The association between infarct location and hemorrhagic transformation of acute ischemic stroke after mechanical thrombectomy is not understood. We aimed to evaluate the association between ...CTP-based ischemic core variables at admission and hemorrhagic transformation after a successful thrombectomy.
We retrospectively analyzed patients who underwent endovascular thrombectomy for acute anterior circulation large-vessel occlusion between October 2019 and June 2021. We enrolled 146 patients with visible ischemic core on pretreatment CTP who had successful reperfusion. The ischemic core infarct territories were classified into the cortical and subcortical areas and then qualitatively and quantitatively analyzed by CTP. Logistic regression and receiver operating characteristic curve analyses were performed to determine the association between ischemic core variables and hemorrhagic transformation.
Of the 146 patients analyzed, 72 (49.3%) had hemorrhagic transformation and 23 (15.8%) had symptomatic intracerebral hemorrhage. Multivariate analysis showed that subcortical infarcts were independently associated with hemorrhagic transformation (OR, 8.06; 95% CI, 2.31-28.10;
= .001) and subcortical infarct volume was independently linked to symptomatic intracerebral hemorrhage (OR, 1.05; 95% CI, 1.01-1.09;
= .039). The receiver operating characteristic curve indicated that subcortical infarcts can predict hemorrhagic transformation accurately (area under the curve = 0.755; 95% CI, 0.68-0.82;
< .001) and subcortical infarct volume can predict symptomatic intracerebral hemorrhage (area under the curve = 0.694; 95% CI, 0.61-0.77;
= .002).
Subcortical infarcts seen on CTP at admission are associated with hemorrhagic transformation in patients after successful thrombectomy, and subcortical infarct volume may influence the risk of symptomatic intracerebral hemorrhage.
A simple, efficient scheme was developed to obtain near-gigaelectronvolt electron beams with energy spreads of few per-mille level in a single-stage laser wakefield accelerator. Longitudinal plasma ...density was tailored to control relativistic laser-beam evolution, resulting in injection, dechirping, and a quasi-phase-stable acceleration. With this scheme, electron beams with peak energies of 780–840 MeV, rms energy spreads of 2.4‰–4.1‰, charges of 8.5–23.6 pC, and rms divergences of 0.1–0.4 mrad were experimentally obtained. Quasi-three-dimensional particle-in-cell simulations agreed well with the experimental results. The dechirping strength was estimated to reach up to 11 TeV/mm/m, which is higher than previously obtained results. Such high-quality electron beams will boost the development of compact intense coherent radiation sources and x-ray free-electron lasers.
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Spinocerebellar ataxia (SCA) comprises a large group of heterogeneous neurodegenerative disorders inherited in an autosomal dominant fashion. It is characterized by progressive cerebellar ataxia with ...oculomotor dysfunction, dysarthria, pyramidal signs, extrapyramidal signs, pigmentary retinopathy, peripheral neuropathy, cognitive impairment and other symptoms. It is classified according to the clinical manifestations or genetic nosology. To date, 40 SCAs have been characterized, and include SCA1–40. The pathogenic genes of 28 SCAs were identified. In recent years, with the widespread clinical use of next‐generation sequencing, the genes underlying SCAs, and the mutants as well as the affected phenotypes were identified. These advances elucidated the phenotype–genotype relationship in SCAs. We reviewed the recent clinical advances, genetic features and phenotype–genotype correlations involving each SCA and its differentiation. The heterogeneity of the disease and the genetic diagnosis might be attributed to the regional distribution and clinical characteristics. Therefore, recognition of the phenotype–genotype relationship facilitates genetic testing, prognosis and monitoring of symptoms.
Abstract
We use state-of-the-art chemical models to track the cosmic evolution of the CNO isotopes in the interstellar medium of galaxies, yielding powerful constraints on their stellar initial mass ...function (IMF). We re-assess the relative roles of massive stars, asymptotic giant branch (AGB) stars and novae in the production of rare isotopes such as 13C, 15N, 17O and 18O, along with 12C, 14N and 16O. The CNO isotope yields of super-AGB stars, novae and fast-rotating massive stars are included. Having reproduced the available isotope enrichment data in the solar neighbourhood, and across the Galaxy, and having assessed the sensitivity of our models to the remaining uncertainties, e.g. nova yields and star formation history, we show that we can meaningfully constrain the stellar IMF in galaxies using C, O and N isotope abundance ratios. In starburst galaxies, where data for multiple isotopologue lines are available, we find compelling new evidence for a top-heavy stellar IMF, with profound implications for their star formation rates and efficiencies, perhaps also their stellar masses. Neither chemical fractionation nor selective photodissociation can significantly perturb globally averaged isotopologue abundance ratios away from the corresponding isotope ones, as both these processes will typically affect only small mass fractions of molecular clouds in galaxies. Thus, the Atacama Large Millimeter
Array now stands ready to probe the stellar IMF, and even the ages of specific starburst events in star-forming galaxies across cosmic time unaffected by the dust obscuration effects that plague optical/near-infrared studies.
Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in malignant tumors and has important roles in multiple aspects of cancer aggressiveness. Thus targeting STAT3 ...promises to be an attractive strategy for treatment of advanced metastatic tumors. Although many STAT3 inhibitors targeting the SH2 domain have been reported, few have moved into clinical trials. Targeting the DNA-binding domain (DBD) of STAT3, however, has been avoided due to its 'undruggable' nature and potentially limited selectivity. In a previous study, we reported an improved in silico approach targeting the DBD of STAT3 that resulted in a small-molecule STAT3 inhibitor (inS3-54). Further studies, however, showed that inS3-54 has off-target effect although it is selective to STAT3 over STAT1. In this study, we describe an extensive structure and activity-guided hit optimization and mechanistic characterization effort, which led to identification of an improved lead compound (inS3-54A18) with increased specificity and pharmacological properties. InS3-54A18 not only binds directly to the DBD and inhibits the DNA-binding activity of STAT3 both in vitro and in situ but also effectively inhibits the constitutive and interleukin-6-stimulated expression of STAT3 downstream target genes. InS3-54A18 is completely soluble in an oral formulation and effectively inhibits lung xenograft tumor growth and metastasis with little adverse effect on animals. Thus inS3-54A18 may serve as a potential candidate for further development as anticancer therapeutics targeting the DBD of human STAT3 and DBD of transcription factors may not be 'undruggable' as previously thought.
Endovascular recanalization has been attempted in patients with symptomatic chronic ICA occlusion, however, the heterogeneity of recanalization outcomes and the perioperative complications present ...challenges for the clinical application. Our aim was to evaluate the safety and efficacy of endovascular recanalization for symptomatic chronic ICA occlusion and identify potential predictors for successful recanalization.
This study included 47 consecutive patients with symptomatic chronic ICA occlusion who underwent endovascular recanalization at our institution. Patients' clinical information, radiologic characteristics, procedural results, and outcomes were recorded. Factors related to technical success were analyzed by univariate and multivariate analyses.
The technical success rate was 74.5% (35/47); 12.8% of patients (6/47) experienced intraoperative complications, but none had permanent neurologic deficits. Three months after recanalization, 21 of the 29 recanalized patients (72.4%) and 3 of the 10 failed patients (30.0%) demonstrated improved mRS scores. Restenosis or re-occlusion occurred in 12.9% of patients (4/31) with successful recanalization. Multivariate analysis showed that tapered or blunt stump (
= .016), distal ICA occlusion segment (below the cavernous segment versus at or above the ophthalmic segment,
= .003; at the cavernous or clinoid segment versus at or above the ophthalmic segment,
= .027), and radiologic occlusion to recanalization of ≤3 months (
= .044) were significantly associated with successful recanalization. Patients were assigned points according to the coefficients of the prediction model, and the technical success rates were 0%, 46.2%, 90.5%, and 100% in patients with 1, 2, 3, and 4 points, respectively.
Endovascular recanalization is a safe and effective treatment for symptomatic chronic ICA occlusion in selected patients. A residual stump, low levels of the distal ICA occlusion segment, and a short radiologic occlusion time were identified as positive predictors of technical success.
Essentials
Perioperative blood loss and inflammatory response can significantly affect recovery after surgery.
We studied the effects of multiple‐dose oral tranexamic acid on blood loss and ...inflammatory response.
A postoperative four‐dose regimen brought about maximum reduction in postoperative blood loss.
A postoperative four‐dose regimen reduced inflammatory response and promoted early rehabilitation.
Summary
Background
Tranexamic acid (TXA) can reduce blood loss and the inflammatory response at multiple doses in total knee arthroplasty patients. However, the optimal regimen has not been determined.
Objectives
To identify the most effective regimen for achieving maximum reductions in blood loss and the inflammatory response.
Patients/Methods
Two hundred and seventy‐five patients were randomized to receive a placebo (group A), a single 2‐g oral dose of TXA 2 h preoperatively followed by 1 g of oral TXA 3 h postoperatively (group B), a single dose followed by 1 g of oral TXA 3 h and 7 h postoperatively (group C), a single dose followed by 1 g of oral TXA 3 h, 7 h and 11 h postoperatively (group D), or a single dose followed by 1 g of oral TXA 3 h, 7 h, 11 h and 15 h postoperatively (group E). The primary outcome was total blood loss on postoperative day (POD) 3. Secondary outcomes included a decrease in the hemoglobin level, coagulation parameters, inflammatory marker levels, and thromboembolic complications.
Results
Groups D and E had significantly lower blood loss and smaller decreases in hemoglobin level than groups A, B, and C, with no significant difference on POD 3 between groups D and E. Significantly enhanced coagulation was identified for the four multiple‐dose regimens; however, all thromboelastographic parameters remained within normal ranges. Group E had the lowest inflammatory marker levels and pain, and the greatest range of motion. No thromboembolic complications were identified.
Conclusion
The four‐dose regimen yielded the maximum reductions in blood loss and inflammatory response, improved analgesia, and promoted early rehabilitation. Further studies are required to ensure that these findings are reproducible.
The South Atlantic Anomaly (SAA) refers to a region where the strength of the magnetic field is notably weaker compared to a dipole field. While previous studies have primarily focused on its effects ...on the inner radiation belt, this study investigates its impact on the aurora system. By analyzing 2 years' worth of data obtained by the Fengyun‐3E/ACMag instrument, we discover that magnetic fluctuations within the auroral oval are significantly weaker in the longitude sector corresponding to the SAA, as compared to those outside this area. This characteristic remains permanent and independent of seasons and geomagnetic activities. Additional investigation using Defense Meteorological Satellite Program/Special Sensor Ultraviolet Spectrographic Imager (DMSP/SSUSI) observations reveals a similar phenomenon in the auroral intensity. Therefore, our results demonstrate that the SAA substantially weakens the aurora system, shedding new light on the effects of magnetic anomalies on planetary auroras and magnetosphere‐ionosphere‐thermosphere coupling.
Plain Language Summary
The South Atlantic Anomaly (SAA) is a unique location on Earth where the magnetic field is weaker than normal. This region has drawn a lot of attention because its weakened magnetic field brings the inner Van Allen radiation belt unusually close to the Earth's surface, which poses a threat to satellites passing through it. Here, we uncovered another interesting aspect of the SAA: its impact on the aurora system. To investigate this, we first examined 2 years' worth of data from the ACMag instruments on the Fengyun‐3E satellite, which orbits the Earth at an altitude of 836 km in a dawn‐dusk, Sun‐synchronous orbit. Our findings reveal that the magnetic fluctuations within the southern auroral oval are significantly weaker in the region that aligns with the SAA. This weakening effect is consistently present, regardless of the season or the level of geomagnetic activity. To reinforce our results, we also analyzed auroral intensity from the Special Sensor Ultraviolet Spectrographic Imager (SSUSI) instrument on the Defense Meteorological Satellite Program (DMSP) satellite, and it corroborated the same weakening trend in this data set. In conclusion, our observations demonstrate that the SAA has a substantial impact on weakening the aurora system. This discovery deepens our understanding of how magnetic anomalies can influence planetary auroras.
Key Points
The effects of the South Atlantic Anomaly (SAA) on the terrestrial aurora system are examined using multiple instruments
Observations reveal a substantial weakening of auroral magnetic fluctuations and auroral intensity in the SAA longitude sector
The results indicate considering magnetic anomalies like the SAA is essential for comprehensively understanding planetary aurora systems
Subclinical hypothyroidism (SCH) has been shown to be associated with microbiota. However, the association between SCH and oral microbiota has not yet been elucidated. The results of our previous ...clinical studies showed that Prevotella intermedia was abundant in the oral microbiota of SCH patients. This study aimed to investigate the relationship between SCH and oral microbiota, verify the pathogenicity of P. intermedia in SCH, and preliminarily explore the possible mechanism. The SCH mouse model with oral application of P. intermedia was established, and the variance in the mouse oral microbiota and changes in thyroid function and metabolism were detected in mice. Student’s t test and analysis of variance were used for statistical analysis. Oral application of P. intermedia changed the composition of the oral microbiota of SCH mice, which enhanced the damage to the thyroid and decreased the expression of functional genes of the thyroid. Moreover, P. intermedia decreased oxygen consumption and aggravated glucose and lipid metabolism disorders in SCH mice. Glucose tolerance and insulin tolerance decreased, and the triglyceride content of the liver and inflammatory infiltration in adipose tissue increased in SCH mice after P. intermedia stimulation. Mechanistically, P. intermedia increased the proportion of CD4+ T cells in cervical lymph nodes and thyroids in SCH mice. Th1 cells were suggested to play an important role in the pathogenesis of SCH involving P. intermedia. In conclusion, P. intermedia aggravated SCH manifestations, including thyroid dysfunction and glucose and lipid metabolism disorders, by causing immune imbalance in mice. This study sheds new light on the pathogenesis of SCH from the perspective of oral microbiota.
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