bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuropathic Pain After Burn Injury: A Severe and Common Problem in Recovery
Authors: Stanton Eloise , Kowalske Karen , Won Paul , Schneider Jeffrey C. , Ryan Colleen , Carrougher Gretchen , McMullen Kara , Yenikomshian Haig A. 
Published: November 2023

Objective:
To address the limited understanding of neuropathic pain (NP) among burn survivors by comprehensively examining its prevalence and related factors on a national scale using the Burn Model System (BMS) National Database.

Summary Background Data:
NP is a common but underexplored complaint among burn survivors, greatly affecting their quality of life and functionality well beyond the initial injury. Existing data on NP and its consequences in burn survivors are limited to select single-institution studies, lacking a comprehensive national perspective.

Methods:
The BMS National Database was queried to identify burn patients responding to NP-related questions at enrollment, six months, 12 months, two years, and five years post-injury. Descriptive statistics and regression analyses were used to explore associations between demographic/clinical characteristics and self-reported NP at different time points.

Results:
There were 915 patients included for analysis. At discharge, 66.5% of patients experienced NP in their burn scars. Those with NP had significantly higher PROMIS-29 pain inference, itch, anxiety, depression, and sleep disturbance scores and were less able to partake in social roles. Multiple logistic regression revealed male sex, %TBSA, and moderate-to-severe pain as predictors of NP at six months. At 12 months, %TBSA and moderate-to-severe pain remained significant predictors, while ethnicity and employment status emerged as significant predictors at 24 months.

Conclusions:
This study highlights the significant prevalence of NP in burn patients and its adverse impacts on their physical, psychological, and social well-being. The findings underscore the necessity of a comprehensive approach to NP treatment, addressing both physical symptoms and psychosocial factors.
Serial Dependence in face-gender classification revealed in low-beta frequency EEG
Authors: Ranieri Giacomo , Burr David C. , Bell Jason , Morrone Maria Concetta 
Published: November 2023

AbstractPerception depends not only on current sensory input but is also heavily influenced by the immediate past perceptual experience, a phenomenon known as “serial dependence”. It is particularly robust in face perception. We measured face-gender classification for a sequence of intermingled male, female and androgynous images. The classification showed strong serial dependence (androgynous images biased male when preceded by male and female when preceded by female). The strength of the bias oscillated over time in the beta range, at 14 Hz for female prior stimuli, 17 Hz for male. Using classification techniques, we were able to successfully classify the previous stimulus from current EEG activity. Classification accuracy correlated well with the strength of serial dependence in individual participants, confirming that the neural signal from the past trial biased face perception. Bandpass filtering of the signal within the beta range showed that the best information to classify gender was around 14 Hz when the previous response was “female”, and around 17 Hz when it was “male”, reinforcing the psychophysical results showing serial dependence to be carried at those frequencies. Overall, the results suggest that recent experience of face-gender is selectively represented in beta-frequency (14–20 Hz) spectral components of intrinsic neural oscillations.Significance StatementThe neurophysiological mechanisms of how past perceptual experience affects current perception are poorly understood. Using classification techniques, we demonstrate that the gender of face images can be decoded from the neural activity of the EEG response to the successive face stimulus, showing that relevant neural signals are maintained over trials. Classification accuracy was higher for participants with strong serial dependence, strongly implicating these signals as the neural substrate for serial dependence. The best information to classify gender was around 14 Hz for “female” faces, and around 17 Hz for “male”, reinforcing the psychophysical results showing serial dependence to be carried at those beta-frequencies.
Hyperactive PI3Kinase delta enables long distance regeneration of the rat corticospinal tract
Authors: Karova Kristyna , Polcanova Zuzana , Suchankova Stepanka , Knight Lydia , Nieuwenhuis Bart , Holota Radovan , Herynek Vit , Urdzikova Lucia Machova , Turecek Rostislav , Kwok Jessica C.F. , Verhaagen Joost , Eva Richard , Fawcett James W , Jendelova Pavla 
Published: November 2023

AbstractMaturation of central nervous system neurons leads to loss of their intrinsic regeneration potential. In particular after injury of the adult spinal cord there is minimal regeneration of corticospinal axons, which control gait and fine movement. Previous work has shown that knockdown of PTEN to increase PIP3 levels can promote regeneration in young animals, but the effect is much less in adults probably due to low PIP3 production. Here, we have transduced sensorimotor cortex neurons with a hyperactive form of PI3K, PI3Kδ, which increases PIP3 in mature neurons. This enables cortical neurons to regenerate corticospinal axons and improve behavioural outcomes.We used a C4 dorsal column lesion model in adult rats and injected the right motor cortex at 4 sites concurrently with a mixture AAV1-PIK3CD and AAV1-eGFP or titre matched AAV1-eGFP only. We allowed rats to survive for 6, 9, 12 or 16 weeks. Immunostaining showed 70 - 80% co-expression in cortical neurons which remained stable at both 12 and 16 weeks. We counted GFP labelled axons in 20 μm spinal cord sections. In PI3KCD-treated animals many axons were seen to have regenerated around the margins of lesions, collecting into a knot of axons with the typical appearance of regeneration at the caudal end. Tracing down the cord, and excluding axons and neurites that could have come from unlesioned ventral CST, we found axons extending up to 1 cm below lesions, numbers decreasing with distance from the lesion. After 16 weeks there were circa 200 axons at the caudal end of lesions with a regeneration index of 0.2, with half this number at 12 weeks. Behavioural testing for 16 weeks revealed functional improvements in skilled paw reaching, grip strength and ladder rung walking in rats treated with PIK3CD compared to GFP only controls. In addition to behavioural testing, functional recovery of PIK3CD treated rats was confirmed with electrophysiological recordings during which we stimulated the right pyramid. Cord dorsum potentials (CDPs) above and below lesion and EMG forepaw distal flexor muscles showed greatly increased connectivity compared with GFP only controls, lesion only controls and uninjured shams. We conclude that forcing upregulation of PI3Kδ in cortical neurons leads to robust regeneration after spinal cord injury that results in functional restoration.
Genome-wide DNA methylation changes in human spermatogenesis
Authors: Siebert-Kuss Lara M. , Dietrich Verena , Persio Sara Di , Bhaskaran Jahnavi , Stehling Martin , Cremers Jann-Frederik , Sandmann Sarah , Varghese Julian , Kliesch Sabine , Schlatt Stefan , Vaquerizas Juan M. , Neuhaus Nina , Laurentino Sandra 
Published: November 2023

SummarySperm production and function require the correct establishment of DNA methylation patterns in the germline. Here, we examined the genome-wide DNA methylation changes during human spermatogenesis and its alterations in disturbed spermatogenesis. We found that spermatogenesis is associated with remodeling of the methylome, comprising a global-decline in DNA methylation in primary spermatocytes followed by selective remethylation, resulting in a spermatid-specific methylome. Hypomethylated regions in spermatids were enriched in specific transcription factor binding sites for DMRT and SOX family members and spermatid-specific genes. Intriguingly, while SINEs displayed differential methylation throughout spermatogenesis, LINEs appeared to be protected from changes in DNA methylation. In disturbed spermatogenesis, germ cells exhibited considerable DNA methylation changes, which were significantly enriched at transposable elements and genes involved in spermatogenesis. We detected hypomethylation in SVA and L1HS in disturbed spermatogenesis, suggesting an association between the abnormal programming of these regions and failure of germ cells progressing beyond meiosis.
A human pluripotent stem cell-based somitogenesis model using microfluidics
Authors: Liu Yue , Kim Yung Su , Xue Xufeng , Kobayashi Norio , Sun Shiyu , Yang Qiong , Pourquié Olivier , Fu Jianping 
Published: November 2023

SUMMARYEmerging human pluripotent stem cell (hPSC)-based embryo models are useful for studying human embryogenesis. Particularly, there are hPSC-based somitogenesis models using free-floating culture that recapitulate somite formation. Somitogenesisin vivoinvolves intricately orchestrated bio-chemical and -mechanical events. However, none of the current somitogenesis models controls biochemical gradients or biomechanical signals in the culture, limiting their applicability to untangle complex biochemical-biomechanical interactions that drive somitogenesis. Here we report a new human somitogenesis model by confining hPSC-derived presomitic mesoderm (PSM) tissues in microfabricated trenches. Exogenous microfluidic morphogen gradients imposed on PSM cause axial patterning and trigger spontaneous rostral-to-caudal somite formation. A mechanical theory is developed to explain the size dependency between somites and PSM. The microfluidic somitogenesis model is further exploited to reveal regulatory roles of cellular and tissue biomechanics in somite formation. This study presents a useful microengineered, hPSC-based model for understanding the bio-chemical and -mechanical events that guide somite formation.
Nano-pulling stimulates axon regeneration in dorsal root ganglia by inducing stabilization of axonal microtubules and activation of local translation
Authors: Falconieri Alessandro , Folino Pietro , Palmata Lorenzo Da , Raffa Vittoria 
Published: November 2023

AbstractAxonal plasticity is a phenomenon strongly related to neuronal development as well as regeneration. Recently, it has been demonstrated that active mechanical tension, intended as an extrinsic factor, is a valid contribution to the modulation of axonal plasticity. In previous publications, our team validated a method, the “nano-pulling”, for applying mechanical forces on developing axons of isolated primary neurons using magnetic nanoparticles (MNP) actuated by static magnetic fields. This method was found to promote axon growth and synaptic maturation. Here, we explore the possibility to use nano-pulling as an extrinsic factor to promote axon regeneration in a neuronal tissue explant. Having this in mind, whole dorsal root ganglia (DRG) have been dissected from mouse spinal cord, incubated with MNPs, and then stretched. We found that particles were able to penetrate the ganglion and to localise both into the somas and in sprouting axons. Our results point that the nano-pulling doubles the regeneration rate, documented by an increase in the arborizing capacity of axons, and an accumulation of cellular organelles related to mass addition (endoplasmic reticulum and mitochondria) with respect to spontaneous regeneration. In line with the previous results on isolated hippocampal neurons, we observed an increase in the density of stable microtubules and activation of local translation in stretched ganglions. The collected data demonstrate that the nano-pulling is able to enhance axon regeneration in whole spinal ganglia exposed to MNPs and external magnetic fields. The preliminary data represent an encouraging starting point for proposing the nano-pulling as biophysical tool to design novel therapies based on the use of force as an extrinsic factor for promoting nerve regeneration.
The mindful brain at rest: neural oscillations and aperiodic activity in experienced meditators
Authors: McQueen Brittany , Murphy Oscar W , Fitzgerald Paul B , Bailey Neil W. 
Published: November 2023

AbstractObjectivesPrevious research has demonstrated that mindfulness meditation is associated with a variety of benefits, including improved mental health. Researchers have suggested these benefits may be underpinned by differences in neural oscillations. However, previous studies measuring neural oscillations have not controlled for non-oscillatory neural activity, the power spectrum of which follows a 1/f distribution and contributes to power measurements within oscillation frequencies of interest. In this study, we applied recently developed methods to determine if past findings related to neural oscillations in meditation are present even after controlling for non-oscillatory 1/f activity.Methods48 experienced meditators and 44 non-meditators provided resting electroencephalography (EEG) recordings. Whole scalp EEG comparisons (topographical ANOVAs) were used to test for differences between meditators and non-meditators in the distribution or global power of activity for theta, alpha, beta, and gamma oscillations, and for the 1/f components slope and intercept.ResultsResults indicated that meditators showed differences in theta, alpha, and gamma oscillatory power compared to non-meditators (allp< 0.05). Post-hoc testing suggested that the oscillatory differences were primarily driven by differences in the distribution of neural activity between meditators and non-meditators, rather than differences in the overall power across all scalp electrodes.ConclusionOur results suggest that experience with meditation is associated with higher oscillatory power and altered distributions of theta, alpha and gamma oscillations, even after controlling for non-oscillatory 1/f activity. Band-specific differences in oscillatory activity may be a mechanism through which meditation leads to neurophysiological benefits.
Multimodal mismatch responses in mouse auditory cortex
Authors: Solyga Magdalena , Keller Georg B. 
Published: November 2023

SUMMARYOur movements result in predictable sensory feedback that is often multimodal. Based on deviations between predictions and actual sensory input, primary sensory areas of cortex have been shown to compute sensorimotor prediction errors. How prediction errors in one sensory modality influence the computation of prediction errors in another modality is still unclear. To investigate multimodal prediction errors in mouse auditory cortex (ACx), we used a virtual environment to experimentally couple running to both self-generated auditory and visual feedback. Using two-photon microscopy, we first characterized responses of layer 2/3 (L2/3) neurons to sounds, visual stimuli, and running onsets and found responses to all three stimuli. Probing responses evoked by audiomotor mismatches, we found that they closely resemble visuomotor mismatch responses in visual cortex (V1). Finally, testing for cross modal influence on audiomotor mismatch responses by coupling both sound amplitude and visual flow speed to the speed of running, we found that audiomotor mismatch responses were amplified when paired with concurrent visuomotor mismatches. Our results demonstrate that multimodal and non-hierarchical interactions shape prediction error responses in cortical L2/3.
Inferring therapeutic vulnerability within tumors through integration of pan-cancer cell line and single-cell transcriptomic profiles
Authors: Zhang Weijie , Maeser Danielle , Lee Adam , Huang Yingbo , Gruener Robert F. , Abdelbar Israa G. , Jena Sampreeti , Patel Anand G. , Huang R. Stephanie 
Published: November 2023

AbstractSingle-cell RNA sequencing greatly advanced our understanding of intratumoral heterogeneity through identifying tumor subpopulations with distinct biologies. However, translating biological differences into treatment strategies is challenging, as we still lack tools to facilitate efficient drug discovery that tackles heterogeneous tumors. One key component of such approaches tackles accurate prediction of drug response at the single-cell level to offer therapeutic options to specific cell subpopulations. Here, we present a transparent computational framework (nicknamed scIDUC) to predict therapeutic efficacies on an individual-cell basis by integrating single-cell transcriptomic profiles with large, data-rich pan-cancer cell line screening datasets. Our method achieves high accuracy, with predicted sensitivities easily able to separate cells into their true cellular drug resistance status as measured by effect size (Cohen’s d > 1.0). More importantly, we examine our method’s utility with three distinct prospective tests covering different diseases (rhabdomyosarcoma, pancreatic ductal adenocarcinoma, and castration-resistant prostate cancer), and in each our predicted results are accurate and mirrored biological expectations. In the first two, we identified drugs for cell subpopulations that are resistant to standard-of-care (SOC) therapies due to intrinsic resistance or effects of tumor microenvironments. Our results showed high consistency with experimental findings from the original studies. In the third test, we generated SOC therapy resistant cell lines, used scIDUC to identify efficacious drugs for the resistant line, and validated the predictions with in-vitro experiments. Together, scIDUC quickly translates scRNA-seq data into drug response for individual cells, displaying the potential as a first-line tool for nuanced and heterogeneity-aware drug discovery.
Walking (and talking) the plank: Dual-task performance costs in a virtual balance-threatening environment
Authors: Raffegeau Tiphanie E. , Brinkerhoff Sarah A. , Clark Mindie , McBride Ashlee D. , Williams A. Mark , Fino Peter C. , Fawver Bradley 
Published: November 2023

AbstractWe evaluated the effects of engaging in extemporaneous speech while walking in virtual environments meant to elicit low or high levels of mobility-related anxiety. We expected that mobility-related anxiety imposed by a simulated balance threat (i.e. virtual high elevation) would impair walking behavior and lead to greater dual-task costs. Altogether, 15 adults (age = 25.6 ± 4.7 yrs, 7 women) walked at their self-selected speed within low (ground) and high elevation (15 meters) VR settings while speaking extemporaneously (dual-task) or not speaking (single-task). Likert-scale ratings of cognitive and somatic anxiety, confidence, and mental effort were evaluated after experiencing each condition, and gait speed, step length, and step width, and the variability of each, was calculated for each trial using the position of trackers attached to participants’ ankles. Silent speech pauses (>150ms) were determined from audio recordings to infer the cognitive costs of extemporaneous speech planning at low and high virtual elevation. The presence of a balance threat and the inclusion of a concurrent speech task both perturbed gait kinematics, but only the virtual height illusion increased anxiety and mental effort while decreasing confidence. Extemporaneous speech pauses were longer on average when walking, but no effects of virtual elevation were reported. Trends toward interaction effects arose in self-reported responses, participants reported more comfort walking at virtual heights if they engaged in extemporaneous speech. Walking at virtual elevation and walking while talking have independent and significant effects on gait; both effects were robust and did not support an interaction when combined (i.e., walking and talking at virtual heights). Rather than additive cognitive-motor demands, the nature of extemporaneous speech may have distracted participants from the detrimental effects of walking in anxiety-inducing settings.
Efficient coding explains neural response homeostasis and stimulus-specific adaptation
Authors: Young Edward James , Ahmadian Yashar 
Published: November 2023

AbstractIn the absence of adaptation, the average firing rate of neurons would rise or drop when changes in the environment make their preferred stimuli more or less prevalent. However, by adjusting the responsiveness of neurons, adaptation can yield firing rate homeostasis and stabilise the average rates of neurons at fixed levels, despite changes in stimulus statistics. In sensory cortex, adaptation is typically also stimulus specific, in that neurons reduce their responsiveness to over-represented stimuli, but maintain or even increase their responsiveness to stimuli far from over-represented ones. Here, we present a normative explanation of firing rate homeostasis grounded in the efficient coding principle, showing that this homeostasis yields an optimal trade-off between coding fidelity and the metabolic cost of neural firing. Unlike previous efficient coding theories, we formulate the problem in a computation-agnostic manner, enabling our framework to apply far from the sensory periphery. We then apply this general framework to Distributed Distributional Codes, a specific computational theory of neural representations serving Bayesian inference. We demonstrate how homeostatic coding, combined with such Bayesian neural representations, provides a normative explanation for stimulus-specific adaptation, widely observed across the brain, and how this coding scheme can be accomplished by divisive normalisation with adaptive weights. Further, we develop a model within this combined framework, and by fitting it to previously published experimental data, quantitatively account for measures of stimulus-specific and homeostatic adaption in the primary visual cortex.
Within-species floral evolution reveals convergence in adaptive walks during incipient pollinator shift
Authors: Wenzell Katherine E. , Neequaye Mikhaela , Paajanen Pirita , Hill Lionel , Brett Paul , Byers Kelsey J.R.P. 
Published: November 2023

ABSTRACTUnderstanding how evolution proceeds from molecules to organisms to interactions is critical for evolutionary biology and requires integrative studies that span biological levels. By linking phenotypic changes with associated genes and fitness implications, we gain insight on the repeatability of evolution and how adaptive walks move organisms between fitness peaks, which remains poorly understood at intermediate stages,e.g.potential fitness valleys. Floral trait evolution can proceed rapidly, confer reproductive isolation, and provides numerous examples of convergent evolution associated with pollinator guilds. Within the monkeyflowers (Mimulussect.Erythranthe), intraspecific shifts to yellow flowers within red hummingbird-pollinated species have arisen at least twice and may represent incipient shifts between optima of pollinator adaptation. Here, we compare two natural yellow-flowered forms ofM. cardinalisandM. verbenaceusto their red conspecifics in floral phenotypes, biochemistry, transcriptomic and genomic variation, and interactions with pollinators. We find convergent evolution in the adaptive walks of yellow morphs in both species, with consistent changes in traits of large effect (floral pigments and associated gene expression), which result in strong preference for yellow flowers by bumblebees. Shifts in additional traits (scent emissions and floral opening size) are also consistent with bee pollination, which may represent smaller-effect steps in an ongoing walk from hummingbird to bee pollination. By examining intraspecific variation representing incipient pollinator shifts in two related species, this work elucidates how adaptive walks proceed at early stages by highlighting how convergent large effect mutations (floral color) may drive pollinator attraction, preceding smaller effect changes controlling pollinator fit and reward access. This work integrates phenotypic, biochemical, genomic, and behavioral evidence to shed light on how repeated steps in adaptive walks to new fitness optima may impact reproductive isolation and incipient speciation via convergent evolution.