was linked to slow‐growing, stress‐tolerant natives that failed to rapidly recover space and resources. In contrast, in the less invasible introduced range, highly competitive native perennials quickly filled the disturbance gap, demonstrating high community resilience that appeared to limit invader recruitment.

Synthesis: Biogeographic influences on local species pools can facilitate invader success following disturbance, but final invasion outcomes are conditioned by native community resilience.
Leaf nitrogen affects photosynthesis and water use efficiency similarly in nitrogen‐fixing and non‐fixing trees
Authors: Bytnerowicz Thomas A. , Funk Jennifer L. , Menge Duncan N. L. , Perakis Steven S. , Wolf Amelia A.
Published: September 2023

Nitrogen (N)‐fixing trees are thought to break a basic rule of leaf economics: higher leaf N concentrations do not translate into higher rates of carbon assimilation. Understanding how leaf N affects photosynthesis and water use efficiency (WUE) in this ecologically important group is critical.

We grew six N‐fixing and four non‐fixing tree species for 4–5 years at four fertilization treatments in field experiments in temperate and tropical regions to assess how functional type (N fixer vs. non‐fixer) and N limitation affected leaf N and how leaf N affected light‐saturated photosynthesis (Asat), stomatal conductance (gsw) and WUE (WUEi and δ13C).

Asat, WUEi and δ13C, but not gsw, increased with higher leaf N. Surprisingly, N‐fixing and non‐fixing trees displayed similar scaling between leaf N and these physiological variables, and this finding was supported by reanalysis of a global dataset. N fixers generally had higher leaf N than non‐fixers, even when non‐fixers were not N‐limited at the leaf level. Leaf‐level N limitation did not alter the relationship of Asat, gsw, WUEi and δ13C with leaf N, although it did affect the photosynthetic N use efficiency. Higher WUE was associated with higher productivity, whereas higher Asat was not.

Synthesis: The ecological success of N‐fixing trees depends on the effect of leaf N on carbon gain and water loss. Using a field fertilization experiment and reanalysis of a global dataset, we show that high leaf‐level photosynthesis and WUE in N fixers stems from their higher average leaf N, rather than a difference between N fixers and non‐fixers in the scaling of photosynthesis and WUE with leaf N. By clarifying the mechanism by which N fixers achieve and benefit from high WUE, our results further the understanding of global N fixer distributions.
Circ_0002295 facilitated myocardial fibrosis progression through the miR‐1287/CXCR2 axis
Authors: Ma Guo‐Bin , Chen Wen‐Xu , Zhan Fang‐Jie , Xie Wen‐Jing , Chen Rong‐Wei , Chen Hong , Ye Wei‐Lin , Jiang Yu , Xu Jian‐Ping
Published: September 2023

Myocardial fibrosis (MF) is involved in hypertension, myocardial infarction and heart failure. It has been reported that circular RNA (circRNA) is a key regulatory factor of MF progression. In this study, we revealed that circ_0002295 and CXCR2 were elevated, and miR‐1287 was reduced in MF patients. Knockdown of circ_0002295 effectively suppressed the proliferation, migration and MF progression. Circ_0002295 was the molecular sponge of miR‐12878, and miR‐1287 inhibitor reversed the biological functions of circ_0002295 on the myocardial fibrosis. CXCR2 was a target gene of miR‐1287, and CXCR2 silencing relieved the impacts of miR‐1287 inhibitor on cardiac myofibroblasts. Circ_0002295 promoted MF progression by regulating the miR‐1287/CXCR2 axis, providing a possible circRNA‐targeted therapy for MF.
Furosemide versus placebo for fluid overload in intensive care patients—The randomised GODIF trial second version: Statistical analysis plan
Authors: Wichmann Sine , Lange Theis , Perner Anders , Gluud Christian , Itenov Theis S. , Berthelsen Rasmus E. , Nebrich Lars , Wiis Jørgen , Brøchner Anne C. , Nielsen Louise G. , Behzadi Meike T. , Damgaard Kjeld , Andreasen Anne S. , Strand Kristian , Järvisalo Mikko , Strøm Thomas , Eschen Camilla T. , Vang Marianne L. , Hildebrandt Thomas , Andersen Finn H. , Sigurdsson Martin I. , Thomar Katrin M. , Thygesen Sandra K. , Troelsen Thomas T. , Uusalo Panu , Jalkanen Ville , Illum Dorte , Sølling Christoffer , Keus Frederik , Pfortmueller Carmen A. , Wahlin Rebecka R. , Ostermann Marlies , Aneman Anders , Bestle Morten H.
Published: September 2023

Background

Fluid overload is associated with increased mortality in intensive care unit (ICU) patients. The GODIF trial aims to assess the benefits and harms of fluid removal with furosemide versus placebo in stable adult patients with moderate to severe fluid overload in the ICU. This article describes the detailed statistical analysis plan for the primary results of the second version of the GODIF trial.

Methods

The GODIF trial is an international, multi‐centre, randomised, stratified, blinded, parallel‐group, pragmatic clinical trial, allocating 1000 adult ICU patients with moderate to severe fluid overload 1:1 to furosemide versus placebo. The primary outcome is days alive and out of hospital within 90 days post‐randomisation. With a power of 90% and an alpha level of 5%, we may reject or detect an improvement of 8%. The primary analyses of all outcomes will be performed in the intention‐to‐treat population. For the primary outcome, the Kryger Jensen and Lange method will be used to compare the two treatment groups adjusted for stratification variables supplemented with sensitivity analyses in the per‐protocol population and with further adjustments for prognostic variables. Secondary outcomes will be analysed with multiple linear regressions, logistic regressions or the Kryger Jensen and Lange method as suitable with adjustment for stratification variables.

Conclusion

The GODIF trial data will increase the certainty about the effects of fluid removal using furosemide in adult ICU patients with fluid overload.

Trial Registrations: EudraCT identifier: 2019‐004292‐40 and ClinicalTrials.org: NCT04180397.
Epigenomic signature of accelerated ageing in progeroid Cockayne syndrome
Authors: Crochemore Clément , Chica Claudia , Garagnani Paolo , Lattanzi Giovanna , Horvath Steve , Sarasin Alain , Franceschi Claudio , Bacalini Maria Giulia , Ricchetti Miria
Published: September 2023

Cockayne syndrome (CS) and UV‐sensitive syndrome (UVSS) are rare genetic disorders caused by mutation of the DNA repair and multifunctional CSA or CSB protein, but only CS patients display a progeroid and neurodegenerative phenotype, providing a unique conceptual and experimental paradigm. As DNA methylation (DNAm) remodelling is a major ageing marker, we performed genome‐wide analysis of DNAm of fibroblasts from healthy, UVSS and CS individuals. Differential analysis highlighted a CS‐specific epigenomic signature (progeroid‐related; not present in UVSS) enriched in three categories: developmental transcription factors, ion/neurotransmitter membrane transporters and synaptic neuro‐developmental genes. A large fraction of CS‐specific DNAm changes were associated with expression changes in CS samples, including in previously reported post‐mortem cerebella. The progeroid phenotype of CS was further supported by epigenomic hallmarks of ageing: the prediction of DNAm of repetitive elements suggested an hypomethylation of Alu sequences in CS, and the epigenetic clock returned a marked increase in CS biological age respect to healthy and UVSS cells. The epigenomic remodelling of accelerated ageing in CS displayed both commonalities and differences with other progeroid diseases and regular ageing. CS shared DNAm changes with normal ageing more than other progeroid diseases do, and included genes functionally validated for regular ageing. Collectively, our results support the existence of an epigenomic basis of accelerated ageing in CS and unveil new genes and pathways that are potentially associated with the progeroid/degenerative phenotype.
Oral analgesic for musculoskeletal injuries in children: A systematic review and network meta‐analysis
Authors: Utsumi Shu , Amagasa Shunsuke , Moriwaki Taro , Uematsu Satoko
Published: September 2023

Objective

Pain in pediatric musculoskeletal (MSK) injuries can lead to increased anxiety, fear, and avoidance of medical care, making analgesic management critical. Therefore, we evaluated analgesic efficacy and adverse effects to select the optimal analgesic agent in pediatric patients with MSK injuries.

Methods

Four databases were searched from inception to March 2023 for peer‐reviewed, open randomized controlled trials (RCTs). Inclusion criteria were: (1) trials with RCT design, (2) children aged 1 month–18 years with MSK injury, (3) outpatient setting, (4) interventions and control, (5) primary outcome of pain score at 60 and 120 min and secondary outcome of adverse effects, and (6) full‐text and peer‐reviewed articles. Two reviewers screened, extracted data, and assessed the risk of bias. A frequentist random‐effects network meta‐analysis (NMA) was performed. Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation working group approach.

Results

We included eight trials comprising 1645 children. Ibuprofen was significantly associated with pain reduction at 120 min, compared with acetaminophen (SMD 0.31 [95% CI 0.11–0.51]; moderate certainty) and opioids (SMD 0.34 [95% CI 0.20–0.48]; moderate certainty). Compared with opioids alone, ibuprofen–opioid combination was significantly associated with pain reduction at 120 min (SMD 0.19 [95% CI 0.03–0.35]). No significant differences were found in pain interventions at 60 min. Ibuprofen had statistically fewer adverse events than opioids (RR, 0.54 [95% CI 0.33–0.90]; moderate certainty) and ibuprofen with opioids (RR 0.47 [95% CI 0.25–0.89]; moderate certainty). In terms of limitations, the eight RCTs included had relatively small sample sizes; only two were high‐quality RCTs.

Conclusions

Our NMA found ibuprofen to be the most effective and least adverse analgesic in pediatric patients with MSK injuries.
Explicating the role of amygdala substructure alterations in the link between hypoleptinemia and rumination in anorexia nervosa
Authors: Wronski Marie‐Louis , Hohnemann Charlotte , Bernardoni Fabio , Bahnsen Klaas , Doose Arne , Arold Dominic , Borucki Katrin , Holsen Laura M. , Lawson Elizabeth A. , Plessow Franziska , Weidner Kerstin , Roessner Veit , Diestel Stefan , King Joseph A. , Seidel Maria , Ehrlich Stefan
Published: September 2023

Objective

The amygdaloid complex plays a pivotal role in emotion processing and has been associated with rumination transdiagnostically. In anorexia nervosa (AN), we previously observed differential reductions of amygdala nuclei volumes (rostral‐medial cluster substantially affected) and, in another study, elevated food−/weight‐related rumination. Both amygdala volumes and rumination frequency correlated with characteristically suppressed leptin levels in AN. Thus, we hypothesized that amygdala nuclei alterations might be associated with AN‐related rumination and potentially mediate the leptin‐rumination relationship in AN.

Methods

Rumination (food−/weight‐related) was assessed using ecological momentary assessment for a 14‐day period. We employed frequentist and Bayesian linear mixed effects models in females with AN (n = 51, 12–29 years, majority admitted to inpatient treatment) and age‐matched healthy females (n = 51) to investigate associations between rostral‐medial amygdala nuclei volume alterations (accessory basal, cortical, medial nuclei, corticoamygdaloid transitions) and rumination. We analyzed mediation effects using multi‐level structural equation models.

Results

Reduced right accessory basal and cortical nuclei volumes predicted more frequent weight‐related rumination in AN; both nuclei fully mediated the effect of leptin on weight‐related rumination. In contrast, we found robust evidence for the absence of amygdala nuclei volume effects on rumination in healthy females.

Conclusion

This study provides first evidence for the relevance of specific amygdala substructure reductions regarding cognitive symptom severity in AN and points toward novel mechanistic insight into the relationship between hypoleptinemia and rumination, which might involve the amygdaloid complex. Our findings in AN may have important clinical value with respect to understanding the beneficial neuropsychiatric effects of leptin (treatment) in AN and potentially other psychiatric conditions such as depression.
Aberrant resting‐state functional connectivity underlies cognitive and functional impairments in remitted patients with bipolar disorder
Authors: Fortea Lydia , Ysbæk‐Nielsen Alexander T. , Macoveanu Julian , Petersen Jeff Zarp , Fisher Patrick M. , Kessing Lars V. , Knudsen Gitte M. , Radua Joaquim , Vieta Eduard , Miskowiak Kamilla W.
Published: September 2023

Background

Bipolar disorder (BD) is commonly associated with cognitive impairments, that directly contribute to patients' functional disability. However, there is no effective treatment targeting cognition in BD. A key reason for the lack of pro‐cognitive interventions is the limited insight into the brain correlates of cognitive impairments in these patients. This is the first study investigating the resting‐state neural underpinnings of cognitive impairments in different neurocognitive subgroups of patients with BD.

Method

Patients with BD in full or partial remission and healthy controls (final sample of n = 144 and n = 50, respectively) underwent neuropsychological assessment and resting‐state functional magnetic resonance imaging. We classified the patients into cognitively impaired (n = 83) and cognitively normal (n = 61) subgroups using hierarchical cluster analysis of the four cognitive domains. We used independent component analysis (ICA) to investigate the differences between the neurocognitive subgroups and healthy controls in resting‐state functional connectivity (rsFC) in the default mode network (DMN), executive central network (ECN), and frontoparietal network (FPN).

Results

Cognitively impaired patients displayed greater positive rsFC within the DMN and less negative rsFC within the ECN than healthy controls. Across cognitively impaired patients, lower positive connectivity within DMN and lower negative rsFC within ECN correlated with worse global cognitive performance.

Conclusion

Cognitive impairments in BD seem to be associated with a hyper‐connectivity within the DMN, which may explain the failure to suppress task‐irrelevant DMN activity during the cognitive performance, and blunted anticorrelation in the ECN. Thus, aberrant connectivity within the DMN and ECN may serve as brain targets for pro‐cognitive interventions.
Orthodontic treatment in patients with periodontitis – a narrative literature review
Authors: Oruba Z , Gibas‐Stanek M , Pihut M , Cześnikiewicz‐Guzik M , Stós W
Published: September 2023

Patients with periodontitis often require an inter‐disciplinary approach, including orthodontic treatment, for effective rehabilitation of masticatory function, aesthetics and quality of life. The aim of this narrative review was to comprehensively discuss literature focusing on the biology, indications and inter‐disciplinary connections related to the orthodontic approach in patients with periodontitis and to present clinical concepts in accordance with valid guidelines. The outcomes of the experimental studies indicate that orthodontic tooth movement (OTM) can be performed safely for teeth with reduced periodontium, provided infection and inflammation are controlled. Orthodontic treatment can correct pathological tooth migration, is not associated with deterioration of clinical periodontal parameters and improves aesthetics. Intrusion is safe when performed with light forces and under a strict oral hygiene regimen. Teeth can be moved either towards or away from the intrabony defect previously subjected to regenerative procedures, and research suggests that OTM has the potential to enhance bone formation after regenerative therapy. The data on orthodontic movement of teeth with furcation involvement are very scarce. The improvement in furcation involvement following either combined periodontal and orthodontic treatment was only documented in animal model studies. Due to bone and tooth loss, special consideration should be given to orthodontic treatment mechanics. © 2023 Australian Dental Association.
Critical analysis of a new system to classify root and canal morphology — A systematic review
Authors: Ahmed Hany Mohamed Aly , Rossi‐Fedele Giampiero , Dummer Paul Michael Howell
Published: September 2023

A novel system to classify root and canal morphology was recently introduced (Ahmed et al. 2017). This systematic review aimed to answer the following research question: Does the Ahmed et al. system provide a more accurate and practical classification of root and canal anatomy compared to other classifications? A literature search was conducted in Google Scholar, Scopus and Wiley Online Library to identify the citation counts for the article entitled ‘A new system for classifying root and root canal morphology; doi.org/10.1111/iej.12685’. After removal of duplicates and unrelated articles, 15 studies were included and analysed. All studies compared the Ahmed et al. system with the Vertucci classification. Results revealed that both systems were able to classify simple canal configurations in single‐rooted anterior and premolar teeth, disto‐buccal and palatal roots of maxillary molars. However, the Ahmed et al. system provided more accurate and comprehensive categorisations of single‐rooted teeth with complex canal anatomy, multi‐rooted maxillary and mandibular premolars and the mesio‐buccal root of maxillary molars. Further evidence on the utility of the Ahmed et al. system is required using other diagnostic devices especially in molars.