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Abstract The observed cooling in the subpolar North Atlantic, known as the warming hole, is receiving much attention because of its relationship with the climate sensitivity in the Earth System Models (ESMs). However, the impact of its future projection on the global climate remains unclear due to large uncertainties. Here, we show that the future warming hole changes will affect the interhemispheric asymmetry of temperature and precipitation by modulating the Northern Hemisphere (NH) warming. Models with a weaker warming hole in the future project stronger NH warming by injecting more non‐radiative fluxes to the atmosphere. This leads to an asymmetric warming contrast between the two hemispheres, resulting in a meridional shift of the Inter‐Tropical Convergence Zone and more precipitation increases in the NH. Our study implies that the future warming hole controls the interhemispheric heat exchanges and associated changes in the global temperature and precipitation, suggesting that its improved simulation is essential.

Abstract Background Extramammary Paget's disease (EMPD) is rare. There are no standard treatments due to its rarity and few clinical trials. Methods The objective of this multicenter study was to investigate treatment outcomes of Korean patients with advanced/metastatic EMPD. Data were collected retrospectively from 14 institutions participating in Korean Cancer Study Group (KCSG) Rare Cancer Committee. Results A total of 37 patients were identified. Of these 37 patients, 6 received locoregional therapy as a first‐line treatment. In 31 patients who received systemic chemotherapy as a first‐line treatment, platinum‐based chemotherapy (n = 22) achieved an objective response rate (ORR) of 45.5% and a median progression‐free survival (PFS) of 7.89 months. Taxane‐based chemotherapy (n = 8) achieved an objective response rate of 62.5% and median PFS of 9.73 months. In second‐line chemotherapy, platinum‐based chemotherapy (n = 4) had a disease control rate (DCR) of 75.0% and median PFS of 3.45 months. Taxane‐based chemotherapy (n = 8) had a DCR of 75.0% and a median PFS of 8.67 months. Six patients received anti‐human epidermal growth factor receptor 2 (HER2) antibody during first‐ and second‐line chemotherapy. Overall, systemic chemotherapy combined with anti‐HER2 antibody had an ORR of 100% and a median PFS of 13.31 months. The ORR and PFS with systemic chemotherapy combined with trastuzumab was better than platinum‐ and taxane‐based chemotherapy only. Conclusions Due to its rarity, advanced or metastatic EMPD still has no established standard treatment. Results of our study indicate that the combination of trastuzumab with taxane has longer survival than trastuzumab monotherapy or conventional platinum‐ or taxane‐based chemotherapy.

Abstract The ice‐free Arctic in summer not only symbolizes human‐induced climate change but also highlights the need to critically consider climate change adaptation policies. To constrain projections when the Arctic Ocean will first become ice‐free, studies have typically combined the historical observations of the Arctic sea ice area (SIA) with future emission scenario simulations. However, these studies primarily relied on the historical climatology and trend of the Arctic SIA, without considering regional variations. In this study, we analyze September SIA projections using the Coupled Model Intercomparison Project Phase 6 (CMIP6) model simulations, while considering Arctic sub‐regions. Additionally, we assess the impact of incorporating sub‐region September SIA when constraining the first year of ice‐free Arctic in September. CMIP6 models generally overestimate the historical September SIA decreasing trend in the central Arctic, whereas they underestimate this trend in the surrounding shelf seas. The central Arctic, where the region expected to retain sea ice for the longest period in the future, holds particular significance for projecting when the Arctic will first become ice‐free. Consequently, when we employ the historical trend of September SIA in the central Arctic as a constraint, observationally‐constrained projections suggest a delay of 12 years (2056) for the first ice‐free September compared to raw/unconstrained projections (2044 in model average) under a high‐emission scenario. These findings underscore the importance of considering model biases in central Arctic SIA when constraining projections of the first year of ice‐free Arctic, which may occur later than previously projected in many studies.

Abstract When projecting future monsoon changes by carbon dioxide (CO2) pathway, most studies have analyzed precipitation responses without considering monsoon area (total area of monsoon domain, MA) variations. However, how MA responds to CO2 removal remains uncertain. This study evaluates MA variations and impacts in idealized CO2 ramp‐up (toward CO2 quadrupling), ramp‐down, and stabilized simulations using the Community Earth System Model version 1. Global MA negatively overshoots (i.e., recovery with decreasing tendency beyond the original MA) during the ramp‐down period due to reduced or rapidly recovered MA in several regional monsoons, including Northern and Southern Africa, South and East Asia, and South America, showing hysteresis when comparing CO2 ramp‐up and ramp‐down periods despite similar global warming levels. These non‐linear regional MA variations come from distinct regional summer and winter precipitation variations, which are found to be mostly associated with Intertropical Convergence Zone movements and El Niño‐like response. Further, regional monsoon precipitation characteristics also vary through CO2 ramp‐up and ramp‐down periods consistently with overall hysteresis. Changes in total monsoon precipitation resemble the distinct responses of MA. Our results suggest that regions characterized by a monsoonal climate may experience reduced seasonal rainfall variations under net‐negative CO2 emissions.

Abstract Global warming will soon reach the Paris Agreement targets of 1.5°C/2°C temperature increase above pre‐industrial levels. Under a business‐as‐usual scenario, the time to reach these targets varies widely among climate models. Using Coupled Model Intercomparison Project Phase 5 and 6, we show that a 2°C global warming is determined by Southern Ocean (SO) state closely tied with a low‐level cloud (LLC) amount feedback strength during reference (1861–1900) period; climate models with cold SO tend to accompany more low‐level cloudiness and Antarctic sea ice concentration due to a strong LLC amount feedback. Consequently, initially cold SO models tend to simulate a fast global warming by absorbing more downward shortwave radiation compared to initially warm SO models because more LLC disappears due to a strong LLC amount feedback during the 2°C rise. Our results demonstrate that climate models that correctly simulate initial SO state can improve 2°C warming projections with reduced uncertainties.

Abstract Under the ongoing and potential risks from anthropogenic warming, net negative carbon dioxide (CO2) emissions are inevitable to stabilize or recover the Earth's climate. It is important not only to understand climate irreversibility in response to CO2 removal but also to understand how fast each component of the climate system will recover to its original state. Based on idealized CO2 ramp‐up and ‐down ensemble simulations, here we show that the initial buoyancy states of the Arctic Ocean, such as upper ocean salinity and density, are vital to determining how fast Arctic and global mean temperatures will recover on a centennial time scale. The denser initial Arctic oceanic condition is linked to faster recovery of the Atlantic meridional overturning circulation (AMOC) in the ramp‐down period, which is further accelerated by strong positive AMOC‐salt‐advection feedback. Faster AMOC recovery can delay Arctic temperature recovery by transporting warmer water into the northern subpolar Atlantic during the ramp‐down period. In addition, denser Arctic water enhances vertical mixing, which also results in delayed Arctic cooling under a strong vertical temperature gradient in the subpolar‐to‐polar Atlantic. Our findings suggest that the Arctic's initial states have a centennial memory for the future Arctic and global climate changes.

Abstract The reversibility of global mean surface temperature was examined by a transient CO2 reversibility experiment using an Earth system model. The results showed that after CO2 ramp‐up toward CO2 quadrupling and ramp‐down returned to the present‐day level, the global mean surface temperature kept decreasing but stopped to change for ∼40 years in the early net‐zero CO2 emission period. This period, referred to a cooling hiatus, resulted from a compensation between Southern Hemisphere cooling and Northern Hemisphere warming. The Northern Hemisphere warming was centered over the North Atlantic. This localized warming was caused by an excessive heat advection by a delayed and surpassed Atlantic Meridional Overturning Circulation (AMOC) to CO2 forcing. During the progression of CO2 change, the meridional salinity gradient between subtropic and subpolar regions was enhanced, and the oceanic stratification in subpolar North Atlantic was reduced due to accumulated heat and reduced vertical salt import in the deeper ocean. As AMOC started to recover, consequently, the enhanced salt advection feedback and the relaxed buoyant force resulted in AMOC overshoot.

Abstract The linear recharge oscillator model for the El Niño–Southern Oscillation (ENSO) was expanded to a nonlinear model, thus allowing identification of a nonlinear dynamic ENSO index. This index was applied for a dynamic examination of the El Niño‐La Niña asymmetry. Here, the nonlinear physical processes including the nonlinear dynamical heating were implemented into the linear recharge oscillator model in the form of quadratic nonlinearity. This nonlinear recharge oscillator model revealed that nonlinear (linear) physical processes play a critical role in the long‐term ENSO skewness (amplitude) changes quantitatively. Particularly, the large part of the long‐term ENSO skewness change could be explained by the quadratic nonlinearity associated with the nonlinear ocean dynamical heating, which is closely related to change in mean thermocline. This research provides a unified framework to understand better the past‐present‐future ENSO changes by applying the interdecadal change dynamics on a low hierarchical level.

BACKGROUND: Osmotic release oral system (OROS®) hydromorphone is a potent, long-acting opioid analgesic, effective and safe for controlling cancer pain in patients who have received other strong opioids. To date, few studies have examined the efficacy of hydromorphone for pain relief in opioid-naive cancer patients.

Purposes. The study introduced the concept of “consecutive macular edema” and evaluated the validity of visual outcome in macular edema (ME) secondary to branch retinal vein occlusion (BRVO). Methods. Patients were categorized into the gainer group and the nongainer group according to the final visual acuity. We analyzed clinical characteristics involving total and consecutive duration of ME between the two groups. Results. Among the total 71 eyes of 71 patients, intravitreal bevacizumab injection (26 patients), triamcinolone (21), and natural course (33) were enrolled. The consecutive duration of ME was shorter in the gainer group than in the nongainer group (3.33 ± 1.50 and 5.24 ± 2.39 months; P=0.000). After exclusion of macular ischemia, consecutive duration of ME in gainer group was also significantly shorter than in nongainer group (3.62 ± 1.60 and 6.11 ± 4.20 months; P=0.010). Conclusions. The duration of ME in the nongainer group was longer than in the gainer group. In particular, the consecutive duration was an important factor in determining the final visual outcome. Clinical Trial Registration. Approval by Hallym University Sacred Heart Hospital Institutional Review Board/Ethics Committee was obtained for this retrospective study.

This study investigated the seasonality of tropical instability waves (TIWs) and its feedback to the seasonal cycle in the tropical eastern Pacific using a high-resolution ocean model covering 1958–2007. The climatological mean of the TIWs featured intraseasonal fluctuations, implying that TIWs are not occurring randomly, but their amplitude is partly in phase from one year to another. This seasonality of TIW activity is attributed to their dependency on the seasonal mean variation of current and temperature. Energy conversion analysis confirmed that the strong variability of TIWs near 4°N was due to the barotropic energy conversion associated with the large meridional shear of NECC and SEC and that at another pole near 2°N was due to the baroclinic energy conversion associated with the temperature front in the mixed layer. The former and latter poles are somehow largely responsible for amplifying the dynamic and thermal eddies of TIWs, respectively. The intensified TIWs during a boreal fall increase the tropical eastern Pacific SST by associating the warm thermal advection by anomalous currents, with a rate of up to 1°C/month in September. Therefore, this leads to interactive feedback between seasonal and intraseasonal variations, that is, TIWs in the tropical eastern Pacific.