Early Time Research Articles

Abstract B013: Hallmarks of progression in early neoantigen-expressing lung adenocarcinoma

Abstract Lung adenocarcinoma (LUAD) is the leading cause of cancer-related mortality, largely due to its high prevalence rate and limited therapeutic options. Immunotherapy remains one of the most promising therapeutic avenues, yet further research is necessary to enhance therapy effectiveness for a broader range of patients. Central to the mechanism of immunotherapy is the detection of tumor neoantigens by cytotoxic T cells, which trigger the elimination of tumor cells. However, it is largely unknown how the early interaction between T cells and neoantigen-expressing tumor cells affects the acquisition of cancer hallmarks and tumor progression. To study this, our lab has developed the iNversion-INduced Joined neoAntigen (NINJA) genetically engineered mouse model in which we can initiate expression of a neoantigen in Kras-mutant, Trp53-null, tdTomato-expressing lung adenocarcinoma cells (KPT-NINJA). This system enables us to analyze tumor initiation, progression, and advanced LUAD development over 20 weeks in both neoantigen-expressing and non-expressing tumors. We defined cancer hallmark acquisition and tumor progression in our model by using a combination of multiplex immunofluorescence and computational algorithms to quantify tumor size, immune infiltration, metastasis, and expression of cancer molecular markers p-ERK and Ki67. We isolated tumor cell and immune cell subsets using neural networks to segment cells and tumor structures and used the colocalization of molecular markers to confirm the identity of various cell types. Our initial data validated that within immunogenic tumors there is an increase of T cell infiltration in tumors and have found immunogenic tumors are associated with overall smaller tumors at early time points. Interestingly, these tumors are associated with a decrease in p-ERK expression, suggesting immune infiltration is negatively correlated with p-ERK expression and tumor size. Together, these data indicate that increased immunogenic pressure may be disrupting early tumor proliferation and hallmark progression, shaping the trajectory of development at a very early stage. We are also correlating other molecular markers of tumor progression with immune infiltration, such as Ki67 expression, which we will colocalize with the other findings to construct a model of how tumors acquire hallmark capabilities from an immunogenic perspective. By isolating the mechanism of early tumor progression in immunogenic contexts, we can begin to predict disease trajectory. This will contribute to a better understanding of the mechanisms behind immune evasion and may uncover crucial insights to broaden immune therapy efficacy. Citation Format: Ishan Bansal, Jennifer Loza, Brian G. Hunt, Kelli Connolly, Srividhya Venkatesan, Nikhil Joshi. Hallmarks of progression in early neoantigen-expressing lung adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B013.

Quantum real-time evolution of entanglement and hadronization in jet production: Lessons from the massive Schwinger model

The possible link between entanglement and thermalization, and the dynamics of hadronization are addressed by studying the real-time response of the massive Schwinger model coupled to external sources. This setup mimics the production and fragmentation of quark jets, as the Schwinger model and quantum chromodynamics (QCD) share the properties of confinement and chiral symmetry breaking. By using simulations of quantum dynamics on classical hardware, we study the entanglement between the produced jets, and observe the growth of the corresponding entanglement entropy in time. This growth arises from the increased number of contributing eigenstates of the reduced density matrix with sufficiently large and close eigenvalues. We also investigate the physical nature of these eigenstates, and find that at early times they correspond to fermionic Fock states. We then observe the transition from these fermionic Fock states to mesonlike bound states as a function of time. In other words, we observe how hadronization develops in real time. At late times, the local observables at midrapidity (such as the fermion density and the electric field) approach approximately constant values, suggesting the onset of equilibrium and approach to thermalization. Published by the American Physical Society 2024

A Comparative Analysis of Bhumija-Style Gondeshwar Temple’s Acoustic Characteristics with Hemadpanti-Style Temples

ABSTRACT The study of the Hindu temple’s acoustics, acoustic characteristics, sound quality for clarity of music and speech intelligibility, and other applicable acoustic parameters must be addressed more in the literature. This study has conducted field measurements in Bhumija-style Gondeshwar temples in Nashik district, India. The temple has a distinctive tiered domed concave ceiling design in the pavilion and sanctum space and unique acoustic properties shaped by its architectural features. The research aims to report and investigate the acoustic characteristics through the well-known Impulse Response (IR) method to investigate empty temple conditions. A 3D model was imported and calibrated in ODEON 12.10 to compare scenarios when the worshippers were 100% present in the temple for various musical and chanting activities. Objective room-acoustic parameters such as Early Decay Time (EDT), Reverberation Time (T30), Clarity of Music (C80), Definition (D50), and Speech Transmission Index (STI) were measured and analyzed. The field measurements were also compared with previously studied Hemadpanti-style Hindu temples, such as the Markanda and Mrikunda temples. The results indicated that the tiered ceiling in Hemadpanti temples indicates a balance and moderate T30 values for all frequency ranges, as compared to the tiered concave domed ceiling in Bhumija-style Gondeshwar temple with higher T30 values observed at the lower frequency.

Reconstruction of 30 m Land Cover in the Qilian Mountains from 1980 to 1990 Based on Super-Resolution Generative Adversarial Networks

Long time series of annual land cover with fine spatio-temporal resolutions play a crucial role in studying environmental climate change, biophysical modeling, carbon cycling models, and land management. Despite a strong consistency exhibited by several publicly available medium to fine resolution global land cover datasets, significant discrepancies exist at the regional scale; moreover, only every 5/10 year land cover were available. Consequently, high-quality annual land cover datasets before 2000 are unavailable in China. In this study, we proposed a deep learning-based method by integrating multiple remote sensing data from different platforms with historical high spatial resolution land cover datasets (CNLUCC) to derive the 30 m annual land cover maps from 1980 to 1990 for Qilian Mountain. First, the super-resolution generative adversarial network models for upscaling the 5.5 km AVHRR NDVI to 250 m were established by employing the AVHRR and MODIS NDVI data with the same year as input, and the early time series AVHRR NDVI data were subsequently upscaled to 250 m through the above models. Second, the breaks for the additive seasonal and trend (BFAST) change detection algorithm was applied to the upscaled time series NDVI data to detect the change time of different land cover types. Third, the CNLUCC data in 1980 and 1990 were updated to annual land cover datasets from 1980 to 1990 and the annual mapping results provided insights into the dynamic processes of urbanization, deforestation, water bodies, and farmland from 1980 to 1990. Finally, comprehensive analysis and validation were carried out for evaluation and an overall accuracy of 77.26% for the land cover product in 1986 was achieved.

HPB SO10 - Evaluation of the impact of an Enhanced Recovery Pathway on clinical outcomes after Pancreaticoduodenectomy

Abstract Background Southampton General Hospital (SGH) is a high-volume HPB centre with a well-established Enhanced Recovery After Surgery pathway (ERAS). Despite the morbidity associated with pancreatic surgery, there is a large body of evidence supporting the use of a multi-modal approach to accelerate patient recovery. Within SGH, ERAS is utilised for all patients undergoing Pancreaticoduodenectomy (PD). Initial assessment of the pathway in SGH demonstrated a reduction in length of stay. Since its implementation, ERAS has been modified to optimise the pathway. The aim of this study was to assess whether the impact of ERAS had progressed over time. Method Single centre retrospective analysis of patients undergoing open PD from 2007-2023. Pancreatic reconstruction was with pancreaticojejunostomy. Pre and Post ERAS data were analysed. Post ERAS data was subdivided into Early, Middle and Late implementation time phases. Length of Stay, Complications (Clavien-Dindo Grade 3 and above), Readmissions and Mortality were all examined. Non-parametric data analysis was undertaken with Kruskal-Wallis, Spearman rank correlation and Wilcoxon rank-sum tests. Significance further assessed with Multi-variate regression (MVR). All Data were analysed using STATA. Results Overall, 861 patients underwent an open PD, the yearly volume increasing with time. Mean age was 66 years, which did not change with time. With ERAS implementation, Median Length of Stay (LOS) fell 13 to 9 days (p<0.01) and there was no statistically significant increase in Grade 3 complications or Readmissions (p=0.931, p=0.163). Grade 3 complications increased LOS (p<0.01). Increased age led to a small increase in LOS (p<0.01). Median LOS across Early, Middle and Late ERAS periods was 10, 9 and 9 respectively. LOS did not consistently demonstrate a statistically significant improvement across ERAS phases (MVR p=0.387, K-Wallis p<0.05). Conclusion The implementation of ERAS significantly reduced the median LOS for patients undergoing PD, without increasing their risk of complications or readmissions. This benefit has also been safely maintained across the period of its implementation.

Contextual Fear Conditioning Uncovers Spine and Learning Deficits in the Retrosplenial Cortex in a Familial Alzheimer’s Disease Mouse Model

While excitatory synapse loss is documented in the brains of Alzheimer’s Disease (AD) patients, its role in episodic learning decline, one of the first evident AD symptoms, is unclear. The retrosplenial cortex (RSC), a cortical structure required for episodic learning, provides an ideal entry point to study the role of synapse loss in cognitive decline in AD since it is a site of high amyloid load and dysfunctional early in AD progression. Further, excitatory synapse assembly, both turnover and clustered synapse formation, is highly correlated with episodic learning performance in the RSC. We hypothesize alterations in synapse assembly in the RSC of AD patients contribute to early cognitive decline in the disease. To address this hypothesis, we examined both excitatory synapse density in the RSC and contextual learning in a familial AD (fAD) mouse model, an early onset amyloid model of AD. Importantly, we find age-dependent excitatory synapse loss in the RSC of fAD mice, as measured by imaging and quantification of GFP-labeled dendritic spines. Further, prior to frank spine loss in 5-month-old fAD mice we found episodic learning deficits, as measured by contextual fear conditioning (CFC). Using this early time point, we examined spine dynamics in vivo with MP imaging in the RSC of fAD mice or controls while engaged in CFC learning. Interestingly, we find deficits both in spine turnover and clustered spine formation and a loss of correlations of these spine metrics with CFC performance, suggesting aberrant spine dynamics may be causal in episodic learning deficits in this AD model, consistent with our hypothesis. Future studies will pharmacologically target these aberrant spine dynamics in fAD mice in an effort to strengthen the causal link between alterations in synapse assembly and cognitive decline in AD as well as provide potential therapeutic approaches to reverse early stages of the disease.

Reinforcement of Oracle Bones Using a Novel Silicone Coupling Reagent for Preservation

Oracle bones are artifacts of great significance and value in the study of Chinese history and culture. Because of soil and bacterial erosion, bones become fragile, and the inscriptions on the surface become blurred, resulting in the loss of historical information on the bones. In early times, scholars often used adhesives for bonding and reinforcement, whereas in modern times, organic and inorganic materials have been used as reinforcement for oracle bones. In this study, the surface of oracle bone was protected and reinforced by a new silicone coupling reagent that could self-polymerize in the format of colorless solution with good antimicrobial properties. The DESPMA was applied to the surface of oracle bone by dropwise addition and curing, effectively protecting it from bacteria and slowing down the yellowing process. The results showed that the reagent could significantly improve the antimicrobial properties of bone samples and reduce the yellowing and discoloration caused by bacterial attack. The reagent barely affected the appearance of the bone samples. These findings are promising and valuable for effective application in bone protection and utilization.

CNSC-04. UNDERSTANDING PEDIATRIC BRAIN TUMOR CHEMOTHERAPY INDUCED LONG-TERM DEFICITS IN HIGH-ORDER NEUROCOGNITIVE AND SENSORIMOTOR FUNCTION

Abstract Because of major advancements in cancer treatment especially chemotherapy, 85% of children with cancer are predicted to survive for 5 years or more. However, chemotherapy can cause long-term health problems when childhood cancer survivors enter adulthood (known as late effects). The neurocognitive features of these late effects (chemobrain) include trouble in concentrating, memorizing, and decreased processing speed, and results in lower IQ and academic achievement, poor hand-eye coordination, and slower development over time. Despite such a negative impact on the quality of life of cancer-surviving children, the mechanism is poorly understood and there is no FDA-approved drug to prevent or cure these side effects. To gain a better understanding of the mechanism underlying chemotherapy-induced cognitive impairments, we developed a pre-clinical model using carboplatin in juvenile mice to study long-term neurological defects. Carboplatin is commonly used chemotherapy drug in pediatric brain tumor patients. We have tested the capacity of different doses of carboplatin and its long-term effect on cognitive and sensorimotor function and performed single nuclear RNA sequencing (snRNAseq) of the hippocampus. Our preliminary data demonstrated dose-dependent deficits in executive and sensorimotor function 7-9 weeks after carboplatin administration in the mice of both sexes. snRNAseq of the hippocampus showed changes in the glial cell number as well as genes associated with oxidative phosphorylation and neurodegeneration at early and late time points. Bioenergetics using Seahorse in the brain synaptosomes revealed mitochondrial dysfunction in the form of decreased maximum respiratory capacity long after carboplatin treatment. This study established a preclinical model that can be leveraged to mechanistically understand the long-term neurocognitive side effects of brain tumor chemotherapy during childhood. Future studies will aim to identify potential targets to prevent and/or treat the neurotoxic effects of cancer treatment in pediatric patients.

The cooler past of the intracluster medium in TNG-Cluster

Abstract The intracluster medium (ICM) today is comprised largely of hot gas with clouds of cooler gas of unknown origin and lifespan. We analyze the evolution of cool gas (temperatures ≲ 104.5 K) in the ICM of 352 galaxy clusters from the TNG-Cluster simulations, with present-day mass ∼1014.3 − 15.4 M⊙. We follow the main progenitors of these clusters over the past ∼13 billion years (since z ≲ 7) and find that, according to TNG-Cluster, the cool ICM mass increases with redshift at fixed cluster mass, implying that this cooler past of the ICM is due to more than just halo growth. The cool cluster gas at z ≲ 0.5 is mostly located in and around satellite galaxies, while at z ≳ 2 cool gas can also accrete via filaments from the intergalactic medium. Lower-mass and higher-redshift clusters are more susceptible to cooling. The cool ICM mass correlates with the number of gaseous satellites and inversely with the central supermassive black hole (SMBH) mass. The average number of gaseous satellites decreases since z = 2, correlating with the decline in the cool ICM mass over cosmic time, suggesting a link between the two. Concurrently, kinetic SMBH feedback shifts the ICM temperature distribution, decreasing the cool ICM mass inside-out. At z ≈ 0.5, the predicted Mg ii column densities are in the ballpark of recent observations, where satellites and other halos contribute significantly to the total Mg ii column density. Suggestively, a non-negligible amount of the ICM cool gas forms stars in-situ at early times, reaching ∼102 M⊙ yr−1 and an Hα surface brightness of ∼10−17 erg s−1 cm−2 arcsec−2 at z ≈ 2, detectable with Euclid and JWST.

Fitness of SARS-CoV-2 Omicron subvariants in respiratory and gastrointestinal cell lines as determined by RT-ddPCR and whole genome sequencing.

The fitness of SARS-CoV-2 Omicron subvariants was determined in human epithelial and continuous cells of the respiratory and gastrointestinal tracts. Competition experiments over 4 days were performed followed by quantification of variant ratios by reverse transcription-droplet digital PCR. These quantitative data were correlated with whole genome sequencing. In competition experiments of two subvariants, the more recent XBB.1 subvariant outcompeted the BA.1.15 subvariant at early time points in the upper respiratory tract epithelium. No difference in replication was observed between the two subvariants in the lower respiratory tract. Furthermore, XBB.1 predominated over BA.1.15 and JN.1.1 subvariants in the gastrointestinal tract.

Three-Dimensional Printed Customized Scaffolds Covered with Decellularized Bone Extracellular Matrix for Open-Wedge High-Tibial Osteotomy

Void fillers are required for osseous gaps generated after orthopedic procedures as medial open-wedge high-tibial osteotomy (MOWHTO) to provide sufficient structural support and a rapid osteosynthesis. We developed a novel three-dimensional (3D) printing-based platform technology using the customized 3D scaffolds covered with polycaprolactone (PCL)/β-tri-calcium phosphates (β-TCP)/bone decellularized extracellular matrix (dECM) for use as bone substitute scaffold, which can be effectively exploited to estimate the calculated correction angle with preoperative simulations. PCL/β-TCP/bone dECM scaffolds demonstrated significantly higher cell contain levels in cell seeding efficiency, excellent proliferation capacity, and promotion of early osteogenic differentiation compared with PCL/β-TCP scaffolds. The scaffolds promoted bone mineralization at the early time points of an in vivo study (8 weeks) and exhibited biodegradable properties (38% for 16 weeks). The correction angle measured after osteotomy using 3D printed scaffolds was estimated with high accuracy with low errors (10.3° ± 0.9°) and was not significantly different even in the presence of lateral cortical hinge fractures. The customized 3D scaffold enriched with PCL/β-TCP/bone dECM yielded excellent cell seeding efficiency, proliferation capacity, early osteogenic differentiation, and bone mineralization outcomes. It is expected to solve the disadvantages related to bone union in MOWHTO and to replace autografts in the future.

Ultrafast Excitonic Transitions in Enantiopure and Racemic Squaraine Thin Films

ABSTRACTWhile chirality is a prevalent character of numerous biological and synthetic organic molecules, its selective absorption of circularly polarized light, known as circular dichroism (CD), is typically small due to intrinsically weak coupling between magnetic and electric dipoles. However, thin films of aggregated, enantiopure prolinol‐derived squaraine molecules (ProSQ‐C16) exhibit an unusually large excitonic CD signal, although the underlying mechanism is not yet known. In this study, we employ steady‐state and ultrafast transient absorption spectroscopy to investigate the nature and dynamics of excitons in aggregates of enantiopure and racemic ProSQ‐C16 thin films. Highly resembling transient responses of enantiopure thin films under excitations at different photon energies strongly indicate that a single type of aggregate dominates the linear optical response, that is, a strong red‐shifted (J‐like) and weak blue‐shifted (H‐like) absorption band. On the other hand, the transient properties of the racemic thin film deviate from this pattern and remain largely ambiguous. The short lifetime of excited states and coherent oscillations present in the dynamics of the transient absorption signal indicate that the early time dynamics are governed by a transition towards a dark intermediate state, which might arise from intermolecular charge transfer with potential contributions from the coupling of excitons to the vibrations. This non‐radiative relaxation pathway explains the unusually weak fluorescence of the predominately J‐like behaving aggregate. Our findings conclusively show that the chiral aggregate structure has a strong impact on the optical and dynamic response of the excitons and underline the significance of non‐Frenkel exciton states for the optical properties of anilino squaraine dyes.

Irreducible cosmological backgrounds of a real scalar with a broken symmetry

We explore the irreducible cosmological implications of a singlet real scalar field. Our focus is on theories with an approximate and spontaneously broken Z2 symmetry where quasistable domain walls can form at early times. This seemingly simple framework bears a wealth of phenomenological implications that can be tackled by means of different cosmological and astrophysical probes. We elucidate the connection between domain wall dynamics and the production of dark matter and gravitational waves. In particular, we identify three main benchmark scenarios. The gravitational wave signal observed by pulsar timing arrays can be generated by the domain walls if the mass of the singlet is ms∼PeV. For lower masses, but with ms≳10 GeV, scalars produced in the annihilation of the domain walls can be dark matter with a distinctive feature in their power spectrum. Finally, the thermal bath provides an unavoidable source of unstable scalars via the freeze-in mechanism whose subsequent decays can be tested by their imprints on cosmological and terrestrial observables. Published by the American Physical Society 2024

Một số yếu tố ảnh hưởng đến thời gian nhập viện ở bệnh nhân nhồi máu não cấp

Object: Some factors affect hospitalization time in patients with acute cerebral infarctionMethod: Cross-sectional, retrospective descriptive study including 150 patients with acute cerebral infarction treated at the Neurology Center and Stroke Center, Bach Mai Hospital from January 2023 to December 2023.Result: The average hospital admission time was 661.5 minutes (11 hours); Only 26 patients were hospitalized early before 4.5 hours, accounting for 17.3%; Factors affecting the early hospitalization time of patients are high educational level (OR: 2.362; 95% CI [1.002-5.565]), daytime onset time (OR: 3.787; 95% CI [ 0.081-0.996]), having a witness at the time of symptom onset (OR: 5.928; 95% CI [1.336-26.308]), using ambulance transportation (OR: 32.445; 95% CI [9,916-106,223]), history of stroke or TIA (OR: 5.9; 95% CI [1.73-20,121]), recognition of symptoms of stroke (OR: 256.82; 95% CI [31] ,69-2081.44]) and knowledge of fibrinolytic drugs (OR: 83.18; 95% CI [16.81-411.69]); Factors affecting the patient's late hospitalization time include: distance to the hospital >15km (OR: 0.33; 95% CI [0.117-0.931]), admission to a front-line medical facility (OR: : 0.165; 95% CI [0.054-0.507]).Conclusion: Factors affecting the patient's early hospitalization time include: high educational level, time of illness onset during the day, presence of witnesses at the time of symptom onset, use of public transport ambulance, history of stroke or TIA, recognition of stroke symptoms and knowledge of thrombolytic drugs.

Current-vortex-sheet model of the magnetic Rayleigh-Taylor instability

This study investigates the Rayleigh-Taylor instability in the magnetic field applied parallel to the interface. The motion of the interface is described using a current-vortex-sheet model. The growth rate of the interface is obtained from a linear stability analysis of the model. The interface of a single mode k=1 is linearly stable for RA≤1, where RA denotes the Alfvén number. Further, we conduct numerical computations for the evolution of the interface from the model for both regimes of RA≤1 and RA>1. For RA≤1, the interface oscillates vertically but does not intrude into the opposite phase. The amplitude of the interface and the oscillation period decrease with decrease in RA. For 1<RA≲1.5, the interface undergoes some growth at early times and then decreases. This oscillation is repeated, and no roll-ups are observed at the interface. Therefore, the nonlinear growth of the Rayleigh-Taylor instability is stabilized by a sufficiently strong magnetic field. For RA≳3 the interface is unstable and the pattern of the interface evolution differs from the density ratio. In addition, the magnetic field is greatly amplified as RA increases. Published by the American Physical Society 2024

RECONSTRUCTION OF THE SUBSIDENCE DYNAMICS AND PALAEOTEMPERATURE REGIME OF THE NORTHERN MARGIN OF THE SIBERIAN PLATFORM

The formation mechanisms of sedimentary basins are considered as a response of deep processes in the mantle, therefore they carry important information about the geodynamics and thermal regime of the lithosphere. For different sectors of the northern margin of the Siberian Platform, the dynamics of sedimentation and subsidence was reconstructed. The analysis of subsidence curves shows that during the Late Paleozoic the sedimentary infill formed in the foreland basin environment. In the Late Permian–Early Triassic time, in the central and western sectors, the subsidence was accelerating due to the development of a thick trap complex; after the Permian and Triassic boundary the subsidence slowed down. During the period of trap magmatism, an anomalously high subsidence rate up to 4.8 km/Ma in the central and up to 0.5–1.1 km/Ma in the eastern and western parts was reconstructed. The high rate and short duration of accumulation of volcanogenic sediments can be explained by an episode of short-term extension under the influence of a plume, followed by a long period of thermal subsidence. Numerical modelling of the temperature regime near mafic intrusive bodies was carried out, which showed that when determining the paleoheat flow, the influence of trap intrusions can be traced up to 400–500 m from the contacts. Estimates of the paleoheat flow for the Permian–Triassic stage of tectonic evolution of the eastern sector were obtained. It was calibrated using the PetroMod software package, based on laboratory measurements of modern values of vitrinite reflectance for rock samples from wells, modern temperature and heat flow in the sedimentary cover. It was determined that trap magmatism occurred at temperatures increased to 100 mW/m2, while the mantle component of the heat flow reached 38–72 mW/m2; it is several times higher as compared to modern one. The obtained paleoheat flow estimates for the Late Permian–Early Triassic stage appear to correspond to anomalously high values of modern continental rifts.

Impact of time from symptom onset to puncture, and puncture to reperfusion, in endovascular therapy in the late time window (>6 hours).

Background- Increased times from symptom onset to puncture (TSOP) and from puncture to reperfusion (TPTR) are associated with worse outcome in ischemic stroke patients treated with endovascular therapy (EVT) in the early time window (<6 hours). However, these associations are less described in the late window (>6 hours), where patients may benefit from EVT because of a more favorable imaging profile (late window paradox). We sought to compare the effect of these timeframes between these two periods on efficacy and safety outcomes.Methods- The ETIS Registry (Endovascular Treatment in Ischemic Stroke) is an ongoing, prospective, observational study in 21 centers that perform EVT in France. We included adult patients with an anterior occlusion, successfully treated by EVT (mTICI 2b-3) between January 2015 and June 2023, with a known time of stroke onset. The cohort was divided into 2 groups according to the TSOP (≤6h vs >6h). Primary outcome was favorable outcome (modified Rankin Scale 0-2 at 90 days).Results- 7,516 patients were included, with 5,936 patients being treated ≤6h and 1,580 >6h. In the early window, TSOP and TPTR were associated with worse outcomes at 90 days (adjusted OR=0.68 per hour; 95%CI, 0.64-0.73; p<0.001 and aOR=0.92 per 10 minutes increment; 95%CI, 0.90-0.94, p<0.001, respectively). TSOP was not associated with worse outcomes at 90 days in the late window (p=0.955), but TPTR was associated with worse outcomes (aOR=0.91 per 10 minutes increment; 95%CI, 0.86-0.96, p=0.001), every 10 additional minutes in TPTR being associated with a 1.7% (95%CI, 0.6%-2.7%) decreased probability of favorable outcome.Conclusions- Only EVT procedural time is associated to unfavorable outcomes at 90 days in late window patients. These results highlight how the late window paradox may end at the start of EVT and underscore the need for timely management, particularly for the EVT, even for late window patients with a presumed more favorable imaging profile.

Comparative Analysis of Factors Influencing Optimal and Timely Antenatal Care Uptake in Kenya, South Africa, and Nigeria: A Cross-Section Study

Background Adequate antenatal care (ANC) visits and early timing are crucial for maternal and foetal health. However, many pregnant women in Kenya, South Africa, and Nigeria delay ANC initiation and fail to meet recommended visit numbers. This study aimed to identify factors associated with timely ANC initiation and achieving optimal number of ANC visits in these countries. Methods A cross-sectional analysis with data from the most recent Demographic Health Survey (DHS) datasets for Kenya (2022), Nigeria (2018) and South Africa (2016) were used. The study included 35,219 women aged 15–49 who had given birth within the previous two years. The women's sociodemographic and maternal health care-seeking characteristics were summarised using descriptive statistics. Multiple logistic regression was used to identify associations between explanatory variables, the timing of the first ANC visit, and the frequency of ANC visits. Results Optimal ANC visits (≥4 visits) were 67.2% in Kenya, South Africa (75.5%), and Nigeria (56.9%). Early timing of first ANC visits (≤3 months) was 30.2% in Kenya, 47.3% in South Africa and 18.3% in Nigeria. Factors associated with adequate ANC visits were maternal age, wealth status, and caesarean section, while parity and household size reduced the odds of optimal ANC visits. Maternal age, caesarean section, wealth status, and others were associated with increased odds of early timing of ANC visits. Parity, male-headed households, employed women and women who had a challenge with treatment costs had reduced the odds of timely ANC uptake. Conclusion More than half of the participants had optimal ANC visits, while less than half initiated ANC early. Tailored interventions addressing specific social, cultural, and economic contexts are crucial to improving early ANC visits and the frequency of ANC visits. Mixed methods research could provide in-depth insights into barriers and facilitators of ANC uptake, informing the design of targeted interventions.

Crimson Behemoth: A massive clumpy structure hosting a dusty AGN at z=4.91

Abstract The current paradigm for the co-evolution of galaxies and their supermassive black holes postulates that dust-obscured active galactic nuclei (AGNs) represent a transitional phase towards a more luminous and unobscured state. However, our understanding of dusty AGNs and their host galaxies at early cosmic times is inadequate due to observational limitations. Here, we present JWST observations of CID-931, an X-ray-detected AGN at a spectroscopic redshift of $z_{\rm spec}=4.91$. Multiband NIRCam imaging from the COSMOS-Web program reveals an unresolved red core, similar to JWST-discovered dusty AGNs. Strikingly, the red core is surrounded by at least eight massive star-forming clumps spread over ${1{^{\prime \prime}_{.}}6} \approx 10\,\,{\rm kpc}$, each of which has a stellar mass of $10^9$–$10^{10}\, M_{\odot }$ and a radius of $\sim$0.1–1 kpc. The whole system amounts to $10^{11}\, M_{\odot }$ in stellar mass, higher than typical star-forming galaxies at the same epoch. In this system, gas inflows and/or complex merger events may trigger clump formation and AGN activity, thus leading to the rapid formation of a massive galaxy hosting a supermassive black hole. Future follow-up observations will provide new insights into the evolution of the galaxy–black hole relationship during such transitional phases in the early universe.

Effect of Delaying High School Start Time on Teen Physical Activity, Screen Use, and Sports and Extracurricular Activity Participation: Results From START.

We aimed to characterize relationships between delayed high school start time policy, which is known to lengthen school night sleep duration, and patterns in activity outcomes: physical activity, non-school electronic screen time (non-schoolwork), and sports and extracurricular activity among adolescents. We used data from the START study, a multi-site evaluation of a natural experiment, assessing the effects of a school start time policy change in high schools in the Minneapolis, Minnesota metropolitan area. The study follows students in 2 schools that shifted to a later start time (8:20 or 8:50 am) after baseline year and 3 schools that maintained a consistent, early start time (7:30 am) over the 3-year study period. Activity was measured by participant self-report on an in-school survey. The analysis used a difference-in-differences estimator, in which the changes in each outcome observed in the comparison schools estimate the changes in each outcome that would have been observed in the late-start adopting schools had they not delayed their start times after baseline. Over 2 years of follow-up, no changes emerged to suggest that later school start times either interfered with, or promoted, any activity-related outcome that was measured. Communities interested in promoting sleep by delaying start times may do so knowing that there are unlikely to be adverse effects on adolescent physical activity, electronic screen time, or organized sports and activity participation. A shift to later school start times does not appear to enhance or detract from the healthfulness of students' activity level.