bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of speech masking on the human subcortical response to continuous speech
Authors: Polonenko Melissa J. , Maddox Ross K.
Published: December 2024

Auditory masking—the interference of the encoding and processing of an acoustic stimulus imposed by one or more competing stimuli—is nearly omnipresent in daily life, and presents a critical barrier to many listeners, including people with hearing loss, users of hearing aids and cochlear implants, and people with auditory processing disorders. The perceptual aspects of masking have been actively studied for several decades, and particular emphasis has been placed on masking of speech by other speech sounds. The neural effects of such masking, especially at the subcortical level, have been much less studied, in large part due to the technical limitations of making such measurements. Recent work has allowed estimation of the auditory brainstem response (ABR), whose characteristic waves are linked to specific subcortical areas, to naturalistic speech. In this study, we used those techniques to measure the encoding of speech stimuli that were masked by one or more simultaneous other speech stimuli. We presented listeners with simultaneous speech from one, two, three, or five simultaneous talkers, corresponding to a range of signal-to-noise ratios (SNR; Clean, 0, −3, and −6 dB), and derived the ABR to each talker in the mixture. Each talker in a mixture was treated in turn as a target sound masked by other talkers, making the response quicker to acquire. We found consistently across listeners that ABR wave V amplitudes decreased and latencies increased as the number of competing talkers increased.

Significance statement

Trying to listen to someone speak in a noisy setting is a common challenge for most people, due to auditory masking. Masking has been studied extensively at the behavioral level, and more recently in the cortex using EEG and other neurophysiological methods. Much less is known, however, about how masking affects speech encoding in the subcortical auditory system. Here we presented listeners with mixtures of simultaneous speech streams ranging from one to five talkers. We used recently developed tools for measuring subcortical speech encoding to determine how the encoding of each speech stream was impacted by the masker speech. We show that the subcortical response to masked speech becomes smaller and increasingly delayed as the masking becomes more severe.
Bacterial Lytic Polysaccharide Monooxygenases negatively affect insect larvae growth
Authors: Baranek Jakub , Wojtkowiak Filip , Belińska Kinga , Wojtkowiak Paulina , Zielezinski Andrzej
Published: December 2024

BACKGROUND

Lytic Polysaccharide Monooxygenases (LPMOs) are recently discovered redox enzymes broadly distributed across various taxa, including bacteria, fungi, and viruses. LPMO proteins can oxidatively cleave the glycosidic chains found in carbohydrate polymers, allowing efficient decomposition of recalcitrant polysaccharides such as chitin or cellulose. While LPMOs have primarily been studied for their role in biomass conversion, other biological roles of these enzymes are not well understood.

RESULTS

Here, we assess the influence of four different LMPOs, derived fromBacillus thuringiensisandSerratia marcescensbacteria, onSpodoptera exigualarvae. The tested proteins administeredper osresulted in significant growth impairment, with the mean body weight of the treated larvae being lower than the control group by 30-69 percentage points, depending on the specific LPMO.

CONCLUSION

This work indicates that LPMO enzymes are capable of insect larvae development inhibition and thus may play an important role in insect pathogenesis caused by bacteria. Moreover, the results obtained in this study are an early sign of the potential use of LPMOs in future pest management strategies.
Ungulate personality and the human shield contribute to long-distance migration loss
Authors: Cotterill Gavin G. , Cross Paul C. , Cole Eric K. , Dewey Sarah R. , Wise Benjamin L. , Graves Tabitha A.
Published: December 2024

Long-distance ungulate migrations are declining and past research has focused on preserving migration paths where habitat fragmentation and loss disrupts movement corridors. However, changing residency-migration tradeoffs are the stronger driver of long-distance migration loss in some populations. The human shield effect relative to predation risk and anthropogenic food resources likely shapes these tradeoffs, but individual animals also vary in their propensity to tolerate proximity to humans and developed areas. We investigated how personality relative to human-habituation affects migration behavior. We categorized elk as bold or shy based on use of anthropogenic food resources identified through a clustering algorithm applied to GPS collar data. Bold elk were 4 times more likely to select wintering areas close to human activity and migrated 60% shorter distances compared to shy elk. As a result, elk wintering grounds were spatially structured such that conflict- and disease-prone individuals selected areas adjacent to human activity. Our results suggest that bold personality traits act as a precursor to human-habituation, which permits bold elk to reap the forage and predation rewards that occur in suburban landscapes. A multi-pronged approach beyond just maintaining habitat corridors may be necessary to conserve long-distance migrations for species that can become human-habituated.
ColBuilder: Flexible structure generation of crosslinked collagen fibrils
Authors: Monego Debora , Brosz Matthias , Buck Johanna , Viliuga Vsevolod , Jung Jaewoon , Stuehn Torsten , Schmies Matthias , Sugita Yuji , Gräter Frauke
Published: December 2024

Collagen fibrils are fundamental building blocks of connective tissues, yet generating accurate molecular models of their structure remains challenging due to their hierarchical organization and complex crosslinking patterns. ColBuilder has been developed to automate the generation of atomistic models of crosslinked collagen fibrils and facilitate the setup of molecular simulations. The tool integrates homology modeling, higher-order structure generation and optimization to build complete fibril structures with precise control over sequence composition, crosslinking patterns, and dimensions. Users can explore different collagen sequences, manipulate crosslink chemistry through mixed ratios and densities, and generate fibrils of varying diameter and length. All-atom molecular dynamics simulations of 335 nm-long fibrils validate the generated structures, showing excellent agreement with experimental measurements of D-band periodicity and force-extension behavior. ColBuilder is available both as an open-source command-line application and through a web interface at colbuilder.mpip-mainz.mpg.de.
Quantification of morphological, functional, and biochemical features of H9c2 rat cardiomyoblast retinoic acid differentiation
Authors: York Nicole S. , Rivera Joel E. , Manesh Mohammadreza Rahmani , Lynes-Ford K’sana Wood , Smith Rory , Wicki-Stordeur Leigh E. , Arbour Laura T. , Swayne Leigh Anne
Published: December 2024

Cell culture models enable advancement in our understanding of heart development and heart disease. The H9c2 rat ventricular cardiomyoblast cell line can be differentiated, recapitulating certain components of cardiomyocyte development; however, morphological, functional, and biochemical changes are rarely investigated in parallel, thereby limiting fulsome understanding. We therefore characterized morphology, Ca2+handling, and gene expression after five days (5days-in-vitro, DIV5), and fourteen days (DIV14) of exposure to differentiation stimuli, consisting of retinoic acid and low serum. Subpopulations of cells showed evidence of differentiation to a cardiomyocyte-like phenotype that was enhanced over time. Differentiation was also associated with the formation of cytoplasmic actin clusters. Spontaneous Ca2+transients in differentiated H9c2 cells had decreased frequency and synchronicity compared to those observed in primary cardiomyocytes. Additionally, key cardiomyocyte cytoskeletal proteins and ion channel transcript and protein expression levels changed significantly with differentiation, in alignment with changes normally observed in cardiomyocyte development. Our findings suggest H9c2 cells may be used as a high throughput screening model to investigate cardiomyocyte biology in certain developmental contexts with relevance to heart health and disease.

Significance statement

Retinoic acid-differentiated rat ventricular H9c2 cardiomyoblast cells model aspects of cardiomyocyte development with quick turnover rates and potentially relatively high homogeneity compared to other common cell culture models. Characterizing morphology, Ca2+handling, and gene expression changes will help experimental design and contextualizing outcomes.

Subsets of differentiated H9c2 cells exhibit morphology changes consistent with a cardiomyocyte-like phenotype, Ca2+signaling, and gene expression changes.

These outcomes suggest H9c2 responses to differentiation increase over time and are somewhat heterogenous as only sub-populations appear to respond. These findings provide insight for designing cardiomyocyte development studies using H9c2 cells in healthy and disease state contexts.
Bicoid-nucleosome competition sets a concentration threshold for transcription constrained by genome replication
Authors: Degen Eleanor A. , Croslyn Corinne , Mangan Niall M. , Blythe Shelby A.
Published: December 2024

Transcription factors (TFs) regulate gene expression despite constraints from chromatin structure and the cell cycle. Here we examine the concentration-dependent regulation ofhunchbackby the Bicoid morphogen through a combination of quantitative imaging, mathematical modeling and epigenomics inDrosophilaembryos. By live imaging of MS2 reporters, we find that, following mitosis, the timing of transcriptional activation driven by thehunchbackP2 (hbP2) enhancer directly reflects Bicoid concentration. We build a stochastic model that can explainin vivoonset time distributions by accounting for both the competition between Bicoid and nucleosomes athbP2 and a negative influence of DNA replication on transcriptional elongation. Experimental modulation of nucleosome stability alters onset time distributions and the posterior boundary ofhunchbackexpression. We conclude that TF-nucleosome competition is the molecular mechanism whereby the Bicoid morphogen gradient specifies the posterior boundary ofhunchbackexpression.
Monitoring in vivo transcription with synthetic serum markers
Authors: Watanabe Sho , Lee Sangsin , Harb Manwal , Nouraein Shirin , Raisley Emma , Li Honghao , Buitrago Nicolas , Pforr Beatrice , Szablowski Jerzy O.
Published: December 2024

Understanding transcription profiles of living tissues is critical for biology and medicine. However, measurement of the transcript levels is typically done in homogenized tissues post-mortem. Here, we present a new platform that enables non-invasive monitoring of specific mRNA levelsin vivo, without tissue destruction. We achieved this by combining two cutting-edge tools - synthetic serum markers, called Released Markers of Activity (RMAs), and RNA-based sensors of transcription. We call this platform IN-vivo Tracking of ACtive Transcription, orINTACT. In INTACT, when the target mRNA is expressed, the RNA sensor detects it and triggers the production and release of RMA reporters into the blood. Once in blood, the RMAs can be easily measured through a simple blood draw. Our data shows that INTACT can measure transcription of transgenes, as well as endogenous transcripts, such asc-FosorArc, bothin vivoin the brain and in tissue culture. INTACT enables simple measurement of transcript level histories in genetically-targetable cell populations of living animals.
All ribosomal RNAs and 45S spacers from humans to worms are packed with organism-specific motifs whose other copies are found predominantly in numerous nervous system genes including many associated with human disorders
Authors: Rigoutsos Isidore , Nersisyan Stepan , Londin Eric , Nazeraj Iliza , Dong Bonnie , Vourekas Anastasios , Loher Phillipe
Published: December 2024

The nucleotide sequences of ribosomal RNAs (rRNAs) and the spacers of 45S are tuned to fulfill optimally their respective roles during ribosome biosynthesis and function. We report that these sequences satisfy additional genome-wide constraints in humans, mice, fruit flies, and worms. In all four organisms, the rRNAs and 45S spacers are densely packed with organism-specific nucleotide motifs with many additional identical copies throughout the genome. The human rRNAs and 45S spacers contain 1,723 motifs whose sequences are unique to the rRNAs/spacers of primates. These motifs have numerous additional exact intronic and exonic copies whose genomic placement is also unique to primates. Specific combinations of the motifs appear exclusively in 3,430 human nervous system and developmental genes, including 1,046 risk genes for autism, schizophrenia, and bipolar disorder. RNA/RNA crosslinking experiments show that the rRNA/spacer motifs are contact points for rRNA-mRNA and mRNA-mRNA heteroduplexes. RNA binding protein (RBP) assays show that these motifs are also in the binding sites of 113 RBPs. RNA sequencing reveals that rRNAs and spacers produce endogenous small non-coding RNAs (sncRNAs) that carry the same primate-specific motifs. Lastly, the motifs’ intergenic and intronic copies overlap 131 GWAS polymorphisms associated with neuropathologies (p-val<3.9e-12). The findings suggest that the motifs facilitate RNA/RNA and RBP/RNA interactions that are affected by polymorphisms and modulated by rRNA- and spacer-derived sncRNAs carrying the same motifs. Our study also genetically links for the first time rRNAs and 45S spacers to autism and other typically human neurological disorders. Mutation panels based on these motifs can lead to new molecular diagnostics for these disorders, whereas snRNAs carrying these motifs can serve as drugs or potential therapeutic targets.

Graphical abstract

The human ribosomal RNAs and the 45S spacers share primate-specific motifs with thousands of nervous system genes, including risk genes for autism and other neurological disorders. Similar links between rRNAs/spacers and nervous system genes exist in mice, fruit flies, and worms but are achieved through motifs that are unique to each organism. In humans, the motifs are at the contact points of endogenous gene-gene and rRNA-gene heteroduplexes, as well as the binding sites of RNA binding proteins (RBPs) in genes and rRNAs/spacers. Endogenous small RNAs carrying these shared motifs modulate these endogenous interactions and are disrupted by mutations at the motifs’ genomic copies. Mutation panels based on these motifs can lead to new diagnostics for autism and other disorders, while the small RNAs carrying the motifs can serve as drugs or potential therapeutic targets.
Jan and mini-Jan, a model system for potato functional genomics
Authors: Xin Haoyang , Strickland Luke W. , Hamilton John P. , Trusky Jacob K. , Fang Chao , Butler Nathaniel M. , Douches David S. , Buell C. Robin , Jiang Jiming
Published: December 2024

Potato (Solanum tuberosum) is the third most important food crop in the world. Although the potato genome has been fully sequenced, functional genomics research of potato lags relative to other major food crops due primarily to the lack of a model experimental potato line. Here, we present a diploid potato line, ‘Jan’, which possesses all essential characteristics for facile functional genomics studies. Jan has a high level of homozygosity after seven generations of self-pollination. Jan is vigorous and highly fertile with outstanding tuber traits, high regeneration rates, and excellent transformation efficiencies. We generated a chromosome-scale genome assembly for Jan, annotated genes, and identified syntelogs relative to the potato reference genome assembly DMv6.1 to facilitate functional genomics. To miniaturize plant architecture, we developed two “mini-Jan” lines with compact and dwarf plant stature using CRISPR/Cas9-mediated mutagenesis targeting theDwarfandErectagenes related to growth. Mini-Jan mutants are fully fertile and will permit higher-throughput studies in limited growth chamber and greenhouse space. Thus, Jan and mini-Jan provide an outstanding model system that can be leveraged for gene editing and functional genomics research in potato.
HDAC6-Mediated FoxO1 Acetylation And Phosphorylation Control Periodontal Inflammatory Responses
Authors: Lohner Hannah , Han Xiao , Ren Junling , Liang Shuang , Liang Ruqiang , Wang Huizhi
Published: December 2024

Post-translational modifications (PTMs) are critical regulators of protein function and cellular signaling. While histone deacetylation by histone deacetylases (HDACs) is well established, the role of specific HDACs in modulating non-histone protein PTMs, particularly in an infectious context, is poorly understood. Here, we reveal a pivotal role for HDAC6 in orchestrating periodontal inflammation through its dual regulatory effects on FoxO1 acetylation and phosphorylation. UsingPorphyromonas gingivalis, a key periodontal pathogen, as a model pathogen, we observed that infection induces HDAC6 activation, driving inflammatory responses via modulating FoxO1 activity. HDAC6 depletion increased FoxO1 acetylation and phosphorylation, leading to its cytoplasmic sequestration and subsequent suppression of FoxO1- mediated pro-inflammatory cytokine production in macrophages. Mechanistically, HDAC6 deficiency not only directly enhances the acetylation of FoxO1 but also upregulates the expression of Rictor, a critical component of the mTORC2 complex, thereby promoting Akt phosphorylation and subsequently FoxO1 phosphorylation. This results in its cytoplasmic retention and attenuated inflammatory transcriptional activity. Functional studies demonstrated that HDAC6 depletion suppressed the production of key inflammatory mediators, including TNFα, IL-6, IL-12p40, and MIP-2, while promoting macrophage polarization toward anti-inflammatory M2 phenotypes.In vivo, using oral gavage infection and ligature-induced mouse periodontitis models, HDAC6 deficiency significantly reduced inflammatory cell infiltration in gingival tissues and protected against alveolar bone loss. These findings establish HDAC6 as a central regulator of periodontal inflammation, acting through the coordinated modulation of FoxO1 acetylation and phosphorylation. Beyond its role in oral pathology, HDAC6 may serve as a promising therapeutic target for managing inflammatory diseases linked to immune dysregulation.
MuSkeMo: Open-source software to construct, analyze, and visualize human and animal musculoskeletal models and movements in Blender
Authors: van Bijlert Pasha A.
Published: December 2024

Musculoskeletal models for multibody dynamic analysis provide unique insights into human and animal movement. Although some biomechanical simulators provide model-building tools, these presuppose substantial preprocessing by the user, and resulting models are generally not cross-platform compatible. Thus, the workflow from anatomical 3D scans to musculoskeletal model is time-consuming, requiring numerous processing and conversions steps between software packages, and the process differs between simulators. Despite the popularity of musculoskeletal modelling within biomechanics, no cross-platform, open source software package exists for constructing musculoskeletal models.

Here, I introduce MuSkeMo: A software suite for defining 3D musculoskeletal models entirely within Blender (open-source 3D computer graphics software). MuSkeMo provides a visual interface, enabling users to interactively define all aspects of a musculoskeletal model (including rigid bodies, skeletal geometry, joint centres, muscles, landmarks, and body-fixed reference frames). MuSkeMo can calculate 3D inertial tensors from arbitrary meshes (e.g., from CT scans), and also implements automated convex-hull based mass-estimation approaches from the literature. Joints can be defined using shape-fitting of bony surfaces, and muscles can wrap around primitive shapes.

Models can be analyzed within MuSkeMo using popular pose-sampling procedures, or exported to multiple text-based formats for use in biomechanical simulators. A conversion script to OpenSim is included.

MuSkeMo is compatible with models created for popular biomechanical simulators (OpenSim and Gaitsym). MuSkeMo can import these models and simulation trajectories, enabling users to create publication-ready stills and animations with Blender’s ray tracing. These visualisations include volumetric muscles based on the contractile parameters, which can be more visually intuitive than traditional constant-diameter tube segments.

Whether the end goal is a highly-detailed subject-specific human model, or a simplified animal model, MuSkeMo includes features that can aid this process. By consolidating many elements of common model construction workflows into a cohesive package, MuSkeMo substantially simplifies musculoskeletal modelling.
Downstream branches of receptor tyrosine kinase signaling act interdependently to shape the face
Authors: Hanne Nicholas , Hu Diane , Vidal-García Marta , Allen Charlie , Shakir M. Bilal , Liu Wei , Hallgrímsson Benedikt , Marcucio Ralph
Published: December 2024

Background

Previously we found that increasing fibroblast growth factor (FGF) signaling in the neural crest cells within the frontonasal process (FNP) of the chicken embryo caused dysmorphology that was correlated with reduced proliferation, disrupted cellular orientation, and lower MAPK activation but no change in PLCy and PI3K activation. This suggests RTK signaling may drive craniofacial morphogenesis through specific downstream effectors that affect cellular activities. In this study we inhibited three downstream branches of RTK signaling to determine their role in regulating cellular activities and how these changes affect morphogenesis of the FNP.

Results

Small molecule inhibitors of MEK1/2, PI3K, and PLCy were delivered individually and in tandem to the right FNP of chicken embryos. All treatments caused asymmetric proximodistal truncation on the treated side and a mild expansion on the untreated side compared to DMSO control treated FNPs. Inhibiting each pathway caused similar decreased proliferation and disrupted cellular orientation, but did not affect apoptosis.

Conclusions

Since RTK signaling is a ubiquitous and tightly regulated biochemical system we conclude that the downstream pathways are robust to developmental perturbation through redundant signaling systems.

Bullet points

Inhibiting three downstream effectors of receptor tyrosine kinase (RTK) signaling (MEK1/2, PLCy, and PI3K) in the frontonasal process of chicken embryos caused similar mild truncation of growth. Combining all three inhibitors had a slightly stronger effect on truncation.

Individual inhibitors did not have specific effects on cellular proliferation, apoptosis, or cellular orientation.

The downstream branches of RTK signaling likely have shared interdependent effects on cellular activities that contribute to morphogenesis.
A spreading, multi-tissue wound signal initiates whole-body regeneration
Authors: Breen Catriona , Srivastava Mansi
Published: December 2024

ABSTRACT

Animal bodies are equipped to sense injuries and respond, and rapid activation of ERK signaling at wound sites has emerged as a recurring mechanism across metazoans. During whole-body regeneration, distant species including cnidarians, planarians and echinoderms activate ERK at wounds to drive early transcriptional changes. However, it is unclear to what extent these are distinct phenomena, utilizing a common effector pathway but with different upstream inputs and downstream functions, or are more deeply alike, sharing upstream inputs, activating cell type(s), or spatiotemporal dynamics. To facilitate thorough comparisons across animals, we examined wound-induced ERK during whole-body regeneration in the acoelHofstenia miamia. ERK signaling is induced at wound sites within 10 minutes post-amputation and peaks in activity within one hour. ERK is required for head and tail regeneration and inhibiting ERK suppresses the expression of wound-induced genes, which are themselves required for regeneration. Quantification of spatial dynamics revealed that active ERK spreads rapidly away from the wound site during the first 30 minutes post-amputation and continues to expand in space through 3-6 hours, albeit at lower levels. Multiple cell types activate ERK including neoblasts (stem cells) and muscle, and ERK is spatially dynamic within both cell types, however, ERK activation in muscle does not require neoblasts. Finally,neuregulin-1, a putative ligand produced exclusively by muscle cells, is required for ERK activation at wounds. Altogether, our data identify a key signaling role of muscle cells in driving ERK activation in multiple cell types after injury, and describe a spatial spreading phenomenon with parallels to dynamic ERK patterns in other systems.
Solution structure of the Z0 domain from transcription repressor BCL11A sheds light on the sequence properties of protein-binding zinc-fingers
Authors: Harris Rilee E. , Whitehead Richard D. , Alexandrescu Andrei T.
Published: December 2024

The transcription repressor BCL11A, which governs the switch from fetal to adult hemoglobin during development, is the target of the first FDA-approved CRISPR/Cas9 gene-editing therapy in humans. By targeting BCL11A, fetal hemoglobin expression is de-repressed to substitute for defective adult hemoglobin in inherited diseases including beta-thalassemia and sickle-cell anemia. BCL11A has six CCHH-type zinc-fingers of which domains 4-6 are necessary and sufficient for dsDNA binding. Here, we focus on the CCHC-type ZNF at the N-terminus of BCL11A (residues 46-72), Z0, thought to modulate oligomerization of the transcription repressor. Using NMR and CD spectroscopy, Z0 is shown to be a thermostable CCHC zinc-finger with a pM dissociation constant for zinc. The NMR structure of Z0 has a prototypical beta-beta-alpha fold, with a hydrophobic knob comprising about half the structure. The unusual proportion of hydrophobic residues in Z0 led us to investigate if this is more general in zinc-fingers that do not bind dsDNA. We used the ZF and WebLogo servers to examine sequences of zinc fingers with demonstrated DNA-binding function, non-binders, and the CCHC-type family of protein-binders. DNA-binders are distinguished by contiguous stretches of high-scoring zinc-fingers. Non-DNA-binders show a depletion of polar residues at the positions expected to contact nucleotides and increased divergence from sequence consensus making these domains more likely to be annotated as atypical, degenerate, or to be missed as zinc-fingers. We anticipate these sequence patterns will help distinguish DNA-binders from non-binders, an open problem in the functional understanding of zinc-finger motifs.
The Right Tool for the Task: Body-Weight Supported Treadmill or Total Body Recumbent Stepper for Mobility-Adapted Cardiopulmonary Exercise Testing in Multiple Sclerosis Patients with Disability
Authors: Hadjizadeh Anvar Saman , Kelly Liam P , Newell Caitlin , Alcock Lynsey , Ploughman Michelle
Published: December 2024

Objective

Cardiopulmonary Exercise Testing (CPET) is challenging among persons with mobility disability. We sought the optimal adapted device to achieve a maximal CPET.

Design

Randomized crossover trial, within-subjects, repeated measures design

Setting

Primary Care and Referral Center

Participants

Clinic-referred persons with multiple sclerosis (PwMS) (n=10) with three-month stability, no exercise obstruction, MoCa>24, ability to walk with or without assistance, and sex- and age-matched (±3 years) Controls (n=7) recruited by convenience sampling

Interventions

CPET on body weight-supported treadmill (BWST) and total body recumbent stepper (TBRS)

Main Outcome Measures

Standard aerobic metrics (V̇O2max, % normative values for V̇O2max[%V̇O2max], heart rate maximum [HRmax], age-predicted HRmax, and Respiratory Exchange Ratio)

Results

PwMS achieved similar V̇O2max(mL·min-1·kg-1) on the TBRS and BWST (26.53±8.7 vs. 24.24±7.8) while Controls obtained higher values on BWST than TBRS (40.27±7.6 vs. 34.32±7.1,p<0.001). PwMS more consistently achieved criteria for maximum CPET using TBRS. During the preliminary investigation of the MS subgroup with a higher mobility disability, CPET using BWST exaggerated already low CPET metrics.

Conclusions

Although Controls achieved higher CPET values on BWST, V̇O2maxbetween devices were similar among PwMS. Only when using BWST, PwMS V̇O2maxand %V̇O2maxwere lower than Controls, likely because of leg fatigue and weakness. Using TBRS permits persons with mobility disability to achieve more criteria for a maximum CPET. Our results suggest that CPET using BWST, being reliant on the lower body, likely disadvantages PwMS, especially those with mobility disability.
Determinants of Public Participation in Primary Health Care Worldwide: A Scoping Review Protocol
Authors: Jazi Kimia , Mahmoodi Amirhosein , Azizkhani Mohammadreza , joulaei hassan
Published: December 2024

Public participation is a key component to achieve effective primary health care (PHC) and considering human rights to health. Multiple factors affect community involvement regarding varied health systems worldwide. Obstacles should be addressed in each country, regarding health system regulations and community willingness. This scoping review will systematically map literature on varied models, potential barriers, as well as challenges and future opportunities to public participation in PHC around the world.

This study will follow and will be conducted through Joanna Briggs Institute (JBI) guidelines. The PRISMA Extension for Scoping Reviews (PRISMA-ScR) will also guide the reporting. The search will be conducted across PubMed, Scopus, Web of Science Core Collection, Cochrane Central Register of Controlled Trials Embase, SID, and Magiran databases focusing on studies published from 2010 to January 2025 in English and Farsi. Two independent reviewers will screen titles and abstracts, followed by full-text screening. Data will be extracted in a standardized form by two authors and all disparities will be resolved through consulting a third author. Diagrams, tables, and figures will be applied to illustrate extracted data.
Protocol paper: A.I. Based STroke Risk fActor Classification and Treatment (ABSTRACT) study
Authors: Heseltine-Carp William , Kasabe Aishwarya , Courtman Megan , Allen Michael , Streeter Adam , Thurston Mark , Wang Hongrui , Mcgavin Lucy , Ifeachor Emmanuel , Mullin Stephen
Published: December 2024

Background

Stroke is a leading cause of death and disability in the UK. Much of stroke management revolves around addressing risk factors with medications and lifestyle modification. However, 30% of those who suffer stroke have no known risk factors. Hence, there is need to better identify individuals who are at high risk of stroke, and particularly those where the benefit of treatment outweighs the risk.

ABSTRACT is a three phase study that looks to address this issue by (1) using artificial intelligence (AI) to predict stroke risk from routine hospital data, (2) to validate this model on external datasets, and (3) validate the ability to improve outcome by guiding clinical decision making. In this paper we focus on phase I of the project.

Aims

Phase I of this study has 4 main objectives

To create four separate machine learning (ML) models to predict stroke risk from routine hospital data. One for CT/MRI/PMH brain data, one for ECG/echo/PMH data and one for laboratory test/PMH data.

To perform explainability analysis on these models to identify important and novel risk factors for stroke

To calibrate these models and align them with real world probabilities

To combine these models to ensemble stroke prediction model

Methods

In this retrospective observational cohort study we will analyze data from 9155 stroke patients and 109,875 controls in southwest England. Stroke cases will be sourced from the SSNAP database and historical brain imaging (CT/MRI), ECG, echocardiography, laboratory tests, ultrasound and medical history will be obtained from hospital and GP records. These data will then be linked to form a single de-identified dataset of cases and controls. ML techniques will then be trained on these data to predict stroke risk and identify novel risk factors for stroke.

Discussion

This protocol paper outlines phase one of ABSTRACTs approach in creating a novel stroke risk prediction model by integrating multimodal data types such as routine brain imaging, ECG, echocardiography, and laboratory results. In particular we outline a bespoke data handling protocol in order to comply with UK ethical governance when processing large volumes of confidential data. We also discuss our strategy in cleaning and preparing data prior to ML algorithms to predict stroke
LPSGM: A Unified Flexible Large PSG Model for Sleep Staging and Mental Disorder Diagnosis
Authors: Deng Guifeng , Niu Mengfan , Luo Yuxi , Rao Shuying , Sun Jing , Xie Junyi , Yu Zhenghe , Liu Wenjuan , Zhao Sha , Pan Gang , Li Xiaojing , Deng Wei , Guo Wanjun , Li Tao , Jiang Haiteng
Published: December 2024

We present the Large PSG Model (LPSGM), a unified and flexible framework for sleep staging and disease diagnosis using polysomnography (PSG) data. LPSGM is designed to address the challenges of cross-center generalization in sleep staging and to enable fine-tuning for downstream disease diagnosis tasks. LPSGM introduces a unified training framework for heterogeneous datasets and allows flexible channel input adjustments during inference. The model is first trained on 220,500 hours whole-night PSG from 16 public datasets, achieving robust sleep staging performance. It is then fine-tuned on target center data for various disease classification tasks, including narcolepsy diagnosis, anxiety and depression detection, and the classification of healthy versus depressed individuals. LPSGM outperforms baseline models on both sleep staging and disease diagnosis tasks. Our results demonstrate that LPSGM not only enhances sleep staging accuracy but also improves the diagnosis of sleep-related and psychiatric disorders, showing promise for clinical applications in sleep medicine and psychiatry.
Remifentanil as an alternative in modified rapid sequence induction: A Proof-of-concept study in a selected paediatric population
Authors: Pico Julien , Sola Chrystelle , Hertz Laurent , Riera Julien , Scott Christopher , Chapron Kévin , Pirat Philippe , Bringuier Sophie , Dadure Christophe
Published: December 2024

Introduction

Rapid sequence induction (RSI) is widely used in paediatric anaesthesia. Concerns over complications associated with classical RSI have prompted the exploration of alternatives. This study was conducted to determine the feasibility and safety of using bolus remifentanil in combination with a hypnotic agent for paediatric RSI.

Methods

This proof-of-concept study analysed data from paediatric patients, with at least one risk factor for pulmonary aspiration, undergoing RSI with remifentanil at the Montpellier University Hospital between December 2021 and August 2023. Exclusion criteria included the planned use of a neuromuscular blocking agent for RSI, preoperative hypoxemia, hemodynamic shock or difficult intubation risk factors. Remifentanil was administered by direct intravenous injection with optional prophylactic administration of atropine. Data on intubation success rates, major and minor complications and rescue treatment were collected and analysed.

Results

The study included 267 children with a mean age of 7.8 +/- 4.4 years. The success rate for the first intubation attempt was 92.9% (95% CI, 88.9-95.6). No major complication or pulmonary aspiration was reported. Minor complications, primarily hypotension, occurred in 15.7% of patients. The prophylactic use of atropine was correlated with a reduction in minor complications.

Discussion

This study supports the use of remifentanil for RSI in a selected paediatric population. Remifentanil offers good intubation conditions with a high success rate at the first attempt and a high safety profile with no major complication reported. Prophylactic atropine administration seems beneficial in reducing minor complications. These findings advocate for integrating remifentanil as an alternative in protocols for modified RSI. Further randomised studies are required to validate such outcomes and refine clinical approaches.
Integrating multi-modal omics to identify therapeutic atherosclerosis pathways for coronary heart disease
Authors: de Ruiter Sophie C. , van Vugt Marion , Finan Chris , Grobbee Diederick E. , de Kleijn Dominique P.V. , Pasterkamp Gerard , den Ruijter Hester M. , Diez Benavente Ernest , Peters Sanne A.E. , Schmidt A. Floriaan
Published: December 2024

Introduction

Urinary metabolism breakdown products reflect metabolic changes in atherosclerosis-relevant tissues and may contain relevant therapeutic leads. We integrated data on urinary metabolism breakdown products, plasma proteins, atherosclerotic plaque tissue, and single-cell expression to identify druggable metabolic pathways for coronary heart disease (CHD).

Methods

Mendelian randomisation was employed to interrogate findings from independent genome-wide association studies on 954 urinary metabolism breakdown products, 1,562 unique proteins, and 181,522 CHD cases, establishing directionally concordant associations. Using the Athero-Express Biobank, concordant plasma proteins were linked to plaque vulnerability using protein and mRNA expression in plaque. Single-cell RNA sequencing data obtained from carotid plaque samples were used to test for differential expression of concordant proteins across plaque cell types.

Results

In total, 29 urinary metabolism breakdown products associated with CHD, predominantly originating from amino acid metabolism (n=12) or unclassified origin (n=9). We identified 113 plasma proteins with directionally concordant associations with these urinary metabolism breakdown products and CHD. Of the 110 proteins available in plaque, 16 were associated with plaque vulnerability. This included positive control proteins targeted by drugs indicated for CHD, such as CAH1 (targeted by aspirin), IL6R (targeted by tocilizumab), and AT1B2 (targeted by digoxin), as well as two potential repurposing opportunities C1S (targeted by C1-esterase inhibitor and sutimlimab) and CATH (targeted by bortezomib).

Conclusion

We have identified amino acid metabolism as an important contributing pathway to CHD risk and prioritised 16 proteins relevant for CHD with involvement in atherosclerotic plaques, providing important insights for drug development.
Epidemiological indices with multiple circulating pathogen strains
Authors: Trevisin Cristiano , Mari Lorenzo , Gatto Marino , Colizza Vittoria , Rinaldo Andrea
Published: December 2024

Epidemiological indicators, such as reproduction numbers and epidemicity indices, describe an ongoing epidemic’s long- and short-term behaviour. Their evolving values provide context for designing control measures, as maintaining both indices below one warrants a waning epidemic. However, current models for the computation of epidemiological metrics do not consider the pathogen stratification into variants endowed with different infectivity and epidemiological severity, as was the case with SARS-CoV-2. Failing to account for such stratification prevents the resulting epidemiological indices from spotting the possible onset of uncontrolled growth of one variant within the total of new infections, thus limiting the prognostic value of the indicators. Here, we expand an existing framework for the computation of spatially explicit reproduction numbers and epidemicity indices to account for arising variants. By contrasting the data of the COVID-19 pandemic in Italy, we show that embedding additional layers of complexity in the mathematical model reveals epidemiological metrics at the emergence of new variants significantly exceeding their threshold. Such values foresee a recrudescence in new infections that only became evident after emerging variants effectively replaced the previous strains. These higher values flag the presence of a specific variant that grows more rapidly than the growth of the total number of infections generated by all variants combined. Variant-stratified epidemiological indicators do therefore allow control measures to be better tailored to the shifting severity of an ongoing epidemic.
Development and comparison of natural language processing models for abdominal aortic aneurysm repair identification and classification using unstructured electronic health records
Authors: Thompson Daniel , Mofidi Reza
Published: December 2024

Background

Patient identification for national registries often relies upon clinician recognition of cases or retrospective searches using potentially inaccurate clinical codes, potentially leading to incomplete data capture and inefficiencies. Natural Language Processing (NLP) offers a promising solution by automating analysis of electronic health records (EHRs). This study aimed to develop NLP models for identifying and classifying abdominal aortic aneurysm (AAA) repairs from unstructured EHRs, demonstrating proof-of-concept for automated patient identification in registries like the National Vascular Registry.

Method

Using the MIMIC-IV-Note dataset, a multi-tiered approach was developed to identify vascular patients (Task 1), AAA repairs (Task 2), and classify repairs as primary or revision (Task 3). Four NLP models were trained and evaluated using 4,870 annotated records: scispaCy, BERT-base, Bio-clinicalBERT, and a scispaCy/Bio-clinicalBERT ensemble. Models were compared using accuracy, precision, recall, F1-score, and area under the receiver operating characteristic curve.

Results

The scispaCy model demonstrated the fastest training (2 mins/epoch) and inference times (2.87 samples/sec). For Task 1, scispaCy and ensemble models achieved the highest accuracy (0.97). In Task 2, all models performed exceptionally well, with ensemble, scispaCy, and Bio-clinicalBERT models achieving 0.99 accuracy and 1.00 AUC. For Task 3, Bio-clinicalBERT and the ensemble model achieved an AUC of 1.00, with Bio-clinicalBERT displaying the best overall accuracy (0.98).

Conclusion

This study demonstrates that NLP models can accurately identify and classify AAA repair cases from unstructured EHRs, suggesting significant potential for automating patient identification in vascular surgery and other medical registries, reducing administrative burden and improving data capture for audit and research.
Improving HIV Outcomes in Miami’s Black populations with clinic-based community health workers protocol: The integrated navigation and support for treatment adherence, counseling, and research (INSTACARE) randomized controlled trial
Authors: Kenya Sonjia , Young BreAnne , Escarfuller Sebastian , Jones-Weiss Deborah , Carrasquillo Olveen , Riccio Ana , Yue Pan
Published: December 2024

Miami-Dade is an HIV epicenter where Black populations experience excess AIDS-related deaths due to poor medication adherence, which prevents achieving an undetectable HIV viral load (VL). A promising approach to improving HIV outcomes in Black populations has been the use of community health workers (CHWs). Evidence shows CHWs trained in motivational interviewing (MI) may further improve outcomes, however little data exists about Black CHWs trained in MI who support Black patients with HIV. While CHWs traditionally help address social determinants of health in nonclinical locations, there is less information on CHWs who provide support in clinical settings, which may result in even greater improvements in HIV outcomes. To examine effects of CHWs trained in MI who provide HIV care in both clinic and community settings, a randomized controlled trial (RCT) is being conducted in Miami-Dade’s largest public hospital. The Integrated Navigation and Support for Treatment, Adherence, Counseling, and Research intervention is a RCT of 300 Black adults with an unmanaged HIV VL (> 200 copies/mL). CHWs trained in MI are embedded into HIV clinical care teams and participate in hospital rounds with clinicians treating inpatients. Participants randomized into the CHW intervention arm receive 12 months of CHW-led health education and assistance with health care navigation and social services. The primary outcome is change in HIV viral load suppression at 12 months. Secondary outcomes include changes in medication adherence and social determinants of health. Study enrollment began in 2023 and will be completed by 2027. The first results are expected to be submitted for publication in 2025. INSTACARE is one of the first RCTs to examine effects of clinic-based support provided by CHWs trained in MI on Black populations with an unmanaged VL and will provide evidence on the impact of such strategies on medication adherence and social determinants of health.
From Traits to Puffs: The Interplay of Personality, Pandemic Stress, and Smoking Behaviors
Authors: Tian Ying , Xiang Weiyi , Dzhugaryan Silvia , Bae Dayoung , Barrington-Trimis Jessica , Church Terry
Published: December 2024

Smoking, a leading cause of chronic diseases, is often used to cope with stress, which has been heightened by the pandemic due to health and economic concerns. Studies have shown that the Big Five personality traits are linked to smoking behavior, suggesting that different personality traits influence nicotine use in varying ways. However, there remains a significant gap in understanding how individuals with different personalities respond to nicotine use under stress. This study aims to investigate how nicotine dependence changes for different Big Five personalities under the pandemic stress and whether other stress-related factors influence nicotine dependence during COVID-19. This cross-sectional study collect data from randomly selected adults aged 18-30 in the US. The Big Five Personality Model assessed personality traits, and nicotine dependence was measured with the Hooked-on Nicotine Checklist. Stress was evaluated using the Perceived Stress Scale, while demographics and other pandemic-related stressors were gathered through structured questions. Correlation and multiple logistic regression models were used for data analysis. The main findings showed that both before (r = −.25, p < .001) and during (r = −.19, p < .001) the pandemic, agreeableness was significantly negatively associated with nicotine dependence, indicating that higher agreeableness was linked to lower nicotine dependence. Similarly, conscientiousness was negatively correlated with nicotine dependence both before (r = −.123, p < .001) and during COVID-19 (r = −.19, p < .001). Although no direct association was found between perceived stress, personality traits, and smoking behavior, the analysis identified that external stressors played a moderating role. These findings emphasize the importance of understanding how different personality traits influence young people’s dependence on nicotine under stress. The outcome can guide the design of targeted nicotine withdrawal interventions and inform effective public health strategies.