Predictors of outcome in large vessel occlusion stroke patients with intravenous tirofiban treatment: a post hoc analysis of the RESCUE BT clinical trial.

OBJECTIVE: The aim of this study was to investigate the factors influencing good outcomes in patients receiving only intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. METHODS: Post hoc exploratory analysis using the RESCUE BT trial identified consecutive patients who received intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke in 55 comprehensive stroke centers from October 2018 to January 2022 in China. RESULTS: A total of 521 patients received intravenous tirofiban, 253 of whom achieved a good 90-day outcome (modified Rankin Scale [mRS] 0-2). Younger age (adjusted odds ratio [aOR]: 0.965, 95% confidence interval [CI]: 0.947-0.982; p < 0.001), lower serum glucose (aOR: 0.865, 95%CI: 0.807-0.928; p < 0.001), lower baseline National Institutes of Health Stroke Scale (NIHSS) score (aOR: 0.907, 95%CI: 0.869-0.947; p < 0.001), fewer total passes (aOR: 0.791, 95%CI: 0.665-0.939; p = 0.008), shorter punctures to recanalization time (aOR: 0.995, 95%CI:0.991-0.999; p = 0.017), and modified Thrombolysis in Cerebral Infarction (mTICI) score 2b to 3 (aOR: 8.330, 95%CI: 2.705-25.653; p < 0.001) were independent predictors of good outcomes after intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. CONCLUSION: Younger age, lower serum glucose level, lower baseline NIHSS score, fewer total passes, shorter punctures to recanalization time, and mTICI scores of 2b to 3 were independent predictors of good outcomes after intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. CHINESE CLINICAL TRIAL REGISTRY IDENTIFIER: ChiCTR-IOR-17014167.

SLC4A4 is a novel driver of enzalutamide resistance in prostate cancer.

The androgen receptor signaling inhibitor (ARSI) enzalutamide (Enz) has shown critical efficacy in the treatment of advanced prostate cancer (PCa). However, the development of drug resistance is a significant factor contributing to mortality in PCa patients. We aimed to explore the key mechanisms of Enz-resistance. Through analysis of GEO databases, we identified SLC4A4 as a novel driver in Enz resistance. Long-term Enz treatment leads to the up-regulation of SLC4A4, which in turn mediates P53 lactylation via the NF-κB/STAT3/SLC4A4 axis, ultimately leading to the development of Enz resistance and progression of PCa. SLC4A4 knockdown overcomes Enz resistance both in vitro and in vivo. Hence, our results suggest that targeting SLC4A4 could be a promising therapeutic strategy for Enz resistance. STATEMENT OF SIGNIFICANCE: SLC4A4 is a novel driver of enzalutamide resistance.

Improved optimization for the neural-network quantum states and tests on the chromium dimer.

The advent of Neural-network Quantum States (NQS) has significantly advanced wave function ansatz research, sparking a resurgence in orbital space variational Monte Carlo (VMC) exploration. This work introduces three algorithmic enhancements to reduce computational demands of VMC optimization using NQS: an adaptive learning rate algorithm, constrained optimization, and block optimization. We evaluate the refined algorithm on complex multireference bond stretches of H2O and N2 within the cc-pVDZ basis set and calculate the ground-state energy of the strongly correlated chromium dimer (Cr2) in the Ahlrichs SV basis set. Our results achieve superior accuracy compared to coupled cluster theory at a relatively modest CPU cost. This work demonstrates how to enhance optimization efficiency and robustness using these strategies, opening a new path to optimize large-scale restricted Boltzmann machine-based NQS more effectively and marking a substantial advancement in NQS's practical quantum chemistry applications.

Association of Renal Impairment with Clinical Outcomes Following Endovascular Therapy in Acute Basilar Artery Occlusion.

Purpose: Renal impairment (RI) is associated with unfavourable outcome after acute ischaemic stroke with anterior circulation large vessel occlusion. We assessed the association of RI with clinical outcomes in patients with acute basilar artery occlusion (ABAO), and the impact of RI on the effects of endovascular therapy (EVT) versus standard medical treatment (SMT). Patients and Methods: We used data from the BASILAR registry, an observational, prospective, nationwide study of patients with ABAO in routine clinical practice in China. Baseline estimated glomerular filtration rate (eGFR) was recorded at admission. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included favourable outcome (mRS score 0-3), mortality, and symptomatic intracranial haemorrhage (sICH). Multivariate logistic regression was used to assess the association of RI with mortality and functional improvement at 90 days. Results: Among 829 patients enrolled, 747 patients were analysed. The median baseline eGFR was 89 mL/min/1.73m2 (IQR, 71-100), and 350 (46.8%), 297 (39.8%), and 100 (13.4%) patients had baseline eGFR values of ≥90, 60-89, and <60 mL/min/1.73m2, respectively. RI was associated with increased mortality (adjusted odds ratio [aOR], 1.97; 95% CI, 1.15-3.67) at 90 days and decreased survival probability (aOR 1.74; 95% CI, 1.30-2.33) within 1 year. EVT was associated with better functional improvement (common aOR, 2.50; 95% CI, 1.43-4.35), favourable outcome (aOR 5.42; 95% CI, 1.92-15.29) and lower mortality (aOR 0.47; 95% CI, 0.25-0.88) in ABAO patients with eGFR ≥90 mL/min/1.73m2. However, RI was not modified the relationship of EVT with functional improvement (common aOR, 3.03; 95% CI, 0.81-11.11), favourable outcome (aOR 2.10; 95% CI, 0.45-9.79), and mortality (aOR 0.56; 95% CI, 0.15-2.06) by eGFR categories. Conclusion: RI is associated with reduced efficacy of EVT and worse functional outcome and higher mortality at 3 months and lower survival probability at 1 year in patients with ABAO.

Endovascular treatment versus standard medical treatment in patients with established large infarct: a cohort study.

BACKGROUND: Previous trials confirmed the benefit of endovascular treatment (EVT) in acute large core stroke, but the effect of EVT on outcomes in these patients based on non-contrast computed tomography (NCCT) in real-world clinical practice was unclear. The aim of this study was to explore the effect of EVT versus standard medical treatment (SMT) in patients with large ischemic core stroke defined as Alberta Stroke Program Early CT Score (ASPECTS)≤5 based on NCCT alone. MATERIALS AND METHODS: Patients with acute large core stroke at 38 Chinese centers between November 2021 and February 2023 were reviewed from prospectively maintained databases. The primary outcome was favorable functional outcome (modified Rankin Scale score [mRS], 0-3) at 90 days. Safety outcomes included 48-hour symptomatic intracerebral hemorrhage (sICH) and 90-day mortality. RESULTS: Of 745 eligible patients recruited at 38 stroke centers between November 2021 and February 2023, 490 were treated with EVT and 255 with SMT alone. One hundred and eighty-one (36.9%) in the EVT group achieved favorable functional independence versus 48 (18.8%) treated with SMT only (adjusted risk ratio [RR], 1.86; 95% CI, 1.43 to 2.42, P<0.001; adjusted risk difference [RD], 13.77; 95% CI, 7.40 to 20.15, P<0.001). The proportion of sICH was significantly higher in patients undergoing EVT (13.3% vs. 2.4%; adjusted RR, 5.17; 95% CI, 2.17 to 12.32, P<0.001; adjusted RD, 10.10; 95% CI, 6.12 to 14.09, P<0.001). No significant difference of mortality between the groups was observed (41.8% vs. 49.0%; adjusted RR, 0.91; 95% CI, 0.77 to 1.07, P=0.24; adjusted RD, -5.91; 95% CI, -12.91 to 1.09, P=0.1). CONCLUSION: Among patients with acute large core stroke based on NCCT in real world, EVT is associated with better functional outcomes at 90 days despite of higher risk of sICH. Rates of procedure-related complications were high in the EVT group.

Endovascular Therapy and Outcomes Among Patients With Very Large Ischemic Core Stroke.

Importance: The association of endovascular therapy (EVT) with outcomes is unclear for patients with very low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) within 24 hours of stroke onset. Objective: To explore the association of EVT with functional and safety outcomes among patients with ASPECTS of 0 to 2 scored with noncontrast computed tomography. Design, Setting, and Participants: This cohort study used data from an ongoing, prospective, observational, nationwide registry including all patients treated at 38 stroke centers in China with an occlusion in the internal carotid artery or M1 or M2 segment of the middle cerebral artery within 24 hours of witnessed symptom onset. Patients with ASPECTS of 0 to 2 between November 1, 2021, and February 8, 2023, were included in analysis. Data were analyzed October to November 2023. Exposures: EVT vs standard medical treatment (SMT). Main Outcomes and Measures: The primary outcome was favorable functional outcome, defined as modified Rankin Scale score (mRS) of 0 to 3, at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage (sICH) within 48 hours and mortality at 90 days. Results: A total of 245 patients (median [IQR] age, 71 [63-78] years; 118 [48%] women) with ASPECTS of 0 to 2 were included, of whom 111 patients (45.1%) received SMT and 135 patients (54.9%) received EVT. The EVT group had significantly greater odds of favorable functional outcome at 90 days than the SMT group (30 patients [22.2%] vs 11 patients [9.9%]; P = .01; adjusted odds ratio [aOR], 3.07 [95% CI, 1.29-7.31]; P = .01). Patients in the EVT group, compared with the SMT group, had significantly greater odds of any ICH (56 patients [41.5%] vs 16 patients [11.4%]; P < .001; aOR, 4.27 [95% CI, 2.19-8.35]; P < .001) and sICH (24 patients [17.8%] vs 1 patient [0.9%]; P < .001; aOR, 23.07 [95% CI, 2.99-177.79]; P = .003) within 48 hours. There were no differences between groups for 90-day mortality (80 patients [59.3%] vs 59 patients [53.2%]; P = .34; aOR, 1.38 [95% CI, 0.77-2.47]; P = .28). The results remained robust in the propensity score-matched analysis. Conclusions and Relevance: In this cohort study of patients with very low ASPECTS based on NCCT within 24 hours of stroke onset, those treated with EVT had higher odds of a favorable functional outcome compared with those who received SMT. Randomized clinical trials are needed to assess these findings.

Photocatalytic degradation of p-aminobenzoic acid on N-biomass charcoal etched with Fe-Al-bilayer hydroxide: New insights through spectroscopic investigation.

We investigated the photocatalytic property of etched iron­aluminum layered double hydroxide (LDH) composites using urea-modified biochar (N-BC) carrier to degrade para-aminobenzoic acid (PABA), a refractory organic pollutant. The prepared FeAl-LDH@FeSx-N-BC composite exhibited excellent photocatalytic performance, attributed to the enhanced photogenerated charge-carrier separation by the etched LDH and the improved comparative surface areas by the doped N-BC. The composite photocatalytically degraded 96 % of PABA. The performance was affected by solute concentration, pH and photocatalyst dose. Adding p-benzoquinone and EDTA-2Na significantly decreased the degradation rate, suggesting that superoxide radicals and holes were co-involved in PABA degradation. The excellent PABA removal efficiency was consistent for three consecutive runs. The samples' reactive oxygen species was confirmed, as electron paramagnetic reverberation explained the photodegradation mechanism. Under xenon lamp irradiation, two PABA photocatalytic degradation pathways were proposed using Liquid Chromatograph Mass Spectrometer (LCMS) and density functional theory. As expected, FeAl-LDH@FeSx-N-BC showed excellent photocatalytic performance, expanding a new direction and possibility for future photocatalytic treatment of water pollutants.

The impacts of venous outflow profiles on outcomes among large vessel occlusion patients receiving endovascular treatment in the late window.

OBJECTIVES: To investigate the association between venous outflow (VO) profiles and outcomes among acute ischemic stroke caused by anterior circulation large vessel occlusion (AIS-LVO) patients who had undergone endovascular treatment (EVT) in the late window of 6-24 h from stroke onset. METHODS: This was a post-hoc analysis of our preceding RESCUE-BT trial, with findings validated in an external cohort. Baseline computed tomographic angiography (CTA) was performed to assess VO using the Cortical Vein Opacification Score (COVES). The primary clinical outcome was functional independence at 90 days (modified Rankin Scale score of 0-2). The adjusted odd ratio (aOR) and confidence interval (CI) were obtained from multivariable logistic regressions. RESULTS: A total of 440 patients were included in the present study. After identifying the cutoff of COVES by marginal effects approach, enrolled patients were divided into the favorable VO group (COVES 4-6) and the poor VO (COVES 0-3) group. Multivariable logistic regression analysis showed that favorable VO (aOR 2.25; 95% CI 1.31-3.86; p = 0.003) was associated with functional independence. Similar results were detected in the external validation cohort. Among those with poor arterial collateralization, favorable VO was still an independent predictor of functional independence (aOR 2.09; 95% CI 1.06-4.10; p = 0.032). CONCLUSION: The robust VO profile indicated by COVES 4-6 could promote the frequency of functional independence among AIS-LVO patients receiving EVT in the late window, and the prognostic value of VO was independent of the arterial collateral status. CLINICAL RELEVANCE STATEMENT: The robust venous outflow profile was a valid predictor for functional independence among AIS-LVO patients receiving EVT in the late window (6-24 h) and the predictive role of venous outflow did not rely on the status of arterial collateral circulation.

Association of functional outcomes between intravenous tirofiban and endovascular thrombectomy in imaging-screened patients with large vessel occlusion stroke: a secondary analysis of randomized clinical trial.

BACKGROUND: In the RESCUE BT (Endovascular Treatment With versus Without Tirofiban for Stroke Patients with Large Vessel Occlusion) trial, enrollment in extended time window was based on non-contrast computed tomography. To assess whether perioperative intravenous tirofiban would further enhance the clinical benefit of endovascular therapy in the RESCUE BT trial according to advanced imaging criteria based on current American Heart Association/American Stroke Association (AHA/ASA) guidelines. METHODS: This is a secondary analysis of the RESCUE BT trial. Patients who were eligible for endovascular thrombectomy in the 6-hour window and met the criteria of the DAWN or DEFUSE 3 trials in the extended window according to the AHA/ASA guidelines were analyzed. The primary outcome was the distribution of the 90-day modified Rankin Scale (mRS) scores. Safety outcomes included the incidence of symptomatic intracranial hemorrhage (sICH) within 48 hours and 90-day mortality. RESULTS: A total of 652 patients (319 in tirofiban group and 333 in placebo group) who meeting the AHA/ASA guidelines were included in this analysis, with median (IQR) age of 68 (58-75) years, 278 (42.6%) were women. The median 90-day mRS score was 3 (IQR, 1-4) in the tirofiban group, and 3 (IQR, 1-4) in the placebo group. The adjusted common odds ratio (OR) for a lower level of disability with tirofiban than with placebo was 1.08 (95% confidence interval [CI], 0.83-1.42). The incidence of sICH (10.1% versus 6.3%; adjusted OR 1.70; [95% CI, 0.95-3.04]) was not significantly different between groups. However, intravenous tirofiban might be associated with lower disability level (adjusted common OR, 1.74 [95% CI, 1.14-2.65]; P=0.01) in patients with large artery atherosclerosis. CONCLUSIONS: There was no significant difference in the severity of disability at 90 days with intravenous tirofiban compared to placebo in patients who underwent endovascular therapy according to AHA/ASA guidelines. We observed potential benefits of tirofiban in patients with large artery atherosclerosis, but there was an increased risk of sICH in patients with cardioembolism stroke.

Photo-electrochemical activation of persulfate for the simultaneous degradation of microplastics and personal care products.

The recent widespread use of microplastics (MPs), especially in pharmaceuticals and personal care products (PPCPs), has caused significant water pollution. This study presents a UV/electrically co-facilitated activated persulfate (PS) system to co-degrade a typical microplastic polyvinyl chloride (PVC) and an organic sunscreen p-aminobenzoic acid (PABA). We investigated the effect of various reaction conditions on the degradation. PVC and PABA degradation was 37% and 99.22%, respectively. Furthermore, we observed alterations in the surface topography and chemical characteristics of PVC throughout degradation. The possible degradation pathways of PVC and PABA were proposed by analyzing the intermediate products and the free radicals generated. This study reveals the co-promoting effect of multiple mechanisms in the activation by ultraviolet light and electricity.

LEET: stock market forecast with long-term emotional change enhanced temporal model.

The stock market serves as a macroeconomic indicator, and stock price forecasting aids investors in analysing market trends and industry dynamics. Several deep learning network models have been proposed and extensively applied for stock price prediction and trading scenarios in recent times. Although numerous studies have indicated a significant correlation between market sentiment and stock prices, the majority of stock price predictions rely solely on historical indicator data, with minimal effort to incorporate sentiment analysis into stock price forecasting. Additionally, many deep learning models struggle with handling the long-distance dependencies of large datasets. This can cause them to overlook unexpected stock price fluctuations that may arise from long-term market sentiment, making it challenging to effectively utilise long-term market sentiment information. To address the aforementioned issues, this investigation suggests implementing a new technique called Long-term Sentiment Change Enhanced Temporal Analysis (LEET) which effectively incorporates long-term market sentiment and enhances the precision of stock price forecasts. The LEET method proposes two market sentiment index estimation methods: Exponential Weighted Sentiment Analysis (EWSA) and Weighted Average Sentiment Analysis (WASA). These methods are utilized to extract the market sentiment index. Additionally, the study proposes a Transformer architecture based on ProbAttention with rotational position encoding for enhanced positional information capture of long-term emotions. The LEET methodology underwent validation using the Standard & Poor's 500 (SP500) and FTSE 100 indices. These indices accurately reflect the state of the US and UK equity markets, respectively. The experimental results obtained from a genuine dataset demonstrate that this method is superior to the majority of deep learning network architectures when it comes to predicting stock prices.

The Association Between National Institutes of Health Stroke Scale Score and Clinical Outcome in Patients with Large Core Infarctions Undergoing Endovascular Treatment.

INTRODUCTION: This study aimed to analyze the association between baseline National Institutes of Health Stroke Scale (NIHSS) scores and clinical outcomes in patients with large core infarctions undergoing endovascular treatment (EVT), a relationship that remains unclear. METHODS: Data were obtained from the MAGIC study, a prospective multicenter cohort study focusing on patients with acute large core ischemic stroke. This analysis evaluated the impact of NIHSS scores on EVT outcomes in patients with large core infarctions. Primary outcome metrics included favorable outcomes (modified Rankin Scale [mRS] of 0-3 at 90 days), while secondary outcomes encompassed shifts in mRS scores, functional independence (mRS score of 0-2), mRS score of 0-4, and successful recanalization rates. Adverse events considered were symptomatic intracranial hemorrhage (sICH) and mortality. RESULTS: A total of 490 patients were enrolled in this study. Higher baseline NIHSS scores were inversely correlated with favorable outcomes (adjusted odds ratio [OR] in model 3, 0.848 [0.797-0.903], P < 0.001), particularly in patients with NIHSS scores above 20 (adjusted OR in model 3, 0.518 [0.306-0.878] vs. 0.290 [0.161-0.523]). Regarding adverse events, higher baseline NIHSS scores significantly correlated with increased 90-day mortality rates (adjusted OR in model 3, 1.129 [1.072-1.189], P < 0.001). This correlation became insignificant when baseline NIHSS scores exceeded 22. Additionally, baseline NIHSS scores partially mediated the association between age (indirect effect = - 0.0005, 19.39% mediated) and sex (indirect effect = 0.0457, 25.08% mediated) with the primary outcome. CONCLUSIONS: The findings indicate that higher baseline NIHSS scores correlate with poorer outcomes and increased mortality, particularly when scores exceed 20. Moreover, age and sex indirectly influence favorable outcomes through their association with baseline NIHSS scores.

CRISPR genome-wide screening identifies PAK1 as a critical driver of ARSI cross-resistance in prostate cancer progression.

Next-generation androgen receptor signaling inhibitors (ARSIs), such as enzalutamide (Enza) and darolutamide (Daro), are initially effective for the treatment of advanced prostate cancer (PCa) and castration-resistant prostate cancer (CRPC). However, patients often relapse and develop cross-resistance, which consequently makes drug resistance an inevitable cause of CRPC-related mortality. By conducting a comprehensive analysis of GEO datasets, CRISPR genome-wide screening results, ATAC-seq data, and RNA-seq data, we systemically identified PAK1 as a significant contributor to ARSI cross-resistance due to the activation of the PAK1/RELA/hnRNPA1/AR-V7 axis. Inhibition of PAK1 followed by suppression of NF-κB pathways and AR-V7 expression effectively overcomes ARSI cross-resistance. Our findings indicate that PAK1 represents a promising therapeutic target gene for the treatment of ARSI cross-resistant PCa patients in the clinic. STATEMENT OF SIGNIFICANCE: PAK1 drives ARSI cross-resistance in prostate cancer progression.

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke: The MARVEL Randomized Clinical Trial.

Importance: It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023. Interventions: Eligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures: The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance: Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability. Trial Registration: ChiCTR.org.cn Identifier: ChiCTR2100051729.

Establishment and characterization of a highly metastatic hepatocellular carcinoma cell line.

The prevalence of alcohol-related hepatocellular carcinoma (HCC) has been increasing during the last decade. Cancer research requires cell lines suitable for both in vitro and in vivo assays. However, there is a lack of cell lines with a high in vivo metastatic capacity for this HCC subtype. Herein, a new HCC cell line was established, named HCC-ZJ, using cells from a patient diagnosed with alcohol-related HCC. The karyotype of HCC-ZJ was 46, XY, del (p11.2). Whole-exome sequencing identified several genetic variations in HCC-Z that occur frequently in alcohol-associated HCC, such as mutations in TERT, CTNNB1, ARID1A, CDKN2A, SMARCA2, and HGF. Cell counting kit-8 assays, colony formation assays, and Transwell assays were performed to evaluate the proliferation, migration, and sensitivity to sorafenib and lenvatinib of HCC-Z in vitro. HCC-ZJ showed a robust proliferation rate, a weak foci-forming ability, a strong migration capacity, and a moderate invasion tendency in vitro. Finally, the tumorigenicity and metastatic capacity of HCC-Z were evaluated using a subcutaneous xenograft model, an orthotopic xenograft model, and a tail-veil injection model. HCCZJ exhibited strong tumorigenicity in the subcutaneous xenograft and orthotopic tumor models. Moreover, HCC-ZJ spontaneously formed pulmonary metastases in the orthotopic tumor model. In summary, a new HCC cell line derived from a patient with alcohol-related HCC was established, which showed a high metastatic capacity and could be applied for in vitro and in vivo experiments during pre-clinical research.Highlights• An alcohol-related HCC cell line, HCC-ZJ, was established• HCC-ZJ was applicable for in vitro functional experiment and gene editing• HCC-ZJ was applicable for in vivo tumor growth and spontaneous metastasis models.

The impact of stress hyperglycemia ratio on short-term and long-term outcomes for acute basilar artery occlusion underwent endovascular treatment.

BACKGROUND: Stress hyperglycemia ratio (SHR) reflects a true acute hyperglycemic state during acute basilar artery occlusion (ABAO). We aimed to investigate the association between SHR and short-term and long-term outcomes in patients with ABAO receiving endovascular treatment (EVT). METHODS: We selected patients treated with EVT from the BASILAR study, a nationwide prospective registry. A total 250 patients with documented glucose and glycated hemoglobin (HbA1C) values at admission were included. SHR was calculated as the ratio of glucose/HbA1C. All 250 patients completed 90 days of follow-up and 234 patients (93.6%) completed 1 year of follow-up. The primary outcome was the favorable outcome defined as modified Rankin Scale (mRS) score ≤ 3 at 90 days. Safety outcomes included mortality at 90 days and 1 year, and intracranial hemorrhage. RESULTS: Among the 250 patients included, patients with higher tertiles of SHR were associated with decreased odds of a favorable functional outcome at 90 days (adjusted OR, 0.26; 95% CI, 0.12-0.56; P = 0.001 and adjusted OR, 0.37; 95% CI, 0.18-0.80; P = 0.01; respectively) and 1 year (adjusted OR, 0.34; 95% CI, 0.16-0.73; P = 0.006 and adjusted OR, 0.38; 95% CI, 0.18-0.82; P = 0.01; respectively) after adjusting for confounding covariates. The mortality was comparable across tertiles of SHR groups at 90 days and 1 year. CONCLUSIONS: Our study showed that SHR was associated with a decreased probability of favorable functional outcome both at 90 days and 1 year after EVT in patients with ABAO. The relationship was more pronounced in non-diabetes patients. TRIAL REGISTRATION: Clinical Trial Registry Identifier: ChiCTR1800014759 (November 12, 2013).

Systemic THrombolysis Randomization IN Endovascular Stroke Therapy (SHRINE) Collaboration: a patient-level pooled analysis of the SKIP and DEVT Trials.

OBJECTIVE: To evaluate the non-inferiority of endovascular treatment (EVT) alone versus intravenous thrombolysis (IVT) followed by EVT and to assess its heterogeneity across prespecified subgroups. METHODS: We pooled data from two trials (SKIP in Japan; DEVT in China). Individual patient data were pooled to assess outcomes and heterogeneity of treatment effect. The primary outcome was functional independence (modified Rankin Scale score 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and 90-day mortality. RESULTS: We included 438 patients (217 EVT alone; 221 combined IVT+EVT). The meta-analysis failed to demonstrate the non-inferiority of EVT alone over combined IVT+EVT in achieving 90-day functional independence (56.7% vs 51.6%; adjusted common odds ratio (cOR)=1.27, 95% CI 0.84 to 1.92, pnon-inferiority=0.06). Effect sizes favoring EVT alone were present with stroke onset to puncture time longer than 180 min (cOR=2.28, 95% CI 1.18 to 4.38, pinteraction ≤180 vs >180 min=0.02) and intracranial internal carotid artery ICA occlusions (for ICA cOR=3.04, 95% CI 1.10 to 8.43, pinteraction ICA vs MCA=0.08). The rates of sICH (6.5% vs 9.0%; cOR=0.77, 95% CI 0.37 to 1.61) and 90-day mortality (12.9% vs 13.6%; cOR=1.05, 95% CI 0.58 to 1.89) were comparable. CONCLUSIONS: The cumulative data of these two recent Asian trials failed to unequivocally demonstrate the non-inferiority of EVT alone over combined IVT+EVT. However, our study suggests a potential role for more individualized decision-making. Specifically, Asian patients with stroke onset to EVT longer than 180 min, as well as those with intracranial ICA occlusions and those with atrial fibrillation might have better outcomes with EVT alone than with combined IVT+EVT.

Effects of tirofiban on large vessel occlusion stroke are modified by etiology and renal function.

OBJECTIVE: Renal function can modify the outcomes of large vessel occlusion (LVO) stroke across stroke etiologies in disparate degrees. The presence of renal function deficit can also impair the pharmacokinetics of tirofiban. Hence, this study aimed to investigate the roles of renal function in determining efficacy and safety of intravenous tirofiban before endovascular treatment (EVT) for acute ischemic stroke patients with large vessel occlusion (LVO). METHODS: This study was a post hoc exploratory analysis of the RESCUE-BT trial. The primary outcome was the proportion of patients achieving functional independence (modified Rankin scale 0-2) at 90 days, and the primary safety outcome was the rate of symptomatic intracranial hemorrhage (sICH). RESULTS: Among 908 individuals with available serum creatinine, decreased estimated glomerular filtration rate (eGFR) status was noted more commonly in patients with cardioembolic stroke (CE), while large artery atherosclerosis (LAA) was predominant in patients with normal renal function. In LAA with normal renal function, tirofiban was associated with higher rates of functional independence at 90 days (41.67% vs 59.80%, p = 0.003). However, for LVO patients with renal dysfunction, tirofiban did not improve functional outcomes for any of the etiologies (LAA, p = 0.876; CE, p = 0.662; others, p = 0.894) and significantly increased the risk of sICH among non-LAA patients (p = 0.020). Mediation analysis showed tirofiban reduced thrombectomy passes (12.27%) and drug/placebo to recanalization time (14.25%) mediated its effects on functional independence. CONCLUSION: This present study demonstrated the importance of evaluating renal function before administering intravenous tirofiban among patients with LVO who are planned to undergo EVT.

Mucosal DNA methylome alteration in Crohn's disease: surgical and non-surgical groups.

Crohn's disease (CD) is characterized as a chronic, relapsing, and progressive disorder with a complex etiology involving interactions between host, microbiome, and the external environment. Genome wide association studies (GWAS) suggest several genetic variations in the diseased individuals but that explains only a small proportion of susceptibility to disease conditions. This indicates the possible role of epigenome which links environmental factors to the genetic variation in the disease etiology. The current study is focused on the DNA methylome evolution with disease progression. We performed Reduced Representation Bisulfite Sequencing (RRBS) to analyze differential DNA methylation in the diseased and healthy mucosal tissues of 2 different groups of CD patients: non-surgical and surgical, categorized based on the severity of disease and standard of care needed. Patients in both groups have unique DNA methylation signature compared to the healthy tissue. After removing single nucleotide polymorphisms (SNPs), 1,671 differentially methylated loci were found in the non-surgical and 3,334 in the surgical group of which only 206 were found overlapping in both groups. Furthermore, differential DNA methylation was noted in some of the GWAS associated genes implicated in CD. Also, functional enrichment analysis showed high representation of several key pathways where differential methylations were observed, and these can be implicated in CD pathogenesis. We identified specific DNA methylation patterns in the mucosal DNA of surgical and non-surgical CD patients which indicates evolution of the methylome as the disease progresses from initial to the advance stage. These unique patterns can be used as DNA methylation signatures to identify different stages of the disease.

A Nonstochastic Optimization Algorithm for Neural-Network Quantum States.

Neural-network quantum states (NQS) employ artificial neural networks to encode many-body wave functions in a second quantization through variational Monte Carlo (VMC). They have recently been applied to accurately describe electronic wave functions of molecules and have shown the challenges in efficiency compared with traditional quantum chemistry methods. Here, we introduce a general nonstochastic optimization algorithm for NQS in chemical systems, which deterministically generates a selected set of important configurations simultaneously with energy evaluation of NQS. This method bypasses the need for Markov-chain Monte Carlo within the VMC framework, thereby accelerating the entire optimization process. Furthermore, this newly developed nonstochastic optimization algorithm for NQS offers comparable or superior accuracy compared to its stochastic counterpart and ensures more stable convergence. The application of this model to test molecules exhibiting strong electron correlations provides further insight into the performance of NQS in chemical systems and opens avenues for future enhancements.