bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing a psychosocial competency framework for adult and older adult acute mental health inpatient care
Authors: Wood Lisa , Williams Claire , Luxon Leah , Kumary Ajvir , Roth Anthony
Published: February 2025

Objectives

Acute mental health inpatient settings care for those with acute and complex mental health needs. This study aimed to develop a psychosocial competency framework for use by multidisciplinary professional practitioners working in adult and older adult acute mental health inpatient settings.

Methods

The competence framework was developed through an iterative developmental process. Initially, the relevant literature was reviewed to draft the framework. A multidisciplinary Expert Reference Group provided their expertise to refine and develop the framework and provide professional advice on areas with a weaker evidence base.

Results

A competency framework was produced and nine key areas of competency were developed; ‘Basic knowledge of issues related to acute mental health inpatient care’, ‘Communication skills’, ‘Professional competences for all healthcare workers’, ‘Generic relationship competences’, ‘Assessment, formulation and planning’, ‘Structured care and intervention’, ‘Psychosocial interventions’, ‘Meta‐competences’, and ‘Professional competences for organisations’.

Conclusions

This competency framework will enable stakeholders to understand which competences are needed for high‐quality acute mental health inpatient care provision. It can be used to underpin training packages in this field. Our framework has been recommended as a best‐practice resource in the NHS England Acute Inpatient Mental Health Care guidance for adults and older adults.
Combining the CowPEAsy Web Application With in Planta Agroinfiltration for Native Promoter Validation in Vigna unguiculata
Authors: Jeong Jooyeon , Harris Jake , de Souza Larissa Larocca , Leonelli Lauriebeth
Published: February 2025

Cowpea (Vigna unguiculata) is an important protein source in Sub‐Saharan Africa. Optimizing resilience and productivity through genetic engineering in cowpea has been slow due in part to a lack of defined species‐specific regulatory elements and difficulty testing gene function within the native system. In many plant species, Agrobacterium‐mediated transient gene expression is widely used to validate constructs before investing in transgenic lines, but its implementation in legumes has been challenging. In this study, we optimized an in planta agroinfiltration assay in trifoliate cowpea leaves using a betalain reporter. To demonstrate the “intact plant” aspect of this system, we used this assay to characterize drought‐inducible promoters by challenging cowpea plants with drought stress. Subsequently, to identify and broaden the pool of native promoters known in cowpea, we developed a user‐friendly web application, CowPEAsy, allowing users to interrogate gene expression from our canopy‐level, developmental‐series RNA‐Seq data set. Finally, using CowPEAsy, we identified six promoters that showed constitutive expression across all conditions and verified these promoters with our transient system. This work provides an in vivo platform for preliminary validation of regulatory elements in cowpea and other legumes and enhances current genetic resources by identifying a suite of physiologically relevant promoters of varying strengths.
Genome‐Wide Association Study Elucidates the Genetic Architecture of Manganese Tolerance in Brassica napus
Authors: Raman Harsh , Bai Zetao , McVittie Brett , Mukherjee Sourav , Goold Hugh D. , Zhang Yuanyuan , Khin Nay Chi , Qiu Yu , Shamaya Nawar , Liu Shengyi , Delourme Regine , Pogson Barry J. , Balasubramanian Sureshkumar , Raman Rosy
Published: February 2025

Brassica napus (canola) is a significant contributor to the world's oil production and is cultivated across continents, yet acidic soils with aluminium (Al3+) and manganese (Mn2+) toxicities limit its production. The genetic determinants underlying natural variation for acidic soil tolerance in canola are unknown and need to be determined. Through genome‐wide association analysis of 326 canola accessions, we identified three QTLs for tolerance to Mn2+ toxicity on chromosomes A09, C03, and C09. Allelism tests between four tolerance sources confirmed that at least one locus on A09 controls Mn2+ tolerance in canola. Integrated analyses of genomic and expression QTL and Mn2+ tolerance data revealed that BnMTP8.A09, possibly in conjunction with BnMATE.C03, BnMTP8.C04 and BnMTP8.C08, play a central role in conferring Mn2+ tolerance in canola. Gene expression analysis showed that variation in BnMTP8.A09 expression could account for upto 74% of the variation in Mn2+ tolerance between individuals with extreme phenotypes. Yeast complementation assays and ectopic expression in Arabidopsis show that BnMTP8.A09 can complement manganese‐hypersensitive yeast mutant strain PMR1∆ and Arabidopsis atmtp8 mutant background, respectively and restore Mn2+ tolerance to wild‐type levels. Our multi‐omics research approach unveils the genetic architecture of Mn2+ tolerance and identifies BnMTP8.A09 as a causal gene imparting tolerance to Mn2+ toxicity in canola.
Unearthing Role Dynamics Within Innovation Ecosystem Emergence: A Case Study of Data‐Driven Circularity
Authors: Kortus Lukas , Gutmann Tobias , Kreutzer Markus
Published: February 2025

Innovation ecosystems (IE) are increasingly regarded as important vehicles for creating value from complex value propositions and addressing grand challenges through the development of a circular economy (CE). While current research emphasizes that inter‐organizational relationships can facilitate transformation toward a CE, this study enhances our understanding of collaboration in ecosystem emergence. We conducted an 18‐month ethnographic case study of an IE aimed at developing data‐driven CE solutions within the German automotive industry. This study sheds light on ecosystem dynamics by examining how the roles of partners within an IE evolve during the highly volatile emergence phase to maximize value creation. We uncover two role dimensions that differ in their temporal dynamics and offer an integrative process model of role evolution. Our study thereby contributes to the literature on role theory and CE ecosystems by outlining how partner firms collaborate in IEs to develop data‐driven CE solutions.
Conservation in conflict: Examining rural–urban discourse in wolf reintroduction policy in Colorado
Authors: Gabehart Kayla M.
Published: February 2025

Wolf reintroduction and management is a highly conflictual topic in both the United States and Europe, enflaming rural–urban tensions and pitting agriculture interests against environmentalists. This study examines the case of gray wolf reintroduction in Colorado. The reintroduction decision was decided by state popular vote on a citizen‐introduced ballot initiative, Proposition 114, in 2020. While a majority of Coloradans voted in favor of reintroduction, this vote was almost exclusively divided along rural–urban geographic lines. To analyze these cleavages and the conflict therein, this study examines the changing coalitional discourse surrounding wolf reintroduction policy in Colorado. This study captures changes in the policy conflict from the beginning of 2020 when the ballot initiative to reintroduce gray wolves was first proposed, to the passage of that initiative on the November 2020 ballot, through the related legislative bills proposed in the spring of 2021 in an effort to maintain rural representation in the reintroduction process. This case utilizes the advocacy coalition framework (ACF) and emotion belief analysis (EBA) to analyze news media and legislative testimony.
Grain‐fabric alignments in a mixed carbonate–siliciclastic mass‐transport complex: The Cutoff Formation, Permian Basin, Texas
Authors: Simabrata Hanaga , Jobe Zane R. , Hou Pengfei , Wood Lesli J. , Kus Kaci , Hurd Gregory
Published: February 2025

Mass‐transport complexes undergo fabric modification during emplacement that results in the alignment of elongated grains. Grain‐fabric alignments promote mechanical and petrophysical anisotropy, which has broad implications for hydrocarbon extraction, carbon sequestration and geohazard assessment. These implications are likely more pronounced in mass‐transport complexes with carbonate components, where the proportion of elongated grains can be much higher as compared to siliciclastic mass‐transport complexes. However, the characteristics of grain‐fabric alignments in mass‐transport complexes are poorly understood. This study inspects the predictive properties of grain‐fabric alignments that include three‐dimensional orientation, fine‐scale heterogeneity, as well as the control of grain lengths and clay‐mineral abundance. The mixed carbonate–siliciclastic mass‐transport complex of the Cutoff Formation contains prolific spicule bioclasts (prolate‐shaped), which enabled qualitative and quantitative grain‐fabric analysis. Investigation of over 29 000 spicule bioclasts from oriented thin sections indicates that: (i) the long‐axes of elongated grains rest on the plane of lamination, which can be parallel or tilted/folded with respect to bedding; (ii) the long‐axes are transverse to palaeotransport direction; (iii) the homogeneity of alignment (termed here ‘H‐index’) of elongated grains are variable across samples, as well as locally within the same sample; (iv) H‐index increases with greater grain lengths (approximately constant aspect ratio) and with the presence of clay minerals; and (v) H‐index is likely controlled by differential stress and/or variation in microstructure types. These results improve current understanding and predictability of grain‐fabric alignments and deformation in mass‐transport complexes, as well as the associated mechanical and permeability anisotropy.
Dynamic Analysis of Aortic Flows: Transient Response of Flow-Compliance and Flow-Resistance When Subjected to Sinusoidal Variations of Input Pressure
Authors: Nisar Syed Anas , Banerjee Debjyoti
Published: February 2025

The dynamic response of the ascending aorta to sinusoidal pressure inputs using the hyperelastic Mooney–Rivlin model was explored in this study. Flow capacitance models were deployed to estimate the capacity of the aorta by predicting the change in blood volume as a function of the pressure variation. The results gleaned from this study are crucial for understanding the cardiovascular malfunction. The numerical predictions obtained from the hyperelastic model were validated using results in the literature. The numerical model was formulated using nonlinear stress–strain characteristics of aortic tissues, and this strategy provides sufficient accuracy for predicting the response of the aorta to pressure variations (that mirror natural heart rhythms). The results from this study demonstrate the essential role of the aorta in mitigating the effects of pulsatile blood flow, thereby protecting the vascular system from significant pressure spikes by acting as a damper that leverages flow capacitance effects. By emphasizing the need to integrate realistic, patient-specific bio-mechanical properties into simulation models, the results obtained from this study set the stage for advancing diagnostic, therapeutic, and management strategies in cardiovascular therapy. These models can be refined extensively using actual patient data and can provide a platform for future exploration by integrating them into clinical diagnostic systems, which in turn, can improve therapeutic outcomes for cardiovascular patients.
Nonlinearity Measure for Nonlinear Dynamic Systems Using a Multi-Model Framework
Authors: Ahmadi Mahdi
Published: February 2025

This article is concerned with the assessment of nonlinearity in nonlinear dynamic systems to determine the feasibility of controlling a nonlinear system with either a single linear controller or a multi-model controller. The nonlinear system is decomposed into a bank of linear models, resulting in exploiting the gap metric and the maximum stability margin value of these linear models to introduce two key attributes. The first attribute, termed “slavery quality,” quantifies the behavior of the linear models by examining the feasibility of stabilizing each linear model through the use of other local controllers. In contrast, the second attribute, referred to as “mastery quality,” assesses the ability of each local controller to stabilize the linear systems. The collaboration of the mastery and the slavery qualities not only facilitates assessing the nonlinearity degree of a nonlinear system but also supports the selection of nominal linear models. Three nonlinear systems with different characteristics are investigated. The simulations validate the effectiveness and benefits of the proposed method in understanding the adequacy of a single linear controller or a multi-model controller for a given nonlinear system.
DGEN Aeropropulsion Research Turbofan Core/Combustor-Noise Measurements—Source Separation
Authors: Hultgren Lennart , Boyle Devin / K , Henderson Brenda
Published: February 2025

Acoustic data obtained using a small turbofan engine are further analyzed to improve the understanding of core/combustor noise. The relative impact of this propulsion-noise source for civilian-transport aircraft on airport community noise is expected to significantly increase in the future. Simultaneous high-data-rate acoustic measurements acquired using a circumferential infinite-tube-probe array at the core-nozzle exit in conjunction with a farfield microphone array are processed. The test matrix contains engine operational points from idle to the engine-maximum setting, with measurements repeated for different circumferential array configurations, as well as for redundancy. The combustor-noise contribution to the farfield noise signature is obtained using an advanced source separation method that correlates the farfield microphone measurements with a modal decomposition of the unsteady pressure field at the core-nozzle exit. The advantages of the present approach compared to the classical two-signal source-separation method are discussed.
Computational Study on SPL and DPL Bio-heat Models of Heat Transfer in Irregular Tumors during Magnetic Nanoparticles Hyperthermia
Authors: Kumar Sushil , Meena Bhagya Shree
Published: February 2025

The ability to accurately predict and control the tissue temperature distribution profile is critical to the success of hyperthermia treatment. Magnetic nanoparticle hyperthermia is a subclass of hyperthermia treatment that can selectively heat a tumor without damaging the surrounding healthy tissues. Living tissues are highly non-homogeneous, and non-Fourier thermal behavior is observed experimentally in tissues. The two-dimensional single phase lag and dual phase lag models with non-Fourier boundary conditions have been considered to investigate the temperature profile in biological tissues during hyperthermia treatment. Arbitrary-shaped and circular-shaped tumor tissue domains surrounded by healthy circular tissue are considered for simulation. We obtain the numerical solution for the models by combining Gaussian RBFs and shifted Chebyshev polynomials for the spatial and temporal directions, respectively. The impacts of phase lag times τq, τT and heat source parameters (H0, ϕ, f) on thermal responses in tumors are investigated. The analysis shows that tumor domains are heated without causing much harm to the healthy tissue domain.
Adjuster Absorber Rods Return To Service At Plngs
Authors: Krishnamoorthy Jaswin , Deveaux Dominique , Mullin Derek , Usalp Can , Sun Liqun , Sharpe Jason , Rouben Daniel
Published: February 2025

The original CANDU® 600 design utilizes adjuster absorber rods to flatten the flux shape in the reactor core optimize power output, compensate for fuel burnup, provide excess reactivity to overcome 135Xe buildup following a power reduction, and allow for reactivity shim. At Point Lepreau Nuclear Generating Station (PLNGS) in 1999, adjuster absorber banks 6 and 7 were locked in the reactor core and removed from service. Later in 2019 adjuster absorber banks 1 through 5 were placed on manual. Since then, a significant program was put in place to restore adjuster banks 1 through 6 to service, which was successfully completed in October 2023. Adjuster absorber bank 7 remains locked in-core. This paper summarizes the rationale for removing the PLNGS adjuster absorbers from service, the effort required for their restoration, applicable lessons learned, and next steps.
Lateral and Transverse Stiffness Requirements for Supports of Pipeline Systems Conveying Fluids
Authors: Attia Saher/Salama , Mohareb Magdi , Botros Kamal K. , Adeeb Samer
Published: February 2025

Elevated pipelines systems are commonly supported by flexible steel frames at regular intervals. During operation, these systems can be subjected to sources of harmonic excitations. In order to control the vibration response for such systems, designers may target a threshold minimum fundamental natural frequency for the system. Within this context, the study first shows that, within the ranges of straight pipelines geometries commonly used in the oil and gas industry, the fluid mass and stiffness of the intermediate flexible supports significantly impact the fundamental natural frequency of the system, while fluid velocity within the practical range of the oil and gas industry, temperature differential between the installation and operating temperatures, and pipe self-weight are less important or negligible. The study further extends the analysis to non-straight piping systems with L-Shape and S-Shape configurations. In conclusion, design formulas are proposed to estimate the required lateral and transverse stiffnesses for the supporting systems to attain a specified fundamental natural frequency for straight and curved pipelines. Natural frequency comparisons with finite element solutions show the validity of the proposed design formulas.
Transient Mechanics: A Perspective on Bioresorbable Electronics
Authors: Liu Pei , Lee Chihtong , Carusetta Nicole , Avila Raudel
Published: February 2025

Materials, devices, and systems with the ability to physically disappear create unique opportunities for vanishing electronic technologies in biomedicine. Their transient response, achieved by resorption, degradation, and disintegration, can be carefully programmed through material selection and mechanical design to last from days to weeks when exposed to physiological environments. In this perspective, we examine the mechanics functionality of transient electronics and their diverse applications ranging from compact medical implants to zero-waste environmental hardware. Using a question–answer structure, we highlight the important role of temporary, yet stable, properties for mechanical, electrical, and chemical disintegration over controlled operational lifetimes. Mechanics and electromagnetic strategies are discussed to devise new classes of bioresorbable electronics for the unconventional biomedicine opportunities that can be achieved by vanishing electronic technologies.
Influence of thickness profile and bracing pattern in the radiation patterns of archtop guitars
Authors: Longo Giacomo , Gonzalez Sebastian , Dalisay Jon Dewitt Enriquez , Nania Thomas , Antonacci Fabio
Published: February 2025

In this study, we investigate the influence of the thickness profile of the top plate and bracing pattern on the vibrational and acoustic properties of archtop guitars through finite element simulations. Starting from a laser scan of a real archtop guitar, we develop a fully parametric three-dimensional model of the guitar body. The thickness profile is parametrically controlled by adjusting the lower surface while maintaining the fixed upper surface. Both geometric and numerical modeling techniques are used to analyze the mechanical behavior of the guitar, including modal analysis, and acoustic behavior, focusing on sound intensity, and directivity. Our simulations reveal that variations in the thickness profile significantly affect the modal response and sound radiation patterns. In particular, we highlight the relationship between the vibrational modes and radiation patterns, demonstrating that changes in thickness lead to shifts in eigenfrequencies and variations in radiated sound pressure levels. The models and simulation code are made openly available to facilitate further research in the acoustics of archtop guitars.
Comparative Validity of Two Thigh-Worn Activity Monitors in Free-Living Conditions
Authors: Duhamahoro Jimmy , Lamoureux Nicholas R. , Hibbing Paul R. , Taylor Matthew A. , Welk Gregory J.
Published: February 2025

Background: There is considerable interest in evaluating 24-hr activity cycles; however, the ideal tools for doing so have yet to be identified. Monitor-based approaches are widely endorsed for capturing movement, but novel methods are needed to assess the context of physical behaviors. This study evaluated the validity of two thigh-worn devices in assessing physical behaviors during a 24-hr period. Methods: 21 participants concurrently wore Move 4 and activPAL 3 microdevices on the thigh for a full day and then completed the Activities Completed over Time in 24 Hours recall survey. Equivalence tests (with activPAL as a reference) and mean absolute percent error were utilized to assess device agreement (at the minute and day levels) for energy expenditure (METs), steps, and time in different physical behaviors (moderate-to-vigorous physical activity, light physical activity, sedentary, and sleep). The Activities Completed over Time in 24 Hours data were used to evaluate the agreement in specific contexts. Findings: Devices had good agreement across 24-hr behaviors and for steps and METs at both day and minute levels. Estimates from the Move 4 were equivalent to activPAL for moderate-to-vigorous physical activity, sedentary, and steps, whereas METs, light physical activity, and sleep behaviors were not equivalent. The mean absolute percent error for METs in commonly reported activities ranged from 11.31% (watching television) to 20.88% (weightlifting). Conclusion: There was moderate-to-high convergent validity between Move 4 and activPAL in profiling 24-hr physical behaviors. The study highlights the value of combining device-based and report-based measures to evaluate physical behaviors over a 24-hr period. However, more research with larger and more diverse samples is warranted.
Developing a Conceptual Model for Collective Patterns and Leisure-Time Physical Activity Inequalities Among Adults
Authors: Jones Sophie Marie , Hunter Ruth F. , Garcia Leandro
Published: February 2025

Background: Despite extensive efforts to tackle the unequal levels of leisure-time physical activity (LTPA) among adults, our understanding of how these inequalities are sustained over time is minimal. Existing approaches often overlook the complex dynamic, and typically nonlinear interactions, which shape physical activity patterns. Therefore, this paper aims to capture these dynamic interactions and processes which influence an individual’s decision to practice LTPA, with a specific focus on the influence of income. Methods: The conceptual model was developed in 4 main stages: (1) initial draft development, (2) realist reviews, (3) expert consultation, and (4) finalization. Results: The conceptual model has intention as its central construct to practice LTPA, and intention is directly influenced by dynamic interrelated processes between individual’s economic, psychosocial, and perceived physical environment factors. Conclusion: From the multiple theories, evidence, and expert agreement, we are confident that our conceptual model expresses the dynamic interactions which shape an individual’s decision to practice LTPA in a context of socioeconomic inequalities. Going forward, this work will be used to conceptualize and inform the development of an agent-based model to simulate LTPA inequalities among adults and can be expanded or adapted to other uses, such as intervention development.
Rehabilitation and Implementation of a Continuum for Return to Sport in an Amateur Basketball Player With Subtalar Dislocation: A Case Report
Authors: Soliño Santiago , Fabani Franco , Bossio Tomás , López Joaquín , Cruz Porollan Juan
Published: February 2025

Context: Subtalar dislocation is a rare but severe condition that usually requires emergency attention and could be associated with secondary injuries. Most of the research about this injury is case reports focused on the medical management, so there are no guidelines for rehabilitation and return to sport (RTS). This case report describes the rehabilitation and RTS in an amateur basketball player with an isolated medial subtalar dislocation on his right foot. Case Presentation: A 20-year-old amateur basketball player suffered a forced foot inversion after landing on an opponent’s foot. The patient was taken to the emergency department for a closed reduction under anesthesia, followed by 2 weeks in a cast and 3 weeks in a walker boot. Management and Outcomes: Rehabilitation started after the immobilization period with the main objective of returning to the same level of competition. It was organized through a 4 phase continuum with a stepwise approach. After 16 weeks since injury, the patient returned to team training. Conclusions: To our knowledge, this is the first report to inform on rehabilitation and RTS of medial subtalar dislocation. The 4 phases continuum model could be useful for clinicians for safe progression in this rare condition.
Interpretable AI for inference of causal molecular relationships from omics data
Authors: Dibaeinia Payam , Ojha Abhishek , Sinha Saurabh
Published: February 2025

The discovery of molecular relationships from high-dimensional data is a major open problem in bioinformatics. Machine learning and feature attribution models have shown great promise in this context but lack causal interpretation. Here, we show that a popular feature attribution model, under certain assumptions, estimates an average of a causal quantity reflecting the direct influence of one variable on another. We leverage this insight to propose a precise definition of a gene regulatory relationship and implement a new tool, CIMLA (Counterfactual Inference by Machine Learning and Attribution Models), to identify differences in gene regulatory networks between biological conditions, a problem that has received great attention in recent years. Using extensive benchmarking on simulated data, we show that CIMLA is more robust to confounding variables and is more accurate than leading methods. Last, we use CIMLA to analyze a previously published single-cell RNA sequencing dataset from subjects with and without Alzheimer’s disease (AD), discovering several potential regulators of AD.
Biglycan fragment modulates TGF-β activity in intervertebral disc via an eIF6-coupled intracellular path
Authors: Zhu Manyu , Wu Stanley Chun Ming , Tam Wai-Kit , Wong Chun Kit , Liao Peng , Cheah Kathryn S. , Chan Danny , James Aaron W. , Leung Victor Y.
Published: February 2025

Biglycan, a pericellular small leucine-rich proteoglycan, is crucial in skeletal development and regeneration. Intervertebral disc degeneration (IDD) contributes to back pain and disability. Previous studies have shown that biglycan promotes hypoxic survival of disc progenitor cells, while its depletion accelerates IDD. An association of pathological tissue remodeling with a biglycan fragment
344
YWEVQPATFR, termed Bgm1, has been reported, however its role is yet to be defined. Using a custom antibody, we detected Bgm1 in human and mouse nucleus pulposus, with prominent intracellular expression in notochordal cells. Proteomic analysis revealed that Bgm1 interacts with eukaryotic translation initiation factor 6 (eIF6), a key player in ribosome biogenesis. Bgm1 dysregulates eIF6 localization in notochordal cells, affecting nucleocytoplasmic transport. Induced IDD in mice showed elevated nuclear eIF6 expression and reduced Bgm1 in degenerating nucleus pulposus. Transcriptome analysis suggests that Bgm1 regulates fatty acid metabolism and glycolysis in a transforming growth factor–β–dependent manner, highlighting its potential role in metabolic control in spinal joint homeostasis.
ATR-hippo drives force signaling to nuclear F-actin and links mechanotransduction to neurological disorders
Authors: Chatzifrangkeskou Maria , Stanly Tess , Koennig Delia , Campos-Soares Luana , Eyres Michael , Hasson Alexander , Perdiou Alexandra , Vendrell Iolanda , Fischer Roman , Das Sayoni , Gardner Steve , Go Simei , Futcher Ben , Newton Ashley , Skourides Paris , Szele Francis , O’Neill Eric
Published: February 2025

The mechanical environment is sensed through cell-matrix contacts with the cytoskeleton, but how signals transit the nuclear envelope to affect cell fate decisions remains unknown. Nuclear actin coordinates chromatin motility during differentiation and genome maintenance, yet it remains unclear how nuclear actin responds to mechanical force. The DNA-damage kinase ataxia telangiectasia and Rad3-related protein (ATR) translocates to the nuclear envelope to protect the nucleus during cell motility or compression. Here, we show that ATR drives nuclear actin assembly via recruitment of Filamin-A to the inner nuclear membrane through binding of the hippo pathway scaffold and ATR substrate, RASSF1A. Moreover, we demonstrate how germline RASSF1 mutation disables nuclear mechanotransduction resulting in cerebral cortex thinning and associates with common psychological traits. Thus, defective mechanical-regulated pathways may contribute to complex neurological disorders.
A reassessment of the “hard-steps” model for the evolution of intelligent life
Authors: Mills Daniel B. , Macalady Jennifer L. , Frank Adam , Wright Jason T.
Published: February 2025

According to the “hard-steps” model, the origin of humanity required “successful passage through a number of intermediate steps” (so-called “hard steps”) that were intrinsically improbable in the time available for biological evolution on Earth. This model similarly predicts that technological life analogous to human life on Earth is “exceedingly rare” in the Universe. Here, we critically reevaluate core assumptions of the hard-steps model through the lens of historical geobiology. Specifically, we propose an alternative model where there are no hard steps, and evolutionary singularities required for human origins can be explained via mechanisms outside of intrinsic improbability. Furthermore, if Earth’s surface environment was initially inhospitable not only to human life, but also to certain key intermediate steps required for human existence, then the timing of human origins was controlled by the sequential opening of new global environmental windows of habitability over Earth history.
Decoding aptamer-protein binding kinetics for continuous biosensing using single-molecule techniques
Authors: Filius Mike , Fasching Lena , van Wee Raman , Rwei Alina Y. , Joo Chirlmin
Published: February 2025

Continuous biosensing provides real-time information about biochemical processes and holds great potential for health monitoring. Aptamers have emerged as promising alternatives over traditional biorecognition elements. However, the underlying aptamer-target binding interactions are often poorly understood. Here, we present a technique that can decode aptamer-protein binding interactions at the single-molecule level. We demonstrate that our single-molecule assay is able to decode the underlying binding kinetics of aptamers despite their similar binding affinity. Guided by computational simulations and validated with quartz crystal microbalance experiments, we show that the quantitative insights generated by this single-molecule technique enabled the rational understanding of biosensor performance (i.e., the sensitivity and limit of detection). This capability was demonstrated with thrombin as the analyte and the structurally similar aptamers HD1, RE31, and NU172 as the biorecognition elements. This work decodes aptamer-protein interactions with high temporal resolution, paving the way for the rational design of aptamer-based biosensors.
Epithelialized chimeric repairing patch supports in situ healing of tracheal fistula
Authors: Song Xingqi , Bai Baoshuai , Li Ke , Wei Xun , Wang Yuesheng , Jia Zenghui , Ma Yuanqi , Zhang Yixin , Ji Guangyu , Zhou Guangdong , Lei Dong
Published: February 2025

Tracheal fistula (TF) is a severe thoracic disease characterized by high mortality rates, and current treatment methods present substantial risks while presenting challenges in reepithelialization. In this study, we developed a chimeric repairing patch (CRP) featuring a double-disc structure, designed to seal TF defects and promote organized tissue regeneration. The CRP incorporates a double–cross-linking silk fibroin network and hierarchical micropores, resulting in a flexible, hydrophilic, and biocompatible patch with tissue-matching mechanical properties. The CRP could effectively seal defects and encourage tissue ingrowth, successfully repairing TF. A tissue-engineered epithelialized CRP (E-CRP) was further developed to enhance in situ reepithelialization. The CRP demonstrated reliable structural stability and facilitated effective tissue regeneration and functional reconstruction of TF defects in a large animal model. Furthermore, the customized CRPs might be preloaded into a bronchoscope and precisely delivered to TF defects via noninvasive implantation. Consequently, the proposed CRP/E-CRP represents a promising scaffold for TF treatment, with substantial transformative potential in clinical practice.
A platform supporting generation and isolation of random transposon mutants in
Chlamydia trachomatis
Authors: Hawk Caroline , Hamdzah Nur , Dimond Zoe , Fields Kenneth A.
Published: February 2025

Chlamydia
species represent a paradigm for understanding successful obligate intracellular parasitism. Despite limited genetic malleability, development of genetic tools has facilitated the elucidation of molecular mechanisms governing infectivity. Random mutagenesis approaches provide one of the most powerful strategies available to accomplish untargeted elucidation of gene function. Unfortunately, initial progress in transposon-mediated mutagenesis of
Chlamydia
has been challenging. To increase efficiency, we developed a plasmid-based system that couples conditional plasmid maintenance with a previously described strategy leveraging inducible expression of the
Himar1
-derived C9 transposase. Our pOri-Tn(Q) construct was maintained in
Chlamydia trachomatis
cultivated with antibiotics but was rapidly cured in the absence of antibiotic selection. pOri-Tn(Q) supported transposition events when transposase expression was induced during infection. Induction was accompanied by loss of the plasmid backbone when penicillin G was used to select for only the transposable element. C9 induction during iterative passaging was used to increase the overall insertion frequency and accumulate an expanded pool of transposon mutants. The approach supported isolation of individual mutant strains from the mixed pool, and whole-genome sequencing confirmed that the recovered strains harbored single insertions.

IMPORTANCE

Chlamydia trachomatis
is a prevalent human pathogen exerting a tremendous negative impact on human health. A complete understanding of how these bacteria create and maintain an intracellular niche and avoid/subvert host defense mechanisms to cause disease is lacking. The utility of transposon-mediated, random mutagenesis in supporting forward genetic studies is well established in a multitude of genetically tractable systems. This study reports the development of a plasmid-based system capable of generating mutant pools and supporting subsequent isolation of individual transposon mutants. This step is an important advance in providing a mechanism capable of supporting downstream studies interrogating chlamydial biology.
Rickettsial pathogen augments tick vesicular-associated membrane proteins for infection and survival in the vector host
Authors: Namjoshi Prachi , Kolape Jaydeep , Patel Avni , Sultana Hameeda , Neelakanta Girish
Published: February 2025

Anaplasma phagocytophilum
is an obligate intracellular rickettsial pathogen that infects humans and animals. The black-legged tick
Ixodes scapularis
acts as a vector and transmits this bacterium to the vertebrate host. Upon entry into a host cell,
A. phagocytophilum
resides and multiplies in a host-derived vacuole called morulae. There is not much information available on the molecules that play an important role(s) in
A. phagocytophilum
entry and formation of these morulae in tick cells. In this study, we provide evidence that tick vesicular-associated membrane proteins, VAMP3 and VAMP4, play important roles in this phenomenon. Quantitative real-time polymerase chain reaction (QRT-PCR) analysis showed that both
vamp3
and
vamp4
transcripts are significantly upregulated at early time points of
A. phagocytophilum
infection in tick cells. We noted that both VAMP3 and VAMP4 predominantly localized to the
A. phagocytophilum
-containing vacuole. RNAi-mediated silencing of
vamp3
and/or
vamp4
expression, followed by confocal microscopy and expression analysis, indicated an impairment in
A. phagocytophilum
morulae formation in tick cells. We also noted that VAMP3 and VAMP4 play a role in the
A. phagocytophilum
persistent infection of ticks and tick cells. Furthermore, RNAi-mediated silencing of expression of arthropod
vamp3
and
vamp4
affected bacterial acquisition from an infected murine host to ticks. Collectively, this study not only provides evidence on the role of arthropod vesicular-associated membrane proteins in
A. phagocytophilum
morulae formation in tick cells but also demonstrates that these proteins are important for bacterial acquisition from an infected vertebrate host into ticks.

IMPORTANCE

Anaplasma phagocytophilu
m is a tick-borne pathogen primarily transmitted by black-legged Ixodes scapularis ticks to humans and animals. This bacterium enters host cells, forms a host-derived vacuole, and multiplies within this vacuole. The molecules that are critical in the formation of host-derived vacuole in tick cells is currently not well-characterized. In this study, we provide evidence that arthropod vesicular-associated membrane proteins, VAMP3 and VAMP4, are critical for
A. phagocytophilum
early and persistent infection in tick cells. These arthropod proteins are important for the formation of host-derived vacuoles in tick cells. Our study also provides evidence that these proteins are important for
A. phagocytophilum
acquisition from the infected murine host into ticks. Characterization of tick molecules important in bacterial entry and/or survival in the vector host could lead to the development of strategies to target this and perhaps other rickettsial pathogens.
12. Case Studies
Authors: Lawrence Ursula , Roberts Toby , Powrie William , Preene Martin , Lee Mark , de Freitas Michael , Blower Tim , Marinos Vassilis
Published: February 2025

This chapter contains nine relevant case studies demonstrating the management of groundwater risk in engineering geological situations. The chapters include scenarios including modelling, risk management and both surface and subsurface works.
DUTNG: Employing dynamically updating traffic network graph for short-term traffic flow prediction
Authors: Lou Jungang , Wu xuhong , Zhao Kang , Shen Qing , Yang Jinnan
Published: February 2025

The complex topology of actual road networks and the interlinked nature of traffic flow with spatiotemporal factors pose challenges to traditional node-static correlation models. Therefore, the DUTNG model—a short-term traffic flow prediction model leveraging dynamically updated traffic network graphs—has been proposed to address these issues. Initially, a parameterized dynamic graph learning module is employed for real-time road condition modeling, enhancing the expressiveness of the short-term traffic network. Subsequently, a dynamic time extraction network is integrated into the dynamic graph to address the extraction of features from traffic flows across various time ranges. Additionally, stacked dynamic spatial extraction network modules resolve challenges related to varying regional influences. Finally, these three modules are sequentially integrated, enhancing the model’s ability to extract spatiotemporal correlations. Experimental studies on real-world datasets (California highway network) demonstrate that this model significantly outperforms machine learning models. Compared to recent benchmark models, its performance improves by 5.3% to 18.7%.
Deciphering the Impacts of Al, Fe, Li Sulfate Impurities on the Synthesis and Performances of LiNi0.6Mn0.2Co0.2O2 Cathode Materials
Authors: Chable Johann , Bohn Nicole , Raab Monika , Al-Tobul Shadi , Bergfeldt Thomas , Müller Marcus , Binder Joachim R.
Published: February 2025

The recycling of LiNi0.6Mn0.2Co0.2O2 cathode active material (CAM) from Li-ion batteries cannot avoid the presence of impurities in the recycled Ni-, Co-, or Mn sulfates. The precise understanding of the impurities influence on the resynthesis is of uttermost importance. To tackle this goal, this study simulated the resynthesis process by adding on purpose and separately Al-, Fe-, and Li-sulfate in the regular CAM synthesis. Their effects on the morphology, elemental composition, crystal structure, and electrochemical performances of Ni0.6Mn0.2Co0.2Mx(OH)2 and LiNi0.6Mn0.2Co0.2MxO2 were systematically investigated for x = 0.0005, 0.005, and 0.05. The in-house reference material synthesized via a coprecipitation reaction allowed to produce a well-characterized basis. Above xAl = 0.0005, the hydroxide secondary particles lost their spherical form and above xFe = 0.005, the crystal structure was affected. Both effects led to cell capacity decay, contrary to the discrete influence of Li. The absence of any positive effects reported by similar studies, the complexity of the various influences of these foreign ions and the limitations of the coin cells tests were pointed out. These results are a solid groundwork for future academic and industrial studies in the field of circular economy, by determining a tolerance threshold for each impurity.
Mass Cytometric Analysis of Circulating Monocyte Subsets in a Murine Model of Diabetic Gastroparesis
Authors: AlAsfoor Shefaa , Jessen Erik , Pullapantula Suraj R. , Voisin Jennifer R. , Hsi Linda C. , Pavelko Kevin D. , Farwana Samera , Patraw Jack A. , Chai Xin-yi , Ji Sihan , Strausbauch Michael A. , Cipriani Gianluca , Wei Lai , Linden David R. , Hou Ruixue , Myers Richard , Bhattarai Yogesh , Wykosky Jill , Burns Alan J. , Dasari Surendra , Farrugia Gianrico , Grover Madhusudan
Published: February 2025

Circulating monocytes (Mo) are precursors to a subset of gastric resident-muscularis macrophages. Changes in muscularis-macrophages (MMs) result in delayed gastric emptying (DGE) in diabetic gastroparesis. However, the dynamics of Mo in the development of DGE in an animal model are unknown. Using CyTOF and computational approaches, we show a high heterogeneity within the Mo-population. In DGE mice, via unbiased clustering, we identified two reduced Mo clusters which exhibit migratory phenotype (Ly6ChiCCR2hi-intCD62LhiLy6GhiCD45RhiMERTKhiintLGALS3intCD14intCX3CR1lowSiglec-Hint-low) resembling classical-Mo (CMo-like). All markers enriched in these clusters are known to regulate cell differentiation, proliferation, adhesion, and migration. Trajectory inference analysis predicted these Mo as precursors to subsequent Mo-lineages. In gastric muscle tissue, we demonstrated an increase in the gene expression levels of chemokine receptor Ccr2 and its ligand Ccl2, suggesting increased trafficking of classical-Mo. These findings establish a link between two CMo-like clusters and the development of DGE phenotype and contribute to better understanding of the heterogenicity of the Mo-population.
Altitude-induced central sleep apnea does not affect mean sleep oxygen saturation in young healthy males
Authors: Heiniger G. , Raemy F. , Solelhac G. , Imler T. , Waeber A. , Lambercy K. , Bradley B. , Lecciso G. , Degache F. , Heinzer Raphael C
Published: February 2025

At high-altitude, periodic breathing (PB) can occur during sleep in healthy individuals. PB is characterized by a cyclical ventilatory pattern that alternates between central sleep apnea and brief episodes of hyperventilation. The aim of this study was to evaluate the effect of periodic breathing on sleep SpO2.

36 healthy males subjects (median-age:26[24-28]years old, median BMI:22.7[21.1-23.8]Kg/m2) underwent a polysomnography at a simulated altitude of 3,500 meters(FiO2:13%). Correlations were sought between the Apnea-Hypopnea Index(AHI), Oxygen Desaturation Index(ODI), percentage of total sleep time spent in PB, and mean SpO2 throughout the entire sleep period by calculating the Spearman's rank correlation test. We identified 20 participants who had experienced at least 3 minutes of PB adjacent to at least 3 minutes of regular breathing(RB). We compared the mean SpO2 between the two respiratory patterns using Wilcoxon signed-rank test.

At simulated-altitude, the subjects spent a median-IQR of 43.9[12.5-79.1]% of sleep in PB and the median-AHI was 77.3[31.4-127.5]/h. Median awake and asleep SpO2 were 75.4[24-28]% and 68.5[66.4-72.5]% respectively. We found no within subject difference in SpO2 between RB and PB periods (median-IQR RB vs PB: 67.2%{63.8-74.8%} vs 67.5%{64.5-73.9%},p=0.43). No significant correlation was found between the mean sleep SpO2 and AHI(n=36,rs=-0.19,p=0.26), ODI(n=36,rs=-0.23,p=0.18) or PB(n=36,rs=-0.07,p=0.67). Awake SpO2 was correlated with mean SpO2 during sleep(n=36,rs=0.55;p=0.001).

PB per se does not have a detrimental effect on mean SpO2 in young healthy males. Correlation between awake and sleep SpO2, suggests that sleep SpO2 at high-altitude is primarily determined by baseline oxygen saturation rather than the respiratory pattern developed during sleep.
Incidentally Discovered Duodenal Gastrointestinal Stromal Tumour (GIST): Operative Treatment and Problems After Surgery—A Case Report and Literature Review
Authors: Lüthje Peter , Nurmi-Lüthje Ilona
Published: February 2025

Background: Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours of the digestive tract that can involve any part of the tract. The tumours can be harmless or life‐threatening.

Materials and Methods: A case report of a surgeon who fell in a Finnish sauna, and he immediately felt that some ribs were broken. Magnetic resonance imaging and ultrasound showed three fractured ribs and an intrasplenic haematoma. Contrast‐enhanced computed tomography (CT) demonstrated a small intrasplenic anomaly but no haematoma. Incidentally, an incidentaloma in the left adrenal gland was diagnosed. Three months later, a control CT scan was performed. The radiological findings on the adrenal gland and laboratory examinations matched those of a benign adenoma. Incidentally, a small duodenal tumour was diagnosed. At the same time, anaemia (haemoglobin: 104 g/L) and iron deficiency (ferritin: 8 μg/L) were noticed. An esophagogastroduodenoscopy showed an intramural tumour localised after the bulb‐descending junction. Because the tumour was submucosal, the pathological diagnosis failed. Three months later, a radical surgical resection of the tumour with a resection margin of 2 mm and primary closing of the duodenum was performed. Pathological examination showed a well‐circumscribed submucosal mesenchymal tumour with spindle cells. A tumour‐free margin was uncertain. Immunohistochemistry findings showed a GIST. Due to the uncertain margin, an esophagogastroduodenoscopy control was planned at 2 years postoperatively. The patient disagreed with the decision and ordered a private control CT 3 months after the operation. The new CT found no local recurrence or metastasis. The patient contacted the head surgeon of the clinic, who ordered a 1‐year postoperative CT. The 1‐year follow‐up CT finding agreed with the previous findings.

Conclusion: The aftertreatment of a radical‐operated GIST is extremely important if histologic examination of the tumour‐free margin is uncertain. In that case, CT controls should be considered once a year for at least 3 years.