bluuebunny/crossref_metadata_2025 huggingface dataset:
Managing Pregnancies of Unknown Location With the M4 Prediction Model or the NICE Algorithm: A Randomised Controlled Trial With Cross‐Sectional Diagnostic Accuracy Data
Authors: Fistouris Johan , Garbergs Helen , Bergman Katja , Bergh Christina , Strandell Annika
Published: January 2025

Objective

To determine the diagnostic performance and clinical utility of the M4 prediction model and the NICE algorithm managing women with pregnancy of unknown location (PUL).

Design

The study has a superiority design regarding specificity for non‐ectopic pregnancy for M4, given that the primary outcome of sensitivity for ectopic pregnancy (EP) is non‐inferior in comparison with the NICE algorithm.

Setting

Emergency gynaecology units in Sweden.

Population

595 women with PUL.

Methods

Participants were randomised (1:1) to M4 or the NICE algorithm after two serum human chorionic (hCG) levels and were categorised as high or low risk of having an EP. The diagnostic performance was evaluated on cross‐sectional data and utility by parallel groups.

Main Outcome Measures

The proportion of EP categorised as high risk (sensitivity) and non‐ectopic pregnancies categorised as low risk (specificity). Clinical outcomes were assessed.

Results

The sensitivity for EP was 79% (115 of 146) for M4 versus 85% (124 of 146) for the NICE algorithm, p = 0.1496 and the specificity for non‐ectopic pregnancies was 67% (300 of 449) for M4 and 74% (334 of 449) for the NICE algorithm, p = 0.0003. Clinical outcomes were similar between groups.

Conclusions

The sensitivity for EP by M4 was non‐inferior to NICE, but specificity was better for the NICE algorithm. No between group differences were observed for clinical outcomes.

Trial Registration

NCT 03461835, https://www.clinicaltrials.gov
Burdens of Tracheal, Bronchus, and Lung Cancer From 1990 to 2021 in China Compared to the Global Projection of 2036: Findings From the 2021 Global Burden of Disease Study
Authors: Chen Yuxing , Zeng Qingpeng , Li Muyu , Jin Jiahui , Zhao Jun
Published: January 2025

Background

Tracheal, bronchial, and lung cancers (TBL cancers) pose a significant global health challenge, with rising incidence and mortality rates, particularly in China. Studies from the Global Burden of Disease (GBD), 2021, can guide screening and prevention strategies for TBL cancer. This study aims to provide a comprehensive analysis of the burden of TBL cancers in China compared to global data.

Methods

We conducted an analysis of incidence, prevalence, mortality, and disability‐adjusted life years (DALYs) from 1990 to 2021. We also performed Joinpoint regression analysis and Bayesian age‐period‐cohort (BAPC) modeling to project future trends.

Results

From 1990 to 2021, there was a substantial increase in TBL cancer indicators for all sexes in China, with the most significant rise observed in females. The female population showed alarming increases in age‐standardized incidence rate (ASIR) and age‐standardized prevalence rate (ASPR). While global efforts have managed to stabilize these rates, China's figures remain high, suggesting the impact of persistent risk factors such as smoking and air pollution, coupled with an aging population. Furthermore, we utilized the projection model in China to estimate that these indicators of TBL cancers in females will likely follow continuous and rapid upward trends, while the burden of TBL cancers among males is expected to have a steady trend.

Conclusion

Although global efforts have been effective in reducing the burden of TBL cancers over the past three decades, there still remains strong regional and gender heterogeneity. TBL cancers need more screening strategies and medical attention in China and in the female population.
Make an environmental impact beyond organizational boundaries through green leisure crafting of employees
Authors: Chen I‐Shuo , Wu Szu‐Hsin , Choi Jin Nam
Published: January 2025

This study explores the impact of green human resource management (HRM) practices on employees' pro‐environmental behaviors beyond the workplace. To explore this cross‐domain resource transfer process, we draw on self‐determination theory and propose that workplace environmental training can inspire employees to engage in green leisure crafting outside of work, thereby enhancing spontaneous personal green behaviors. In addition, building on person–environment fit theory, we further identify employees' environmental values as a positive contingency of the proposed cross‐domain resource transfer. Our empirical analysis, based on two‐wave data from 404 employees, reveals that green leisure crafting mediates the relationship between workplace environmental training and employees' green behaviors in their personal lives. These findings offer valuable insights into how modern organizations can meet the growing demand for environmental management and create social value by empowering their employees to contribute to environmental sustainability beyond organizational boundaries.
The association between depressive symptoms and lower urinary tract symptoms and impact among women: Investigating behavioural, cognitive and physiological pathways
Authors: Brady Sonya S. , Arguedas Andrés , Huling Jared D. , Hellemann Gerhard , Jacobs David R. , Lewis Cora E. , Fok Cynthia S. , Schreiner Pamela J. , Van Den Eeden Stephen K. , Markland Alayne D.
Published: January 2025

Objective

Mechanistic studies are needed to understand why depressive symptoms are associated with poorer physical health. The objective of this study was to examine whether behavioural, cognitive and physiological factors mediated an association between depressive symptoms, measured in early adulthood, and lower urinary tract symptoms (LUTS) and their impact, a composite variable measured in mid‐life adulthood, among women in the Coronary Artery Risk Development in Young Adults study, conducted in four regions of the United States.

Design

Prospective cohort study.

Methods

Data were examined for 871 women. Depressive symptoms were measured and averaged across Years 5, 10 and 15. Year 20 health behaviour combined information about smoking, physical activity and diet. Year 25 cognitive function combined performance on different cognitive tests. Year 25 metabolic syndrome combined standard risk criteria for waist circumference, triglycerides, high‐density lipoprotein, blood pressure and glucose. A cluster analysis of urinary incontinence, other LUTS and impact data—collected two years after Year 25—was used to group women into one of four categories: no or very mild symptoms with no impact (bladder health) versus mild, moderate or severe symptoms/impact.

Results

Structural equation modelling showed a statistically significant direct path between depressive symptoms and LUTS/impact. Tests of indirect paths showed that health behaviours, cognitive function and metabolic syndrome did not mediate the association between depressive symptoms and LUTS/impact.

Conclusions

Depressive symptoms in early adulthood appear to be associated with LUTS and their impact in mid‐life adulthood over and above health behaviours, cognitive function and metabolic syndrome.
The impact of host biogeography, ecology, evolutionary history, and architecture on the structure of rolled‐leaf beetle assemblages of Costa Rican Zingiberales
Authors: Chaves‐Fallas José Miguel , García‐Robledo Carlos , Carlsen Mónica M. , Vargas Orlando , Rojas‐Gómez Mónica , Marquis Robert J.
Published: January 2025

Determining the factors affecting the structure of insect herbivore communities is a major challenge in ecology. Previous research demonstrated that plant defenses determine plant‐herbivore associations. However, non‐defensive variables may also explain why some plant species are associated with more diverse insect herbivore assemblages than others. Neotropical rolled‐leaf beetles (Cephaloleia and Chelobasis) complete their life cycle inside the young rolled leaves of their host plants in the order Zingiberales. The diet breadth of each species in this assemblage is particularly well‐known at our study site, La Selva Biological Station in Costa Rica. This study focused on the following non‐defensive variables: host plant elevational and geographic range size, soil type, habitat, local abundance, plant size, and leaf size. Because plant characteristics among closely related plants are not independent, we analyzed these variables in a phylogenetic context. We detected a positive effect of leaf width on rolled‐leaf beetle species richness (explaining 55% of the variation), abundance (28% of the variation and 57% when habitat is included in the model), diversity (37% of the variation), and community structure (6% of the variation, and 21%–26% when taxonomic family is included in the model). Our study demonstrates that Zingiberales leaf width influences positively rolled‐leaf beetle species richness, abundance, and diversity. This effect varies among plant families. Our study shows that plant architecture plays an important role in structuring insect herbivore assemblages in Zingiberales. Our results highlight the importance of including variables beyond plant defenses to understand the ecology and evolution of plant‐herbivore interactions.
Climate Heterogeneity Shapes the Diversity of Specialist Beetle Species Across Mountains in Malaysia
Authors: Musthafa Muneeb M. , Sánchez‐Reyes Uriel Jeshua , Abdullah Fauziah , Bhassu Subha , Ruzzier Enrico
Published: January 2025

The importance of maintaining biodiversity is well recognized, although the impacts of the ongoing climate crisis on biodiversity are still poorly understood for many groups, including insects. Therefore, the objectives of this study are (1) to identify the climatic niche breadth of beetle species among nine different Malaysian mountains, (2) to characterize the role of environmental (climatic) factors in niche determination, and (3) to relate the climatic niche of the species to the mountain environmental heterogeneity. The Outlying Mean Index (OMI), which compares the multivariate distance between the average environmental conditions of a given area and the specific range of conditions in which each species occurs (marginality), was used to quantify the niche parameters. Among the 875 species, only 130 presented significant responses to the nine tested parameters, 113 of which were identified as specialists, whereas 17 were classified as generalists of the climate environment. The remaining 745 species were not related to the environmental variables under study. Mountains with more heterogeneous climates and greater climate variation between sampling sites or elevations had fewer specialist beetles. Conversely, mountains with more homogeneous climates had a greater number of specialist beetles.
The Association Between Aspartate Transaminase to Alanine Transaminase Ratio and Perioperative Ischemic Stroke in Patients With Diabetes: A Retrospective Cohort Study
Authors: Liu Siyuan , Wang Binbin , Ma Libin , Yang Huikai , Liu Min , Song Yuxiang , Zhou Zhikang , Lou Jingsheng , Zhou Daming , Cao Jiangbei , Liu Yanhong , Mi Weidong , Ma Yulong
Published: January 2025

Background

Patients with diabetes are at a high risk for perioperative ischemic stroke (PIS). The use of biomarkers to identify high‐risk patients and predict PIS may provide considerable reference value in clinical decision‐making. The aspartate transaminase/alanine transaminase ratio (De Ritis ratio) has been proven to be associated with specific diabetic complications. However, the association between the De Ritis ratio and PIS has not been evaluated in this population. This retrospective cohort study aimed to evaluate the association between the preoperative De Ritis ratio and PIS in patients with type 2 diabetes undergoing noncardiovascular surgery.

Methods

Data from surgical patients were collected from January 2008 to August 2019. A total of 27,643 patients with type 2 diabetes mellitus (DM) undergoing noncardiovascular surgery under general anesthesia were screened. The optimal De Ritis ratio cutoff value was identified using the receiver operating characteristic (ROC) curve. Logistic regression models were used to evaluate the association between the preoperative De Ritis ratio and PIS. Propensity score matching (PSM), sensitivity analyses, and subgroup analyses were performed to further validate the robustness of this association.

Results

A total of 151 patients experienced PIS. A De Ritis ratio ≥ 1.04 was associated with an elevated risk of PIS after adjusting for baseline characteristics (OR [95% CI]: 2.25 [1.59–3.21]; p < 0.001), intraoperative parameters (2.50 [1.80–3.49]; p < 0.001), and all confounding variables (2.29 [1.61–3.29]; p < 0.001). In the propensity score‐matched cohort, the association between the De Ritis ratio and PIS remained significant (2.04 [1.38–3.05]; p < 0.001). These associations were also consistently maintained in the sensitivity and subgroup analyses.

Conclusions

An elevated De Ritis ratio is strongly associated with a higher risk of PIS in patients with type 2 DM undergoing noncardiovascular surgery. This may provide additional information on PIS risk assessment in patients with type 2 DM undergoing noncardiovascular surgery.
Association between lymphovascular invasion and lymph node metastases in colon cancer: A National Cancer Database analysis
Authors: Emile Sameh Hany , Horesh Nir , Garoufalia Zoe , Wignakumar Anjelli , Boutros Marylise , Wexner Steven D.
Published: January 2025

Aim

Lymphovascular invasion (LVI) is a well‐known risk factor in colorectal cancer that is associated with a worse prognosis. The present study aimed to assess the characteristics of patients with LVI‐positive colon cancer according to the status of nodal metastases and to study the association between LVI‐nodal status and survival.

Method

This retrospective study assessed the association between LVI and lymph node metastases in colon cancer, using data from the National Cancer Database. Patients were classified according to the pathological N stage into pN0 and pN1‐2. The risk factors for LVI were determined in each group using multivariable regression analyses. The primary outcome was LVI and the secondary outcome was 5‐year overall survival (OS). A modification of the tumour, node, metastasis (TNM) staging system that incorporates LVI in each stage was proposed.

Results

The study included 357 724 patients (51.1% female, median age 70 years). LVI was detected in 11.6% and 52.5% of patients with node‐negative and node‐positive disease, respectively. The independent predictors of LVI in pN0 stage were poorly differentiated carcinomas (OR: 3.6, p < 0.001), undifferentiated carcinomas (OR: 3.3, p < 0.001), mucinous carcinomas (OR: 0.61, p < 0.001), and perineural invasion (OR: 4.2, p < 0.001). The independent predictors of LVI in pN1‐2 disease were poorly differentiated carcinomas (OR: 2.36, p < 0.001), undifferentiated carcinomas (OR: 3.23, p < 0.001), and perineural invasion (OR: 3.33, p < 0.001). LVI was significantly associated with worse 5‐year OS and the adverse survival impact of LVI was higher in pN1‐2 disease (HR: 1.47, p < 0.001) than in pN0 disease (HR: 1.28, p < 0.001). When LVI was present, the 5‐year OS was reduced by 1.5% in stage I, 5.6% in stage II, and 11.5% in stage III.

Conclusion

LVI was more prevalent in patients with colon cancer with lymph node metastases than in patients with node‐negative disease. However, LVI was not detected in approximately half of patients with nodal disease. The adverse survival effect of LVI was proportional to the stage of colon cancer.
The Differential Effect of Regulatory Signals on Shareholder Dissent: The Case of Shareholder Voting in Director Elections
Authors: Uchida Daisuke , Yoshikawa Toru
Published: January 2025

Research Question/Issue

In the Japanese context of shareholder voting in director elections, this study examines how regulatory signals differently influence shareholder dissent depending on their resource dependence relationship with regulatory bodies.

Research Findings/Insights

We find that the effect of a regulatory change in the disclosure of voting records on shareholder dissent is strengthened as shareholdings by domestic institutional investors increase, while it is mitigated as shareholdings by foreign institutional investors increase. Moreover, we find that this effect is pronounced under conditions where directors seemingly fail to fulfill or to qualify for their role.

Theoretical/Academic Implications

This study develops a resource dependence perspective of shareholder dissent and argues that shareholder dissent can be shaped by regulatory signals from regulatory bodies who provide them with legitimacy. This study enriches the existing insights on corporate governance role of institutional investors by focusing on their resource dependence on regulatory bodies.

Practitioner/Policy Implications

This study sheds light on the dynamic nature of shareholder behavior and suggests that shareholder preferences are not only heterogeneous but also mutable over time in response to regulatory signals. This implies that managers need to pay attention not only to current shareholder preferences but also to future anticipated shareholder preferences to successfully manage their relationships with shareholders.
Association of GLP1R locus with mental ill‐health endophenotypes and cardiometabolic traits: A trans‐ancestry study in UK Biobank
Authors: Hayman Madeleine M. E. , Jones Waneisha , Aman Alisha , Ward Joey , Anderson Jana , Lyall Donald M. , Pell Jill P. , Sattar Naveed , Welsh Paul , Strawbridge Rona J.
Published: January 2025

Aims

Glucagon‐like peptide 1 receptor agonists (GLP1RA), used to treat type 2 diabetes and obesity, have been associated with off‐target behavioural effects. We systematically assessed genetic variation in the GLP1R locus for impact on mental ill‐health (MIH) and cardiometabolic phenotypes across diverse populations within UK Biobank.

Materials and Methods

All genetic variants with minor allele frequency >1% in the GLP1R locus were investigated for associations with MIH phenotypes and cardiometabolic phenotypes. Linear or Logistic regression analyses (adjusted for age, sex, population structure and genotyping chip) were conducted separately in unrelated individuals of self‐reported white British (N = 408 774), white European (N = 50 314), South Asian (N = 7667), multiple‐ancestry groups (N = 10 437) or African‐Caribbean (N = 7641) subsets. All ancestries were subsequently combined in an inverse variance‐weighted fixed effects meta‐analysis. Bonferroni correction for multiple testing was applied (for number of independent genetic variants).

Results

Associations were identified between GLP1R variants and body mass index (BMI), blood pressure and type 2 diabetes in all ancestries. All ancestries except South Asian had significant MIH associations (mood instability: rs111265626‐G, odds ratio [OR] 0.851 [confidence interval, CI 0.79–0.92], risk‐taking behaviour: rs75408972‐T, OR 1.05 [CI 1.03–1.08] or chronic pain: rs9296280‐C, OR 0.645 [CI 0.54–0.78]). The trans‐ancestry meta‐analysis showed mainly consistent effect sizes and directions for metabolic traits, but discordant directions MIH associations. Only signals for chronic pain, stroke and BMI influenced expression of GLP1R.

Conclusions

GLP1R variants have consistent cardiometabolic effects across ancestries, but effects on MIH phenotypes are more varied. Any observed behavioural changes with GLP1RA are likely not acting directly through GLP1R.
The safety, tolerability, pharmacokinetics and pharmacodynamics of an optimized dual GLP‐1/GIP receptor agonist (BGM0504) in healthy volunteers: A dose‐escalation Phase I study
Authors: Fan Yuxin , Yuan Jiandong , Dong Lichun , Yu Chongjing , Ding Haifeng , Xie Daosheng , Guan Runfang , Li Ruixia , Zou Wenhong , Long Shuxian , Chen Jion , Huang Yu , Yang Mei , He Jianchang , Wen Weibo
Published: January 2025

Objective

Previous experiments have demonstrated that BGM0504, a GLP‐1R/GIPR dual agonist drug by molecular dynamics‐guided optimization, had enhanced agonistic activity compared to tirzepatide. This study aims to investigate its safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) in Chinese healthy volunteers.

Methods

A randomized, double‐blind, placebo‐controlled and dose‐escalation Phase I study was conducted as follows: a single dose (2.5 mg) and once‐weekly administration for 2 weeks to reach target doses (5, 10 and 15 mg) by titration.

Results

A total of 40 volunteers received at least one dose of BGM0504 or placebo. The PK profile of BGM0504 was investigated over a wide dose range and supported once‐weekly administration. It was observed that Cmax and AUC of BGM0504 were linearly proportional to the dose from 2.5–15 mg. The change in body weight (%) from baseline in BGM0504 groups was greater than that in the placebo group, with −3.24%, −6.26%, −7.09% and − 8.30% in 2.5, 5, 10 and 15 mg groups, respectively, indicating a certain dose correlation. Meanwhile, the potential roles of BGM0504 in glycaemic control were also observed. The most frequent adverse events reported were gastrointestinal (vomiting, nausea, decreased appetite, diarrhoea and abdominal distension).

Conclusion

BGM0504 was generally safe and well tolerated with favourable PK profile and potential role in weight loss was also confirmed. These findings support subsequent development of BGM0504 for type 2 diabetes mellitus (T2DM) and obesity.
Antiseizure medication use in acute symptomatic seizures: A narrative review
Authors: Yardi Ruta , Vasireddy Rani Priyanka , Galovic Marian , Punia Vineet
Published: January 2025

Acute symptomatic seizures, occurring shortly after a central nervous system insult, constitute nearly half of all seizure cases. However, there is a conspicuous absence of clear, comprehensive, and cohesive guidelines for the management of these seizures with antiseizure medications, especially their duration of use. This lack of consensus on the optimal duration of therapy leads to prolonged treatments that may carry adverse consequences. The primary objective of this narrative review is to present the existing evidence‐based literature on the management of acute symptomatic seizures within the context of the underlying pathologies that trigger them. We explore the risk of developing epilepsy for each specific etiology and identify the factors that influence this risk. Finally, to facilitate decision‐making regarding treatment duration, we categorize acute seizures based on the temporal characteristics of hyperexcitability as acute, subacute, and prolonged. Such a rubric may offer clarity in an area where consensus and guidelines are lacking.
Reasons to be fearful? Rising proportions of positive faecal worm egg counts among UK horses (2007–2023)
Authors: Whitlock Fleur , van Dijk Jan , Hodgkinson Jane E. , Grewar John Duncan , Newton J. Richard
Published: January 2025

Background

Anthelmintic resistance (AR) threatens effective equine parasite control. Quarterly data summaries from faecal worm egg count testing (FWECT) performed by UK laboratories have appeared in Equine Quarterly Disease Surveillance Reports (EQDSR) since 2007, but have not previously been assessed.

Objectives

To assess strongyle FWECT methods and thresholds used by UK laboratories. To investigate factors associated with quarterly laboratory FWECT positivity rates between 2007 and 2023.

Study design

Laboratory surveys and analysis of laboratory summary data.

Methods

Laboratories were surveyed in Q3 2018 and again in Q4 2023. Proportions of FWECTs reported positive (PTP) each quarter by individual laboratories between 2007 and 2023 were analysed using multiple mixed‐effects linear regression, evaluating laboratory‐level random‐effects and fixed‐effects variables for ordered categories of FWECT‐thresholds, year‐quarters and consecutive year groups.

Results

Ten laboratories responded in 2018 and 13 laboratories in 2023. Samples were commonly reported positive at >0 to <100 eggs per gram (epg) and ≥200 epg. Regression modelling of 1190 EQDSR submissions confirmed significantly decreased PTP for thresholds ≥100 to <300 epg (level‐2: −12.0%, p = 0.03), ≥300 epg (level‐3: −18.0%, p = 0.03) and when thresholds were not specified (level‐4: −12.2%, p = 0.0), relative to level‐1 baseline (>0 to <100 epg). No significant seasonal variation in PTP between year‐quarters was evident. Overall, controlling for between‐laboratory variation and FWECT thresholds, there remained evidence for a significant gradient in increasing PTP over the study period relative to baseline (2007–2009). There were increases in PTP of +6.9% in 2010–2011 (p < 0.001), +10.1% in 2012–2013 (p < 0.001), +14.1% in 2014–2015 (p < 0.001), +16.0% in 2016–2017 (p < 0.001), +15.6% in 2018–2019 (p < 0.001), +17.1% in 2020–2021 (p < 0.001) and +18.9% in 2022–2023 (p < 0.001).

Main limitations

Survey responses were limited and most laboratories' FWECT thresholds were not known.

Conclusions

Controlling for laboratories and FWECT thresholds there was strong residual evidence from FWECT summary data for increasing egg counts in UK horses between 2007 and 2023.
WDR74‐Mediated Ribosome Biogenesis and Proteome Dynamics During Mouse Preimplantation Development
Authors: Kakihara Ayaka , Maemura Marino , Hatano Atsushi , Matsumoto Masaki , Tsukada Yu‐ichi
Published: January 2025

Preimplantation embryonic development is orchestrated by dynamic changes in the proteome and transcriptome, regulated by mechanisms such as maternal‐to‐zygotic transition. Here, we employed label‐free quantitative proteomics to comprehensively analyze proteome dynamics from germinal vesicle oocytes to blastocysts in mouse embryos. We identified 3490 proteins, including 715 consistently detected across all stages, revealing stage‐specific changes in proteins associated with translation, protein modification, and mitochondrial metabolism. Comparison with transcriptomic data highlighted a low correlation between mRNA and protein levels, underscoring the significance of non‐transcriptional regulatory mechanisms during early development. Additionally, we analyzed WD repeat‐containing protein 74 (WDR74)‐deficient embryos generated using CRISPR‐Cas9 genome editing. WDR74, a pre‐60S ribosome maturation factor, was found to be critical for ribosome biogenesis and cell division. Furthermore, WDR74 deficiency led to a significant reduction in ribosomal protein large subunit and impaired progression beyond the morula stage. Key ribosomal proteins such as ribosomal protein L24 (RPL24) and ribosomal protein L26 (RPL26), which influence cell division timing, were notably affected, while small subunit proteins remained largely unchanged. Taken together, our study demonstrates the utility of integrating genome editing with proteomic analysis to elucidate molecular mechanisms underlying early embryogenesis, and provides new insights into protein‐level regulation of preimplantation development.
Transnational mobility in Moldova: Exploring socio‐economic triggers for migration aspirations
Authors: Bogdan Ludmila
Published: January 2025

This study examines the relationship between socio‐economic factors and migration aspirations among Moldovans using a mixed‐methods approach. It combines quantitative analysis of demographic and economic variables with qualitative interviews to explore the factors that drive migration considerations. The findings show that economically disadvantaged individuals are less likely to migrate due to concerns about social costs, while wealthier individuals are more inclined to move. Contrary to expectations, social capital, remittances, and overseas networks play a limited role in encouraging migration, often reinforcing the decision to stay. These results challenge existing migration theories and highlight the need to consider Moldova's unique socio‐economic context when analyzing migration aspirations.
Emotional Movement Kinematics Guide Twelve‐Month‐Olds’ Visual, but Not Manual, Exploration
Authors: Rutkowska Joanna M. , Mermier Julia , Meyer Marlene , Bulf Hermann , Turati Chiara , Hunnius Sabine
Published: January 2025

The ability to recognize and act on others' emotions is crucial for navigating social interactions successfully and learning about the world. One way in which others' emotions are observable is through their movement kinematics. Movement information is available even at a distance or when an individual's face is not visible. Infants have been shown to be sensitive to emotions in movement kinematics of transporting actions, like moving an object from one to another place. However, it is still unknown whether they associate the manipulated object with the emotions contained in moving it, and whether they use this information to guide their own exploration of this object. In this study, 12‐month‐old infants watched actors transporting two toys with positive or negative emotional valence. Then, infants were given the possibility to interact with the same toys. We expected the infants to look at and touch the toy handled in a positive manner more, compared to the toy handled in a negative manner. Our results showed that infants looked at the positive toys more than at the negative toys, but that infants touched both toys for the same amount of time. Also, there was no difference in which toy they manually explored first.
Design, Preparation, and Ex Vivo Skin Permeation of Doxepin Microemulsion System for Topical Delivery
Authors: Kaydan Hossein Heidari , Moghimipour Eskandar , Dalvand Hossein , Jamali Nasibeh , Salimi Arghavan , Salimi Anayatollah
Published: January 2025

Background

Doxepin (DX) is used orally to relieve itching but can cause side effects like blurred vision, dry mouth, and drowsiness due to its antimuscarinic effect. To reduce these adverse effects and improve skin permeation, DX is being developed in topical formulations. This study aims to improve DX skin absorption by developing a microemulsion (ME) formulation (ME‐DX).

Method and Materials

ME formulations containing 5% DX were prepared using the phase diagram method with a mixture of essential oil (oleic acid), surfactant (Tween 80 and Labrazol), and cosurfactant (propylene glycol or PG). The physicochemical properties of these formulations were assessed to improve the topical application of DX.

Results

ME droplet sizes ranged from 9.8 to 61.6 nm, with viscosities between 114 and 239 cps. Studies showed a significant correlation between DX release percentages and viscosity. ME‐DX‐2 released 46.51% of the drug after 24 h. Selected ME‐DX formulations demonstrated Weibull, Log Wagner, and zero‐order release kinetics, and improved skin permeability. ME‐DX‐8 exhibited an eightfold increase in Jss and P parameters compared to the control group. MEs maintained 99.9% of DX after 6 months without color changes or phase separation, indicating long‐term stability.

Conclusion

This research demonstrates that altering the content and composition of MEs can change the physicochemical properties and permeability characteristics of DX when introduced into rats. Additionally, ME formulation shows promise as an effective vehicle for topical DX delivery in atopic dermatitis treatment.
It's Amazing – But Terrifying!: Unveiling the Combined Effect of Emotional and Cognitive Trust on Organizational Member' Behaviours, AI Performance, and Adoption
Authors: Vuori Natalia , Burkhard Barbara , Pitkäranta Leena
Published: January 2025

We conducted a qualitative, real‐life study where we tracked the introduction, implementation, and use of a new AI technology in a company. We identified four distinct trust configurations among organizational members: full trust (high cognitive/high emotional), full distrust (low cognitive/low emotional), uncomfortable trust (high cognitive/low emotional), and blind trust (low cognitive/high emotional). Furthermore, we found that organizational members exhibited distinct behaviours under the four trust configurations: Some responded by detailing their digital footprints, while others engaged in manipulating, confining, or withdrawing them. These behaviours triggered a ‘vicious cycle’, where biased (due to manipulation) and unbalanced and asymmetric (due to detailing, confining, or withdrawing) data inputs degraded AI performance, further eroding trust and stalling adoption. Our primary contribution is a model that explains how organizational members behave under different trust configurations and how these behaviours affect AI performance and, ultimately, AI adoption in organizations. We also provide valuable insights for managers.
Simultaneous Activation of Beta‐Oxidation and De Novo Lipogenesis in MASLD‐HCC: A New Paradigm
Authors: Dahboul Fatima , Sun Jihan , Buchard Benjamin , Abeywickrama‐Samarakoon Natali , Pujos‐Guillot Estelle , Durand Stéphanie , Petera Mélanie , Centeno Delphine , Guerrieri Francesca , Cocca Massimiliano , Levrero Massimo , Rossary Adrien , Weil Delphine , Di Martino Vincent , Demidem Aicha , Abergel Armando
Published: January 2025

Background and Aims

Metabolic dysfunction‐associated steatotic liver disease (MASLD) is the most common cause of hepatocellular carcinoma (HCC). In this study, we combine metabolomic and gene expression analysis to compare HCC tissues with non‐tumoural tissues (NTT).

Methods

A non‐targeted metabolomic strategy LC–MS was applied to 52 pairs of human MASLD‐HCC and NTT separated into 2 groups according to fibrosis severity F0F1‐F2 versus F3F4. The expression of genes related to de Novo lipogenesis (DNL) and fatty acid oxidation (FAO) has been analysed by quantitative RT‐PCR and/or interrogation of RNA‐seq datasets in 259 pairs of tissues (MASLD‐HCC vs. VIRUS‐HCC).

Results

Metabolomic analysis revealed that acylcarnitines were the main discriminating metabolites according to fibrosis severity when we compared MASLD‐HCC‐F0F1‐F2 versus NTT and MASLD‐HCC‐F3F4 versus NTT. Based on these metabolomic data, the analysis of a panel of 15 selected genes related to DNL and FAO indicated that there is no difference between the 2 groups of MASLD‐HCC. In contrast the same comparative gene analysis according to the aetiology of HCC: MASLD‐HCC versus VIRUS‐HCC showed that both aetiologies shared the same upregulation of genes involved in DNL. However, five genes involved in FAO (HADHA, CRAT, CPT1, CPT2 and PPARA) are upregulated exclusively in MASLD‐HCC. This result indicates that FAO and DNL pathways are simultaneously activated in MASLD‐HCC in contrast to VIRUS‐HCC.

Conclusions

These results suggest that, the involvement of adaptive metabolic pathways is different depending on the aetiology of HCC. Moreover, the dogma that simultaneous activation of FAO and DNL is incompatible in cancer would not apply to MASLD‐HCC.
Mortality in Autoimmune Liver Disease in Sweden: A Population‐Based Cohort Study of 9,654 Patients
Authors: Lasyte Imante , Widman Linnea , Bergquist Annika , Hagström Hannes
Published: January 2025

Background/Aims

Epidemiological data on mortality in autoimmune liver diseases (AILDs) are scarce. We examined all‐cause and cancer‐related mortality in individuals with AILD from Sweden.

Methods

We identified 9654 individuals with AILD (3342 with autoimmune hepatitis (AIH), 3751 with primary biliary cholangitis (PBC), and 2561 with primary sclerosing cholangitis (PSC)) using national Swedish registries between 2001 and 2020. These were matched with 80 685 comparators from the general population at a ratio of 1:10 on age, sex, year of diagnosis and municipality. Rates of outcomes were estimated using Cox regression models, adjusted for matching factors and cardiovascular disease, diabetes, inflammatory bowel disease, chronic obstructive pulmonary disease, and education.

Results

Individuals with AILD had higher mortality than comparators (adjusted hazard ratio (aHR) = 2.3, 95% CI = 2.2–2.4) and higher rates of cancer‐related death (aHR = 2.1, 95% CI = 1.9–2.3). The presence of liver cirrhosis in AILD was related to even higher mortality, with aHR 5.8 (95% CI = 5.1–6.6). Both males and females with AILD had increased mortality (males aHR = 2.6, 95% CI = 2.4–3.0, and females aHR = 2.2, 95% CI = 2.1–2.3). The mortality was higher in individuals aged 18–50 years (aHR = 4.6, 95% CI = 3.6–5.8), than in individuals above 50 years (aHR = 2.2, 95% CI = 2.1–2.3). Overall mortality rates and cancer‐related death were particularly high in individuals with PSC compared to their matched comparators, with aHR = 4.1 (95% CI = 3.2–5.2) and aHR = 6.4 (95% CI = 4.0–10.3), respectively.

Conclusions

Patients with AILDs have increased rates of overall and cancer‐related mortality compared to matched comparators, and relative risks are highest in cirrhosis, younger age and PSC.
Factors associated with early onset hypocalcemia: A retrospective cohort study
Authors: Shin Baek Sup , Shin Seung Han , Kim Ee‐Kyung , Kim Han‐Suk
Published: January 2025

Background

Early onset hypocalcemia, occurring within 3 days of birth, is prevalent among preterm infants. A central line is required to deliver calcium (Ca). The prediction of hypocalcemia is therefore clinically important when the requirement for initial intravascular calcium administration is anticipated.

Methods

This retrospective study included preterm infants born between 2019 and 2023 with a birthweight <1500 g or a gestational age (GA) <32 weeks in a single tertiary center. Hypocalcemia was defined as serum Ca <7 mg/dL or ionized calcium (iCa) <0.8 mmol/L within 72 h after birth. Perinatal factors and laboratory test results associated with hypocalcemia were collected and analyzed.

Results

Of the 348 infants, 20 died within 7 postnatal days, 22 were transferred to other hospitals, and eight were transferred from other hospitals and were thus excluded. Of 298 enrolled infants, 20 were diagnosed with hypocalcemia. In multivariate analysis, male sex, elevated day 1 phosphorus (d1P), magnesium (d1Mg) levels, and maternal premature rupture of membranes (PROM) were significant risk factors for early onset hypocalcemia. These factors, along with birthweight, a widely recognized risk factor, were used to develop predictive models for early onset hypocalcemia. Among the six suggested models, logistic regression exhibited the highest accuracy. Conversely, the random forest model outperformed others in the Youden index and area under the receiver operating characteristic curve.

Conclusions

In our cohort, early onset hypocalcemia was linked to male sex, lower GA, higher d1P and d1Mg, and maternal PROM. Notably, higher d1P has not been previously reported as a risk factor.
Trends in Specific Family Refusals for Pediatric Organ and Tissue Donation: A Cross‐Sectional Study
Authors: de Souza Danton Matheus , Miranda Niflyer Costa , da Silva Pimentel Rafael Rodrigo , de Moraes Edvaldo Leal , dos Santos Marcelo José
Published: January 2025

Background

When a family decides to donate the organs or tissues of their child with brain death, it is necessary to consider which organs or tissues will be donated. This phenomenon presents an ethical dilemma that is underexplored in the scientific literature, making it essential to examine this context to understand how refusals occur within donations.

Objective

To analyze the rates and trends of specific refusals for each organ and tissue from pediatric donors with brain death occurring between 2001 and 2020 in an Organ Procurement Organization in the State of São Paulo, Brazil.

Methods

This was a cross‐sectional, exploratory, retrospective, quantitative study. Data were derived from a database consisting of copies of organ and tissue donation authorization forms, organized, and subjected to descriptive and inferential analyses. This study adhered to international ethical guidelines.

Results

Data from 109 real donors were analyzed. The bones, skin, and blood vessels had the highest refusal rates among tissues, as well as the pancreas and lungs for solid organs. Most organs and tissues showed a decreasing refusal trend except for the corneas, liver, and kidneys, which exhibited a stationary trend.

Conclusions

This study illustrates the refusals within real donations, with high refusal rates for tissues compared to solid organs.
Living Donor Liver Transplantation for Young Biliary Atresia Recipients Is Associated With Improved Outcomes in the Modern Era
Authors: Ziogas Ioannis A. , Yoeli Dor , Adams Megan A. , Wachs Michael E. , Feldman Amy G. , Taylor Sarah A.
Published: January 2025

Introduction

Biliary atresia (BA) is the most common indication for liver transplantation (LT) in children. We aimed to identify risk factors associated with survival in young patients with BA in the modern era.

Methods

We performed a retrospective analysis of BA patients aged < 2 years who received their first isolated LT with available data from the United Network for Organ Sharing database (01/2013–12/2022). Factors included in the multivariable Cox regression were graft type, race/ethnicity, insurance status, laboratory pediatric end‐stage liver disease (PELD) score, history of portal vein thrombosis, and intensive care unit (ICU) status.

Results

1226 BA LT recipients aged < 2 years were included, of whom 501 (40.9%) received deceased donor whole grafts (DDWG), 425 (34.7%) received deceased donor technical variants (DDTV), and 300 (24.5%) received living donor LT (LDLT). LDLT recipients were more likely to be white (p = 0.008) and have private insurance (p < 0.001). Multivariable analysis demonstrated that ICU status (hazard ratio [HR] = 3.23, 95% confidence interval [95% CI]: 1.72–6.08, p < 0.001) and DDTV graft vs. LDLT (HR = 3.03, 95% CI: 1.14–8.04, p = 0.03) were associated with an increased risk of patient mortality. Factors associated with an increased risk of graft loss included ICU status (HR = 1.89, 95% CI: 1.19–3.00, p = 0.007) and both DDWG (HR = 3.37, 95% CI: 1.65–6.87, p = 0.001) and DDTV (HR = 3.47, 95% CI: 1.69–7.14, p = 0.001) grafts vs. LDLT.

Conclusion

LDLT is associated with improved survival in patients with BA aged < 2 years; however, socioeconomic differences exist between LDLT and non‐LDLT recipients. Efforts to promote early equitable referral to centers offering LDLT are essential for improving outcomes in young children with BA.
CMV Reactivation Following Allogeneic Transplantation in Children From a High‐Seroprevalence Population: A Single‐Center Experience in Colombia
Authors: Arias Andres , Builes Natalia , Niño‐Serna Laura , Diaz Alejandro , Aristizabal Beatriz H. , Trujillo Monica
Published: January 2025

Introduction

Cytomegalovirus (CMV) infection is a frequent complication among hematopoietic stem cell transplant (HSCT) recipients. Data regarding CMV reactivation in children in underdeveloped countries is scarce. This is especially notable considering the increasing utilization of haploidentical‐related HSCT with the post‐transplant cyclophosphamide platform. This study aimed to describe the incidence, clinical characteristics, and evolution of children with CMV reactivation after HSCT and the possible impact of unmanipulated stem cells with PTCy for GvHD prophylaxis.

Methods

Retrospective cohort study of children undergoing hematopoietic stem cell transplantation from January 2012 to June 2022. Baseline characteristics and the clinical course were described. Duration of treatment, initial viral load, and time to clearance of DNAemia by type of transplant were compared using the Kruskal‐Wallis test. Survival analysis was performed with the Kaplan–Meier method and log‐rank test. All statistical analysis was performed using SPSS software, version 20.0.

Results

One hundred sixty‐six children were included. Among them, 87% of recipients and 88% of donors were CMV positive. The cumulative incidence of cytomegalovirus DNAemia was 28% at 100 days post‐transplantation. There were no differences between different donor types. Overall survival at 1 year was 60%, and non‐relapse mortality was observed in 28%. CMV reactivation did not appear to negatively impact 1‐year overall survival (OS).

Conclusions

Our study found no differences in CMV reactivation rates, treatment duration, viral clearance times, co‐infections, or 1‐year overall survival across different HSCT donor types. Studies are needed to establish more precise criteria for monitoring recipients, particularly in regions where unmanipulated stem cells with PTCy for GvHD prophylaxis are increasing.
The Role of Memes in Shaping Political Discourse on Social Media
Authors: AlAfnan Mohammad Awad
Published: January 2025

The article explores the role of memes in shaping political discourse on social media platforms, examining their influence on public opinion, political behavior, and the dynamics of ideological polarization. With the rapid proliferation of meme culture across platforms such as Twitter (X), Instagram, TikTok, and Facebook, memes have emerged as potent tools for political communication, serving as vehicles for political expression and instruments for reinforcing ideological divides. By analyzing political memes’ circulation, engagement, and sentiment, this study reveals how memes predominantly circulate within political echo chambers, fostering increased engagement within ideologically homogenous groups while limiting exposure to opposing viewpoints. Additionally, the emotional resonance of memes and their viral potential contribute significantly to their effectiveness in influencing political opinions and mobilizing support for political movements. However, the study also highlights concerns regarding the spread of misinformation and the role of memes in exacerbating political polarization. The findings suggest that memes facilitate political participation and awareness and challenge democratic discourse by amplifying divisiveness. The article calls for further research into the long-term effects of meme-driven political communication on voter behavior, civic engagement, and democratic processes.
Evaluating the Combined Neurotoxicity of Amyloid Beta and Tau Oligomers in Alzheimer's Disease: A Novel Cellular-Level Criterion
Authors: Kuznetsov Andrey V.
Published: January 2025

A criterion characterizing the combined neurotoxicity of amyloid beta and tau oligomers is suggested. A mathematical model for calculating the value of this criterion during senile plaque and neurofibrillary tangle (NFT) formation is proposed. Computations show that for physiologically relevant parameter values, the value of the criterion increases approximately linearly with time. Once neurofibrillary tangles begin forming in addition to senile plaques, there is an increase in the slope characterizing the rate at which the criterion increases. The critical value of the criterion at which a neuron dies is estimated. Unless the production rates of amyloid beta and tau monomers are very large, computations predict that for the accumulated toxicity to reach the critical value, the neural machinery responsible for the degradation of amyloid beta and tau monomers and aggregates must become dysfunctional. The value of the criterion after 20 years of the aggregation process is strongly influenced by the deposition rates of amyloid beta and tau oligomers into senile plaques and NFTs. This suggests that deposition of amyloid beta and tau oligomers into senile plaques and NFTs may reduce accumulated toxicity by sequestering more toxic oligomeric species into less toxic insoluble aggregates.