bluuebunny/crossref_metadata_2025 huggingface dataset:
Scalable ultra-high-throughput single-cell chromatin and RNA sequencing reveals gene regulatory dynamics linking macrophage polarization to autoimmune disease
Authors: Lobato-Moreno Sara , Yildiz Umut , Claringbould Annique , Servaas Nila H. , Vlachou Evi P. , Arnold Christian , Bauersachs Hanke Gwendolyn , Campos-Fornés Víctor , Prummel Karin D. , Noh Kyung Min , Marttinen Mikael , Zaugg Judith B.
Published: December 2023

Enhancers and transcription factors (TFs) are crucial in regulating cellular processes, including disease-associated cell states. Current multiomic technologies to study these elements in gene regulatory mechanisms lack multiplexing capability and scalability. Here, we present SUM-seq, a cost-effective, scalableSingle-cellUltra-high-throughputMultiomic sequencing method for co-assaying chromatin accessibility and gene expression in single nuclei. SUM-seq enables profiling hundreds of samples at the million cell scale and outperforms current high-throughput single-cell methods. We applied SUM-seq to dissect the gene regulatory mechanisms governing macrophage polarization and explored their link to traits from genome-wide association studies (GWAS). Our analyses confirmed known TFs orchestrating M1 and M2 macrophage programs, unveiled key regulators, and demonstrated extensive enhancer rewiring. Integration with GWAS data further pinpointed the impact of specific TFs on a set of immune traits. Notably, inferred enhancers regulated by the STAT1/STAT2/IRF9 (ISGF3) complex were enriched for genetic variants associated with Crohn’s disease, ulcerative colitis and multiple sclerosis, and their target genes included known drug targets. This highlights the potential of SUM-seq for dissecting molecular disease mechanisms. SUM-seq offers a cost-effective, scalable solution for ultra-high-throughput single-cell multiomic sequencing, excelling in unraveling complex gene regulatory networks in cell differentiation, responses to perturbations, and disease studies.
Feeding-state dependent neuropeptidergic modulation of reciprocally interconnected inhibitory neurons biases sensorimotor decisions inDrosophila
Authors: de Tredern Eloïse , Manceau Dylan , Blanc Alexandre , Sakagiannis Panagiotis , Barre Chloe , Sus Victoria , Viscido Francesca , Hasan Md Amit , Autran Sandra , Nawrot Martin , Masson Jean-Baptiste , Jovanic Tihana
Published: December 2023

Animals’ feeding state changes behavioral priorities and thus influences even non-feeding related decisions. How is the feeding state information transmitted to non-feeding related circuits and what are the circuit mechanisms involved in biasing non-feeding related decisions remains an open question. By combining calcium imaging, neuronal manipulations, behavioral analysis and computational modeling, we determined that the competition between different aversive responses to mechanical cues is biased by feeding state changes. We found that this is achieved by differential modulation of two different types of reciprocally connected inhibitory neurons promoting opposing actions. This modulation results in a more frequent active type of response and less frequently a protective type of response if larvae are fed sugar compared to when they are fed a balanced diet. The information about the internal state is conveyed to the inhibitory neurons through homologues of the vertebrate neuropeptide Y known to be involved in regulating feeding behavior.
Relentless Selection: The importance of within-generation selection in heterogeneous habitats
Authors: Ehrlich Moritz A. , DeLiberto Amanda N. , Drown Melissa K. , Oleksiak Marjorie F. , Crawford Douglas L.
Published: December 2023

Natural selection relentlessly reshapes the genetic and phenotypic composition of populations, yet often adaptations cannot emerge due to excessive migration and gene flow. Nevertheless, in heterogeneous habitats strong selection could temporarily establish significant trait divergence among environmental patches. Here, we show that inFundulus heteroclitus,a single generation of selection drives significant phenotypic divergence (5-15%) in organismal metabolic rate, cardiac metabolic rate and hypoxia tolerance. This divergence occurs among individuals of the same panmictic population residing in environmentally distinct microhabitats. Phenotypic divergence remains observable following long-term common-gardening and is supported by previous work documenting fine-scale, genetic divergence among microhabitat residents. We show that the magnitude of within-generation trait divergence is on the order of what is commonly observed among more isolated populations that have diverged over multiple generations. Although panmictic reproduction among microhabitat residents erodes trait divergence every generation, strong selection could potentially reestablish it in the next. In heterogeneous habitats, transient, fine-scale divergence could have a considerable impact on eco-evolutionary dynamics. Ignoring its contribution to overall trait variance could limit our ability to define meaningful, evolved divergence.

Natural selection can lead to changes in organisms’ traits over time. Typically, these changes occur slowly over multiple generations and over large spatial scales. By studying a wild population of Atlantic killifish, we show that a single generation of natural selection can generate substantial trait variation over short distances. We observe significant differences in several physiological traits among individuals inhabiting distinct ‘microhabitats’ in a patchy salt marsh environment. These differences are unlikely due to physiological acclimation and are best explained by strong, natural selection removing those individuals not suited to a particular microhabitat. Previous studies support natural selection as the most likely explanation, having shown subtle genetic differences among microhabitat residents. Remarkably, the magnitude of trait divergence is on the order of what is typically observed among populations that have diverged over multiple generations and larger spatial scales. Our results highlight the significant contribution of natural selection to trait variation in patchy environments, even over exceptionally short time and small spatial scales.
Identification of active transposable element candidates from ROH in a de novo assembled chromosome-scale genome of a Nishikigoi, an ornamental fish derived from Common carp (Cyprinus carpio)
Authors: Hosaka Aoi
Published: December 2023

Transposable Elements (TEs) are major components of the genome. To understand their function and evolution, it is necessary to identify active TEs from a diverse range of organisms. Here, I report the genome of the Nishikigoi, an ornamental fish derived from the Common carp, and the novel approach to detecting active TE candidates.

I constructed a chromosome-scale assembly using long-read sequencing and Hi-C methods. It revealed that Nishikigoi has Robertsonian-like chromosomal translocations not seen in Common carp. I also found that Nishikigoi has a significantly different genetic background from Common carp, reflecting the intensive breeding history.

Furthermore, by focusing on Runs of Homozygosity (ROH) islands in the Nishikigoi genome and analyzing structural variations with long-read sequencing, I identified several active TE candidates.

This study not only revealed the unique genetic features of Nishikigoi but also demonstrated the potential for a novel approach in the search for active TEs.
All three MutL complexes are required for repeat expansion in a human stem cell model of CAG-repeat expansion mediated glutaminase deficiency
Authors: Hayward Bruce , Kumari Daman , Santra Saikat , van Karnebeek Clara D.M. , van Kuilenburg André B.P. , Usdin Karen
Published: December 2023

The Repeat Expansion Diseases (REDs) arise from the expansion of a disease-specific short tandem repeat (STR). Different REDs differ with respect to the repeat involved, the cells that are most expansion prone and the extent of expansion. Furthermore, whether these diseases share a common expansion mechanism is unclear. To date, expansion has only been studied in a limited number of REDs. Here we report the first studies of the expansion mechanism in induced pluripotent stem cells derived from a patient with a form of the glutaminase deficiency disorder known as Global Developmental Delay, Progressive Ataxia, And Elevated Glutamine (GDPAG; OMIM# 618412) caused by the expansion of a CAG-STR in the 5’ UTR of the glutaminase (GLS) gene. We show that alleles with as few as ∼120 repeats show detectable expansions in culture despite relatively low levels of R-loops formed at this locus. Additionally, using a CRISPR-Cas9 knockout approach we show that PMS2 and MLH3, the constituents of MutLα and MutLγ, the 2 mammalian MutL complexes known to be involved in mismatch repair (MMR), are essential for expansion. Furthermore, PMS1, a component of a less well understood MutL complex, MutLβ, is also important, if not essential, for repeat expansion in these cells. Our results provide insights into the factors important for expansion and lend weight to the idea that, despite some differences, the same mechanism is responsible for expansion in many, if not all, REDs.
Drought impact on phellem development: identification of novel gene regulators and evidence of photosynthetic activity
Authors: Barros Pedro M. , Sapeta Helena , Lucas Diogo A. , Oliveira M. Margarida
Published: December 2023

Quercus suber(cork oak) is a sustainably exploited forest resource, producing a unique renewable raw material known as cork. With drought events imposing a negative impact on tree vitality, we need more knowledge on the genetic and environmental regulation of cork development to protect the cork sector. We focused on characterizing long-term drought-induced molecular adaptations occurring in stems, and identifying key genetic pathways regulating phellem development. One-year-old cork oak plants were grown for 6 months under well-watered, or water-deficit (WD) conditions and main stems were targeted for histological characterization and transcriptomic analysis. WD treatment impaired secondary growth, by reducing meristem activity at both vascular cambium and phellogen. We analyzed the transcriptional changes imposed by WD in phellem, inner bark, and xylem, and found a global downregulation of genes related to cell division, differentiation, and cell wall biogenesis. Phellem and inner bark showed upregulation of photosynthesis-related genes, highlighting a determinant role of stem photosynthesis in the adaptation to long-term drought. We show that developing phellem cells contain chloroplasts and their abundance increases under WD. Finally, we propose new candidate regulatory genes involved in the regulation of phellogen activity and demonstrate the involvement of phellem in drought-induced bark photosynthesis in young plants.

Highlight

Phellem development in cork oak is impaired in drought adaptation, by negative regulation of cell division and differentiation programs, while photosynthesis is induced to contributing to CO2recycling in the stem.
Stabilization of F-actin bySalmonellaeffector SipA resembles the structural effects of inorganic phosphate and phalloidin
Authors: Niedzialkowska Ewa , Runyan Lucas A. , Kudryashova Elena , Egelman Edward H. , Kudryashov Dmitri S.
Published: December 2023

Entry ofSalmonellainto host enterocytes strictly relies on its pathogenicity island 1 effector SipA. We found that SipA binds to F-actin in a unique mode in a 1:2 stoichiometry with picomolar affinity. A cryo-EM reconstruction revealed that SipA’s globular core binds at the grove between actin strands, whereas the extended C-terminal arm penetrates deeply into the inter-strand space, stabilizing F-actin from within. The unusually strong binding of SipA is achieved via a combination of fast association via the core and very slow dissociation dictated by the arm. Similarly to Pi, BeF3, and phalloidin, SipA potently inhibited actin depolymerization by ADF/cofilin, which correlated with the increased filament stiffness, supporting the hypothesis that F-actin’s mechanical properties contribute to the recognition of its nucleotide state by protein partners. The remarkably strong binding to F-actin maximizes the toxin’s effects at the injection site while minimizing global influence on the cytoskeleton and preventing pathogen detection by the host cell.
MERITS: a web-based integratedMycobacterialPE/PPE protein database
Authors: He Zhijie , Wang Cong , Guo Xudong , Sun Heyun , Bi Yue , Pitt Miranda E. , Li Chen , Song Jiangning , Coin Lachlan JM , Li Fuyi
Published: December 2023

Motivation

PE/PPE proteins, highly abundant in theMycobacteriumgenome, play a vital role in virulence and immune modulation. Understanding their functions is key to comprehending the internal mechanisms ofMycobacterium. However, a lack of dedicated resources has limited research into PE/PPE proteins.

Results

Addressing this gap, we introduce MERITS, a comprehensive 3D structure database specifically designed for PE/PPE proteins. MERITS hosts 22,353 non-redundant PE/PPE proteins, encompassing details like physicochemical properties, subcellular localisation, post-translational modification sites, protein functions, and measures of antigenicity, toxicity, and allergenicity. MERITS also includes data on their secondary and tertiary structure, along with other relevant biological information. MERITS is designed to be user-friendly, offering interactive search and data browsing Features to aid researchers in exploring the potential functions of PE/PPE proteins. MERITS is expected to become a crucial resource in the field, aiding in developing new diagnostics and vaccines by elucidating the sequence-structure-functional relationships of PE/PPE proteins.

Availability and implementation

MERITS is freely accessible athttp://merits.unimelb-biotools.cloud.edu.au/.
Beyond the medical file: a scoping review on patients’ perspectives on guideline-oriented depression treatment in primary care
Authors: Biersack Katharina , Sattel Heribert , Schönweger Petra , Kaspar Lea , Lehnen Nadine , Gensichen Jochen , Henningsen Peter ,   the POKAL group
Published: December 2023

Objectives

Depressive disorders are common in the primary care setting. Primary care practitioners must deal with different disorders and keep up with evidence-based treatment. Clinical practice guidelines (CPG) offer accessible information about up-to-date care but are poorly implemented. Research on the implementation of CPGs has focused on the practitioners’ perspective but has neglected the patients’ perspective largely.

This scoping review aimed to identify terms related to the concept of ‘patients’ perspectives on depression treatment in primary care building a comprehensive framework and to identify researched barriers and facilitators to partaking in care.

Methods

We conducted a scoping review on Medline and Psycinfo. Eligible publications contained information from the patients’ point of view on depression treatment in primary care in OECD member states. We used the PCC-framework to obtain inclusion criteria. Publications until August 2nd 2023 were considered.

Results

We included 232 publications. Current literature focuses on behavioral and easily collected measures like satisfaction and on patient-sided barriers and facilitators to adherence. Other treatment-related behaviors are less researched. Patients often report exclusively or mainly physical symptoms in their visits which can impede diagnosis.

Conclusion

This review provides a comprehensive framework for the concept. Research on the patients’ perspective on depression treatment in primary care is still inconclusive.

Registration

This review is registered via OSF (https://osf.io/p9rnc).
Navigating the digital travel landscape: understanding the role of technology readiness in OTAs acceptance and usage for hotel bookings
Authors: Azdel Abdul Aziz , Awang Khairil Wahidin , Yusof Raja Nerina Raja , Hanafiah Mohd Hafiz
Published: December 2023

Purpose

This paper delves into the multi-faceted factors influencing the adoption and utilisation of online travel agencies (OTAs) for reserving hotel accommodations. The study aims to expand upon the unified theory of acceptance and use of technology (UTAUT2) framework to accomplish this objective by integrating the critical dimension of technology readiness (TR).

Design/methodology/approach

Four hundred and fifty-three (453) inbound tourists were asked to share their feedbacks on their recent OTA booking experience. Structural equation modelling (SEM) was used to confirm the study model and test the study hypotheses.

Findings

This study found that the motivating TR attributes favourably affect the acceptance and actual use of OTAs, while the inhibitors TR reflects adverse effects on OTA’s usage. On the other hand, the OTAs usage attributes: performance expectancy, effort expectancy, social influence, facilitating condition, hedonic motivation, price value and habit are all significant determinants of consumers' behavioural intention.

Originality/value

The originality of this study lies in providing a more comprehensive explanation and prediction of consumer behaviour in relation to OTAs. Specifically, it recognises the importance of TR as a significant determinant of technology adoption and usage within the service industry realm.
The role of institutional and stakeholder interaction in integrated reporting policy development
Authors: AbuRaya Rania
Published: December 2023

Purpose

This study aims to investigate the role of institutional and stakeholder interaction in the development of integrated reporting policy by the International Integrated Reporting Council (IIRC). It helps advance the theory of integrated reporting and offers insights into its fundamental concepts and relevant issues.

Design/methodology/approach

A flexible pattern-matching qualitative research approach is used and an analytical framework of integrated reporting historical foundations and conceptual background is developed. An IIRC case analysis is conducted by using a chronological content analysis of the International Integrated Reporting Framework and related initiatives and publications for integrated reporting policy pronouncements.

Findings

Institutional and stakeholder pressures within both the organization’s macro and micro contexts have played an effective role in transforming corporate reporting practices. In an integrated reporting context, institutional forces of normative and mimetic isomorphism seem to have more influence on organizations than coercive pressures, where stakeholder pressures with limited official power derive influence from their legitimacy while urgency is evidently implied. Findings indicate that integrated reporting policy has emerged analogously with the institutional environment and stakeholders’ expectations. The distinct nature of integrated reporting has caused a paradigm shift from silo thinking of wealth creation to integrated thinking of value creation.

Research limitations/implications

This is an exploratory study that does not consider different prominent integrated reporting models. It has important implications for policymakers in articulating the integration of financial and nonfinancial metrics for reporting overall corporate performance. It can help academics build on integrated reporting foundations for conducting future research and assist practitioners in operationalizing integrated reporting policy into practice. Moreover, it has potential prospects for international business in developing integrated reporting policies and strategies aimed at creating mutual value in specific international contexts.

Originality/value

Integrated reporting represents a new internationally developing reporting trend with distinct reporting features and foundations for value creation. The study provides considerable addition to emerging research into the growing awareness of integrated reporting policy, develops a conceptual model of institutional and stakeholder interaction and theorizes on such interplay, identifies the potential influences under which integrated reporting is likely to occur and offers key insights into integrated reporting policy. Hence, it contributes to the ongoing global challenge of promoting the reporting transition to integrated reporting and its perceived future endorsement.
The moderating effect of financial constraints on the relationship between stock price crash risk and managerial ability
Authors: Shelih Ragia , Wang Li
Published: December 2023

Purpose

This study aims to empirically explore the influence of managerial ability on crash risk and the moderating effect of financial constraints on this interrelationship.

Design/methodology/approach

Using a sample of listed corporations in the Egyptian Stock Exchange during 2018–2021, the authors test the hypotheses by using the measures and methods well established in prior literature. The authors also conduct multiple robustness analyses to ensure the validity of the empirical results.

Findings

The findings suggest that managerial ability can effectively inhibit crash risk. In addition, the authors report that financial constraints significantly dampen this relationship. Thus, financial restrictions play a striking role in hampering the managerial ability to prevent stock crashes. Furthermore, the authors document that the moderating role of severe financing constraints is more prominent during the Covid-19 pandemic period.

Originality/value

The originality of this study stems from the following considerations. First, this study enriches relevant studies on crash risk by providing evidence from one of the emerging markets in the Middle East; thereby, contrasting with those in developed economies. Second, to the best of the authors’ knowledge, this is the first study investigating the moderating impact of financing constraints on the managerial ability and crash risk nexus. Therefore, this work adds value to the extant knowledge by scrutinizing this important issue and providing novel empirical evidence.
Exploring a comprehensive evaluation model for measuring spatial equity in the layout of city community elderly service facilities: a case study in Xi’an, China
Authors: Wang Peiyu , Zhang Qian , Li Zhimin , Wang Fang , Shi Ying
Published: December 2023

Purpose

The study aims to devise a comprehensive evaluation model (CEM) for evaluating spatial equity in the layout of elderly service facilities (ESFs) to address the inequity in the layout of ESFs within city center communities characterized by limited land resources and a dense elderly population.

Design/methodology/approach

The CEM incorporates a suite of analytical tools, including accessibility assessment, Lorenz curve and Gini coefficient evaluations and spatial autocorrelation analysis. Utilizing this model, the study scrutinized the distributional equity of three distinct categories of ESFs in the city center of Xi’an and proposed targeted optimization strategies.

Findings

The findings reveal that (1) there are disparities in ESFs’ accessibility among different categories and communities, manifesting a distinct center (high) and periphery (low) distribution pattern; (2) there exists inequality in ESFs distribution, with nearly 50% of older adults accessing only 18% of elderly services, and these inequalities are more pronounced in urban areas with lower accessibility, and (3) approximately 14.7% of communities experience a supply-demand disequilibrium, with demand surpassing supply as a predominant issue in the ongoing development of ESFs.

Originality/value

The CEM formulated in this study offers policymakers, urban planners and service providers a scientific foundation and guidance for decision-making or policy amendment by promptly assessing and pinpointing areas of spatial inequity in ESFs and identifying deficiencies in their development.
Gendering the beginning of life: Taiwanese gay fathers’ navigation of preimplantation genetic diagnosis‐assisted sex selection in transnational third‐party reproduction
Authors: Chen Jung
Published: December 2023

Preimplantation genetic diagnosis (PGD) has been used not only to avoid genetic diseases and increase conception success rates but also to perform non‐medical sex selection, particularly in the surging cross‐border reproductive care (CBRC). In the context of commercialised biomedicine, assisted reproductive technologies, such as lifestyle sex selection, have been tailored to meet intended parents’ preferences. However, there is a lack of analysis on how individuals’ reproductive decisions on PGD‐assisted sex selection were shaped within the sociocultural norms and CBRC. This article explores Taiwanese gay fathers’ navigations on sex selection while seeking third‐party reproduction overseas because of local legal constraints. Drawing on in‐depth interviews with 53 gay fathers (to‐be), I analysed how ‘individual preferences’ were dynamically shaped by local sociocultural norms and embedded within transnational settings of routinising PGD in chosen repro‐destinations. The findings showed that gay fathers mobilised strategic discourses on non‐medical sex selection from both the local and the global to negotiate their decisions in coherence with their LGBTQ+ identity and their role as sons carrying familial responsibility to procreate male heirs. This article proposed a nuanced understanding of gay fathers’ reproductive practices of ‘gendering the beginning of life’ through PGD‐assisted sex selection.
State home and community‐based services expenditures and unmet care needs in the United States: Has everyone benefitted equally?
Authors: Yang Yulin , Lee Ah‐Reum , Rapp Thomas , Chen Ruijia , Glymour M. Maria , Torres Jacqueline M.
Published: December 2023

Objective

To test whether the impacts of Medicaid's Home and Community‐Based Services (HCBS) expenditures have been equitable.

Data Sources and Study Setting

This is a secondary data analysis. We linked annual data on state‐level Medicaid HCBS expenditures with individual data from U.S. Health and Retirement Study (HRS; 2006–2016).

Study Design

We evaluated the association between state‐level HCBS expenditure quartiles and the risk of experiencing challenges in basic or instrumental activities of daily living (I/ADLs) without assistance (unmet needs for care). We fitted generalized estimating equations (GEE) with a Poisson distribution, log link function, and an unstructured covariance matrix. We controlled demographics, time, and place‐based fixed effects and estimated models stratified by race and ethnicity, gender, and urbanicity. We tested the robustness of results with negative controls.

Data Collection/Extraction Methods

Our analytic sample included HRS Medicaid beneficiaries, aged 55+, who had difficulty with ≥1 I/ADL (n = 2607 unique respondents contributing 4719 person‐wave observations).

Principal Findings

Among adults with IADL difficulty, higher quartiles of HCBS expenditure (vs. the lowest quartile) were associated with a lower overall prevalence of unmet needs for care (e.g., Prevalence Ratio [PR], Q4 vs. Q1: 0.91, 95% CI: 0.84–0.98). This protective association was concentrated among non‐Hispanic white respondents (Q4 vs. Q1: 0.82, 95% CI: 0.73–0.93); estimates were imprecise for Hispanic individuals and largely null for non‐Hispanic Black participants. We found no evidence of heterogeneity by gender or urbanicity. Negative control robustness checks indicated that higher quartiles of HCBS expenditure were not associated with (1) the risk of reporting I/ADL difficulty among 55+ Medicaid beneficiaries, and (2) the risk of unmet care needs among non‐Medicaid beneficiaries.

Conclusion

The returns to higher state‐level HCBS expenditures under Medicaid for older adults with I/ADL disability do not appear to have been equitable by race and ethnicity.
Nursing educational framework: A new nurse‐driven, conceptually guided approach
Authors: Choperena Ana , Rosa‐Salas Virginia La , Esandi‐Larramendi Nuria , Diez‐Del‐Corral Mercedes P. , Jones Dorothy
Published: December 2023

Purpose

The aim of this article is to present the Nursing Educational Framework (NEF) as an opportunity to integrate core elements of a humanistic person/family‐centered view and as guidance in structuring a relationship‐based curriculum.

Data sources

Empirical and theoretical literature studies were reviewed to define the framework rationale and its components.

Data synthesis

A deductive/inductive collaborative expert‐informed approach was undertaken to develop this evidence‐based codesigned framework. Its mission, along with unique components, implementation strategies, and outcomes, were successively integrated into the framework to guide nursing knowledge, learning, and curriculum development. A hermeneutic collaborative process of circular reflection was used in the development process.

Conclusions

The NEF contains central guiding principles and concepts that are intended to provide structural consistency across its included programs from a humanistic person/family‐centered approach.

Implications for nursing practice

This comprehensive theory‐guided framework allows educators to suggest specific directions for nursing practice within the nursing discipline and articulate nursing's unique and specialized approach to promoting excellent patient care outcomes. It can assist students to develop critical lens from a person/family‐centered relationship‐based practice approach.
Testosterone replacement therapy: association with mortality in high‐risk patient subgroups
Authors: Mann Amar , Strange Richard C , König Carola S , Hackett Geoffrey , Haider Ahmad , Haider Karim Sultan , Desnerck Peter , Ramachandran Sudarshan
Published: December 2023

Objectives

We describe studies determining the association between testosterone therapy (TTh) and mortality.

Materials & methods

We used a registry database of 737 men with adult‐onset testosterone deficiency defined as presenting with low serum total testosterone (TT) levels ≤12.1 nmol/L and associated symptoms over a near 10‐year follow‐up. We compared associations between testosterone undecanoate (TU), cardio‐metabolic risk factors and mortality using non‐parametric statistics followed by separate Cox regression models to determine if any association between TU and morality was independent of age and cardio‐metabolic risk factors. Finally, the association between TU and mortality was studied in men stratified by cardio‐metabolic risk.

Results

During a median follow‐up interquartile range (IQR) of 114 (84–132) months, 94 of the 737 men died. TU (ref: non‐treatment) was associated with mortality; hazard ratio = 0.23, 95% confidence intervals = 0.14–0.40. Cox's regression models showed the above association to be independent of baseline age, waist circumference, hemoglobin A1c, lipids, blood pressure, smoking, and type 2 diabetes. These variables remained associated with mortality. We finally stratified the men by the high‐risk baseline variables and established that the association between mortality and TU was only evident in men at higher risk. A possible explanation could lie with the “law of initial value,” where greater improvements are evident following treatment in patients with worse baseline values.

Conclusions

This study with long follow‐up confirms that TTh is associated with lower mortality in men with adult‐onset TD. This association was evident only in men with greater cardio‐metabolic risk factors who demonstrated greater benefit.
Deglaciation of the highest mountains in Scandinavia at the Younger Dryas–Holocene transition: evidence from surface exposure‐age dating of ice‐marginal moraines
Authors: Matthews John A. , Linge Henriette , Nesje Atle , Wilson Peter , Mourne Richard W. , Winkler Stefan , Owen Geraint , Hill Jennifer L. , Haselberger Stefan , Olsen Jesper
Published: December 2023

Surface exposure–age dating was applied to rock surfaces associated with ice‐marginal moraines at elevations of ~1520–1780 m a.s.l. on the slopes of Galdhøpiggen and Glittertinden, the two highest mountains in Scandinavia located in the Jotunheimen mountains of central southern Norway. This is important for understanding the pattern and timing of wastage of the Scandinavian Ice Sheet at the Younger Dryas–Holocene transition. Cosmogenic exposure dating (here 10Be dating) of boulders from the moraine ridges yielded overall mean ages (corrected for glacio‐isostatic uplift, surface erosion and snow shielding) of ~11.6 ka from Galdhøpiggen and ~11.2 ka from Glittertinden. Similar 10Be ages were also obtained from additionally collected proximal and distal erratic boulders and bedrock samples. These enabled age calibration of Schmidt‐hammer R‐values and independent Schmidt‐hammer exposure‐age dating (SHD) of the moraine ridges, which yielded comparable mean SHD ages of ~10.8 and ~10.6 ka from the Galdhøpiggen and Glittertinden sites, respectively. Taking account of the age resolution and other limitations of both dating techniques, the results suggest that the two sets of moraines have approximately the same age but that neither technique can distinguish unambiguously between moraine formation in the late Younger Dryas or Early Holocene. Together with features of moraine‐ridge morphology and estimates of equilibrium‐line altitude depression of ~360–575 m (corrected for land uplift), the results imply moraine formation during short‐lived re‐advances of active glaciers, at least the lower reaches of which were warm‐based. It is concluded that the local glaciers remained active and advanced during deglaciation either very late in the Younger Dryas or very early in the Holocene, possibly in response to the Preboreal Oscillation at ~11.4 ka. The study supports the concept of a thin Younger Dryas ice sheet and places time constraints on the timing of final deglaciation in southern Norway.
Sex‐specific behavioural, metabolic, and immunohistochemical changes after repeated administration of the synthetic cannabinoid AKB48 in mice
Authors: Corli Giorgia , Roda Elisa , Tirri Micaela , Bilel Sabrine , De Luca Fabrizio , Strano‐Rossi Sabina , Gaudio Rosa Maria , De‐Giorgio Fabio , Fattore Liana , Locatelli Carlo Alessandro , Marti Matteo
Published: December 2023

Background and Purpose

AKB48 is a synthetic cannabinoid illegally sold for its psychoactive cannabis‐like effects that have been associated with acute intoxication and whose effects are poorly known.

Experimental Approach

Using a behavioural, neurochemical, and immunohistochemical approach, we investigated the pharmaco‐toxicological effects, pharmacokinetics, and neuroplasticity at cannabinoid CB1 receptors in the cerebellum and cortex induced by repeated AKB48 administration in male and female mice.

Key Results

The effects of AKB48 varied significantly depending on sex and treatment duration. The first injection impaired sensorimotor responses and reduced body temperature, analgesia, and breath rate to a greater extent in females than in males; the second injection induced stronger effects in males while the third injection of AKB48 induced weaker responses in both sexes, suggesting emergence of tolerance. The CB1 receptor antagonist NESS‐0327 prevented the effects induced by repeated AKB48, confirming a CB1 receptor‐mediated action. Blood AKB48 levels were higher in females than in males and repeated administration caused a progressive rise of AKB48 levels in both sexes, suggesting an inhibitory effect on cytochrome activity. Finally, immunohistochemical analysis revealed higher expression of CB1 receptors in the cerebellum and cortex of females, and a rapid CB1 receptor down‐regulation in cerebellar and cortical areas following repeated AKB48 injections, with neuroadaptation occurring generally more rapidly in females than in males.

Conclusion and Implications

We have shown for the first time that AKB48 effects significantly vary with prolonged use and that sex affects the pharmacodynamic/pharmacokinetic responses to repeated administration, suggesting a sex‐tailored approach in managing AKB48‐induced intoxication.
Scavenging with invasive species
Authors: Newsome Thomas , Cairncross Rhys , Cunningham Calum X. , Spencer Emma E. , Barton Philip S. , Ripple William J. , Wirsing Aaron J.
Published: December 2023

Carrion acts as a hotspot of animal activity within many ecosystems globally, attracting scavengers that rely on this food source. However, many scavengers are invasive species whose impacts on scavenging food webs and ecosystem processes linked to decomposition are poorly understood. Here, we use Australia as a case study to review the extent of scavenging by invasive species that have colonised the continent since European settlement, identify the factors that influence their use of carcasses, and highlight the lesser‐known ecological effects of invasive scavengers. From 44 published studies we identified six invasive species from 48 vertebrates and four main groups of arthropods (beetles, flies, ants and wasps) that scavenge. Invasive red foxes (Vulpes vulpes), domestic dogs (Canis familiaris), feral pigs (Sus scrofa), black rats (Rattus rattus) and feral cats (Felis catus) were ranked as highly common vertebrate scavengers. Invasive European wasps (Vespula germanica) are also common scavengers where they occur. We found that the diversity of native vertebrate scavengers is lower when the proportion of invasive scavengers is higher. We highlight that the presence of large (apex) native vertebrate scavengers can decrease rates of scavenging by invasive species, but that invasive scavengers can monopolise carcass resources, outcompete native scavengers, predate other species around carcass resources and even facilitate invasion meltdowns that affect other species and ecological processes including altered decomposition rates and nutrient cycling. Such effects are likely to be widespread where invasive scavengers occur and suggest a need to determine whether excessive or readily available carcass loads are facilitating or exacerbating the impacts of invasive species on ecosystems globally.
Social competence of single‐parent children with child abuse in China: Mediation model of resilience
Authors: Wang Miao , Hong Jun Sung
Published: December 2023

Children from single‐parent families typically face severe developmental risks, especially those with prior experience in child abuse. This study aimed to investigate the child abuse experience and social competence of children from single‐parent families and discuss the possible mediation effect of resilience in Mainland China. This study analysed 431 single‐parent children samples collected in China (50% females, Mage = 13.10). Group comparison analyses were conducted to illustrate group differences in social competence between single‐parent children with and without child abuse experience. In addition, path analyses were conducted to examine the mediation effect of resilience between child abuse and social competence. This study findings indicated that single‐parent children with physical and emotional abuse experience did not perform significantly worse in social competence, but those with emotional neglect were found to do worse. Resilience fully mediated the effect of physical abuse and partially mediated the effect of emotional neglect on single‐parent children's social competence, while it did not mediate the impact of emotional abuse. This study contributes to understanding the mechanisms between child abuse, social competence and resilience of children from single‐parent families in Mainland China. The findings have implications for social services for single‐parent children who are abused.
Martensite content effect on fatigue crack growth and fracture energy in dual‐phase steels
Authors: Avendaño‐Rodríguez D. , Rodriguez‐Baracaldo R. , Weber S. , Mujica‐Roncery L.
Published: December 2023

The effect of different microstructural factors on crack growth and fatigue fracture mechanisms in dual‐phase (DP) steels has yet to be fully understood. The present research examines the relationship between crack growth, microstructure, and fracture mechanisms. The samples were intercritically annealed at different temperatures to produce three different martensite volume fractions (MVFs). The results show that the mechanical incompatibility of ferrite and martensite promotes continuous crack tip deflection. MVF increases are associated with elevated fracture tortuosity, more significant fracture energy surface formation, and higher Paris law exponent m values. The interaction of the microstructure with the crack tip, the strain energy density, and the softening caused by secondary microcrack propagation are all illustrated by Electron backscatter diffraction (EBSD) maps. Increasing MVF promotes slow crack growth and a fracture energy increase of 22.9% between the as‐received and heat‐treated steels.
Does biochar improve nitrogen use efficiency in maize?
Authors: Preza Fontes Giovani , Greer Kristin D. , Pittelkow Cameron M.
Published: December 2023

Biochar is promoted as a means of improving soil fertility. Yet, few experiments have investigated its potential to improve nitrogen (N) use efficiency for high‐yielding maize production in the U.S. Midwest. We tested the hypothesis that biochar application increases inorganic soil N availability during maize growth, leading to higher grain yields and N recovery efficiency while reducing the risk of N leaching following harvest. Four N fertilizer rates (0, 90, 179, and 269 kg ha−1 as urea ammonium nitrate [UAN] solution) were applied with or without biochar (10 Mg ha−1) before planting in a two‐year field study. Inorganic soil N concentration was measured during the growing season (0–15 cm), and deep soil cores were obtained following harvest (0–90 cm). Results show that biochar did not affect maize yield, crop N uptake, or N recovery efficiency (by the difference method) across N rates, and there was no biochar by N rate interaction. While biochar lowered soil inorganic N concentrations on several sampling dates, this did not translate into seasonal differences in cumulative soil N availability, although grain yields in the unfertilized control were ~10% lower with biochar, suggesting net N immobilization. Biochar partially reduced the risk of N leaching following harvest by decreasing soil N concentrations at 30–60 cm, but mean concentrations for 0–90 cm were not different. Compared to previous work highlighting the benefits of biochar in arid climates with low soil fertility, we found no evidence of increased crop yield, NRE, or reduced risk of N leaching on Mollisols in a temperate climate.
The troika of energy consumption, economic growth, and CO2 emission: Quantile regression evidences for five Asian economies
Authors: Khan Saleem , Jehan Noor , Rauf Abdur , Nawaz Fahim , Erum Naila
Published: December 2023

This study examined the quadratic role of renewable energy and economic growth on environment quality in Asia's five most populous countries: China, India, Indonesia, Pakistan, and Bangladesh. Previous literature has scarcely addressed these economies and ignores the quadratic role of GDP per capita (GDPPC) and renewable energy (REN) together in a single study. Therefore, using STIRPAT model, we first added the quadratic term of GDPPC and then REN. In both cases, a quantile regression technique is utilised to identify the inclusive relationship between CO2 emissions and determining factors, considering different quantiles (0.25, 0.50, 0.75, 0.90, and 0.95) of CO2 emissions. The findings show that during the annual sample period of 1983–2019, urbanisation, GDPPC, non‐renewable energy, and REN all have an impact on CO2 emissions. Urbanisation and REN have nominal effects, with a 1% change in these variables leading to a 0.19% and 0.05% change in CO2 emissions, respectively. Non‐renewable energy and GDPPC are found to be main sources of CO2 emissions in the region. GDPPC is positively associated with CO2 emissions across all quantiles, but higher quantiles show a stronger correlation (i.e., GDPPC coefficients vary from 0.26 to 0.66). In addition, the results also revealed that the square term of GDPPC and REN significantly reduces CO2 emissions. This implies that our results support the environmental Kuznets curve (EKC) hypothesis; an inverted U‐shaped is established for both GDPPC and REN. These results encourage policy makers to adopt renewable energy that is both growth and environment friendly.
Comparison of one‐stage and chromogenic factor VIII assays to tailor the dose of recombinant factor VIII‐Fc fusion protein (rFVIIIFc, efmoroctocog alfa) in adult patients with haemophilia A: Single‐centre, real‐world experience of surgery
Authors: Désage Stéphanie , Nougier Christophe , Meunier Sandrine , Chamouard Valérie , Jousselme Emilie , Dargaud Yesim , Lienhart Anne
Published: December 2023

Background

Efmoroctocog alfa (rFVIIIFc) is an extended half‐life FVIII used notably in surgery for patients with haemophilia A. More information is needed of its usage in real‐life.

Methods

Adult patients with HA followed at the Lyon Comprehensive Hemophilia Care Center who underwent a surgery with rFVIIIFc were included in this retrospective analysis. The pharmacokinetics of rFVIIIFc was assessed by plasma factor VIII clotting activity (FVIII:C) using both one‐stage (OSA) and chromogenic substrate (CSA) assays.

Results

A total of 39 major and 31 minor surgeries were performed in 49 patients treated with rFVIIIFc. The median dose of rFVIIIFc infused before major and minor surgeries respectively was 67.5 ((interquartile range [IQR] 52.6‐76.9) and 48.0 (38.5‐51.8) IU/kg. For major surgeries, during the first postoperative week, the median residual FVIII:C was 78 (64.5‐101.5) IU/dL with OSA and 99 (71‐118) IU/dL with CSA (p < .0001).

After surgery, rFVIIIFc doses were adjusted according to CSA results. This led to a significant decrease of rFVIIIFc consumption compared to what would have been proposed according to the OSA assay, without unusual bleeding or appearance of inhibitor. Considering the high price of the molecule, this was also associated with a significant cost reduction.

Conclusion

Dose adjustment of rFVIIIFc according to FVIII: C measured by CSA is effective, safe and well tolerated in patients with haemophilia A undergoing invasive surgery.