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This study projects the changes in tropical cyclone (TC) landfalls in the western North Pacific under shared socioeconomic pathway (SSPs) scenarios during the TC peak season by using low‐resolution global climate models participating in the Coupled Model Intercomparison Project phase 6 (CMIP6). Projections are based on the relationship between mid‐ and lower‐level atmospheric circulation and TC landfall frequency during the historical period from 1985 to 2014 and the future climate period from 2015 to 2100. The landfall areas for TCs are divided into northern East Asia (NEA), middle East Asia (MEA) and southern East Asia (SEA); the TC peak seasons are July–September for NEA and MEA, and July–November for SEA. To evaluate reproducibility, both ensemble and individual model outputs for mid‐ and lower‐level atmospheric circulations associated with TC landfall in each East Asian subregion are compared to the reanalysis. An ensemble of seven models with stable results for all three regions is more reasonable in simulating atmospheric circulation patterns than an ensemble of all CMIP6 models. The findings suggest that TC landfall is projected to increase by about 12% and 32% in NEA and MEA, respectively, in the late 21st century under the SSP5‐8.5 scenario compared to the historical period, while decreasing by 13% in SEA. These changes are consistent under both warming scenarios, and are more pronounced in the SSP5‐8.5 scenario compared to SSP1‐2.6, particularly in the later period of this century. An analysis of future atmospheric circulations suggests that global warming will weaken the western North Pacific subtropical high and cause its boundary to retreat eastward. This will lead to changes in the steering flow, which is closely related to TC tracks, resulting in TC landfalls to increase or decrease depending on the East Asian subregion. [ABSTRACT FROM AUTHOR]

Background: Next-generation sequencing (NGS) has been introduced to many Korean institutions to support molecular diagnostics in cancer since 2017, when it became eligible for reimbursement by the National Health Insurance Service. However, the uptake of molecularly guided treatment (MGT) based on NGS results has been limited because of stringent regulations regarding prescriptions outside of approved indications, a lack of clinical trial opportunities, and limited access to molecular tumor boards (MTB) at most institutions. The KOSMOS-II study was designed to demonstrate the feasibility and effectiveness of MGT, informed by MTBs, using a nationwide precision medicine platform. Methods: The KOSMOS-II trial is a large-scale nationwide master observational study. It involves a framework for screening patients with metastatic solid tumors for actionable genetic alterations based on local NGS testing. It recommends MGT through a remote and centralized MTB meeting held biweekly. MGT can include one of the following options: Tier 1, the therapeutic use of investigational drugs targeting genetic alterations such as ALK, EGFR, ERBB2, BRAF, FH, ROS1, and RET, or those with high tumor mutational burden; Tier 2, comprising drugs with approved indications or those permitted for treatment outside of the indications approved by the Health Insurance Review and Assessment Service of Korea; Tier 3, involving clinical trials matching the genetic alterations recommended by the MTB. Given the anticipated proportion of patients receiving MGT in the range of 50% ± 3.25%, this study aims to enroll 1,000 patients. Patients must have progressed to one or more lines of therapy and undergone NGS before enrollment. Discussion: This pragmatic master protocol provides a mass-screening platform for rare genetic alterations and high-quality real-world data. Collateral clinical trials, translational studies, and clinico-genomic databases will contribute to generating evidence for drug repositioning and the development of new biomarkers. Trial registration: NCT05525858. [ABSTRACT FROM AUTHOR]

This study investigates the influence of Okhotsk Sea blocking (OKB) on summer precipitation in East Asia in terms of the movement, enhancement and extension of the monsoon rainband. For this purpose, a composite analysis is conducted for nine OKB events that occur in June and July from 2000 to 2022. The results show that the OKB events that occur in June are associated with decreased precipitation in East Asia, whereas those that occur in July are related to increased precipitation in the same region. The long‐lasting OKB can continuously maintain and intensify anomalous cyclonic circulations in northeastern Asia, leading to enhanced vertically integrated moisture flux convergence (VIMFC) along the northern edge of the Western North Pacific subtropical high. However, there are differences in spatial distribution and displacement of anomalous cyclonic circulations between June and July. The OKB occurring in June is related to simultaneously developing and progressively strengthening anticyclonic circulation in the Okhotsk Sea as well as cyclonic circulation in northeastern Asia. Under the displacement of an intensified and southwardly extended cyclonic circulation, the VIMFC shifts southward and into a southeast‐to‐northwest orientation, compared to climatology, resulting in decreased precipitation in East Asia, particularly in southern China and southern Japan. On the other hand, when the OKB occur in July, anticyclonic circulation in the Okhotsk Sea is developed initially followed by cyclonic circulation in northeastern Asia, amplifying several days after onset. Anomalous cyclonic circulation is much weaker and located more northward than in June, which is favourable for stagnating and enhancing the VIMFC in East Asia. As a result, precipitation can increase in the region, particularly on the Korean Peninsula and in Japan. [ABSTRACT FROM AUTHOR]

Purpose GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a). Materials and Methods Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/wk) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study. Results RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of = grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0 to 8.0). Conclusion GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC. [ABSTRACT FROM AUTHOR]