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Bacillus is characterized by the formation of spores in harsh environments, which makes it suitable for use as a probiotic for feed because of thermostability and high survival rate, even under long-term storage. This study was conducted to investigate the effects of Bacillus-based probiotics on growth performance, nutrient digestibility, intestinal morphology, immune response, and intestinal microbiota of weaned pigs. A total of 40 weaned pigs (7.01 ± 0.86 kg body weight [BW]; 28 d old) were randomly assigned to two treatments (4 pigs/pen; 5 replicates/treatment) in a randomized complete block design (block = BW and sex). The dietary treatment was either a typical nursery diet based on corn and soybean meal (CON) or CON supplemented with 0.01% probiotics containing a mixture of Bacillus subtilis and Bacillus licheniformis (PRO). Fecal samples were collected daily by rectal palpation for the last 3 days after a 4-day adaptation. Blood, ileal digesta, and intestinal tissue samples were collected from one pig in each pen at the respective time points. The PRO group did not affect the feed efficiency, but the average daily gain was significantly improved (p < 0.05). The PRO group showed a trend of improved crude protein digestibility (p < 0.10). The serum transforming growth factor-β1 level tended to be higher (p < 0.10) in the PRO group on days 7 and 14. There was no difference in phylum level of the intestinal microbiota, but there were differences in genus composition and proportions. However, β-diversity analysis showed no statistical differences between the CON and the PRO groups. Taken together, Bacillus-based probiotics had beneficial effects on the growth performance, immune system, and intestinal microbiota of weaned pigs, suggesting that Bacillus can be utilized as a functional probiotic for weaned pigs.

The mode-II dynamic fracture behavior of poly(methyl methacrylate) (PMMA) was experimentally and numerically studied using ultra high-speed photography combined with digital image correlation and meshfree numerical simulations. Experiments were performed by launching a projectile from a gas gun onto pre-notched rectangular PMMA specimens. Two sample geometries were used, double edge notch specimens and single edge notch specimens. Additionally, two variations of the single edge notch specimen experiments were performed, in the first experiment the projectile directly hit the sample and in the second one a buffer was placed between the sample and projectile to ensure uniform loading. Finally, the effect of the notch sharpness was explored. The impact location was below the notch to ensure mode-II loading, which would then transition into mode-I loading once the crack starts to grow. Mode-II critical stress intensity factors were extracted and it was found that notch sharpness and loading conditions can have an effect on the path the crack follows upon fracture. All of these results were compared to numerical simulations of the crack propagation processes using a meshfree method. The numerical model successfully predicted the fracture toughness and the crack-path angle within 4% and 7% of experimental values, respectively. In addition, crack-tip speeds greater than 300 m/s were observed experimentally and numerically.

Background We aimed to assess the gene expression profiles of uninflamed small bowels in patients with Crohn’s disease (CD) to identify its accompanying molecular alterations. Methods We performed RNA sequencing of the uninflamed small bowel tissues obtained from 70 patients with ileal CD, and 9 patients with colon cancer (non-CD controls) during bowel resection. Differentially expressed gene (DEG) analyses were performed using DESeq2. Gene set enrichment, correlation, and cell deconvolution analyses were applied to identify modules and functionally enriched transcriptional signatures of CD. Results A comparison of CD patients and non-CD controls revealed that of the 372 DEGs, 49 protein-coding genes and 5 lncRNAs overlapped with the IBD susceptibility loci. The pathways related to immune and inflammatory reactions were upregulated in CD, while metabolic pathways were downregulated in CD. Compared with non-CD controls, CD patients had significantly higher proportions of immune cells, including plasma cells (P=1.15×10-4), and a lower proportion of epithelial cells (P=1.12×10-4). Co-upregulated genes (M14 module) and co-downregulated genes (M9 module) were identified in CD patients. The M14 module was enriched in immune-related genes and significantly associated with the responses to anti-TNF therapy. Intestinal tissue transcriptomic analysis of 3 independent cohorts, identified M14 module upregulation in non-responders at baseline, which was predictive of response with acceptable discrimination ability (area under the curve of 77~83%). Conclusion The differences in gene expression and cellular composition between CD patients and non-CD controls imply significant molecular alterations, which are associated with the response to anti-TNF treatment.

The charge weight per delay is one of the major variables in empirical models for predicting the peak particle velocity in tunnel blasting. In many instances, the corresponding initiation times of the detonators often overlaps. The overlaps occur because of the initiation time scatter of each of the detonators. The overlap, in turn, causes an increased charge weight per delay, which consequently causes an increase in the blast-induced vibration. In this study, a novel technique is introduced for development of a blasting pattern exploiting the initiation time scatter of the detonators. The initiation time of 423 detonators was measured using a vibration monitoring instrument and a high-speed camera. From the data obtained, a standard deviation of the initiation times of the detonators was determined. The probability of overlap of the initiation times of the detonators was calculated using a Monte Carlo simulation. After simulating both a new blasting pattern utilizing the initiation time scatter of the detonator and the conventional blasting pattern 10,000 times each, it was determined that, in the new blasting pattern, the number of sets in which four or more blastholes initiated simultaneously decreased from 17,595 to 1604. Moreover, the probability that four or more blastholes initiated simultaneously in a blasting round decreased from approximately 70% to 12%.

Methamphetamine (METH) is a psychostimulant with high abuse potential. Currently, there are no pharmacological treatments specific for METH abuse or stimulant use disorder generally. Although phosphodiesterase inhibitors have shown some promise, current animal models have not examined their use in abstinence from stimulant abuse. We employed a METH self-administration model in the rat followed by a forced abstinence period during which roflumilast, a phosphodiesterase 4 inhibitor, was administered. A detailed behavioral analysis of chronic treatment with roflumilast during 7 days of forced abstinence showed that roflumilast reduced METH seeking and METH taking upon subsequent relapse test. Roflumilast treatment during 7 days of forced abstinence did not affect sucrose seeking and sucrose taking behaviors. These data suggest that roflumilast may be a treatment for METH use disorder that is effective when administered only during abstinence.

The clinical characteristics of cutaneous lupus erythematosus (CLE) are well delineated in adults, but pediatric data, particularly in Asian populations, are limited. Therefore, we evaluated the characteristics of pediatric cases by retrospectively reviewing the medical records of children with CLE during a 15-year period in a tertiary care dermatology clinic in South Korea. The study included 21 children (8 males and 13 females), 4 of whom had neonatal lupus erythematosus (NLE). Among 17 patients with CLE, discoid lupus erythematosus (DLE) was most common (47.1%), followed by acute CLE (ACLE, 35.3%). All ACLE cases had systemic lupus erythematosus (SLE). Female predominance was conspicuous in ACLE/SLE (6/11 females versus 0/6 males), as was older age, whereas DLE and NLE showed near-equal sex distributions. The median age at the diagnosis of CLE was significantly higher in females than in males (15 years versus 4.5 years, p = 0.02). All patients with ACLE/SLE simultaneously showed skin and systemic symptoms from onset. The kidney was the most commonly involved organ. This study revealed unique characteristics of pediatric CLE, further warranting a comprehensive review among various ethnicities to understand the wide spectrum of CLE in the pediatric population.

PURPOSE/OBJECTIVE(S) Radiation-induced cardiac toxicity is an importantissue of breast RT. Although a relationship between mean heart dose and acute coronary event (ACE) risk was reported in previous study, the specific relationships between doses to cardiac structures or their sub-regions and subsequent toxicity have not been well defined. In this study, we studied the effect of radiation on specific heart segments on subsequent cardiac toxicity. MATERIALS/METHODS From the 1294 patients with breast cancer where previously demonstrated a relationship between mean heart dose and ACE, 21 patients who developed HF following breast RT and 39 with ACE were identified after an independent review by cardiologists. The study included 21 and 39 controls for respective toxicity who were matched according to age, comorbidities, and physical activity. For each patient who received radiotherapy, substructures were manually drawn, and then dose-distribution parameters of heart and substructures (Mean, Maximum (Max) dose, Relative volume at least given dose from 5-50 Gy in 5 Gy increments) were collected from CT planning data. To specify most critical regions for developing ACE, analysis using High-dimensional Cox regression model (SNet) was performed to reveal the effect of radiation on specific heart segments on subsequent cardiac toxicity. RESULTS In HF (n = 42) and ACE (n = 78) cohorts, characteristics between case and control were well matched. Mean time to develop heart failure, acute coronary events were 40.0 months and 42.2 months, respectively. In HF cohort, there was no significant difference not only in the mean heart dose (3.7 Gy vs 3.1 Gy, P = 0.652), but also in the mean left ventricle (LV) (5.0 Gy vs 4.1 Gy, P = 0.587), mean right ventricle (RV) (4.8 Gy vs 3.6 Gy, P = 0.473). On the other hand, in ACE cohort, there was significant difference in mean dose of heart (2.9 Gy vs 1.3 Gy, P = 0.015), left atrium (LA) (1.0 Gy vs 0.5 Gy, P = 0.008), LV (3.7 Gy vs 1.5 Gy, P = 0.028), left anterior descending artery (LAD) (6.6 Gy vs 2.4 Gy, P = 0.028) and right atrium (RA) (1.5 Gy vs 0.9 Gy, P = 0.025). In univariate analysis, mean dose of heart, LA, LV, LAD and RA was significant factors for acute coronary event free survival. ((Heart; P = 0.006, Hazard ratio (HR) 1.139, 95% Confidence Interval (CI) 1.035-1.253) (LA; P = 0.002, HR 1.735, 95% CI 1.209-2.490), (LV; P = 0.018, HR 1.079, 95% CI 1.012-1.150), (LAD; P = 0.031, HR 1.032, 95% CI 1.002-1.064), (RA; P = 0.008, HR = 1.307, 95% CI 1.068-1.598)). For predicting ACE risk for breast cancer patients, SNet model suggested nomogram based on mean and max LA dose, LAD V10, 15, 20, mean heart dose, mean RA dose and RV V35 in the order of higher predicted point variation. Based on this risk stratification model, event free survival significantly showed difference (P = 0.013). CONCLUSION There was significant difference between cardiac substructure dose parameters in ACE cohort, but not in HF cohort. Further analysis using convolution neural network will be performed to specify most critical region to be spared.

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes not only joint pain but also bone destruction resulting in impairment of quality of life. Tumor necrosis factor inhibitors have improved prognosis of patients with rheumatoid arthritis dramatically, especially in combination with methotrexate, however, the optimal dose of the concomitant methotrexate is unclear.ObjectivesTo evaluate the efficacy and safety of adalimumab in combination with reduced dose of methotrexate in patients with early RA with inadequate response to methotrexate.MethodsThe MIRACLE study was a multinational, randomized, open-label study in patients with RA with inadequate response to methotrexate conducted in Asia. It compared low dose and high dose methotrexate upon starting adalimumab. Methotrexate-naive patients with RA with a disease duration of less than two years started methotrexate at 6 to 8 mg/week and increased it to the maximum tolerable dose by week 12. Patients who have not achieved remission according to simplified disease activity index (SDAI) despite methotrexate ≥ 10 mg/week at week 24 were randomised to the maximum tolerable dose of methotrexate group (10 to 25 mg/week) or the reduced dose group (6 to 8 mg/week) and started to receive subcutaneous adalimumab 40 mg every other week. The primary endpoint was non-inferiority in the achievement of SDAI remission at week 48 in the reduced dose group compared with the maximum tolerable dose group with a non-inferiority margin of -15% based on two-sided 90% confidence interval. (NCT03505008)ResultsA total of 300 patients were enrolled in the study. Among them, 291 started methotrexate and were included in the analysis. The mean age was 57.7±15.2 years, female was 74.6%, and the mean disease duration from the diagnosis of RA was 21.1±56.2 days. Anti-CCP antibody was positive in 211 (73.0%) and the mean SDAI at study enrollment was 26.5±12.4. At week 24, with the mean dose of methotrexate of 12.6±2.9 mg/week, 108 patients (37.1%) achieved remission according to SDAI and continued MTX monotherapy. 134 patients (46.0%) were randomised and started adalimumab with 68 patients in the maximum tolerable dose group and 66 patients in the reduced dose group. At week 48, the remission achievement rates were 38.4 % and 44.8 %, respectively, with the adjusted risk difference of the reduced dose group to the maximum tolerable dose group of 6.4% (-7.0% to 19.8%, 90% CI), which met the criterion for noninferiority. No significant difference was found in health assessment questionnaire disability index ≤0.5 (59.1% vs 62.0%, respectively, p=0.72) and in radiological remission rates (Δmodified total Sharp score ≤0.5, 66.3% vs 62.0 %, respectively, p=0.59). Adverse drug reactions tended to be more frequent in the maximum tolerable dose group than in the reduced dose group (22.1% vs 9.1%, respectively, p=0.06).ConclusionThe MIRACLE randomised study demonstrated that, in patients with inadequate response to methotrexate, the efficacy of adalimumab with reduced dose of concomitant methotrexate was not inferior to that with maximum tolerable dose of methotrexate with better safety profile.Disclosure of InterestsHiroya Tamai Speakers bureau: Eisai, Grant/research support from: Eisai, Kei Ikeda Speakers bureau: AbbVie, Eisai, Eli Lilly, Novartis, Gilead, Asahi-Kasei, Grant/research support from: Mitsubishi-Tanabe, Toshiaki Miyamoto: None declared, Hiroaki Taguchi: None declared, Chang-Fu Kuo: None declared, Kichul Shin: None declared, Shintaro Hirata Speakers bureau: AbbVie, Asahi-Kasei, Astellas, Ayumi, Bristol Myers Squibb, Celgene, Chugai, Eisai, Eli Lilly, Gilead, Glaxo SmithKline, Janssen, Kyorin, Novartis, Pfizer, Sanofi, Tanabe-Mitsubishi, UCB, Paid instructor for: AbbVie, Mitsubishi-Tanabe, Consultant of: AbbVie, Astellas, Bristol Myers Squibb, Eisai, Gilead, Ily Lilly, Grant/research support from: AbbVie, Asahi-Kasei, Eisai, Otsuka, Sanofi, Shionogi, Chugai, Pfizer, Tanabe-Mitsubishi, Eli Lilly, UCB, yutaka okano: None declared, Shinji Sato Speakers bureau: AbbVie, Eisai, Grant/research support from: AbbVie, Eisai, Hidekata Yasuoka Speakers bureau: AbbVie, Asahi Kasei Pharma, Astellas, Daiichi-Sankyo, Eisai, Kissei, Takeda, Mitsubishi-Tanabe, Chugai, Novartis, Eli Lilly, Pfizer, Janssen, Sanofi, Teijin, Boehringer-Ingelheim, Bayer, Glaxo Smith Kline, Paid instructor for: AbbVie, Consultant of: AbbVie, Asahi Kasei, Grant/research support from: Mitsubishi-Tanabe, Takeda, Daiichi-Sankyo, Chugai, Bristol-Myers, MSD, Astellas, In Ah Choi Speakers bureau: Abbvie, Eisai, Sung-Hwan Park: None declared, Meng-Yu Weng Paid instructor for: Novartis, Eli Lilly, ChuGai, Abbvie, Consultant of: Abbvie, Masataka Kuwana Speakers bureau: Astellas, Asahi Kasei Pharma, Boehringer-Ingelheim, Chugai, Eisai, Janssen, Mochida, Nippon Shinyaku, Ono Pharmaceuticals, Pfizer, Mitsubishi-Tanabe, Consultant of: Boehringer-Ingelheim, Kissei, Mochida, Grant/research support from: AbbVie, Asahi Kasei Pharma, Boehringer-Ingelheim, Chugai, Eisai, MBL, Nippon Shinyaku, Ono Pharmaceuticals, Mitsubishi-Tanabe, Yun Jong Lee Grant/research support from: Yuhan, Tomonori Ishii Speakers bureau: Chugai, Mitsubishi-Tanabe, Glaxo Smith Kline, Pfizer, Eli Lilly, Janssen, AbbVie, Eisai, Astellas, Jinhyun Kim: None declared, Hideto Kameda Speakers bureau: AbbVie, Pfizer, Consultant of: AbbVie, Grant/research support from: AbbVie, Eisai, Toshihisa Kojima Speakers bureau: AbbVie, Pfizer, Eisai, Grant/research support from: AbbVie, Han Joo Baek: None declared, Ping-Ning Hsu: None declared, Chun-Ming Huang Paid instructor for: Abbvie, Pfizer, Tien-Tsai Cheng Paid instructor for: Abbvie, Grant/research support from: Abbvie, Wan-Yu Sung: None declared, Takehiro Taninaga Shareholder of: Eisai.co.,Ltd., Employee of: Eisai.co.,Ltd., Masahiko Mori Shareholder of: Eisai.co.,Ltd., Employee of: Eisai.co.,Ltd., Hideaki Miyagishi Shareholder of: Eisai.co.,Ltd., Employee of: Eisai.co.,Ltd., Yasunori Sato Speakers bureau: Eisai Co., Ltd. Kowa Company, Ltd., Consultant of: MOCHIDA PHARMACEUTICAL CO., LTD, Tsutomu Takeuchi Speakers bureau: Astellas, AbbVie, Ayumi, Bristol Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Glaxo Smith Kline, Janssen, Mitsubishi-Tanabe, Nippon-kayaku, Novartis, Pfizer, Sanofi, UCB, Grant/research support from: Asahi Kasei, AbbVie, Ayumi, Boehringer-Ingelheim, Chugai, Eisai, Eli Lilly, Mitsubishi-Tanabe, Sanofi, UCB, Yuko Kaneko Speakers bureau: Asahi Kasei, Astellas, Ayumi, Bristol Myers Squibb, Chugai, Eisai, Elli Lilly, Mitsubishi-Tanabe, Novartis, UCB, Grant/research support from: AbbVie, Chugai, Eisai, Mitsubishi-Tanabe, UCB.

The self-organization of strongly interacting electrons into superlattice structures underlies the properties of many quantum materials. How these electrons arrange within the superlattice dictates what symmetries are broken and what ground states are stabilized. Here we show that cryogenic scanning transmission electron microscopy (cryo-STEM) enables direct mapping of local symmetries and order at the intra-unit-cell level in the model charge-ordered system Nd1/2Sr1/2MnO3. In addition to imaging the prototypical site-centered charge order, we discover the nanoscale coexistence of an exotic intermediate state which mixes site and bond order and breaks inversion symmetry. We further show that nonlinear coupling of distinct lattice modes controls the selection between competing ground states. The results demonstrate the importance of lattice coupling for understanding and manipulating the character of electronic self-organization and that cryo-STEM can reveal local order in strongly correlated systems at the atomic scale., In this paper, the authors demonstrate that cryogenic scanning transmission electron microscopy allows for the direct mapping of the local arrangements and symmetries of electronic order, providing a useful method for studying strongly correlated systems. They show this using the example of Nd1/2Sr1/2MnO3, a model charge ordered material.

Combining multiple fast image acquisitions to mitigate scan noise and drift artifacts has proven essential for picometer precision, quantitative analysis of atomic resolution scanning transmission electron microscopy (STEM) data. For very low signal-to-noise ratio (SNR) image stacks – frequently required for undistorted imaging at liquid nitrogen temperatures – image registration is particularly delicate, and standard approaches may either fail, or produce subtly specious reconstructed lattice images. We present an approach which effectively registers and averages image stacks which are challenging due to their low-SNR and propensity for unit cell misalignments. Registering all possible image pairs in a multi-image stack leads to significant information surplus. In combination with a simple physical picture of stage drift, this enables identification of incorrect image registrations, and determination of the optimal image shifts from the complete set of relative shifts. We demonstrate the effectiveness of our approach on experimental, cryogenic STEM datasets, highlighting subtle artifacts endemic to low-SNR lattice images and how they can be avoided. High-SNR average images with information transfer out to 0.72 A are achieved at 300 kV and with the sample cooled to near liquid nitrogen temperature.

Background:Methotrexate (MTX) is the first-line therapy for rheumatoid arthritis (RA). The concentrations of MTX-polyglutamates (PG) in erythrocytes, an active form of MTX, are useful markers for the optimal usage of MTX in patients with RA. The concentrations of MTX-PG have been reported to be different between Japanese and Caucasians. However, the difference among Asian ethnicity remains unclear.Objectives:To examine MTX-PG concentrations in association with MTX dose during the first 24 weeks after the initiation of MTX for newly diagnosed RA patients in Japan, Korea and Taiwan.Methods:MIRACLE study is a multicenter, open-label, randomized, 48 weeks interventional study conducted in Japan, Korea and Taiwan to evaluate non-inferiority of low dose to high dose of MTX as an add-on therapy to adalimumab in 300 patients with RA who do not achieve remission after 24 weeks MTX monotherapy in stipulated dosage. In the first 24 weeks, MTX was started at 6 to 8 mg/week for newly diagnosed RA patients, and promptly escalated to the maximum tolerable dose in 12 weeks in principle. This interim data evaluation was intended to investigate the differences among countries in the relationship between MTX dose, safety and MTX-PG concentrations in erythrocytes during the first 24 weeks. The efficacy of the treatment is not included at this point.Results:A total of 166 patients (106 in Japan, 35 in Korea, 25 in Taiwan) were included in this interim data. The age at treatment initiation was 57.2 years old on average and female was 79.5%. The time course changes in total and individual MTX-PG levels differed in the three countries. At 24 weeks, whereas the mean total MTX-PG concentrations were comparable (112.9 nmol/L in Japan, 104.4 nmol/L in Korea, and 115.7 nmol/L in Taiwan) with a dose of MTX of 12.3 mg/week, 14.1 mg/week, and 12.2 mg/week, respectively, the individual MTX-PG concentrations were different. The MTX-PG1 and MTX-PG2 concentrations were lower in Korea than Japan and Taiwan whereas MTX-PG3, MTX-PG4 and MTX-PG5 concentrations were the highest in Korea.Conclusion:The distribution of short-chain and long-chain MTX-PG concentrations were various among Asian countries despite similar dose of MTX administration: NCT03505008.Disclosure of Interests:Hiroya Tamai: None declared, Yuko Kaneko Speakers bureau: AbbVie, Astellas, Ayumi, Bristol–Myers Squibb, Chugai, Eisai, Eli Lilly, Hisamitsu, Jansen, Kissei, Kirin, Pfizer, Sanofi, Takeda, Tanabe-Mitsubishi, and UCB., Grant/research support from: Sanofi, Hideto Kameda Speakers bureau: AbbVie, Pfizer, Consultant of: AbbVie, Grant/research support from: AbbVie, Eisai, Masataka Kuwana Speakers bureau: Astellas, Asahi Kasei Pharma, Boehringer- Ingelheim, Chugai, Eisai, Janssen, Mochida, Nippon Shinyaku, Ono Pharmaceuticals, Pfizer, Mitsubishi-Tanabe, Consultant of: Corbus, Grant/research support from: AbbVie, Asahi Kasei Pharma, Boehringer- Ingelheim, Chugai, Eisai, MBL, Nippon Shinyaku, Ono Pharmaceuticals, Mitsubishi-Tanabe, Yutaka Okano: None declared, Tomonori Ishii Speakers bureau: Chugai, Mitsubishi- Tanabe, Glaxo Smith Kline, Pfizer, Eli Lilly, Janssen, AbbVie, Eisai, Astellas, Kei Ikeda Speakers bureau: AbbVie, Eli Lilly, Novartis, Mitsubishi-Tanabe, Eisai, BMS, Grant/research support from: Mitsubishi-Tanabe, Hiroaki Taguchi: None declared, Shinji Sato: None declared, Toshiaki Miyamoto: None declared, Shintaro Hirata Speakers bureau: AbbVie, Asahi Kasei Pharma, Astellas, Ayumi, Bristol Myers Squibb, Chugai, Eisai, Eli Lilly, Janssen, Glaxo Smith Kline, Kissei, Pfizer, Sanofi, Mitsubishi- Tanabe, UCB, Paid instructor for: AbbVie, Mitsubishi- Tanabe, Consultant of: AbbVie, Eisai, Gilead, Grant/research support from: AbbVie, Chugai, Mitsubishi-Tanabe, UCB, Hidekata Yasuoka Speakers bureau: AbbVie, Asahi Kasei Pharma, Astellas, Daiichi- Sankyo, Eisai, Kissei, Takeda, Mitsubishi- Tanabe, Chugai, Novartis, Eli Lilly, Pfizer, Janssen, Sanofi, Teijin, Boehringer- Ingelheim, Bayer, Glaxo Smith Kline, Paid instructor for: AbbVie, Consultant of: AbbVie, Asahi Kasei, Grant/research support from: Mitsubishi-Tanabe, Takeda, Daiichi-Sankyo, Chugai, Bristol-Myers, MSD, Astellas, Toshihisa Kojima Speakers bureau: AbbVie, Pfizer, Eisai, Grant/research support from: AbbVie, Sung-Hwan Park: None declared, Kichul Shin: None declared, Han Joo Baek: None declared, Yun Jong Lee Grant/research support from: research fund, In Ah Choi Speakers bureau: Abbvie, Eizai, Grant/research support from: Abbvie, Eizai, Jinhyun Kim: None declared, Ping-Ning Hsu: None declared, Chang-Fu Kuo: None declared, Chun-Ming Huang Paid instructor for: AbbVie, Pfizer, Meng-Yu Weng Consultant of: AbbVie, Wan-Yu Sung: None declared, Wen-Chan Tsai: None declared, Tien-Tsai Cheng Paid instructor for: AbbVie, Grant/research support from: AbbVie, Takehiro Taninaga Shareholder of: Eisai Co., Ltd., Employee of: Eisai Co., Ltd., Masahiko Mori Shareholder of: Eisai Co., Ltd., Employee of: Eisai Co., Ltd., Hideaki Miyagishi Employee of: Eisai Co., Ltd., Yasunori Sato: None declared, Tsutomu Takeuchi Speakers bureau: Astellas, Abbvie, Daiichi Sankyo, Ayumi, Eisai, GlaxoSmithKline, Mitsubishi Tanabe, Chugai, Novartis, Eli Lilly, Pfizer, Bristol Myers Squibb, Janssen, UCB, TaishoToyama, Sanofi–Aventis, Nipponkayaku, Taiho, Gilead, Boehringer Ingelheim, Grant/research support from: Asahikasei, Astellas, Abbvie, Daiichi Sankyo, Ayumi, Eisai, Takeda, Mitsubishi Tanabe, Chugai, Eli Lilly, UCB, Sanofi–Aventis, Nipponkayaku, Boehringer Ingelheim

Purpose Acute ischemic strokes caused by steno-occlusive lesion of the cervical internal carotid artery are associated with poor clinical outcome. We evaluated the clinical efficacy of emergent carotid artery stenting for the management of these lesions. We compared the clinical outcomes regarding the intracranial lesion, namely tandem occlusions versus isolated cervical internal carotid artery occlusion. Materials and methods We retrospectively reviewed patients with acute ischemic stroke who underwent carotid artery stenting for cervical internal carotid artery steno-occlusive lesion between 2011 and 2018. After dividing the patients into two groups according to the presence or absence of intracranial lesions (tandem group and isolated cervical group), we analyzed demographic data, angiographic findings, and clinical outcomes. A modified Rankin Scale score ≤2 was defined as a favorable clinical outcome. Results Of 75 patients, 46 patients (61.3%) had tandem lesions, and the remaining 29 had only cervical internal carotid artery steno-occlusive lesion. Successful stenting was performed in all patients with favorable clinical outcomes (64.0%). Successful reperfusion score (thrombolysis in cerebral infarction ≥2 b) was 84.0%; tandem group (76.1%) versus isolated cervical group (96.6%) of cases. Mean modified Rankin Scale score at 90-days was 2.09. The rate of favorable clinical outcome showed no statistically significant difference between the two groups ( p = 0.454). Conclusions Endovascular treatment in patients with acute ischemic stroke due to cervical internal carotid artery steno-occlusive lesion is a technically feasible and clinically effective intervention regardless of intracranial occlusion. Therefore, we recommend endovascular treatment regardless of the presence of concomitant intracranial artery occlusion for patients with acute ischemic stroke caused by cervical internal carotid artery steno-occlusive lesion.

The self-organization of strongly interacting electrons into superlattice structures underlies the properties of many quantum materials. How these electrons arrange within the superlattice dictates what symmetries are broken and what ground states are stabilized. Here we show that cryogenic scanning transmission electron microscopy enables direct mapping of local symmetries and order at the intra-unit-cell level in the model charge-ordered system Nd1/2Sr1/2MnO3. In addition to imaging the prototypical site-centered charge order, we discover the nanoscale coexistence of an exotic intermediate state which mixes site and bond order and breaks inversion symmetry. We further show that nonlinear coupling of distinct lattice modes controls the selection between competing ground states. The results demonstrate the importance of lattice coupling for understanding and manipulating the character of electronic self-organization and highlight a novel method for probing local order in a broad range of strongly correlated systems.