bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the Quality of Narrative Feedback for Entrustable Professional Activities in a Surgery Residency Program
Authors: Fernandes Rosephine Del , de Vries Ingrid , McEwen Laura , Mann Steve , Phillips Timothy , Zevin Boris 
Published: April 2024

Objective:
To assess the quality of narrative feedback given to surgical residents during the first 5 years of competency-based medical education implementation.

Background:
Competency-based medical education requires ongoing formative assessments and feedback on learners’ performance.

Methods:
We conducted a retrospective cross-sectional study using assessments of entrustable professional activities (EPAs) in the Surgical Foundations curriculum at Queen’s University from 2017 to 2022. Two raters independently evaluated the quality of narrative feedback using the Quality of Assessment of Learning score (0–5).

Results:
A total of 3900 EPA assessments were completed over 5 years. Of assessments, 57% (2229/3900) had narrative feedback documented with a mean Quality of Assessment of Learning score of 2.16 ± 1.49. Of these, 1614 (72.4%) provided evidence about the resident’s performance, 951 (42.7%) provided suggestions for improvement, and 499/2229 (22.4%) connected suggestions to the evidence. There was no meaningful change in narrative feedback quality over time (r = 0.067, P = 0.002). Variables associated with lower quality of narrative feedback include: attending role (2.04 ± 1.48) compared with the medical student (3.13 ± 1.12, P < 0.001) and clinical fellow (2.47 ± 1.54, P < 0.001), concordant specialties between the assessor and learner (2.06 ± 1.50 vs 2.21 ± 1.49, P = 0.025), completion of the assessment 1 month or more after the encounter versus 1 week (1.85 ± 1.48 vs 2.23 ± 1.49, P < 0.001), and resident entrusted versus not entrusted to perform the assessed EPA (2.13 ± 1.45 vs 2.35 ± 1.66; P = 0.008). The quality of narrative feedback was similar for assessments completed under direct and indirect observation (2.18 ± 1.47 vs 2.06 ± 1.54; P = 0.153).

Conclusions:
Just over half of the EPA assessments of surgery residents contained narrative feedback with overall fair quality. There was no meaningful change in the quality of feedback over 5 years. These findings prompt future research and faculty development.
National Football League Game Officials Self-Rating of Knowledge in Neuro-Ophthalmic Principles and Practice: A Pilot Program to Improve Precision and Accuracy of Game Official Calls
Authors: Carrabba Nicole V. , Ong Joshua , Vogt Ashtyn Z. , Panzo Nicholas J. , Memon Hamza , Lee Virginia A. , Waisberg Ethan , Sarker Prithul , Zaman Nasif , Tavakkoli Alireza , Laylani Noor A. , Lee Andrew G. 
Published: April 2024

Background:
To determine whether a neuro-ophthalmic curriculum would improve National Football League (NFL) game officials' self-rated knowledge and interest in neuro-ophthalmic principles to improve precision and accuracy of NFL play-calling.

Methods:
The formalized and structured neuro-ophthalmic principles (NOP) curriculum was introduced to 121 NFL game officials, 17 replay officials, and 4 officiating staff who attended the NFL Official Training Camp in Irving, Texas, on September 8 and 9, 2023. Before and after the lecture and videos were introduced, participants completed an optional hard-copy feedback form pertaining to self-reported NOP knowledge, likelihood of using said terms, and interest in future content of NOP applicable NFL officiating. Paired 2-tailed t tests were used for statistical analysis to directly compare the self-reported knowledge before and after the neuro-ophthalmic curriculum introduction.

Results:
One hundred forty-two participants completed the prelecture and postlecture feedback forms self-reported knowledge after the NOP curriculum was given to the NFL officiating staff. All (142/142) participants completed a survey. There was a statistically significant improvement in the mean ratings of the prelecture vs. postlecture understanding of the specific neuro-ophthalmic terms pertinent to NFL game officials (2.6 [95% CI, 2.3–3.0] vs. 7.9 [95% CI, 7.6–8.2], P < 0.001) and 2.7 [95% CI, 2.3–3.0] vs. 7.7 [95% CI, 7.4–8.0]), respectively. There was a statistically significant greater likelihood of using said terms prelecture vs. postlecture (2.9 [95% CI, 2.4–3.4] vs. 7.5 [95% CI, 7.2–7.9], P < 0.001).

Conclusions:
This study found a statistically significant improvement in neuro-ophthalmic knowledge and a greater likelihood of using NOP terms following the NOP curriculum. NFL game officials, replay officials, and staff are interested in expanding their knowledge in the vision science of neuro-ophthalmic concepts and applications involved in play-calling. We hope that our pilot data will lead to a model of education that will improve the precision and accuracy of NFL play-calls by officials on game days.
Non-resolving neuroinflammation regulates axon regeneration in chronic spinal cord injury
Authors: Stewart Andrew N. , Bosse-Joseph Christopher C. , Kumari Reena , Bailey William M. , Park Kennedy A. , Slone Victoria K. , Gensel John C. 
Published: April 2024

AbstractChronic spinal cord injury (SCI) lesions retain increased densities of microglia and macrophages. In acute SCI, macrophages induce growth cone collapse, facilitate axon retraction away from lesion boundaries, as well as play a key role in orchestrating the growth-inhibitory glial scar. Little is known about the role of sustained inflammation in chronic SCI, or whether chronic inflammation affects repair and regeneration. We performed transcriptional analysis using the Nanostring Neuropathology panel to characterize the resolution of inflammation into chronic SCI, to characterize the chronic SCI microenvironment, as well as to identify spinal cord responses to macrophage depletion and repopulation using the CSF1R inhibitor, PLX-5622. We determined the ability for macrophage depletion and repopulation to augment axon growth into chronic lesions both with and without regenerative stimulation using neuronal-specific PTEN knockout (PTEN-KO). PTEN-KO was delivered with spinal injections of retrogradely transported adeno associated viruses (AAVrg’s). Both transcriptional analyses and immunohistochemistry revealed the ability for PLX-5622 to significantly deplete inflammation around and within chronic SCI lesions, with a return to pre-depleted inflammatory densities after treatment removal. Neuronal-specific transcripts were significantly elevated in mice after inflammatory repopulation, but no significant effects were observed with macrophage depletion alone. Axon densities significantly increased within the lesion after PLX-5622 treatment with a more consistent effect observed in mice with inflammatory repopulation. PTEN-KO did not further increase axon densities within the lesion beyond effects induced by PLX-5622. We identified that PLX-5622 increased axon densities within the lesion that are histologically identified as 5-HT+and CGRP+, both of which are not robustly transduced by AAVrg’s. Our work identified that increased macrophage/microglia densities in the chronic SCI environment may be actively retained by homeostatic mechanisms likely affiliated with a sustained elevated expression of CSF1 and other chemokines. Finally, we identify a novel role of sustained inflammation as a prospective barrier to axon regeneration in chronic SCI.HighlightsMacrophages and microglia repopulate the chronically injured spinal cord after depletion.CSF1R antagonism in chronic SCI augments the growth of specific axon types in the lesion.CSF1R antagonism does not augment a PTEN-knockout-induced functional recovery.
Novel inhibitors of acute, axonal DLK palmitoylation are neuroprotective and avoid the deleterious side effects of cell-wide DLK inhibition
Authors: Zhang Xiaotian , Jeong Heykyeong , Niu Jingwen , Holland Sabrina M. , Rotanz Brittany N. , Gordon John , Einarson Margret B. , Childers Wayne E. , Thomas Gareth M. 
Published: April 2024

AbstractDual leucine-zipper kinase (DLK) drives acute and chronic forms of neurodegeneration, suggesting that inhibiting DLK signaling could ameliorate diverse neuropathological conditions. However, direct inhibition of DLK’s kinase domain in human patients and conditional knockout of DLK in mice both cause unintended side effects, including elevated plasma neurofilament levels, indicative of neuronal cytoskeletal disruption. Indeed, we found that a DLK kinase domain inhibitor acutely disrupted the axonal cytoskeleton and caused vesicle aggregation in cultured dorsal root ganglion (DRG) neurons, further cautioning against this therapeutic strategy. In seeking a more precise intervention, we found that retrograde (axon-to-soma) pro-degenerative signaling requires acute, axonal palmitoylation of DLK and hypothesized that modulating this post-translational modification might be more specifically neuroprotective than cell-wide DLK inhibition. To address this possibility, we screened >28,000 compounds using a high-content imaging assay that quantitatively evaluates DLK’s palmitoylation-dependent subcellular localization. Of the 33 hits that significantly altered DLK localization in non-neuronal cells, several reduced DLK retrograde signaling and protected cultured DRG neurons from DLK-dependent neurodegeneration. Mechanistically, the two most neuroprotective compounds selectively prevent stimulus-dependent palmitoylation of axonal pools of DLK, a process crucial for DLK’s recruitment to axonal vesicles. In contrast, these compounds minimally impact DLK localization and signaling in healthy neurons and avoid the cytoskeletal disruption associated with direct DLK inhibition. Importantly, our hit compounds also reduce pro-degenerative retrograde signaling in vivo, suggesting that modulating DLK’s palmitoylation-dependent localization could be a novel neuroprotective strategy.
A straightforward cell culture insert model to incorporate biochemical and biophysical stromal properties into transplacental transport studies
Authors: Nelson Katherine M. , Ferrick Bryan J. , Karimi Hassan , Hatem Christine L. , Gleghorn Jason P. 
Published: April 2024

IntroductionThe placental extracellular matrix (ECM) dynamically remodels over pregnancy and in disease. How these changes impact placental barrier function is poorly understood as there are limitedin vitromodels of the placenta with a modifiable stromal compartment to mechanistically investigate these extracellular factors. We developed a straightforward method to incorporate uniform hydrogels into standard cell culture inserts for transplacental transport studies.MethodsUniform polyacrylamide (PAA) gels were polymerized within cell culture inserts by (re)using the insert packaging to create a closed, controllable environmental chamber. PAA pre-polymer solution was added dropwise via a syringe to the cell culture insert and the atmosphere was purged with an inert gas. Transport and cell culture studies were conducted to validate the model.ResultsWe successfully incorporated and ECM functionalized uniform PAA gels to cell culture inserts enable cell adhesion and monolayer formation. Imaging and analyte transport studies validated gel formation and expected mass transport results and successful cell studies confirmed cell viability, monolayer formation, and that the model could be used transplacental transport studies. Detailed methods and validation protocols are included.DiscussionIt is well appreciated that ECM biophysical and biochemical properties impact cell phenotype and cell signaling in many tissues including the placenta. The incorporation of a PAA gel within a cell culture insert enables independent study of placental ECM biophysical and biochemical properties in the context of transplacental transport. These straightforward and low-cost methods to build three dimensional cellular models are readily adoptable by the wider scientific community.
Quantifying and controlling the proteolytic degradation of cell adhesion peptides
Authors: Rozans Samuel J. , Moghaddam Abolfazl Salehi , Wu Yingjie , Atanasoff Kayleigh , Nino Liliana , Dunne Katelyn , Pashuck E. Thomas 
Published: April 2024

AbstractPeptides are widely used within biomaterials to improve cell adhesion, incorporate bioactive ligands, and enable cell-mediated degradation of the matrix. While many of the peptides incorporated into biomaterials are intended to be present throughout the life of the material, their stability is not typically quantified during culture. In this work we designed a series of peptide libraries containing four different N-terminal peptide functionalizations and three C-terminal functionalization to better understand how simple modifications can be used to reduce non-specific degradation of peptides. We tested these libraries with three cell types commonly used in biomaterials research, including mesenchymal stem/stromal cells (hMSCs), endothelial cells, and macrophages, and quantified how these cell types non-specifically degraded peptide as a function of terminal amino acid and chemistry. We found that peptides in solution which contained N-terminal amines were almost entirely degraded by 48 hours, irrespective of the terminal amino acid, and that degradation occurred even at high peptide concentrations. Peptides with C-terminal carboxylic acids also had significant degradation when cultured with cells. We found that simple modifications to the termini could significantly reduce or completely abolish non-specific degradation when soluble peptides were added to cells cultured on tissue culture plastic or within hydrogel matrices, and that functionalizations which mimicked peptide conjugations to hydrogel matrices significantly slowed non-specific degradation. We also found that there were minimal differences across cell donors, and that sequences mimicking different peptides commonly-used to functionalized biomaterials all had significant non-specific degradation. Finally, we saw that there was a positive trend between RGD stability and hMSC spreading within hydrogels, indicating that improving the stability of peptides within biomaterial matrices may improve the performance of engineered matrices.
300 Hz transcutaneous auricular vagus nerve stimulation (taVNS) impacts pupil size nonlinearly as a function of intensity
Authors: Phillips Ian , Johns Michael A. , Pandža Nick B. , Calloway Regina C. , Karuzis Valerie P. , Kuchinsky Stefanie E. 
Published: April 2024

AbstractTranscutaneous auricular vagus nerve stimulation (taVNS) is a neuromodulatory technique that may have numerous potential health and human performance benefits. However, optimal stimulation parameters for maximizing taVNS efficacy are unknown. Progress is impeded by disagreement on the identification of a biomarker that reliably indexes activation of neuromodulatory systems targeted by taVNS, including the locus coeruleus-norepinephrine (LC-NE) system. Pupil size varies with LC-NE activity and is one potential taVNS biomarker that has shown inconsistent sensitivity to taVNS in prior studies. The present study examined the relationship between pupil size and taVNS using stimulation parameters that have shown promising behavioral effects in prior studies but have received comparatively little attention. Participants received 30-second trains of 50 μs taVNS pulses delivered below perceptual threshold at 300 Hz to the left external acoustic meatus (EAM) while pupil size was recorded during a pupillary light reflex task. Analysis of pupil size using generalized additive mixed modelling (GAMM) revealed a nonlinear relationship between taVNS intensity and pupil diameter. Active taVNS increased pupil size during stimulation for participants who received taVNS between 2 and approximately 4.8 mA, but not for participants who received higher intensity taVNS (up to 8.1 mA). In addition, taVNS effects persisted in subsequent blocks, mitigating decreases in pupil size over the course of the task. These findings suggest 300 Hz taVNS activates the LC-NE system when applied to the EAM, but its effects may be counteracted at higher intensities.
The spatial and cellular portrait of Transposable Element expression during Gastric Cancer
Authors: Valdebenito-Maturana Braulio 
Published: April 2024

AbstractGastric Cancer (GC) is a lethal malignancy, with urgent need for the discovery of novel biomarkers for its early detection. I previously showed that Transposable Elements (TEs) become activated in early GC (EGC), suggesting a role in gene expression. Here, I follow-up on that evidence using single-cell data from gastritis to EGC, and show that TEs are expressed and follow the disease progression, with 2,430 of them being cell populations markers. Pseudotemporal trajectory modeling revealed 111 TEs associated with the origination of cancer cells. Analysis of spatial data from GC also confirms TE expression, with 204 TEs being spatially enriched. Finally, a network of TE-mediated gene regulation was modeled, indicating that ∼2,000 genes could be modulated by TEs, with ∼500 of them already implicated in cancer. These results suggest that TEs might play a functional role in GC progression, and highlights them as potential biomarker for its early detection.
A recurrent neural circuit inDrosophiladeblurs visual inputs
Authors: Pang Michelle M. , Chen Feng , Xie Marjorie , Druckmann Shaul , Clandinin Thomas R. , Yang Helen H. 
Published: April 2024

SummaryA critical goal of vision is to detect changes in light intensity, even when these changes are blurred by the spatial resolution of the eye and the motion of the animal. Here we describe a recurrent neural circuit inDrosophilathat compensates for blur and thereby selectively enhances the perceived contrast of moving edges. Usingin vivo, two-photon voltage imaging, we measured the temporal response properties of L1 and L2, two cell types that receive direct synaptic input from photoreceptors. These neurons have biphasic responses to brief flashes of light, a hallmark of cells that encode changes in stimulus intensity. However, the second phase was often much larger than the first, creating an unusual temporal filter. Genetic dissection revealed that recurrent neural circuitry strongly shapes the second phase of the response, informing the structure of a dynamical model. By applying this model to moving natural images, we demonstrate that rather than veridically representing stimulus changes, this temporal processing strategy systematically enhances them, amplifying and sharpening responses. Comparing the measured responses of L2 to model predictions across both artificial and natural stimuli revealed that L2 tunes its properties as the model predicts in order to deblur images. Since this strategy is tunable to behavioral context, generalizable to any time-varying sensory input, and implementable with a common circuit motif, we propose that it could be broadly used to selectively enhance sharp and salient changes.
PLM_Sol: predicting protein solubility by benchmarking multiple protein language models with the updatedEscherichia coliprotein solubility dataset
Authors: Zhang Xuechun , Hu Xiaoxuan , Zhang Tongtong , Yang Ling , Liu Chunhong , Xu Ning , Wang Haoyi , Sun Wen 
Published: April 2024

AbstractProtein solubility plays a crucial role in various biotechnological, industrial and biomedical applications. With the reduction in sequencing and gene synthesis costs, the adoption of high-throughput experimental screening coupled with tailored bioinformatic prediction has witnessed a rapidly growing trend for the development of novel functional enzymes of interest (EOI). High protein solubility rates are essential in this process and accurate prediction of solubility is a challenging task. As deep learning technology continues to evolve, attention-based protein language models (PLMs) can extract intrinsic information from protein sequences to a greater extent. Leveraging these models along with the increasing availability of protein solubility data inferred from structural database like the Protein Data Bank (PDB), holds great potential to enhance the prediction of protein solubility. In this study, we curated an UpdatedEscherichia coli(E.coli) protein Solubility DataSet (UESolDS) and employed a combination of multiple PLMs and classification layers to predict protein solubility. The resulting best-performing model, named Protein Language Model-based protein Solubility prediction model (PLM_Sol), demonstrated significant improvements over previous reported models, achieving a notable 5.7% increase in accuracy, 9% increase in F1_score, and 10.4% increase in MCC score on the independent test set. Moreover, additional evaluation utilizing our in-house synthesized protein resource as test data, encompassing diverse types of enzymes, also showcased the superior performance of PLM_Sol. Overall, PLM_Sol exhibited consistent and promising performance across both independent test set and experimental set, thereby making it well-suited for facilitating large-scale EOI studies. PLM_Sol is available as a standalone program and as an easy-to-use model athttps://zenodo.org/doi/10.5281/zenodo.10675340.
Phase 2 Study of Sorafenib, Valproic Acid, and Sildenafil in the Treatment of Recurrent High-Grade Glioma
Authors: Poklepovic Andrew S. , Shah Palak , Tombes Mary Beth , Shrader Ellen , Bandyopadhyay Dipankar , Deng Xiaoyan , Roberts Catherine H. , Ryan Alison A. , Hudson Daniel , Sankala Heidi , Kmieciak Maciej , Dent Paul , Malkin Mark G. 
Published: April 2024

AbstractHere we report the results of a single-center phase 2 clinical trial combining sorafenib tosylate, valproic acid, and sildenafil for the treatment of patients with recurrent high-grade glioma (NCT01817751). Clinical toxicities were grade 1 and grade 2, with one grade 3 toxicity for maculopapular rash (6.4%). For all evaluable patients, the median progression-free survival was 3.65 months and overall survival (OS) 10.0 months. There was promising evidence showing clinical activity and benefit. In the 33 evaluable patients, low protein levels of the chaperone GRP78 (HSPA5) was significantly associated with a better OS (p < 0.0026). A correlation between the expression of PDGFRα and OS approached significance (p < 0.0728). Five patients presently have a mean OS of 73.6 months and remain alive. This is the first therapeutic intervention glioblastoma trial to significantly associate GRP78 expression to OS. Our data suggest that the combination of sorafenib tosylate, valproic acid, and sildenafil requires additional clinical development in the recurrent glioma population.