Tumor-intrinsic perinuclear LOXL2: Prognostic relevance and relationship with YAP1 activation status in oral squamous cell carcinoma.

INTRODUCTION: Lysyl Oxidase-Like 2 (LOXL2) expression and function is frequently altered in different cancers, but scarcely explored in oral squamous cell carcinoma (OSCC). This prompted us to investigate the clinical relevance of LOXL2 expression pattern in OSCC and also a possible crosstalk with Hippo/YAP1 pathway signaling. METHODS: Immunohistochemical analysis of LOXL2 protein expression was performed in 158 OSCC patient samples, together with Yes-associated protein 1 (YAP1) activation status. Correlations with clinicopathological parameters and patient survival were assessed. RESULTS: Tumor cell-intrinsic LOXL2 expression showed two distinct expression patterns: diffuse cytoplasmic staining (64.6%), and heterogeneous perinuclear staining (35.4%). Remarkably, perinuclear LOXL2 staining was significantly associated with lymph node metastasis, advanced clinical stage and perineural invasion. Moreover, patients harboring tumors with perinuclear LOXL2 expression exhibited significantly poorer disease-specific survival (DSS) rates. Strikingly, we also found that perinuclear LOXL2 positivity gradually increased in relation to YAP1 activation, and patients harboring tumors with concomitant perinuclear LOXL2 and fully active YAP1 exhibited the worst DSS. Multivariate Cox analysis further revealed combined perinuclear LOXL2 and fully active YAP1 as a significant independent predictor of poor DSS. CONCLUSION: Tumor-intrinsic perinuclear LOXL2 emerges as a clinically and biologically relevant feature associated with advanced disease, tumor aggressiveness, and poor prognosis in OSCC. Moreover, this study unprecedentedly uncovers a functional relationship between perinuclear LOXL2 and YAP1 activation with major prognostic implications. Notably, combined perinuclear LOXL2 and fully active YAP1 was revealed as independent predictor of poor prognosis. These findings encourage targeting oncogenic LOXL2 functions for personalized treatment regimens.

Mapping the spatial dynamics of the CD4+ T cell spectrum in classical Hodgkin lymphoma.

As around 25-30% of classical Hodgkin Lymphoma (cHL) patients with advanced stages do not respond to standard therapies, the tumor microenvironment (TME) of cHL is one avenue that may be explored with the aim of improving risk stratification. CD4+ T cells are thought to be one of the main cell types in the TME. However, few immune signatures have been studied, and many of these lack related spatial data. Thus, our aim is to spatially resolve the CD4+ T cell subtypes that influence cHL outcome, depicting new immune signatures or transcriptional patterns that are in crosstalk with the tumor cells. This study was conducted using the Nanostring GeoMx DSP technology, based on the selection of distinct functional areas of patients' tissues followed by the gene-expression profiling. The goals were to assess the differences in CD4+ T cell populations between tumor-rich and immune-predominant areas defined by different CD30 and PD-L1 expression levels and to seek correlations with clinical metadata. Our results depict a complex map of CD4+ T cells with different functions and differentiation states that are enriched at distinct locations, the flux of cytokines and chemokines that could be related to these, and the specific relationships with the clinical outcome.

Decisional Conflict Regarding Disease-Modifying Treatment Choices Among Patients with Mid-Stage Relapsing-Remitting Multiple Sclerosis.

Purpose: Shared decision-making is critical in multiple sclerosis (MS) due to the uncertainty of the disease trajectory over time and the large number of treatment options with differing efficacy, safety and administration characteristics. The aim of this study was to assess patients' decisional conflict regarding the choice of a disease-modifying therapy and its associated factors in patients with mid-stage relapsing-remitting multiple sclerosis (RRMS). Methods: A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS (2017 revised McDonald criteria) and disease duration of 3 to 8 years were included. The level of uncertainty experienced by a patient when faced with making a treatment choice was assessed using the 4-item Decisional Conflict Scale. A battery of patient-reported and clinician-rated measures was administered to obtain information on symptom severity, illness perception, illness-related uncertainty, regret, MS knowledge, risk taking behavior, preferred role in the decision-making process, cognition, and self-management. Patients were recruited during routine follow-up visits and completed all questionnaires online using electronic tablets at the hospital. A multivariate logistic regression analysis was conducted. Results: A total of 201 patients were studied. Mean age (Standard deviation) was 38.7 (8.4) years and 74.1% were female. Median disease duration (Interquartile range) was 6.0 (4.0-7.0) years. Median EDSS score was 1.0 (0-2.0). Sixty-seven (33.3%) patients reported a decisional conflict. These patients had lower MS knowledge and more illness uncertainty, anxiety, depressive symptoms, fatigue, subjective symptom severity, a threatening illness perception, and poorer quality of life than their counterparts. Lack of decisional conflict was associated with MS knowledge (Odds ratio [OR]=1.195, 95% CI 1.045, 1.383, p=0.013), self-management (OR=1.049, 95% CI 1.013, 1.093, p=0.018), and regret after a healthcare decision (OR=0.860, 95% CI 0.756, 0.973, p=0.018) in the multivariate analysis. Conclusion: Decisional conflict regarding the selection of a disease-modifying therapy was a common phenomenon in patients with mid-stage RRMS. Identifying factors associated with decisional conflict may be useful to implement preventive strategies that help patients better understand their condition and strengthen their self-management resources.

Assessing illness-related uncertainty in relapsing-remitting multiple sclerosis: A psychometric analysis of the Mishel Uncertainty of Illness Scale.

A multicenter study involving 204 adults with relapsing-remitting multiple sclerosis (RRMS) assessed the dimensionality and item characteristics of the Mishel-Uncertainty of Illness Scale (MUIS), a generic self-assessment tool. Mokken analysis identified two dimensions in the MUIS with an appropriate item and overall scale scalability after excluding nonclassifiable items. A refined 12-item MUIS, employing a grade response model, effectively discriminated uncertainty levels among RRMS patients (likelihood ratio test p-value = .03). These findings suggest the potential value of the 12-item MUIS as a reliable measure for assessing uncertainty associated with the course of illness in RRMS.

Circulating tumor DNA for monitoring classic Hodgkin lymphoma patients: Correlation with FDG-PET/CT.

The value of circulating tumor DNA (ctDNA) as a biomarker of disease activity in classic Hodgkin lymphoma (cHL) patients has not yet been well established. By profiling primary tumors and ctDNA, we identified common variants between primary tumors and longitudinal plasma samples in most of the cases, confirming high spatial and temporal heterogeneity. Although ctDNA analyses mirrored HRS cell genetics overall, the prevalence of variants shows that none of them can be used as a single biomarker. Conversely, the estimation of hGE/mL, based on measures of total ctDNA, reflects disease activity and is almost perfectly correlated with standard parameters such as PET/CT that are associated with refractoriness.

Immune and stromal transcriptional patterns that influence the outcome of classic Hodgkin lymphoma.

Classic Hodgkin lymphoma (cHL) is characterized by a rich immune microenvironment as the main tumor component. It involves a broad range of cell populations, which are largely unexplored, even though they are known to be essential for growth and survival of Hodgkin and Reed-Sternberg cells. We profiled the gene expression of 25 FFPE cHL samples using NanoString technology and resolved their microenvironment compositions using cell-deconvolution tools, thereby generating patient-specific signatures. The results confirm individual immune fingerprints and recognize multiple clusters enriched in refractory patients, highlighting the relevance of: (1) the composition of immune cells and their functional status, including myeloid cell populations (M1-like, M2-like, plasmacytoid dendritic cells, myeloid-derived suppressor cells, etc.), CD4-positive T cells (exhausted, regulatory, Th17, etc.), cytotoxic CD8 T and natural killer cells; (2) the balance between inflammatory signatures (such as IL6, TNF, IFN-γ/TGF-ß) and MHC-I/MHC-II molecules; and (3) several cells, pathways and genes related to the stroma and extracellular matrix remodeling. A validation model combining relevant immune and stromal signatures identifies patients with unfavorable outcomes, producing the same results in an independent cHL series. Our results reveal the heterogeneity of immune responses among patients, confirm previous findings, and identify new functional phenotypes of prognostic and predictive utility.

Statistical analysis plan for the multicenter, open, randomized controlled clinical trial to assess the efficacy and safety of intravenous tirofiban vs aspirin in acute ischemic stroke due to tandem lesion, undergoing recanalization therapy by endovascular treatment (ATILA trial).

RATIONALE: In-stent reocclusion after endovascular therapy has a negative impact on outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Optimal antiplatelet therapy approach in these patients to avoid in-stent reocclusion is yet to be elucidated. AIMS: To assess efficacy and safety of intravenous tirofiban versus intravenous aspirin in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. SAMPLE SIZE ESTIMATES: Two hundred forty patients will be enrolled, 120 in every treatment arm. METHODS AND DESIGN: A multicenter, prospective, randomized, controlled (aspirin group), assessor-blinded clinical trial will be conducted. Patients fulfilling the inclusion criteria will be randomized at MT onset to the experimental or control group (1:1). Intravenous aspirin will be administered at a 500-mg single dose and tirofiban at a 500-mcg bolus followed by a 200-mcg/h infusion during the first 24 h. All patients will be followed for up to 3 months. STUDY OUTCOMES: Primary efficacy outcome will be the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. Primary safety outcome will be the rate of symptomatic intracranial hemorrhage. DISCUSSION: This will be the first clinical trial to assess the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. TRIAL REGISTRATION: The trial is registered as NCT05225961. February, 7th, 2022.

Offspring sex modifies the association between early-pregnancy adiposity and 2-year-old physical activity-The Glowing Study.

BACKGROUND: Rodent models suggest that in utero exposure to under and overnutrition programs offspring physical activity (PA) behaviors. Such nexus has not been established in humans. This study evaluated the association of early pregnancy maternal adiposity with offspring PA at age 2 years (2-yo-PA) taking into consideration prenatal and postnatal factors. METHODS: Women (n = 153) were enrolled early in pregnancy (<10 weeks). At enrollment, maternal adiposity [air displacement plethysmography, fat mass index (FMI, kg/m2)] and PA (accelerometers, activity counts) were measured, and age, race, and education self-reported. Gestational weight gain was measured at the research facility. Offspring birthweight and sex were self-reported. At age 2 years, parental feeding practices (child feeding questionnaire) were assessed, whereas anthropometrics (length and weight) and physical activity (accelerometers) were objectively measured. Offspring body mass index z-scores were calculated. Generalized linear regression analysis modeled the association of maternal FMI and 2-yo-PA [average activity counts (AC)4/day]. RESULTS: In bivariate associations, 2-yo-PA did not associate with maternal FMI (ß = -0.22, CI = -0.73 to 0.29, p = 0.398). However, maternal FMI interacted with offspring sex in association with 2-yo-PA. Specifically, 2-yo-PA was lower in girls (ß = -1.14, CI = -2.1 to -0.18, p = 0.02) compared to boys when maternal FMI was ≥7 kg/m2. When stratified by sex, 2-yo-PA of girls negatively associated with maternal FMI (ß = -0.82, CI = -1.43 to 0.29, p = 0.009) while no association was found between maternal FMI and boy's PA (ß = 0.32, CI = -0.38 to 1.01, p = 0.376). CONCLUSIONS: The association of 2-yo-PA and early pregnancy maternal adiposity was modified by offspring sex. Offspring's physical activity decreased with increasing early pregnancy adiposity maternal in girls but not boys in second parity dyads.

Impact of Balloon Guide Catheters in Elderly Patients Treated with Mechanical Thrombectomy: Insights from the ROSSETTI Registry.

BACKGROUND AND PURPOSE: Several nonrandomized studies have demonstrated the effectiveness of balloon guide catheters in treating patients with anterior circulation large-vessel occlusion. However, their impact on the elderly populations has been underreported. We aimed to analyze the effect of balloon guide catheters in a cohort of elderly patients (80 years of age or older) with anterior circulation large-vessel occlusion. MATERIALS AND METHODS: Consecutive patients from June 2019 to June 2022 were collected from the ROSSETTI Registry. Demographic and clinical data, angiographic endovascular technique, and clinical outcome were compared between balloon guide catheter and non-balloon guide catheter groups. We studied the association between balloon guide catheters and the rate of complete recanalization after a single first-pass effect modified TICI 2c-3, as well as their association with functional independence at 3 months. RESULTS: A total of 808 patients were included during this period, 465 (57.5%) of whom were treated with balloon guide catheters. Patients treated with balloon guide catheters were older, had more neurologic severity at admission and lower baseline ASPECTS, and were less likely to receive IV fibrinolytics. No differences were observed in terms of the modified first-pass effect between groups (45.8 versus 39.9%, P = .096). In the multivariable regression analysis, balloon guide catheter use was not independently associated with a modified first-pass effect or the final modified TICI 2c-3, or with functional independence at 3 months. CONCLUSIONS: In our study, balloon guide catheter use during endovascular treatment of anterior circulation large-vessel occlusion in elderly patients did not predict the first-pass effect, near-complete final recanalization, or functional independence at 3 months. Further studies, including randomized clinical trials, are needed to confirm these results.

Effect of Water and Carbon Dioxide on the Performance of Basolite Metal-Organic Frameworks for Methane Adsorption.

MOFs are potential adsorbents for methane separation from nitrogen, including recovery in diluted streams. However, water and carbon dioxide can seriously affect the adsorption performance. Three commercial MOFs, basolite C300, F300, and A100, were studied under similar conditions to fugitive methane streams, such as water (75 and 100% relative humidity) and carbon dioxide (0.33%) presence in a fixed bed. The presence of available open metal sites of copper (Cu2+) and aluminum (Al3+) in the case of basolite C300 and A100, respectively, constitutes a clear drawback under humid conditions, since water adsorbs on them, leading to significant methane capacity losses. Surprisingly, basolite F300 is the most resistant material due to its amorphous structure, which hinders water access. The combination of carbon dioxide and water creates a synergy that seriously affects basolite A100, closely related to its breathing effect, but does not constitute an important issue for basolite C300 and F300.

Picosecond spin-orbit torque-induced coherent magnetization switching in a ferromagnet.

Electrically controllable nonvolatile magnetic memories show great potential for the replacement of conventional semiconductor-based memory technologies. Here, we experimentally demonstrate ultrafast spin-orbit torque (SOT)-induced coherent magnetization switching dynamics in a ferromagnet. We use an ultrafast photoconducting switch and a coplanar strip line to generate and guide a ~9-picosecond electrical pulse into a heavy metal/ferromagnet multilayer to induce ultrafast SOT. We then use magneto-optical probing to investigate the magnetization dynamics with sub-picosecond resolution. Ultrafast heating by the approximately 9 picosecond current pulse induces a thermal anisotropy torque which, in combination with the damping-like torque, coherently rotates the magnetization to obtain zero-crossing of magnetization in ~70 picoseconds. A macro-magnetic simulation coupled with an ultrafast heating model agrees well with the experiment and suggests coherent magnetization switching without any incubation delay on an unprecedented time scale. Our work proposes a unique magnetization switching mechanism toward markedly increasing the writing speed of SOT magnetic random-access memory devices.

Effects of short-term supervised exercise training on liver fat in adolescents with obesity: a randomized controlled trial.

OBJECTIVE: The objective of this study was to quantify the effects of a 4-week, supervised, high-intensity interval training (HIIT) on intrahepatic triglyceride content (IHTG, percentage), cardiorespiratory fitness (CRF), and cardiometabolic markers in adolescents with obesity. METHODS: A total of 40 adolescents (age 13-18 y, BMI 36.7 ± 5.8 kg/m2 ) at risk for metabolic dysfunction-associated steatotic liver disease (MASLD) based on obesity and elevated Fibroscan measured controlled attenuation parameter (CAP) scores were randomized to HIIT three times a week for 4 weeks (n = 34) or observation (control; n = 6). Liver magnetic resonance imaging proton-density fat-fraction (MRI-PDFF), CAP, oral glucose tolerance test, serum alanine aminotransferase, dual-energy x-ray absorptiometry, and CRF tests were performed before and after intervention. Within- and between-group differences were compared. RESULTS: A total of 13 (38%) and 4 (66%) children had MASLD by MRI-PDFF (IHTG ≥ 5%) in the HIIT and control groups, respectively. The implemented HIIT protocol had no impact on CRF or IHTG (baseline 5.26%, Δ = -0.31 percentage points, 95% CI: -0.77 to 0.15; p = 0.179), but it decreased the 2-h glucose concentration (baseline 116 mg/dL, Δ = -11 mg/dL; 95% CI: -17.6 to -5.5; p < 0.001). When limiting the analysis to participants with MASLD (n = 17), HIIT decreased IHTG (baseline 8.81%, Δ = -1.05 percentage points, 95% CI: -2.08 to -0.01; p = 0.048). Between-group comparisons were not different. CONCLUSIONS: The implemented exercise protocol did not reduce IHTG, but it led to modest improvement in markers of cardiometabolic health.

Offspring-sex modifies the association between early-pregnancy adiposity and 2-year-old total physical activity - The Glowing Study.

Background: Rodent models suggest that in utero exposure to under and overnutrition programs offspring physical activity (PA) behaviors. Such nexus has not been established in humans. This study evaluated the association of early pregnancy maternal adiposity with offspring PA at age 2 years (2-yo-PA) taking into consideration prenatal and postnatal factors. Methods: Women (n=153) were enrolled early in pregnancy (<10 weeks). At enrollment, maternal adiposity [air displacement plethysmography, fat mass index (FMI, kg/m2)] and PA (accelerometers, activity counts) were measured, and age, race, and education self-reported. Gestational weight gain was measured at the research facility. Offspring birthweight and sex were self-reported. At age 2 years, parental feeding practices (child feeding questionnaire) were assessed, whereas anthropometrics (length and weight) and physical activity (accelerometers) were objectively measured. Offspring body mass index z-scores were calculated. Generalized linear regression analysis modeled the association of maternal FMI and 2-yo-PA [average activity counts (AC)4/day]. Results: There was an interaction between maternal FMI and offspring sex in association with 2-yo-PA (ß= -1.03, p= 0.030). Specifically, 2-yo-PA was lower in girls compared to boys when maternal FMI was ≥7 kg/m2. Maternal PA early in pregnancy positively associated with 2-yo-PA (ß= 0.21, p= 0.005). In addition, children born to women with college education tended to be more active compared to children born to women without college education (ß= 3.46, p= 0.059). Conclusions: Sexual dimorphism was observed in the associations of maternal adiposity with 2-yo-PA, with girls being less active compared to boys only when maternal FMI was ≥7 kg/m2.

BET inhibitors induce NF-κB and E2F downregulation in Hodgkin and Reed-Sternberg cells.

The prognosis of patients with relapsed and/or refractory classic Hodgkin lymphoma (cHL) continues to be poor. Therefore, there is a continuing need to develop novel therapies and to rationalize the use of target combinations. In recent years there has been growing interest in epigenetic targets for hematological malignancies under the rationale of the presence of common alterations in epigenetic transcriptional regulation. Since Hodgkin and Reed-Sternberg (HRS) cells have frequent inactivating mutations of the CREBBP and EP300 acetyltransferases, bromodomain and extra-terminal (BET) inhibitors can be a rational therapy for cHL. Here we aimed to confirm the efficacy of BET inhibitors (iBETs) using representative cell models and functional experiments, and to further explore biological mechanisms under iBET treatment using whole-transcriptome analyses. Our results reveal cytostatic rather than cytotoxic activity through the induction of G1/S and G2/M cell-cycle arrest, in addition to variable MYC downregulation. Additionally, massive changes in the transcriptome induced by the treatment include downregulation of relevant pathways in cHL disease: NF-kB and E2F, among others. Our findings support the therapeutic use of iBETs in selected cHL patients and reveal previously unknown biological mechanisms and consequences of pan-BET inhibition.

Dolomite industrial by-products as active material for CO2 adsorption and catalyst for the acetone condensation.

The feasibility of using dolomite powders, by-product from the refractory industry, as a CO2 adsorbent and as a catalyst for the acetone liquid-phase self-condensation is demonstrated in this article. The performance of this material can be largely improved by combining physical pretreatments (hydrothermal ageing, sonication) and thermal activation at different temperatures (500-800 °C). The highest CO2 adsorption capacity was observed for the sample after sonication and activated at 500 °C (46 mg·g-1). As to the acetone condensation, the best results were obtained also with the sonicated dolomites, mainly after activation at 800 °C (17.4% of conversion after 5 h at 120 °C). The kinetic model reveals that this material optimizes the equilibrium between catalytic activity (proportional to the total basicity) and deactivation by water (specific adsorption process). These results demonstrate that the valorisation of dolomite fines is feasible, proposing attractive pretreatments for obtaining activated materials with promising results as adsorbents and basic catalysts.

Spatially patterned 3D model mimics key features of cancer metastasis to bone.

Bone is the most common target of metastasis in breast cancer and prostate cancer, leading to significant mortality due to lack of effective treatments. The discovery of novel therapies has been hampered by a lack of physiologically relevant in vitro models that can mimic key clinical features of bone metastases. To fill this critical gap, here we report spatially patterned, tissue engineered 3D models of breast cancer and prostate cancer bone metastasis which mimic bone-specific invasion, cancer aggressiveness, cancer-induced dysregulation of bone remodeling, and in vivo drug response. We demonstrate the potential of integrating such 3D models with single-cell RNA sequencing to identify key signaling drivers of cancer metastasis to bone. Together, these results validate that spatially patterned 3D bone metastasis models mimic key clinical features of bone metastasis and can serve as a novel research tool to elucidate bone metastasis biology and expedite drug discovery.

Elevated LDL-C, high blood pressure, and low peak V ˙ O2 associate with platelet mitochondria function in children-The Arkansas Active Kids Study.

Purpose: To evaluate the association of platelet (PL) mitochondria respiration with markers of cardiovascular health in children ages 7-10 years. Methods: PL mitochondrial respiration (n = 91) was assessed by high resolution respirometry (HRR): Routine (R) respiration, complex (C) I linked respiration (CI), and maximal uncoupled electron transport capacity of CII (CIIE) were measured. The respiratory control ratio (RCR) was calculated as the ratio of maximal oxidative phosphorylation capacity of CI and CI leak respiration (PCI/LCI). Peak V ˙ O2 (incremental bike test) and body composition (dual-energy X-ray absorptiometry) were measured. Multiple generalized linear regression analysis was used to model the association of measures by HRR with variables of interest: adiposity, low-density lipoprotein (LDL-C) and triglyceride (TG) status (normal vs. elevated) HOMA2-IR, blood pressure status (normal vs. high), and demographics. Results: R and CI-linked respiration positively associated with adiposity, high blood pressure (HBP), and peak V ˙ O2. R and CI-linked respiration had inverse association with age and elevated LDL-C. CIIE was higher in children with elevated LDL-C (log-ß = -0.54, p = 0.010). HBP and peak V ˙ O2 interacted in relation to RCR (log-ß = -0.01, p = 0.028). Specifically, RCR was lowest among children with HBP and low aerobic capacity (i.e., mean peak V ˙ O2 -1SD). HOMA2-IR did not associate with measures of PL mitochondria respiration. Conclusion: In PL, R and CI-linked mitochondrial respiration directly associate with adiposity, peak V ˙ O2 and HBP. Elevated LDL-C associates with lower CI-linked respiration which is compensated by increasing CII respiration. PL bioenergetics phenotypes in children associate with whole-body metabolic health status.

Safety and efficacy of tirofiban in acute ischemic stroke due to tandem lesions undergoing mechanical thrombectomy: A multicenter randomized clinical trial (ATILA) protocol.

Background: In-stent thrombosis after mechanical thrombectomy (MT) worsen outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Although an optimal antiplatelet therapy is needed, the best approach to avoid in-stent thrombosis is yet to be elucidated. Hypothesis: Low-dose intravenous tirofiban is superior to intravenous aspirin in avoiding in-stent thrombosis in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. Methods: The ATILA-trial is a multicenter, prospective, phase IV, randomized, controlled (aspirin group as control), assessor-blinded clinical trial. Patients fulfilling inclusion criteria (AIS due to TL, ASPECTS ⩾ 6, pre-stroke modified Rankin Scale ⩽2 and onset <24 h) will be randomized (1:1) at MT onset to experimental (intravenous tirofiban) or control group (intravenous aspirin). Intravenous aspirin will be administered at a 500 mg single dose and tirofiban at a 500 µg bolus followed by a 200 µg/h infusion during first 22 h. All patients will be followed up to 3 months. Sample size estimated is 240 patients. Outcomes: The primary efficacy outcome is the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. The primary safety outcome is the rate of symptomatic intracranial hemorrhage. Secondary outcomes include functional independence defined as modified Rankin Scale 0-2, proportion of patients undergoing rescue therapy due to in-stent aggregation during MT and carotid reocclusion at 30 days. Discussion: ATILA-trial will be the first clinical trial regarding the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. Trial registration: NCT0522596.

Optically induced ultrafast magnetization switching in ferromagnetic spin valves.

The discovery of spin-transfer torque (STT) enabled the control of the magnetization direction in magnetic devices in nanoseconds using an electrical current. Ultrashort optical pulses have also been used to manipulate the magnetization of ferrimagnets at picosecond timescales by bringing the system out of equilibrium. So far, these methods of magnetization manipulation have mostly been developed independently within the fields of spintronics and ultrafast magnetism. Here we show optically induced ultrafast magnetization reversal taking place within less than a picosecond in rare-earth-free archetypal spin valves of [Pt/Co]/Cu/[Co/Pt] commonly used for current-induced STT switching. We find that the magnetization of the free layer can be switched from a parallel to an antiparallel alignment, as in STT, indicating the presence of an unexpected, intense and ultrafast source of opposite angular momentum in our structures. Our findings provide a route to ultrafast magnetization control by bridging concepts from spintronics and ultrafast magnetism.