bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping genes for human face shape: exploration of univariate phenotyping strategies
Authors: Yuan Meng , Goovaerts Seppe , Vanneste Michiel , Matthews Harold , Hoskens Hanne , Richmond Stephen , Klein Ophir D , Spritz Richard A , Hallgrimsson Benedikt , Walsh Susan , Shriver Mark D , Shaffer John R , Weinberg Seth M , Peeters Hilde , Claes Peter
Published: June 2024

Human facial shape, while strongly heritable, involves both genetic and structural complexity, necessitating precise phenotyping for accurate assessment. Common phenotyping strategies include simplifying 3D facial features into univariate traits such as anthropometric measurements (e.g., inter-landmark distances), unsupervised dimensionality reductions (e.g., principal component analysis (PCA) and auto-encoder (AE) approaches), and assessing resemblance to particular facial gestalts (e.g., syndromic facial archetypes). This study provides a comparative assessment of these strategies in genome-wide association studies (GWASs) of 3D facial shape. Specifically, we investigated inter-landmark distances, PCA and AE-derived latent dimensions, and facial resemblance to random, extreme, and syndromic gestalts within a GWAS of 8,426 individuals of recent European ancestry. Inter-landmark distances exhibit the highest SNP-based heritability as estimated via LD score regression, followed by AE dimensions. Conversely, resemblance scores to extreme and syndromic facial gestalts display the lowest heritability, in line with expectations. Notably, the aggregation of multiple GWASs on facial resemblance to random gestalts reveals the highest number of independent genetic loci. This novel, easy-to-implement phenotyping approach holds significant promise for capturing genetically relevant morphological traits derived from complex biomedical imaging datasets, and its applications extend beyond faces. Nevertheless, these different phenotyping strategies capture different genetic influences on craniofacial shape. Thus, it remains valuable to explore these strategies individually and in combination to gain a more comprehensive understanding of the genetic factors underlying craniofacial shape and related traits.

Author Summary

Advancements linking variation in the human genome to phenotypes have rapidly evolved in recent decades and have revealed that most human traits are influenced by genetic variants to at least some degree. While many traits, such as stature, are straightforward to acquire and investigate, the multivariate and multipartite nature of facial shape makes quantification more challenging. In this study, we compared the impact of different facial phenotyping approaches on gene mapping outcomes. Our findings suggest that the choice of facial phenotyping method has an impact on apparent trait heritability and the ability to detect genetic association signals. These results offer valuable insights into the importance of phenotyping in genetic investigations, especially when dealing with highly complex morphological traits.
Learning the natural history of human disease with generative transformers
Authors: Shmatko Artem , Jung Alexander Wolfgang , Gaurav Kumar , Brunak Søren , Mortensen Laust , Birney Ewan , Fitzgerald Tom , Gerstung Moritz
Published: June 2024

Decision-making in healthcare relies on the ability to understand patients’ past and current health state to predict, and ultimately change, their future course. Artificial intelligence (AI) methods promise to aid this task by learning patterns of disease progression from large corpora of health records to predict detailed outcomes for an individual. However, the potential of AI has not yet been fully investigated at scale.

Here, we modify the GPT (generative pretrained transformer) architecture to model the temporal progression and competing nature of human diseases in a population scale cohort. We train this model, termed Delphi-2M, on data from 0.4 million participants of the UK Biobank and validate it using external data from 1.9 million Danish individuals with no change in parameters.

Delphi-2M predicts the rates of more than 1,000 different ICD-10 coded diseases and death, conditional on each individual’s past disease history, age, sex and baseline lifestyle information, and with accuracy comparable to existing single-disease models. Delphi-2M’s generative nature also enables sampling future health trajectories at any point within an individual’s life course with outcomes across the entire disease spectrum. Sampled health trajectories provide meaningful estimates of future disease burden for up to 20 years and enable training AI models which have never seen actual data.

Explainable AI methods provide insights into Delphi-2M’s predictions, revealing temporal clusters of co-morbidities within and across different disease chapters and their time-dependent consequences on the future health course. These analyses, however, also reveal that biases underlying the available training data, which in the case of the UK Biobank stem from distinct healthcare sources, are learned and highlighted.

In summary, GPT-based models appear well suited for predictive and generative health-related tasks, are applicable to population scale health data sets and provide insights into the temporal dependencies of past events that shape future health, impacting our ability to obtain an instantaneous view of personalised health state.
Human iPSC-derived pericyte-like cells carrying APP Swedish mutation overproduce beta-amyloid and induce cerebral amyloid angiopathy-like changes
Authors: Wu Ying-Chieh , Lehtonen Šárka , Trontti Kalevi , Kauppinen Riitta , Kettunen Pinja , Leinonen Ville , Laakso Markku , Kuusisto Johanna , Hiltunen Mikko , Hovatta Iiris , Freude Kristine , Dhungana Hiramani , Koistinaho Jari , Rolova Taisia
Published: June 2024

Alzheimer’s disease (AD) patients often exhibit cerebral amyloid angiopathy (CAA), i.e beta-amyloid (Aβ) accumulation within cerebral blood vessels causing cerebrovascular dysfunction. Pericytes wrap around vascular capillaries, thus regulating cerebral blood flow, angiogenesis, and vessel stability. Vascular dysfunction can promote the development and progression of neurodegenerative diseases, yet the specific contribution of pericytes to AD pathology remains unclear. Here we show that human induced pluripotent stem cell (iPSC)-derived pericyte-like cells (iPLCs) can generate Aβ peptides, and that the cells carrying Swedish mutation in amyloid precursor protein (APPswe) secrete 10 times more Aβ1-42 than the control cells. Additionally, APPswe iPLCs have an impaired capacity to support angiogenesis and barrier integrity, exhibit a prolonged contractile response, and produce increased levels of pro-inflammatory cytokines upon inflammatory stimulation. These functional alterations in APPswe iPLCs are accompanied by transcriptional upregulation of actin cytoskeleton and extracellular matrix organization-related genes. Therefore, the APPswe mutation in iPLCs recapitulates several features of CAA pathologyin vitro. Our iPSC-based vascular cell model may thus serve as a platform for drug discovery targeting vascular dysfunction in AD.
Toward telomere-to-telomere cat genomes for precision medicine and conservation biology
Authors: Murphy William J. , Harris Andrew J.
Published: June 2024

Genomic data from species of the cat family Felidae promise to stimulate veterinary and human medical advances, and clarify the coherence of genome organization. We describe how interspecies hybrids have been instrumental in the genetic analysis of cats, from the first genetic maps to propelling cat genomes toward the T2T standard set by the human genome project. Genotype-to-phenotype mapping in cat models has revealed dozens of health-related genetic variants, the molecular basis for mammalian pigmentation and patterning, and species-specific adaptations. Improved genomic surveillance of natural and captive populations across the cat family tree will increase our understanding of the genetic architecture of traits, population dynamics, and guide a future of genome-enabled biodiversity conservation.
Route to minimally dissipative switching in magnets via terahertz phonon pumping
Authors: Strungaru Mara , Ellis Matthew O. A. , Ruta Sergiu , Evans Richard F. L. , Chantrell Roy W. , Chubykalo-Fesenko Oksana
Published: June 2024

Ultrafast switching of magnetic materials has been shown to be predominantly thermally driven, but excess heating limits the energy efficiency of this process. By employing atomistic spin-lattice dynamics simulations, we show that efficient coherent magnetization switching of an insulating magnet can be triggered by a THz excitation of phonons. We find that switching is driven by excitation near the P point of the phonon spectrum in conditions where spins typically cannot be excited and when manifold k phonon modes are accessible at the same frequency. Our model determines the necessary ingredients for low-dissipative switching and provides insight into THz-excited spin dynamics with a route to energy efficient ultrafast devices.

Published by the American Physical Society
2024
Neutron Star Matter as a Dilute Solution of Protons in Neutrons
Authors: Keller J. , Hebeler K. , Pethick C. J. , Schwenk A.
Published: June 2024

Neutron stars contain neutron-rich matter with around 5% protons at nuclear saturation density. In this Letter, we consider equilibrium between bulk phases of matter based on asymmetric nuclear matter calculations using chiral effective field theory interactions rather than, as has been done in the past, by interpolation between the properties of symmetric nuclear matter and pure neutron matter. Neutron drip (coexistence of nuclear matter with pure neutrons) is well established, but from earlier work it is unclear whether proton drip (equilibrium between two phases, both of which contain protons and neutrons) is possible. We find that proton drip is a robust prediction of any physically reasonable equation of state, but that it occurs over a limited region of densities and proton fractions. An analytical model based on expanding the energy in powers of the proton density, rather than the neutron excess, is able to account for these features of the phase diagram.

Published by the American Physical Society
2024
Single-sized phase-change metasurfaces for dynamic information multiplexing and encryption
Authors: Liu Tingting , Li Jie , Xiao Shuyuan
Published: June 2024

Optical metasurfaces empower us to manipulate the electromagnetic space and control light propagation at the nanoscale, offering a powerful tool to achieve modulation of light for information processing and storage. In this paper, we propose a phase-change metasurface to realize dynamic multiplexing and encryption of near-field information. Based on the orientation degeneracy and polarization control governed by Malus's law, we elaborately design the orientation distribution of Sb2S3 meta-atoms with the same dimension to simultaneously satisfy the amplitude modulation requirements of three independent channels. Using the corresponding polarization control as decoding keys, three different nanoprinting images can be displayed, and these multiplexed images can be switched on and off by leveraging the reversible tunability of the Sb2S3 meta-atoms between the amorphous and crystalline states. With the unparalleled advantages of ultracompactness, simple design strategy, high information density and security, the proposed metasurfaces afford promising prospects for high-end applications in ultracompact and intelligent dynamic display, high-dense optical data storage, and optical information encryption.

Published by the American Physical Society
2024
Observation of quasi-Bragg scattering by Goebel mirrors
Authors: Reunov Dmitriy G. , Akhsakhalyan Anton A. , Akhsakhalyan Aram D. , Chkhalo Nikolay I. , Shaposhnikov Roman A. , Drozdov Yuri N.
Published: June 2024

This paper reports the first observation of quasi-Bragg scattering from collimating Goebel mirrors in a real instrument. On the basis of the experimental data obtained and the numerical analysis performed, it is concluded that it is necessary to take into account the effect of quasi-Bragg scattering when constructing real devices with multilayer mirrors for use in X-ray diffractometry and in spectroscopy, especially for small-angle scattering with position-sensitive detectors.
Towards an understanding of the digital transformation of facility management in healthcare: perspectives from practice
Authors: Schmitter Paul , Shahgholian Azar , Tucker Matthew
Published: June 2024

Purpose

Facility management (FM) in healthcare is an organisational function that provides non-medical activities, ensuring operational functionality of critical health infrastructure. FM leaders are under pressure to implement the digital transformation, confronted with a highly complex and challenging operational environment. However, the current scope and understanding of the digital transformation in FM is rather limited, with a strong focus on technology. This perspective is inadequate to realise a digital transformation in healthcare organisations and requires a new framework. To ensure the practical applicability, a clearer depiction on how FM practitioners in the field, currently understand the digital transformation, is necessary.

Design/methodology/approach

A sequential exploratory mixed-methods design was chosen with a qualitative data collection and quantitative data analysis phase. A total of 23 semi-structured research interviews with professionals from FM in healthcare in Switzerland were carried out. Topic modeling was used to analyse, identify and cluster topics.

Findings

In total, nine distinct digital transformation topics were generated: ‘addressing future organisational and people needs’, ‘end-user-oriented processes’, ‘digitalisation management vs. digital tools’, ‘major organisational change’, ‘information exchange and work culture’, ‘digital systems’, ‘pressure’, ‘company-wide strategy’ and ‘management support and communication involving non-medical support services’. The findings indicate that FM practitioners perceive the digital transformation beyond the purely technological viewpoint, although they lack the know-how and instruments necessary to implement the digital transformation.

Originality/value

This study employs an innovative research design, resulting in foundational insights on how FM in healthcare perceives the digital transformation. As such, the study expands the notion on what the digital transformation means for the FM field.
Mitigating the aftermath of relationship conflict between the owners and contractors: a contract enforcement approach
Authors: Gan Xueqing , Jia Jianyao , Le Yun , Liu Tingting , Xue Yutong
Published: June 2024

Purpose

Relationship conflict between the owners and contractors is inevitable, which could induce negative consequences. Yet, the existing literature mostly focused on its direct effects on project performance and ignored the process by which relationship conflict gradually deteriorates cooperation as well as corresponding managerial approaches. Given the fact that relationship conflict originates from interdependent tasks, the proposed theoretical model is intended to measure relational behavior as an instant outcome of relationship conflict, and explore the buffering role of contract enforcement approach.

Design/methodology/approach

This paper develops the conceptual model based on the literature review. Then the questionnaire survey was conducted. The dyadic data obtained from 168 Chinese construction project professionals were analyzed by the Partial Least squares Structural Equation Modeling (PLS-SEM) technique.

Findings

The results show that relational behavior partially mediates the link between relationship conflict and project performance. Besides, three types of contract enforcement approaches are found to differentially change the negative link between relationship conflict and relational behavior. Rigid contract enforcement can worsen the adverse effects of relationship conflict on relational behavior, whereas flexible contract enforcement can alleviate these negative effects. The level of mitigation hinges on whether compromising behaviors or obliging behaviors are chosen.

Originality/value

The study extends the knowledge of conflict theory and contract theory in the construction field. Based on the proposed conceptual model and PLS-SEM results, this study contributes to the understanding of relationship conflict’s consequences between the owners and contractors and enriches conflict management approaches in the construction field.
Investigation of the effects of different needle hole covering techniques on seam characteristics of waterproof breathable fabric
Authors: Kumar Abhishek , Manshahia Manpreet
Published: June 2024

Purpose

Stitching is the traditional method of creating seams using needles and threads. However, this is not useful for waterproof breathable garments as needle holes allow water to penetrate inside the garment, compromising its functionality. This study aims to investigate different techniques for covering the needle holes formed during stitching to achieve a seam that is waterproof, durable and functionally effective.

Design/methodology/approach

This study investigates different methods to cover needle holes formed during stitching with the help of seam tape, seam grip adhesive and fuser thread. The emphasis is on evaluating the seam characteristics, including seam strength, seam efficiency, puckering, bending stiffness and resistance to water penetration. Statistical analysis involves the use of the Shapiro–Wilk test, Levene statistic, one-way ANOVA and Tukey’s HSD and Tamhane post-hoc tests.

Findings

The experimental results suggest that seam tape is effective in enhancing water resistance, seam strength and seam efficiency, but it contributes to stiffness and aesthetically degrades seams due to increased puckering. Meanwhile, the use of fuser thread presents an alternative, exhibiting improved waterproof properties compared to regular stitching. It offers more flexibility and less puckering compared to seam tape.

Originality/value

This study contributes novel insights by shifting the focus from alternative seaming methods such as bonding and welding, to enhancing traditional stitching for waterproof seam construction. While prior research primarily explored alternatives to stitching, this study uniquely addresses the effectiveness of different techniques in covering needle holes to achieve waterproof seams. The findings provide valuable information for enhancing the functionality of stitched seams in the production of waterproof breathable garments.
Navigating pregnancy in detention: lived experiences in a Philippine women’s prison
Authors: Nieva Jr Romulo Fernandez
Published: June 2024

Purpose

Imprisonment impacts women’s childbearing and mothering experiences. Using sociological concepts of total institutions, pains of imprisonment and gendered pains of imprisonment, this study aims to explore the childbearing experiences of 18 Filipino incarcerated women.

Design/methodology/approach

A qualitative, inductive approach was undertaken to explore imprisoned women’s pregnancy experiences. This research project used reflexive thematic analysis to examine the data from semi-structured interviews with 18 Filipino pregnant prisoners.

Findings

The participants’ experiences of childbearing in prison were reflected in three overarching themes: lack of autonomy over pregnancy; reduced capacity to manage discomforts and needs; and coping with prison deprivations. These themes embody women’s experiences of how imprisonment disrupts Filipino women’s childbearing and mothering experiences. Furthermore, the results illustrated how the women navigated the prison regime to address their needs and cope with the pains of imprisonment.

Originality/value

Although there is a small but growing body of research specifically focusing on mothering and imprisonment, little consideration has been given to analyzing Filipino women’s pregnancy experiences in custody. This paper highlights an urgent need to reform correctional policies and practices to address incarcerated women’s distinct needs.
The role of relationship commitment in managing logistics outsourcing in the digital economy
Authors: Shi Rongrong , Yang Baojun , Chu Zhaofang , Lai Fujun
Published: June 2024

Purpose

Digitalization brings complexity and challenges to the relationship governance between logistics outsourcers and their providers. Drawn on resource dependence theory (RDT) and resource-based view (RBV), this study aims to examine the role of relationship commitment in simultaneously managing dependence and improving operational performance in logistics outsourcing in the digital economy, as well as the contingent factors (i.e. communication, relationship length, and company size) that affect the effectiveness of relationship commitment.

Design/methodology/approach

Based on data collected from 130 third-party logistics (3PL) users in China, our model was tested with the partial least squares (PLS) approach.

Findings

First, relationship commitment is necessary for 3PL users to manage dependence on 3PL providers and improve operational performance in the digital economy. Second, communication helps 3PL users to develop higher relationship commitment but weakens the motivating effect of dependence on relationship commitment. Third, a long relationship history develops inertia to diminish the effectiveness of dependence on driving relationship commitment while it boosts the impact of relationship commitment on operational performance. Last, company size is an important signal to amplify the effectiveness of relationship commitment for operational performance enhancement.

Originality/value

This study contributes to the logistics outsourcing literature by integrating RDT and RBV to explain the twofold roles of relationship commitment, simultaneously tackling dependence and enhancing operational performance in the digital economy. Additionally, it expands the understanding of the boundary conditions (e.g. communication, relationship length, and company size) on these twofold roles.
Social attitudes in sustainable fashion: the role of environmental knowledge on sustainable development goals (SDGs)
Authors: Djossouvi Adjoa Candide Douce , Luo Biao , Sayibu Muhideen , Debongo Devincy Yanne Sylvaire , Rauf Aisha
Published: June 2024

Purpose

This study investigates and explores sustainable fashion based on social attitudes toward culture and sustainable fashion effects in sub-Saharan Africa (SSA), based on environmental knowledge and consumer satisfaction initiatives. It explicates sustainable fashion on the sustainable development agenda in addressing the gap of cultural value, environmental knowledge and sustainable fashion in SSA.

Design/methodology/approach

Using a quantitative approach, the study employed a web-based online cross-sectional survey to extract tangible information from 620 participants from SSA. The study integrated theory of planned behaviors (TPB) model and hypotheses. A structural equation model (SEM) was used to test all proposed hypotheses.

Findings

The results show that low environmental knowledge, influenced by geographical and cultural differences, affected fashion value, as which is predictively significant for sustainable fashion. However, attitude and cultural value results found statistical significance for consumer satisfaction in sustainable fashion. Furthermore, mediation was attained between consumer behavioral and environmental knowledge of sustainable fashion. The study recommends government policies on educational awareness and textile regulations for environmental garbage disposal possible harmful effects of climate change and finally, designing innovative initiatives for environmentally friendly fashion.

Originality/value

This study examines the environmental and social attitudes as well as behavioral effects, of an ecosystem that would most likely have a short life period, eliminate disposal dumps and foster an environmental control policy. Consequently, the study’s conceptual model and extended TPB contribute to how sustainable fashion supports environmental knowledge, consumer attitudes and cultural behaviors in fashion among Sub-Saharan Africans.
How positive leadership leads to employees’ interpersonal citizenship behavior: a self-consistency perspective
Authors: Li Hsien-Ta
Published: June 2024

Purpose

Although researchers have carried out considerable work on organizational citizenship behavior (OCB), the questions of whether and how adopting a positive leadership style leads subordinate employees to engage in interpersonal citizenship behavior (ICB) remain, thus far, unanswered. To address this research gap, this study aimed to uncover the possible underlying mediation mechanism.

Design/methodology/approach

Partial least squares structural equation modeling (PLS-SEM) was used to test the research model using data collected by means of a three-wave online survey with 166 respondents.

Findings

The results indicated that the organization-based self-esteem (OBSE) of subordinate employees mediated the effect of supervisors using a positive leadership style on subordinates engaging in person-focused ICB.

Originality/value

The importance of positive leadership is revealed in the finding of a self-consistency-based positive spillover effect, according to which the use of a positive leadership style directly benefits subordinates by enhancing their OBSE. This subsequently motivates them to engage in person-focused ICB, which benefits their coworkers. Thus, a positive leadership style creates a positive dynamic in the workplace.
‘Good Work’ and Alternative Food Initiatives: A Workplace Spirituality Perspective
Authors: Gjorevska Natasha
Published: June 2024

This paper explores ‘good work’ as purpose‐driven organizing for positive social impact in the case of alternative food initiatives (AFIs). AFIs accommodate alternative ways of food production and consumption that tackle the world's pressing sustainability challenges. Considering the centrality of workers’ motives, beliefs for generating/sustaining alternative and spiritual work/organizational contexts, this study bridges the knowledge on AFIs and workplace spirituality (WS) through the individual‐level perspective. The paper explores AFI members’ workplace motives and experiences to understand how these individuals make sense of their work, and to draw insights on what ‘good work’ entails in this organizational realm. Data were collected via a two‐phase study from a total of 28 members of organizations based in Glasgow, Scotland. The results show that AFI members’ work drivers include spiritual (as other‐regarding) motives and that the perceived value of their work is in contributing to the welfare of others through a workspace of belonging, freedom and care. The findings suggest that a WS perspective can help in understanding how AFI members approach their work to create (greater) good. Drawing on the lessons from the case analysis within the AFI context, this paper highlights the relevance of WS for repurposing work and organizing.
Chromosome‐level genome of the parthenogenetic booklouse Liposcelis bostrychophila reveals high heterozygosity and a nonhomologous chromosome
Authors: Jiang Shi‐Die , Chen Yu‐Ang , Guo Peng‐Yu , Sun Jun , Feng Hua‐Yue , Li Yi , Wang Jin‐Jun , Wei Dan‐Dan
Published: June 2024

Psocodean species are emerging as significant sanitary and stored‐product pests, posing threats to human health and global food security. Out of an estimated 10 000 species, the whole genome sequences of only 4 species have been published. Genomic resources are crucial for establishing effective pest control and enhancing our understanding of the evolution of psocodean species. In this study, we employed Illumina and PacBio sequencing along with Hi‐C scaffolding techniques to generate a chromosome‐level genome assembly for the parthenogenetic booklouse Liposcelis bostrychophila. The assembled genome of this booklouse measures 291.67 Mb in length and comprises 9 chromosomes. Notably, the genome of L. bostrychophila exhibits a high level of heterozygosity and features a distinctive nonhomologous chromosome. This heterozygous characteristic of the parthenogenetic booklouse genome may arise from high mutation rates, based on genomic variations analysis across multiple generations. Our analysis revealed significantly expanded gene families, primarily associated with the detoxification and feeding habits of L. bostrychophila. These include integument esterases (ESTs), ATP‐binding cassette (ABC) transporter genes and gustatory receptors (GRs). The high‐quality genome sequence of L. bostrychophila provides valuable resources for further study on the molecular mechanisms of stress resistance. It enables researchers to identify crucial functional genes and facilitates research on the population genetics, evolution and phylogeny of booklice.
Physicochemical characterization of wheat starch and variation of fatty acid composition in deep‐fried dough sticks with different treatments
Authors: Liu Yan , Hu Xueying , Jian Xinhang , Guo Liping , Xiao Junxia , Li Xiaodan
Published: June 2024

The present study investigated the effects of different deep‐frying times and temperatures on the amylose content, crystal structure, thermodynamics, and other properties of deep‐fried dough sticks. Results showed that the change of amylose content in deep‐fried dough sticks during the deep‐frying process was positively correlated with time and temperature. Moreover, the deep‐frying process of deep‐fried dough sticks was accompanied by the formation of starch–lipid complexes that led to the destruction of starch structure. The degreased sample and the oil sample had the same absorption peaks at 2854 and 1746 cm−1, respectively. The melting enthalpy (ΔH) of the starch–lipid complex decreased significantly. In addition, the viscosity of starch reduced as the deep‐frying time and temperature increased. Furthermore, it was found that the effect of increasing deep‐frying temperature was greater than that of time.

Practical Application

As a popular deep‐fried food, the main component of deep‐fried dough sticks is starch. Starch gelatinization, protein denaturation, and interaction among components occurred during deep‐frying. At present, there are few studies focusing on the properties of starch in deep‐fried dough sticks in the real deep‐frying system. Therefore, this study provided a theoretical basis for subsequent research by measuring the effects of different deep‐frying conditions on the properties of starch in deep‐fried dough sticks.
Risk factors and risk stratification approaches for delirium screening: A Geriatric Emergency Department Guidelines 2.0 systematic review
Authors: Seidenfeld Justine , Lee Sangil , Ragsdale Luna , Nickel Christian H. , Liu Shan W. , Kennedy Maura
Published: June 2024

Objective

As part of the Geriatric Emergency Department (ED) Guidelines 2.0 project, we conducted a systematic review to find risk factors or risk stratification approaches that can be used to identify subsets of older adults who may benefit from targeted ED delirium screening.

Methods

An electronic search strategy was developed with a medical librarian, conducted in April 2021 and November 2022. Full‐text studies of patients ≥65 years assessed for prevalent delirium in the ED were included. Risk of bias was assessed using the McMaster University Clarity Group tool. Outcomes measures pertained to the risk stratification method used. Due to heterogeneity of patient populations, risk stratification methods, and outcomes, a meta‐analysis was not conducted.

Results

Our search yielded 1878 unique citations, of which 13 were included. Six studies developed a novel delirium risk score with or without evaluation of specific risk factors, six studies evaluated specific risk factors only, and one study evaluated an existing nondelirium risk score for association with delirium. The most common risk factor was history of dementia, with odds ratios ranging from 3.3 (95% confidence interval [CI] 1.2–8.9) to 18.33 (95% CI 8.08–43.64). Other risk factors that were consistently associated with increased risk of delirium included older age, use of certain medications (such as antipsychotics, antidepressants, and opioids, among others), and functional impairments. Of the studies that developed novel risk scores, the reported area under the curve ranged from 0.77 to 0.90. Only two studies reported potential impact of the risk stratification tool on screening burden.

Conclusions

There is significant heterogeneity, but results suggest that factors such as dementia, age over 75, and functional impairments should be used to identify older adults who are at highest risk for ED delirium. No studies evaluated implementation of a risk stratification method for delirium screening or evaluated patient‐oriented outcomes.
Locked In: Reindustrialisation and the Production of Multiple Marginalities in an Old Mining Town of Hungary
Authors: Nagy Erika , Bródy Luca Sára , Mihály Melinda
Published: June 2024

This paper aims to unfold how peripheral reindustrialisation in Central and Eastern Europe (CEE) produced multiple marginalities in local spaces. Relying on a cultural political economic (CPE) approach, we analyse how the imaginary of reindustrialisation encompassed the discourses on development and the strategies and practices of powerful agents of economic restructuring in an old mining town of Hungary, which entailed new dimensions and depths of poverty. By discussing the changing labour, housing, and environmental conditions of the local poor, we relate structural changes to the changing conditions of social reproduction and local history, and highlight how the new economic trajectory produced marginalised spaces within a dynamic region. In this way, we also extend CPE‐guided research more to the realms of social reproduction and ethnic social relations to get a more fine‐grained understanding of inequalities rooted in peripheral industrialisation and scrutinise prevailing narratives of economic development in CEE.
Frequency of workplace incidents and injuries in veterinarians, veterinary nurses and veterinary students and measures to control these
Authors: Johnson L , Fritschi L
Published: June 2024

Background

Veterinarians, veterinary nurses and veterinary students work and train in a variety of environments and are exposed to a wide range of hazards.

Objectives

(1) To compare the rate of health and safety incidents and injuries between veterinarians, veterinary nurses and veterinary students. (2) To investigate the health and safety hazard controls present in Australian veterinary workplaces.

Study Design

A cross‐sectional study, using an online questionnaire.

Methods

Anonymous links to the questionnaire were disseminated to Australian veterinarians, veterinary nurses and veterinary students.

Results

A total of 494 veterinarians, 484 veterinary nurses and 212 veterinary students completed the survey. Incidents and injuries were common, particularly sharps‐related injuries and animal bites. Australian veterinary nurses and veterinarians experienced the studied incidents at similar rates to each other. Veterinary students experienced some incidents and injuries at rates higher than both veterinarians and veterinary nurses, including heatstroke, hypothermia, sunburn, electric shock, loss of consciousness, being rammed or pushed over by an animal and farm equipment injuries. Of the workplace hazard controls reported, first aid boxes were most commonly present, and safety meetings occurred least commonly. Veterinary nurses received Q fever and rabies vaccines much less frequently than veterinarians and veterinary students.

Conclusion

This study demonstrated that improvements need to be made to the occupational health and safety standards in the Australian veterinary sector. Veterinarians and veterinary nurses had suboptimal rates of access to many of the required and critical workplace health and safety controls. Improvements to the standard of health and safety training of veterinary students are indicated, given their higher rates of certain incidents and injury.
‘Under pressure’: The role of therapeutic drug monitoring in the treatment of hypertension
Authors: Versmissen Jorie , van Steenkiste Job , Koch Birgit C. P. , Peeters Laura E. J.
Published: June 2024

Antihypertensive drugs do not qualify as optimal candidates for therapeutic drug monitoring (TDM), given their obvious physiological effect, the absence of a clear relationship between drug concentrations and pharmacodynamic outcomes and their wide therapeutic range. However, since non‐adherence is a major challenge in hypertension management, using drug concentrations can be of value to identify non‐adherence as a first step towards better blood pressure control. In this article we discuss the key challenges associated with measuring and interpreting antihypertensive drug concentrations that are important when TDM is used to improve non‐adherence. Additionally, we elaborate on the role of TDM in optimizing antihypertensive drug treatment besides addressing non‐adherence by highlighting its value in specific patient groups with altered pharmacokinetic parameters such as female vs. male or elderly patients.
Staying in control: Characterizing the mechanisms underlying cognitive control in high and low arousal states
Authors: Alameda Clara , Avancini Chiara , Sanabria Daniel , Bekinschtein Tristan A. , Canales‐Johnson Andrés , Ciria Luis F.
Published: June 2024

Throughout the day, humans show natural fluctuations in arousal that impact cognitive function. To study the behavioural dynamics of cognitive control during high and low arousal states, healthy participants performed an auditory conflict task during high‐intensity physical exercise (N = 39) or drowsiness (N = 33). In line with the pre‐registered hypotheses, conflict and conflict adaptation effects were preserved during both altered arousal states. Overall task performance was markedly poorer during low arousal, but not for high arousal. Modelling behavioural dynamics with drift diffusion analysis revealed evidence accumulation and non‐decision time decelerated, and decisional boundaries became wider during low arousal, whereas high arousal was unexpectedly associated with a decrease in the interference of task‐irrelevant information processing. These findings show how arousal differentially modulates cognitive control at both sides of normal alertness, and further validate drowsiness and physical exercise as key experimental models to disentangle the interaction between physiological fluctuations on cognitive dynamics.
Single‐cell landscape reveals the immune heterogeneity of bone marrow involvement in peripheral T‐cell lymphoma
Authors: Liu Jun , Xia Baijing , Jiang Xinmiao , Cao Lixue , Xi Zhihui , Liang Liting , Zhang Shaojun , Zhang Hui , Li Wenyu
Published: June 2024

The prognosis of patients with peripheral T‐cell lymphoma (PTCL) depends on bone marrow involvement (BMI). The bone marrow (BM) tumor microenvironment in PTCL remains unclear. We performed single‐cell RNA sequencing (scRNA‐seq) on 11 fresh BM samples from patients with BMI to reveal the associations of immune landscape and genetic variations with the prognosis of PTCL patients. Compared with PTCL not otherwise specified (NOS), angioimmunoblastic T‐cell lymphoma (AITL) had a higher number of T cells, lower number of lymphocytes, and greater inflammation. Immune heterogeneity in AITL is associated with prognosis. In particular, specific T‐cell receptor (TCR) T cells are enriched in patients with good response to anti‐CD30 therapy. We observed RhoA mutation‐associated neoantigens. Chidamide‐treated patients had a higher number of CD4+ regulatory cells and a better treatment response compared with other patients. In the nonresponder group, T‐cell enrichment progressed to secondary B‐cell enrichment and subsequently diffuse large B‐cell lymphoma. Moreover, AITL patients with lymphoma‐associated hemophagocytic syndrome had more T follicular helper (Tfh) cells with copy number variations in CHR5. To our knowledge, this study is the first to reveal the single‐cell landscape of BM microenvironment heterogeneity in PTCL patients with BMI. scRNA‐seq can be used to investigate the immune heterogeneity and genetic variations in AITL associated with prognosis.
USP15, activated by TFAP4 transcriptionally, stabilizes SHC1 via deubiquitination and deteriorates renal cell carcinoma
Authors: Shi Yaxing , Zhang Jing , Li Jiaxing , He Jieqian , Wu Si , Yu Miao , Yang Da , Ju Lincheng
Published: June 2024

Ubiquitin‐specific peptidase 15 (USP15), a critical deubiquitinating enzyme, has been demonstrated to improve substrate stabilization by hydrolyzing the bond between the substrate and ubiquitin, and is implicated in multiple carcinogenic processes. Prompted by the information cited from The Cancer Genome Atlas (TCGA) database and the Cancer Proteogenomic Data Analysis Site (cProSite), USP15 is selectively overexpressed in clear cell renal cell carcinoma (ccRCC) samples. We aimed to investigate the function of USP15 on ccRCC malignant features, which was emphasized in its deubiquitination of SHC adaptor protein 1 (SHC1). The overexpression of USP15 promoted the capacity of proliferation, migration, and invasion in ccRCC CAKI1 and 769‐P cells, and these malignant biological properties were diminished by USP15 deletion in 786‐O cells. USP15 accelerated tumor growth and lung metastasis in vivo. In addition, deubiquitinase USP15 was further identified as a new protector for SHC1 from degradation by the ubiquitination pathway, the post‐translational modification. In sequence, transcription factor activating enhancer binding protein 4 (TFAP4) was shown to be partly responsible for USP15 expression at the level of transcription, as manifested by the chromatin immunoprecipitation and pull‐down assay. Based on the in vitro and in vivo data, we postulate that USP15 regulated by TFAP4 transcriptionally deteriorates ccRCC malignant biological properties via stabilizing SHC1 by deubiquitination.
Accuracy of artificial intelligence‐based segmentation of the mandibular canal in CBCT
Authors: Ntovas Panagiotis , Marchand Laurent , Finkelman Matthew , Revilla‐León Marta , Att Wael
Published: June 2024

Objectives

To investigate the accuracy of artificial intelligence (AI)‐based segmentation of the mandibular canal, compared to the conventional manual tracing, implementing implant planning software.

Materials and methods

Localization of the mandibular canals was performed for 104 randomly selected patients. A localization was performed by three experienced clinicians in order to serve as control. Five tracings were performed: One from a clinician with a moderate experience with a manual tracing (I1), followed by the implementation of an automatic refinement (I2), one manual from a dental student (S1), and one from the experienced clinician, followed by an automatic refinement (E). Subsequently, two fully automatic AI‐driven segmentations were performed (A1,A2). The accuracy between each method was measured using root mean square error calculation.

Results

The discrepancy among the models of the mandibular canals, between the experienced clinicians and each investigated method ranged from 0.21 to 7.65 mm with a mean of 3.5 mm RMS error. The analysis of each separate mandibular canal's section revealed that mean RMS error was higher in the posterior and anterior loop compared to the middle section. Regarding time efficiency, tracing by experienced users required more time compared to AI‐driven segmentation.

Conclusions

The experience of the clinician had a significant influence on the accuracy of mandibular canal's localization. An AI‐driven segmentation of the mandibular canal constitutes a time‐efficient and reliable procedure for pre‐operative implant planning. Nevertheless, AI‐based segmentation results should always be verified, as a subsequent manual refinement of the initial segmentation may be required to avoid clinical significant errors.
SCN8A self‐limited infantile epilepsy: Does epilepsy resolve?
Authors: Young Emma , Harris Rebekah , Lieffering Nico , de Valles‐Ibáñez Guillem , Nyaga Denis , Bennett Mark F. , Hildebrand Michael S. , Scheffer Ingrid E. , Sadleir Lynette G.
Published: June 2024

SCN8A variants cause a spectrum of epilepsy phenotypes ranging from self‐limited infantile epilepsy (SeLIE) to developmental and epileptic encephalopathy. SeLIE is an infantile onset focal epilepsy, occurring in developmentally normal infants, which often resolves by 3 years. Our aim was to ascertain when epilepsy resolves in SCN8A‐SeLIE. We identified unpublished individuals with SCN8A‐SeLIE and performed detailed phenotyping. Literature was searched for published SCN8A‐SeLIE cases. Nine unpublished individuals from four families were identified (age at study = 3.5–66 years). Six had their last seizure after 3 years (range = 4–21 years); although drug‐responsive and despite multiple weaning attempts (1–5), five of six remain on antiseizure medications (carbamazepine, n = 3; lamotrigine, n = 2). We identified 29 published individuals with SCN8A‐SeLIE who had data on seizure progression. Of the 22 individuals aged at least 10 years, reported here or in the literature, nine of 22 (41%) had seizure offset prior to 3 years, five of 22 (23%) had seizure offset between 3 and 10 years, and eight of 22 (36%) had seizures after 10 years. Our data highlight that more than half of individuals with SCN8A‐SeLIE continue to have seizures into late childhood. In contrast to SeLIE due to other etiologies, many individuals have a more persistent, albeit drug‐responsive, form of epilepsy.
Yearling laryngeal function in Thoroughbreds that underwent a laryngoplasty differs from controls
Authors: Hardwick Josephine L. , Ahern Benjamin J. , Crawford Kylie L. , Allen Kate J. , Franklin Samantha H.
Published: June 2024

Background

Yearling laryngeal function (YLF) is frequently assessed at the time of sale and the outcomes of these assessments can have significant economic implications. The YLF of horses that subsequently underwent a prosthetic laryngoplasty (PL) is unknown.

Objectives

We hypothesised horses with YLF ≥grade II.2 would be at increased risk of requiring PL, compared with YLF <grade II.2.

Study design

Case–control.

Methods

There were 150 PL cases from 2019 to 2021 with an available yearling post‐sale videoendoscopic examination and 600 controls. Two observers unaware of the outcome graded YLF using the Havemeyer system. The risk of PL for each YLF grade was calculated using multivariable conditional logistic regression.

Results

The proportions of each YLF grade in the control group and PL group, respectively, were grade I: 25.8% and 13.3%, grade II.1: 54.3% and 35.3%, grade II.2: 16.7% and 26%, grade III.1: 3% and 20.7%, grade III.2: 0.2% and 3.3%, grade III.3: 0% and 0.7%, grade IV: 0% and 0.7%. The odds ratio (OR, 95% confidence interval) of requiring PL compared with the referent grade I were: grade II.1: 1.2 (0.7, 2.2, p = 0.5), grade II.2: 3.4 (1.8, 6.1, p < 0.001), grade III.1: 13.8 (6.0, 31.6, p < 0.001), grade III.2: 55.5 (10.3, 299.2, p < 0.001), grade III.3: 2930,000 (398173.7, 21 600,000, p < 0.001), grade IV: 26300,000 (3 420 000, 202 000 000, p < 0.001). Yearling LF ≥grade II.2 had an OR of 4.61 (3.0, 7.1, p < 0.001) compared with <grade II.2; YLF ≥grade III.1 had an OR of 10.7 (5.6, 20.4, p < 0.001) compared with <grade III.1.

Main limitations

Lack of performance data to compare the PL and control groups. The control group was not ‘disease‐free’ and may have developed disease and been retired or undergone surgery elsewhere.

Conclusions

Three‐quarters of the PL group had ≤grade II.2 YLF, demonstrating deterioration in LF post‐sale was common. The risk of requiring PL increased from YLF grade II.2 upwards.