bluuebunny/crossref_metadata_2025 huggingface dataset:
Unlocking insights: text mining analysis on the health, welfare, and behavior of cows in automated milking systems
Authors: Gislon Giulia , Bava Luciana , Zucali Maddalena , Tamburini Alberto , Sandrucci Anna
Published: June 2024

Automated Milking Systems (AMS) have undergone significant evolution over the past 30 yr, and their adoption continues to increase, as evidenced by the growing scientific literature. These systems offer advantages such as a reduced milking workload and increased milk yield per cow. However, given concerns about the welfare of farmed animals, studying the effects of AMS on the health and welfare of animals becomes crucial for the overall sustainability of the dairy sector. In the last few years, some analysis conducted through text mining (TM) and topic analysis (TA) approaches have become increasingly widespread in the livestock sector. The aim of the study was to analyze the scientific literature on the impact of AMS on dairy cow health, welfare, and behavior: the paper aimed to produce a comprehensive analysis on this topic using TM and TA approaches. After a preprocessing phase, a dataset of 427 documents was analyzed. The abstracts of the selected papers were analyzed by TM and a TA using Software R 4.3.1. A Term Frequency-Inverse Document Frequency (TFIDF) technique was used to assign a relative weight to each term. According to the results of the TM, the ten most important terms, both words and roots, were feed, farm, teat, concentr, mastiti, group, SCC (somatic cell count), herd, lame and pasture. The 10 most important terms showed TFIDF values greater than 3.5, with feed showing a value of TFIDF of 5.43 and pasture of 3.66. Eight topics were selected with TA, namely: 1) Cow traffic and time budget, 2) Farm management, 3) Udder health, 4) Comparison with conventional milking, 5) Milk production, 6) Analysis of AMS data, 7) Disease detection, 8) Feeding management. Over the years, the focus of documents has shifted from cow traffic, udder health and cow feeding to the analysis of data recorded by the robot to monitor animal conditions and welfare and promptly identify the onset of stress or diseases. The analysis reveals the complex nature of the relationship between AMS and animal welfare, health, and behavior: on one hand, the robot offers interesting opportunities to safeguard animal welfare and health, especially for the possibility of early identification of anomalous conditions using sensors and data; on the other hand, it poses potential risks, which requires further investigations. TM offers an alternative approach to information retrieval in livestock science, especially when dealing with a substantial volume of documents.
The symbiosome—a transient organelle in evolution
Authors: Adema Kelvin , Kohlen Wouter
Published: June 2024

This article comments on:

Casaes PA, Ferreira dos Santos JM, Silva VC, Rhem MFK, Teixeira Cota MM, de Faria SM, Rando JG, James EK, Gross E. 2024. The radiation of nodulated Chamaecrista species from the rainforest into more diverse habitats has been accompanied by a reduction in growth form and a shift from fixation threads to symbiosomes. Journal of Experimental Botany 75, 3643–3662.
Focal leptomeningeal vascular anomalies on brain MRI: A mimic of leptomeningeal metastatic disease
Authors: Boutet Alexandre , Malik Mikail , Yang Andrew Z , Germann Jurgen , Haile Samuel S , Son Hyo Jin , Vetkas Artur , Pai Vivek , Mason Warren P , Zadeh Gelareh , Mandell Daniel M
Published: June 2024

Background

The diagnosis of leptomeningeal metastatic disease has major prognostic and therapeutic implications. We report 13 patients with a radiologically distinct kind of focal, enhancing leptomeningeal lesion on brain MRI that mimics leptomeningeal metastatic disease.

Methods

These patients were assessed at University Health Network (Toronto, Canada) between January 2001 and December 2023.

Results

Median age was 68 years (range, 55–78 years) and 10 patients were women. All patients had brain magnetic resonance imaging (MRI) including contrast-enhanced T2-weighted fluid attenuation inversion recovery (FLAIR) and T1-weighted spin echo sequences. MRI in all 13 patients showed a focal enhancing lesion located along the leptomeningeal surface of the brain. The MRI exams were reported as possible or likely leptomeningeal metastatic disease for the majority (9/13) of patients. Each lesion was curvilinear rather than sheet-like, and some lesions consisted of multiple connected/branching curvilinear structures with the appearance of abnormal vessels. The lesions were distinct from normal blood vessels. Some lesions had a visible connection with a nearby cortical vein. Follow-up contrast-enhanced brain MRI for 8/13 (62%) patients at a median of 3.9 years (IQR 2.4–6.6 years) showed all lesions were unchanged over time. Another 2/13 (15%) patients had clinical and CT brain follow-up after one year with no evidence of metastatic disease.

Conclusions

We describe a distinct kind of focal, enhancing leptomeningeal lesion on brain MRI that mimics metastatic disease. These lesions are likely a type of low-flow vascular anomaly. Their curvilinear/branching shape and intense enhancement particularly on T2-weighted FLAIR images distinguish these lesions from tumors.
IIOld English
Authors: Burns Rachel A , Heller Simon , Kehoe Niamh , Knowles Emma , Leneghan Francis , Pascual Rafael J , Ponirakis Eleni
Published: June 2024

This chapter has ten sections: 1. Manuscript Studies; 2. Prose; 3. Beowulf; 4. Other Secular Heroic Poems; 5. Biblical Poetry; 6. Riddles, Wisdom Poetry, and Other Shorter Poetry; 7. Lyric Poetry; 8. Verse Hagiography; 9. Reception. Sections 1 and 6 are by Rachel A. Burns; section 2 is by Niamh Kehoe; sections 3 and 4 are by Rafael J. Pascual; section 5 is by Emma Knowles, with contributions from Francis Leneghan; sections 7 and 8 are by Eleni Ponirakis; section 9 is by Simon Heller, with contributions from Rafael J. Pascual
Assessment of iron status
Authors: Von Holle Ann
Published: June 2024

Purpose of review

Iron is an essential trace element in human health that can be harmful at abnormal levels such as iron overload or deficiency. Measured iron status in the body can depend on health outcomes experienced by the individual and this can complicate its accurate assessment. This review will highlight recent research on iron assessment in the literature.

Recent findings

Research on iron assessment within the past 18 months included some common themes spanning new methods and biomarkers, as well as existing problems in assessing iron deficiency and overload. Heterogeneity in associations between inflammation and iron levels are reflected across different inflammatory biomarkers. New methods relevant to low- and high-resource settings may improve assessment in tissues with iron deficiency and overload. Consensus papers outlined best practices when using MRI to assess iron status. Outside of newer methods, traditional serum markers are the subject of a call for updated guidance when assessing iron status.

Research continues on the topic of iron assessment, underlying its complex metabolism in the body and resulting challenges in assessment. Current literature underscores progress to make iron assessment more accessible, improve existing methods, and update current assessment methods so they correspond with recent research to improve human health.
Comparing sucrose solution with distilled water for pain management in premature infant venipuncture: randomized clinical trial
Authors: Habibzadeh Hossein , Salamat Bakhsh Maryam , Hosseini Mina , Khalkhali Hamid Reza
Published: June 2024

Introduction and importance:

Managing pain is critical, especially for premature infants undergoing frequent painful procedures. Uncontrolled pain can lead to lasting harm in growth, cognitive development, and future pain responses.

Methods:

A double-blinded clinical investigation involving 150 premature infants was performed in a neonatal intensive care unit. They were randomly divided into three groups: Sucrose 20% (50 infants), distilled water (50 infants), and a control group (50 infants). The infants’ behavioral responses were assessed using an infant pain measurement tool before, at 2, and 7 min after the intervention through direct observation.

Results:

The study revealed that mean pain scores before, 2 min after, and 7 min after the intervention in the sucrose group were (4.78±0.91), (3.18±1.15), and (2±1.02), respectively. In the distilled water group, scores were (4.66±0.89), (3.04±1.15), and (3.08±1.10), while in the control group, they were (4.0±0.79), (4.94±0.79), and (4.72±0.96). The trend of pain scores varied among the groups over time, with a significant difference in mean pain scores at different time points (P<0.001). Initially comparable, pain scores notably decreased after 2 min in the sucrose and distilled water groups (P<0.001), differing from the control group.

Conclusion:

The study indicated that 20% sucrose and distilled water equally reduce infant pain post-venipuncture, suggesting their viability for clinical pain management. Distilled water, however, provides additional benefits, including economic considerations and ease of preparation.
Knowledge and attitude of medical students towards artificial intelligence in ophthalmology in Riyadh, Saudi Arabia: a cross-sectional study
Authors: Faroog Zainudheen , Dirar Qais Saif Eldaula , Zaidi Abdul Rehman Zia , Khan Mohammad Salman , Mahamud Golam , Ambia Saad Rahman , Al-Hazzaa Selwa
Published: June 2024

Background:

The use of artificial intelligence (AI) in ophthalmology represents a transformative leap in healthcare. AI-powered technologies, such as machine learning and computer vision, enhance the accuracy and efficiency of ophthalmic diagnosis and treatment.

Objective:

This study aimed to determine medical students’ awareness and attitudes towards the use of artificial intelligence in ophthalmology.

Methods:

This cross-sectional, questionnaire-based study was conducted between November 2022 and January 2023 using online questionnaires. Data collection was carried out using convenience sampling among medical students at the University. IBM SPSS version 23 was used to analyze the data.

Results:

The current finding shows that most of the participants N=309 (89.6%) had heard of the use of AI in medicine, and N=294 (85.2%) heard of the use of AI in ophthalmology. 98.6% (n=340) of respondents believed AI would be a helpful tool in ophthalmology. Along this line of questioning, a significant majority of respondents, 332 (96.2%) selected screening, 332 (96.2%) selected diagnosis, and 293 (84.9%) selected prevention as a usage of AI ophthalmology. However, the majority, 76.5%) of students had little understanding of the development of AI in ophthalmology. In addition, a significant relationship between sex, academic year, cumulative GPA (cGPA), and awareness of AI in ophthalmology (P<0.001) was found in this study.

Conclusions:

Overall, medical students in Saudi Arabia appear to have favorable thoughts about AI and positive perceptions towards AI in ophthalmology. However, the findings of this study emphasize the limited understanding and low confidence levels of medical students in Saudi Arabia regarding the use of AI in ophthalmology. As a result, early exposure to AI-related materials in medical curricula is crucial for addressing these challenges through comprehensive AI education and practical exposure to prepare future ophthalmologists.
Exploring the association between atrial fibrillation and celiac disease: a comprehensive review
Authors: Subedi Rasish , Soulat Amna , Rauf Butt Samia , Mohan Anmol , Danish Butt Muhammad , Arwani Suneel , Ahmed Gulzar , Majumder Koushik , Mohan Lal Priyanka , Kumar Vikash , Tejwaney Usha , Ram Nanik , Kumar Sarwan
Published: June 2024

Objective:

This paper aims to provide a comprehensive overview of the pathophysiology of atrial fibrillation (AF) and celiac disease (CD) individually while also exploring the emerging evidence of a potential association between the two conditions.

Methods:

The pathophysiology of AF, the most prevalent arrhythmia globally, and CD, an autoimmune condition triggered by gluten consumption, is examined. Genetic, structural, electrophysiological, and inflammatory factors contributing to their development are explored.

Results:

AF involves irregular atrial activity leading to electrical and structural remodeling of the atrium. CD is characterized by an immune response to gluten, primarily associated with HLA-DQ2 and HLA-DQ8 genetic mutations, resulting in damage to intestinal tissue. Emerging research suggests a link between AF and CD, possibly mediated through inflammation, fibrosis, and electromechanical delays in the atrium.

Conclusion:

Understanding the association between AF and CD carries significant clinical implications. Recognition of this relationship can assist in identifying individuals at higher risk for AF and inform proactive management strategies. Additionally, it underscores the importance of comprehensive care for CD patients, considering potential cardiac implications. Further research is warranted to elucidate precise mechanisms and explore potential therapeutic interventions targeting common pathways, opening avenues for enhanced patient care and future investigations.
Potential for and challenges of menstrual blood as a non-invasive diagnostic specimen: current status and future directions
Authors: Zaheer Amna , Komel Aqsa , Abu Bakr Mohammad Baraa , Singh Achit Kumar , Saji Alen Sam , Kharal Manahil Mansha , Ahsan Areeba , Khan Muhammad Hamza , Akbar Anum
Published: June 2024

Menstrual blood, which is often discarded as a waste product, has emerged as a valuable source of health information. The components of menstrual blood, such as endometrial cells, immune cells, proteins, and microbial signatures, provide insights into health. Studies have shown encouraging results for using menstrual blood to diagnose a variety of conditions, including hormonal imbalances, cervical cancer, endometriosis, chlamydia, diabetes, and other endocrine disorders. This review examines the potential of menstrual blood as a non-invasive diagnostic specimen, exploring its composition, promising applications, and recent advances. This review also discusses challenges to utilizing menstrual blood testing, including ethical considerations, the lack of standardized collection protocols, extensive validation studies, and the societal stigma around menstruation. Overcoming these challenges will open new avenues for personalized medicine and revolutionize healthcare for individuals who menstruate.
Association between gallstone disease and carotid intima-media thickness: a prospective observational cross-sectional study in a tertiary care center
Authors: Thapa Lokendra , Katwal Shailendra , Thapa Bikash Raj
Published: June 2024

Background and objectives:

Gallstone disease (GD) is a prevalent health issue globally, particularly in developed nations, and has notable associations with cardiovascular disease (CVD). This prospective observational cross-sectional study aimed to investigate the association between gallstone disease and carotid intima-media thickness (CIMT), a marker of carotid atherosclerosis, in a tertiary care setting.

Method:

Conducted at a tertiary care center, the study included 96 participants (48 with gallstone disease and 48 age and sex-matched controls). Data collection involved demographic information, BMI calculation, abdominal ultrasonography for gallstone detection, and carotid ultrasonography for CIMT measurement. Statistical analysis was performed using SPSS version 26.

Results:

The study revealed higher CIMT values in GD patients compared to controls (P<0.001). Additionally, a positive correlation was observed between CIMT and age (r=0.450, P<0.001) and BMI (r=0.550, P<0.001). The Cohen’s d-test indicated a clinically significant difference in CIMT between GD patients and controls (d=1.47).

Conclusion:

This study revealed a significant association between gallstone disease and elevated CIMT, correlating with higher BMI indicating a potential link between gallstone disease and increased risk of carotid atherosclerosis. These findings highlight the importance of assessing cardiovascular risk in patients with gallstone disease, highlighting the potential utility of carotid ultrasonography as a non-invasive screening tool. Early intervention strategies may be warranted to mitigate cardiovascular risks associated with gallstone disease.
The Microbiome and Irritable Bowel Syndrome
Authors: Gleasman-DeSimone Sara
Published: June 2024

Irritable bowel syndrome is a gastrointestinal disorder that affects 15%–20% of the US population. Its symptoms can have negative effects on a person's quality of life, and its treatment can be associated with high medical costs. An emerging area of irritable bowel syndrome research concerns the relationship between this condition and the gut microbiome. The purpose of this article is not only to review irritable bowel syndrome, and the role that the microbiome can play in its symptoms, but also to examine new emerging pathways that could blaze the trail for more individualized treatments. If equipped with this knowledge, gastrointestinal nurses and providers of care can be better prepared to help patients with irritable bowel syndrome in order to manage symptoms and improve their quality of life.
Analysis of micropolar elastic multi-laminated composite and its application to bioceramic materials for bone reconstruction
Authors: Rodríguez-Ramos R. , Espinosa-Almeyda Y. , Guinovart-Sanjuán D. , Camacho-Montes H. , Rodríguez-Bermúdez P. , Brito-Santana H. , Otero J. A. , Sabina F. J.
Published: June 2024

The asymptotic homogenization method is applied to characterize the effective behaviour of periodic multi-laminated micropolar elastic heterogeneous composites under perfect contact conditions. The local problem formulations and the analytical expressions for the effective stiffness and torque coefficients are derived for the centrosymmetric case. One of the main findings in this work is the analysis of the rotations effect of the layers’ constitutive properties on the mechanical response of bi-laminated composites. The effects of microstructure and interfacial interactions on the composite’s mechanical behaviour are captured through the independent effective moduli. Comparisons with the classical elastic case show the approach validation. Some numerical examples are shown. Furthermore, considering the micropolar media’s prevalence in bio-inspired systems, the model’s applicability is evaluated for reconstructing bone fractures using multi-laminated biocomposites. An important finding in this bio-inspired simulation is related to the analysis of a periodic bi-laminated micropolar composite whose isotropic constituents are a bioceramic material and a compact bone. This artificial bio-inspired material should integrate with host tissue to support cell growth and be stable and compatible. These characteristics are crucial in the enhancement of the fractured bone.
Hierarchical looping results in extreme extensibility of silk fibre composites produced by Southern house spiders (
Kukulcania hibernalis
)
Authors: Liprandi Daniele , Ramírez Martin , Schlüter Sascha , Baumgart Lucas , Joel Anna-Christin , Michalik Peter , Wolff Jonas O.
Published: June 2024

Spider silk is a tough and versatile biological material combining high tensile strength and extensibility through nanocomposite structure and its nonlinear elastic behaviour. Notably, spiders rarely use single silk fibres in isolation, but instead process them into more complex composites, such as silk fibre bundles, sheets and anchorages, involving a combination of spinneret, leg and body movements. While the material properties of single silk fibres have been extensively studied, the mechanical properties of silk composites and meta-structures are poorly understood and exhibit a hereto largely untapped potential for the bio-inspired design of novel fabrics with outstanding mechanical properties. In this study, we report on the tensile mechanics of the adhesive capture threads of the Southern house spider (
Kukulcania hibernalis
), which exhibit extreme extensibility, surpassing that of the viscid capture threads of orb weavers by up to tenfold. By combining high-resolution mechanical testing, microscopy and
in silico
experiments based on a hierarchical modified version of the Fibre Bundle Model, we demonstrate that extreme extensibility is based on a hierarchical loops-on-loops structure combining linear and coiled elements. The stepwise unravelling of the loops leads to the repeated fracture of the connected linear fibres, delaying terminal failure and enhancing energy absorption. This principle could be used to achieve tailored fabrics and materials that are able to sustain high deformation without failure.
Elasmoid fish scales as a natural fibre composite: microscopic heterogeneities in structure, mineral distribution, and mechanical properties
Authors: Tan Yiming , Jia Zian , Deng Zhifei , Li Ling
Published: June 2024

The elasmoid scales in teleost fish serve as exemplary models for natural fibre composites with integrated flexibility and protection. Yet, limited research has been focused on the potential structural, chemical, and mechanical heterogeneity within individual scales. This study presents systematic characterizations of the elasmoid scales from black drum fish (
Pogonias cromis
) at different zones within individual scales as a natural fibre composite, focusing on the microscopic structural heterogeneities and corresponding mechanical effects. The focus field at the centre of the scales exhibits a classical tri-layered collagen-based composite design, consisting of the mineralized outermost limiting layer, external elasmodine layer in the middle, and the unmineralized internal elasmodine layer. In comparison, the rostral field at the anterior end of the scales exhibits a two-layered design: the mineralized outermost limiting layer exhibits radii sections on the outer surface, and the inner elasmodine layer consists of collagen fibre-based sublayers with alternating mineralization levels. Chemical and nanoindentation analysis suggests a close correlation between the mineralization levels and the local nanomechanical properties. Comparative finite element modelling shows that the rostral-field scales achieve increased flexibility under both concave and convex bending. Moreover, the evolving geometries of isolated Mandle’s corpuscles in the internal elasmodine layer, transitioning from irregular shapes to faceted octahedrons, suggest the mechanisms of mineral growth and space-filling to thicken the mineralized layers in scales during growth, which enhances the bonding strength between the adjacent collagen fibre layers. This work offers new insights into the structural variations in individual elasmoid scales, providing strategies for bioinspired fibre composite designs with local-adapted functional requirements.
Multi-omic analyses unveil contrasting composition and spatial distribution of specialized metabolites in seeds ofCamelina sativaand other Brassicaceae
Authors: Barreda Léa , Brosse Céline , Boutet Stéphanie , Klewko Nicolas , De Vos Delphine , Francois Tracy , Collet Boris , Grain Damaris , Boulard Céline , Totozafy Jean Chrisologue , Bernay Benoît , Perreau François , Lepiniec Loïc , Rajjou Loïc , Corso Massimiliano
Published: June 2024

Seeds of Brassicaceae produce a large diversity of beneficial and antinutritional specialized metabolites (SMs) that influence their quality and provide resistance to stresses. While the distribution of these compounds has been described in leaves and roots tissues, limited information is available about their spatio-temporal accumulation in seeds.

Camelina sativa(camelina) is an oilseed Brassicaceae cultivated for human and animal nutrition, and for industrial uses. While we previously explored SM diversity and plasticity, no information is available about SM distribution and expression of related proteins and genes in camelina seeds.

In this study, we used a multi-omic approach, integrating untargeted metabolomics, data-independent acquisition proteomics, and transcriptomics to investigate the synthesis, modifications and degradations of SMs accumulated in the different seed tissues (i.e. seed coat, endosperm, and embryo) at 6 developmental and 2 germination stages. Our results showed distinct patterns of SMs and their related pathways, highlighting significant contrasts in seed composition and spatial distribution for the defence-related and antinutritional glucosinolate (GSL) compounds among camelina,Arabidopsis thaliana,andBrassica napus,three closely-related Brassicaceae species. Notably, the variation in GSL spatial distributions was primarily driven by differences in their structure and transport mechanisms. Long chain C8-C11 methylsulfinylalkyl GSLs were predominantly accumulated in the seed coat and endosperm, while mid- and short-chain C3-C7 methylsulfinylalkyl GSLs were accumulated in the embryo.

Characterizing the spatial dynamics of seed SMs provides valuable insights that can guide the development of crops with optimized distribution of beneficial and toxic metabolites, improving seed nutritional profiles for feed and food.
A Regularized Bayesian Dirichlet-multinomial Regression Model for Integrating Single-cell-level Omics and Patient-level Clinical Study Data
Authors: Guo Yanghong , Yu Lei , Guo Lei , Xu Lin , Li Qiwei
Published: June 2024

The abundance of various cell types can vary significantly among patients with varying phenotypes and even those with the same phenotype. Recent scientific advancements provide mounting evidence that other clinical variables, such as age, gender, and lifestyle habits, can also influence the abundance of certain cell types. However, current methods for integrating single-cell-level omics data with clinical variables are inadequate. In this study, we propose a regularized Bayesian Dirichlet-multinomial regression framework to investigate the relationship between single-cell RNA sequencing data and patient-level clinical data. Additionally, the model employs a novel hierarchical tree structure to identify such relationships at different cell-type levels. Our model successfully uncovers significant associations between specific cell types and clinical variables across three distinct diseases: pulmonary fibrosis, COVID-19, and non-small cell lung cancer. This integrative analysis provides biological insights and could potentially inform clinical interventions for various diseases.
Hyperactive GluN2B impairs neuroplasticity and cognition in phenylketonuria
Authors: Song Woo Seok , Bae Young-Soo , Yoon Sang Ho , Kim Myoung-Hwan
Published: June 2024

Phenylketonuria (PKU), an inborn error of phenylalanine (Phe) metabolism, is a common cause of intellectual disability. However, the mechanism by which elevated Phe levels causes cognitive impairment remains unclear. Here, we show that submillimolar Phe perturbs synaptic plasticity through the hyperactivation of GluN2B-containing NMDARs. L-Phe exhibited dose-dependent bidirectional effects on NMDA-induced currents, without affecting synaptic NMDARs in hippocampal CA1 neurons. L-Phe-induced hyperactivation of extrasynaptic GluN2B resulted in an activity-dependent downregulation of AMPARs during burst or sustained synaptic activity. Administration of L-Phe in mice decreased neural activity and impaired memory, which were blocked by pretreatment of GluN2B inhibitors. Furthermore, pharmacological and virus-mediated suppression of GluN2B reversed impaired learning in the PahEnu2PKU model. Collectively, these results suggest that the concentration of Phe in the cerebrospinal fluid of patients with PKU perturbs extrasynaptic NMDAR and synaptic plasticity, and that suppression of GluN2B may be a therapeutic strategy for improving cognitive function in patients with PKU.
Prioritising Functionally Distinct and Globally Endangered (FuDGE) sharks for conservation action
Authors: Webster Ceri , Barker Joanna , Curnick David , Gollock Matthew , Hansford James , Hoffmann Michael , Pettorelli Nathalie , Turvey Samuel T. , Walkden Patrick A. , Wang Jiaqi , Rosindell James , Gumbs Rikki
Published: June 2024

Robust species-level methods for quantifying ecological differences have yet to be incorporated into conservation strategies. Here, we describe a new approach to measure the unique contribution of species to overall functional diversity and incorporate it into an actionable conservation metric. The Functionally Distinct and Globally Endangered (FuDGE) metric directs conservation action to species whose extinction would result in significant losses of irreplaceable functional diversity. We apply FuDGE to the world’s sharks and compare it with the phylogeny-based Evolutionarily Distinct and Globally Endangered (EDGE) metric to highlight shared and divergent priorities for conservation. Identifying threatened species revealed that functionally distinct species are disproportionately threatened, with 17-24% of extant shark trait space at risk of extinction. We show that exploitation by humans threatens to disproportionately erode shark trait space, with 70% of trait space at risk. We hope our FuDGE metric will be used to guide the conservation of functionally irreplaceable species in the face of human impacts.
The 6-OHDA Parkinson’s Disease Mouse Model Shows Deficits in Sensory Behavior
Authors: Linen Savannah R. , Chang Nelson H. , Hess Ellen J. , Stanley Garrett B. , Waiblinger Christian
Published: June 2024

Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta, leading to dopamine depletion in the striatum and the hallmark motor symptoms of the disease. However, non-motor deficits, particularly sensory symptoms, often precede motor manifestations, offering a potential early diagnostic window. The impact of non-motor deficits on sensation behavior and the underlying mechanisms remain poorly understood. In this study, we examined changes in tactile sensation within a parkinsonian state by employing a mouse model of PD induced by 6-hydroxydopamine (6-OHDA) to deplete striatal DA. Leveraging the conserved mouse whisker system as a model for tactile-sensory stimulation, we conducted psychophysical experiments to assess sensory-driven behavioral performance during a tactile detection task in both the healthy and PD-like state. Our findings reveal a range of deficits across subjects following 6-OHDA lesion, including DA loss, motor asymmetry, weight loss, and varying levels of altered tactile sensation behavior. Behavioral changes ranged from no impairments in minor cases to isolated sensory-behavioral deficits in moderate cases and severe motor dysfunction in advanced stages. These results underscore the complex relationship between DA imbalance and sensory-motor processing, emphasizing the need for precise and multifaceted behavioral measurements to accurately capture the diverse manifestations of PD.

SIGNIFICANCE STATEMENT

This study explores sensory-motor aspects of Parkinson’s disease using a 6-OHDA mouse model. Leveraging the mouse whisker system, we reveal diverse deficits in tactile sensation behavior due to dopamine depletion. Our findings emphasize the importance of sensory assessments in understanding the diverse spectrum of PD symptoms.
Scalable electron tomography for connectomics
Authors: Kuan Aaron T. , Phan Sébastien , Kim Keun-Young , Mackey Mason , Kim Minsu , Peltier Steven T. , Ellisman Mark , Lee Wei-Chung Allen
Published: June 2024

We demonstrate limited-tilt, serial section electron tomography (ET), which can non-destructively map brain circuits over large 3D volumes and reveal high-resolution, supramolecular details within subvolumes of interest. We show accelerated ET imaging of thick sections (>500 nm) with the capacity to resolve key features of neuronal circuits including chemical synapses, endocytic structures, and gap junctions. Furthermore, we systematically assessed how imaging parameters affect image quality and speed to enable connectomic-scale projects.
Exploring intra- and intergenomic variation in haplotype-resolved pangenomes
Authors: Jonkheer Eef M. , de Ridder Dick , van der Lee Theo A.J. , de Haan Jorn R. , Berke Lidija , Smit Sandra
Published: June 2024

With advances in long-read sequencing and assembly techniques, haplotype-resolved (phased) genome assemblies are becoming more common, also in the field of plant genomics. Computational tools to effectively explore these phased genomes, particularly for polyploid genomes are currently limited. Here we describe a new strategy adopting a pangenome approach. To analyze both intra- and intergenomic variation in phased genome assemblies, we have made the software package PanTools ploidy-aware by updating the pangenome graph representation and adding several novel functionalities to assess synteny and gene retention, profile repeats and calculate synonymous and nonsynyonymous mutation rates. Using PanTools, we constructed and analyzed a pangenome comprising of one diploid and four tetraploid potato cultivars, and a pangenome of five diploid apple species. Both pangenomes show high intra- and intergenomic allelic diversity in terms of gene absence/presence, SNPs, indels and larger structural variants. Our findings show that the new functionalities and visualizations are useful to discover introgressions and detect likely misassemblies in phased genomes. PanTools is available at https://git.wur.nl/bioinformatics/pantools.
The Unique Pt(II)-Induced Nucleolar Stress Response and its Deviation from DNA Damage Response Pathways
Authors: Pigg Hannah C. , Alley Katelyn R. , Griffin Christopher R. , Moon Caleb H. , Kraske Sarah J. , DeRose Victoria J.
Published: June 2024

The mechanisms of action for the platinum compounds cisplatin and oxaliplatin have yet to be fully elucidated, despite the worldwide use of these drugs. Recent studies suggest that the two compounds may be working through different mechanisms, with cisplatin inducing cell death via the DNA damage response (DDR) and oxaliplatin utilizing a nucleolar stress-based cell death pathway. While cisplatin- induced DDR has been subject to much research, the mechanisms for oxaliplatin’s influence on the nucleolus are not well understood. Prior work has outlined structural parameters for Pt(II) derivatives capable of nucleolar stress induction. In this work, we gain insight into the nucleolar stress response induced by these Pt(II) derivatives by investigating potential correlations between this unique pathway and DDR. Key findings from this study indicate that Pt(II)-induced nucleolar stress occurs when DDR is inhibited and works independently of the ATM/ATR-dependent DDR pathway. We also determine that Pt(II)-induced stress may be linked to the G1 cell cycle phase, as cisplatin can induce nucleolar stress when cell cycle inhibition occurs at the G1/S checkpoint. Finally, we compare Pt(II)-induced nucleolar stress with other small-molecule nucleolar stress-inducing compounds Actinomycin D, BMH-21, and CX-5461, and find that only Pt(II) compounds cause irreversible nucleolar stress. Taken together, these findings contribute to a better understanding of Pt(II)-induced nucleolar stress, its deviation from ATM/ATR- dependent DDR, and the possible influence of cell cycle on the ability of Pt(II) compounds to cause nucleolar stress.
Role of microglia in stress-induced alcohol intake in female and male mice
Authors: Soares Alexa R. , Garcia-Rivas Vernon , Fai Caroline , Thomas Merrilee A. , Zheng Xiaoying , Picciotto Marina R. , Mineur Yann S.
Published: June 2024

Rates of alcohol use disorder (AUD) have escalated in recent years, with a particular increase among women. Women are more susceptible to stress-induced alcohol drinking, and preclinical data suggest that stress can increase alcohol intake in female rodents; however, a comprehensive understanding of sex-specific neurobiological substrates underlying this phenomenon is still emerging. Microglia, the resident macrophages of the brain, are essential for reshaping neuronal processes, and microglial activity contributes to overall neuronal plasticity. We investigated microglial dynamics and morphology in limbic brain structures of male and female mice following exposure to stress, alcohol or both challenges. In a modified paradigm of intermittent binge drinking (repeated “drinking in the dark”), we determined that female, but not male, mice increased their alcohol consumption after exposure to a physical stressor and re-exposure trials in the stress-paired context. Ethanol (EtOH) drinking and stress altered a number of microglial parameters, including overall number, in subregions of the amygdala and hippocampus, with effects that were somewhat more pronounced in female mice. We used the CSF1R antagonist PLX3397 to deplete microglia in female mice to determine whether microglia contribute to stress-induced escalation of EtOH intake. We observed that microglial depletion attenuated stress-induced alcohol intake with no effect in the unstressed group. These findings suggest that microglial activity can contribute to alcohol intake under stressful conditions, and highlight the importance of evaluating sex-specific mechanisms that could result in tailored interventions for AUD in women.
Repeatome landscapes and cytogenetics of hortensias provide a framework to traceHydrangeaevolution and domestication
Authors: Taniguchi Shota , Ishiguro Sara , Schmidt Nicola , Jost Matthias , Wanke Stefan , Heitkam Tony , Ohmido Nobuko
Published: June 2024

Background and Aims

Ornamental hortensias are bred from a reservoir of over 200 species in the genusHydrangeas.l. and are valued in gardens, households and landscapes across the globe. The phenotypic diversity of hortensia cultivars, hybrids and wild relatives is mirrored by their genomic variation, with differences in genome size, base chromosome numbers and ploidy level. We aim to understand the genomic and chromosomal basis of hortensia genome variation. Therefore, we analyze six hortensias with different origins and chromosomal setups for repeatome divergence, the genome fraction with the highest sequence turnover. This holds information from the hortensia’s evolutionary paths and can inform breeding initiatives.

Methods

We compiled a hortensia genotype panel representing members of the sectionsMacrophyllae,Hydrangea, Asperae, andHeteromallaeand reconstructed a plastome-based phylogenetic hypothesis as evolutionary basis for all our analyses. We comprehensively characterized the repeatomes by whole genome sequencing and comparative repeat clustering. Major tandem repeats were localized by multi-color FISH.

Key Results

TheHydrangeaspecies show differing repeat profiles reflecting their separation into the two majorHydrangeaclades: DiploidHydrangeaspecies from Japan show a conserved repeat profile, distinguishing them from Japanese polyploids as well as Chinese and American hortensias. These results are in line with plastome-based phylogenies. The presence of specific repeats indicates thatH. paniculatawas not polyploidized directly from the common ancestor of JapaneseHydrangeaspecies, but evolved from a distinct progenitor. Major satellite DNAs were detected over allH. macrophyllachromosomes.

Conclusions

Repeat composition among theHydrangeaspecies varies in congruence with their origins and phylogeny. Identified species-specific satDNAs may be used as cytogenetic markers to identifyHydrangeaspecies and cultivars, and to infer parental species of oldHydrangeavarieties. This repeatome and cytogenetics information helps to expand the genetic toolbox for tracing hortensia evolution and informing future hortensia breeding.
Exploring the Trajectory of Catatonia in Neurodiverse and Neurotypical Pediatric Hospitalizations: A Multicenter Longitudinal Analysis
Authors: Luccarelli James , Clauss Jacqueline A. , York Tasia , Baldwin Isaac , Vandekar Simon , McGonigle Trey , Fricchione Gregory , Fuchs Catherine , Smith Joshua R.
Published: June 2024

Objective

Catatonia is a neuropsychiatric disorder that occurs in pediatric patients with a range of associated medical, psychiatric, and neurodevelopmental disorders (NDDs). This study describes hospital care of pediatric catatonia patients and compares treatments for neurotypical patients and those with NDDs.

Methods

Retrospective cohort study from 1/1/2018 to 6/1/2023 of two academic medical centers of patients aged 18 and younger with catatonia. Patients were retrospectively assessed using the clinical global impressions-improvement (CGI-I) by two independent reviewers.

Results

One hundred sixty-five patients were hospitalized for catatonia, of whom 50.3% had an NDD. Median age was 15. One hundred sixty-four patients were treated with a benzodiazepine, with a median maximum 24-hour dose of 6 mg lorazepam-equivalents, which did not differ for patients with and without NDDs. Electroconvulsive therapy (ECT) was utilized in 14.5% of patients. Median length of medical hospitalization was 5 days and hospitalizations were longer in neurotypical patients than in patients with NDDs. In an ordinal regression model, the probability of observing at least “much improvement” (CGI < 3) was 88.3% (95% CI: 82.4% to 92.3%), with NDD diagnosis associated with a lower odds of clinical response.

Conclusions

The probability of patients achieving a CGI-I score indicating at least “much improvement” was 88.3%. Administered benzodiazepine dose and ECT treatment were similar for all patients, but neurotypical patients had longer hospitalizations than those with NDDs and had a higher odds of a more favorable clinical response. Research under controlled conditions is needed to optimize and endure equitable catatonia treatment in youth.
Can Artificial Intelligence Improve the Appropriate Use and Decrease the Misuse of REBOA?
Authors: Bokenkamp Mary , Ma Yu , Dorken-Gallastegi Ander , Proaño-Zamudio Jefferson A. , Gebran Anthony , Velmahos George C. , Bertsimas Dimitris , Kaafarani Haytham M.A. ,   MPH
Published: June 2024

BACKGROUND

The use of resuscitative endovascular balloon occlusion of the aorta (REBOA) for control of noncompressible torso hemorrhage remains controversial. We aimed to utilize a novel and transparent/interpretable artificial intelligence (AI) method called Optimal Policy Trees (OPT), to improve the appropriate use and decrease the misuse of REBOA in hemodynamically unstable blunt trauma patients.

METHODS

We trained then validated OPTs that “prescribe” REBOA in a 50:50 split on all hemorrhagic shock blunt trauma patients in the 2010-2019 ACS-TQIP database based on rates of survival. Hemorrhagic shock was defined as a systolic blood pressure ≤ 90 on arrival or transfusion requirement of ≥ 4 units of blood in the first 4 hours of presentation. The expected 24-hour mortality rate following OPT prescription was compared to the observed 24-hour mortality rate in patients who were or were not treated with REBOA.

RESULTS

Out of 4.5 million patients, 100,615 were included and 803 underwent REBOA. REBOA patients had a higher rate of pelvic fracture, femur fracture, hemothorax, pneumothorax, and thoracic aorta injury (p<0.001). The 24-hour mortality rate for the REBOA vs. non-REBOA group was 47% vs. 21%, respectively (p<0.001). OPTs resulted in an 18% reduction in 24-hour mortality for REBOA and 0.8% reduction in non-REBOA patients.

CONCLUSION

Interpretable AI models can improve mortality in unstable blunt trauma patients by optimizing the use and decreasing the misuse of REBOA. These models to date have been used to predict outcomes, but their groundbreaking use will be prescribing interventions and changing outcomes.

LEVEL OF EVIDENCE

Level IV, Prognostic
Quantifying the risk of measles importation and spread in the United States in 2024
Authors: Bidari Subekshya , Yuan Haokun , Yang Wan
Published: June 2024

Measles outbreaks have increased globally following the COVID-19 pandemic. We combine multiple data sets on global measles incidence, air travels, and vaccinations to assess the risk of travel-related importation and subsequent dissemination of measles in the United States in 2024, and identify months and states with higher measles outbreak risks.
Alterations in Aortic Elasticity Indices among Type 2 Diabetes Patients in a Low and Middle Income Country Using M-Mode Echocardiography: A Cross-Sectional Comparative Study
Authors: Dang Hai Nguyen Ngoc , Luong Thang Viet , Nguyen Khoi Quan , Nguyen Uyen Ngoc Phuong , Pham Nguyen Nguyen Khoi , Tran Hieu Thi Nguyen , Tran Hung Khanh , Cao Mai Thi Thu , Ho Binh Anh , Doan Thang Chi , Nguyen Hung Minh , Anh Hoang Tien , Van Huynh Minh
Published: June 2024

Background

Diabetes is one of the leading causes of noncommunicable diseases worldwide. It is known to induce cardiovascular remodeling, which can result in a variety of complications, including a considerable increase in aortic stiffness. While studies in Western populations have explored these effects, data on Asians, particularly Vietnamese, are limited. This study aimed to assess aortic elasticity in type 2 diabetes mellitus (T2DM) patients compared to healthy individuals.

Methods

Aortic elasticity indices were measured using M-mode echocardiography. A comparison between the healthy group and the T2DM group revealed substantial differences in aortic elasticity indices.

Results

The aortic stiffness index (ASI) was significantly greater in the T2DM group than in the control group, with median values of 6.10 (3.64-12.47) and 3.79 (2.40-8.50), respectively (p = 0.003). Aortic strain (AS) was substantially lower in the T2DM group than in the control group, with median values of 8.21 (4.24 - 13.07) and 10.66 (6.01 - 18.23), respectively (p = 0.039). Furthermore, the median aortic compliance (AC) and aortic distensibility (AD) in individuals with T2DM were 4.07 (2.28-7.44) and 3.08 (1.57-5.26), respectively, lower than those in the control group, with median values of 6.40 (3.08-10.75) and 5.33 (2.80-9.79), respectively. A longer diabetes duration was linked to a greater ASI (r = 0.43, p < 0.05), while the AS decreased (r = -0.37, p < 0.05).

Conclusions

Substantial variations in aorta elasticity indices were found using M-mode echocardiography. More research is needed to investigate the consequences of these discrepancies and their significance for clinical purposes.

Graphical Abstract
The N-terminal Region of α-Synuclein Controls Amyloid Nucleation at the Condensate Interface
Authors: Thrush Rebecca J. , Vadukul Devkee M. , Allerton Siân C. , Storch Marko , Aprile Francesco A.
Published: June 2024

α-Synuclein can self-assemble into amyloid fibrils in neurodegenerative diseases, including Parkinson’s disease. Recent studies show α-synuclein can also undergo liquid-liquid phase separation, forming biomolecular condensates. The interconnection between α-synuclein amyloid formation and liquid-liquid phase separation is evident as these condensates can mature into solid gel-like condensates containing amyloid fibrils. Furthermore, N-terminally truncated α-synuclein fragments have been found in aggregates isolated from Parkinson’s disease affected brains and are known to affectin vitroaggregation.

Here, we show that physiologically relevant N-terminal truncation of residues 1-4 significantly enhances α-synuclein self-assembly. Combining amyloid aggregation and liquid-liquid phase separation studies, we determined that this truncation increases the surface-dependent aggregation of α-synuclein, specifically at the fibril and lipid-vesicle surface, and the condensate interface. Our results enhance the understanding of α-synuclein pathology, offering new targets for therapeutic treatment. Furthermore, our quantitative approach can be extended to other systems to broaden the understanding of liquid-liquid phase separation in biology.