bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analyzing the Evolution of Needle and Ultrasound Probe Manipulation Skills of Interventional Radiology Trainees With Time and Experience
Authors: Weinstein Jeffrey L. , Ali Hamza , Mitchell John D. , Sarwar Ammar , Palmer Matthew R. , MacLellan Christopher , Matyal Robina , Ahmed Muneeb 
Published: June 2024

Purpose
To test the hypothesis that hand motion analysis can measure the progression of needle and ultrasound probe manipulation skills of interventional radiology trainees in central venous line placement.

Materials and Methods
An expert cohort of 6 interventional radiologists and 4 anesthesiologists and a trainee cohort of 6 novice trainees (<50 central lines) and 5 experienced trainees (>50 central lines) performed simulated central venous access. Four novices and 1 experienced trainee repeated the task 1 year later. An electromagnetic motion tracking system tracked the needle hand and ultrasound probe. Path length, translational, and rotational movements were calculated separately for the needle hand and probe sensor. These metrics were used to calculate motion metrics based scores on a scale of 0 to 3 for each sensor. Nonparametric statistics were used, and the data are reported as median ± interquartile range.

Results
Comparing novice and experienced trainees, there was a significant difference in probe scores (experienced vs. novice: 1 ± 2 vs. 0 ± 0, P = 0.04) but not in needle-hand scores (1 ± 1.5 vs. 0 ± 1, P = 0.26). Trainees showed a significant increase in probe scores at the 1-year follow-up (baseline vs. follow-up: 0 ± 1 vs. 2.5 ± 1.8, P = 0.003), but no significant difference was observed in the needle manipulation metrics. Experts differed significantly from experienced trainees for all metrics for both sensors (P < 0.05), with the exception of the path length of the probe.

Conclusions
Acquisition of improved dexterity of the probe may occur before improvement in the dexterity with the needle hand for interventional radiology trainees.
Corpus Callosum–Mediated Interhemispheric Interactions in Cervical Spondylotic Myelopathy
Authors: Lo Yew Long , Hwang Ruby , Teng Peggy Pei Chee , Tan Yam Eng 
Published: June 2024

Purpose:
The corpus callosum is crucial for interhemispheric interactions in the motor control of limb functions. Human and animal studies suggested spinal cord pathologies may induce cortical reorganization in sensorimotor areas. We investigate participation of the corpus callosum in executions of a simple motor task in patients with cervical spondylotic myelopathy (CSM) using transcranial magnetic stimulation.

Methods:
Twenty patients with CSM with various MRI grades of severity of cord compression were compared with 19 normal controls. Ipsilateral silent period, contralateral silent period, central motor conduction time, and transcallosal conduction time (TCT) were determined.

Results:
In both upper and lower limbs, TCTs were significantly increased for patients with CSM than normal controls (p < 0.001 for all), without side-to-side differences. Ipsilateral silent period and contralateral silent period durations were significantly increased bilaterally for upper limbs in comparison to controls (p < 0.01 for all), without side-to-side differences. There were no significant correlations of TCT with central motor conduction time nor severity of CSM for both upper and lower limbs (p > 0.05 for all) bilaterally.

Conclusions:
Previous transcranial magnetic stimulation studies show increased motor cortex excitability in CSM; hence, increased TCTs observed bilaterally may be a compensatory mechanism for effective unidirectional and uniplanar execution of muscle activation in the distal limb muscles. Lack of correlation of TCTs with severity of CSM or central motor conduction time may be in keeping with a preexistent role of the corpus callosum as a predominantly inhibitory pathway for counteracting redundant movements resulting from increased motor cortex excitability occurring after spinal cord lesions.
Understanding and Assisting the Recovery of Non-English-Speaking Trauma Survivors: Assessment of the NESTS Pathway
Authors: Antunez Alexis G , Herrera-Escobar Juan P , Ilkhani Saba , Hoffman Ana , Foley Katie M , Zier Carolyn , Campbell Lorna , Pinkes Nathaniel , Valverde Madeline D , Ortega Gezzer , Reidy Emma , Reich Amanda J , Salim Ali , Levy-Carrick Nomi , Anderson Geoffrey A 
Published: June 2024

BACKGROUND:
Spanish-speaking trauma and burn patients have unique needs in their postdischarge care navigation. The confluence of limited English proficiency, injury recovery, mental health, socioeconomic disadvantages, and acute stressors after hospital admission converge to enhance patients’ vulnerability, but their specific needs and means of meeting these needs have not been well described.

STUDY DESIGN:
This prospective, cross-sectional survey study describes the results of a multi-institutional initiative devised to help Spanish-speaking trauma and burn patients in their care navigation after hospitalization. The pathway consisted of informational resources, intake and follow-up surveys, and multiple points of contact with a community health worker who aids in accessing community resources and navigating the healthcare system.

RESULTS:
From January 2022 to November 2023, there were 114 patients identified as eligible for the Non-English-Speaking Trauma Survivors pathway. Of these, 80 (70.2%) were reachable and consented to participate, and 68 were approached in person during their initial hospitalization. After initial screening, 60 (75.0%) eligible patients had a mental health, social services, or other need identified via our survey instrument. During the initial consultation with the community health worker, 48 of 60 patients with any identified need were connected to a resource (80%). Food support was the most prevalent need (46, 57.5%). More patients were connected to mental health resources (16) than reported need in this domain (7).

CONCLUSIONS:
The Non-English-Speaking Trauma Survivors pathway identified the specific needs of Spanish-speaking trauma and burn patients in their recovery, notably food, transportation, and utilities. The pathway also addressed disparities in postdischarge care by connecting patients with community resources, with particular improvement in access to mental healthcare.
Electroconvulsive Therapy Changes Immunological Markers in Patients With Major Depressive Disorder
Authors: Young Jonathan R. , Evans Mariah K. , Hwang Julie , Kritzer Michael D. , Kellner Charles H. , Weiner Richard D. 
Published: June 2024

Abstract
Major depressive disorder (MDD) is a highly prevalent and disabling condition. As such, understanding the causes of and treatment options for MDD is critical. Electroconvulsive therapy (ECT) remains the gold standard depression treatment, but the molecular mechanisms that underlie its effects are still largely unknown. One such explanation hinges on the immuno-inflammatory correlates of ECT treatment, given mounting evidence supporting the inflammatory hypothesis of depression. This review aims to provide an overview of the suggested immunomodulatory effects of ECT and the predictive value of immune biomarkers in relation to treatment outcomes and side effects. We conducted a preregistered, systematic literature search utilizing MEDLINE (PubMed), Embase (Elsevier), and PsycINFO (EBSCO) databases. We employed keywords related to MDD, ECT, gut microbiome, and the immune system. We only included human subjects research published between 1985 and January 13, 2021. Twenty-six unique studies were included in our analyses. Findings indicate a proinflammatory profile associated with MDD, with immune biomarkers exhibiting acute and chronic changes following ECT. Consistently, lower baseline interleukin 6 levels and higher C-reactive protein levels are correlated with a greater reduction in depressive symptoms following ECT. Furthermore, included studies emphasize the predictive value of peripheral immune changes, specifically interleukin 6 and tumor necrosis factor α, on cognitive outcomes following ECT. Given these results, further exploration of the potential roles of immunomodulatory effects on ECT treatment outcomes, as well as adverse cognitive side effects, is indicated.
Correlation Between ECT Quality Measures and Likelihood to Transition From Acute to Continuation and Maintenance ECT
Authors: Schuster Haley , Walters Ryan W. , Mathy Jacob , Ramaswamy Sriram , Alsakaf Imad 
Published: June 2024

Objectives
To evaluate the association between 3 ECT quality measures (seizure duration, Postictal Suppression Index [PSI], and heart rate response) and therapeutic compliance as indicated by transitioning from acute to continuation to maintenance phases of ECT.

Methods
This was a retrospective chart review of patients who received ECT between July 2016 and July 2019. ECT quality measures were lagged by 1 ECT session to examine the effect of the prior session's quality measure on progressing to a higher ECT phase at the subsequent ECT session. Associations with therapeutic compliance were analyzed using mixed-effects ordinal regression and mixed-effects partial proportional odds models.

Results
Seizure duration was associated with 8% higher adjusted odds of progressing to out of the acute phase (95% confidence interval [CI]: 2% to 15%, P = 0.007) and 18% higher adjusted odds of progressing to the maintenance phase (95% CI: 10% to 28%, P < 0.001); PSI was associated with 9% higher adjusted odds of progressing out of the acute phase (95% CI: 3% to 16%, P = 0.005), whereas heart rate response was not statistically associated with therapeutic compliance. Greater therapeutic compliance was also associated with bilateral electrode placement and older age.

Conclusions
Longer seizure duration was associated with greater therapeutic compliance across all ECT phases, PSI was associated with progressing out of the acute phase, and heart rate response was not associated with therapeutic compliance. Our findings assist ECT psychiatrists in optimizing ECT quality measures to promote better compliance with ECT.
Structure transfer and consolidation in visual implicit learning
Authors: Garber Dominik , Fiser József 
Published: June 2024

AbstractTransfer learning, the re-application of previously learned higher-level regularities to novel input, is a key challenge in cognition. While previous empirical studies investigated human transfer learning in supervised or reinforcement learning for explicit knowledge, it is unknown whether such transfer occurs during naturally more common implicit and unsupervised learning and, if so, how it is related to memory consolidation. We compared the transfer of newly acquired explicit and implicit abstract knowledge during unsupervised learning by extending a visual statistical learning paradigm to a transfer learning context. We found transfer during unsupervised learning but with important differences depending on the explicitness/implicitness of the acquired knowledge. Observers acquiring explicit knowledge during initial learning could transfer the learned structures immediately. In contrast, observers with the same amount but implicit knowledge showed the opposite effect, a structural interference during transfer. However, with sleep between the learning phases, implicit observers, while still remaining implicit, switched their behaviour and showed the same pattern of transfer as explicit observers did. This effect was specific to sleep and not found after non-sleep consolidation. Our results highlight similarities and differences between explicit and implicit learning while acquiring generalizable higher-level knowledge and relying on consolidation for restructuring internal representations.
Baseline dependent differences in the perception of changes in visuomotor delay
Authors: Vigh Gesche , Limanowski Jakub 
Published: June 2024

AbstractThe detection of, and adaptation to delayed visual movement feedback has been extensively studied. One important open question is whether the Weber-Fechner Laws hold in the domain of visuomotor delay; i.e., whether the perception of changes in visuomotor delay depends on the amount of delay already present during movement. To address this, we developed a virtual reality based, continuous hand movement task, during which participants had to detect changes in visuomotor mapping (delay): Participants (N=40) performed continuous, auditory-paced grasping movements, which were measured with a data glove and transmitted to a virtual hand model. The movements of the virtual hand were delayed between 0-700ms with the delay changing repeatedly in a roving oddball design. Participants had to indicate any perceived delay changes by key press. This design allowed us to investigate detection accuracy and speed related to the magnitude of the delay change, and to the “baseline” delay present during movement, respectively. As expected, larger delay changes were detected more accurately than smaller ones. Surprisingly, delay changes were detected more accurately and faster when participants moved under large > small delays. These results suggest that visual movement feedback delay indeed affects the detection of changes in visuomotor delay, but not as predicted by the Weber-Fechner Laws. Instead, bodily action under small delays may have entailed a larger tolerance for delay changes due to embodiment-related intersensory conflict attenuation; whereas better change detection at large delays may have resulted from their (visual) saliency due to a strong violation of visuomotor predictions.
Interferon-γ and IL-27 positively regulate type 1 regulatory T-cell development during adaptive tolerance
Authors: Lecky David A.J. , Sheriff Lozan , Rouvray Sophie T. , George Lorna S. , Drummond Rebecca A. , Wraith David C. , Bending David 
Published: June 2024

SummaryStrong T-cell receptor (TCR) and IL-27 signalling influence type-1 regulatory (Tr1) T-cell development but whether other signals determine their differentiation is unclear. Utilising Tg4 TCR transgenic mice we established a model for rapid Tr1 cell induction. A single high dose of [4Y]-MBP peptide drove the differentiation ofIl10+T-cells withbona fideTr1 cell protein and mRNA signatures. Kinetic transcriptional analysis revealed that the Tr1 cell module was transient and preceded by a burst ofIfngtranscription in CD4+ T-cells. Neutralisation of IFNγ reduced Tr1 cell frequency and strong TCR signalling markers, which was correlated with reduced macrophage activation. Antibody depletion experiments inferred that T-cells – but not NK cells – provided the relevant source of IFNγ. Additionally, we show that blocking IL-27 in combination with IFNγ neutralisation additively reduced Tr1 cell frequencyin vivo. These findings reveal that during strong tolerogenic TCR signalling IFN-γ has a non-redundant regulatory role in augmenting the differentiation of Tr1 cellsin vivo.
SuperSpot: Coarse Graining Spatial Transcriptomic Data into Metaspots
Authors: Teleman Matei , Gabriel Aurélie AG , Hérault Léonard , Gfeller David 
Published: June 2024

AbstractSummarySpatial Transcriptomics is revolutionizing our ability to phenotypically characterize complex biological tissues and decipher cellular niches. As of today, thousands of genes can be detected across hundreds of thousands of spots. Akin to standard single-cell RNA-Seq data, spatial transcriptomic data are very sparse due to the limited amount of RNA within each spot. Building upon the metacell concept, we present a workflow, called SuperSpot, to combine adjacent and transcriptionally similar spots into “metaspots”. The process involves representing spots as nodes in a graph with edges connecting spots in spatial proximity and edge weights representing transcriptional similarity. Hierarchical clustering is used to aggregate spots into metaspots at a user-defined resolution. We demonstrate that metaspots can be used to reduce the size of spatial transcriptomic data and remove some of the dropout noise.Availability and implementationSuperSpot is an R package available athttps://github.com/GfellerLab/SuperSpot.
AFC kinases function as thermosensors that regulate warm temperature-responsive growth inArabidopsis
Authors: Dimos-Röhl Benjamin , Ostwaldt Felix , Bäsmann Jannik , Hausmann Paula , Kreisz Philipp , Krischke Markus , Lutsch Christoffer , Müller Philipp C. , Strauch Miriam , Weiste Christoph , Zhu Tingting , De Smet Ive , Heyd Florian , Maag Daniel 
Published: June 2024

AbstractPlants respond to elevated temperatures with enhanced elongation growth and an upward movement of their leaves. These adaptive growth responses depend on a rapid transcriptional, post-transcriptional and post-translational reprogramming. It is unclear, however, how temperature information is sensed and integrated with the cellular splicing machinery to establish warm-temperature dependent splicing patterns. In animals, CDC2-LIKE KINASES (CLKs) function as body temperature sensors that control temperature-dependent alternative splicing through the phosphorylation of serine/arginine-rich (SR) proteins. Here, we demonstrate that the CLK-homologous ARABIDOPSIS FUS3-COMPLEMENTING (AFC) kinases function as temperature sensors that regulate post-transcriptional RNA processing to control warm temperature-dependent growth responses in Arabidopsis. We show that the contrasting temperature-activity profiles of the three Arabidopsis AFCs depend on specific structural elements including a conserved activation segment within the kinase domain. By combining protein structure prediction with site-directed mutagenesis, we provide insights into structural features that determine different temperature-activity profiles of the three AFC paralogs. Subsequent analyses ofafcmutant plants demonstrate their requirement for hypocotyl elongation growth and thermonastic leaf movement at elevated temperature. Impaired hypocotyl elongation ofafctriple mutant seedlings was accompanied by defects in temperature-dependent splicing especially affecting the post-transcriptional regulation of transcripts encoding splicing factors. Finally, based on transcriptomics, immunodetection and mutant analyses our data indicate SR34 and SR34a as phosphorylation targets that mediate temperature-dependent post-transcriptional RNA processing downstream of AFCs. In conclusion, the characterisation of Arabidopsis AFC kinases as thermosensors provides compelling evidence that temperature-controlled AFC activity is evolutionarily conserved between plants and animals.
Senescent cell heterogeneity and responses to senolytic treatment are related to cell cycle status during cell growth arrest
Authors: Neri Francesco , Zheng Shuyuan , Watson Mark , Desprez Pierre-Yves , Gerencser Akos A. , Campisi Judith , Wirtz Denis , Wu Pei-Hsun , Schilling Birgit 
Published: June 2024

AbstractCellular senescence has been strongly linked to aging and age-related diseases. It is well established that the phenotype of senescent cells is highly heterogeneous and influenced by their cell type and senescence-inducing stimulus. Recent single-cell RNA-sequencing studies identified heterogeneity within senescent cell populations. However, proof of functional differences between such subpopulations is lacking. To identify functionally distinct senescent cell subpopulations, we employed high-content image analysis to measure senescence marker expression in primary human endothelial cells and fibroblasts. We found that G2-arrested senescent cells feature higher senescence marker expression than G1-arrested senescent cells. To investigate functional differences, we compared IL-6 secretion and response to ABT263 senolytic treatment in G1 and G2 senescent cells. We determined that G2-arrested senescent cells secrete more IL-6 and are more sensitive to ABT263 than G1-arrested cells. We hypothesize that cell cycle dependent DNA content is a key contributor to the heterogeneity within senescent cell populations. This study demonstrates the existence of functionally distinct senescent subpopulations even in culture. This data provides the first evidence of selective cell response to senolytic treatment among senescent cell subpopulations. Overall, this study emphasizes the importance of considering the senescent cell heterogeneity in the development of future senolytic therapies.
A combinatorially complete epistatic fitness landscape in an enzyme active site
Authors: Johnston Kadina E. , Almhjell Patrick J. , Watkins-Dulaney Ella J. , Liu Grace , Porter Nicholas J. , Yang Jason , Arnold Frances H. 
Published: June 2024

AbstractProtein engineering often targets binding pockets or active sites which are enriched in epistasis— non-additive interactions between amino acid substitutions—and where the combined effects of multiple single substitutions are difficult to predict. Few existing sequence-fitness datasets capture epistasis at large scale, especially for enzyme catalysis, limiting the development and assessment of model-guided enzyme engineering approaches. We present here a combinatorially complete, 160,000-variant fitness landscape across four residues in the active site of an enzyme. Assaying the native reaction of a thermostable β-subunit of tryptophan synthase (TrpB) in a non-native environment yielded a landscape characterized by significant epistasis and many local optima. These effects prevent simulated directed evolution approaches from efficiently reaching the global optimum. There is nonetheless wide variability in the effectiveness of different directed evolution approaches, which together provide experimental benchmarks for computational and machine learning workflows. The most-fit TrpB variants contain a substitution that is nearly absent in natural TrpB sequences—a result that conservation-based predictions would not capture. Thus, although fitness prediction using evolutionary data can enrich in more-active variants, these approaches struggle to identify and differentiate among the most-active variants, even for this near-native function. Overall, this work presents a new, large-scale testing ground for model-guided enzyme engineering and suggests that efficient navigation of epistatic fitness landscapes can be improved by advances in both machine learning and physical modeling.Significance statementPredictive models for protein engineering seek to capture the relationship between protein sequence and function. While many methods and datasets exist for predicting the effects of single substitutions across a range of protein functions, fewer capture interactions among substitutions, which are much more difficult to predict. Even fewer do this comprehensively for a catalytic function. To provide a testbed for evaluating predictive models for enzyme engineering, we constructed and analyzed a 160,000-member enzyme sequence-fitness dataset at four interacting residues near the active site of tryptophan synthase, capturing significant non-additive effects of substitutions on catalytic function. It is necessary to predict and understand such interactions in order to efficiently traverse evolutionary landscapes and build machine learning models that accelerate protein engineering.