bluuebunny/crossref_metadata_2025_split huggingface dataset:
Less is more: The use of single biodegradable stenting to treat biliary anastomotic strictures in pediatric liver transplantation
Authors: Quintero Bernabeu Jesús , Juamperez Goñi Javier , Mercadal Hally Maria , Padrós Fornieles Cristina , Larrarte King Mauricio , Molino Gahete José Andrés , Coma Muñoz Anna , Diez Miranda Iratxe , Pérez Lafuente Mercedes , Charco Torra Ramon , Hidalgo Llompart Ernest 
Published: September 2024

This study reports our experience of using biodegradable biliary stents (BBSs) for anastomotic biliary strictures (ABSs) in pediatric patients undergoing liver transplants. It involves the analysis of a retrospective data collection from January 2014 to January 2023, including all pediatric recipients of liver transplants in our center treated for ABSs with BBSs. In phase 1 (2014–2019), there was an initial percutaneous transhepatic cholangiography with anastomotic dilatation followed 2 weeks after a second percutaneous transhepatic cholangiography with BBS insertion. In phase 2 (2019–2023), the BBS was placed shortly after ABS dilatation, requiring only 1 percutaneous transhepatic cholangiography. All patients were followed up with routine tests and ultrasound. Forty-six ABSs were diagnosed in 43 pediatric recipients of liver transplants with a median of 6.7 months after liver transplantation (0.1–246.8 mo). Eight out of 46 ABSs (17.4%) treated with BBSs relapsed (median recurrence time: 6.5 mo; 1.6–17.0 mo). Four resolved with further BBS placement; only 4 needed surgical revision (8.7%) after a median follow-up time of 43.9 months (0.3–106.3). There were no differences in ABS recurrence rate, time between stent placement and recurrence, or the presence of cholangitis based on whether the BBS was deployed in 1 or 2 steps. Patients with end-to-end anastomosis had a higher ABS recurrence (OR 10.8; 1.4–81.3, p = 0.008) than those with bilioenteric anastomosis. The use of biodegradable stents could be a good option for treating ABSs in pediatric patients undergoing liver transplants, with our series showing a success rate of over 90% and an average follow-up of 43.9 months.
Modified McKissock Technique for Secondary Breast Reduction – A Prospective Study on Safety, Surgical and Aesthetic Outcomes
Authors: Feldler Sandra , Zaussinger Maximilian , Ehebruster Gudrun , Bachleitner Kathrin , Steinkellner Theresia , Schmidt Manfred 
Published: September 2024

Summary:
Numbers of secondary breast reductions are increasing but those are potentially associated with higher complication rates than primary mammaplasty. Necrosis of the Nipple-Areola-Complex (NAC) is a devastating complication that can occur after repeated NAC transposition, particularly when the initially used pedicle is unknown. Thus, the authors established a modification of McKissock’s technique for secondary breast reductions including three pedicle components to ensure safe vascular supply of the NAC. The presented technique incorporates a superior and inferior dermoglandular pedicle according to McKissock and an additional central pedicle. The technique was applied for secondary breast reduction in a series of 25 breasts (14 patients: 11 bilateral, 3 unilateral). Complication rates, pre- and postoperative BREAST-Q scores, and aesthetic outcomes were evaluated. Mean resection weight was 299 g (range, 40-646), and the NAC was transposed by 4.2 cm on average (range, 1-10). No case of NAC-necrosis was observed, and comparison of pre- and postoperative BREAST-Q values indicated substantial improvement in all domains. Postoperatively, 84.6% of patients reported excellent satisfaction with breast appearance. According to those results, the modified McKissock-technique is a safe technique for patients requiring secondary breast reduction, even if the primarily used pedicle is unknown. Additionally, the established technique is associated with improved postoperative patient-reported outcomes and yields aesthetically favorable results.
Caveolin-1 regulates context-dependent signaling and survival in Ewing sarcoma
Authors: Segal Dagan , Wang Xiaoyu , Mazloom-Farisbaf Hanieh , Rajendran Divya , Butler Erin , Chen Bingying , Chang Bo-Jui , Ahuja Khushi , Perny Averi , Bhatt Kushal , Reed Dana Kim , Castrillon Diego H. , Lee Jeon , Jeffery Elise , Wang Lei , Nguyen Khai , Williams Noelle S. , Skapek Stephen X. , Rajaram Satwik , Fiolka Reto , Jaqaman Khuloud , Hon Gary , Amatruda James F. , Danuser Gaudenz 
Published: September 2024

ABSTRACTPlasticity is a hallmark function of cancer cells, but many of the underlying mechanisms have yet to be discovered. In this study, we identify Caveolin-1, a scaffolding protein that organizes plasma membrane domains, as a context-dependent regulator of survival signaling in Ewing sarcoma (EwS). Single cell analyses reveal a distinct subpopulation of EwS cells, which highly express the surface marker CD99 as well as Caveolin-1.CD99 Highcells exhibit distinct morphology, gene expression, and enhanced survival capabilities compared toCD99 Lowcells, both under chemotherapeutic challenge andin vivo.Mechanistically, we show that elevated Caveolin-1 expression inCD99 Highcells orchestrates PI3K/AKT survival signaling by modulating the spatial organization of PI3K activity at the cell surface. Notably, CD99 itself is not directly involved in this pathway, making it a useful independent marker for identifying these subpopulations. We propose a model where theCD99 Highstate establishes a Cav-1-driven signaling network to support cell survival that is distinct from the survival mechanisms ofCD99 Lowcells. This work reveals a dynamic state transition in EwS cells and highlights Caveolin-1 as a key driver of context-specific survival signaling.
Video-based biomechanical analysis captures disease-specific movement signatures of different neuromuscular diseases
Authors: Ruth Parker S. , Uhlrich Scott D. , de Monts Constance , Falisse Antoine , Muccini Julie , Covitz Sydney , Vogt-Domke Shelby , Day John , Duong Tina , Delp Scott L. 
Published: September 2024

ABSTRACTAssessing human movement is essential for diagnosing and monitoring movement-related conditions. Timed function tests (TFTs) are among the most widespread assessments due to their speed and simplicity. However, TFTs cannot capture disease-specific movement patterns. Recent advances in smartphone video-based biomechanical analysis allow detailed movement quantification with the ease and speed required for clinical settings. To compare video-based analysis against TFTs, we collected data from 129 individuals: 28 with facioscapulohumeral muscular dystrophy, 58 with myotonic dystrophy, and 43 with typical movement. Video-based movement recordings took a median time of 16 minutes per participant. In addition to reproducing TFTs (r > 0.98), video metrics can outperform TFTs at disease classification (p < 0.001). Video-based analysis also identifies differences in gait kinematics and arm range of motion not evident in TFTs. We conclude that video-based biomechanical analysis can complement existing functional movement assessments and capture more sensitive, disease-specific outcomes from human movement.
Cannabidiol treatment is associated with broadband spectral electrophysiological changes and improved cognition in boys with low-functioning autism spectrum disorder
Authors: Cazares C. , Hutton A. , Paez G. , Trauner D. , Voytek B. 
Published: September 2024

AbstractOral cannabidiol (CBD) treatment has been suggested to alleviate negative symptoms of autism spectrum disorder (ASD). While many CBD preparations have been studied in randomized clinical trials involving ASD, none have used purified CBD preparations or preparations approved by the U.S. Food and Drug Administration, nor have they focused on low-functioning children with ASD. Previous studies have identified several candidate electrophysiological biomarkers for the cognitive and behavioral disabilities in ASD, with one emerging biomarker being aperiodic neural activity. Here we examined whether periodic (oscillatory) and/or aperiodic electroencephalography (EEG) features are predictive of any symptomatic changes in ASD following pharmacological CBD intervention. To do this, we leveraged resting-state EEG from children with low-functioning ASD (24 boys, aged 7-14 years) using data obtained during a prior double-blind, placebo-controlled, crossover Phase III Clinical Trial (NCT04517799) that investigated using cannabidiol to treat severe behavior problems in children with ASD. Using linear mixed effect models, we found that aperiodic EEG signal features varied directly with 7-COOH-CBD metabolite levels in blood, as evidenced by a larger aperiodic offset (p < 0.001) and decreased aperiodic exponent (p < 0.05) across the scalp. Furthermore, 7-COOH-CBD metabolite levels in blood had a positive association with nonverbal intelligence and visuomotor coordination (p < 0.05). Finally, changes in visuomotor coordination attributed to occipital oscillatory EEG activity were mediated by changes in 7-COOH-CBD metabolite levels in blood, with distinct effects observed for the delta frequency band (p < 0.05). Our analytical results suggest that this daily CBD preparation and administration schedule exerted some benefits, with improvements to cognitive and behavioral abilities in a low-functioning ASD children population. Our findings support the inclusion of resting-state, aperiodic signal features as candidate biomarkers for tracking the clinical impact of CBD treatment, in addition to traditional oscillatory EEG measures, within a neurodevelopmental context.
Breaking the cycle: How targeting CD44v6/MET signaling disrupts colorectal cancer cell plasticity
Authors: Sonnentag S. J. , Goldbach S. , Hoch D. , Andrieux G. , Becker J. , Fromm H. , Munoz-Sagredo L. , Heneka Y. M. , Grimm D. , Greten F. R. , Orian-Rousseau Veronique 
Published: September 2024

SummaryThe concept of cancer stemness is undergoing rapid evolution, facilitated by technological advances allowing the tracking and elimination of stem cellsin vivo. Following their identification in solid tumors, cancer stem cells were placed at the center of tumor initiation, growth and metastasis. However, increasing evidence suggests that stemness is a cellular state that can be acquired by differentiated cells in a process called plasticity. Here we show that CD44v6 may act as a molecular switch controlling plasticity of colorectal cancer cells. CD44v6/MET signaling controls the reappearance of Lgr5+cells after ablation,in vitroandin vivoas demonstrated in tumor organoids derived fromLgr5DTR/eGFPmice using a CD44v6 blocking peptide. CD44v6 also affects the YAP/TAZ signaling pathway, involved in the very first steps of plasticity. In view of the essential role of plasticity for the establishment of metastases, blocking CD44v6 signaling may represent a pivotal and promising therapy.Graphical Abstract
A balanced CAR-T cell metabolism driven by CD28 or 4-1BB co-stimulation correlates with clinical success in lymphoma patients
Authors: Cook Molly S. , Flaherty Katie R. , Papa Sophie , Benjamin Reuben , Schurich Anna 
Published: September 2024

AbstractChimeric antigen receptor (CAR) T cell therapy has led to unprecedented success in treating relapsed/refractory diffuse large B cell lymphoma (DLBCL). The most common CAR-T cell products currently in the clinic for DLBCL differ in their co-stimulation moiety, containing either CD28 or 4-1BB, which initiate distinct signalling pathways. Previous work has highlighted the importance of T cell metabolism in fuelling anti-cancer function. We have studied the metabolic characteristics induced by CD28 versus 4-1BB co-stimulation in patient CAR-T cellsex vivo. Our data show that in patients, CD28 and 4-1BB drive significantly divergent metabolic profiles. CD28 signalling endows T cells with a preferentially glycolytic metabolism supporting an effector phenotype and increased expansion capacity, while 4-1BB co-stimulation preserves mitochondrial fitness and results in memory-like differentiation. Despite this divergent programming, T cells in patients responding successfully to therapy were metabolically similar, irrespective of co-stimulator, suggesting that efficient fuelling of CAR-T cells in lymphoma requires a ‘balanced’metabolism. In contrast, CAR-T cells in non-responders were pushed to their metabolic extremes.One sentence summaryCD28 and 4-1BB signalling drive divergent metabolic profiles in patient CAR-T cells, however patients that respond to therapy have CAR-T cells that maintain metabolic balance.
AMEF2Ctranscription factor network regulates proliferation of glomerular endothelial cells in diabetic kidney disease
Authors: Ferreira Ricardo Melo , Gisch Debora L. , Phillips Carrie L. , Cheng Ying-Hua , Asthana Maansi , Lake Blue B. , Bowen William S. , Fang Fang , Asghari Mahla , Sabo Angela , Barwinska Daria , Ferkowicz Michael J. , Toto Robert D. , Sedor John R. , Rosas Sylvia E. , Bjornstad Petter , Hodgin Jeffrey B , Alpers Charles E. , Sarder Pinaki , Himmelfarb Jonathan , Schaub Jennifer A. , Nair Viji , Winfree Seth , Sutton Timothy A. , Kelly Katherine J. ,   The Kidney Precision Medicine Project, Kretzler Matthias , Jain Sanjay , El-Achkar Tarek M. , Dagher Pierre C. , Eadon Michael T. 
Published: September 2024

AbstractThe maintenance of a healthy epithelial-endothelial juxtaposition requires cross-talk within glomerular cellular niches. We sought to understand the spatially-anchored regulation and transition of endothelial and mesangial cells from health to injury in DKD. From 74 human kidney samples, an integrated multi-omics approach was leveraged to identify cellular niches, cell-cell communication, cell injury trajectories, and regulatory transcription factor (TF) networks in glomerular capillary endothelial (EC-GC) and mesangial cells. Data were culled from single nucleus RNA and ATAC sequencing and three orthogonal spatial transcriptomic technologies for correlation with histopathological and clinical trial data. We identified a cellular niche in diabetic glomeruli enriched in a proliferative endothelial cell subtype (prEC) and altered vascular smooth muscle cells (VSMCs). Cellular communication within this niche maintained pro-angiogenic signaling with loss of anti-angiogenic factors. We identified a TF network of MEF2C, MEF2A, and TRPS1 which regulated SEMA6A and PLXNA2, a receptor-ligand pair opposing angiogenesis. In silico knockout of the TF network accelerated the transition from healthy EC-GCs toward a degenerative (injury) endothelial phenotype, with concomitant disruption of EC-GC and prEC expression patterns. Glomeruli enriched in the prEC niche had histologic evidence of neovascularization. MEF2C activity was increased in diabetic glomeruli with nodular mesangial sclerosis. The gene regulatory network (GRN) of MEF2C was dysregulated in EC-GCs of patients with DKD, but sodium glucose transporter-2 inhibitor (SGLT2i) treatment reversed the MEF2C GRN effects of DKD. The MEF2C, MEF2A, and TRPS1 TF network carefully balances the fate of the EC-GC in DKD. When the TF network is “on” or over-expressed in DKD, EC-GCs may progress to a prEC state, while TF suppression leads to cell death. SGLT2i therapy may restore the balance of MEF2C activity.
Implications of carbon source-sink feedbacks for plant growth responses to environmental factors
Authors: Friend Andrew D. , Chen Yizhao , Eckes-Shephard Annemarie H. , Fonti Patrick , Hellmann Eva , Rademacher Tim T. , Richardson Andrew D. , Thomas Patrick R. 
Published: September 2024

SummaryGlobal models of vegetation dynamics are largely carbon (C) source-driven, with behaviour primarily determined by the environmental responses of photosynthesis. However, real plants operate as integrated wholes, with feedbacks between sources and sinks resulting in homeostatic concentrations of metabolites such as sugars. An approach to implementing such behaviour in a plant growth model is presented and its implications for responses to generic environmental factors assessed. The approach is based on Hill functions representing inhibition of C sources (net photosynthesis) and activation of sinks (structural growth) based on sugar concentrations. The model is parameterised for a mature tropical rainforest site and its qualitative behaviour is found to be consistent with experimental observations. Key findings are that sinks and sources strongly regulate each other. For example, doubling potential net photosynthesis (i.e. the rate that would occur without feedback) results in growth increasing by only 1/3 at equilibrium, with increased sugar concentration causing feedback-inhibition of photosynthesis. A source-only driven response, as in current global models, would result in close to a doubling of growth. Hence environmental factors that affect potential net photosynthesis, such as atmospheric CO2, have greatly reduced effects on growth when homeostatic behaviour of sugars is considered. The implications of considering source-sink coupling for the behaviour of models of vegetation dynamics are likely to be profound.
In Silicoidentification and modelling of FDA-approved drugs targeting T-type calcium channels
Authors: Fong Pedro , Garcia Susana Roman , Stefan Melanie I , Sterratt David C 
Published: September 2024

AbstractStudies have shown that inhibition of the Cav3.1 T-type calcium channel can prevent or suppress neurological diseases, such as epileptic seizures and diabetic neuropathy. In this study we aimed to usein silicosimulations to identify a U.S. Food and Drug Administration (FDA)-approved drug that can bind to the Cav3.1 T-type calcium channel. We used the automated docking suite GOLD v5.5 with the genetic algorithm to simulate molecular docking and predict the protein-ligand binding modes, and the ChemPLP empirical scoring function to estimate the binding affinities of 2,115 FDA-approved drugs to the human Cav3.1 channel. Drugs with high binding affinity and appropriate pharmacodynamic and pharmacokinetic properties were selected for molecular mechanics Poisson–Boltzmann surface area (MMPBSA) and molecular mechanics generalised Born surface area (MMGBSA) binding free energy calculations, GROMACS molecular dynamics (MD) simulations and Monte Carlo Cell (MCell) simulations. The docking results indicated that the FDA-approved drug montelukast has a high binding affinity to Cav3.1, and data from the literature suggested that montelukast has the appropriate drug-like properties to cross the human blood-brain barrier and reach synapses in the central nervous system. MMPBSA, MMGBSA and MD simulations showed the high stability of the montelukast-Cav3.1 complex. MCell simulations indicated that the blockage of Cav3.1 by montelukast reduced the number of synaptic vesicles being released from the pre-synaptic region to the synaptic cleft, which may reduce the probability and amplitude of postsynaptic potentials.Author SummaryNew drugs for current illnesses or disorders are always necessary to enhance therapeutic outcomes or can be utilised for patients who have experienced side effects from current medicines. The Cav3.1 T-type calcium channel has been found to be linked to neurological diseases, such as epilepsy and diabetes. Consequently, identifying a drug that could bind to these receptors may yield therapeutic effects on these neurological conditions. This study utilises various computational methods to sift through 2,115 FDA-approved drugs that have been used for other diseases, not neurological ones, to determine whether some of these drugs could bind to the Cav3.1 T-type calcium channel and potentially produce therapeutic effects on neurological diseases. Our research indicates that the current asthma drug montelukast has the potential to bind to the calcium channel and is worthy of further investigation.
Molecular signatures of altered energy metabolism and circadian rhythm perturbations in a model of extra-nigral Synucleinopathy
Authors: Lin Lin , Jensen Nanna M. , Ferreira Sara A. , Delaidelli Alberto , Gomes Moreira Diana , Ahlgreen Ole A. , Richner Mette , Sorensen Poul H. , Romero-Ramos Marina , Vægter Christian B. , Jensen Poul H. , Mackenzie Ian R. , Nyengaard Jens R. , Jan Asad 
Published: September 2024

ABSTRACTA pathological role of alpha-Synuclein (aSyn) aggregation in the central nervous system (CNS) is a recognized feature in Parkinson disease (PD) and related neurodegenerative conditions termed synucleinopathies. In order to characterize the cellular response in CNS to incipient and advanced aSyn pathology, we applied spatial transcriptomics on brain sections derived from a transgenic mouse model (M83+/+line,Prnp-SNCA*A53T) in which aSyn aggregation was induced in a prion-like fashion through hindlimb intramuscular delivery of pre-formed fibrillar (PFF) murine aSyn. Our spatially-resolved transcriptomics (ST) data point to unique perturbations in brain energy metabolism during the progression of aSyn pathology, such that the early stage of aSyn aggregate pathology activates molecular pathways controlling metabolic flux through glycolysis, oxidative phosphorylation and fatty acid metabolism. In contrast, the ST data indicate a profound decline in mitochondrial metabolism in the brains of symptomatic animals with advanced aSyn pathology. The latter stage was also associated with drastic reduction in mRNA translation machinery, along with aberrant expression of molecular drivers involved in RNA splicing and inflammatory response. Intriguingly, our ST data also point to perturbed regulation of circadian rhythm, was corroborated by increased immunodetection of CREB-binding protein (a modulator of core clock machinery) in the brains of symptomatic animals, and transcriptional upregulation ofCREBBPin 4 independent PD microarray datasets. Collectively, we anticipate that our findings offer novel opportunities in knowledge translation for mechanism-based drug discovery and biomarkers in neurodegenerative synucleinopathies.
Sedentary lifestyle induces oxidative stress and atrophy in rat skeletal muscle
Authors: Gungor-Orhan Irem , Akin Senay , Powers Scott K. , Olgaz-Bingol Seda , Demirel Haydar 
Published: September 2024

AbstractAbundant evidence indicates that skeletal muscle is an important endocrine organ that plays a key role in regulating metabolic homeostasis. Therefore, maintaining healthy skeletal muscles is essential to good health. While it is established that prolonged skeletal muscle inactivity results in both oxidative stress and muscle atrophy, it remains unknown if the change from an active to a sedentary lifestyle promotes a similar increase in oxidative stress and locomotor muscle atrophy. We tested the hypothesis that the transition from active to sedentary living results in the rapid development of oxidative damage and fiber atrophy in locomotor skeletal muscles. Adult Wistar rats were randomly divided into control (CON; n=8) and sedentary (SED; n=8) groups. During a seven-day experimental period, animals in the CON group were housed in standard size cages permitting free movement, while animals in the SED group were housed in small cages that promoted sedentary behavior. At the end of the experimental protocol, soleus muscles were removed and the activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) were determined along with two biomarkers of muscle oxidative stress (i.e., levels of advanced protein oxidation (AOPP) and 4-hydroxynonenal (4-HNE)). Living in the reduced-size cage resulted in muscle atrophy as evidenced by a 17.2% decrease in the soleus to body weight ratio (P<0.001). Moreover, the activities of SOD, CAT and GPX in the soleus muscle were significantly decreased in SED animals compared to CON (P<0.05). Finally, compared to CON, sedentary living increased both AOPP and 4-HNE levels in muscles of SED animals (P<0.001 andP<0.05, respectively). These findings provide the first evidence that the transition from an active to sedentary lifestyle results in the rapid onset of oxidative stress and atrophy in locomotor skeletal muscles. Importantly, these results suggest that an impaired antioxidant defense contributes to sedentary behavior-induced oxidative stress in locomotor muscles.