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One of the major problems in teaching social sciences is finding the appropriate strategies to deliver the lessons to students. The researchers are determined to develop proper guidelines in using educational strategies to improve the learning process, one of which is the Utilization of Technology-Aided Strategies, that a social science teacher could implement inside the four corners of the classroom, especially in the 21st century, where one of the major problems of teachers are engaging students’ participation. Descriptive quantitative research method was used in conducting this study. Through the process of purposive sampling technique, a total number of 50 teachers in a national high school was selected to participate in the study. The major instruments used were survey questionnaires. The data gathered were analyzed. The findings demonstrated the importance of understanding the Utilization of Technology-Aided Strategies, when it comes to teaching Social Science. In order to make sure that the right tools and materials were available for them to work with, teachers should be aware of the profiles and learning styles of the learners. The teaching and learning process should be improved by teachers and school officials, boosting its effectiveness and efficiency.

The preparation of halogenated benzene-1,2,3,4-tetracarboxylic diimide derivatives is challenging because of the possibility of competitive incorrect cyclizations and S

To assess whether conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI) could non-invasively predict p53 and Ki-67 labelling index (LI) and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status in adult isocitrate dehydrogenase (IDH) wild-type glioblastomas.The conventional MRI, DWI, and DSC-PWI results of 120 adult patients with IDH wild-type glioblastomas were reviewed retrospectively and their efficacy was analysed using chi-square tests or Fisher's exact test. Relative minimum apparent diffusion coefficient (rADCGlioblastomas with a high p53 LI were more likely to show a well-defined enhancement margin (p=0.047). Glioblastomas in the high-Ki-67-LI group demonstrated significantly lower rADCThe present results suggest that conventional and DWI and DSC-PWI results are influenced by the molecular status of the glioblastoma and indicate that DWI and DSC-PWI may help to identify regions of high invasiveness within heterogeneous glioblastomas.

Progress in cytokine engineering is driving therapeutic translation by overcoming the inherent limitations of these proteins as drugs. The interleukin-2 (IL-2) cytokine harbors great promise as an immune stimulant for cancer treatment. However, the cytokine’s concurrent activation of both pro-inflammatory immune effector cells and anti-inflammatory regulatory T cells, its toxicity at high doses, and its short serum half-life have limited clinical application. One promising approach to improve the selectivity, safety, and longevity of IL-2 is complexation with anti-IL-2 antibodies that bias the cytokine towards the activation of immune effector cells (i.e., effector T cells and natural killer cells). Although this strategy shows therapeutic potential in preclinical cancer models, clinical translation of a cytokine/antibody complex is complicated by challenges in formulating a multi-protein drug and concerns about complex stability. Here, we introduce a versatile approach to designing intramolecularly assembled single-agent fusion proteins (immunocytokines, ICs) comprising IL-2 and a biasing anti-IL-2 antibody that directs the cytokine’s activities towards immune effector cells. We establish the optimal IC construction and further engineer the cytokine/antibody affinity to improve immune biasing function. We demonstrate that our IC preferentially activates and expands immune effector cells, leading to superior antitumor activity compared to natural IL-2 without inducing toxicities associated with IL-2 administration. Collectively, this work presents a roadmap for the design and translation of immunomodulatory cytokine/antibody fusion proteins.One Sentence SummaryWe developed an IL-2/antibody fusion protein that expands immune effector cells and shows superior tumor suppression and toxicity profile versus IL-2.

This figure shows that ASNS mediates protein translation during amino acid deprivation.

Supplementary Table 2 shows differential gene expression in LUAD cells treated with ISRIB during asparagine deprivation.

Supplementary Table 4 list the results from Reverse phase protein array analysis of LUAD cells treated with ISRIB during asparagine deprivation.

This file list contains the legends for supplementary Figures and tables.

Supplementary Table 1 shows Gene ontology analysis of ATF4 target genes up-regulated in late stage LUADs.

Supplementary Table 3 lists the results of Pathway analysis of differential gene expression in LUAD cells treated with ISRIB during asparagine deprivation.

Immune surveillance cells such as T cells and phagocytes utilize integral plasma membrane receptors to recognize surface signatures on triggered and activated cells such as those in apoptosis. One such family of plasma membrane sensors, the transmembrane immunoglobulin and mucin domain (Tim) proteins, specifically recognize phosphatidylserine (PS) but elicit distinct immunological responses. The molecular basis for the recognition of lipid signals on target cell surfaces is not well understood. Previous results suggest that basic side chains present at the membrane interface on the Tim proteins might facilitate association with additional anionic lipids including but not necessarily limited to PS. We, therefore, performed a comparative quantitative analysis of the binding of the murine Tim1, Tim3, and Tim4, to synthetic anionic phospholipid membranes under physiologically relevant conditions. X-ray reflectivity and vesicle binding studies were used to compare the water-soluble domain of Tim3 with results previously obtained for Tim1 and Tim4. Although a calcium link was essential for all three proteins, the three homologs differed in how they balance the hydrophobic and electrostatic interactions driving membrane association. The proteins also varied in their sensing of phospholipid chain unsaturation and showed different degrees of cooperativity in their dependence on bilayer PS concentration. Surprisingly, trace amounts of anionic phosphatidic acid greatly strengthened the bilayer association of Tim3 and Tim4, but not Tim1. A novel mathematical model provided values for the binding parameters and illuminated the complex interplay among ligands. In conclusion, our results provide a quantitative description of the contrasting selectivity used by three Tim proteins in the recognition of phospholipids presented on target cell surfaces. This paradigm is generally applicable to the analysis of the binding of peripheral proteins to target membranes through the heterotropic cooperative interactions of multiple ligands.

On the OMEGA laser system, the beam-pointing accuracy is verified by irradiating a 4 mm diameter Au-coated spherical target with ∼23 kJ of laser energy. Up to ten x-ray pinhole cameras record the x-ray emission from all 60-beam spots. A new set of algorithms has been developed to improve the accuracy of the pointing evaluation. An updated edge-finding procedure allows one to infer the center of the sphere with subpixel accuracy. A new approach was introduced to back-propagate the pixel locations on the 2D image to the 3D surface of the sphere. A fast Fourier transform-based de-noising method significantly improves the signal-to-noise of the data. Based on the beam-pointing analysis, hard-sphere calculations of the laser-drive illumination uniformity on the target surface and the decomposition of the illumination distribution into lower order modes (1–10) are evaluated.

Our aim was to explore the prognostic role of baseline albumin-bilirubin levels (ALBI) on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC).This retrospective study enrolled 58 cases of advanced NSCLC patients who received immune checkpoint inhibitor therapy from January 2019 to February 2022 in People's Hospital of Macheng. Patients were grouped according to the levels of baseline ALBI. The corresponding cut-off values ​​were determined by receiver operating characteristic (ROC) curves. We also assessed potential predictive models for predicting efficacy of immunotherapy in advanced NSCLC.The median overall survival (OS) was not reached. The median OS of patients with PS ≤ 1 after immunotherapy was significantly longer than that of PS ≥ 2, which was NR vs. 6.67 months (HR=0.14, 95% CI: 0.05-0.46; p0.01). The risk of death for patients with low ALBI (-2.52) was significantly lower than that of patients with high ALBI (HR=0.28, 95% CI: 0.08-0.94; p=0.03). Univariate analysis showed that baseline ALBI and PS were factors significantly affecting OS in patients with advanced NSCLC after immunotherapy (p0.05 for all). The combination of ALBI and PS showed a good predictive value in prognosis of these patients after immunotherapy (p0.01).The baseline ALBI and PS may serve as prognostic factors for advanced NSCLC patients treated with immunotherapy.

Background Patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) remain at increased risk of recurrent ischemic events. An abbreviated dual antiplatelet therapy (DAPT) duration as short as 1 month has been suggested for those at high bleeding risk (HBR). Whether the benefits of 1-month DAPT are preserved in HBR patients presenting with non-ST-elevation ACS (NSTE-ACS) is subject of debate. Purpose To assess the impact of NSTE-ACS presentation on the ischemic and bleeding outcomes of HBR patients undergoing PCI with a cobalt-chromium everolimus-eluting stent followed by a 1-month versus 3-month DAPT. Methods The XIENCE Short DAPT Program encompasses three prospective, international, single-arm studies evaluating the safety and efficacy of a 1-month (XIENCE 28 USA and Global) or 3-month (XIENCE 90) DAPT duration. The program enrolled HBR patients who had undergone successful XIENCE stent implantation for acute or chronic coronary syndrome (excluding ST-elevation ACS). Event-free subjects discontinued DAPT at 1 or 3 months post-PCI. The primary endpoint was the composite of all-cause death or myocardial infarction (MI), while the key secondary endpoint was Bleeding Academic Research Consortium (BARC) type 2–5 bleeding between 1 and 12 months post-PCI. Ischemic and bleeding events associated with 1-month versus 3-month DAPT were assessed according to clinical presentation using propensity-score (PS) adjustment. Results Out of 3,364 HBR patients (n=1,392 on 1-month DAPT and n=1,972 on 3-month DAPT), 1164 (34.6%) underwent PCI for NSTE-ACS. At 12 months, the risk of death or MI was similar between 1- and 3-month DAPT in patients with (adjHR 1.12, 95% CI 0.73–1.70) and without NSTE-ACS (adjHR 0.92, 95% CI 0.65–1.29; p-interaction = 0.33). Landmark analysis between 1 and 3 months post-PCI showed significant treatment effect modification according to clinical presentation (p-interaction = 0.03) with greater benefit of 1-month DAPT in stable patients. BARC 2–5 bleeding was consistently reduced in both NSTE-ACS (adjHR 0.58, 95% CI 0.38–0.90) and stable patients (adjHR 0.86, 95% CI 0.63–1.18; p-interaction = 0.15). Conclusions Among HBR patients undergoing PCI with an everolimus-eluting stent, 1-month compared with 3-month DAPT was associated with similar 1-year risk of ischemic events and reduced bleeding, irrespective of clinical presentation. Between 1 and 3 months post-PCI, however, stable patients seemed to derive greater net benefit from 1-month DAPT compared to those with NSTE-ACS. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Abbott

We discuss the analyses of gated, x-ray imaging data from polar-direct-drive experiments with cryogenically layered deuterium–tritium targets on the OMEGA laser. The in-flight shell asymmetries were diagnosed at various times during the implosion, which was caused by the beam pointing geometry and preimposed variations in the energy partition between the different groups of laser beams. The shape of the ablation surface during the acceleration phase of the implosion was measured along two different lines of sight, and a Legendre mode ( ℓ-mode) decomposition was applied for modes of up to ten to investigate shell asymmetries. A clear causal relationship between the imposed beam imbalance and the shape of the in-flight shell asymmetries was observed. The imploded shell with a balanced energy ratio shows smaller values of the amplitudes of ℓ-mode 2 compared to that from implosions with an imbalanced ring energy ratio. The amplitudes of ℓ-modes 4 and 6 are the same within the measurement uncertainty with respect to the change in beam energy ratio.

Background The Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention (TWILIGHT) randomized clinical trial demonstrated that in selected high risk patients who took ticagrelor and aspirin for 3 months after percutaneous coronary intervention (PCI), continuing ticagrelor alone was associated with significantly less bleeding events than ticagrelor plus aspirin and did not lead to ischemic harm over a period of 1 year (1). The prevalence and risk of adverse events of patients fulfilling the TWILIGHT inclusion criteria in real-world setting is unclear. Purpose To elucidate the prevalence and prognosis of patients fulfilling the TWILIGHT inclusion criteria. Methods Patients that received at least one drug eluting stent in a coronary artery at a large tertiary center (Mount Sinai Hospital, New York) were considered for inclusion. As in the TWILIGHT trial, individuals on chronic oral anticoagulation treatment, with STEMI, cardiogenic shock, on dialysis, with prior stroke, or platelet count 30mm, thrombotic target lesion, bifurcation requiring 2 stents, left main or proximal left anterior descending artery lesion, atherectomy device use, SYNTAX score ≥23) TWILIGHT inclusion criterion; 2) Non-TWILIGHT-like patients, who did not fulfil at least one clinical and one angiographic TWILIGHT inclusion criterion. The primary outcome was a composite of death, myocardial infarction (MI), stroke. Secondary outcomes included bleeding, components of the primary outcome, target vessel and target lesion revascularization, stent thrombosis. All events were assessed at 1 year after PCI. Results Out of 30,470 patients undergoing PCI between 2012 and 2019, 13,236 were included in the current analysis. TWILIGHT criteria were met in 11,018 (83%) patients. Established vascular disease and multivessel CAD were the most frequently fulfilled criteria. At 1 year, TWILIGHT-like patients were at higher risk for the primary outcome (3.2% vs 1.1%, HR 2.85, 95% CI 1.83–4.44), severe bleeding (3.3% vs 1.8%, HR 1.86, 95% CI 1.32–2.62), all-cause death (1.4% vs 0.4%, HR 3.63, 95% CI 1.70–7.77), myocardial infarction (1.8% vs 0.6%, HR 2.81 95% CI 1.56–5.04), TVR (7.8% vs 4.1%, HR 1.94, 95% CI 1.53–2.47), TLR (5.1% vs 1.7%, HR 2.98 95% CI 2.07–4.29). Stent thrombosis and stroke rate were generally low and did not differ between patients meeting or not the TWILIGHT inclusion criteria. Conclusion Among all-comer patients undergoing PCI, the fulfillment of the TWILIGHT inclusion criteria is frequent and is associated with a higher risk of death, ischemic and bleeding complications Funding Acknowledgement Type of funding sources: None.

Aims The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) is still debated. We appraised an abbreviated compared with a more prolonged DAPT regimen in this setting by using the totality of existing evidence. Methods and results A systematic review and meta-analysis was performed to search randomized clinical trials comparing abbreviated (i.e., short [3 months] or very-short [1 month]) with standard (≥6 months) DAPT in HBR patients. Six trials with 8,409 patients were included. Major or clinically relevant non-major bleeding (MCRB) and major adverse cardiovascular events (MACE) were the co-primary safety and efficacy endpoints. MCRB was lower with abbreviated compared to standard DAPT (risk ratio [RR] 0.63, 95% CI 0.41–0.95; I2=74%). No difference in terms of MACE (RR 1.03, 95% CI 0.89–1.20; I2=0%) all-cause death, cardiovascular death, stent thrombosis or myocardial infarction were observed. Network meta-analysis showed short or very-short DAPT to have the highest probability to prevent bleeding in HBR patients. Conclusion Abbreviated DAPT reduced bleeding without apparent increase in ischemic events in HBR patients undergoing PCI. Three-month or one-month DAPT courses appeared similarly effective to optimize the trade-off for ischemia and bleeding in this population. Funding Acknowledgement Type of funding sources: None.

Background Recent advances in drug eluting stents (DES) design have significantly decreased the rates of in-stent restenosis (ISR). Nonetheless, ISR remains a major problem, affecting 5–10% of patients undergoing percutaneous coronary intervention (PCI). Furthermore, PCI for ISR is often a poor prognostic factor for outcomes after the procedure. Historically, obese patients tended to have better outcomes when undergoing PCI, however it is unclear if this trend continues for the same population undergoing PCI for ISR. Purpose Investigate the outcomes of patients undergoing PCI for ISR in the overweight and normal weight population. Methods All patients undergoing PCI with DES implantation at a tertiary care center from January 2012 to December 2019 were included. Normal weight was defined as a body mass index (BMI) greater than or equal to 18.5 kg/m2 and less than 25 kg/m2, while overweight was defined as a BMI greater than or equal to 25 kg/m2. Patients with BMI Results Out of 16,234 patients with available data on BMI, 12,444 (76.7%) were overweight and 3,790 (23.3%) were normal weight. Among overweight patients, 2,879 (23.1%) underwent PCI for ISR versus 815 (21.5%) of normal weight patients. Regardless of BMI status, patients undergoing PCI for ISR had higher rates of co-morbidities such as hypertension, hyperlipidemia, and diabetes mellitus than non-ISR counterparts. At one year post PCI, both overweight and normal weight patients undergoing PCI for ISR had increased risk of MACE (overweight: 18.4% vs. 6.7%; HR 2.83; 95% CI 2.50–3.20; normal weight: 18.8% vs. 7.8%, HR 2.43, 95% CI 1.95–3.04) when compared to non-ISR counterparts, mostly driven by TVR (overweight: 16% vs. 4.6%; HR 3.58; 95% CI 3.11–4.13; normal weight: 15.2% vs. 4.1%; HR 3.69; 95% CI 2.80–4.86). However, only overweight patients undergoing PCI for ISR had higher risk of all cause mortality (2.2% vs. 1.5%; HR 1.42; 95% CI 1.03–1.95) and MI (3.0% vs. 1.3%, HR 2.22; 95% CI 1.64–2.99) when compared to non-ISR counterparts (Figure 1). Conclusions PCI for ISR was associated with increased risk of MACE, irrespective of body weight. The risks of all-cause mortality and MI in ISR vs non-ISR patients only reached statistical significance in overweight patients. Funding Acknowledgement Type of funding sources: None.

Background Biodegradable polymer (BP) drug-eluting stents (DES) have shown similar safety and efficacy compared with second-generation durable polymer (DP)-DES in several randomized trials and meta-analyses. However, study participants were generally maintained on a standard dual antiplatelet therapy (DAPT) for at least 6 months after percutaneous coronary intervention (PCI). Therefore, the differences in thrombogenicity between these two stent technologies may have been unappreciated, especially among patients with acute coronary syndrome (ACS). Purpose We aimed to compare the safety and efficacy of BP Biolimus-Eluting Stent (BP-BES) versus 2nd generation DP-DES among ACS patients undergoing PCI and receiving ticagrelor alone or in combination with aspirin. Methods We pooled individual patient-level data from two randomized controlled trials, the Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention (TWILIGHT, n=9,006) (1) and the GLOBAL LEADERS Adjudication Sub-Study (GLASSY, n=7,585) (2). In order to reduce biases related to trial design differences, only NST-ACS patients not fulfilling any exclusion criterion of both studies were included and 2 separate analysis for short (0 to 3 months after PCI) and long-term (3 to 12 months after PCI) outcomes were performed. Patients were stratified according to the stent used at index PCI (BP-BES vs 2nd generation DP-DES). In both analysis, the primary outcome was major adverse cardiovascular events (MACE, a composite of cardiovascular death, myocardial infarction and definite or probable stent thrombosis); the key secondary outcomes were target-vessel failure (TVF) and BARC 2, 3 or 5 bleeding. Events rate and risk were assessed separately for the two study periods and subsequently 12-months risk estimates were derived by pooling the results of the two analysis. Results Out of 7,729 and 6,572 NST-ACS patients included in the two analysis, 2,321 (30%) and 2,211 (33.6%) received a BP-BES, respectively. Among patients treated with BP-BES versus DP-DES, the occurrence of MACE was similar at 3 months after PCI (1.1% vs 1.4%, adjusted HR 0.81, 95% CI 0.51–1.29), while it was significantly lower in the former group between 3 and 12 months (1.7% vs 3.1%, adj. HR 0.46, 95% CI 0.32–0.67) and in the overall period (pooled adjusted HR estimate 0.58, 95% CI 0.43–0.77). Similarly, significant differences were observed for TVF and BARC 2, 3, or 5 bleeding, whose risk at 12 months was lower among BP-BES than DP-DES patients (pooled adj. HR estimate 0.49, 95% CI 0.38–0.63 and 0.79, 95% CI 0.79, 95% CI 0.65–0.97, respectively). Conclusion As compared to 2nd generation DP-DES, BP-BES was associated with a lower risk of MACE, TVF and bleeding among NST-ACS patients undergoing PCI and treated with ticagrelor with or without aspirin. The findings of this analysis are exploratory and need further confirmation. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Biosensors (Singapore)

Background The Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention (TWILIGHT) trial showed that a regimen consisting of a 3-month dual antiplatelet therapy (DAPT) followed by ticagrelor monotherapy reduces the rate of bleeding events without increasing ischemic complications compared with standard DAPT [1]. Previous studies, such as Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients (PARIS) demonstrated how deviation or cessation of the prescribed antiplatelet regimen might negatively affect clinical outcomes [2]. Purpose The proposed analysis aims to assess the impact of different antiplatelet therapy cessation patterns on ischemic and bleeding outcomes in patients treated with ticagrelor with or without aspirin after percutaneous coronary intervention (PCI). Methods All 7,119 patients randomized at 3 months post-PCI in the TWILIGHT study will be included. The analyses will be conducted separately in the two treatment arms (ticagrelor plus placebo and ticagrelor plus aspirin). According to the PARIS study definitions and as prespecified in the TWILIGHT trial protocol, the occurrence of the three following antiplatelet cessation modes will be assessed: 1) discontinuation (e.g., caused by intolerable side effects or because of a safety concern); 2) interruption (temporary, The primary endpoint will be the composite of all-cause death, myocardial infarction (MI), or stroke at 12 months after randomization. The key secondary endpoint will be BARC type 2, 3 or 5 bleeding. Other secondary endpoints will include the components of the primary endpoint, cardiovascular death, definite or probable stent thrombosis and BARC types 3 or 5 bleeding. The number of events will be estimated according to the antiplatelet cessation status before the clinical event. Hazard ratios and 95% confidence intervals will be generated using Cox proportional hazards models including antiplatelet therapy cessation as a time-updated variable. If more than one cessation event occurred during follow-up, the antiplatelet therapy cessation category will change only if the more recent mode is worse than the previous: disruption will have priority over interruption, which in turn will have priority over discontinuation. Patients without cessation events will represent the reference group. All adverse events and episodes of antiplatelet cessation were independently adjudicated. Results The results of this analysis will be presented for the first time at ESC 2022. Conclusion This prespecified analysis of the TWILIGHT study will show for the first time the impact on clinical outcomes of different antiplatelet therapy cessation modes when a regimen of Ticagrelor with our without aspirin is prescribed after PCI. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Astra Zeneca, United Kingdom

Background A short DAPT duration after coronary stenting has been associated with similar ischemic outcomes and fewer bleeding complications in patients at high bleeding risk (HBR). Whether these effects are preserved irrespective of concomitant oral anticoagulant (OAC) therapy remains unclear. Purpose To evaluate the safety and efficacy of 1-month versus 3-month DAPT among HBR patients with or without indication to OAC therapy who undergo cobalt-chromium everolimus-eluting stent implantation. Methods The XIENCE Short DAPT Program comprises three prospective, international, single-arm studies evaluating 1-month (XIENCE 28 USA and Global) or 3-month (XIENCE 90) DAPT in HBR patients who had undergone successful everolimus-eluting XIENCE stent implantation. OAC therapy at discharge was a study inclusion criterion. Subjects were eligible to discontinue DAPT at 1 or 3 months if free from ischemic events and adherent to DAPT. The primary endpoint was the composite of all-cause death or any myocardial infarction (MI). The major secondary endpoint was Bleeding Academic Research Consortium (BARC) type 2–5 bleeding. In this exploratory analysis, HBR patients on 1-month DAPT were compared with those on 3-month DAPT according to the presence of background OAC therapy. Ischemic and bleeding outcomes were assessed between 1 and 12 months after index PCI using propensity-score (PS) adjustment. Results A total of 3,364 patients, 1,392 on 1-month DAPT and 1,972 on 3-month DAPT, were eligible for the analyses. Patients on OAC therapy (n=1424, 42.3%) were younger, more often male and of white race, and with a lower prevalence of other HBR criteria such as chronic kidney disease and anemia. The incidence of death or MI at 12 months was similar between the two groups (8.0% vs 7.9%) while BARC 2–5 bleeding was higher in OAC patients (12.2% vs 7.2%). After PS adjustment, 1-month DAPT, compared with 3-month DAPT, did not increase the 1-year risk of death or MI in both OAC (adjHR 0.71, 95% CI 0.47–1.08) and non-OAC patients (adjHR 1.24, 95% CI 0.88–1.75; p-interaction = 0.11). The risk of BARC 2–5 bleeding was consistently reduced in both OAC (adjHR 0.71, 95% CI 0.51–1.00) and non-OAC patients (adjHR 0.77, 95% CI 0.53–1.11; p-interaction = 0.69). Conclusions Among HBR patients undergoing everolimus-eluting stent implantation, 1-month DAPT compared with 3-month DAPT was associated with similar ischemic outcomes and reduced bleeding, regardless of concomitant OAC therapy. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Abbott

Objective To describe the clinical characteristics of transmasculine individuals who underwent hysterectomy and characterize surgical pathology findings. Methods Under an institutional review board-approved protocol, transmasculine individuals who were undergoing hysterectomy and bilateral salpingectomy or bilateral salpingo-oophorectomy were retrospectively identified from a single institution. Past medical, surgical, obstetric, and gynecologic history were collected, including prior testosterone use, cervical cancer screening status, and preoperative pelvic imaging. Surgical pathologic findings of the endometrium, ovaries, and cervix were collected. Results A total of 72 individuals were included. The median age was 30 years (range 19-51). The majority of patients had private insurance (n=53, 74%) and were on testosterone at time of the preoperative visit (n=63, 88%). Forty-two patients (58%) reported anxiety, depression, or bipolar disorder, and 34 patients (47%) were taking an antidepressant or mood stabilizer. Of the 68 patients eligible for cervical cancer screening, 33 (49%) were up to date before their surgical consultation visits. Pelvic pain was the leading indication for surgery (n=65, 90%), and 29 patients (40%) had multiple listed indications for surgery. Surgical pathology results included cervical intraepithelial neoplasia 2-3 in three patients (4%), endometrial or cervical atrophy in 13 patients (18%), and ovarian or paratubal cysts in 16 patients (22%). Conclusion This study describes the distinct clinical characteristics and surgical pathology findings that health care professionals should consider when caring for this unique patient population, including a relatively high rate of mental health conditions, pelvic pain as the leading indication for surgery, and the presence of endometrial or cervical atrophy and ovarian or paratubal cysts on surgical pathology.

Spherical implosions in inertial confinement fusion are inherently sensitive to perturbations that may arise from experimental constraints and errors. Control and mitigation of low-mode (long wavelength) perturbations is a key milestone to improving implosion performances. We present the first 3D radiation-hydrodynamic simulations of directly driven inertial confinement fusion implosions with an inline package for polarized crossed-beam energy transfer. Simulations match bang times, yields (separately accounting for laser-induced high modes and fuel age), hot spot flow velocities and direction, for which polarized crossed-beam energy transfer contributes to the systematic flow orientation evident in the OMEGA implosion database. Current levels of beam mispointing, imbalance, target offset, and asymmetry from polarized crossed-beam energy transfer degrade yields by more than 40%. The effectiveness of two mitigation strategies for low modes is explored.

Three dimensional discrete element (DEM) analyses were performed in Particle Flow Code (PFC3D) to study the effects of intermediate principal stress ratio and particle breakage on the critical state behaviors of granular materials. The variation of intermediate principal stress ratio is achieved by increasing intermediate and major principal stresses at different ratios. The breakage of calcareous sand particles is simulated in DEM with clumped particles using the octahedral shear stress crushing criterion. The macroscopic behaviors of crushable and uncrushable particles during shearing and at the critical state are compared. It is found that intermediate principal stress ratio and particle breakage affect the dilation and peak strength but have different effects on the critical stress ratios of the assemblies. The evolutions of micromechanical parameters such as redundancy factor, fabric and force anisotropies are examined to explain the difference between the behaviors of crushable and uncrushable assemblies under different stress paths.

Background Endovascular aortic repair is the common approach for abdominal aortic aneurysms, but endoleaks remain a significant problem with long-term success. Endoanchors have been found to reduce the incidence of type 1A endoleaks and can treat intraoperative type 1a endoleaks. However, little is known about the optimal number and position of endoanchors to achieve the best outcome. Methods Using image segmentation and a computational model derived from a reconstructed native patient abdominal aortic aneurysm geometry, the stability of the proximal seal zone was examined through finite element analysis in Abaqus (Dassault Systèmes, Providence, RI). The biomechanical parameter of contact area was compared for varying numbers (0, 2, 4, 8) and positions (proximal, medial, distal) of endoanchors under different adhesion strengths and physiologic pressure conditions. Results In every simulation, an increase in adhesion strength is associated with maintenance of proximal seal. For biologically plausible adhesion strengths, under conditions of normal blood pressure (120 mm Hg), the addition of any number of endoanchors increases the stability of the endograft-wall interface at the proximal seal zone by approximately 10% compared with no endoanchors. At hypertensive pressures (200 mm Hg), endoanchors increase the stability of the interface by 20% to 60% compared with no endoanchors. The positioning of endoanchors within the proximal seal zone has a greater effect at hypertensive pressures, with proximal positioning increasing stability by 15% compared with medial and distal positioning and 30% compared with no endoanchors. Conclusions Endoanchors improve fixation within the proximal seal zone particularly under conditions of high peak systolic pressure. Seal zone stabilization provides a mechanism through which endoanchor addition may translate into lower rates of type 1a endoleaks for patients., Clinical Relevance Endovascular aortic repairs are commonly used to treat abdominal aortic aneurysms. Type 1a endoleaks threaten the long-term durability of repairs. Endoanchors have been found to reduce the incidence of this complication. Herein, we examine parameters surrounding optimal endoanchor number and positioning to reduce endovascular aortic repair failure. The computational modeling allowed for testing of endoanchors in varied adhesion strength between the endograft and the aorta, as well as hemodynamic conditions to mimic normotension vs hypertension. The results of the finite element analysis suggest that the addition of any number of endoanchors in the proximal seal zone is beneficial, especially with hypertensive loading.

Objectives: The aims of this study were to evaluate if digital quantification of proliferation marker Ki-67 and mitotic marker phosphohistone H3 (PHH3) can reliably distinguish leiomyosarcoma (LMS) from smooth muscle tumors of uncertain malignant potential (STUMP), leiomyoma with bizarre nuclei (LMBN), and leiomyoma (LM), and if digital quantification of these markers correlates with clinical outcomes. Methods: Cases of LMS, STUMP, LMBN, and LM for which paraffin-embedded tissue was available were identified from a single institution. Manual evaluation of mitotic count was performed using hematoxylin and eosin (H&E) evaluation on 50 high powered fields (5 mm2). Immunohistochemical staining for Ki-67 and PHH3 was performed on one section from each case, and a high throughput digital quantification system was used to calculate an average percent stain. Receiver operating characteristic (ROC) curves for the ability of Ki-67 and PHH3 to predict LMS versus the other diagnostic groups were generated. Univariate Cox regression assessed for associations between each marker and progression-free survival (PFS) among patients with available follow-up. Results: A total of 39 cases (17 LMS, 5 STUMP, 10 LMBN, and 7 LM) were included. Mitotic count, Ki-67, and PHH3 were significantly correlated. When comparing the LMS group to the STUMP, LMBN, and LM groups combined, LMS showed a significantly greater digital quantification of Ki-67 (median 10.6% versus 0.4%, p Download : Download high-res image (67KB) Download : Download full-size image Conclusions: This study provides preliminary evidence that digital quantification of Ki-67, and possibly PHH3, can aid in a fast and reliable diagnosis of LMS versus other uterine smooth muscle tumors.

Immunotherapy is important in treating small-cell lung cancer (SCLC), and its anti-tumor effects are better when combined with radiotherapy. However, the toxicity of this combination is little known. This study assessed the incidences of adverse events when adding radiotherapy to ICIs in patients with SCLC. We searched the online databases to identify eligible studies and included nine references. For extensive-stage SCLC patients, the median PFS ranged from 4.5 to 12.5 months, and median OS ranged from 8.4 to NR months, respectively. The incidences of grade 3 or higher pneumonitis, lung infection, diarrhea, and fatal adverse events were 8.7% (95% CI: 5%-14.7%), 6.7% (95% CI: 2.5%-16.5%), 12.6% (95% CI: 7.6%-20%), and 5.1% (95% CI: 2.1%-11.6%), respectively. Our findings suggest that radiotherapy plus ICIs may provide acceptable safety and favorable efficacy for SCLC patients.