bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synapses do not facilitate prion-like transfer of alpha-synuclein: a quantitative study in reconstructed unidirectional neural networks
Authors: Courte Josquin , Le Ngoc Anh , Pan Teng , Bousset Luc , Melki Ronald , Villard Catherine , Peyrin Jean-Michel 
Published: September 2023

AbstractAlpha-synuclein (aSyn) aggregation spreads between cells and underlies the progression of neuronal lesions in the brain of patients with synucleinopathies such as Parkinson’s diseases. The mechanisms of cell-to-cell propagation of aggregates, which dictate how aggregation progresses at the network level, remain poorly understood. Notably, while prion and prion-like spreading is often simplistically envisioned as a “domino-like” spreading scenario where connected neurons sequentially propagate protein aggregation to each other, the reality is likely to be more nuanced. Here, we demonstrate that the spreading of preformed aSyn aggregates is a limited process that occurs through molecular sieving of large aSyn seeds. We further show that this process is not facilitated by synaptic connections. This was achieved through the development and characterization of a new microfluidic platform that allows reconstruction of binary fully oriented neuronal networks in vitro with no unwanted backward connections, and through the careful quantification of fluorescent aSyn aggregates spreading between neurons. While this allowed us for the first time to extract quantitative data of protein seeds dissemination along neural pathways, our data suggest that prion-like dissemination of proteinopathic seeding aggregates occurs very progressively and leads to highly compartmentalized pattern of protein seeding in neural networks.
Metformin induces tolerogenicity of dendritic cells by promoting metabolic reprogramming
Authors: Liu Xianmei , Yu Peng , Xu Yujun , Wang Yun , Chen Jin , Tang Fuzhou , Hu Zuquan , Zhou Jing , Liu Lina , Qiu Wei , Ye Yuannong , Jia Yi , Yao Weijuan , Long Jinhua , Zeng Zhu 
Published: September 2023

AbstractDendritic cells (DCs) can mediate immune responses or immune tolerance depending on their immunophenotype and functional status. Remodeling of DCs’ immune functions can develop proper therapeutic regimens for different immune-mediated diseases. In the immunopathology of autoimmune diseases (ADs), activated DCs notably promote effector T-cell polarization and exacerbate the disease. Recent evidence indicates that metformin can attenuate the clinical symptoms of ADs due to its anti-inflammatory properties. Whether and how the therapeutic effects of metformin on ADs are associated with DCs remain unknown. In this study, metformin was added to a culture system of LPS-induced DC maturation. The results revealed that metformin shifted DC into a tolerant phenotype, resulting in reduced surface expression of MHC-II, costimulatory molecules and CCR7, decreased levels of proinflammatory cytokines (TNF-α and IFN-γ), increased level of IL-10, upregulated immunomodulatory molecules (ICOSL and PD-L) and an enhanced capacity to promote regulatory T-cell (Treg) differentiation. Further results demonstrated that the anti-inflammatory effects of metformin in vivo were closely related to remodeling the immunophenotype of DCs. Mechanistically, metformin could mediate the metabolic reprogramming of DCs through FoxO3a signaling pathways, including disturbing the balance of fatty acid synthesis (FAS) and fatty acid oxidation (FAO), increasing glycolysis but inhibiting the tricarboxylic acid cycle (TAC) and pentose phosphate pathway (PPP), which resulted in the accumulation of fatty acids (FAs) and lactic acid, as well as low anabolism in DCs. Our findings indicated that metformin could induce tolerance in DCs by reprogramming their metabolic patterns and play anti-inflammatory roles in vitro and in vivo.
The origin of brain malignancies at the blood–brain barrier
Authors: McDonald Brennan , Barth Kathrin , Schmidt Mirko H. H. 
Published: September 2023

AbstractDespite improvements in extracranial therapy, survival rate for patients suffering from brain metastases remains very poor. This is coupled with the incidence of brain metastases continuing to rise. In this review, we focus on core contributions of the blood–brain barrier to the origin of brain metastases. We first provide an overview of the structure and function of the blood–brain barrier under physiological conditions. Next, we discuss the emerging idea of a pre-metastatic niche, namely that secreted factors and extracellular vesicles from a primary tumor site are able to travel through the circulation and prime the neurovasculature for metastatic invasion. We then consider the neurotropic mechanisms that circulating tumor cells possess or develop that facilitate disruption of the blood–brain barrier and survival in the brain’s parenchyma. Finally, we compare and contrast brain metastases at the blood–brain barrier to the primary brain tumor, glioma, examining the process of vessel co-option that favors the survival and outgrowth of brain malignancies.
Ongoing shielding behavior one year post COVID-19: results from a longitudinal study of patients with inflammatory arthritis
Authors: Sweeney Melissa , Carpenter Lewis , de Souza Savia , Chaplin Hema , Tung Hsiu , Caton Emma , Galloway James , Cope Andrew , Yates Mark , Nikiphorou Elena , Norton Sam 
Published: September 2023

AbstractMany patients with inflammatory arthritis (IA) were instructed to shield during the COVID-19 pandemic. Despite the ending of lockdowns and vaccination, large proportions of IA patients were continuing to shield when it is no longer needed. Given the detrimental effects of shielding on mental and physical health, understanding the rates and reasons for shielding is needed to help clinicians advise patients accordingly. This study was a 12-month prospective study following participants with IA during the COVID-19 pandemic. The proportions of IA patients shielding at each time point were calculated. Additionally, regressions and odds ratios for shielding were determined to assess medication type, mental health, and risk perception. While the extent of shielding fluctuated over the year of lockdowns, nearly all IA patients (93.5%) were still engaging in some shielding in 2021, with nearly half (43%) still shielding most or all of the time. Medications that were previously considered higher risk were not significantly associated with higher rates of shielding (OR = 1.60, p = 0.29), but greater symptoms of depression in June 2020 (OR = 1.07, p = 0.03) was both associated with increased the odds of shielding in June 2021. The high rates of IA patients continuing to shield in 2021 put more strain on patients and professionals as social isolation is linked with worsening mental and physical health, as well as greater difficulty with self-management. It is important for clinicians to be aware of this trend to ease the stress on patients.
Longitudinal MR-based proton-density fat fraction (PDFF) and T2* for the assessment of associations between bone marrow changes and myelotoxic chemotherapy
Authors: Gassert Felix G. , Kranz Julia , Gassert Florian T. , Schwaiger Benedikt J. , Bogner Christian , Makowski Marcus R. , Glanz Leander , Stelter Jonathan , Baum Thomas , Braren Rickmer , Karampinos Dimitrios C. , Gersing Alexandra S. 
Published: September 2023

Abstract
Objectives
MR imaging-based proton density fat fraction (PDFF) and T2* imaging has shown to be useful for the evaluation of degenerative changes in the spine. Therefore, the aim of this study was to investigate the influence of myelotoxic chemotherapy on the PDFF and T2* of the thoracolumbar spine in comparison to changes in bone mineral density (BMD).

Methods
In this study, 19 patients were included who had received myelotoxic chemotherapy (MC) and had received a MR imaging scan of the thoracolumbar vertebrates before and after the MC. Every patient was matched for age, sex, and time between the MRI scans to two controls without MC. All patients underwent 3-T MR imaging including the thoracolumbar spine comprising chemical shift encoding-based water-fat imaging to extract PDFF and T2* maps. Moreover, trabecular BMD values were determined before and after chemotherapy. Longitudinal changes in PDFF and T2* were evaluated and compared to changes in BMD.

Results
Absolute mean differences of PDFF values between scans before and after MC were at 8.7% (p = 0.01) and at −0.5% (p = 0.57) in the control group, resulting in significantly higher changes in PDFF in patients with MC (p = 0.008). BMD and T2* values neither showed significant changes in patients with nor in those without myelotoxic chemotherapy (p = 0.15 and p = 0.47). There was an inverse, yet non-significant correlation between changes in PDFF and BMD found in patients with myelotoxic chemotherapy (r = −0.41, p = 0.12).

Conclusion
Therefore, PDFF could be a useful non-invasive biomarker in order to detect changes in the bone marrow in patients receiving myelotoxic therapy.

Clinical relevance statement
Using PDFF as a non-invasive biomarker for early bone marrow changes in oncologic patients undergoing myelotoxic treatment may help enable more targeted countermeasures at commencing states of bone marrow degradation and reduce risks of possible fragility fractures.

Key Points

Quantifying changes in bone marrow fat fraction, as well as T2* caused by myelotoxic pharmaceuticals using proton density fat fraction, is feasible.

Proton density fat fraction could potentially be established as a non-invasive biomarker for early bone marrow changes in oncologic patients undergoing myelotoxic treatment.
Anatomic repair and ligament bracing as an alternative treatment option for acute combined PCL injuries involving the posteromedial or posterolateral corner—results of a multicentre study
Authors: Gensior Tobias J. , Mester Bastian , Achtnich Andrea , Winkler Philipp W. , Henkelmann Ralf , Hepp Pierre , Glaab Richard , Krause Matthias , Frosch Karl-Heinz , Zellner Johannes , Schoepp Christian 
Published: September 2023

Abstract
Introduction
Combined PCL injuries involving the posteromedial/-lateral corner (PMC/PLC) usually require surgical management. Literature shows controversy regarding the standards of treatment. Suture-augmented repair leads to excellent results in acute knee dislocations but has not been investigated clinically in combined PCL injuries. The purpose of this multicentre study was to evaluate the clinical outcome of this technique in acute combined PCL injuries.

Materials & methods
N = 33 patients with acute combined PCL injuries involving the PMC/PLC were treated by one-stage suture repair with ligament bracing of the PCL and suture repair of the accompanying PMC/PLC injuries with/without ligament bracing or primary augmentation by semitendinosus autograft. Outcome was assessed by IKDC questionnaire, Lysholm Score, Tegner Activity Scale and KOOS. Additional PCL stress-radiography was performed.

Results
N = 31 patients with combined PCL injuries (female: male = 7:24; age 39.1 ± 13.8 years) with a follow-up of 16.8 ± 9.6 months were finally evaluated. 18 had PMC injuries, 13 PLC injuries. 32.2% presented with accompanying meniscal tears (70% medial meniscus). 19.4% showed cartilage injuries grade III-IV. Complications included one infection and four knee stiffnesses. Three had symptomatic postoperative instability, all affiliated to the PLC group. The IKDC was 69.8 ± 16.5, Lysholm score 85 ± 14.4 and KOOS 89.7 ± 8.1. Median loss of activity (Tegner) was 0.89 ± 1.31. Comparing PMC and PLC, all scores showed a tendency towards more favourable outcomes in the PMC group (n.s.). Stress-radiography showed an overall side-to-side difference of 3.7 ± 3.8 mm. Subgroup evaluation showed statistically significant better results (p = 0.035) of PMC (2.5 ± 1.5 mm) versus PLC (5.8 ± 5.6 mm).

Conclusions
One-stage suture repair with ligament bracing is a viable technique for acute combined PCL injuries and predominantly leads to good and excellent clinical outcomes. Patients with PLC injuries show a tendency towards inferior outcomes and higher instability rates compared to PMC injuries. These results may help in therapy planning and counselling patients with these rare injury pattern.

Level of evidence
Level II.
Insomnia and sleep-disordered breathing in FKRP-related limb-girdle muscular dystrophy R9. The Norwegian LGMDR9 cohort study (2020)
Authors: Jensen Synnøve , Abeler Karin , Friborg Oddgeir , Rosner Assami , Olsborg Caroline , Mellgren Svein Ivar , Müller Kai Ivar , Rosenberger Andreas Dybesland , Vold Monica L. , Arntzen Kjell Arne 
Published: September 2023

AbstractLimb-girdle muscular dystrophy R9 (LGMDR9) is a progressive and disabling genetic muscle disease. Sleep is relevant in the patient care as it impacts on health, functioning, and well-being. LGMDR9 may potentially affect sleep by physical or emotional symptoms, myalgia, or sleep-disordered breathing (SDB) through cardiorespiratory involvement. The objective was to investigate the occurrence of insomnia and unrecognized or untreated SDB in LGMDR9, associated factors, and relationships with fatigue and health-related quality of life (HRQoL). All 90 adults in a Norwegian LGMDR9 cohort received questionnaires on sleep, fatigue, and HRQoL. Forty-nine of them underwent clinical assessments and 26 without mask-based therapy for respiration disorders additionally underwent polysomnography (PSG) and capnometry. Among 77 questionnaire respondents, 31% received mask-based therapy. The prevalence of insomnia was 32% of both those with and without such therapy but was significantly increased in fatigued respondents (54% vs 21%). Insomnia levels correlated inversely with mental HRQoL. Among 26 PSG candidates, an apnea–hypopnea index (AHI) ≥ 5/h was observed in 16/26 subjects (≥ 15/h in 8/26) with median 6.8 obstructive apneas and 0.2 central apneas per hour of sleep. The AHI was related to advancing age and an ejection fraction < 50%. Sleep-related hypoventilation was detected in one subject. Fatigue severity did not correlate with motor function or nocturnal metrics of respiration or sleep but with Maximal Inspiratory Pressure (r = − 0.46). The results indicate that insomnia and SDB are underrecognized comorbidities in LGMDR9 and associated with HRQoL impairment and heart failure, respectively. We propose an increased attention to insomnia and SDB in the interdisciplinary care of LGMDR9. Insomnia and pulmonary function should be examined in fatigued patients.
Power-oriented resistance training combined with high-intensity interval training in pre-frail and frail older people: comparison between traditional and cluster training set configurations on the force–velocity relationship, physical function and frailty
Authors: Baltasar-Fernandez Ivan , Alcazar Julian , Martín-Braojos Susana , Ara Ignacio , Alegre Luis M. , García-García Francisco José , Alfaro-Acha Ana , Losa-Reyna José 
Published: September 2023

Abstract
Objectives
To analyse the force–velocity relationship changes in response to two different training programmes differing in the set configuration (cluster vs. traditional), and their impact on physical function and frailty in pre-frail and frail older adults.

Methods
43 pre-frail and frail (Frailty Phenotype ≥ 1 criteria) older adults (81.4 ± 5.1 years) participated in this study. Participants were assigned to cluster (CT; n = 10; 10-s intra-set rest), traditional (TT; n = 13; no intra-set rest) or control (CON; n = 20) groups. Force–velocity relationship (F0, V0 and Pmax), physical function (Short Physical Performance Battery, SPPB) and frailty (Frailty Phenotype, FP) were assessed at baseline and after the training programme.

Results
Both CT and TT groups showed similar improvements in Pmax after training (CT =  + 36.7 ± 34.2 W; TT =  + 33.8 ± 44.6 W; both p < 0.01). V0 was improved by both CT (+ 0.08 ± 0.06 m s−1; p < 0.01), and TT (+ 0.07 ± 0.15 m s−1, p > 0.05). F0 remained unchanged in CT (+ 68.6 ± 224.2 N, p > 0.05) but increased in TT (+ 125.4 ± 226.8 N, p < 0.05). Finally, SPPB improved in both training conditions (CT =  + 2.3 ± 1.3 points; TT =  + 3.0 ± 1.2 points; both p < 0.05) and in the CON group (+ 0.9 ± 1.4 points, p < 0.05). CT and TT reduced their FP (CT = − 1.1 criteria; TT = − 1.6 criteria; both p < 0.01), while no changes were observed in the CON group (− 0.2 criteria, p = 0.38).

Conclusions
Both training methods were equally effective for improving Pmax, physical function and reducing frailty in pre-frail and frail older people. TT may be effective for improving both force and velocity parameters, while CT may be effective for improving velocity parameters alone, although further research is required to confirm these findings.
Comprehensive voxel-wise, tract-based, and network lesion mapping reveals unique architectures of right and left visuospatial neglect
Authors: Moore Margaret Jane , Hearne Luke , Demeyere Nele , Mattingley Jason B. 
Published: September 2023

AbstractVisuospatial neglect is a common, post-stroke cognitive impairment which is widely considered to be a disconnection syndrome. However, the patterns of disconnectivity associated with visuospatial neglect remain unclear. Here, we had 480 acute stroke survivors [age = 72.8 (SD = 13.3), 44.3% female, 7.5 days post-stroke (SD = 11.3)] undertake routine clinical imaging and standardised visuospatial neglect testing. The data were used to conduct voxel-wise, tract-level, and network-level lesion-mapping analyses aimed at localising the neural correlates of left and right egocentric (body-centred) and allocentric (object-centred) visuospatial neglect. Only minimal anatomical homogeneity was present between the correlates of right and left egocentric neglect across all analysis types. This finding challenges previous work suggesting that right and left visuospatial neglect are anatomically homologous, and instead suggests that egocentric neglect may involve damage to a shared, but hemispherically asymmetric attention network. By contrast, egocentric and allocentric neglect was associated with disconnectivity in a distinct but overlapping set of network edges, with both deficits related to damage across the dorsal and ventral attention networks. Critically, this finding suggests that the distinction between egocentric and allocentric neglect is unlikely to reflect a simple dichotomy between dorsal versus ventral networks dysfunction, as is commonly asserted. Taken together, the current findings provide a fresh perspective on the neural circuitry involved in regulating visuospatial attention, and provide important clues to understanding the cognitive and perceptual processes involved in this common and debilitating neuropsychological syndrome.
Calcium electroporation of esophageal cancer induces gene expression changes: a sub-study of a phase I clinical trial
Authors: Egeland Charlotte , Balsevicius Lukas , Gögenur Ismail , Gehl Julie , Baeksgaard Lene , Garbyal Rajendra Singh , Achiam Michael Patrick 
Published: September 2023

Abstract
Purpose
In this study, we aim to investigate gene expression changes in tumor samples obtained from patients with esophageal cancer treated with calcium electroporation. Previously, local treatment with calcium electroporation has been shown to induce gene expression alterations, potentially contributing to a more tumor-hostile microenvironment.

Methods
In this sub-study of a phase I clinical trial, we included five patients with esophageal cancer treated with calcium electroporation. We compared cancer-associated gene expression patterns in tumor samples before and after treatment. Furthermore, we used linear support vector regression to predict the cellular composition of tumor samples.

Results
Using differential expression analysis, we identified the downregulation of CXCL14 and upregulation of CCL21, ANGPTL4, and CRABP2 genes. We also found a decreased predicted proportion of dendritic cells while the proportion of neutrophils was increased.

Conclusion
This study provides evidence that calcium electroporation for esophageal cancer induces local transcriptional changes and possibly alters the cellular composition of the tumor microenvironment. The results are explorative, larger studies are needed to confirm and further correlate our findings with clinical outcomes.
Assessment of early macular microangiopathy in subjects with prediabetes using optical coherence tomography angiography and fundus photography
Authors: El Sawy Shereen , Bekhit Mirrette , Abdelhamid Alaa , Esmat Sohair , Ashraf Hala , Naguib Mervat 
Published: September 2023

Abstract
Aims
Early detection of retinal microangiopathy in patients with prediabetes may reduce diabetic retinopathy complications. The aim of this study was to assess early macular vascular changes in prediabetics before development of over diabetes using OCTA and fundus photography.

Methods
In this cross-sectional study, 66 prediabetic individuals and 66 normal controls underwent clinical, laboratory, and fundus photography evaluation followed by OCTA macular imaging to examine for the foveal avascular zone, and area of capillary non-perfusion, thickness, disorganization of vessels, and vessel density perfusion percentage of superficial capillary plexus and deep capillary plexus.

Results
Retinal microangiopathy was detected in 36.4% of prediabetics by OCTA and only in 10.6% by fundus photography. None of clinical or laboratory parameters had significant association with DR. Area of capillary non-perfusion and disorganization of SCP were detected in 53.8% and 56.8%, respectively, in prediabetics. VDP of SCP and DCP of whole image, parafoveal, and perifoveal areas was significantly lower in prediabetes group compared to normal control. VDP of DCP of perifoveal area (β coefficient: − 0.10, OR: 0.91, 95% CI: 0.86–0.96, P < 0.001) and disorganization of DCP (β coefficient: 1.93, OR: 6.89, 95% CI: 2.5–18.8, P < 0.001) were significant predictors of DR in prediabetics. There was no difference in FAZ in prediabetics with and without retinopathy.

Conclusions
OCTA could detect early retinal vascular changes during the prediabetic state before developing diabetes. VDP was significantly reduced in prediabetic patients. Furthermore, VDP of DCP of perifoveal area and disorganization of DCP were the most important predictors of retinopathy in prediabetic patients.
Dynamic analysis of 2DFGM porous nanobeams under moving load with surface stress and microstructure effects using Ritz method
Authors: Attia Mohamed A. , Shanab Rabab A. 
Published: September 2023

AbstractThis paper investigates the dynamic behavior of micro/nanobeams made of two-dimensional functionally graded porous material (2DFGPM) under accelerated, decelerated, and uniform moving harmonic load, using surface elasticity and modified couple stress theories. The key feature of this formulation is that it deals with a higher order shear deformation beam theory. The non-classical equilibrium equations are developed using Lagrange's equation and the concept of physical neutral surface. The equations of motion are derived using the same approach, accounting for the porosity effect and the modified power-law distribution of material properties. The trigonometric Ritz method is used with sinusoidal trial functions for the displacement field, and the Newmark method is applied to obtain the dynamical response of 2DFGPM nanobeams. The results are compared with previous studies, and the impact of critical parameters such as gradation indices, volume fraction ratio, pattern of porosity, velocity, frequency, and motion type of the applied force are explored. This study highlights the importance of considering the porosity effect, as neglecting it can lead to significant errors in the predicted results. Additionally, the study found that the accelerated and decelerated motions of the applied load have a greater impact on the dynamical deflection of 2DFGPM nanobeams than the uniform motion. The findings of this study can provide guidance for the optimal design of micro/nanobeams subjected to a moving force with multifunctional properties.