bluuebunny/crossref_metadata_2025 huggingface dataset:
Validating peak frequency mapping for atrial far-field electrogram detection: insights from a pulmonary vein isolation model
Authors: Martinez Cossiani M , Castrejon-Castrejon S , Sanroman-Junquera M , Kim S , Relan J , De La Vieja Alarcon J J , Guido L , Merino D E , Jauregui Abularach M E , Sanchez Somonte P , Martinez Maldonado M E , Sanz Verdejo B , Carton A , Escobar Cervantes C , Merino J L
Published: May 2024

Introduction

Effective pulmonary vein isolation (PVI) is the cornerstone of AF ablation, and conduction block from the atrium to the pulmonary veins (PV) is the accepted method to demonstrate it. However, far-field electrograms may make challenging to establish whether PVI has been achieved.

Purpose

This study aimed to evaluate whether peak frequency (PF) mapping can effectively identify far-field electrograms in the superior PVs following a redo PVI procedure.

Methods

Left atrium and PV activation and voltage bipolar 3D electroanatomical maps were generated using a steerable catheter with a 16-grid-patterned electrode configuration (HD-Grid) during coronary sinus pacing, both before and after the redo PVI. PF maps were developed offline using specialized experimental software. Only reconnected superior PVs from the redo PVI procedure were included in the analysis.

Results

Twenty consecutive patients (mean age 63±12 years, 12 male) were prospectively enrolled in the study, with 15 presenting reconnected PVs after the redo PVI. Conduction gaps were identified in the superior PVs of 9 patients (7 in the left superior PV, 5 in the right superior PV). Following the redo PVI, both voltage (0.96±1.1 mV vs. 0.49±1.21, P<0.01) and PF (285±134 vs. 153±112 Hz, P<0.001) were significantly reduced in both superior PVs. This reduction was more prominent in the right superior PV (0.83±0.75 vs. 0.20±0.39 mV, 299±159 vs. 132±116 Hz) than in the left superior PV (1.08±1.32 vs. 0.83±1.67 mV, 272±105 vs. 178±101 Hz). High-voltage (>0.3 mV) electrograms remained prevalent in the right (12%) and left (37%) superior PVs after the redo PVI. However, high PF (>250 Hz) electrograms significantly decreased following PVI in both the right (64% before vs. 6% after PVI) and left (66% before vs. 22% after PVI) PVs. Only a small percentage (5.3% in the right PV and 12% in the left PV) of all electrograms exhibited both high voltage and high PF following the PVI (see figure).

Conclusion

PF mapping proves to be a valuable tool in distinguishing far-field electrograms from atrial activity in the PVs, offering additional insights to complement voltage mapping, particularly in the context of redo PVI procedures.
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

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

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

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

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

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

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

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

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

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

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

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.
Alzheimer disease–related biomarkers and cancer-related cognitive decline: the Thinking and Living with Cancer study
Authors: Mandelblatt Jeanne , Dage Jeffrey L , Zhou Xingtao , Small Brent J , Ahles Tim A , Ahn Jaeil , Artese Ashley , Bethea Traci N , Breen Elizabeth C , Carroll Judith E , Cohen Harvey J , Extermann Martine , Graham Deena , Claudine Isaacs , Jim Heather S L , McDonald Brenna C , Nakamura Zev M , Patel Sunita K , Rebeck G William , Rentscher Kelly E , Root James C , Russ Kristen A , Tometich Danielle B , Turner R Scott , Van Dyk Kathleen , Zhai Wanting , Huang Li-Wen , Saykin Andrew J
Published: May 2024

Purpose

We evaluated whether plasma Alzheimer disease (AD)–related biomarkers were associated with cancer-related cognitive decline among older breast cancer survivors.

Methods

We included survivors aged 60-90 years with primary stage 0-III breast cancers (n = 236) and frequency-matched noncancer control paricipant (n = 154) who passed a cognitive screen and had banked plasma specimens. Participants were assessed at baseline (presystemic therapy) and annually for up to 60 months. Cognition was measured using tests of attention, processing speed, and executive function and learning and memory; perceived cognition was measured by the Functional Assessment of Cancer Therapy-Cognitive Function v3 Perceived Cognitive Impairments. Baseline plasma neurofilament light, glial fibrillary acidic protein, β-amyloid 42 and 40 and phosphorylated tau 181 were assayed using single molecule arrays. Mixed models tested associations between cognition and baseline AD biomarkers, time, group (survivor vs control participant), and their 2- and 3-way interactions, controlling for age, race, Wide Range 4 Achievement Test Word Reading score, comorbidity, and body mass index; 2-sided P values of .05 were considered statistically significant.

Results

There were no group differences in baseline AD-related biomarkers except survivors had higher baseline neurofilament light levels than control participants (P = .013). Survivors had lower adjusted longitudinal attention, processing speed, and executive function than control participants starting from baseline and continuing over time (P ≤ .002). However, baseline AD-related biomarker levels were not independently associated with adjusted cognition over time, except control participants had lower attention, processing speed, and executive function scores with higher glial fibrillary acidic protein levels (P = .008).

Conclusion

The results do not support a relationship between baseline AD-related biomarkers and cancer-related cognitive decline. Further investigation is warranted to confirm the findings, test effects of longitudinal changes in AD-related biomarkers, and examine other mechanisms and factors affecting cognition presystemic therapy.
‘If I Knew How to Speak English…’: How language shapes refugee mothers’ perceptions of past, present, and future in Canada
Authors: Omar Laila
Published: May 2024

What role does language learning play in refugees’ memory-construction on the one hand, and imagining of the future self on the other? Using a temporal perspective on migration, I extend scholarship examining the role of language in the space-time continuum of resettlement. With three waves of semi-structured interviews with twenty Syrian refugee mothers (N = 60) who have recently arrived in Canada, this article examines how their experiences with time and future projections are influenced by their experiences of language learning in the host country. First, mothers’ lack of English proficiency and struggle to learn leads to a sense of nostalgia towards the past, where their proficiency in Arabic is associated with past feelings of comfort, security, and mastery. In addition, mothers find themselves ‘stuck’ in the present, where multiple structural barriers (e.g., absence of extended kin; limited government support) and individual challenges (e.g., health issues; having children with disability) significantly slow down their language acquisition process and prevent them from achieving other goals. This leads to a clear conflict between government expectations for the long-term future and the mothers’ immediate priorities. Finally, despite those government temporal expectations building on newcomers’ language acquisition, mothers do not want to envision the future due to past experiences of uncertainty, belief in divine control, and a foreclosure of the future. This article demonstrates the ways in which language, space, and time co-construct notions of the future, and a sense of potential ‘stuckness,’ well beyond the temporal limits of intensive state intervention in refugee lives.
Direct and vicarious administrative burden: Experiences of UK public services as Homes for Ukraine host
Authors: Tomlinson Joe , Kasoulide Eleana , Meers Jed , Halliday Simon
Published: May 2024

This article shows, through a study of hosts’ experiences of the UK’s Homes for Ukraine scheme, the ways in which sponsoring refugees can impose burdens on sponsors by virtue of the state’s administrative processes. Specifically, it shows how sponsors incur learning, compliance, and psychological costs from administrative burdens and that these burdens are encountered both directly, through their own engagements with public bodies, and vicariously, through the experiences of their guests. The article thus makes a significant contribution to the understanding of the ground-level experience of refugee sponsorship while also expanding the burgeoning theory of administrative burden by demonstrating the relevance of burdens experienced vicariously.
Re-weighting the randomized controlled trial for generalization: finite-sample error and variable selection
Authors: Colnet Bénédicte , Josse Julie , Varoquaux Gaël , Scornet Erwan
Published: May 2024

Randomized controlled trials (RCTs) may suffer from limited scope. In particular, samples may be unrepresentative: some RCTs over- or under-sample individuals with certain characteristics compared to the target population, for which one wants conclusions on treatment effectiveness. Re-weighting trial individuals to match the target population can improve the treatment effect estimation. In this work, we establish the expressions of the bias and variance of such re-weighting procedures—also called inverse propensity of sampling weighting (IPSW)—in presence of categorical covariates for any sample size. Such results allow us to compare the theoretical performance of different versions of IPSW estimates. Besides, our results show how the performance (bias, variance, and quadratic risk) of IPSW estimates depends on the two sample sizes (RCT and target population). A by-product of our work is the proof of consistency of IPSW estimates. In addition, we analyse how including covariates that are not necessary for identifiability of the causal effect may impact the asymptotic variance. Including covariates that are shifted between the two samples but not treatment-effect modifiers increases the variance while non-shifted but treatment-effect modifiers do not. We illustrate all the takeaways in a didactic example, and on a semi-synthetic simulation inspired from critical care medicine.
Bayesian causal forests for multivariate outcomes: application to Irish data from an international large scale education assessment
Authors: McJames Nathan , O’Shea Ann , Goh Yong Chen , Parnell Andrew
Published: May 2024

Bayesian Causal Forests (BCF) is a causal inference machine learning model based on the flexible non-parametric regression and classification tool, Bayesian Additive Regression Trees (BART). Motivated by data from the Trends in International Mathematics and Science Study (TIMSS), which includes data on student achievement in both mathematics and science, we present a multivariate extension of the BCF algorithm. With the help of simulation studies, we show that our approach can accurately estimate causal effects for multiple outcomes subject to the same treatment. We apply our model to Irish data from TIMSS 2019. Our findings reveal the positive effects of having access to a study desk at home (Mathematics ATE 95% CI: [−0.50, 10.14]) while also highlighting the negative consequences of students often feeling hungry at school (Mathematics ATE 95% CI: [−8.86, −1.56] , Science ATE 95% CI: [−10.35, −0.94]) or often being absent (Mathematics ATE 95% CI: [−11.88, −2.27]). Code for replicating the results can be found at https://github.com/Nathan-McJames/MVBCF-Paper.
Dynamic factor models for binary data in circular spaces: an application to the US Supreme Court
Authors: Lei Rayleigh , Rodriguez Abel
Published: May 2024

Latent factor models are widely used in the social and behavioural sciences as scaling tools to map discrete multivariate outcomes into low-dimensional, continuous scales. In political science, dynamic versions of classical factor models have been widely used to study the evolution of justices’ preferences in multi-judge courts. In this paper, we discuss a new dynamic factor model that relies on a latent circular space that can accommodate voting behaviours in which justices commonly understood to be on opposite ends of the ideological spectrum vote together on a substantial number of otherwise closely divided opinions. We apply this model to data on nonunanimous decisions made by the US Supreme Court between 1937 and 2021, and show that for most of this period, voting patterns can be better described by a circular latent space.
Travel and sex: addressing the spread of sexually transmitted infections
Authors: Caumes Eric
Published: May 2024

Travellers are at risk of STIs. The relationship between travel and STIs is obvious, as evidenced by the histories of syphilis, HIV infection and more recently, Mpox. STIs continue to emerge. Antimicrobial resistance is a huge concern. Thus, the importance of safer sex and condom use should be re-emphasized.
Spatially resolved spectroscopic observations of gas emission in dwarf galaxies hosting accreting black hole candidate
Authors: Heckler Kelly F , Riffel Rogemar A , Ricci Tiago V
Published: May 2024

Recent studies on dwarf galaxies reveal that some of them harbour a massive black hole (BH), which is believed to have a similar mass of the supermassive BH ‘seeds’ at early times. The origin and growth of the primitive BHs are still open questions, since these BH seeds are hardly observed at high redshifts. Therefore, MBH of dwarf galaxies can be the perfect candidates to untangle BH ‘seeds’ properties and their influence on their host galaxy evolution, since MBH may preserve their initial conditions due to its quiet merger and accretion histories. We use optical integral field unit observations, obtained with the Gemini GMOS-IFU, to study the gas emission and kinematics in four dwarf galaxies, candidates to host MBH, based on the analysis of their [Fe x] luminosities measured from SDSS spectra. The [Fe x] emission line is not detected in our GMOS in any of the galaxies, prompting speculation that its absence in our recent data may stem from a past tidal disruption event coinciding with the observation period of the SDSS data. All galaxies exhibit extended gas emissions, and the spatially resolved emission-line ratio diagnostic diagrams present values that suggest active galactic nuclei (AGN) photoionization from the [S ii]–BPT diagram. The gas velocity fields of all galaxies are indicative of disturbed rotation patterns, with no detection of gas outflows in any of the sources. Although the [S ii]–BPT diagrams indicate AGN photoionization, further confirmation through multiwavelength observations is required to validate this scenario.
A search for transient, monochromatic light in a 6-deg swath along the galactic plane
Authors: Marcy Geoffrey W , Tellis Nathaniel K
Published: May 2024

We searched the Milky Way Plane along a 6-deg swath for pulses of monochromatic light as faint as 15th mag (V band) using a wide-field telescope equipped with a prism. Pulses with duration less than 1 s that occur more often than once every 10 min would be detected, and pulses arriving less frequently would be detected with proportionally lower probability. A ‘difference-image’ algorithm revealed 36 monochromatic sources. Subsequent assessment showed all were simply astrophysical objects emitting known atomic emission lines. No unexplainable monochromatic emission, pulsed or continuous, was detected. The detection threshold corresponds to an ∼70 GW laser having a diffraction-limited 10-m aperture 1 kpc away (depending on wavelength). Past all-sky optical and radio-wave surveys revealed thousands of unexpected objects exhibiting extraordinary spectral emission, but none were technological. Hypotheses of our Milky Way Galaxy teeming with advanced life must be demoted.
The influence of ionized gas kinematics on H ii galaxies – the cases of Tol 1004-296 and Tol 0957-278
Authors: Plana Henri , Alves Vitor G , Carvalho Maiara S
Published: May 2024

Blue compact galaxies, also known as H ii galaxies, are dwarf, star-forming objects with relatively simple dynamics, which allows for the investigation of star formation mechanisms in a cleaner manner compared to late-type objects. In this study, we have examined various characteristics of the interstellar medium, in connection with the kinematics and dynamics of ionized gas, in Tol 1004-296 and Tol 0957-278. These two objects were observed using the SOAR Integral Field Spectrometer (SIFS) attached to the Southern Observatory for Astrophysical Research (SOAR). Both galaxies were observed with two gratings: one with medium resolution for monochromatic and abundance maps, and another with high resolution for kinematics and profile analysis. Additionally, we conducted an analysis on the velocity and velocity dispersion maps using intensity–velocity dispersion (I-σ) and velocity–velocity dispersion (Vr-σ) diagrams. Neither object exhibits a rotation pattern, and only Tol 1004-296 shows a velocity gradient between the two principal knots. However, the study reveals the significant role played by velocity dispersion in the star formation process. Specifically, we identified a relationship between monochromatic intensity, metallicity, and velocity dispersion, where high emission corresponds to low metallicity and low velocity dispersion. Tol 1004-296, in particular, exhibits a distinctive linear high velocity dispersion pattern between the two main knots, suggesting that both star formation sites are pushing the gas in opposite directions.
An accurate and realistic polarization model for night-sky brightness
Authors: Kocifaj M , Markoš P , Kundracik F , Barentine J C , Wallner S
Published: May 2024

Most measurements of the diffuse light of the night sky to date consider only the intensity of the light field, and current models can successfully reproduce these measurements. However, this approach is incomplete as it overlooks the polarization state of the light. Few measurements (and no successful models) of night-sky polarimetry appear in the literature. We present a new model of night-sky polarization that successfully reproduces observations in a heterogeneous environment and for a real distribution of finite-sized light sources over the intermediate region surrounding the observer. The model compares favourably with field measurements made in Slovakia in 2021 May. The results described herein help advance understanding of the angular distributions of artificial light at night from ground sources and the relative contributions of sources to the overall brightness of the night sky.
Severe Bottleneck Impacted the Genomic Structure of Egg-Eating Cichlids in Lake Victoria
Authors: Imamoto Minami , Nakamura Haruna , Aibara Mitsuto , Hatashima Ryo , Kimirei Ismael A , Kashindye Benedicto B , Itoh Takehiko , Nikaido Masato
Published: May 2024

Within 15,000 years, the explosive adaptive radiation of haplochromine cichlids in Lake Victoria, East Africa, generated 500 endemic species. In the 1980s, the upsurge of Nile perch, a carnivorous fish artificially introduced to the lake, drove the extinction of more than 200 endemic cichlids. The Nile perch predation particularly harmed piscivorous cichlids, including paedophages, cichlids eat eggs and fries, which is an example of the unique trophic adaptation seen in African cichlids. Here, aiming to investigate past demographic events possibly triggered by the invasion of Nile perch and the subsequent impacts on the genetic structure of cichlids, we conducted large-scale comparative genomics. We discovered evidence of recent bottleneck events in 4 species, including 2 paedophages, which began during the 1970s to 1980s, and population size rebounded during the 1990s to 2000s. The timing of the bottleneck corresponded to the historical records of endemic haplochromines” disappearance and later resurgence, which is likely associated with the introduction of Nile perch by commercial demand to Lake Victoria in the 1950s. Interestingly, among the 4 species that likely experienced bottleneck, Haplochromis sp. “matumbi hunter,” a paedophagous cichlid, showed the most severe bottleneck signatures. The components of shared ancestry inferred by ADMIXTURE suggested a high genetic differentiation between matumbi hunter and other species. In contrast, our phylogenetic analyses highly supported the monophyly of the 5 paedophages, consistent with the results of previous studies. We conclude that high genetic differentiation of matumbi hunter occurred due to the loss of shared genetic components among haplochromines in Lake Victoria caused by the recent severe bottleneck.
Murine uterine gland branching is necessary for gland function in implantation
Authors: Granger Katrina , Fitch Sarah , Shen May , Lloyd Jarrett , Bhurke Aishwarya , Hancock Jonathan , Ye Xiaoqin , Arora Ripla
Published: May 2024

Uterine glands are branched, tubular structures whose secretions are essential for pregnancy success. It is known that pre-implantation glandular expression of leukemia inhibitory factor (LIF) is crucial for embryo implantation; however, the contribution of uterine gland structure to gland secretions, such as LIF, is not known. Here, we use mice deficient in estrogen receptor 1 (ESR1) signaling to uncover the role of ESR1 signaling in gland branching and the role of a branched structure in LIF secretion and embryo implantation. We observed that deletion of ESR1 in neonatal uterine epithelium, stroma, and muscle using the progesterone receptor PgrCre causes a block in uterine gland development at the gland bud stage. Embryonic epithelial deletion of ESR1 using a Müllerian duct Cre line, Pax2Cre, displays gland bud elongation but a failure in gland branching. Reduction of ESR1 in adult uterine epithelium using the lactoferrin-Cre (LtfCre) displays normally branched uterine glands. Unbranched glands from Pax2Cre Esr1flox/flox uteri fail to express glandular pre-implantation Lif, preventing implantation chamber formation and embryo alignment along the uterine mesometrial–antimesometrial axis. In contrast, branched glands from LtfCre Esr1flox/flox uteri display reduced expression of ESR1 and glandular Lif resulting in delayed implantation chamber formation and embryo–uterine axes alignment but mice deliver a normal number of pups. Finally, pre-pubertal unbranched glands in control mice express Lif in the luminal epithelium but fail to express Lif in the glandular epithelium, even in the presence of estrogen. These data strongly suggest that branched glands are necessary for pre-implantation glandular Lif expression for implantation success. Our study is the first to identify a relationship between the branched structure and secretory function of uterine glands and provides a framework for understanding how uterine gland structure–function contributes to pregnancy success.
Efficacy and safety of tumor necrosis factor inhibitors for systemic juvenile idiopathic arthritis: A systematic review
Authors: Ishikawa Takashi , Nishimura Kenichi , Okamoto Nami , Akamine Keiji , Inoue Natsumi , Irabu Hitoshi , Kato Kentaro , Keino Hiroshi , Kojima Masayo , Kubo Hiroshi , Maruyama Kazuichi , Mizuta Mao , Shabana Kosuke , Shimizu Masaki , Sugita Yuko , Takakuwa Yukiko , Takanashi Satoshi , Takase Hiroshi , Umebayashi Hiroaki , Umezawa Natsuka , Yamanishi Shingo , Yamazaki Kazuko , Yashiro Masato , Yasumi Takahiro , Mori Masaaki
Published: May 2024

Objectives

This systematic review assessed the efficacy and safety of tumor necrosis factor (TNF) inhibitors in patients with systemic juvenile idiopathic arthritis (JIA).

Methods

Studies were searched using PubMed, Embase, Cochrane, Ichushi-Web, and clinical trial registries (from 2000 to 2021). The risk of bias was assessed using the Cochrane Risk of Bias version 2 for randomized controlled trials (RCTs) and the manual of Minds for observational studies.

Results

One RCT and 22 observational studies were included. In the RCT on infliximab, the American College of Rheumatology pediatric (ACR Pedi) 30/50/70 responses at 14 weeks were 63.8%/50.0%/22.4%, with relative risks of 1.30 [95% confidence interval (CI): 0.94–1.79]/1.48 (95% CI: 0.95–2.29)/1.89 (95% CI: 0.81–4.40), respectively. In the observational studies, ACR Pedi 30/50/70 responses for etanercept at 12 months were 76.7%/64.7%/46.4%, respectively. Infliximab treatment caused anaphylaxis in 17% and an infusion reaction in 23% of patients. The incidence of macrophage activation syndrome, serious infection, and malignancy caused by TNF inhibitors was 0–4%.

Conclusions

Thus, although TNF inhibitors were relatively safe, they were unlikely to be preferentially administered in patients with systemic JIA because of their inadequate efficacy. Further studies, especially well-designed RCTs, are needed to accumulate clinical data.