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Venus, lacking an intrinsic global dipole magnetic field, serves as a textbook example of an induced magnetosphere, formed by interplanetary magnetic fields (IMF) enveloping the planet. Yet, various aspects of its magnetospheric dynamics and planetary ion outflows are complex and not well understood. Here we analyze plasma and magnetic field data acquired during the fourth Venus flyby of the Parker Solar Probe (PSP) mission and show evidence for closed topology in the nightside and downstream portion of the Venus magnetosphere (i.e., the magnetotail). The formation of the closed topology involves magnetic reconnection-a process rarely observed at non-magnetized planets. In addition, our study provides an evidence linking the cold Venusian ion flow in the magnetotail directly to magnetic connectivity to the ionosphere, akin to observations at Mars. These findings not only help the understanding of the complex ion flow patterns at Venus but also suggest that magnetic topology is one piece of key information for resolving ion escape mechanisms and thus the atmospheric evolution across various planetary environments and exoplanets.

Bioluminescence is a widespread phenomenon that has evolved multiple times across the tree of life, converging among diverse fauna and habitat types. The ubiquity of bioluminescence, particularly in marine environments where it is commonly used for communication and defense, highlights the adaptive value of this trait, though the evolutionary origins and timing of emergence remain elusive for a majority of luminous organisms. Anthozoan cnidarians are a diverse group of animals with numerous bioluminescent species found throughout the worlds oceans, from shallow waters to the light-limited deep sea where bioluminescence is particularly prominent. This study documents the presence of bioluminescent Anthozoa across depth and explores the diversity and evolutionary origins of bioluminescence among Octocorallia-a major anthozoan group of marine luminous organisms. Using a phylogenomic approach and ancestral state reconstruction, we provide evidence for a single origin of bioluminescence in Octocorallia and infer the age of occurrence to around the Cambrian era, approximately 540 Ma-setting a new record for the earliest timing of emergence of bioluminescence in the marine environment. Our results further suggest this trait was largely maintained in descendants of a deep-water ancestor and bioluminescent capabilities may have facilitated anthozoan diversification in the deep sea.

Abstract Purpose Eosinophilic esophagitis (EoE), a chronic immune-mediated progressive disease, causes dysphagia, food impaction, abdominal pain, vomiting, and heartburn. EoE requires long-term monitoring and can affect quality of life owing to its symptoms and associated emotional and social burden. This study aimed to understand patients’ experiences with EoE. Methods Semi-structured longitudinal interviews were conducted with patients from MESSINA, a phase 3 placebo-controlled trial evaluating benralizumab for EoE. Interviews were held at two different times to assess the impact of EoE on patients’ lives before and during trial participation. Data were analyzed qualitatively to develop detailed patient profiles. Results The MESSINA trial was terminated prematurely. Of the 34 patients recruited for the first interview, 15 (44%) completed the second interview and 11 patient profiles were developed. Patients were a demographically diverse group with varying experiences. The primary reported symptom was difficulty swallowing (n = 11), leading to serious consequences like choking and hospitalization (n = 2). Other symptoms included pain when swallowing (n = 7), reflux (n = 6), and stomachache (n = 6). In the second interview, most (n = 9) patients reported moderate improvements in symptoms, while others experienced symptom recurrence or worsening. EoE had a significant negative impact on social and emotional well-being, and professional lives. Trial participation improved emotional well-being for some; however, concerns about the need for ongoing treatment were noted. Conclusion This study highlighted emotional and social burdens of EoE. The encouraging feedback on study participation underscores the importance of patient insights in developing holistic management strategies for EoE.

Abstract Background For children under age six, regular preventative primary care is needed for administration of vaccinations, surveillance of development, and early diagnosis and intervention for any potential health conditions or developmental delays. The COVID-19 pandemic created many barriers to providing and accessing primary care. While many studies have explored these barriers, it is important to understand how primary care adapted to ensure these crucial early-years appointments were not missed throughout the pandemic. The objective of this study, therefore, was to discover innovative programs or services that were used, and suggestions for programs or services that could have been implemented, to facilitate delivery of, and access to, primary care for young children during the COVID-19 pandemic (March 2020-May 2023). Methods This qualitative descriptive study used a survey and semi-structured interviews to discuss primary care programs or services with parents or caregivers of children who were under the age of 6 during the pandemic and with primary care providers who deliver care to young children. The survey was sent to parent groups and primary care providers across the Canadian provinces of Ontario and Quebec from May to October 2023. Survey participants who indicated interest in further participation were subsequently contacted for an interview. Results were analyzed using content and thematic analyses. Results 102 individuals (33 primary care providers and 69 parents or caregivers) responded to the survey and of those, 19 participated in the interviews. Six themes emerged from the innovative services or procedures that were discussed: Prioritization of young children; Creation or modification of primary care spaces; Clear decision-making guidelines; Virtual care integration; Proactive communication; and Interdisciplinary collaboration. Conclusions This qualitative study explored some creative and positive solutions to the struggle of providing and accessing primary care for young children during the COVID-19 pandemic. The results from this research highlight the importance of flexibility and innovation within the primary care system, especially under circumstances of sudden and unexpected increases in barriers to providing and accessing care. On-going development of innovations that improve communication, take a more collaborative approach, and adapt systems, spaces, and methods will improve primary care access and delivery. Clinical trial number Not applicable.

The ecological landscape of Caribbean reefs is rapidly changing as octocorals fill the void left by declining scleractinian populations. Effective molecular barcodes are necessary to accurately identify these octocorals and monitor this shifting ecosystem. We tested the efficacy of the 28S rDNA as a barcode compared to the most commonly used mtMutS barcode on a collection of octocorals from across the Caribbean. Based on pairwise genetic distance values, 28S appeared to be more effective at differentiating species within the families Plexauridae and Gorgoniidae, while mtMutS was slightly more effective at distinguishing species of Pterogorgiidae. However, the standard 28S rDNA primers did not amplify all species as effectively as mtMutS, especially those belonging to the genus Eunicea. A shorter 28S barcode developed for eDNA applications distinguished species as effectively as the complete 28S barcode.

ABSTRACT: Increased transcription of genes involved in lactose synthesis is a key feature of secretory activation of the mammary gland. We determined which genes are transcriptionally regulated during the transition from colostrum to milk in cows and whether more frequent milking of one udder half would increase milk yields and alter gene expression. We enrolled 12 Holstein cows immediately after calving, harvested colostrum, then randomly assigned one udder half to 12-h (2X) or 6-h (4X) milking intervals for 48 h after first milking. After 48 h, all quarters were milked twice daily until d 7, when final quarter milk yields were collected. Yields and composition of colostrum and milk were recorded for each 12-h interval. After each milking, a strip sample of hind milk was collected for isolation of RNA from milk fat and quantification of selected transcripts via quantitative PCR. Milk, milk fat, total protein, and lactose yields increased significantly over the initial 48 h and at d7 after calving. Quarters on 4X treatment produced more milk than the contralateral 2X quarters. Genes upregulated concomitantly with milk yields encoded α-LA (LALBA), β-1,4-galactosyltransferase (B4GALT1), fatty acid synthase (FASN), β-CN (CSN2), and folate receptor α (FOLR1). Downregulated genes encoded monosaccharide transporters (SLC2A3, SLC2A8, SLC35A2) and enzymes involved in galactose synthesis (HK1, PGM1, GALE). Three genes were initially downregulated but later upregulated at d7 (LPIN1, SLC2A1, UGP2). Notably, milking frequency had no effect on gene expression. Sequential upregulation first of genes encoding the former enzymes, then of UGP2, may be necessary for copious milk production. However, the local effects of milking frequency on milk production during lactogenesis do not appear to be controlled by transcription of these genes related to lactose synthesis.

In the United States (US), biosafety and biosecurity oversight of research on viruses is being reappraised. Safety in virology research is paramount and oversight frameworks should be reviewed periodically. Changes should be made with care, however, to avoid impeding science that is essential for rapidly reducing and responding to pandemic threats as well as addressing more common challenges caused by infectious diseases. Decades of research uniquely positioned the US to be able to respond to the COVID-19 crisis with astounding speed, delivering life-saving vaccines within a year of identifying the virus. We should embolden and empower this strength, which is a vital part of protecting the health, economy, and security of US citizens. Herein, we offer our perspectives on priorities for revised rules governing virology research in the US.

Seasonal influenza results in 3 to 5 million cases of severe disease and 250,000 to 500,000 deaths annually. Macrophages have been implicated in both the resolution and progression of the disease, but the drivers of these outcomes are poorly understood. We probed mouse lung transcriptomic datasets using the Digital Cell Quantifier algorithm to predict immune cell subsets that correlated with mild or severe influenza A virus (IAV) infection outcomes. We identified a unique lung macrophage population that transcriptionally resembled small serosal cavity macrophages and whose presence correlated with mild disease. Until now, the study of serosal macrophage translocation in the context of viral infections has been neglected. Here, we show that pleural macrophages (PMs) migrate from the pleural cavity to the lung after infection with IAV. We found that the depletion of PMs increased morbidity and pulmonary inflammation. There were increased proinflammatory cytokines in the pleural cavity and an influx of neutrophils within the lung. Our results show that PMs are recruited to the lung during IAV infection and contribute to recovery from influenza. This study expands our knowledge of PM plasticity and identifies a source of lung macrophages independent of monocyte recruitment and local proliferation.

Background and objectivesCurative intent therapy is the standard of care for early-stage hepatocellular carcinoma (HCC). However, these therapies are under-utilized, with several treatment and survival disparities. We sought to demonstrate whether the type of facility and distance from treatment center (with transplant capabilities) contributed to disparities in curative-intent treatment and survival for early-stage HCC in California.MethodsWe performed a retrospective analysis of the California Cancer Registry for patients diagnosed with stage I or II primary HCC between 2005 and 2017. Primary and secondary outcomes were receipt of treatment and overall survival, respectively. Multivariable logistic regression and Multivariable Cox proportional hazards regression were used to evaluate associations.ResultsOf 19 059 patients with early-stage HCC, only 36% (6778) received curative-intent treatment. Compared to Non-Hispanic White patients, Hispanic patients were less likely, and Asian/Pacific Islander patients were more likely to receive curative-intent treatment. Our results showed that rural residence, public insurance, lower neighborhood SES, and care at non-National Cancer Institute-designated cancer center were associated with not receiving treatment and decreased survival.ConclusionsAlthough multiple factors influence receipt of treatment for early-HCC, our findings suggest that early intervention programs should target travel barriers and access to specialist care to help improve oncologic outcomes.

Abstract Retina-derived growth signals relayed from the choroid to the sclera cause remodeling of the extracellular scleral matrix, resulting in myopic ocular elongation. However, to the best of our knowledge, no studies have assessed changes in choroidal stromal biomechanical properties during myopia progression. Here we utilized 7 µm-resolution scanning acoustic microscopy (SAM) to assess biomechanical properties (bulk modulus (K) and mass density (rho)) of choroidal stroma from guinea pig eyes with form-deprivation (FD) induced myopia. The choroidal stroma had considerable intrinsic strength arising from its biomechanical properties and these were differentially affected by myopia in central and peripheral regions. Choroidal stromal biomechanical values were also highly correlated with those in adjacent scleral regions, and the choroidal stromal-scleral association was stronger in myopic eyes. Biomechanical changes observed in the choroidal stroma of myopic eyes were mirrored to those observed in the adjacent sclera. These findings suggest that choroidal stromal remodeling may accompany myopia and open the door to the source of the signals that cause scleral remodeling in myopia.

Abstract We report direct measurements of the magnetic field screening at the limits of the Meissner phase for two superconducting niobium (Nb) samples. The samples are processed with two different surface treatments that have been developed for superconducting radio-frequency (SRF) cavity applications—a “baseline” treatment and an oxygen-doping (“O-doping”) treatment. The measurements show: (1) that the screening length is significantly longer in the “O-doping” sample compared to the “baseline” sample; (2) that the screening length near the limits of the Meissner phase increases with applied field; (3) the evolution of the screening profile as the material transitions from the Meissner phase to the mixed phase; and (4) a demonstration of the absence of any screening profile for the highest applied field, indicative of the full flux entering the sample. Measurements are performed utilizing the $$\beta$$ β -detected nuclear magnetic resonance ( $$\beta$$ β -NMR) technique that allows depth resolved studies of the local magnetic field within the first 100 nm of the surface. The study takes advantage of the $$\beta$$ β -SRF beamline, a new facility at TRIUMF, Canada, where field levels up to 200 mT are available parallel to the sample surface to replicate radio frequency fields near the Meissner breakdown limits of Nb.

ABSTRACT On May 26, 2021, the European Medical Device Regulation (EU-MDR) entered into effect resulting in a major shift in the requirements for assessment of medical devices in Europe. The EU-MDR Cardiovascular Collaboratory (EU-MCVC) was founded to contribute to the development of faster, more efficient, and more effective pathways for innovation of cardiac medical devices. A registry is an organized system that collects uniform data and evaluates specified outcomes in a population defined by a disease, condition, or exposure. Most registries have been created to improve the quality of care and provide feedback to physicians, hospitals, and health providers. Clinical registries represent an ideal construct for scientific, clinical, and policy-making collaboration. We describe diverse experiences from 5 European countries and address the traditional quality components in clinical trials. Continued collaboration is expected among academics, clinical trialists, patient representatives, regulatory experts, research organizations, registry platforms, regulatory bodies, and industry partners. Data quality is a primary concern and registry leaders need to optimize data quality to become regulatory compliant. A collaborative approach among medical device stakeholders may improve quality of care, reduce costs, and provide faster access to innovative technologies, with the common objective of improving cardiovascular care and outcomes.

RESUMEN El 26 de mayo de 2021 entró en vigor el Reglamento Europeo de Productos Sanitarios (EU-MDR), que supuso un importante cambio en los requisitos de evaluación de los productos sanitarios en Europa. El EU-MDR Cardiovascular Collaboratory (EU-MCVC) se fundó con el fin de contribuir al desarrollo de vías más rápidas, eficientes y eficaces para la innovación de productos sanitarios cardiacos. Un registro es un sistema organizado que recoge datos uniformes y evalúa resultados específicos en una población definida por una enfermedad, afección o exposición. La mayoría de los registros se han desarrollado para mejorar la calidad de la atención y proporcionar información a médicos, hospitales y proveedores de servicios sanitarios. Los registros clínicos representan una construcción ideal para la colaboración científica, clínica y política. Describimos diversas experiencias de 5 países europeos y abordamos los componentes de calidad tradicionales en los ensayos clínicos. Se espera una colaboración continua entre académicos, especialistas en ensayos clínicos, representantes de pacientes, expertos en regulación, organizaciones de investigación, plataformas de registros, organismos reguladores y socios de la industria. La calidad de los datos es una preocupación primordial y los responsables de los registros deben optimizarla para cumplir con la normativa. Un enfoque colaborativo entre las partes interesadas en los dispositivos médicos puede mejorar la calidad de la atención, reducir los costes y proporcionar un acceso más rápido a tecnologías innovadoras, con el objetivo común de mejorar la atención y los resultados cardiovasculares.

Abstract Long-term synaptic plasticity is critical for adaptive function of the brain, but presynaptic mechanisms of functional plasticity remain poorly understood. Here, we show that changes in synaptic efficacy induced by activation of the cannabinoid type-1 receptor (CB1R), one of the most widespread G-protein coupled receptors in the brain, requires contractility of the neuronal actomyosin cytoskeleton. Specifically, using a synaptophysin-pHluorin probe (sypH2), we show that inhibitors of non-muscle myosin II (NMII) ATPase as well as one of its upstream effectors Rho-associated kinase (ROCK) prevent the reduction of synaptic vesicle release induced by CB1R activation. Using 3D STORM super-resolution microscopy, we find that activation of CB1R induces a redistribution of synaptic vesicles within presynaptic boutons in an actomyosin dependent manner, leading to vesicle clustering within the bouton and depletion of synaptic vesicles from the active zone. We further show, using sypH2, that inhibitors of NMII and ROCK specifically restore the release of the readily releasable pool of synaptic vesicles from the inhibition induced by CB1R activation. Finally, using slice electrophysiology, we find that activation of both NMII and ROCK is necessary for the long-term, but not the short-term, form of CB1R induced synaptic plasticity at excitatory cortico-striatal synapses. We thus propose a novel mechanism underlying CB1R-induced plasticity, whereby CB1R activation leads to a contraction of the actomyosin cytoskeleton inducing a reorganization of the functional presynaptic vesicle pool, preventing vesicle release and inducing long-term depression.

Rett syndrome (RTT) is a paediatric neurodevelopmental disorder spanning four developmental stages. This multi-system disorder offers a unique window to explore genotype–phenotype relationships in a disease model. However, genetic prognosticators of RTT have limited clinical value due to the disorder’s heterogeneity on multiple levels. This case report used a precision medicine approach to better understand the clinical phenotype of RTT twins with an identical pathogenic MECP2 mutation and discordant neurodevelopmental profiles. Targeted genotyping, objective physiological monitoring of heart rate variability (HRV) parameters, and clinical severity were assessed in a RTT twin pair (5 years 7 months old) with an identical pathogenic MECP2 mutation. Longitudinal assessment of autonomic HRV parameters was conducted using the Empatica E4 wristband device, and clinical severity was assessed using the RTT-anchored Clinical Global Impression Scale (RTT-CGI) and the Multi-System Profile of Symptoms Scale (MPSS). Genotype data revealed impaired BDNF function for twin A when compared to twin B. Twin A also had poorer autonomic health than twin B, as indicated by lower autonomic metrics (autonomic inflexibility). Hospitalisation, RTT-CGI-S, and MPSS subscale scores were used as measures of clinical severity, and these were worse in twin A. Treatment using buspirone shifted twin A from an inflexible to a flexible autonomic profile. This was mirrored in the MPSS scores, which showed a reduction in autonomic and cardiac symptoms following buspirone treatment. Our findings showed that a combination of a co-occurring rs6265 BDNF polymorphism, and worse autonomic and clinical profiles led to a poorer prognosis for twin A compared to twin B. Buspirone was able to shift a rigid autonomic profile to a more flexible one for twin A and thereby prevent cardiac and autonomic symptoms from worsening. The clinical profile for twin A represents a departure from the disorder trajectory typically observed in RTT and underscores the importance of wider genotype profiling and longitudinal objective physiological monitoring alongside measures of clinical symptoms and severity when assessing genotype–phenotype relationships in RTT patients with identical pathogenic mutations. A precision medicine approach that assesses genetic and physiological risk factors can be extended to other neurodevelopmental disorders to monitor risk when genotype–phenotype relationships are not so obvious.

Assessment of language skills for upper elementary and middle schoolers is important due to the strong link between language and reading comprehension. Yet, currently few practical, reliable, valid, and instructionally informative assessments of language exist. This study provides validation evidence for Monster, P.I., which is a gamified, standardized, computer-adaptive assessment (CAT) of language for fifth to eighth grade students. Creating Monster, P.I. involved an assessment of the dimensionality of morphology and vocabulary and an assessment of syntax. Results using multiple-group item response theory (IRT) with 3,214 fifth through eighth graders indicated morphology and vocabulary were best assessed via bifactor models and syntax unidimensionally. Therefore, Monster, P.I. provides scores on three component areas of language (multidimensional morphology and vocabulary and unidimensional syntax) with the goal of informing instruction. Validity results also suggest that Monster, P.I. scores show moderate correlations with each other and with standardized reading vocabulary and reading comprehension assessments. Furthermore, hierarchical regression results suggest an important link between Monster, P.I. and standardized reading comprehension, explaining between 56% and 75% of the variance. Such results indicate that Monster, P.I. can provide meaningful understandings of language performance which can guide instruction that can impact reading comprehension performance.