Large Core Research Articles

Projections of Endovascular Therapy-Eligible Patients With Stroke for the US Population.

As stroke endovascular thrombectomy (EVT) treatment indications expand, understanding population-based EVT eligibility becomes critical for resource planning. We aimed to project current and future population-based EVT eligibility in the United States. We conducted a post hoc analysis of the physician-adjudicated GCNKSS (Greater Cincinnati Northern Kentucky Stroke Study; 2015 epoch), a population-based, cross sectional, observational study of stroke incidence, treatment, and outcomes across a 5-county region. All hospitalized patients ≥18 years of age with acute ischemic stroke were ascertained using the International Classification of Diseases, Ninth Revision codes 430-436 and Tenth Revision codes I60-I67 and G45-G46 and extrapolated to the US adult census 2020. We determined the rate of EVT eligibility within the GCNKSS population using time from last known well to presentation (0-5 versus 5-23 hours), presenting National Institutes of Health Stroke Scale, and prestroke modified Rankin Scale. Both conservative and liberal estimates of prevalence of large vessel occlusion and large core were then applied based on literature review (unavailable within the 2015 GCNKSS). This eligibility was then extrapolated to the 2020 US population. Of the 1 057 183 adults within GCNKSS in 2015, 2741 had an ischemic stroke and 2176 had data available for analysis. We calculated that 8659 to 17 219 patients (conservative to liberal) meet the current guideline-recommended EVT criteria (nonlarge core, no prestroke disability, and National Institutes of Health Stroke Scale score ≥6) in the United States. Estimates (conservative to liberal) for expanded EVT eligibility subpopulations include (1) 5316 to 10 635 by large core; (2) 10 635 to 21 270 by mild presenting deficits with low National Institutes of Health Stroke Scale score; (3) 13 572 to 27 089 by higher prestroke disability; and (4) 7039 to 14 180 by >1 criteria. These expanded eligibility subpopulations amount to 36 562 to 73 174 patients. An estimated 8659 to 17 219 adult patients in the United States met strict EVT eligibility criteria in 2020. A 4-fold increase in population-based EVT eligibility can be anticipated with incremental adoption of recent or future positive trials. US stroke systems need to be rapidly optimized to handle all EVT-eligible patients with stroke.

TOI-837 b: Characterisation, formation, and evolutionary history of an infant warm Saturn-mass planet

Context. The detection and characterisation of planets younger than ~100 Myr offer the opportunity to get snapshots of systems immediately after their formation, where the main evolutionary processes that sculpt mature planetary systems are still ongoing. Known infant exoplanets are currently scarce, and dedicated surveys are required to increase their number. Aims. We aim to determine the fundamental properties of the ~35 Myr old star TOI-837 and its close-in Saturn-sized planet, and to investigate the system’s formation and evolutionary history. Methods. We analysed TESS photometry and HARPS spectroscopic data, measured stellar and planetary parameters, and characterised the stellar activity. We performed population synthesis simulations to track the formation history of TOI-837 b, and to reconstruct its possible internal structure. We investigated the planetary atmospheric evolution through photo-evaporation, and quantified the prospects for atmospheric characterisation with JWST. Results. TOI-837 b has similar radius, mass, and bulk density to those of Saturn (rb=9.71−0.60+0.93 R⊕, mb=116−18+17 M⊕, and ρb=0.68−0.18+0.20 g cm−3) and is on a primordial circular orbit. Population synthesis and early migration simulations suggest that the planet could have originally formed between 2 and 4 au, and have either a large and massive core, or a smaller Saturn-like core, depending on the opacity of the protoplanetary gas and on the growth rate of the core. We find that photo-evaporation produced negligible effects even at early ages (3–10 Myr). Transmission spectroscopy with JWST is very promising, and is expected to provide constraints on atmospheric metallicity and the abundances of H2O, CO2, and CH4 molecules, and to probe the presence of refractory elements. Conclusions. TOI-837 offers valuable prospects for follow-up observations, which are needed for a thorough characterisation. JWST will help to better constrain the formation and evolution history of the system, and to clarify whether or not TOI-837 b is a Saturn-analogue.

Exploring ischemic core growth rate and endovascular therapy benefit in large core patients.

After stroke onset, ischemic brain tissue will progress to infarction unless blood flow is restored. Core growth rate measures the infarction speed from stroke onset. This multicenter cohort study aimed to explore whether core growth rate influences benefit from the reperfusion treatment of endovascular thrombectomy in large ischemic core stroke patients. It identified 134 patients with large core volume >70 mL assessed on brain perfusion image within 9 hours of stroke onset. Of 134 patients, 71 received endovascular thrombectomy and 63 did not receive the treatment. Overall, poor outcomes were frequent, with 3-month severed disability or death rate at 56% in treatment group and 68% in no treatment group (p = 0.156). Patients were then stratified by core growth rate. For patients with 'ultrafast core growth' of >70 mL/hour, rates of poor outcome were especially high in patients without endovascular thrombectomy (n = 13/14, 93%) and relatively lower in patients received the treatment (n = 12/20, 60%, p = 0.033). In contrast, for patients with core growth rate <70 mL/hour, there was not a large difference in poor outcomes between patients with and without the treatment (55% vs. 61%, p = 0.522). Therefore, patients with 'ultrafast core growth' might stand to benefit the most from endovascular treatment.

Mechanical Thrombectomy in Ischemic Stroke with a Large Infarct Core: A Meta-Analysis of Randomized Controlled Trials.

Background/Objectives: Endovascular treatment (EVT) is recommended for acute ischemic stroke due to large-vessel occlusion (LVO) and an Alberta Stroke Program Early CT Score (ASPECTS) ≥ 6. Randomized controlled trials (RCTs) have recently become available on EVT effects in people with LVO-related large core stroke (ASPECTS 0-5). Here, we provide an updated meta-analysis of the EVT effect on functional neurological status in people with large-core stroke. Methods: The study followed the PRISMA guidelines. PubMed, EMBASE and Cochrane Central were searched for RCTs comparing EVT vs. best medical treatment (BMT) in large-core LVO stroke. The primary outcome was functional independence at 90 days (modified Rankin Scale; mRS 0-2). The secondary outcomes were symptomatic intracranial hemorrhage (sICH), good functional outcome (mRS 0-3) and excellent functional outcome (mRS 0-1). EVT vs. BMT was compared through random effect meta-analysis. Heterogeneity was assessed with the I2 and Q test and risk of bias reported according to the RoB2 tool. Results: Six RCTs were included (n = 1656 patients). All studies had a moderate risk of bias, with blinding bias due to the nature of the intervention, potential allocation bias and incomplete outcome reporting. Functional independence was significantly more frequent in the EVT vs. BMT group (OR = 2.47, 95% CI = 1.52-4.03, p < 0.001). sICH rates (OR = 1.77, 95% CI = 1.01-3.11, p = 0.04) and good functional outcome (OR = 2.20; 95% CI = 1.72-2.81, p < 0.001) were more frequent in the EVT vs. BMT group, while the rates of mRS 0-1 did not differ. Conclusions: In patients with large-core stroke and LVO, EVT plus BMT as compared to BMT alone carries a significant increase in independent ambulation and good functional outcome at 3 months despite the marginal increase in sICH.

Population genomics of emerging multidrug-resistant Salmonella derby from pork and human in Guangdong, China

Salmonella is a foodborne pathogen that poses a severe public health threat. Salmonella enterica serovar Derby (S. Derby) is one of the top five serovars isolated from humans and animals, and it carries the potential risk of transmission to humans through consumption of pork and related products. This study isolated 98 S. Derby, mainly from pork, and clinical samples in Guangdong to investigate and compare their molecular characteristics, phylogenetic relationships, transmission routes, antimicrobial resistance phenotypes, genotypes, and virulence profiles. Whole-genome sequencing (WGS) revealed that all S. Derby isolates belonged to ST40 and displayed a relatively large core genome. Phylogenomic analysis indicated the possibility of clonal transmission of S. Derby not only between pork and humans but also across geographic areas in Guangdong over an extended period of time. Discriminant analysis of principal components (DAPC) model showed that a significant proportion of S. Derby isolates retrieved from multiple hosts originated from pork. Furthermore, similar antimicrobial resistance phenotypes and genotypes were found in S. Derby strains recovered from animal products and humans. All S. Derby isolates were found to contain numerous virulence genes, primarily related to fimbrial adherence determinants and secretion system components. This study offers valuable insights into the transmission routes of S. Derby between pork and humans and provides essential data for public health management.

Endovascular therapy in patients with a large ischemic volume at presentation: An aggregate patient-level analysis

IntroductionRecently, four randomized controlled trials (RCTs) have demonstrated the benefits of mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) caused by anterior large vessel occlusion (LVO) and a large ischemic core at baseline (LIC). The purpose of this study was to investigate the features influencing the clinical outcome and the benefits of mechanical thrombectomy in this subgroup. MethodsWe conducted a multicenter retrospective aggregate cohort study of patients with AIS-LVO and a LIC, assessed with quantitative core volume measures, treated with MT between 2012 and 2019. The data were queried through four registries, including patients with core volumes ≥50cc. Multivariable logistic regression models were employed to determine factors independently associated with clinical outcomes in patients with successful recanalization (modified-Thrombolysis-in-Cerebral-Infarction-score, mTICI=2b-3) and unsuccessful recanalization group (mTICI=0–2a). The primary endpoint was a favorable functional outcome at day-90, defined as a modified Rankin scale (mRS) of 0–3, accounting for the inherent severity of AIS with baseline LIC. Secondary outcomes included functional independence (mRS 0–2) at day-90, mortality, and symptomatic Intracranial Hemorrhage (sICH). ResultsA total of 460 patients were included (mean age 66±14.2 years; 39.6 % females). The mean baseline NIHSS was 20±5.2, and the core volume was 103.2±54.6 ml. Overall, 39.8 % (183/460) of patients achieved a favorable outcome at day-90 (mRS 0–3). Successful recanalization was significantly associated with a more frequent favorable outcome (aOR, 4.79; 95 %CI, 2.73–8.38; P<0.01) and functional independence (P<0.01). This benefit remained significant in older patients and in patients with cores above 100cc. At 90 days, 147/460 patients (32 %) were deceased, with successful recanalization significantly associated with less frequent mortality (OR, 0.34; 95 %CI, 0.22–0.53; P<0.01). The rate of sICH was 17.4 % and did not differ significantly between groups. ConclusionsIn this large, pooled-cohort study of AIS-LVO patients with infarct cores over 50cc at baseline, we demonstrated that successful recanalization was associated with a better functional outcome, lower mortality, and similar rates of symptomatic intracranial hemorrhage for a wide spectrum of patients.

Numerical investigation gaseous ammonia basic jet and mixing characteristics in the constant volume vessel

Ammonia is considered a promising zero-carbon fuel under the dual-carbon targets. Systematically understanding ammonia's basic jet and mixing characteristics can promote its practical application in the engine field. Thus, a three-dimensional computational fluid dynamics (CFD) model of constant volume vessel (CVV) is established in this paper, and the forecasting abilities of the Large Eddy Simulation (LES) and Reynolds-Averaged Navier-Stokes (RANS) models for the gaseous ammonia jet process are compared based on the experimental data. Then, the ammonia jet development rule and mixing characteristics under different ambient temperatures, ambient pressures, and fuel temperatures are investigated. The variation laws of key data such as penetration distance, jet area, ammonia mass concentration distribution, equivalence ratio, and turbulent kinetic energy are obtained and analyzed. The results show that during the injection process, the airflow on the left and right sides of the jet rotates in opposite directions. A higher temperature and lower pressure within the CVV lead to a larger flammable range for ammonia jets. Moreover, the distribution of ammonia mass concentration on the radial plane shows a dynamic development law with time, meaning that it first increases to a maximum value, then gradually decreases, and finally remains stable. The farther the radial plane is from the nozzle outlet position, the lower the ammonia mass concentration. In addition, the ammonia jet's turbulent kinetic energy has a large core region and symmetrical distribution along the central axis. At the beginning of the injection, the core length is small, gradually increasing with time and finally stabilizing.

Radial reflector macroscopic cross sections preparation impact on the low neutron leakage core Beavrs

Full core nodal calculations are essential for safe nuclear power plant operation. The accuracy and compliance with the calculation and the experiment are based on the proper macroscopic data preparation model. While fuel assembly data preparation is usually based on the simple infinite lattice model simulation, the reflector data preparation is not standardised and the influence of the reflector macroscopic data on full core simulation is not quantified. The paper evaluates the large core with low neutron leakage behaviour with the different reflector cross section preparation models with respect to criticality and power distribution prediction. However, in opposition to the first insight, the different reflector model cannot increase the compliance with the power prediction near the fuel assembly reflector boundary. However, the usage of a special rehomogenization model can be helpful for pin power reconstruction compliance near the edge of the core.

Functional Outcome and Hemorrhage Rates After Bridging Therapy With Tenecteplase or Alteplase in Patients With Large Ischemic Core.

IV tenecteplase is an alternative to alteplase before mechanical thrombectomy (MT) in patients with large-vessel occlusion (LVO) ischemic stroke. Little data are available on its use in patients with large ischemic core. We aimed to compare the efficacy and safety of both thrombolytics in this population. We conducted a retrospective analysis of patients with anterior circulation LVO strokes and diffusion-weighed imaging Alberta Stroke Program Early CT Score (DWI-ASPECTS) ≤5 treated with tenecteplase or alteplase before MT from the TETRIS (tenecteplase) and ETIS (alteplase) French multicenter registries. Primary outcome was reduced disability at 3 months (ordinal analysis of the modified Rankin scale [mRS]). Safety outcomes were 3-month mortality, parenchymal hematoma (PH), and symptomatic intracranial hemorrhage (sICH). We used propensity score overlap weighting to reduce baseline differences between treatment groups. We analyzed 647 patients (tenecteplase: n = 194; alteplase: n = 453; inclusion period 2015-2022). Median (interquartile range) age was 71 (57-81) years, with NIH Stroke Scale score 19 (16-22), DWI-ASPECTS 4 (3-5), and last seen well-to-IV thrombolysis and puncture times 165 minutes (130-226) and 260 minutes (203-349), respectively. After MT, the successful reperfusion rate was 83.1%. After propensity score overlap weighting, all baseline variables were well balanced between both treatment groups. Compared with patients treated with alteplase, patients treated with tenecteplase had better 3-month mRS (common odds ratio [OR] for reduced disability: 1.37, 1.01-1.87, p = 0.046) and lower 3-month mortality (OR 0.52, 0.33-0.81, p < 0.01). There were no significant differences between thrombolytics for PH (OR 0.84, 0.55-1.30, p = 0.44) and sICH incidence (OR 0.70, 0.42-1.18, p = 0.18). Our data are encouraging regarding the efficacy and reassuring regarding the safety of tenecteplase compared with that of alteplase in bridging therapy for patients with LVO strokes and a large ischemic core in routine clinical care. These results support its consideration as an alternative to alteplase in bridging therapy for patients with large ischemic cores. NCT03776877 (ETIS registry) and NCT05534360 (TETRIS registry). This study provides Class III evidence that patients with anterior circulation LVO stroke and DWI-ASPECTS ≤5 treated with tenecteplase vs alteplase before MT experienced better functional outcomes and lower mortality at 3 months.

Self-Interacting Dark Matter Solves the Final Parsec Problem of Supermassive Black Hole Mergers.

Evidence for a stochastic gravitational wave (GW) background, plausibly originating from the merger of supermassive black holes (SMBHs), is accumulating with observations from pulsar timing arrays. An outstanding question is how inspiraling SMBHs get past the "final parsec" of separation, where they have a tendency to stall before GW emission alone can make the binary coalesce. We argue that dynamical friction from the dark matter (DM) spike surrounding the black holes is sufficient to resolve this puzzle, if the DM has a self-interaction cross section of order cm^{2}/g. The same effect leads to a softening of the GW spectrum at low frequencies as suggested by the current data. For collisionless cold DM, the friction deposits so much energy that the spike is disrupted and cannot bridge the final parsec, while for self-interacting DM, the isothermal core of the halo can act as a reservoir for the energy liberated from the SMBH orbits. A realistic velocity dependence, such as generated by the exchange of a massive mediator like a dark photon, is favored to give a good fit to the GW spectrum while providing a large enough core. A similar velocity dependence has been advocated for solving the small-scale structure problems of cold DM.

Effect of intravenous thrombolysis before endovascular therapy on outcomes in acute ischemic stroke with large core: a systematic review and meta-analysis.

To investigate the effect of intravenous thrombolysis (IVT) before endovascular therapy (EVT) on outcomes in acute ischemic stroke of large core. The studies comparing functional outcomes after EVT with and without IVT were systematically searched up to October 10th, 2023. Odds ratio (OR) was pooled using random effects model. Subgroup analysis was performed stratified by study design, country or region, study date, imaging methods and time window. Thirteen studies were included, enrolling 1717 patients. The pooled rate of functional independence in patients receiving IVT + EVT was 26% (95% CI 20% - 33%), significantly higher than 18% (95% CI 15% - 20%) in those receiving EVT alone (OR 1.55, 95% CI 1.13-2.12, P = 0.006; I²= 23.9%). In subgroup analysis, prior IVT increased the probability of functional independence in retrospective studies (OR 1.97, 95% 1.47-2.63, P < 0.00001; I2 = 0). Non-Asian patients benefit from IVT before EVT for functional independence (OR 2.04, 95% 1.48-2.81, P < 0.0001; I2 = 0), but Asian patients did not (OR 1.45, 95% 0.90-2.35, p = 0.13; I2 = 0). The pooled rate of symptomatic intracranial hemorrhage in patients receiving IVT + EVT was 16% (95% CI 12% - 20%), inclining to be higher than 11% (95% CI 6% - 15%) in those receiving EVT alone without significant difference (OR 1.42, 0.83-2.41, P = 0.20; I²= 12%). IVT before EVT might increase the probability of functional independence in non-Asian patients with large ischemic core. The results provided clinicians with additional information on selecting eligible patients for EVT.

Endovascular thrombectomy for ischemic stroke with large infarct, short- and long-term outcomes: a meta-analysis of 6 randomised control trials.

Endovascular Thrombectomy (EVT) as first-line treatment of patients with large core ischemic infarct is a subject of debate. A systematic literature search was conducted in four electronic databases for randomized control trials (RCTs) comparing EVT to best medical treatment (BMT) for large core infarcts (ASPECTS ≤ 5). Relevant studies were added after screening for titles, abstracts, and complete text. Meta-analysis was performed. The continuous outcomes were analyzed using the standardized mean difference (SMD) and 95% CI, while the binary outcomes were analyzed using the risk ratio (RR) and 95% confidence interval (CI). A funnel plot was used to visually evaluate publication bias, and if feasible, Egger's test was used to validate. We included 1918 patients from six RCTs that compared EVT plus BMT and BMT alone in patients with large core infarct due to large vessel occlusion in the anterior circulation. There were 946 patients in the EVT group and 972 patients in the BMT group. The one-year outcomes are available for 314 patients in the EVT group and 292 patents in the BMT group from two RCTs. EVT group had statistically significant higher rate of 90-day mRS 0-1 (RR = 3.1, P-value < 0.0001), mRS 0-2 (RR = 2.64, P-value < 0.0001), mRS 0-3 (RR = 1.80, P-value < 0.0001), lower 90-day mean mRS score (SMD = -0.29, P-value < 0.0001), lower 90-day mortality rate (RR = 0.85, P-value = 0.015), and greater early neurological improvement (RR = 2.16, P-value < 0.00001) compared to the BMT group. However, the rates of symptomatic intracerebral hemorrhage (sICH) (RR = 1.76, P-value = 0.01) and any ICH (RR = 2.18, P-value < 0.00001) were higher in EVT group. Our finding showed that EVT plus BMT led to in an absolute improvement of 5%, 12%, and 16% in 90-day mRS 0-1, 0-2, and 0-3, respectively. In addition, patients in EVT plus BMT group had a 3% increased probability of experiencing sICH and were 32% more susceptible to any ICH. Moreover, the one-year mRS 0-2 (RR = 2.16, P-value < 0.00001) and mRS 0-3 (RR = 1.80, P-value < 0.0001) was significantly favor the EVT plus BMT over BMT alone. Although, the one-year mortality rate was not significantly differed between two groups (RR = 0.91, P-value = 0.31). There was no statistically significant difference observed between the EVT plus BMT group and the BMT group concerning new stroke, decompressive craniectomy, and serious adverse events. Combined data from six RCTs shows that EVT plus BMT provides significantly better short- and long-term functional outcomes with minimal increase in symptomatic hemorrhage over BMT in patient with large core infarcts.

AC-ASPECTS, ACh-ASPECTS, and H-ASPECTS: new imaging scales to assess territorial and total cerebral hemispheric ischemic injury.

The extent of ischemic injury in acute stroke is assessed in clinical practice using the Acute Stroke Prognosis Early CT Score (ASPECTS) rating system. However, current ASPECTS semi-quantitative topographic scales assess only the middle cerebral artery (MCA) (original ASPECTS) and posterior cerebral (PC-ASPECTS) territories. For treatment decision-making in patients with anterior cerebral artery (ACA) occlusions and internal carotid artery (ICA) occlusions with large ischemic cores, measures of all hemispheric regions are desirable. In this cohort study, anatomic rating systems were developed for the anterior cerebral (AC-ASPECTS, 3 points) and anterior choroidal artery (ACh-ASPECTS, 1 point) territories. In addition, a total supratentorial hemisphere (H-ASPECTS, 16 points) score was calculated as the sum of the MCA ASPECTS (10 regions), supratentorial PC-ASPECTS (2 regions), AC-ASPECTS (3 regions), and ACh-ASPECTS (1 region). Three raters applied these scales to initial and 24 h CT and MR images in consecutive patients with ischemic stroke (IS) due to ICA, M1-MCA, and ACA occlusions. Imaging ratings were obtained for 96 scans in 50 consecutive patients with age 74.8 (±14.0), 60% female, NIHSS 15.5 (9.25-20), and occlusion locations ICA 34%; M1-MCA 58%; and ACA 8%. Treatments included endovascular thrombectomy +/- thrombolysis in 72%, thrombolysis alone in 8%, and hemicraniectomy in 4%. Among experienced clinicians, inter-rater reliability for AC-, ACh-, and H-ASPECTS scores was substantial (kappa values 0.61-0.80). AC-ASPECTS abnormality was present in 14% of patients, and ACh-ASPECTS abnormality in 2%. Among patients with ACA and ICA occlusions, H-ASPECTS scores compared with original ASPECTS scores were more strongly associated with disability level at discharge, ambulatory status at discharge, discharge destination, and combined inpatient mortality and hospice discharge. AC-ASPECTS, ACh-ASPECTS, and H-ASPECTS expand the scope of acute IS imaging scores and increase correlation with functional outcomes. This additional information may enhance prognostication and decision-making, including endovascular thrombectomy and hemicraniectomy.

Structural basis of the human transcriptional Mediator complex modulated by its dissociable Kinase module.

The eukaryotic Mediator, comprising a large Core (cMED) and a dissociable CDK8 kinase module (CKM), regulates RNA Polymerase II (Pol II)-dependent transcription. cMED recruits Pol II and promotes pre-initiation complex (PIC) formation in a manner inhibited by the CKM, which is also implicated in post-initiation control of gene expression. Herein we report cryo-electron microscopy structures of the human complete Mediator and its CKM, which explains the basis for CKM inhibition of cMED-activated transcription. The CKM binds to cMED through an intrinsically disordered region (IDR) in MED13 and HEAT repeats in MED12. The CKM inhibits transcription by allocating its MED13 IDR to occlude binding of Pol II and MED26 to cMED and further obstructing cMED-PIC assembly through steric hindrance with TFIIH and the +1 nucleosome. Notably, MED12 binds to the cMED Hook, positioning CDK8 downstream of the transcription start site, which sheds new light on its stimulatory function in post-initiation events.

Association of Mismatch Profiles and Clinical Outcome from Endovascular Therapy in Large Infarct: A Post-Hoc Analysis of the ANGEL-ASPECT Trial.

We investigated whether patients with large infarct and the presence or absence of perfusion mismatch are associated with endovascular treatment benefit. This is a post-hoc analysis of the Endovascular Therapy in Anterior Circulation Large Vessel Occlusion with a Large Infarct (ANGEL-ASPECT) randomized trial, which enrolled patients within 24 hours of onset with ASPECTS 3 to 5 or ASPECTS 0 to 2 with an infarct core 70 to 100 ml. Mismatch ratio was defined as time-to-maximum (Tmax) >6 s cerebral volume/ischemic core volume, and mismatch volume was defined as Tmax >6 s volume minus ischemic core volume. We divided patients into mismatch ratio ≥1.2 and mismatch volume ≥10 ml, and mismatch ratio ≥1.8 and mismatch volume ≥15 ml groups. The primary outcome was the 90-day modified Rankin Scale score ordinal distribution. Safety outcomes were symptomatic intracranial hemorrhage and 90-day mortality. There were 425 patients included. In both the mismatch ratio ≥1.2 and mismatch volume ≥10 ml (mismatch+, n = 395; mismatch-, n = 31) and mismatch ratio ≥1.8 and mismatch volume ≥15 ml groups (mismatch+, n = 346; mismatch-, n = 80), better 90-day modified Rankin Scale outcomes were found in the endovascular treatment group compared with the MM group (4 [2-5] vs 4 [3-5], common odds ratio [cOR], 1.9, 95% confidence interval [CI] 1.3-2.7, p = 0.001; 4 [2-5] vs 4 [3-5], cOR, 1.9, 95% CI 1.3-2.8, p = 0.001, respectively), but not in patients without mismatch ratio ≥1.2 and mismatch volume ≥10 ml (5 [3-6] vs 5 [4-6], cOR, 1.2, 95% CI 0.3-4.1, p = 0.83), and mismatch ratio ≥1.8 and mismatch volume ≥15 ml (4 [3-6] vs 5 [3-6], cOR, 1.2, 95% CI 0.6-2.7, p = 0.60). However, no interaction effect was found in both subgroups (p interaction >0.10). Endovascular treatment was more efficacious than MM in patients with mismatch profiles, but no treatment effect or interaction was noted in the no mismatch profile patients. However, the small sample size of patients with no mismatch may have underpowered our analysis. A pooled analysis of large core trials stratified by mismatch is warranted. ANN NEUROL 2024.

Assessing forest fragmentation due to land use changes from 1992 to 2023: A spatio-temporal analysis using remote sensing data

The increasing pressures of urban development and agricultural expansion have significant implications for land use and land cover (LULC) dynamics, particularly in ecologically sensitive regions like the Murree and Kotli Sattian tehsils of the Rawalpindi district in Pakistan. This study's primary objective is to assess spatial variations within each LULC category over three decades (1992–2023) using cross-tabulation in ArcGIS to identify changes in LULC and investigates into forest fragmentation analysis using the Landscape Fragmentation Tool (LFTv2.0) to classify forest into several classes such as patch, edge, perforated, small core, medium core, and large core. Utilizing remote sensing data from Landsat 5 and Landsat 9 satellites, the research focuses on the temporal dynamics in various land classes including Coniferous Forest (CF), Evergreen Forest (EF), Arable Land (AR), Buildup Area (BU), Barren Land (BA), Water (WA), and Grassland (GL). The Support Vector Machine (SVM) classifier and ArcGIS software were employed for image processing and classification, ensuring accuracy in categorizing different land types. Our results indicate a notable reduction in forested areas, with Coniferous Forest (CF) decreasing from 363.9 km2, constituting 45.0 % of the area in 1992, to 291.5 km2 (36.0 %) in 2023, representing a total decrease of 72.4 km2. Similarly, Evergreen Forests have also seen a significant reduction, from 177.9 km2 (22.0 %) in 1992 to 99.8 km2 (12.3 %) in 2023, a decrease of 78.1 km2. The study investigates into forest fragmentation analysis using the Landscape Fragmentation Tool (LFTv2.0), revealing an increase in fragmentation and a decrease in large core forests from 20.3 % of the total area in 1992 to 7.2 % in 2023. Additionally, the patch forest area increased from 2.4 % in 1992 to 5.9 % in 2023, indicating significant fragmentation. Transition matrices and a Sankey diagram illustrate the transitions between different LULC classes, providing a comprehensive view of the dynamics of land-use changes and their implications for ecosystem services. These findings highlight the critical need for robust conservation strategies and effective land management practices. The study contributes to the understanding of LULC dynamics and forest fragmentation in the Himalayan region of Pakistan, offering insights essential for future land management and policymaking in the face of rapid environmental changes.

Presynaptic sensor and silencer of peptidergic transmission reveal neuropeptides as primary transmitters in pontine fear circuit

Neurons produce and release neuropeptides to communicate with one another. Despite their importance in brain function, circuit-based mechanisms of peptidergic transmission are poorly understood, primarily due to the lack of tools for monitoring and manipulating neuropeptide release invivo. Here, we report the development of two genetically encoded tools for investigating peptidergic transmission in behaving mice: a genetically encoded large dense core vesicle (LDCV) sensor that detects presynaptic neuropeptide release and a genetically encoded silencer that specifically degrades neuropeptides inside LDCVs. Using these tools, we show that neuropeptides, not glutamate, encode the unconditioned stimulus in the parabrachial-to-amygdalar threat pathway during Pavlovian threat learning. We also show that neuropeptides play important roles in encoding positive valence and suppressing conditioned threat response in the amygdala-to-parabrachial endogenous opioidergic circuit. These results show that our sensor and silencer for presynaptic peptidergic transmission are reliable tools to investigate neuropeptidergic systems in awake, behaving animals.

Impact of first pass effect in endovascular treatment of large core stroke: a post-hoc analysis of the ANGEL-ASPECT trial

BackgroundThe first-pass effect (FPE) is linked to better safety and efficacy prognosis in patients with small- to- moderate sized ischemic infarctions. We evaluated the incidence, prognosis, and predictors of FPE...

Halogenated Dibenzo[f,h]quinoxaline Units Constructed 2D-Conjugated Guest Acceptors for 19% Efficiency Organic Solar Cells.

Halogenation of Y-series small-molecule acceptors (Y-SMAs) is identified as an effective strategy to optimize photoelectric properties for achieving improved power-conversion-efficiencies (PCEs) in binary organic solar cells (OSCs). However, the effect of different halogenation in the 2D-structured large π-fused core of guest Y-SMAs on ternary OSCs has not yet been systematically studied. Herein, four 2D-conjugated Y-SMAs (X-QTP-4F, including halogen-free H-QTP-4F, chlorinated Cl-QTP-4F, brominated Br-QTP-4F, and iodinated I-QTP-4F) by attaching different halogens into 2D-conjugation extended dibenzo[f,h]quinoxaline core are developed. Among these X-QTP-4F, Cl-QTP-4F has a higher absorption coefficient, optimized molecular crystallinity and packing, suitable cascade energy levels, and complementary absorption with PM6:L8-BO host. Moreover, among ternary PM6:L8-BO:X-QTP-4F blends, PM6:L8-BO:Cl-QTP-4F obtains a more uniform and size-suitable fibrillary network morphology, improved molecular crystallinity and packing, as well as optimized vertical phase distribution, thus boosting charge generation, transport, extraction, and suppressing energy loss of OSCs. Consequently, the PM6:L8-BO:Cl-QTP-4F-based OSCs achieve a 19.0% efficiency, which is among the state-of-the-art OSCs based on 2D-conjugated Y-SMAs and superior to these devices based on PM6:L8-BO host (17.70%) and with guests of H-QTP-4F (18.23%), Br-QTP-4F (18.39%), and I-QTP-4F (17.62%). The work indicates that halogenation in 2D-structured dibenzo[f,h]quinoxaline core of Y-SMAs guests is a promising strategy to gain efficient ternary OSCs.

Thermal and magnetic evolution of Mercury with a layered Fe-Si(-S) core

Elucidating the structure and composition of Mercury is important for understanding its interior dynamics and evolution. The planet is characterised by unusual chemical characteristics and a weak magnetic field generated in a large metallic core, and its early evolution was also marked by the presence of a magnetic field, widespread volcanism and global contraction. Here we develop a parameterised model of coupled core-mantle thermal and magnetic evolution considering a layered Fe-Si(-S) core structure with chemical and physical properties of the mantle and the core based on previous laboratory studies. We seek successful solutions that are consistent with observations of Mercury's long-lived dynamo, total global contraction, present-day crustal thickness, and present-day interior structure. Successful solutions have a mantle reference viscosity >1021 Pa s (corresponding to a present-day bulk mantle viscosity >2×1020 Pa s), a silicon concentration in the core >13 wt%, a present inner core radius of ∼1000−1200 km and a thermally stable layer ∼ 500−800 km thick below the core-mantle boundary. Our results show that if present, a molten FeS layer atop the core has minimal effect on Mercury's long-term thermal and magnetic evolution. Predictions from our models can be tested with upcoming Bepi-Colombo observations.