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Abstract Characterizing topologically nontrivial photonic lattices by measuring their topological invariants is crucial in topological photonics. In conservative one-dimensional systems, a widely used observable to extract the winding number is the mean-chiral displacement. In many realistic photonic systems, however, losses can hardly be avoided, and little is known on how one can extend the mean-chiral displacement to a driven-dissipative context. Here we theoretically propose an experimentally viable method to directly detect the topological winding number of one-dimensional chiral photonic lattices. The method we propose is a generalization of the mean-chiral displacement to a driven-dissipative context with coherent illumination. By integrating the mean-chiral displacement of the steady state over the pump light frequency, one can obtain the winding number with a correction of the order of the loss rate squared. We demonstrate that this method can be successfully applied to lattices along synthetic frequency dimensions.

Abstract Recurrent pregnancy loss (RPL) is a major reproductive health issue with multifactorial causes, affecting 2.6% of all pregnancies worldwide. Nearly half of the RPL cases lack clinically identifiable causes (e.g., antiphospholipid syndrome, uterine anomalies, and parental chromosomal abnormalities), referred to as unexplained RPL (uRPL). Here, we perform a genome-wide association study focusing on uRPL in 1,728 cases and 24,315 female controls of Japanese ancestry. We detect significant associations in the major histocompatibility complex (MHC) region at 6p21 (lead variant=rs9263738; P = 1.4 × 10−10; odds ratio [OR] = 1.51 [95% CI: 1.33–1.72]; risk allele frequency = 0.871). The MHC associations are fine-mapped to the classical HLA alleles, HLA-C*12:02, HLA-B*52:01, and HLA-DRB1*15:02 (P = 1.1 × 10−10, 1.5 × 10−10, and 1.2 × 10−9, respectively), which constitute a population-specific common long-range haplotype with a protective effect (P = 2.8 × 10−10; OR = 0.65 [95% CI: 0.57–0.75]; haplotype frequency=0.108). Genome-wide copy-number variation (CNV) calling demonstrates rare predicted loss-of-function (pLoF) variants of the cadherin-11 gene (CDH11) conferring the risk of uRPL (P = 1.3 × 10−4; OR = 3.29 [95% CI: 1.78–5.76]). Our study highlights the importance of reproductive immunology and rare variants in the uRPL etiology.

This study aimed to determine the applicability of a tail-attached device in monitoring animal-based indicators (ABI) associated with changes in environmental conditions in calves through investigating the relationship between sensor-derived ABI and the temperature-humidity index (THI). Furthermore, to identify effective ABI indicative of heat stress status, sensor-derived ABI of calves under differing heat stress levels based on rectal temperature (RT) were compared. The tail-attached device, which is capable of measuring skin temperature (ST), activity intensity, and roll angle along the longitudinal axis of the tail at 3-min intervals, was attached to 99 preweaning female Holstein calves for an average of 4 wk (26.4 ± 6.8 d). After selecting data from mild to hot days (daily average THI of ≥55), physiological (daily maximum tail ST) and behavioral (daily average activity intensity, daily total lying time, and daily total body position change) ABI were computed, and their relationship with the daily average THI was determined using piecewise regression analysis. Additionally, during the hot season, RT of 20 randomly selected tested calves were measured thrice a week (every 2.4 ± 0.5 d), and a comparison was conducted between the ABI of calves with normal RT (

Abstract Background Extracellular vesicles (EVs) hold the potential for elucidating the pathogenesis of amyotrophic lateral sclerosis (ALS) and serve as biomarkers. Notably, the comparative and longitudinal alterations in the protein profiles of EVs in serum (sEVs) and cerebrospinal fluid (CSF; cEVs) of sporadic ALS (SALS) patients remain uncharted. Ropinirole hydrochloride (ROPI; dopamine D2 receptor [D2R] agonist), a new anti-ALS drug candidate identified through induced pluripotent stem cell (iPSC)-based drug discovery, has been suggested to inhibit ALS disease progression in the Ropinirole Hydrochloride Remedy for Amyotrophic Lateral Sclerosis (ROPALS) trial, but its mechanism of action is not well understood. Therefore, we tried to reveal longitudinal changes with disease progression and the effects of ROPI on protein profiles of EVs. Methods We collected serum and CSF at fixed intervals from ten controls and from 20 SALS patients participating in the ROPALS trial. Comprehensive proteomic analysis of EVs, extracted from these samples, was conducted using liquid chromatography/mass spectrometer (LC/MS). Furthermore, we generated iPSC-derived astrocytes (iPasts) and performed RNA sequencing on astrocytes with or without ROPI treatment. Results The findings revealed notable disparities yet high congruity in sEVs and cEVs protein profiles concerning disease status, time and ROPI administration. In SALS, both sEVs and cEVs presented elevated levels of inflammation-related proteins but reduced levels associated with unfolded protein response (UPR). These results mirrored the longitudinal changes after disease onset and correlated with the revised ALS Functional Rating Scale (ALSFRS-R) at sampling time, suggesting a link to the onset and progression of SALS. ROPI appeared to counteract these changes, attenuating inflammation-related protein levels and boosting those tied to UPR in SALS, proposing an anti-ALS impact on EV protein profiles. Reverse translational research using iPasts indicated that these changes may partly reflect the DRD2-dependent neuroinflammatory inhibitory effects of ROPI. We have also identified biomarkers that predict diagnosis and disease progression by machine learning-driven biomarker search. Conclusions Despite the limited sample size, this study pioneers in reporting time-series proteomic alterations in serum and CSF EVs from SALS patients, offering comprehensive insights into SALS pathogenesis, ROPI-induced changes, and potential prognostic and diagnostic biomarkers.

Abstract Garnet peridotite xenoliths have been rarely reported from suboceanic mantle. Petrographic and geochemical characteristics of garnet-bearing oceanic peridotite xenoliths provide precious information on dynamics of the suboceanic lithosphere and asthenosphere interaction. We examined a lherzolite xenolith included in olivine nephelinite lava from Aitutaki Island, a member of the Cook-Austral volcanic chain. The lherzolite xenolith contains reddish fine-grained (

Background: Dupilumab has clinical effects in patients with moderate-to-severe asthma. When considering interleukin (IL)-4 and IL-13 signaling, effects of dupilumab on airway mucus hypersecretion and airway remodeling are expected, but they have been reported in only a few short-term studies. Its efficacy for airway hyperresponsiveness (AHR) remains unknown. We comprehensively assessed the efficacy of dupilumab, especially for subjective and objective measures of airway mucus hypersecretion and airway dimensions in moderate-to-severe asthmatic patients. Methods: In 28 adult patients with moderate-to-severe uncontrolled asthma, the comprehensive efficacy of 48-week dupilumab treatment, including the Cough and Sputum Assessment Questionnaire (CASA-Q), radiological mucus scores and airway dimensions on computed tomography (CT), was assessed prospectively. Treatment responsiveness to dupilumab was analyzed. Results: With 48-week dupilumab treatment, all four cough and sputum domain scores of CASA-Q improved significantly. Radiological mucus scores and airway wall thickening on CT were significantly decreased. The decreases in mucus scores were significantly associated with improvements in Asthma Control Questionnaire scores, Asthma Quality of Life Questionnaire (AQLQ) overall scores, airway obstruction, and airway type 2 inflammation. When defined by > 0.5 improvement in AQLQ overall scores, 18 patients (64%) were identified as responders. Conclusions: Dupilumab reversed subjective and objective measures of airway mucus hypersecretion and some aspects of airway remodeling in patients with moderate-to-severe uncontrolled asthma.

Purpose The aim of this study was to evaluate the differences in antithrombotic therapy policies for inferior vena cava (IVC) stent placement among institutions and interventional radiologists in Japan.

This study aimed to examine the relationship between changes in lifestyle habits and presenteeism change according to sex. This retrospective cohort study was conducted using data from health checkups, the World Health Organization Health and Work Performance Questionnaire (WHO-HPQ) short form, and health insurance claims for 9366 Japanese corporate employees in 2015 and 2016. Changes in 11 lifestyle habits of sleeping, eating, exercise, drinking, and smoking were classified into four patterns by combining lifestyle habits (good/poor): (a) no worsening, (b) worsening, (c) no improvement, and (d) improvement. A multiple regression analysis was conducted for each sex, with changes in the WHO-HPQ score as the objective variable, lifestyle habits change (worsening or improvement) as the explanatory variables, and age, job position, department, diseases, lifestyle habits, and WHO-HPQ score at baseline as adjustment variables. The results showed worsening of good lifestyle habits, such as sleeping, regular exercise, and frequency of drinking in men, while sleeping in women was associated with negative changes in the WHO-HPQ score. On the other hand, the improvement of poor lifestyle habit of sleeping was associated with positive changes in the WHO-HPQ score. These findings suggest that maintaining good lifestyle habits of sleeping for both sexes, and exercising and drinking for men, may be beneficial in maintaining work performance, while improving the poor lifestyle habit of sleeping for women may be beneficial in improving work performance.

We previously reported that a high HbA1c level 3 months before vitrectomy for vitreous hemorrhage or a large preoperative decrease in the HbA1c level over 3 months tended to increase the risk of rebleeding in diabetic retinopathy patients evaluated between 2010 and 2014. Here, we aimed to confirm these results with an extended study period and an increased number of operated eyes. This study included 121 diabetic patients who were admitted to Osaka University Hospital between 2010 and 2019 and who underwent vitrectomy for vitreous hemorrhage. Binomial logistic regression analysis was performed with the presence of postoperative bleeding as the outcome. The present study showed that the duration of the operation was associated with rebleeding (odds ratio = 1.02, p = 0.0016). A high HbA1c level just before vitrectomy tended to be associated with the bleeding (odds ratio = 1.27, p = 0.05), while preoperative HbA1c changes were not associated with rebleeding. The results of this study suggest that a high preoperative HbA1c level just before vitrectomy, not a decrease in HbA1c levels, in addition to the duration of the operation may increase the risk of postoperative bleeding after vitrectomy in diabetic retinopathy patients.

The final slope of Une mine experienced sudden increases in displacement in specific sections during the typhoons of 2007 and 2011, as observed through long-term monitoring since the excavation from the top. The rise in groundwater due to increased rainfall was identified as a significant factor leading to measures specifically targeting rainfall. Notably, despite previous instances of heavy rainfall, sudden displacements occurred without clear triggers, emphasizing the need for a comprehensive understanding of the behavior of the rock slope. Future maintenance efforts rely on elucidating these mechanisms, often solely attributed to rainfall. To analyze factors beyond rainfall affecting the final slope's displacement, this study introduces the concept of "unit rainfall displacement," representing displacement per unit rainfall. The unit rainfall displacement is defined as the annual final slope displacement divided by the cumulative effective annual rainfall. The cumulative effective annual rainfall is determined by cumulating rainfall for events with 100 mm or more rainfall for a year, based on previous studies indicating that the final slope exhibits behavior in such conditions. Focusing on the W4, a key fracture zone of Mt.Buko, this study explores the relationship between unit rainfall displacement and the exposure status of W4 on the final slope. ’ and the exposure status of W4 on the final slope. As a result, this study revealed an overview of W4's impact on the variations in unit rainfall displacement, providing insight into the rock slope displacement attributed to W4.

Abstract Neovascular age-related macular degeneration (nAMD) is a prevalent cause of permanent vision loss and blindness in the elderly worldwide, with a significant impact on patients’ daily lives. However, burdens related to nAMD from the patients’ perspective have not been well documented. Here we developed a new questionnaire after eliciting nAMD patients’ daily challenges followed by a pilot survey. Seven daily life burden domains were identified, and a quantitative survey was conducted using the questionnaire in the real-world clinic. Of the total 153 participants (mean age, 76.3 ± 8.3 years), 67 (43.8%) had bilateral nAMD, and 79 (52.7%) were classified into severe nAMD according to the best-corrected visual acuity with cut-off value of 0.52 in logMAR. Patients with bilateral and severe nAMD had significantly higher burden scores across all domains. Network models for the bilateral and severe disease subgroups identified the interactions between “activity of daily living” and “hand–eye coordination” and between “use of electronic devices” and “face recognition” domains, which were considered to be important burdens for the patients. These results can advance ophthalmologists’ understanding of the impact of nAMD on patients’ daily lives and the importance of active and continuing treatment for patients with nAMD.

Abstract Colorectal cancer (CRC) poses a significant global health challenge, demanding reliable prognostic tools to guide treatment decisions. This study introduces a novel prognostic scoring system, the albumin-total lymphocyte count-RAS index (ALRI), integrating serum albumin, lymphocyte count, and RAS gene mutations. A cohort of 445 stage I–III CRC patients undergoing curative resection was analyzed, revealing ALRI's association with clinicopathological factors, including age, tumor location, and invasion depth. The ALRI demonstrated superior prognostic value, with a cutoff value of 2 distinguishing high and low-risk groups. The high-ALRI group exhibited elevated rates of recurrence. Univariate and multivariate analyses identified ALRI as an independent predictor for both 5 year recurrence-free survival (RFS) and overall survival (OS). Kaplan–Meier curves illustrated significant differences in RFS and OS between high and low-ALRI groups, emphasizing ALRI's potential as a prognostic marker. Importantly, ALRI outperformed existing nutritional indices, such as controlling nutritional status and neutrophil-to-lymphocyte ratio, in predicting overall survival. The study underscores the comprehensive insight provided by ALRI, combining inflammatory, nutritional, and genetic information for robust prognostication in CRC patients. This user-friendly tool demonstrates promise for preoperative prognosis and personalized treatment strategies, emphasizing the crucial role of inflammation and nutrition in CRC outcomes.

Abstract Central nervous system tumors have resisted effective chemotherapy because most therapeutics do not penetrate the blood-tumor-brain-barrier. Nanomedicines between ~ 10 and 100 nm accumulate in many solid tumors by the enhanced permeability and retention effect, but it is controversial whether the effect can be exploited for treatment of brain tumors. PLX038A is a long-acting prodrug of the topoisomerase 1 inhibitor SN-38. It is composed of a 15 nm 4-arm 40 kDa PEG tethered to four SN-38 moieties by linkers that slowly cleave to release the SN-38. The prodrug was remarkably effective at suppressing growth of intracranial breast cancer and glioblastoma (GBM), significantly increasing the life span of mice harboring them. We addressed the important issue of whether the prodrug releases SN-38 systemically and then penetrates the brain to exert anti-tumor effects, or whether it directly penetrates the blood-tumor-brain-barrier and releases the SN-38 cargo within the tumor. We argue that the amount of SN-38 formed systemically is insufficient to inhibit the tumors, and show by PET imaging that a close surrogate of the 40 kDa PEG carrier in PLX038A accumulates and is retained in the GBM. We conclude that the prodrug penetrates the blood-tumor-brain-barrier, accumulates in the tumor microenvironment and releases its SN-38 cargo from within. Based on our results, we pose the provocative question as to whether the 40 kDa nanomolecule PEG carrier might serve as a “Trojan horse” to carry other drugs past the blood-tumor-brain-barrier and release them into brain tumors.

Abstract Harnessing non-spatial properties of photons as if they represent an additional independent coordinate underpins the emerging synthetic dimension approach. It enables probing of higher-dimensional physical models within low-dimensional devices, such as on a planar chip where this method is relatively nascent. We demonstrate an integrated thin-film lithium niobate ring resonator that, under dynamic modulation, simulates a tight-binding model with its discrete frequency modes representing lattice sites. Inter-mode coupling, and the simulated lattice geometry, can be reconfigured by controlling the modulating signals. Up to a quasi-3D lattice connectivity with controllable gauge potentials has been achieved by simultaneous synchronized nearest-, second- and third-nearest-neighbor coupling, and verified by acquiring synthetic band structures. Development of synthetic frequency dimension devices in the thin-film lithium niobate photonic integration platform is a key step in increasing the complexity of topological models achievable on a chip, combining efficient electro-optic mode coupling with non-linear effects for long-range mode interactions.

Background Left ventricular noncompaction (LVNC) is a hereditary type of cardiomyopathy characterized by prominent trabeculations. Detailed characteristics of biventricular noncompaction (BiVNC) remain unknown. This study aimed to elucidate the clinical characteristics and genetic landscape of BiVNC. Methods and Results We recruited children with left ventricular noncompaction from Japanese multi‐institutional centers from 2013 to 2021. Left ventricular noncompaction was classified as BiVNC, congenital heart disease, arrhythmia, dilated cardiomyopathy, or normal function. In these patients, cardiomyopathy‐associated genes were screened. A total of 234 patients (127 male; mean age, 4 months [range, 0–6.6 years]) were enrolled in this study, of whom 25 had BiVNC; 55, normal function; 84, dilated cardiomyopathy; 38, congenital heart disease; and 32, arrhythmia. BiVNC was diagnosed during the perinatal period in 10 patients, in whom the prevalence was higher than that in other patients. A total of 14 patients in the group with BiVNC had congenital heart disease, but not necessarily right heart lesions. Left ventricular dyskinesis was frequently observed in the lateral wall (24%) and apex (28%). Eleven pathogenic variants were found in 11 patients with BiVNC (44.0%). The group with BiVNC had a higher ratio of mitochondrial and developmental gene variants than the other groups. Among all groups, the group with BiVNC had the worst survival rate (P=0.0009). Conclusions Pediatric patients with BiVNC had a high rate of ventricular dyskinesis and poor outcome. A comprehensive and careful screening for disease‐causing genes and phenotype may help identify specific patients with left ventricular noncompaction and mortality‐related cardiac phenotypes.

Introdução: A pandemia da covid-19, iniciada em Wuhan, China, teve um impacto global significativo, com o Brasil apresentando mais de 658.000 mortes até março de 2022. A vacinação emergencial começou em janeiro de 2021, com a autorização de quatro plataformas vacinais pela ANVISA (Sinovac-CoronaVac, ChAdOx1 nCoV-19/AZD1222, BNT162b2 e Ad26.COV2.S), todas demonstrando segurança e eficácia na prevenção de complicações graves da Covid-19. Por serem novas para a população, muitos demonstraram receio, então os eventos supostamente atribuíveis à Vacinação ou Imunização (ESAVI) foram monitorados de perto para garantir sua segurança. Objetivo: O estudo teve como objetivo avaliar e descrever o perfil epidemiológico dos pacientes atendidos no ambulatório de eventos adversos pós-vacinação contra a covid-19 do Centro de Referência de Imunobiológicos Especiais do Instituto de Infectologia Emílio Ribas (CRIE-IIER). Método: O estudo descreve a experiência do CRIE-IIER ao longo de um ano, que ofereceu atendimentos gratuitos pelo SUS. Os pacientes foram encaminhados por médicos ou buscaram o serviço espontaneamente, e os dados foram analisados por características dos pacientes, tipo de vacina, sintomas e gravidade dos eventos, coletados de março de 2021 a março de 2022 por meio da revisão de prontuários do Instituto de Infectologia Emílio Ribas. Resultados: Durante o período do estudo, o CRIE-IIER atendeu 72 pacientes, sendo a maioria do sexo feminino (78,5%) e com idade entre 40 e 49 anos. Hipertensão arterial, diabetes e hipotireoidismo foram as comorbidades mais comuns. A maioria dos ESAVI ocorreu após a primeira dose da vacina (81,5%), sendo mais comumente relacionados a vacina ChAdOx1 nCoV-19/AZD1222. As manifestações sistêmicas foram mais comuns (89,2%) que as locais, e a maioria dos casos foi classificada como não grave (76,9%). Após o atendimento 53,8% dos pacientes tiveram como recomendação receber outras doses da vacina. Conclusão: Os resultados indicam que os ESAVI são geralmente não graves, com um risco significativamente menor do que os associados à própria infecção pela covid-19. A imunização em massa é fundamental no combate à pandemia, e oferecer assistência especializada fortalece o acesso ao conhecimento e a importância da vacinação. O acompanhamento contínuo dos pacientes pode fornecer informações valiosas sobre quaisquer reações adversas futuras e descartar reações falsamente atribuídas às vacinas.

Lenvatinib plus pembrolizumab (LP) therapy is currently used in patients with advanced or recurrent endometrial cancer. However, patients with uterine carcinosarcoma (UCS) were not included in the KEYNOTE-775, and the efficacy of LP therapy for patients with UCS in clinical practice remains unclear. We administered LP therapy to five patients with UCS. We aimed to report our clinical experience with LP therapy in these patients and investigate the genomic characteristics of those who responded to LP therapy.We retrospectively reviewed patients with UCS (n = 5) who underwent LP therapy at our hospital from January 2019 to December 2023. Efficacy was assessed using the response rate according to the Response Evaluation Criteria in Solid Tumors version 1.1. Safety was evaluated in terms of adverse events.The median age was 65 (55–78) years, and the mismatch repair status was proficient in all of the patients. One patient had stage II disease, and four had stage III. The median number of LP therapy courses was 8 (1–35). The overall response rate was 40%. None of the patients experienced adverse events that were grade 3 or higher. The median follow-up duration was 9 (1–26) months, median progression-free survival was 9.1 (0.16 to NA) months, and median overall survival was 10.2 (1.41 to NA) months.LP therapy may be effective for patients with UCS. As this report was based on a limited number of patients, more cases are required to investigate the efficacy of LP therapy in patients with UCS.

Peritoneal tumor dissemination and subsequent malignant tumor ascites (MTA) occur unexpectedly and repeatedly in patients with gastrointestinal (GI) cancers, and worsen quality of life and prognosis of the patients. Various treatments have been clinically developed for these patients, while most of the MTA cases are refractory to the treatments. Thus, effective treatments are urgently needed to improve the clinical outcomes. In this study, we identified α-synuclein (SNCA) as an immunological determinant of MTA progression in GI cancer through translational research using mouse tumor models and clinical specimens collected from gastric cancer patients. We found that the SNCA+ subsets were significantly increased in CD3+ T cells, CD56+ NK cells, and CD11b+ myeloid cells within MTA and peripheral blood cells (PBCs) of MTA cases, albeit almost absent in PBCs of healthy donors, and spleen of naive mice. Of note, the SNCA+ T-cell subset was rarely seen in patients that intraperitoneal lavage fluid without tumor cells was collected before surgery as a tumor-free control, suggesting a possible cancer-induced product, especially within the peritoneal cavity. In vivo treatment with anti-SNCA blocking mAb significantly induced anti-tumor effects in mouse MTA models, and synergistically improved anti-PD1 therapeutic efficacy, providing a significantly better prognosis. These suggest that SNCA is involved in severe immunosuppression in the MTA cases, and that blocking SNCA is effective in dramatically improving the immune status in the hosts. Targeting SNCA will be a promising strategy to improve clinical outcomes in the treatment of GI cancer patients, especially with MTA.

A 4-year-old girl presented with complaints of transient speech disorder and left-sided weakness. Magnetic resonance imaging revealed multiple strokes, computed tomography showed a right axillary artery aneurysm of 40 mm, and an angiogram indicated retrograde embolism. She underwent aneurysm resection and reconstruction with a saphenous vein graft. Two years after surgery, a mass lesion occurred in the native artery on the proximal side of the prior surgical anastomosis. Surgical resection and reconstruction were performed. An isolated 1-mm diameter lesion was found in the retrospectively reviewed completion angiogram from the initial surgery, which was the origin of the subsequent progressive lesion. The pathological examination, including after the initial surgery, revealed a myopericytoma.

A 9-year-old American Shorthair, castrated male, weighing 4.3 kg was presented to our hospital because of intermittent ataxia and tetraparesis for 6 weeks. On presentation, the cat was in a stupor and on recumbency, and had vertical nystagmus in both eyes. These clinical signs suggested a brainstem disorder. MRI showed a mass lesion in the caudal aspect of the fourth ventricle with hyperintensity on T2-weighted and FLAIR imaging, low-intensity on T1-weighted imaging, and enhanced margins on post-contrast T1-weighted imaging. The mass compressed the fourth ventricle, causing obstructive hydrocephalus. A second cystic lesion was found rostral to the cerebellum. After MRI, the cat experienced respiratory difficulties and the mass was removed by emergency craniectomy. Although the mass including the cyst wall was successfully removed, the cat was euthanized because spontaneous breathing did not return. The mass was histopathologically diagnosed as epidermoid cyst. A biopsy to the rostral cystic lesion had not been performed and therefore the etiology of this lesion remained unclear. This is the first case of feline intracranial epidermoid cyst in which MRI and surgical excision were performed. MRI findings were similar to those in humans and dogs, suggesting that imaging studies are useful in cats for the diagnosis of intercranial epidermoid cyst.

Developing foundation models for materials science has attracted attention. However, there is a lack of studies on inorganic materials due to the difficulty in the comprehensive representation of geometric concepts composing crystals: local atomic environments, their connections, and the global symmetries. We present a contrastive learning of inorganic crystal structure (CLICS) for embedding the geometric concepts, which contrasts texts representing the contextual patterns of geometries with the crystal graphs. We demonstrate that the geometric concepts are integrally embedded on the CLICS feature space, through experiments of concept prediction from crystal graphs, similar structure search, and few-shot/imbalanced crystal structure classification.

ABSTRACT: Numerical modeling of earthquake dynamics and derived insight for seismic hazard relies on credible, reproducible model results. The sequences of earthquakes and aseismic slip (SEAS) initiative has set out to facilitate community code comparisons, and verify and advance the next generation of physics-based earthquake models that reproduce all phases of the seismic cycle. With the goal of advancing SEAS models to robustly incorporate physical and geometrical complexities, here we present code comparison results from two new benchmark problems: BP1-FD considers full elastodynamic effects, and BP3-QD considers dipping fault geometries. Seven and eight modeling groups participated in BP1-FD and BP3-QD, respectively, allowing us to explore these physical ingredients across multiple codes and better understand associated numerical considerations. With new comparison metrics, we find that numerical resolution and computational domain size are critical parameters to obtain matching results. Codes for BP1-FD implement different criteria for switching between quasi-static and dynamic solvers, which require tuning to obtain matching results. In BP3-QD, proper remote boundary conditions consistent with specified rigid body translation are required to obtain matching surface displacements. With these numerical and mathematical issues resolved, we obtain excellent quantitative agreements among codes in earthquake interevent times, event moments, and coseismic slip, with reasonable agreements made in peak slip rates and rupture arrival time. We find that including full inertial effects generates events with larger slip rates and rupture speeds compared to the quasi-dynamic counterpart. For BP3-QD, both dip angle and sense of motion (thrust versus normal faulting) alter ground motion on the hanging and foot walls, and influence event patterns, with some sequences exhibiting similar-size characteristic earthquakes, and others exhibiting different-size events. These findings underscore the importance of considering full elastodynamics and nonvertical dip angles in SEAS models, as both influence short- and long-term earthquake behavior and are relevant to seismic hazard.