bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and impact on arrhythmia recurreces of atrial fibrillation termination during linear radiofrequency ablation in the left atrium
Authors: Merino Fuentes D , Castrejon Castrejon S , Sanchez Somonte P , Jauregui Abularach M , Guido Lopez L , Martinez Cossiani M , Handayani A , Martinez Maldonado M E , Sanz Verdejo B , Merino Llorens J L 
Published: May 2024

Abstract

Atrial Fibrillation Termination During Linear Radiofrequency Ablation in the Left Atrium: Incidence and Impact on Arrhythmia Recurrences

Background
Termination of atrial fibrillation (AF) during persistent atrial fibrillation (peAF) ablation is infrequent and has shown no clear association with reduced recurrences during follow-up. Linear ablation, often considered to have minimal impact on efficacy, has been primarily explored through creating ablation lines from the mitral annulus to the inferior pulmonary vein or by isolating the posterior wall.

Purpose
This study aims to assess the incidence of AF termination using an alternative linear ablation approach and its correlation with arrhythmia recurrence during follow-up.

Methods
Patients enrolled in the PowerFast III trial (a multicenter randomized trial comparing high- power short-duration radiofrequency (RF) application to conventional RF application) with peAF and undergoing linear ablation were included in this sub-study. Conventional pulmonary vein isolation (PVI) was performed using two different RF settings along with a set of RF lines, including anteroseptal (AS), anterolateral (AL), posterior wall isolation between the pulmonary veins, and between the two anterior lines. Patients were categorized into two groups based on AF termination or flutter organization (Group 1) or no AF termination (Group 2) during RF application. All patients were monitored with EKG transmission for one year.

Results
Fifty-one consecutive patients (mean age 61 years, male 39) were included. AF terminated in 21 patients (41%) during RF application (9 converting to AF and 12 to atrial flutter). AF did not terminate during RF application for PVI, except for one patient during right PV ablation following left PVI. AF termination occurred by posterior wall lines in three patients, roof line in three, and anterior line in two. AF converted into atrial flutter during ablation by a roof line in 5 patients and by an anterior line in 7. No significant differences in atrial arrhythmia recurrence were observed between the two groups (three patients in Group 1 vs. eleven in Group 2, P = 0.11). However, Group 1 exhibited fewer AF recurrences (zero patients) than Group 2 (eight patients, P = 0.015).

Conclusions
Extensive linear RF ablation resulted in a substantial proportion of patients experiencing AF termination or conversion into atrial flutter. AF termination or conversion did not appear to be correlated with atrial arrhythmia freedom during follow-up but was associated with fewer AF recurrences.Any arrhythmia recurrenceAF recurrence
Human induced pluripotent stem cell–derived atrial cardiomyocytes recapitulate contribution of the slowly activating delayed rectifier currents IKs to repolarization in the human atrium
Authors: Sönmez Muhammed Ikbal , Goldack Silvana , Nurkkala Elina , Schulz Carl , Klampe Birgit , Schulze Thomas , Hansen Arne , Eschenhagen Thomas , Koivumäki Jussi , Christ Torsten 
Published: May 2024

Abstract

Aims
Human induced pluripotent stem cell–derived atrial cardiomyocytes (hiPSC-aCM) could be a helpful tool to study the physiology and diseases of the human atrium. To fulfil this expectation, the electrophysiology of hiPSC-aCM should closely resemble the situation in the human atrium. Data on the contribution of the slowly activating delayed rectifier currents (IKs) to repolarization are lacking for both human atrium and hiPSC-aCM.

Methods and results
Human atrial tissues were obtained from patients with sinus rhythm (SR) or atrial fibrillation (AF). Currents were measured in human atrial cardiomyocytes (aCM) and compared with hiPSC-aCM and used to model IKs contribution to action potential (AP) shape. Action potential was recorded by sharp microelectrodes. HMR-1556 (1 µM) was used to identify IKs and to estimate IKs contribution to repolarization. Less than 50% of hiPSC-aCM and aCM possessed IKs. Frequency of occurrence, current densities, activation/deactivation kinetics, and voltage dependency of IKs did not differ significantly between hiPSC-aCM and aCM, neither in SR nor AF. β-Adrenoceptor stimulation with isoprenaline did not increase IKs neither in aCM nor in hiPSC-aCM. In tissue from SR, block of IKs with HMR-1556 did not lengthen the action potential duration, even when repolarization reserve was reduced by block of the ultra-rapid repolarizing current with 4-aminopyridine or the rapidly activating delayed rectifier potassium outward current with E-4031.

Conclusion
I Ks exists in hiPSC-aCM with biophysics not different from aCM. As in adult human atrium (SR and AF), IKs does not appear to relevantly contribute to repolarization in hiPSC-aCM.
Species-level characterization of saliva and dental plaque microbiota reveals putative bacterial and functional biomarkers of periodontal diseases in dogs
Authors: Alessandri Giulia , Fontana Federico , Mancabelli Leonardo , Tarracchini Chiara , Lugli Gabriele Andrea , Argentini Chiara , Longhi Giulia , Rizzo Sonia Mirjam , Vergna Laura Maria , Anzalone Rosaria , Viappiani Alice , Turroni Francesca , Ossiprandi Maria Cristina , Milani Christian , Ventura Marco 
Published: May 2024

Abstract
Periodontal diseases are among the most common bacterial-related pathologies affecting the oral cavity of dogs. Nevertheless, the canine oral ecosystem and its correlations with oral disease development are still far from being fully characterized. In this study, the species-level taxonomic composition of saliva and dental plaque microbiota of 30 healthy dogs was investigated through a shallow shotgun metagenomics approach. The obtained data allowed not only to define the most abundant and prevalent bacterial species of the oral microbiota in healthy dogs, including members of the genera Corynebacterium and Porphyromonas, but also to identify the presence of distinct compositional motifs in the two oral microniches as well as taxonomical differences between dental plaques collected from anterior and posterior teeth. Subsequently, the salivary and dental plaque microbiota of 18 dogs affected by chronic gingival inflammation and 18 dogs with periodontitis were compared to those obtained from the healthy dogs. This analysis allowed the identification of bacterial and metabolic biomarkers correlated with a specific clinical status, including members of the genera Porphyromonas and Fusobacterium as microbial biomarkers of a healthy and diseased oral status, respectively, and genes predicted to encode for metabolites with anti-inflammatory properties as metabolic biomarkers of a healthy status.
Evaluation and comparison of colorimetric outputs for yeast-based biosensors in laboratory and point-of-use settings
Authors: Lind Andrea Clausen , David Florian , Siewers Verena 
Published: May 2024

Abstract
Recent research has shown the potential of yeast-based biosensors (YBBs) for point-of-use detection of pathogens and target molecules in saliva, blood, and urine samples. The choice of output can greatly affect the sensitivity, dynamic range, detection time, and ease-of-use of a sensor. For visual detection without the need for additional reagents or machinery, colorimetric outputs have shown great potential. Here, we evaluated the inducible generation of prodeoxyviolacein and proviolacein as colorimetric YBB outputs and benchmarked these against lycopene. The outputs were induced via the yeast mating pathway and were compared on agar plates, in liquid culture, and on paper slips. We found that all three outputs produced comparable pigment intensity on agar plates, making them applicable for bioengineering settings. In liquid media and on paper slips, lycopene resulted in a higher intensity pigment and a decreased time-of-detection.
Knockdown of NeuroD2 leads to seizure-like behavior, brain neuronal hyperactivity and a leaky blood-brain barrier in a Xenopus laevis tadpole model of DEE72
Authors: Banerjee Sulagna , Szyszka Paul , Beck Caroline W 
Published: May 2024

Abstract
Developmental and Epileptic Encephalopathies (DEE) are a genetically diverse group of severe, early onset seizure disorders. DEE are normally identified clinically in the first six months of life by the presence of frequent, difficult to control seizures and accompanying stalling or regression of development. DEE72 results from de novo mutations of the NEUROD2 gene that result in loss of activity of the encoded transcription factor, and the seizure phenotype was shown to be recapitulated in Xenopus tropicalis tadpoles. We used CRISPR/Cas9 to make a DEE72 model in Xenopus laevis, to further investigate the developmental etiology. NeuroD2.S CRISPR/Cas9 edited tadpoles were more active, swam faster on average, and had more seizures (C-shaped contractions resembling unprovoked C-start escape responses) than their sibling controls. Live imaging of Ca2+ signaling revealed prolongued, strong signals sweeping through the brain, indicative of neuronal hyperactivity. While the resulting tadpole brain appeared grossly normal, the blood-brain barrier (BBB) was found to be leakier than that of controls. Additionally, the TGFβ antagonist Losartan was shown to have a short-term protective effect, reducing neuronal hyperactivity and reducing permeability of the BBB. Treatment of NeuroD2 CRISPant tadpoles with 5 mM Losartan decreased seizure events by more than 4-fold compared to the baseline. Our results support a model of DEE72 resulting from reduced NeuroD2 activity during vertebrate brain development, and indicate that a leaky BBB contributes to epileptogenesis.
Bilateral health agreements of South Africa: an analysis of issues covered
Authors: Hanefeld Johanna , Modisenyane Moeketsi , Vearey Jo , Lunt Neil , Smith Richard , Walls Helen 
Published: May 2024

Abstract
The bilateral agreements signed between South Africa and countries in Southern and Eastern Africa are a rare example of efforts to regulate health-related issues in a world region. As far as we know, there are no comparable bilateral health governance mechanisms in regions elsewhere. Furthermore, the rapidly growing literature on global health governance and governance for global health has to date not addressed the issue of patient mobility and how to govern it. In this study, we examine the issues included in these agreements, highlight key issues that they address, identify areas of omission and provide recommendations for improvement. This analysis should inform the development of such governance agreements both in Southern Africa and in regions elsewhere. We obtained 13 bilateral health agreements between South Africa and 11 neighbouring African countries as part of a broader research project examining the impact on health systems of patient mobility in South Africa, and thematically analysed their content and the governance mechanisms described. The agreements appear to be solidarity mechanisms between neighbouring countries. They contain considerable content on health diplomacy, with little on health governance, management and delivery. Nonetheless, given what they do and do not address, and how, they provide a rare insight into mechanisms of global health diplomacy and attempts to address patient mobility and other health-related issues in practice. The agreements appear to be global health diplomacy mechanisms expressing solidarity, emerging from a post-apartheid period, but with little detail of issues covered, and a range of important issues not addressed. Further empirical work is required to understand what these documents mean, particularly in the Covid-19 context, and to understand challenges with their implementation. The documents also raise the need for particular study of bilateral flows and experience of patients and health workers, and how this relates to health system strengthening.
Landscape of TPMT and NUDT15 Pharmacogenetic Variation in a Cohort of Canadian Pediatric Inflammatory Bowel Disease Patients
Authors: Kennedy April M , Griffiths Anne M , Muise Aleixo M , Walters Thomas D , Ricciuto Amanda , Huynh Hien Q , Wine Eytan , Jacobson Kevan , Lawrence Sally , Carman Nicholas , Mack David R , deBruyn Jennifer C , Otley Anthony R , Deslandres Colette , El-Matary Wael , Zachos Mary , Benchimol Eric I , Critch Jeffrey , Schneider Rilla , Crowley Eileen , Li Michael , Warner Neil , McGovern Dermot P B , Li Dalin , Haritunians Talin , Rudin Sarah , Cohn Iris 
Published: May 2024

Abstract

Background
Patients with inflammatory bowel disease (IBD) exhibit considerable interindividual variability in medication response, highlighting the need for precision medicine approaches to optimize and tailor treatment. Pharmacogenetics (PGx) offers the ability to individualize dosing by examining genetic factors underlying the metabolism of medications such as thiopurines. Pharmacogenetic testing can identify individuals who may be at risk for thiopurine dose-dependent adverse reactions including myelosuppression. We aimed to evaluate PGx variation in genes supported by clinical guidelines that inform dosing of thiopurines and characterize differences in the distribution of actionable PGx variation among diverse ancestral groups.

Methods
Pharmacogenetic variation in TPMT and NUDT15 was captured by genome-wide genotyping of 1083 pediatric IBD patients from a diverse Canadian cohort. Genetic ancestry was inferred using principal component analysis. The proportion of PGx variation and associated metabolizer status phenotypes was compared across 5 genetic ancestral groups within the cohort (Admixed American, African, East Asian, European, and South Asian) and to prior global estimates from corresponding populations.

Results
Collectively, 11% of the cohort was categorized as intermediate or poor metabolizers of thiopurines, which would warrant a significant dose reduction or selection of alternate therapy. Clinically actionable variation in TPMT was more prevalent in participants of European and Admixed American/Latino ancestry (8.7% and 7.5%, respectively), whereas variation in NUDT15 was more prevalent in participants of East Asian and Admixed American/Latino ancestry (16% and 15% respectively).

Conclusions
These findings demonstrate the considerable interpopulation variability in PGx variation underlying thiopurine metabolism, which should be factored into testing diverse patient populations.
Photosymbiont Density Is Correlated with Constitutive and Induced Immunity in the Facultatively Symbiotic Coral, Astrangia poculata
Authors: Changsut Isabella V , Borbee Erin M , Womack Haley R , Shickle Alicia , Sharp Koty H , Fuess Lauren E 
Published: May 2024

Synopsis
Scleractinian corals, essential ecosystem engineers that form the base of coral reef ecosystems, have faced unprecedented mortality in recent decades due to climate change-related stressors, including disease outbreaks. Despite this emergent threat to corals, many questions still remain regarding mechanisms underlying observed variation in disease susceptibility. Recent data suggest at least some degree of variation in disease response may be linked to variability in the relationship between host corals and their algal photosymbionts (Family Symbiodiniaceae). Still, the nuances of connections between symbiosis and immunity in cnidarians, including scleractinian corals, remain poorly understood. Here, we leveraged an emergent model species, the facultatively symbiotic, temperate, scleractinian coral Astrangia poculata, to investigate associations between symbiont density and both constitutive and induced immunity. We used a combination of controlled immune challenges with heat-inactivated pathogens and transcriptomic analyses. Our results demonstrate that A. poculata mounts a robust initial response to pathogenic stimuli that is highly similar to responses documented in tropical corals. We document positive associations between symbiont density and both constitutive and induced immune responses, in agreement with recent preliminary studies in A. poculata. A suite of immune genes, including those coding for antioxidant peroxiredoxin biosynthesis, are positively associated with symbiont density in A. poculata under constitutive conditions. Furthermore, variation in symbiont density is associated with distinct patterns of immune response; low symbiont density corals induce preventative immune mechanisms, whereas high symbiont density corals mobilize energetic resources to fuel humoral immune responses. In summary, our study reveals the need for more nuanced study of symbiosis-immune interplay across diverse scleractinian corals, preferably including quantitative energy budget analysis for full disentanglement of these complex associations and their effects on host pathogen susceptibility.
Queering the Global Governance of Transitional Justice: Tensions and (Im)Possibilities
Authors: Biddolph Caitlin 
Published: May 2024

ABSTRACT∞
In recent years, scholars and activists have been asking queer questions about transitional justice. Queer perspectives advocate for the recognition of anti-queer violence within transitional justice; the inclusion of LGBTQIA+ people in transitional justice processes; and the development of queer decolonial critiques of transitional justice. Informed by this research agenda, I develop a queer perspective to the global governance of transitional justice. I analyse documents from the UN, the International Center for Transitional Justice and the International Criminal Court. Representing mechanisms from across global transitional justice, I trace the (cis-heteronormative, colonial, carceral) violence of transitional justice and its institutionalization at the global level. I reflect on the queer tensions and (im)possibilities of global transitional justice, a site that is violent but holds transformative potential. The global governance of transitional justice must be queered to expand its social, political and conceptual remit, and to seek more radical, liberatory worlds within and beyond formal justice mechanisms.
Discrete anisotropic curve shortening flow in higher codimension
Authors: Deckelnick Klaus , Nürnberg Robert 
Published: May 2024

Abstract
We introduce a novel formulation for the evolution of parametric curves by anisotropic curve shortening flow in ${{\mathbb{R}}}^{d}$, $d\geq 2$. The reformulation hinges on a suitable manipulation of the parameterization’s tangential velocity, leading to a strictly parabolic differential equation. Moreover, the derived equation is in divergence form, giving rise to a natural variational numerical method. For a fully discrete finite element approximation based on piecewise linear elements we prove optimal error estimates. Numerical simulations confirm the theoretical results and demonstrate the practicality of the method.
Respiratory Viral Coinfections in Pediatric Patients in the Primary Care Setting: A Multicenter Prospective Study Within the COPEDICAT Network
Authors: Andrés Cristina , Perramon-Malavez Aida , Creus-Costa Anna , Gatell Anna , Martín-Martín Ramona , Solà-Segura Elisabet , Riera-Bosch Maria Teresa , Biosca Mireia , Soler Isabel , Chiné Maria , Sanz Lidia , Quezada Gabriela , Pérez Sandra , Salvadó Olga , Sau Imma , Prats Clara , Antón Andrés , Soriano-Arandes Antoni 
Published: May 2024

Abstract
Acute respiratory viral infections pose a significant healthcare burden on the pediatric population globally, but data on the dissemination pattern in the community due to the coronavirus disease 2019 (COVID-19) pandemic are scarce. We conducted a 2-year prospective multicenter study in Catalonia (Spain) that examined the prevalence and coinfection dynamics of respiratory viruses among 1276 pediatric patients from different age groups attending primary care. Coinfection analysis demonstrated complex patterns and revealed a coinfection rate of 23.8% for severe acute respiratory syndrome coronavirus 2, often in association with rhinovirus or influenza A. This study provides valuable data to understand postpandemic viral interactions, which is imperative for public health interventions.
Dysfunction of type 1 and type 2 immune cells: a lesson from exhausted-like ILC2s and their activation-induced cell death
Authors: Ebihara Takashi , Yamada Toshiki , Fuchimukai Akane , Takasuga Shunsuke , Endo Tentaro , Yamada Takechiyo , Tatematsu Megumi 
Published: May 2024

Abstract
The concept of immune cell exhaustion/dysfunction has developed mainly to understand impaired type 1 immune responses, especially by CD8 T-cells against tumors or virus-infected cells, and has been applied to other lymphocytes. Natural killer (NK) cells and CD4 T cells support the efficient activation of CD8 T cells but exhibit dysfunctional phenotypes in tumor microenvironments and in chronic viral infections. In contrast, the concept of type 2 immune cell exhaustion/dysfunction is poorly established. Group 2 innate lymphoid cells (ILC2s) and T-helper 2 (Th2) cells are the major lymphocyte subsets that initiate and expand type 2 immune responses for antiparasitic immunity or allergy. In mouse models of chronic parasitic worm infections, Th2 cells display impaired type 2 immune responses. Chronic airway allergy induces exhausted-like ILC2s that quickly fall into activation-induced cell death to suppress exaggerated inflammation. Thus, the modes of exhaustion/dysfunction are quite diverse and rely on the types of inflammation and the cells. In this review, we summarize current knowledge of lymphocyte exhaustion/dysfunction in the context of type 1 and type 2 immune responses and discuss ILC2-specific regulatory mechanisms during chronic allergy.
Notch 2 signaling contributes to intestinal eosinophil adaptations in steady state and tissue burden following oral allergen challenge
Authors: Schworer Stephen A , Olbrich Courtney L , Larsen Leigha D , Howard Emily , Liu Linying , Koyama Kenya , Spencer Lisa A 
Published: May 2024

Abstract
Eosinophils not only function as inflammatory effectors in allergic diseases, but also contribute to tissue homeostasis in steady state. Emerging data are revealing tissue eosinophils to be adaptive cells, imprinted by their local tissue microenvironment and exhibiting distinct functional phenotypes that may contribute to their homeostatic vs. inflammatory capacities. However, signaling pathways that regulate eosinophil tissue adaptations remain elusive. Notch signaling is an evolutionarily conserved pathway that mediates differential cell fate programming of both pre- and postmitotic immune cells. This study investigated a role for notch receptor 2 signaling in regulating eosinophil functions and tissue phenotype in both humans and mice. Notch 2 receptors were constitutively expressed and active in human blood eosinophils. Pharmacologic neutralization of notch 2 in ex vivo stimulated human eosinophils altered their activated transcriptome and prevented their cytokine-mediated survival. Genetic ablation of eosinophil-expressed notch 2 in mice diminished steady-state intestine-specific eosinophil adaptations and impaired their tissue retention in a food allergic response. In contrast, notch 2 had no effect on eosinophil phenotype or tissue inflammation within the context of allergic airways inflammation, suggesting that notch 2–dependent regulation of eosinophil phenotype and function is specific to the gut. These data reveal notch 2 signaling as a cell-intrinsic mechanism that contributes to eosinophil survival, function, and intestine-specific adaptations. The notch 2 pathway may represent a viable strategy to reprogram eosinophil functional phenotypes in gastrointestinal eosinophil-associated diseases.