bluuebunny/crossref_metadata_2025 huggingface dataset:
Bridgingin vitroandin vivoinsights: A PKPD model for effective phage therapy against multidrug-resistantPseudomonas aeruginosa
Authors: Cha Jun Seok , Kim Kyungnam , You Hwa Jeong , Kim Dasom , Park Hyun Hee , Heo SuJin , Kim Choon Ok , Jin Byung Hak , Yong Dongeun , Chae Dongwoo
Published: December 2024

Bacteriophage therapy provides a promising solution for multidrug-resistantPseudomonas aeruginosa. However, optimizing phage combinations and dosages remains challenging. Here, we developed and validated a pharmacokinetic-pharmacodynamic (PKPD) model integratingin vitroandin vivoefficacy data using three phage strains (MP-A, PP-A, and PP-B), administered both alone and in combination.In vitrophage resistance was substantially delayed by combining phages that exhibit collateral sensitivity. However, multiple phage resistance eventually emerged.In vivo,growth of phage-resistant mutants was minimal. Our model suggests that this outcome was due to an initial phage-induced reduction in bacterial load, followed by immune clearance of the phage-resistant bacteria. Simulations indicated that higher phage exposure at the site of infection caused a faster decline in bacterial levels below the immune clearance threshold and prevented excessive immune activation. Overall, this study offers crucial guidance for treatment strategies and highlights the importance of mathematical modeling in advancing phage therapy.
Internal states emerge early during learning of a perceptual decision-making task
Authors: Cuturela Lenca I. ,   The International Brain Laboratory, Pillow Jonathan W.
Published: December 2024

Recent work has shown that during perceptual decision-making tasks, animals frequently alternate between different internal states or strategies. However, the question of how or when these emerge during learning remains an important open problem. Does an animal alternate between multiple strategies from the very start of training, or only after extensive exposure to a task? Here we address this question by developing a dynamic latent state model, which we applied to training data from mice learning to perform a visual decision-making task. Remarkably, we found that mice exhibited distinct “engaged” and “biased” states even during early training, with multiple states apparent from the second training session onward. Moreover, our model revealed that the gradual improvement in task performance over the course of training arose from a combination of two factors: (1) increased sensitivity to stimuli across all states; and (2) increased proportion of time spent in a higher-accuracy “engaged” state relative to biased or disengaged states. These findings highlight the power of our approach for characterizing the temporal evolution of multiple strategies across learning.
Robust characterization of selectivity of individual neurons to distinct task-relevant behavioral states using calcium imaging
Authors: Huang Huixin , Shah Garima , Adwanikar Hita , Mysore Shreesh P.
Published: December 2024

Investigations into the neural basis of behavior have recently employed fluorescence imaging of calcium dynamics in a variety of brain areas to measure neural responses. However, across studies, diverse and seemingly subjective methodological choices have been made in assessing the selectivity of individual neurons to task-relevant behavioral states. Here, we examine systematically the effect of different choices in the values of key parameters from data acquisition through statistical testing on the inference of the selectivity of individual neurons for task states. We do so by using as an experimental testbed, neuronal calcium dynamics imaged in the medial prefrontal cortex of freely behaving mice engaged in a classic exploration-avoidance task involving spontaneous (animal-controlled) state transitions - navigation in the elevated zero maze (EZM). We report that a number of key variables in this pipeline substantially impact the selectivity label assigned to neurons, and do so in distinct ways. By quantitatively comparing newly defined accuracy and robustness metrics for all the 128 possible combinations of levels of the key parameters, we discover in a data-driven manner, two optimal combinations that reliably characterize neuronal selectivity – one using discrete calcium events and another using continuous calcium traces. This work establishes objective and standardized parameter settings for reliable, calcium imaging-based investigations into the neural encoding of task-states.
Anorectic and anxiogenic actions of cocaine– and amphetamine-regulated transcript in the lateral septum
Authors: Shankhatheertha Anjali , Payant Mikayla A , Phy-Lim Jenny , Chee Melissa J
Published: December 2024

Cocaine-and amphetamine-regulated transcript (CART) is produced in several brain regions including the hypothalamus where it is made in cells that also produce melanin-concentrating hormone (MCH). MCH+CART cells densely innervate the lateral septum (LS), which integrates food– and mood-related behaviours. However, while MCH typically promotes feeding and anxiolysis, CART suppresses feeding and promotes anxiogenesis. The LS is a target site of the orexigenic actions of MCH, but it is not known if the actions of CART converge or oppose that of MCH in the LS. We implanted a bilateral cannula over the lateral or central LS of male and female wildtype mice and infused vehicle, CART55–102, or co-infused CART and MCH. CART did not alter chow intake but suppressed the intake of a palatable high sugar diet in male and female mice, especially when delivered in the medial LS. Furthermore, CART also prevented the orexigenic effect of MCH on palatable feeding intake when infused in the medial LS. We then assessed if CART regulated anxiety-like behaviour via the LS and found that intra-LS CART infusion reduced time spent in the center of an open field in male but not female mice. Our findings indicated that CART elicited anorectic and anxiogenic actions and may function in opposition to or independently of MCH in the LS. These outcomes suggested that putative CART and MCH co-release from MCH neurons may provide biphasic regulation of feeding and anxiety via the LS.
Differential Expression of Edar and Xedar During Mouse and Rat Tail Appendage Development
Authors: Wisniewski Slawomir A.
Published: December 2024

Abstract

Skin appendages, such as hair follicles and scales, represent evolutionary adaptations that vary among different species. Mouse and rat tails exhibit distinct appendage types, with mice developing hair follicles and rats developing scales. The study investigated whether the differential expression of Edar and Xedar, critical regulators of ectodermal development, could explain these distinct developmental outcomes by measuring Edar and Xedar expression in mouse and rat tail tissues during embryonic development using quantitative real-time PCR. Expression levels were normalized to actin and analyzed using mathematical modeling and statistical approaches. It was found that distinct temporal patterns of gene expression between species. Mouse tissues showed a dramatic peak in Xedar expression during days 3-4, coinciding with hair follicle initiation, while rat tissues maintained relatively stable Xedar expression. Edar expression showed opposing trends between species, with a gradual increase in mice and a decrease in rats. These findings provide the first quantitative evidence for species-specific regulation of Edar and Xedar during appendage development, suggesting a molecular basis for determining hair versus scale fate.
Single amino acid mutations in histone H3.3 illuminate the functional significance of H3K4 methylation in plants
Authors: Xue Mande , Ma Lijun , Li Xiaoyi , Zhang Huairen , Liu Qian , Jiang Danhua
Published: December 2024

Although numerous data have revealed correlations between histone modifications and chromatin activities such as transcription, proofs of their causal importance in gene expression regulation remain limited. Sequence variants within each histone family expand chromatin diversity and may carry specific modifications, further raising the question of how histone modifications coordinate with different variants. Here, we investigate the regulatory role of lysine 4 (K4) ofArabidopsishistone H3 by point mutating K4 in two major H3 variants, H3.1 and H3.3. K4 is essential for the function of H3.3 but not H3.1 in plant development. H3K4 methylation levels decrease drastically upon K4 mutation in H3.3, and the associated transcriptome changes are similar to those observed in a mutant lacking SDG2, a major enzyme responsible for depositing H3K4 trimethylation (H3K4me3). Moreover, H3.3K4 and SDG2 are required for de novo gene activation and RNA Pol II elongation. H3K4 methylation is preferentially accumulated on H3.3 compared to H3.1, likely due to the close association of the H3.3 deposition and H3K4 methylation machineries. Furthermore, we reveal the diverse impacts of K4 nearby residue mutations on H3K4 methylation and H3.3 function. Collectively, these findings suggest that H3.3 serves as a critical substrate for H3K4 methylation, which is important for gene expression regulation. In addition, our work highlights the potential of using plants as a platform to directly investigate the importance of histone amino acids and their modifications.
A photorespiratory glyoxylate shunt in the cytosol supports photosynthesis and plant growth under high light conditions in Arabidopsis
Authors: Jiang Xiaotong , Koenig Amanda M. , Walker Berkley J. , Hu Jianping
Published: December 2024

Photorespiration, a central aspect of plant metabolism that is tightly connected to photosynthesis, functions in part to support photosynthetic performance, especially under stress conditions such as high light. However, our understanding of the mechanisms underlying the role and regulation of photorespiration in plant response to high light is limited. To identify modulators of photorespiration under high light, we isolated genetic suppressors of the photorespiratory mutanthpr1, which is defective in the peroxisomal hydroxypyruvate reductase 1. A suppressor that partially rescuedhpr1under high light was mapped toGLYR1, which encodes the cytosolic glyoxylate reductase 1 enzyme that converts glyoxylate to glycolate. IndependentGLYR1loss-of-function mutants also partially rescuedhpr1and another photorespiratory mutant,catalase 2. Our genetic, transcriptomic and metabolic profiling analyses together suggested a novel connection between cytosolic glyoxylate and a non-canonical photorespiratory route mediated by the cytosolic HPR2 enzyme, which we named the photorespiratory glyoxylate shunt. This shunt is especially critical under high light intensities when a high rate of photorespiratory flux is required and in the absence of a properly functional major photorespiratory pathway. Our findings support the metabolic flexibility of photorespiration and may help future efforts to improve crop performance under stress.
Self-exploring automated experiments for discovery, optimization, and control of unsteady vortex-dominated flow phenomena
Authors: Mulleners Karen
Published: December 2024

Typical unsteady vortex-dominated flows like those involved in bio-inspired propulsion, airfoil separation, bluff body wakes, and vortex-induced vibrations can be prohibitively expensive to simulate and impossible to measure comprehensively. These examples are governed by nonlinear interactions, and often involve moving boundaries, high-dimensional parameter spaces, and multiscale flow structures. The classical way to get around these challenges has been to reduce the experimental complexity by using canonical motions or simplified unsteady inflow conditions. A paradigm shift is emerging in the form of self-exploring automated experiments that combine the automation of the experimental pipeline with data-science tools to increase experimental throughput and expedite scientific discovery. Such automated experiments can explore and exploit higher-dimensional parameter spaces and cover more realistic and technically relevant unsteady conditions compared to what is traditionally feasible with supervised canonical experiments. This alternative approach can yield robust and generalizable models and control solutions, as well as the discovery of rare and extreme events. Here, we provide a perspective on the transformative potential of self-exploring automated experiments for the discovery, optimization, and control of unsteady vortex-dominated flow phenomena.

Published by the American Physical Society
2024
Do investors care about carbon emissions? Evidence based on stock return co-movement with machine learning-augmented data
Authors: Li Lucas S. , Zhao Yan
Published: December 2024

Purpose

This paper represents the first attempt to examine investor behavior for green stocks through the lens of return co-movement, and provides evidence indicating that green investment practices have gained traction after 2012.

Design/methodology/approach

We empirically test the hypotheses that the stock returns of firms with similar carbon dioxide emissions levels move together and, if so, whether this co-movement has increased over time as people become more “carbon-conscious.” Our baseline sample, based on carbon emissions data from public company disclosures, suffers from limited coverage, particularly before 2016, leading to low statistical power and sample selection bias. To address this, we employ machine learning methodologies to forecast the carbon emissions of firms that do not disclose such information, nearly quadrupling the sample size. Our findings indicate that stocks with similar carbon emissions exhibit higher co-movement in stock returns in both the baseline and augmented data samples. Furthermore, this co-movement has increased during the 2012–2020 period compared to the 2004–2011 period, suggesting that green investment has gained traction over time.

Findings

We find that stocks with similar carbon emissions exhibit higher co-movement in stock returns in both the baseline sample and the augmented data sample, and the co-movement has increased in the 2012–2020 period compared to the 2004–2011 years, suggesting that green investment has gained traction over time.

Originality/value

(1) We use machine learning methodology to augment carbon emissions sample which goes back to 2004. Our approach almost quadruples the original data, enabling large-sample testing. (2) We are the first paper to examine how green companies' stock returns co-move and thus provide complementary results on the research on expected returns and carbon emissions.
How do team faultlines damage team voice behavior? Comparing the effects of objective and perceived faultlines
Authors: Qiu Yong , Gao Yuting , Liu Jianting , Wang Wenzhou , Tian Yalin , Sun Xiaoran
Published: December 2024

Purpose

The continuous upgrading of new technologies and rapid changes in their external environment have made organizations more dependent than ever on the ability of their employees to quickly identify problems and make timely course corrections. This dependency is not limited to individual employee voice but extends to the collective voice of the team. In the Chinese context, collective silence prevails. Following social identity theory, this study aims to explore the mechanisms and conditional processes underlying the relationship between team faultlines and team voice behavior and examine whether there are differences between the effects of objective and perceived faultlines.

Design/methodology/approach

The proposed model was tested through questionnaires with 377 team members from 71 teams, which were conducted through team leader–member pairing survey. The correlation and hierarchical stepwise regression analyses were used to test the hypotheses rigorously, and the questionnaire data was analyzed using SPSS 26.0, AMOS 25.0 and R 3.6.1.

Findings

The results show that both objective and perceived faultlines have a negative impact on team voice behavior and that the latter has a stronger negative effect. Team psychological safety mediates the relationship between team faultlines and team voice behavior. In addition, benevolent leadership, moral leadership and Zhongyong thinking positively moderate the negative effect of objective faultlines on team voice behavior; Zhongyong thinking also moderates the mediating effect of team psychological safety on the relationship between objective faultlines and team voice behavior.

Originality/value

The results of this study provide a deeper understanding of team faultlines and team voice behavior, and practical implications are provided for managers and future researchers to improve voice behavior in organizations.
Cultural intelligence and cooperation in the construction industry: the mediating role of trust
Authors: Paing Kyaw Kyaw , Dodanwala Tharindu C. , Santoso Djoen San
Published: December 2024

Purpose

This study aims to investigate the mediating role of trust in the relationship between cultural intelligence (CQ) and cooperation among construction professionals. Furthermore, this study assesses perceived differences in CQ, trust and cooperation between individuals with and without experience working with foreigners in the construction industry.

Design/methodology/approach

Data were gathered from a cross-sectional survey of 408 engineers in Myanmar’s construction industry. A confirmatory factor analysis validated structural equation modeling approach was used to address research hypotheses, and an independent samples t-test was performed to identify the perceived differences between two categories of respondents.

Findings

The structural equation modeling results identified CQ as a positive direct predictor of cooperation, affect-based trust and cognition-based trust. Both affect-based trust and cognition-based trust directly and positively influenced cooperation. The relationship between CQ and cooperation was partially mediated by affect-based trust and cognition-based trust. The findings of the independent samples t-test revealed that construction employees with prior experience working with foreigners tend to exhibit a higher level of CQ, trust and cooperation than their counterparts.

Originality/value

The present study added the mediating role of trust in CQ and cooperation linkage, an area that has received limited attention in the literature.
The role of women in HRM in family SMEs
Authors: Flamini Giulia , Morelli Chiara , Gnan Luca , Cori Enrico
Published: December 2024

Purpose

This study tries to free women from the “invisible role” prison and understand the different managerial goals and styles adopted by males and females in family small and medium enterprises (SMEs) in managing employees. In particular, this paper grasps the complexity of the relationship between women’s leadership positions and configurational human resource management (HRM) practices in family SMEs.

Design/methodology/approach

The authors use the qualitative fuzzy set comparative analysis (fsQCA) on 623 small and medium Italian family businesses to explore women’s contributions and impacts on adopting HRM practices and business performance.

Findings

The findings confirm that gender-specific leadership styles influence the adoption of distinct bundles of HRM practices and ultimately affect organizational performance in family SMEs. Indeed, women in the family SME social context, to meet certain gender expectations, are more likely to implement steward-oriented HRM practices. This reinforces the role of women as key players in improving organizational performance by adopting people-centered HRM practices that promote employee satisfaction and retention.

Originality/value

Using the fsQCA analysis and the gender theory, family business and HRM literature, the paper investigates the role of women in Italian family SMEs as CEOs or HR managers in implementing HR management practices to achieve good organizational performance.
Exploitative leadership and green innovative behavior of hospitality employees: mediation of emotional exhaustion and moderation of perceived organization support
Authors: Sahibzada Yaseen Ahmad , Ali Muhammad , Toru Naveed , Farooq Jan Muhammad , Ellahi Abida
Published: December 2024

Purpose

This study aimed to investigate the relationship between exploitative leadership (EL) and employee green innovative behavior (GIB) in the hospitality sector organizations of Pakistan. The relationship between EL and GIB is mediated by emotional exhaustion (EE). Perceived organizational support (POS) is used as a moderator between EL and EE.

Design/methodology/approach

The study used convenience and purposive sampling techniques from the population, and the data collected on the structured questionnaire were analyzed through structural equation modeling (SEM) using SmartPLS. The data analysis involved the assessment of the measurement model and structural model.

Findings

The results of the data analysis show that EL has a significant and negative influence on employee GIB, and EE mediates the relationship, meaning EE caused by EL lowers GIB. The moderating effect of perceived organization support between EL and EE also lowers the effects of EL and diminishes EE leading to increased GIB.

Practical implications

The findings of the study suggest that organizations in the hospitality sector like hotels and resorts need to focus on the POS to curb EE in employees due to EL to accelerate positive attitudes at work. Investments of resources in this avenue can enhance employee engagement and improve organizational performance while contributing to environmentally sustainable goals.

Originality/value

The originality of the study lies in the findings that in the presence of higher perceived organization support, the negative effects of EL are mitigated, and this leads to the replenishment of the emotional resources of employees, which allows them to engage in GIBs. GIB is a term that is being researched by the scholars in the hospitality industry of Pakistan. Conservation of natural resources is only possible through individual efforts, especially the efforts of individuals whose livelihoods depend on environmentally related industries, such as hospitality.
How intentions to use of OGD and respective portals changed over time: evidence from a three-year study among Czech students
Authors: Lnenicka Martin , Machova Renata
Published: December 2024

Purpose

Building an open data ecosystem is a long-term process during which it is necessary to collect feedback so that its development corresponds to the preferences and needs of users. The purpose of this paper is to provide findings and recommendations on how the intentions to use of Open Government Data (OGD) and OGD portals by Czech students evolved over the three years period from 2021 to 2023.

Design/methodology/approach

A mixed research approach was used to conduct the research study and to collect input data. A methodology followed the behavioural intention-based analysis using the model developed by Lnenicka et al. (2022) to analyse relationships between respective constructs and test the hypotheses. Each cycle of data collection using structured questionnaires was supplemented with semi-structured interviews to get students’ feedback on the findings.

Findings

The findings revealed that intentions to use of OGD and OGD portals by Czech students slightly decrease every year. Although students believe that using OGD is beneficial, can increase their performance and productivity, as well as they are influenced by other people to try to (re)use OGD, they miss concrete support above their daily activities in which they could use OGD. Therefore, we provided recommendations to improve their (re)use such as linking OGD with life events to show their usefulness for concrete life situations and activities.

Originality/value

The study provides insights into how intentions to use of OGD and OGD portals among Czech students evolved over the years and what should be the actions to consider improving the level of use. It provides governments on all administrative levels the recommendations for further improvements and actions to promote and stimulate the (re)use of OGD by students as well as other stakeholders.
An examination of the valuation process in a low transparent property market – perspectives of property valuers in Nigeria
Authors: Adilieme Chibuikem Michael , Abidoye Rotimi Boluwatife , Lee Chyi Lin
Published: December 2024

Purpose

The finance sector and property market challenges in some global regions have been linked to inefficient property valuation practices. As a result, global valuation professional organisations have set up standards and norms to promote efficient and transparent operations in the property valuation industry. Despite these concerns, valuation industries in some countries still face challenges that threaten their smooth operations. One of such is Nigeria, which faces various problems attributable to its valuation process and regulatory system. Consequently, this paper aims to examine the valuation process in Nigeria with a bid to identify the weaknesses in its valuation process and how it contributes to problems identified in the literature.

Design/methodology/approach

A qualitative research approach was adopted, and semi-structured interviews were conducted with 12 valuers across different segments of the valuation industry in Nigeria. The data were subjected to thematic analysis using Nvivo 12 software.

Findings

Our findings indicate a fundamentally weak valuation system and regulatory system marked by an opaque engagement process, underpricing of valuation services, inefficient domestication of international valuation standards, poor implementation and monitoring system and concerns about the training and certifications to meet global norms. These identified weaknesses contribute to and fuel problems such as client influence and valuation inaccuracy, among others.

Practical implications

The study has some implications for the valuation professional organisations in Nigeria. The valuation professional organisations should devise systems and enact standards that go beyond solely replicating the IVS and RICS Red Book to effective domestication to suit local norms. Given the inefficient implementation and monitoring system, the use of proptech that supplements legal instruments needs to be adopted. Furthermore, the regulations should be strengthened in line with the trends of sustainability, duty of care and use of data as advocated by the IVSC. This will promote trust in the system and allow global stakeholders to transact more confidently with the Nigerian industry, as the current set-up does not evoke sufficient confidence in the system to deliver excellent and transparent valuation assignments.

Originality/value

This study provides perspective from an untransparent property market on the implications of a poor regulatory system and valuation process for valuers and stakeholders who may rely on valuations conducted in such an environment for decision-making. The findings from this study potentially provide input for the valuation professional organisation in Nigeria in identifying the gaps in their framework and current practices and providing some suggestions to promote improvements.
Epidemiological Survey of Canine Distemper Virus Infection: Exploring the Link Between Virus Spread and Invasive Raccoon (Procyon lotor) Population Growth in Hokkaido, Japan
Authors: Minamikawa Miku , Ito Mebuki , Kovba Anastasiia , Kobayashi Yumi , Abe Go , Kooriyama Takanori , Maeda Ken , Shimozuru Michito , Tsubota Toshio , Sashika Mariko
Published: December 2024

Invasive raccoons (Procyon lotor) naturalized in Hokkaido, Japan, potentially spreading infectious diseases. Canine distemper virus infection is a serious epizootic disease, for which the raccoon is one of the hosts. We investigated the virus's prevalence in Hokkaido's wild raccoons, using 611 serum samples collected from captured raccoons in 2007–2012, 2021, and 2022. Higher seropositivity rates were confirmed in 2007 (32.7%), 2021 (46.4%), and 2022 (46.8%) than in 2008–2012 (0.00%–6.06%), suggesting the occurrence of an epidemic in 2007, 2021, and 2022 and its disappearance in 2008–2012. However, the infection status has recently changed, with high seropositivity rates consecutively confirmed in 2021 and 2022. Logistic regression analysis was performed to investigate the relationships among the catch per unit effort (an index of animal population density), host and environmental factors, and antibody status. The catch per unit effort correlated with seropositivity in 2007. As for environmental factors, the forest area ratio had a weak influence on seroprevalence in 2007; however, the residential area ratio had a clear influence on seroprevalence in 2021 and 2022. The epidemic occurred in forested areas in 2007; nonetheless, recent raccoon population growth and habitat expansion may have caused widespread infections even around residential areas in 2021 and 2022. Continuous monitoring of the infection and reinforcement of raccoon control programs are necessary to avoid serious damage through disease transmission to sympatric native raccoon dog (Nyctereutes procyonoides) and fox (Vulpes vulpes) populations, as well as health consequences for domestic dogs (Canis familiaris).
Prediction of suicide attempt in a Swedish population‐based cohort
Authors: Lannoy Séverine , Ohlsson Henrik , Stephenson Mallory , Kendler Kenneth S. , Sundquist Jan , Sundquist Kristina , Edwards Alexis C.
Published: December 2024

Background

Suicidal behaviors are prevalent public health concerns, and we need to improve our predictive ability to better inform prevention efforts.

Methods

Using nationwide longitudinal Swedish registers, we included 344,490 males and 323,177 females born 1982–1990 with information on genetic liability and environmental exposures from birth to age 16: perinatal variables, parental psychopathology (suicide attempt, substance use disorder, major depression), family status, socioeconomic difficulties, peers' psychopathology, and school grades. We conducted sex‐specific analysis and developed data‐driven predictive models including risk factors that occurred between ages 0 and 16 using structural equation modeling.

Results

In both females and males, the best‐fitting models reveal a complex risk pathway to suicide attempt. In females, the model indicates four direct effects on suicide attempt risk: the occurrence of suicide attempt in parents during childhood (β = 0.159, 95% CI: 0.118; 0.199) and adolescence (β = 0.115, 95% CI: 0.077; 0.153), suicide attempt in peers (β = 0.068, 95% CI: 0.057; 0.079), and low academic achievement (β = 0.166, 95% CI: 0.156; 0.175). In males, aggregate genetic liability for suicide attempt (β = 0.130, 95% CI: 0.111; 0.148), suicide attempt in parents during adolescence (β = 0.099, 95% CI: 0.074; 0.124), suicide attempt in peers (β = 0.118, 95% CI: 0.108; 0.129), and low academic achievement (β = 0.61, 95% CI: 0.152; 0.171) were related to later suicide attempt. These factors also acted as mediators to explain the association between environmental exposures in childhood and later suicide attempt.

Conclusions

These findings illustrate sex‐specific pathways to suicide attempt by including risk factors that occur during the development. Results highlight the importance of genetic and family environment but also the prominent role of academic achievement.
A simulation study to assess the influence of population pharmacokinetic model selection on initial dosing recommendations of vancomycin in neonates
Authors: El Hassani Mehdi , Blouin Mathieu , Marsot Amélie
Published: December 2024

Aims

The accuracy of model‐informed precision dosing largely depends on selecting the most appropriate population pharmacokinetic (popPK) model from many available options. This study aims to evaluate the concordance of optimal initial simulated doses among various vancomycin popPK models developed in neonates and to explore the role of predictive performance in explaining the variability in probability of target attainment (PTA).

Methods

A virtual neonatal patient population was created and 26 previously externally evaluated vancomycin popPK models were used to simulate 5 different dosing regimens. For each simulated scenario, the area under the concentration–time curve and PTA were calculated to assess the agreement on optimal initial doses across the 26 models. A multiple regression was performed to explore the impact of the models' predictive performance on PTA.

Results

For most models (15/26), there was an agreement on the optimal dosing regimen. The highest PTA being achieved by the model with the best a priori predictive performance. The multiple regression model significantly predicted mean ln‐transformed PTA, with F(2, 23) = 5.406 and P = .010, yielding an adjusted R2 of .21. PTA was significantly influenced by imprecision (P = .048) but not bias (P = .469).

Conclusion

In conclusion, our study demonstrated that, despite the variability in bias and imprecision, there was a consensus on the initial optimal doses for the majority of models; however, models with superior a priori predictive performance yielded higher PTA values. Bias and imprecision alone only seem to predict a small proportion of the variability in PTA, with imprecision having a more pronounced effect.
Mechanopharmacology: in vitro techniques to advance drug discovery
Authors: Zielinski Jana L. , Lee Chiao Hwei , Gunatilaka Avanka , Gao Bryan , Stewart Alastair G.
Published: December 2024

Mechanopharmacology is an emerging interdisciplinary field that investigates drug action using biomechanically appropriate in vitro systems to the relevant (patho)physiology. This review outlines emerging technologies and techniques which aim to bridge the gap between mechanical cues influencing cellular biology and conventional pharmacology. We delve into the impact of mechanopharmacology on drug development in cancers and fibrotic diseases. Mechanical cues such as stretch, stiffness, circadian rhythms, fluid flow, intercellular signalling cascades and cytoskeletal structures can modulate drug interactions with molecular targets with implications for drug discovery and development. Models incorporating mechanopharmacological cues to investigate pharmacokinetics, pharmacodynamics and therapeutic outcomes are outlined. Furthermore, this review discusses innovations in the use of biomaterials and microfluidics to further enable the emulation of the mechanical microenvironment. We advocate for the application of mechanopharmacological considerations to improve the physiological relevance of methods used in the drug discovery pipeline.
Multi‐omics revealed that DCP1A and SPDL1 determine embryogenesis defects in postovulatory ageing oocytes
Authors: Kong Li , Gong Yutian , Wang Yongyong , Yuan Mengjiao , Liu Wenxiang , Zhou Heyang , Meng Xiangyue , Guo Xinru , Liu Yongbin , Zhou Yang , Zhang Teng
Published: December 2024

Growing evidence indicates that the deterioration of egg quality caused by postovulatory ageing significantly hampers embryonic development. However, the molecular mechanisms by which postovulatory ageing leads to a decline in oocyte quality have not been fully characterized. In this study, we observed an accelerated decay of maternal mRNAs through RNA‐seq analyses in postovulatory‐aged (PostOA) oocytes. We noted that these downregulated mRNAs should be degraded during the 2‐cell stage. Proteomic analyses revealed that the degradation of maternal mRNAs is associated with the accumulation of DCP1A. The injection of exogenous Dcp1a mRNA or siRNA into MII stage oocytes proved that DCP1A could accelerate the degradation of maternal mRNAs. Additionally, we also found that SPDL1 is crucial for maintaining spindle/chromosome structure and chromosome euploidy in PostOA oocytes. Spdl1‐mRNA injection remarkably recovered the meiotic defects in PostOA oocytes. Collectively, our findings provide valuable insights into the molecular mechanisms underlying postovulatory ageing.
Structural and molecular insights of two unique enzymes involved in the biosynthesis of a natural halogenated nitrile
Authors: Chen Chun‐Chi , Li Hao , Huang Jian‐Wen , Guo Rey‐Ting
Published: December 2024

Organohalogen compounds exhibit wide‐ranging bioactivities and potential applications. Understanding natural biosynthetic pathways and improving the production of halogenated compounds has garnered significant attention. Recently, the biosynthetic pathway of a cyanobacterial neurotoxin, aetokthonotoxin, was reported. It contains two unique enzymes: a single‐component flavin‐dependent halogenase AetF and a new type of nitril synthase AetD. The crystal structures of these enzymes in complex with their cofactors and substrates that were recently reported will be presented here. The AetF structures reveal a tri‐domain architecture, the transfer direction of the hydride ion, a possible path to deliver the hypohalous acid, and the unusual bispecific substrate‐recognition mode. The AetD structures demonstrate that the nitrile formation should occur through the action of a diiron cluster, implying that the enzyme should be capable of catalyzing the nitrile formation of alternative amino acids. This information is of central importance for understanding the mechanism of action as well as the applications of these two the‐first‐of‐its‐kind enzymes.
Effect of different sintering process on mechanical properties and microstructure of TiB2‐TiN‐based cermet material
Authors: Han Zhengyi , Xiao Guangchun , Chen Hui , Yi Mingdong , Zhang Jingjie , Chen Zhaoqiang , Xu Chonghai
Published: December 2024

TiB2‐TiN‐NiTi cermet material was prepared by spark plasma sintering technology (SPS). The effects of the sintering process on their relative density, mechanical properties, and microstructure were studied with 74TiB2‐20TiN‐6NiTi as the composition system. The results showed that TiB2‐TiN‐based cermet material with the best mechanical properties was prepared under the sintering temperature of 1650°C and the holding time of 5 min. The relative density, flexural strength, fracture toughness, and hardness are 97.7%, 762.7 MPa, 5.5 MPa·m1/2, and 18.47 GPa, respectively. However, if the holding time keeps for 3 min under the sintering temperature of 900°C and then 5 min under the sintering temperature of 1650°C, the relative density, flexural strength, fracture toughness, and hardness of TiB2‐TiN‐based cermet reach 99.1%, 931.3 MPa, 5.8 MPa·m1/2, and 19.15 GPa, respectively. In comparison, they have been greatly improved by 1.4%, 22.1%, 5.5%, and 3.7%, respectively. The final holding time can also affect the mechanical properties of TiB2‐TiN‐based cermet material. When it is higher than 5 min, it will cause irregular growth and abnormal growth of grains, which can decrease the flexural strength of TiB2‐TiN‐based cermet material.
Face‐Looking as a Real‐Time Process in Mind‐Mindedness: Timely Coordination Between Mothers' Gaze on Infants' Faces and Mind‐Related Comments
Authors: Yamamoto Hiroki , Sunahara Nagomi , Kanakogi Yasuhiro
Published: December 2024

Maternal mind‐mindedness refers to a caregiver's tendency to respond to their infants as individuals with their own thoughts, feelings, desires, and beliefs. Although previous studies have focused on maternal speech in quantifying mind‐mindedness, maternal mind‐mindedness should manifest not only as mind‐related comments but also through non‐verbal behaviors during infant‐mother interactions. In this study, we investigated the relationship between maternal gaze at the infant's face and typical verbal measurement of mind‐mindedness in free‐flowing interactions. Forty 11‐ to 13‐month‐old infants and their mothers participated in the study; the mothers were asked to wear a head‐mounted eye tracker to measure their gaze during infant‐mother free‐play interactions. We measured the proportion of time mothers looked at the infant's face when it was present in the mother's field of view and examined the relationship between the face‐looking proportion and verbal measurement of mothers' mind‐mindedness. Mothers who displayed appropriate mind‐related comments looked at the faces of their infants more frequently. Moreover, their looking was coordinated in a timely manner with appropriate mind‐related comments compared with other comments. Our findings suggest that mothers looking at infants' faces supports comments regarding infants' mental states and shed new light on real‐time behaviors underlying mothers' mentalization processes.
Contribution of childhood lead exposure to psychopathology in the US population over the past 75 years
Authors: McFarland Michael J. , Reuben Aaron , Hauer Matt
Published: December 2024

Background

More than half of the current US population was exposed to adverse lead levels in childhood as a result of lead's past use in gasoline. The total contribution of childhood lead exposures to US‐population mental health and personality has yet to be evaluated.

Methods

We combined serial, cross‐sectional blood–lead level (BLL) data from National Health and Nutrition Examination Surveys (NHANES) with historic leaded‐gasoline data to estimate US childhood BLLs from 1940 to 2015 and calculate population mental‐health symptom elevations from known lead‐psychopathology associations. We utilized five outcomes: (1) General Psychopathology “points”, reflecting an individual's liability to overall mental disorder, scaled to match IQ scores (M = 100, SD = 15); (2) Symptoms of Internalizing disorders (anxiety and depression) and Attention‐deficit/Hyperactivity Disorder (AD/HD), both z‐scored (M = 0, SD = 1); and (3) Differences in the personality traits of Neuroticism and Conscientiousness (M = 0, SD = 1).

Results

Assuming that published lead‐psychopathology associations are causal and not purely correlational: We estimate that by 2015, the US population had gained 602‐million General Psychopathology factor points because of exposure arising from leaded gasoline, reflecting a 0.13‐standard‐deviation increase in overall liability to mental illness in the population and an estimated 151 million excess mental disorders attributable to lead exposure. Investigation of specific disorder‐domain symptoms identified a 0.64‐standard‐deviation increase in population‐level Internalizing symptoms and a 0.42‐standard‐deviation increase in AD/HD symptoms. Population‐level Neuroticism increased by 0.14 standard deviations and Conscientiousness decreased by 0.20 standard deviations. Lead‐associated mental health and personality differences were most pronounced for cohorts born from 1966 through 1986 (Generation X).

Conclusions

A significant burden of mental illness symptomatology and disadvantageous personality differences can be attributed to US children's exposure to lead over the past 75 years. Lead's potential contribution to psychiatry, medicine, and children's health may be larger than previously assumed.
Regulatory Capital Management to Exceed Thresholds
Authors: OROZCO LUCIANA , RUBIO SILVINA
Published: December 2024

We investigate whether a carrot approach, which provides benefits for regulatory compliance rather than penalties for noncompliance, incentivizes banks to reach capital levels above the minimum requirements. We document a significant discontinuity at the 10% regulatory capital threshold, where banks receive benefits for exceeding it. Banks exceed it to pay lower deposit insurance fees, access brokered deposits, and expanded financial activities. Banks often rely on equity to reach this threshold while using accounting discretion primarily when facing small capital shortfalls. Our findings suggest the carrot approach can effectively increase banks' capital positions. However, we find that using accounting discretion to exceed the threshold hurts bank stability.
Mechanical properties of bone cells studied by atomic force microscopy
Authors: Zhang Xiaoqi , Wang Zuobin , Yu Haiyue , Tao Zengren , Ji Wei
Published: December 2024

Osteoblasts are the functional cells capable of bone formation in the bone microenvironment and play an important role in bone growth, development, and the maintenance of bone mass. The cells cultured in vitro are derived from preosteoblasts in tissues and possess the ability to divide and proliferate. Osteoblasts form the bone matrix by secreting collagen and other matrix proteins, which provides a foundation for the deposition of minerals such as calcium and phosphorus, ultimately resulting in the formation of hard bone tissue. Bone diseases affect the quality of life and the aging of the population. Bone diseases such as osteoporosis, fractures, bone tumours, and arthritis have a significant impact on quality of life, especially among the elderly population. These realities remind us that we should pay more attention to bone and joint health. Therefore, it is particularly important to study the imaging and characterisation of mechanical properties of bone cells, which provides a basis for the research of bone diseases in human beings.
Perspectives of Patients Regarding Artificial Intelligence and Its Application in Healthcare: A Qualitative Study
Authors: Tursynbek Alma , Zhaksylykova Dilnaz , Cruz Jonas Preposi , Balay‐odao Ejercito Mangawa
Published: December 2024

Background

Artificial intelligence integration into healthcare has gained significant attention in recent years, with its use ranging from disease diagnosis to surgical assistance. While artificial intelligence's potential to improve patient outcomes and optimise patient care is undeniable, concerns regarding privacy, transparency, and the potential for medical errors persist. To take full advantage of artificial intelligence's transformative abilities, understanding patient perceptions and attitudes towards its integration into medicine is crucial for ethical considerations and health outcomes.

Purpose

This study aimed to describe patients' perceptions of medical artificial intelligence and its integration into the healthcare system, drawing attention to a crucial yet understudied aspect of artificial intelligence adoption in Kazakhstan.

Design

Descriptive qualitative design.

Method

From February to March 2024, the researchers conducted semi‐structured interviews amongst 13 patients. The interviews were audio‐recorded, transcribed, translated, and then analysed using a thematic analysis approach. The study adhered to the COREQ guidelines.

Result

Five themes emerged from 13 interviews: the benefits of artificial intelligence on patient care, the importance of human factors on patient care over artificial intelligence, revolutionising patient care delivery through artificial intelligence, patient education and artificial intelligence, and balancing technology and human interaction in artificial intelligence‐driven intervention.

Conclusion

Patient perceptions of artificial intelligence integration into healthcare were primarily positive. Nevertheless, patients prefer artificial intelligence as a supplementary tool under human supervision due to risks such as possible medical errors and violations of patient privacy.

Patient or Public Contribution

Patients provided the data for this study. The researchers interviewed them about their perceptions of medical artificial intelligence and its integration into the healthcare system. The patients or the public contributed nothing to the other aspects of the study.