bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensory Stimulation and Robot-Assisted Arm Training After Stroke: A Randomized Controlled Trial
Authors: Egger Marion , Bergmann Jeannine , Krewer Carmen , Jahn Klaus , Müller Friedemann 
Published: June 2024

Background and Purpose:
Functional recovery after stroke is often limited, despite various treatment methods such as robot-assisted therapy. Repetitive sensory stimulation (RSS) might be a promising add-on therapy that is thought to directly drive plasticity processes. First positive effects on sensorimotor function have been shown. However, clinical studies are scarce, and the effect of RSS combined with robot-assisted training has not been evaluated yet. Therefore, our objective was to investigate the feasibility and sensorimotor effects of RSS (compared to a control group receiving sham stimulation) followed by robot-assisted arm therapy.

Methods:
Forty participants in the subacute phase (4.4-23.9 weeks) after stroke with a moderate to severe arm paresis were randomized to RSS or control group. Participants received 12 sessions of (sham-) stimulation within 3 weeks. Stimulation of the fingertips and the robot-assisted therapy were each applied in 45-min sessions. Motor and sensory outcome assessments (e.g. Fugl-Meyer-Assessment, grip strength) were measured at baseline, post intervention and at a 3-week follow-up.

Results:
Participants in both groups improved their sensorimotor function from baseline to post and follow-up measurements, as illustrated by most motor and sensory outcome assessments. However, no significant group effects were found for any measures at any time (P > 0.058). Stimulations were well accepted, no safety issues arose.

Discussion and Conclusions:
Feasibility of robot-assisted therapy with preceding RSS in persons with moderate to severe paresis was demonstrated. However, RSS preceding robot-assisted training failed to show a preliminary effect compared to the control intervention. Participants might have been too severely affected to identify changes driven by the RSS, or these might have been diluted or more difficult to identify because of the additional robotic training and neurorehabilitation.

Video Abstract available
for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A478).
Visuospatial Skills Explain Differences in the Ability to Use Propulsion Biofeedback Post-stroke
Authors: Kettlety Sarah A. , Finley James M. , Leech Kristan A. 
Published: June 2024

Background and Purpose:
Visual biofeedback can be used to help people post-stroke reduce biomechanical gait impairments. Using visual biofeedback engages an explicit, cognitively demanding motor learning process. Participants with better overall cognitive function are better able to use visual biofeedback to promote locomotor learning; however, which specific cognitive domains are responsible for this effect are unknown. We aimed to understand which cognitive domains were associated with performance during acquisition and immediate retention when using visual biofeedback to increase paretic propulsion in individuals post-stroke.

Methods:
Participants post-stroke completed cognitive testing, which provided scores for different cognitive domains, including executive function, immediate memory, visuospatial/constructional skills, language, attention, and delayed memory. Next, participants completed a single session of paretic propulsion biofeedback training, where we collected treadmill-walking data for 20 min with biofeedback and 2 min without biofeedback. We fit separate regression models to determine if cognitive domain scores, motor impairment (measured with the lower-extremity Fugl-Meyer), and gait speed could explain propulsion error and variability during biofeedback use and recall error during immediate retention.

Results:
Visuospatial/constructional skills and motor impairment best-explained propulsion error during biofeedback use (adjusted R2 = 0.56, P = 0.0008), and attention best-explained performance variability (adjusted R2 = 0.17, P = 0.048). Language skills best-explained recall error during immediate retention (adjusted R2 = 0.37, P = 0.02).

Discussion and Conclusions:
These results demonstrate that specific cognitive domain impairments explain variability in locomotor learning outcomes in individuals with chronic stroke. This suggests that with further investigation, specific cognitive impairment information may be useful to predict responsiveness to interventions and personalize training parameters to facilitate locomotor learning.
Smooth pursuit deficits impact dynamic visual acuity in macular degeneration
Authors: Shanidze Natela M. , Verghese Preeti 
Published: June 2024

SIGNIFICANCE
Prior studies with large, highly visible targets report low smooth pursuit gains in individuals with macular degeneration (MD). We show that lower gains persist even when observers are pursuing a target that requires discrimination at the acuity limit. This low gain causes retinal slip, potentially leading to motion blur and target disappearance in the scotoma, which further compromise the visibility of moving object.

PURPOSE
In this study, we examine whether the characteristics of smooth pursuit (pursuit gain and placement of the fixational locus relative to the target) change when the task requires dynamic visual acuity.

METHODS
Using the scanning laser ophthalmoscope, we recorded smooth pursuit eye movements in 10 eyes of 6 MD participants and 7 eyes of 4 age-matched controls in response to leftward- or rightward-moving annular targets (O) that briefly (300 milliseconds) changed to a Landolt C at one of several time points during the pursuit trial. Participants were asked to pursue the target and indicate the direction of the C opening.

RESULTS
Individuals with MD had lower pursuit gains and fewer saccades during the C presentation than during the O, compared with their age-matched peers. Further, pursuit gain, but not the distance of the retinal pursuit locus from the target, predicted task performance in the MD group.

CONCLUSIONS
Our findings suggest that compromised pursuit gain in MD participants likely further compromises their dynamic visual acuity and thus ability to view moving targets.
Integrated 68Ga-FAPI-04 PET/MR in Pancreatic Cancer
Authors: Zhang Zeyu , Guo Shiwei , Cheng Chao , Cao Kai , Jiang Hui , Jin Gang , Zuo Changjing 
Published: June 2024

Purpose
This study aimed to investigate the value of 68Ga-fibroblast activation protein inhibitor (FAPI) PET/MR semiquantitative parameters in the prediction of tumor response and resectability after neoadjuvant therapy in patients with pancreatic cancer.

Patients and Methods
This study was performed retrospectively in patients with borderline resectable or locally advanced pancreatic cancer who underwent 68Ga-FAPI PET/MRI from June 2020 to June 2022. The SUVmax, SUVmean, SUVpeak, uptake tumor volume (UTV), and total lesion FAP expression (TLF) of the primary tumor were recorded. The target-to-background ratios (TBRs) of the primary tumor to normal tissue muscle (TBRmuscle) and blood (TBRblood) were also calculated. In addition, the minimum apparent diffusion coefficient value of the tumor was measured. After 3–4 cycles of gemcitabine + nab-paclitaxel chemotherapy, patients were divided into responders and nonresponders groups according to RECIST criteria (v.1.1). They were also divided into resectable and unresectable groups according to the surgical outcome. The variables were compared separately between groups.

Results
A total of 18 patients who met the criteria were included in this study. The UTV and TLF were significantly higher in nonresponders than in responders (P < 0.05). The SUVmax, SUVmean, and TBRmuscle were significantly higher in unresectable patients than in resectable ones (P < 0.05). Receiver operating characteristic curve analysis identified UTV (area under the curve [AUC] = 0.840, P = 0.015) and TLF (AUC = 0.877, P = 0.007) as significant predictors for the response to gemcitabine + nab-paclitaxel chemotherapy, with cutoff values of 25.05 and 167.38, respectively. In addition, SUVmax (AUC = 0.838, P = 0.016), SUVmean (AUC = 0.812, P = 0.026), and TBRmuscle (AUC = 0.787, P = 0.041) were significant predictors of the resectability post-NCT, with cutoff values of 14.0, 6.0, and 13.9, respectively. According to logistic regression analysis, TLF was found to be significantly associated with tumor response (P = 0.032) and was an independent predictor of tumor response (P = 0.032). In addition, apparent diffusion coefficient value was an independent predictor of tumor resectability (P = 0.043).

Conclusions
This pilot study demonstrates the value of 68Ga-FAPI PET/MR for the prediction of tumor response and resectability after neoadjuvant therapy. It may aid in individualized patient management by guiding the treatment regimens.
Hyperons in neutron stars: studies of hyperon spectroscopy and the hyperon–nucleon interaction with the K-long Facility
Authors: Zachariou N. , Fegan S. , Watts D. , Bashkanov M. 
Published: June 2024

Elucidating the role of strange baryons (hyperons) in neutron stars requires detailed knowledge of hyperon–nucleon interactions in the light (u,d,s) quark sector. The structure of the hyperons and their excitation spectra also directly impact, and are an input to, models of big-bang nucleosynthesis. The upcoming K-long Facility will provide a much-needed intense and clean neutral strange meson beam, from which hyperons can be produced at rates where hyperon structure, hyperon–nucleon interactions and higher-order interactions can be studied with a new level of accuracy and for hitherto unreachable measurements. The new facility has the potential to address long-standing questions surrounding the strange sector of the strong force and its relevance to the structure of atomic nuclei, neutron stars and the cosmos at large.
This article is part of the theme issue ‘The liminal position of Nuclear Physics: from hadrons to neutron stars’.
Auxiliary field Quantum Monte Carlo for dilute neutrons on the lattice
Authors: Curry Ryan , Dissanayake Jayani , Gandolfi Stefano , Gezerlis Alexandros 
Published: June 2024

We employ constrained path Auxiliary Field Quantum Monte Carlo (AFQMC) in the pursuit of studying physical nuclear systems using a lattice formalism. Since AFQMC has been widely used in the study of condensed-matter systems such as the Hubbard model, we benchmark our method against published results for both one- and two-dimensional Hubbard model calculations. We then turn our attention to cold atomic and nuclear systems. We use an onsite contact interaction that can be tuned in order to reproduce the known scattering length and effective range of a given interaction. Developing this machinery allows us to extend our calculations to study nuclear systems within a lattice formalism. We perform initial calculations for a range of nuclear systems from two- to few-body neutron systems.
This article is part of the theme issue ‘The liminal position of Nuclear Physics: from hadrons to neutron stars’.
Evolutionary ecology of dispersal in biodiverse spatially structured systems: what is old and what is new?
Authors: Fronhofer Emanuel A. , Bonte Dries , Bestion Elvire , Cote Julien , Deshpande Jhelam N. , Duncan Alison B. , Hovestadt Thomas , Kaltz Oliver , Keith Sally A. , Kokko Hanna , Legrand Delphine , Malusare Sarthak P. , Parmentier Thomas , Saade Camille , Schtickzelle Nicolas , Zilio Giacomo , Massol François 
Published: June 2024

Dispersal is a well-recognized driver of ecological and evolutionary dynamics, and simultaneously an evolving trait. Dispersal evolution has traditionally been studied in single-species metapopulations so that it remains unclear how dispersal evolves in metacommunities and metafoodwebs, which are characterized by a multitude of species interactions. Since most natural systems are both species-rich and spatially structured, this knowledge gap should be bridged. Here, we discuss whether knowledge from dispersal evolutionary ecology established in single-species systems holds in metacommunities and metafoodwebs and we highlight generally valid and fundamental principles. Most biotic interactions form the backdrop to the ecological theatre for the evolutionary dispersal play because interactions mediate patterns of fitness expectations across space and time. While this allows for a simple transposition of certain known principles to a multispecies context, other drivers may require more complex transpositions, or might not be transferred. We discuss an important quantitative modulator of dispersal evolution—increased trait dimensionality of biodiverse meta-systems—and an additional driver: co-dispersal. We speculate that scale and selection pressure mismatches owing to co-dispersal, together with increased trait dimensionality, may lead to a slower and more ‘diffuse’ evolution in biodiverse meta-systems. Open questions and potential consequences in both ecological and evolutionary terms call for more investigation.
This article is part of the theme issue 'Diversity-dependence of dispersal: interspecific interactions determine spatial dynamics'.
Adaptive Wheel Exercise for Mouse Models of Parkinson’s Disease
Authors: Skelton Henry , Grogan Dayton , Kotlure Amrutha , Berglund Ken , Gutekunst Claire-Anne , Gross Robert 
Published: June 2024

AbstractExercise is widely studied as a therapy in mouse models of neurological disease. However, the established techniques for exercise in mice are not ideally suited toward motor deficient disease models, nor do they facilitate active measurement of neurophysiology with tethered assays. To address this, we developed an apparatus and technique for inducing exercise in mice without aversive stimuli, using a motorized wheel with closed-loop acceleration that tracks subject performance. We demonstrated the efficacy of this approach in the 6-hydroxydopamine mouse model of PD, including with single-unit electrophysiology. This approach should allow for exercise to be better studied as a dynamic, physiological intervention in neurological disease models.
Central nucleus of the amygdala to medial prefrontal cortex 5-HTergic neural circuit modulates the recovery of consciousness during sevoflurane anesthesia
Authors: Wang YuLing , Yang Yue , Wu YaXuan , Xu XiaoXia , Xu Qing , Zhang ZiWen , Di XuanYi , Zhang HongHai 
Published: June 2024

AbstractGeneral anesthesia, widely employed for its capacity to induce unconsciousness during surgical and diagnostic procedures, frequently results in postoperative recovery delays, a common complication. The precise mechanisms underpinning this delayed emergence from anesthesia remain not fully understood. Prior research has established a strong association between sleep-wake neural circuits and the anesthetic effects of general anesthetics, with serotonin (5-HT) playing a pivotal role in the regulation of anesthesia emergence. Extensive projections exist between the amygdala and the medial prefrontal cortex (mPFC). In this study, we utilized pharmacological, chemogenetic, and optogenetic techniques to explore the relationship between the 5-HT neural circuitry within the central amygdala (CeA)-mPFC pathway and the process of awakening from general anesthesia. Our findings reveal that modulating the 5-HT system in both the CeA and mPFC, via endogenous and exogenous means, can effectively reverse delayed emergence. This suggests that the 5-HT-ergic pathway within the CeA-mPFC circuit is instrumental in regulating the awakening process from sevoflurane anesthesia. These insights may inform future clinical interventions designed to prevent delayed emergence and reduce postoperative risks.
WT1 targeting multi-epitope vaccine design for glioblastoma multiforme using immuno-informatics approaches
Authors: Ahmed Tanvir 
Published: June 2024

AbstractGlioblastoma multiforme (GBM) is a highly aggressive form of brain cancer classified as grade 4 glioma with a median survival rate of 12-14 months. Currently there is no cure and the conventional treatment outcomes are poor making it imperative to develop novel treatments. WT1, also known as Wilms’ Tumor 1, is a protein that is often found to be overexpressed in GBM and has minimal expression in normal tissues has become a promising target for immunotherapy for its oncogenicity and immunogenicity. This study aimed to develop a multi-epitope vaccine using immuno-informatics approaches that specifically targets the WT1 protein. The WT1 sequence was used to predict B and T cell epitopes which showed probable antigenic, non-allergic and non-toxic properties. Using suitable linker and adjuvants the vaccine construct (370 amino acids) was prepared which were then analyzed for solubility, physicochemical properties, molecular docking to show receptor interactions and molecular dynamics to show stability of the vaccine-receptor complexes. Subsequently, the vaccine sequence was back translated (1110 nucleotides), codon adaptation, pET-28a (+) vector in-silico cloning, and immune response simulations were performed. The designed vaccine lays groundwork for future in-vitro and in-vivo studies and potentially develop it into a novel treatment option for GBM patients.
Suppression of astrocyte BMP signaling improves fragile X syndrome molecular signatures and functional deficits
Authors: Deng James , Labarta-Bajo Lara , Brandebura Ashley N. , Kahn Samuel B. , Pinto Antonio F. M. , Diedrich Jolene K. , Allen Nicola J. 
Published: June 2024

AbstractFragile X syndrome (FXS) is a monogenic neurodevelopmental disorder with manifestations spanning molecular, neuroanatomical, and behavioral changes. Astrocytes contribute to FXS pathogenesis and show hundreds of dysregulated genes and proteins; targeting upstream pathways mediating astrocyte changes in FXS could therefore be a point of intervention. To address this, we focused on the bone morphogenetic protein (BMP) pathway, which is upregulated in FXS astrocytes. We generated a conditional KO (cKO) of Smad4 in astrocytes to suppress BMP signaling, and found this lessens audiogenic seizure severity in FXS mice. To ask how this occurs on a molecular level, we performedin vivotranscriptomic and proteomic profiling of cortical astrocytes, finding upregulation of metabolic pathways, and downregulation of secretory machinery and secreted proteins in FXS astrocytes, with these alterations no longer present when BMP signaling is suppressed. Functionally, astrocyte Smad4 cKO restores deficits in inhibitory synapses present in FXS auditory cortex. Thus, astrocytes contribute to FXS molecular and functional phenotypes, and targeting astrocytes can mitigate FXS symptoms.
Perfringolysin O pore-forming complexes are predominantly integral multiples of six subunits
Authors: Liu Meijun , Qin Xintao , Luo Menglin , Shen Yi , Wang Jiabin , Sun Jielin , Czajkowsky Daniel M. , Shao Zhifeng 
Published: June 2024

AbstractPerfringolysin O is a well-studied bacterial cytolysin that forms large oligomeric pores with a wide range of sizes on membranes via a prepore intermediate. Here we examined the sizes of both PFO prepore and pore complexes electrophoretically using a multi-stack-gradient gel and found that, unexpectedly, there are only at most seven predominant sizes of either pores or prepores. Complexes extracted from each band exhibit contour lengths that are integral multiples of six subunits. High-resolution atomic force microscopy images of PFO pore complexes in supported bilayers also reveal a predominant hexameric-based stoichiometry. Thus, these results reveal a previously unknown structural hierarchy in PFO complexes, with larger complexes apparently built up from hexameric sub-complexes. We suggest that different inter-subunit interactions within and between the hexamers result in a likewise difference in the coordination of the prepore-to-pore transition within and between the hexamers, and is thus a critical feature of the allostery of this large multi-subunit complex.
Self-supervised machine learning methods for protein design improve sampling, but not the identification of high-fitness variants
Authors: Ertelt Moritz , Moretti Rocco , Meiler Jens , Schoeder Clara T. 
Published: June 2024

AbstractMachine learning (ML) is changing the world of computational protein design, with data- driven methods surpassing biophysical-based methods in experimental success rates. However, they are most often reported as case studies, lack integration and standardization across platforms, and are therefore hard to objectively compare. In this study, we established a streamlined and diverse toolbox for methods that predict amino acid probabilities inside the Rosetta software framework that allows for the side-by-side comparison of these models. Subsequently, existing protein fitness landscapes were used to benchmark novel self- supervised machine learning methods in realistic protein design settings. We focused on the traditional problems of protein sequence design: sampling and scoring. A major finding of our study is that novel ML approaches are better at purging the sampling space from deleterious mutations. Nevertheless, scoring resulting mutations without model fine-tuning showed no clear improvement over scoring with Rosetta. This study fills an important gap in the field and allows for the first time a comprehensive head-to-head comparison of different ML and biophysical methods. We conclude that ML currently acts as a complement to, rather than a replacement for, biophysical methods in protein design.
Psychological Resilience as a Mediator Between Depression and Quality of Life in Relapsing-Remitting Multiple Sclerosis Patients
Authors: Broche-Pérez Yunier , Jiménez-Morales Rodneys M. 
Published: June 2024

AbstractDepression represents a significant and prevalent challenge among individuals with multiple sclerosis (MS) substantially impacting their quality of life (QoL). This study explores the mediating role of psychological resilience in the relationship between depression and QoL in a sample of patients with multiple sclerosis (PwMS). This online cross-sectional study involves 179 Relapsing-Remitting Multiple Sclerosis (RRMS) patients. The PwMS completed three questionnaires: the Chicago Multiscale Depression Inventory, the Connor-Davidson Resilience Scale, and the Multiple Sclerosis Quality of Life (MSQOL-29). The results confirmed that higher levels of depression were associated with lower QoL in RRMS patients. However, the inclusion of psychological resilience as a mediator attenuated this direct effect, suggesting that resilience plays a crucial role in mitigating the negative impact of depression on QoL.