bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Surgical Learning Curve for Cervical Disk Replacement
Authors: Federico Vincent P. , Nie James W. , Hartman Timothy J. , Oyetayo Omolabake O. , Zheng Eileen , MacGregor Keith R. , Massel Dustin H. , Sayari Arash J. , Singh Kern 
Published: September 2023

Study Design:
Retrospective study.

Objective:
To characterize an experienced single surgeon learning curve for cervical disk replacement (CDR).

Summary of Background Data:
A single surgeon learning curve has not been established for CDR.

Methods:
Patients undergoing CDR were included. The cumulative sum of operative time was utilized to separate cases into 3 phases: learning, practicing, and mastery. Demographics, perioperative characteristics, complications, patient-reported outcomes (PROs), and radiographic outcomes were collected preoperatively and up to 1 year postoperatively. PROs included Patient-reported Outcomes Measurement Information System Physical Function, 12-item Short Form-12 Physical Component Score, 12-item Short Form-12 Mental Component Score, visual analog scale (VAS) arm, VAS neck, Neck Disability Index. Radiographic outcomes included segmental angle/segmental range of motion/C2-C7 range of motion. Minimum clinically important difference achievement was determined through a comparison of previously established values.

Results:
A total of 173 patients were identified, with 14 patients in the learning phase, 42 patients in the practicing phase, and 117 patients in the mastery phase. Mean operative time and mean postoperative day 0 narcotic consumption were significantly higher in the learning phase. The preoperative segmental angle was significantly lower for the learning phase, though these differences were eliminated at the final postoperative time point. Patients in the learning phase reported worse improvement to 6-week postoperative, final postoperative, and worse overall final postoperative VAS Arm scores compared with practicing and mastery phases.

Conclusions:
For an experienced spine surgeon, the learning phase for CDR was estimated to span 14 patients. During this phase, patients demonstrated longer operative times, higher postoperative narcotic consumption, and worse postoperative VAS Arm scores. Radiographically, no postoperative differences were noted between different phases of mastery. This single surgeon learning curve demonstrates that CDR may be performed safely and with comparable outcomes by experienced spine surgeons despite decreased operative efficiency in the learning phase.
Aperiodic EEG and 7T MRSI evidence for maturation of E/I balance supporting the development of working memory through adolescence
Authors: McKeon Shane D. , Perica Maria I. , Parr Ashley C. , Calabro Finnegan J. , Foran Will , Hetherington Hoby , Moon Chan-Hong , Luna Beatriz 
Published: September 2023

ABSTRACTPostmortem animal and human models suggest changes through adolescence in aspects of excitatory glutamatergic and inhibitory GABAergic function (E/I) in prefrontal cortex (PFC) suggestive of critical period plasticity at a time of significant cognitive development. Recently, using high field 7T Magnetic Resonance Spectroscopic Imaging (MRSI), we foundin vivoevidence for increases in PFC glutamate/GABA balance through adolescence into adulthood. We now extend these MRSI findings by investigating, in the same 164 10– 32-year-old participants, its correspondence with EEG aperiodic activity, an independent measure of E/I balance elucidating changes in neural activity. Results showed decreases in PFC aperiodic activity from adolescence to adulthood, that were associated with MRSI measures of glutamate/GABA balance as well as mediating the association between age and EEG aperiodic activity. Further, changes in aperiodic activity predicted performance on a working memory task, indicating a role for E/I based changes in PFC signaling mechanisms in supporting maturation of cognitive control. Taken together, these results suggest that PFC is undergoing critical period plasticity through adolescence evident in both neurotransmitter and neural function that supports cognitive development.
Periodic shifts in viral load increase risk of spillover from bats
Authors: Lunn Tamika J. , Borremans Benny , Jones Devin N. , Kessler Maureen K. , Dale Adrienne S. , Yinda Kwe C. , Ruiz-Aravena Manuel , Falvo Caylee A , Crowley Dan , Lloyd-Smith James O. , Munster Vincent J. , Eby Peggy , McCallum Hamish , Hudson Peter , Restif Olivier , McGuire Liam P. , Smith Ina L. ,   Bat One Health Group, Plowright Raina K. , Peel Alison J. 
Published: September 2023

AbstractPrediction and management of zoonotic pathogen spillover requires an understanding of infection dynamics within reservoir host populations. Transmission risk is often assessed using prevalence of infected hosts, with infection status based on the presence of genomic material. However, detection of viral genomic material alone does not necessarily indicate the presence of infectious virus, which could decouple prevalence from transmission risk. We undertook a multi-faceted investigation of Hendra virus shedding inPteropusbats, combining insights from virus isolation, viral load proxies, viral prevalence, and longitudinal patterns of shedding, from 6,151 samples. In addition to seasonal and interannual fluctuation in prevalence, we found evidence for periodic shifts in the distribution of viral loads. The proportion of bats shedding high viral loads was higher during peak prevalence periods during which spillover events were observed, and lower during non-peak periods when there were no spillovers. We suggest that prolonged periods of low viral load and low prevalence reflect prolonged shedding of non-infectious RNA, or viral loads that are insufficient or unlikely to overcome dose barriers to spillover infection. These findings show that incorporating viral load (or proxies of viral load) into longitudinal studies of virus excretion will better inform predictions of spillover risk than prevalence alone.Significance statementWe present a comprehensive analysis of a high-profile bat-virus system (Hendra virus in Australian flying-foxes) to demonstrate that both prevalence and viral loads can shift systematically over time, resulting in concentrated periods of increased spillover risk when prevalence and viral loads are high. We further suggest that prolonged periods of low-prevalence, low-load shedding may not reflect excretion of infectious virus, resolving the outstanding puzzle of why spillovers have not been observed during periods of low off-season prevalence in subtropical Australia, or more frequently in tropical Australia despite consistent low-prevalence shedding. The consideration of viral loads (or proxies of viral load) along with prevalence may improve risk inference from longitudinal surveys of zoonotic viruses across wildlife reservoir hosts.
Topographic Axes of Wiring Space Converge to Genetic Topography in Shaping Human Cortical Layout
Authors: Li Deying , Wang Yufan , Ma Liang , Wang Yaping , Cheng Luqi , Liu Yinan , Shi Weiyang , Lu Yuheng , Wang Haiyan , Gao Chaohong , Erichsen Camilla T. , Zhang Yu , Yang Zhengyi , Eickhoff Simon B , Chen Chi-Hua , Jiang Tianzi , Chu Congying , Fan Lingzhong 
Published: September 2023

AbstractGenetic information is involved in the gradual emergence of cortical areas since the neural tube begins to form, shaping the heterogeneous functions of neural circuits in the human brain. Informed by invasive tract-tracing measurements, the cortex exhibits marked interareal variation in connectivity profiles to reveal the heterogeneity across cortical areas. However, it remains unclear about the organizing principles possibly shared by genetics and cortical wiring to manifest the spatial heterogeneity across the cortex. Instead of considering a complex one-to-one mapping between genetic coding and interareal connectivity, we hypothesized the existence of a more efficient way that the organizing principles are embedded in genetic profiles to underpin the cortical wiring space. Leveraging on the vertex-wise tractography in diffusion-weighted MRI, we derived the global connectopies to reliably index the organizing principles of interareal connectivity variation in a low-dimensional space, which specifically captured three dominant topographic patterns along the dorsoventral, rostrocaudal, and mediolateral axes of the cortex. More importantly, we demonstrated that the global connectopies converge to the gradients of vertex-by-vertex genetic correlation matrix on the phenotype of cortical morphology and the cortex-wide spatiomolecular gradients. By diving into the genetic profiles, we found the critical role of genes scaffolding the global connectopies were related to brain morphogenesis and enriched in radial glial cells before birth and excitatory neurons after birth. Taken together, our findings demonstrated the existence of a genetically determined space to encode the interareal connectivity variation, which may give new insights into the links between cortical connections and arealization.
Effects of Savoring Meditation on Positive Emotions and Pain-Related Brain Function: A Mechanistic Randomized Controlled Trial in People With Rheumatoid Arthritis
Authors: Finan Patrick H. , Hunt Carly , Keaser Michael L. , Smith Katie , Lerman Sheera , Bingham Clifton O. , Barrett Frederick , Garland Eric L. , Zeidan Fadel , Seminowicz David A. 
Published: September 2023

AbstractPositive emotions are a promising target for intervention in chronic pain, but mixed findings across trials to date suggest that existing interventions may not be optimized to efficiently engage the target. The aim of the current mechanistic randomized controlled trial was to test the effects of a single skill positive emotion-enhancing intervention called Savoring Meditation on pain-related neural and behavioral targets in patients with rheumatoid arthritis (RA). Participants included 44 patients with a physician-confirmed diagnosis of RA (n=29 included in fMRI analyses), who were randomized to either Savoring Meditation or a Slow Breathing control. Both meditation interventions were brief (four 20-minute sessions). Self-report measures were collected pre- and post-intervention. An fMRI task was conducted at post-intervention, during which participants practiced the meditation technique on which they had been trained while exposed to non-painful and painful thermal stimuli. Relative to Slow Breathing, Savoring significantly reduced experimental pain intensity ratings relative to rest (p<.001), increased cerebral blood flow in the ventromedial prefrontal cortex (vmPFC) and increased connectivity between the vmPFC and caudate during noxious thermal stimulation (z=2.3 voxelwise, FDR cluster corrected p=0.05). Participants in the Savoring condition also reported significantly increased positive emotions (ps<.05) and reduced anhedonic symptoms (p<.01) from pre-to post-intervention. These findings suggest that that Savoring recruits reward-enhancing corticostriatal circuits in the face of pain, and future work should extend these findings to evaluate if these mechanisms of Savoring are associated with improved clinical pain outcomes in diverse patient populations.
Stereotypic persistent B cell receptor clonotypes in Alzheimer’s Disease
Authors: Yang Hyunji , Kim Namphil , Lee Yonghee , Yoo Duck Kyun , Choi Jinny , Kim Ki Woong , Bae Jong Bin , Han Ji Won , Kwon Sunghoon , Chung Junho 
Published: September 2023

AbstractWe constructed B cell receptor (BCR) repertoiresin silicousing peripheral blood (PB) samples collected from 44 Alzheimer’s Disease (AD) patients at baseline and 37 patients at follow-up. For the control group (CG), we used BCR repertoire data from the chronologically collected PB samples of 55 healthy volunteers vaccinated with SARS-CoV-2 mRNA. The AD patients shared 3,983 stereotypic non-naïve BCR clonotypes not found in CG, and their degree of overlap between patient pairs were significantly higher than that of CG pairs, even with the SARS-CoV-2 spike protein triggering a concerted BCR response. Twenty stereotypic non-naïve AD patient-specific BCR clonotypes co-existed in more than four patients and persisted throughout two sampling points. One of these BCR clonotypes encoded an antibody reactive to the Aβ42 peptide. Our findings strongly suggest that AD patients are exposed to common (auto)antigens associated with disease pathology, and their BCR repertoires show unique signatures with diagnostic potential.
Predictive Models and Impact of Interfacial Contacts and Amino Acids on Protein-protein Binding Affinity
Authors: Yi Carey Huang , Taylor Mitchell Lee , Ziebarth Jesse , Wang Yongmei 
Published: September 2023

AbstractProtein-protein interactions (PPIs) play a central role in nearly all cellular processes and that require proteins interact with sufficient binding affinity (BA) to form stable or transient complexes. Despite advancements in our understanding of protein-protein binding, much remains unknown about the interfacial region and its association with BA. Here we investigate the correlation of residue and atomic contacts of different types with BA and reveal the impact of the specific amino acids at the binding interface on BA. We create a series of linear regression (LR) models incorporating different contact features at both residue and atomic levels and examine how different methods of identifying and characterizing these properties impact the performance of these models. Particularly, we introduce a new and simple approach to predict BA based on the quantities of specific amino acids in contacts at the protein-protein interface. We show that the interfacial numbers of amino acids can be used to produce models with consistently good performance across different datasets, indicating the importance of the identities of interfacial amino acids in underlying the strength of BA. When trained on a diverse set of 141 complexes from two benchmark datasets, the best performing BA model (Pearson correlation coefficient R=0.68) was generated with an explicit linear equation involving six amino acids (tyrosine, glycine, serine, arginine, valine, and isoleucine). Tyrosine, in particular, was identified as the key amino acid in the quantitative link between specific amino acids and BA, as it had the strongest correlation with BA and was consistently identified as the most important amino acid in feature importance studies. Glycine, serine, and arginine were identified as the next three most important amino acids in predicting BA. The results from this study further our understanding of the importance of specific amino acids in PPIs and can be used to make improved predictions of BA, giving them implications for drug design and screening in the pharmaceutical industry.
Probing hippocampal stimulation in experimental temporal lobe epilepsy with functional MRI
Authors: Schwaderlapp Niels , Paschen Enya , LeVan Pierre , von Elverfeldt Dominik , Haas Carola 
Published: September 2023

AbstractBackgroundElectrical neurostimulation is a potentially effective therapy in epilepsy but the optimal approach is not yet clear. The parameter space is wide and the effects of different stimulations are not immediately obvious. Functional MRI (fMRI) can reveal which brain areas are affected by stimulation and help understand the induced effects. However, simultaneous deep brain stimulation (DBS)-fMRI examinations in patients are rare and the possibility to investigate multiple stimulation protocols is limited. Preclinical stimulation-fMRI studies can provide predictive value and help identify optimal neurostimulation parameters.ObjectiveTo systematically investigate the brain-wide responses to hippocampal electrical stimulations in a mouse model of mesial temporal lobe epilepsy (mTLE) using fMRI.MethodsWe applied electrical stimulation in the intrahippocampal kainate mouse model of mTLE and assessed the effect of different stimulation amplitudes (80-230 µA) and frequencies (1-100 Hz). In addition, the effect of prolonged 1 Hz stimulation was explored. Saline-injected mice served as controls.ResultsVarying the stimulation amplitudes had little effect on the resulting activation patterns. Low frequency stimulation led to a local response at the stimulation site only, whereas high frequency resulted in a spread of activation from the hippocampal formation into cortical and frontal areas. Prolonged low frequency stimulation reduced excitability.ConclusionsWhile the amplitude parameter offers little opportunity to vary the outcome, the frequency represented the key parameter and determined whether the induced activation remained local or spread across the brain. This is in line with the few DBS-fMRI results obtained in epilepsy patients demonstrating the translational value of fMRI.
Learning site-invariant features of connectomes to harmonize complex network measures
Authors: Newlin Nancy R. , Kanakaraj Praitayini , Li Thomas , Pechman Kimberly , Archer Derek , Jefferson Angela ,   The BIOCARD Study Team, Landman Bennett , Moyer Daniel 
Published: September 2023

ABSTRACTMulti-site diffusion MRI data is often acquired on different scanners and with distinct protocols. Differences in hardware and acquisition result in data that contains site dependent information, which confounds connectome analyses aiming to combine such multi-site data. We propose a data-driven solution that isolates site-invariant information whilst maintaining relevant features of the connectome. We construct a latent space that is uncorrelated with the imaging site and highly correlated with patient age and a connectome summary measure. Here, we focus on network modularity. The proposed model is a conditional, variational autoencoder with three additional prediction tasks: one for patient age, and two for modularity trained exclusively on data from each site. This model enables us to 1) isolate site-invariant biological features, learn site context, and 3) re-inject site context and project biological features to desired site domains. We tested these hypotheses by projecting 77 connectomes from two studies and protocols (Vanderbilt Memory and Aging Project (VMAP) and Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD) to a common site. We find that the resulting dataset of modularity has statistically similar means (p-value <0.05) across sites. In addition, we fit a linear model to the joint dataset and find that positive correlations between age and modularity were preserved.
An efficient peptide ligase engineered from a bamboo asparaginyl endopeptidase
Authors: Wang Xin-Bo , Zhang Cong-Hui , Zhang Teng , Li Hao-Zheng , Liu Ya-Li , Xu Zeng-Guang , Lei Gang , Cai Chun-Ju , Guo Zhan-Yun 
Published: September 2023

ABSTRACTIn recent years, a few asparaginyl endopeptidases (AEPs) from certain higher plants have been identified as efficient peptide ligases with wide applications in protein labeling and cyclic peptide synthesis. Recently, we developed a NanoLuc Binary Technology (NanoBiT)-based peptide ligase activity assay to identify more AEP-type peptide ligases. Herein, we screened 61 bamboo species from 16 genera using this assay and detected AEP-type peptide ligase activity in the crude extract of all tested bamboo leaves. From a popular bamboo species,Bambusa multiplex, we identified a full-length AEP-type peptide ligase candidate (BmAEP1) via transcriptomic sequencing. After its zymogen was overexpressed inEscherichia coliand self-activatedin vitro, BmAEP1 displayed high peptide ligase activity, but with considerable hydrolysis activity. After site-directed mutagenesis of its ligase activity determinants, the mutant zymogen of [G238V]BmAEP1 was normally overexpressed inE. coli, but failed to activate itself. To solve this problem, we developed a novel protease-assisted activation approach in which trypsin was used to cleave the mutant zymogen and was then conveniently removed via an ion-exchange chromatography. After the non-covalently bound cap domain was dissociated from the catalytic core domain under acidic conditions, the recombinant [G238V]BmAEP1 displayed high peptide ligase activity with much lower hydrolysis activity, and could efficiently catalyze inter-molecular protein ligation and intra-molecular peptide cyclization. Thus, the engineered bamboo-derived peptide ligase represents a novel tool for protein labeling and cyclic peptide synthesis.
Body Maps of Uncertainty and Surprise in Musical Chord Progression and its individual differences in Depression and Body Perception Sensitivity
Authors: Daikoku Tatsuya , Tanaka Masaki , Yamawaki Shigeto 
Published: September 2023

AbstractMusic has profoundly shaped the human experience across diverse cultures and generations, yet the mechanisms that it influences our minds and bodies remain elusive. This study examined how the perception of music chords elicits bodily sensations and emotions through predictive processing of the brain. By deploying body-mapping tests and emotional evaluations on 527 participants exposed to chord progressions, we unveil the intricate interplay between musical uncertainty, prediction error, and temporal dynamics in eliciting specific bodily sensations and emotions. Our results demonstrated that the chord progressions characterized by low uncertainty coupled with high surprise or predictability evoke bodily sensations closely associated with interoception including the cardiac and abdominal regions. Notably, these sensations are associated with aesthetic appreciation, with the intensity of cardiac sensations being positively correlated with valence in chord progressions with low uncertainty and high surprise. These results highlight the pivotal role of uncertainty and prediction error in shaping emotional responses and also suggest a hypothesis for emotion generation through predictive processing and sound embodiment. This study offers a tantalizing glimpse into the potential nexus between interoception by music and mental well-being, underscoring the importance of recognizing diverse forms of musical pleasure and their unique effects on our minds and bodies.