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Prior research extensively investigates the delayed influence of El Niño‐Southern Oscillation (ENSO) events on subsequent summer climates, with persistent sea surface temperature anomalies (SSTAs) in remote tropical oceans serving as crucial pathways. This study unveils a previously overlooked midlatitude pathway. During the developing winter, El Niño events induce basin‐scale cold SSTAs in the central North Pacific, which can persist into the following summer. These anomalies significantly influence early‐summer atmospheric circulation by enhancing atmospheric baroclinicity and transient eddy activities. Primarily driven by transient eddy vorticity forcing, an equivalent barotropic geopotential low anomaly emerges over the North Pacific. Enhanced by the southwesterly winds of the atmospheric low, tropical moisture is transported farther northeastward in the early summer, resulting in increased rainfall in the Pacific Northwest region. By elucidating this meridional pathway, our study advances the understanding of ENSO's delayed impacts and associated dynamical processes, in which the midlatitude oceanic feedbacks are emphasized. Plain Language Summary: The El Niño‐Southern Oscillation (ENSO) events are considered as a primary driver of climate anomalies. Even during their decaying phase, its impact on the Northern Hemisphere summer climate remains notable. This study delves into the intricate mechanisms underlying the delayed impacts of ENSO events on subsequent summer climates. While prior research has extensively explored the zonal pathways involving tropical Indian and Atlantic oceans, this study illuminates a previously overlooked meridional pathway. It reveals that El Niño events trigger significant cold sea surface temperature anomalies (SSTAs) in the North Pacific during their mature phase in winter, which persist into the following summer. These SSTAs wield substantial influence over early‐summer atmospheric circulation, fostering atmospheric baroclinicity and transient eddy activities. Consequently, an anomalous low‐pressure system emerges over the North Pacific in early summer, enhancing southwesterly winds and transporting tropical moisture farther northeastward. This moisture influx results in increased rainfall in the Pacific Northwest region. By elucidating this meridional pathway, the study advances our comprehension of ENSO's delayed impacts, highlighting the crucial role of midlatitude oceanic feedbacks. In essence, it demonstrates how ENSO events can influence North American climate anomalies during subsequent early summer, shedding light on a previously unrecognized pathway of ENSO's effect. Key Points: Cold central North Pacific sea surface temperature anomalies (SSTAs), initiated by El Niño events, can endure into the subsequent summerBy transient eddy forcing, these cold SSTAs induce a whole‐layer geopotential low anomaly over North Pacific in post‐El Niño early summerThus, northeastward moisture transport strengthens, boosting increased early‐summer rainfall in Pacific Northwest after El Niño events [ABSTRACT FROM AUTHOR]

Xinjiang suffers compound hot and drought events under global warming. However, less attention has been paid to physical mechanisms of the variability of compound hot and drought events in this region. This article investigates the interannual variation of summer (June–August) compound hot and drought events in Xinjiang and its relationship with the sea surface temperature (SST) over the North Atlantic. The results show that its first empirical orthogonal function (EOF) mode features a spatially homogenous pattern. This mode is closely connected with the simultaneous meridional negative–positive–negative SST anomalies over the North Atlantic. The summer North Atlantic tripole SST anomalies can trigger a remarkable wave train extending from the North Atlantic to Eurasia, consequently inducing an anomalous high pressure system over the Iran–Pamir Plateau, which is conducive to the increase in air temperature from the surface to the upper troposphere over Xinjiang. The warmer troposphere further strengthens the western Asian subtropical meridional temperature gradient and thereby enhances the westerly wind to the north flank of the West Asian subtropical westerly jet (WASWJ). As a result, the WASWJ is displaced northward, which intensifies the sinking motion and prevents the water vapor transport to Xinjiang, leading to a decrease in precipitation in the target region. The higher temperature and less precipitation contribute to the occurrence of compound hot and drought events over Xinjiang. Numerical simulations based on the Community Atmosphere Model, version 4 (CAM4), further confirm the relationship between the North Atlantic tripole SST anomalies and compound hot and drought events in Xinjiang during summer on the interannual time scale. Significance Statement: Xinjiang, located in northwest China, suffers from frequent and intense compound hot and drought events in recent decades. It is thus urgent to understand the physical mechanisms associated with its occurrence in order for disaster prevention and mitigation. In this study, we reveal that the leading mode of summer compound hot and drought events over Xinjiang, featuring a spatially homogenous pattern, is closely correlated with the simultaneous meridional negative–positive–negative SST anomalies over the North Atlantic. The North Atlantic tripole SST anomalies can lead to an anomalous high pressure system over the Iran–Pamir Plateau and a northward shift of the West Asian subtropical westerly jet through exciting a wave train propagating from the North Atlantic to Eurasia, which consequently contributes to the occurrence of compound hot and drought events over Xinjiang. [ABSTRACT FROM AUTHOR]

Ischemic stroke is a cerebrovascular disease which is related to brain function loss induced by cerebral ischemia. Translocator protein (TSPO) is an important regulator in inflammatory diseases, while its role in ischemic stroke remains largely unknown. This research aimed to explore the role and action mechanism of TSPO in oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuron cell damage. The differentially expressed genes in ischemic stroke were predicted using GSE140275 dataset, DisGeNet, and GeneCards databases. Differentiated SH-SY5Y cells and primary neurons were subjected to transfection, and stimulated with OGD/R or MCC950 (NLRP3 inhibitor). Proteins were detected by western blotting and ELISA. Cell apoptosis was evaluated through CCK-8, caspase-3 activity and TUNEL assays. TSPO was upregulated in ischemic stroke and in SH-SY5Y cells and primary neurons after OGD/R treatment. TSPO silencing attenuated OGD/R-induced inflammation and apoptosis by decreasing NLRP3 inflammasome activity. TSPO downregulation increased PPARγ expression and decreased HMGB1 expression in OGD/R-treated cells, which was reversed by silencing PPARγ. PPARγ knockdown abolished the effect of TSPO silence on NLRP3 inflammasome activity, inflammation, and cell apoptosis in OGD/R-treated cells, while PPARγ overexpression alleviated OGD/R-induced injury in SH-SY5Y cells. In conclusion, TSPO knockdown attenuates neuroinflammation and neural apoptosis by decreasing NLRP3 inflammasome activity through PPARγ pathway. • TSPO expression is increased in ischemic stroke and OGD/R-treated cells. • TSPO knockdown attenuates OGD/R-triggered NLRP3 inflammasome activity. • TSPO silence mitigates NLRP3-mediated apoptosis in OGD/R-treated cells. • TSPO knockdown reverses OGD/R-induced inhibition of PPARγ pathway. • Inhibition of the PPARγ pathway abolishes the effect of TSPO silence on OGD/R-induced NLRP3 inflammasome and apoptosis. [ABSTRACT FROM AUTHOR]

West China Autumn Rain (WCAR), the last rainy season in China associated with the East Asian summer monsoon, is prone to flooding and secondary disasters and has profound impacts on the economic society. Thus, it is of great interest to understand its variability. Through an analysis with gridded rainfall data and reanalysis data, this study reveals that the variability of WCAR is positively correlated to the boreal summer (austral winter) sea ice concentration (SIC) in the Southern Indian and Pacific Ocean basins. Such a relationship is supported by the SIC-related changes in atmospheric circulations and water vapor transport. Corresponding to a high summer SIC, both the Lake Balkhash trough and the Asian low pressure are deepened, the East Asian jet shifts northward, and the water vapor transport to West China is enhanced during the boreal autumn, providing a favorable background for the increase of WCAR, and vice versa. The potential mechanism of how the boreal summer SIC affects the autumn atmospheric situation is further investigated. Results show that the atmospheric circulation in the high latitudes of the Southern Hemisphere possesses a seasonal persistence from the boreal summer to autumn due to the sea ice persistence. Thus, the boreal summer SIC-related anomalies in the upper-tropospheric winds over the Southern Indian and Pacific Ocean basins can persist to the following autumn and subsequently exert substantial influences on the Eurasian atmospheric circulations via two meridional teleconnections. The counterpart in the lower troposphere contributes to the water vapor transport toward West China. Certainly, this candidate mechanism is a preliminary explanation, and other processes may also act in their linkage. • Boreal summer sea ice in the Southern Indian and Pacific Ocean basins is positively correlated to West China autumn rain. • Their linkage is well supported by changes of autumn atmospheric circulation and water vapor conditions. • Sea ice resultant upper-tropospheric wind anomalies may affect Eurasian atmospheric circulations via two teleconnections. [ABSTRACT FROM AUTHOR]

Based on daily Japanese 55-year reanalysis data, this study analysed the daily energy budget characteristics of 94 Scandinavian (SCA) events in the positive phase during 62 winters from 1958 to 2020. Low-frequency circulation anomalies characterize the SCA events. The maintenance of low-frequency anomalies mainly comes from the extraction of both available potential energy (APE) and kinetic energy (KE) from the background field during both the developing stage and the decaying stage. This energy conversion characteristic is related to the "locking" effect of the background field. During the developing stage, the interactions among the low-frequency circulation anomalies continuously generate KE, which is the main source for initiating the primary circulation anomalies around western Europe and the Scandinavian Peninsula. Meanwhile, the horizontal KE advection maintains the KE of the circulation anomalies around Lake Baikal. The decay process of the SCA events is mainly related to the damping effect on the APE due to diabatic heating and the interactions among the low-frequency circulation anomalies. The SCA event is a type of atmospheric internal dynamic pattern. • Developing stage of SCA events is dominated by the barotropic eddy term. • Decaying stage of SCA events is due to baroclinic eddy term and diabatic heating. • Background field has a locking effect on the formation of the SCA events. • The SCA events belong to an atmospheric internal dynamic pattern. [ABSTRACT FROM AUTHOR]

KIAA0101, a proliferating cell nuclear antigen (PCNA)-associated factor, is reported to be overexpressed and identified as an oncogene in several human malignancies. The purpose of this study is to determine the function and possible mechanism of KIAA0101 in glioma progression. KIAA0101 expression in glioma patients was analyzed by GSE50161 and GEPIA datasets. Kaplan-Meier survival analysis was used to evaluate the survival distributions. KIAA0101 expression in glioma cells were detected by qRT-PCR and western blot analyses. The function of KIAA0101 was investigated using MTT, flow cytometry, caspase-3 activity, and Transwell assays. Additionally, glycolytic flux was determined by measuring extracellular acidification rate (ECAR), glucose consumption, lactate production, and adenosine triphosphate (ATP) level. The changes of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway were detected by western blot analysis. Results showed that KIAA0101 was upregulated in glioma tissues and cells. High KIAA0101 expression predicted a poor prognosis in glioma patients. KIAA0101 depletion impeded cell proliferation, migration, and invasion and triggered apoptosis in glioma cells. KIAA0101 silencing reduced the ECAR, glucose consumption, lactate production, and ATP level in glioma cells, suggesting that KIAA0101 knockdown inhibited glycolysis in glioma cells. Mechanistically, KIAA0101 knockdown inhibited the PI3K/AKT/mTOR pathway. In conclusion, KIAA0101 silencing inhibited glioma progression and glycolysis by inactivating the PI3K/AKT/mTOR pathway. [ABSTRACT FROM AUTHOR]

The long‐term memory of the ocean makes sea surface temperature anomalies (SSTAs) become a significant predictor for the subsequent atmosphere, and the tropical ocean is primarily regarded as a major source of atmospheric anomalies. While in North Pacific, the local midlatitude SSTAs also have large contributions but have not been adequately considered yet. We discover a strong connection between the Kuroshio‐Oyashio Extension (KOE) SSTAs in spring and the local atmospheric circulation anomalies in following summer at interannual timescale, wherein, the spring KOE SSTAs are generally independent of tropical ocean, and they are primarily induced by the concurrent atmospheric anomalies via surface heat flux and ocean dynamic processes. The spring KOE SSTAs can persist to summer, and then generate nearly reversed whole‐layer atmospheric circulation anomalies in their north side through both diabatic heating and atmospheric transient eddy forcing. Consequently, precipitation anomalies in Pan‐Pacific regions are distinctly modulated from spring to summer. Plain Language Summary: Because of the vast heat‐holding capacity and the long‐term memory of ocean, sea surface temperature anomalies (SSTAs) are usually taken as the significant factors to understand and predict climate anomalies. On interannual timescale, attentions have primarily centered on the tropical SSTAs, but recent studies indicated that the SSTAs in mid‐to‐high latitudes, especially in the Kuroshio‐Oyashio Extension (KOE) could have important feedbacks on the atmosphere. In this study, the KOE SSTAs in spring are discovered to have large interannual variability, and they are independent of the tropical SSTAs but closely linked to the subsequent summer atmospheric anomalies. It is found that the spring KOE SSTAs are mainly forced by the atmosphere via the surface heat flux and the ocean dynamic processes. In turn, they can persist to summer, and then play a dominant role in the air‐sea interaction in North Pacific, inducing remarkable geopotential height anomalies in north side. Consequently, in terms of the KOE SSTAs evolving from spring to summer, the Pan‐Pacific precipitation anomalies are distinctly modulated due to the opposite air‐sea interaction processes in the two seasons. These findings advocate for the use of springtime KOE SSTAs as a predictive indicator for following summer atmospheric and precipitation conditions. Key Points: The spring Kuroshio‐Oyashio Extension (KOE) sea surface temperature anomalies (SSTAs) are independent of tropical ocean and primarily forced by the concurrent local atmosphere at interannual timescaleThe spring KOE SSTAs can persist to summer and exert a delayed cross‐season impact on the subsequent summer atmosphereAssociated with the spring KOE SSTAs, precipitation anomalies in Pan‐Pacific regions are distinctly modulated from spring to summer [ABSTRACT FROM AUTHOR]

Many previous studies have examined the influence of Arctic sea ice on the weather/climate of the Northern Hemisphere. However, the precursor signals of Arctic sea ice regarding East Asian winter low temperatures, which are important for climate prediction, have received little attention. This study identified an out‐of‐phase relationship between the autumn sea ice area of the Kara Sea (SICK) and subsequent winter minimum temperature in Northeast China (NEC) during 1979–2019, that is, diminished SICK facilitates cooling anomalies at NEC. Further results showed that the Arctic Oscillation (AO) acts as a bridge in the linkage between the autumn SICK and minimum temperature in NEC. Diminished autumn SICK leads to a weakened polar vortex in both the troposphere and the stratosphere in the subsequent winter through vertical propagation of planetary waves, contributing to a negative phase of the AO. Accordingly, the SICK is followed by anomalous Rossby wave train that originates from Mediterranean Sea and propagates eastward to Northeast Asia. Thus, the SICK has substantially influences on the Mongolia cyclone and minimum temperature in NEC by modulation of the AO. Moreover, the shrinking SICK could lead to the upper‐level decelerated westerly anomalies at East Asia through altering the equator‐to‐pole temperature gradient and induce negative minimum temperature anomalies at NEC. The results of this study have importance regarding the prediction of low temperature anomalies over NEC. [ABSTRACT FROM AUTHOR]

Integrated energy systems offer significant potential for synergistic utilisation of electricity, heat, and gas, leading to improved energy efficiency. However, effectively controlling numerous small-capacity devices within these systems presents operational challenges. This paper proposes a novel multi-time scale optimisation strategy that aggregates small-capacity controllable devices to address this issue. To enable aggregation, we utilise an approximate Minkowski sum method to unify devices with similar control characteristics. A two-stage scheduling strategy is developed, including day-ahead and intra-day stages. The day-ahead stage involves optimisation based on forecasted information, aiming for economic and low-carbon operation. In the intra-day stage, a rolling optimisation method utilising model predictive control is employed, incorporating a penalty term to achieve precise load response through power adjustment. Extensive simulation experiments validate the feasibility and reliability of the proposed strategy in effectively controlling small-capacity devices within integrated energy systems. [ABSTRACT FROM AUTHOR]

Subseasonal reversal of warm Arctic–cold Eurasia (SR‐WACE) pattern has significant impacts on transitions of weather and climate extremes in Eurasia. This study explored the performances of climate models to simulate the main features of SR‐WACE. For real‐time predictions, most of the state‐of‐the‐art climate models showed limited ability to accurately forecast SR‐WACE in advance. Furthermore, most of the historical simulations from Phase 6 of the Coupled Model Intercomparison Project (CMIP6) had also difficulties in well simulating the SR‐WACE. Further exploration showed that the simultaneous reversal of the Ural blocking high (UB) and Siberian high (SH) is the key atmospheric driver of the SR‐WACE occurrences, which were verified by both of the real‐time predictions and historical simulations. Our results implied that the simulation of SR‐WACE was a huge challenge and the critical solutions included improving simulation of subseasonal reversals of UB and SH in the atmosphere. Plain Language Summary: We explored the performances of climate models to simulate the main features of subseasonal reversal of warm Arctic–cold Eurasia (SR‐WACE) pattern. For real‐time predictions, most of the state‐of‐the‐art climate models showed limited ability to accurately forecast SR‐WACE in advance, which possibly restricted the subseasonal to seasonal forecasts skill of climate anomalies in mid‐low latitudes. Furthermore, the historical simulations from Phase 6 of the Coupled Model Intercomparison Project (CMIP6) had also difficulties in well simulating the SR‐WACE. The most of CMIP6 models only reproduce the SR‐WACE phenomenon with higher order modes and lower explained variances than observations. We further explored the atmospheric circulation associated with the SR‐WACE in CMIP6 models and found that when a strong reversal of the Ural blocking high and Siberian high (SH) is simultaneously simulated can a SR‐WACE occur. This result was also validated in real‐time prediction models. Therefore, the simulation of SR‐WACE was a huge challenge and the critical solutions included improving simulation of subseasonal reversals of UB and SH in the atmosphere. Key Points: Most of climate models had difficulties in well simulating the subseasonal reversal of warm Arctic–cold Eurasia (SR‐WACE) patternMost of CMIP6 models only reproduce the SR‐WACE phenomenon with higher order modes and lower explained variances than observationsThe simultaneous reversal of the Ural blocking high and Siberian high is key for simulating the SR‐WACE [ABSTRACT FROM AUTHOR]

Drug resistance is a major impediment to the successful treatment of glioma. This study aimed to elucidate the effects and mechanisms of the long noncoding RNA membrane‐associated guanylate kinase inverted‐2 antisense RNA 3 (MAGI2‐AS3) on temozolomide (TMZ) resistance in glioma cells. MAGI2‐AS3 expression in TMZ‐resistant glioblastoma (GBM) cells was analyzed using the Gene Expression Omnibus data set GSE113510 and quantitative real‐time PCR (qRT‐PCR). Cell viability and TMZ half‐maximal inhibitory concentration values were determined using the MTT assay. Apoptosis and cell cycle distribution were evaluated using flow cytometry. The expression of multidrug resistance 1 (MDR1), ATP‐binding cassette superfamily G member 2 (ABCG2), protein kinase B (Akt), and phosphorylated Akt was detected using qRT‐PCR and/or western blot analysis. MAGI2‐AS3 was expressed at low levels in TMZ‐resistant GBM cells relative to that in their parental cells. MAGI2‐AS3 re‐expression alleviated TMZ resistance in TMZ‐resistant GBM cells. MAGI2‐AS3 overexpression also accelerated TMZ‐induced apoptosis and G2/M phase arrest. Mechanistically, MAGI2‐AS3 overexpression reduced MDR1 and ABCG2 expression and inhibited the Akt pathway, whereas Akt overexpression abrogated the reduction in MDR1 and ABCG2 expression induced by MAGI2‐AS3. Moreover, activation of the Akt pathway inhibited the effects of MAGI2‐AS3 on TMZ resistance. MAGI2‐AS3 inhibited tumor growth and enhanced the suppressive effect of TMZ on glioma tumorigenesis in vivo. In conclusion, MAGI2‐AS3 reverses TMZ resistance in glioma cells by inactivating the Akt pathway. [ABSTRACT FROM AUTHOR]

Assessing the capability of sub-seasonal rainfall forecast of dynamic model and proposing correction method is quite an important topic in current climate research field. From the perspective of rainfall amount, rainy days and rainfall-belt evolution, the sub-seasonal forecast ability of the European Centre for Medium-Range Weather Forecasts (ECMWF) model for the main rainy-season rainfall in eastern China is evaluated. Evaluation results show that the forecast biases increase gradually with the increase of forecast lead time, characterized by the predicted rainfall amount being obviously higher and the rainy days being much longer than observation. In order to reduce the forecast biases of sub-seasonal rainfall forecast of ECMWF model, the rainy day-based correction (RDC) method is proposed in this study. Cross validation results indicate that RDC method can modify the number of rainy days forecast of ECMWF model with the SCC of rainy days increasing by 12.96% ~ 18.62%, and the RMSE decreasing by 56.49% ~ 63.78%. The problem of maximum continuous rainy days being too long in the model forecast can be also improved. Meanwhile, the spatial correlation coefficient (SCC) of rainfall amount forecast of the ECMWF model with the observation weakly increases by 0.61% ~ 1.56% and the root mean square error (RMSE) decreases by 3.50% ~ 7.60% after the RDC treatment. Therefore, RDC method presents a good performance on improving the sub-seasonal forecast of rainy days, and maximum continuous rainy days, which can be further applied in other models' sub-seasonal forecast error correction. [ABSTRACT FROM AUTHOR]

Summer low-temperature in Northeast China (NEC) could cause local grain reduction. Recent studies have highlighted a notable increase in low-surface air temperature (SAT) events during June in NEC, which diverges significantly from the patterns observed in July, August, and the overall summer average. An analysis of June SAT over NEC from 1961 to 2020 reveals an interdecadal shift around 2003, characterized by decreased periodicity and increased interannual variability. This study investigates the influence of sea surface temperature anomalies (SSTAs) in the North Atlantic during the preceding February on this shift. It is found that the North Atlantic tripole SSTAs (NAT_SST) has a significant impact on June SAT in NEC post-2003. A proposed mechanism is that February NAT_SST can maintain the tripole anomalies into May-June, and inducing SSTAs over the tropical eastern Pacific (SST_EP) after 2003. Both observational and model simulation results support that NAT_SST influences June SAT in NEC through a wave train originating from the North Atlantic, while SST_EP affects SAT in NEC via the Circumglobal teleconnection and British-Baikal corridor-like patterns. The combined effects of May-June NAT_SST and SST_EP resonate to amplify June SAT anomalies over NEC, enhancing both the amplitude of SAT anomalies and interannual variability. Meanwhile, the periodicity of June SAT in NEC shifts to a 2–4 years cycle, aligning with the post-2003 alternation of NAT_SST. This contrasts with the period before 2002, where the relationship between February NAT_SST and May-June SST_EP was inverse, offsets the effects of the two SSTAs. [ABSTRACT FROM AUTHOR]

Arctic sea ice displays the high rates of decay during summer-autumn. Previous studies have revealed the impact of autumn Arctic sea ice on local and remote atmospheric circulation. Few attentions have been paid on the relationship between summer Arctic sea ice and climate variation at Eurasia. This study identifies a strengthened relationship between midsummer rainfall at Northeast China (NEC) and simultaneous sea ice area (SIA) in East Siberian Sea after the 1990s. The NEC’s rainfall shows a significant positive correlation with the SIA during 1994–2016, whereas the relationship is insignificant during 1961–1983. The strengthening of the relationship is attributed to the western elongation of background circulation at the North Pacific and the increased interannual variability of the SIA after the 1990s. The former facilitates the western extension of the SIAI-associated circulation over the Central North Pacific. The enlarged amplitudes of sea ice induce surface heat fluxes in situ, and then it leads to stronger meridional temperature gradient anomalies and intensified interaction between synoptic-scale eddies and mean flow over the North Pacific. These conditions jointly contribute to stronger and western elongation of circulation over the Central North Pacific during 1994–2016. Accordingly, the SIA has an intimate connection with NEC’s rainfall though the modulation of moisture transport and vertical movement. [ABSTRACT FROM AUTHOR]

The effect of soil moisture (SM) on precipitation is an important issue in the land–atmosphere interaction and shows largely regional differences. In this study, the SM of the ERA-Interim reanalysis and precipitation data of the weather stations were used to investigate their relationship over eastern China during July and August. Moreover, the WRF model was applied to further validate the effect of SM on rainfall. In the observations, a significantly negative relationship was found that, when the soil over southern China is wet (dry) in July, the rainfall decreases (increases) over the Huang–Huai–River basin (hereafter HHR) in August. In the model results, the soil can "memorize" its wet anomaly over southern China from July to August. In August, the wet soil increases the latent heat flux at surface and the air moisture at lower levels of the atmosphere, which is generally unstable due to the summer monsoon. Thus, upward motion is prevailing over southern China in August, and the increased surface air moisture is transported upwards. After that, the condensation of water vapor is enhanced at the middle and upper levels, increasing the release of latent heat in the atmosphere. The heat release forms a cyclonic circulation at the lower levels over eastern China, and induces the transport and convergence of water vapor increased over southern China in August. This further strengthens the upward motion over southern China and the cyclonic circulation at the lower levels. Therefore, positive feedback appears between water vapor transport and atmospheric circulation. Meanwhile, the cyclonic circulation over southern China results in a response of water vapor divergence and a downward motion over HHR. Consequently, the negative anomalies of precipitation occur over HHR in August. When the July soil is dry over southern China, the opposite results can be found through the similar mechanism. [ABSTRACT FROM AUTHOR]

Previous modelling and observational studies have shown discrepancies in the interannual relationship of winter surface air temperature (SAT) between Arctic and East Asia, stimulating the debate about whether Arctic change can influence midlatitude climate. This study uses two sets of coordinated experiments (EXP1 and EXP2) from six different atmospheric general circulation models. Both EXP1 and EXP2 consist of 130 ensemble members, each of which in EXP1 (EXP2) was forced by the same observed daily varying sea ice and daily varying (daily climatological) sea surface temperature (SST) for 1982–2014 but with different atmospheric initial conditions. Large spread exists among ensemble members in simulating the Arctic–East Asian SAT relationship. Only a fraction of ensemble members can reproduce the observed deep Arctic warming–cold continent pattern which extends from surface to upper troposphere, implying the important role of atmospheric internal variability. The mechanisms of deep Arctic warming and shallow Arctic warming are further distinguished. Arctic warming aloft is caused primarily by poleward moisture transport, which in conjunction with the surface warming coupled with sea ice melting constitutes the surface-amplified deep Arctic warming throughout the troposphere. These processes associated with the deep Arctic warming may be related to the forcing of remote SST when there is favorable atmospheric circulation such as Rossby wave train propagating from the North Atlantic into the Arctic. [ABSTRACT FROM AUTHOR]

The influence of early spring sea ice at Barents Sea on midsummer rainfall in Northeast China (NEC) is identified based on observational analyses and atmospheric modeling experiments in this study. Increased sea ice area (SIA) in the Barents Sea is ensued by positive rainfall anomalies at north of NEC and by negative anomalies at south, and vice verse. Specifically, due to a good seasonal persistence from spring to summer, the preceding sea ice anomalies exert an impact on midsummer surface air temperature anomalies and vertical stability over Barents Sea via the modulation on turbulent heat flux. The anomalous circulation is further triggered over Europe and the Mediterranean Sea through meridional vertical cells, with a barotropic structure. Accordingly, an effective Rossby wave source is excited over the eastern Mediterranean by the advection of vorticity by divergence wind, and causes an eastward propagation of Silk Road Pattern to East Asia. In addition, another SIA-related wave-like train can diffuse directly southeastward from Arctic to NEC in a polar path. Observations and numerical simulations indicate that, in response to increased sea ice at Barents Sea, an anomalous cyclone emerges over NEC, along with easterly or southeasterly over north of NEC and with northwesterly over south, leading to moisture convergence anomalies at north and divergence anomalies at south. Jointly, ascending (descending) motion anomalies favors a wet (dry) summer over north (south) of NEC. [ABSTRACT FROM AUTHOR]

The Eurasian continent experienced significant warming during the past decades. West Asia is located in an arid/semiarid zone, and its warming amplification has drawn considerable attention. However, the climatic effect of such a warming is not clear yet. In this study, we explored the possible impacts of recent land surface warming over West Asia on the atmospheric general circulation and climate. Results show that abnormal spring land surface warming over West Asia tends to increase precipitation over North China and decrease (increase) precipitation (air temperature) over Northeast China in early summer (June). It is noted that the precipitation anomalies are much stronger over the eastern region of North/Northeast China. Further analysis suggests that abnormal spring land surface warming can trigger eastward-propagating disturbances via diabatic heating, which intensifies the atmospheric circumglobal teleconnection (CGT) pattern, causing anomalous circulation and climate in early summer over northern China. Sensitivity experiments demonstrate that abnormal spring land surface warming can increase the atmospheric baroclinic instability and trigger Rossby waves that propagate along the westerly jet stream (WJS), resulting in the formation of CGT. Due to persistent land surface thermal forcing and the interaction between the basic flow (especially the WJS) and CGT, the CGT tends to be intensified. The anomalous wave center over East Asia in early summer is responsible for the precipitation increases (decreases) over North (Northeast) China and the evident warming in Northeast China. Our results suggest that the spring land surface thermal anomalies over West Asia can be a potential signal for short-term prediction of early summer climate over northern China. [ABSTRACT FROM AUTHOR]

Considering impacts of elevated CO 2 -induced increases in surface resistance on potential evapotranspiration (PET), to revisit and attribute the changes in dryness/wetness is necessary for accurately understanding evolutions of the historical and future drying and wetting conditions. Therefore, we comprehensively investigated the historical (1965–2011) and future (2019–2098; including four scenarios) annual dryness/wetness changes through incorporating CO 2 effect into the Food and Agriculture Organization of the United Nations' report 56 (FAO-56) Penman-Monteith and the self-calibrating Palmer Drought Severity Index. During the historical and future periods, China experienced significant wetting (p < 0.05), and moreover the wetting trends prevailed across most (> 70%) of China, especially for each future scenario with >50% of China with significant (p < 0.05) wetting. A joint-solution method with multiple sensitivity experiments was used to separate each driving factor's contribution to annual dryness/wetness changes. Results showed that for the whole China increased precipitation was responsible for the historical and future wetting trends. However, the determinant factors varied spatially. Across China, the historical major contributors were precipitation, wind speed, air temperature and net solar radiation, totally accounting for 97.6% of China. The annual dryness/wetness across China could be attributed to precipitation, air temperature and net solar radiation for SSP1–2.6 and SSP2–4.5, but precipitation and air temperature for SSP3–7.0 and SSP5–8.5. Moreover, through comparing attributions of the annual dryness/wetness changes with and without CO 2 effect, we found that the CO 2 effect could change the determinant factors mainly in eastern China, and the corresponding area percentages increased with the gas emissions, particularly for SSP3–7.0 and SSP5–8.5 with the largest values above 42%. This finding highlighted that the CO 2 effect should be considered when conducting attribution analysis of the changes in dryness/wetness. [Display omitted] • Impacts of the CO 2 effect on surface resistance were incorporated in this study. • The historical and future dryness/wetness changes in China were attributed. • The historical dominant factors were generally precipitation and wind speed at space. • The future dominant factors were generally temperature and precipitation at space. • The CO 2 effect should be considered when attributing dryness/wetness changes. [ABSTRACT FROM AUTHOR]

This study investigates the first two leading modes of the interannual variability of frequency of snowfall events (FSE) over China in the winter during 1986–2018. The positive phase of the first leading mode (EOF1) is mainly characterized by positive FSE anomalies in northeastern–northwestern China and negative FSE anomalies in the three-river-source region. In contrast, the positive phase of the second leading mode (EOF2) is mainly characterized by positive FSE anomalies in central-eastern China (CEC). EOF1 is affected by the synoptic-scale wave activity over the midlatitudes of the East Asian continent, where active synoptic-scale wave activity over the midlatitudes may cause increased FSE over northeastern–northwestern China, and vice versa. In a winter of a negative phase of the North Atlantic Oscillation, an anomalous deep cold low may occur over Siberia, which may induce increased meridional air temperature gradient, increased atmospheric baroclinicity, and hence increased FSE over the midlatitudes of the East Asian continent. The EOF2 is affected by the interaction between anomalous northerly cold advection and anomalous southerly water vapor transport over CEC. The positive phase of EOF2 is associated with negative sea ice anomalies in the Barents Sea–Kara Sea region and negative sea surface temperature anomalies in the central-eastern tropical Pacific. Reduced sea ice in the Barents Sea–Kara Sea during January–February may cause increased northerly cold advection over CEC, while a La Niña–like condition during January may induce southerly water vapor transport anomalies over CEC. [ABSTRACT FROM AUTHOR]

This study investigated the relationship between the pre-summer soil moisture (SM) over the Indo-China Peninsula (ICP) and the summer precipitation in the middle and lower reaches of the Yangtze River basin (MLR-YRB) under different SST backgrounds. When spring soil over the ICP was dry (wet), summer precipitation in most parts of the MLR-YRB was significantly higher (lower) under normal SST backgrounds (in the inner-quartile years). However, the SM anomalies produced a limited influence on summer precipitation under strong SST conditions (in the outer-quartile years). Further analysis indicates that in the inner-quartile years, the thermal heating anomalies induced by abnormal SM evidently increased (decreased) the geopotential heights above the western tropical Pacific, and enhanced (weakened) the low-level anticyclonic circulation, thereby increasing (decreasing) the warm and moist southerly flow from the ICP and western Pacific regions to the MLR-YRB, which was conducive to more (less) precipitation in the MLR-YRB. In the outer-quartile years, thermal anomalies of the ICP had very weak effects on both the wind fields above the western Pacific and the water vapor flux to the MLR-YRB, thereby leading to a limited increase (decrease) in summer precipitation. The different responses of the local and surrounding atmospheric circulations to pre-summer SM anomalies over the ICP against different SST backgrounds produced distinct impacts on the distribution of summer precipitation in the MLR-YRB. The dry (wet) anomalies of spring SM in the ICP could also increase (decrease) the zonal thermal contrast between the ICP and the South China Sea (SCS) and impact the SCS summer monsoon differently in the inner-quartile and outer-quartile years. Based on numerical experiments with the Community Earth System Model (CESM), this work further confirmed the observational results and explored the physical mechanism by which the ICP spring soil moisture affects the MLR-YRB summer precipitation under various SST backgrounds. The simulation results show that a dry (wet) ICP spring soil significantly increased (decreased) the MLR-YRB rainfall in the following summer. This negative correlation was stronger in the inner-quartile years. The atmospheric response to changes in the surface thermal conditions was more significant in the inner-quartile years. This surface heating anomaly over the ICP led to anomalous southwest wind over the SCS, which could enhance the Asian summer monsoon and increase summer precipitation in the MLR-YRB. [ABSTRACT FROM AUTHOR]

Previous studies detected significant negative correlations between the nonuniform land surface warming and the decadal weakened activities of the summer extratropical cyclones (ECs) over East Asia and the East Asian summer monsoon (EASM) after the early 1990s. Here such relationships are further examined and the possible mechanisms are explored via numerical sensitivity experiments with a regional climate model (RegCM4.5). The positive/negative sensible heat flux (SH) anomalies were added as a forcing to a key region near 50°N of East Asia in RegCM4.5 to simulate the observed ground surface temperature (GST) anomalies. The model results suggest that the nonuniform land surface warming over the Lake Baikal area (50°–60°N, 90°–120°E) can indeed cause the weakening of the extratropical cyclogenesis and affect the decadal weakening of the EASM. Warm (cold) GST forcing over the key GST region can lead to decreasing (increasing) atmospheric baroclinicity and related energy conversion of the EC activity over the key EC region (40°–50°N, 90°–120°E), resulting in an evidently weakening (enhancing) of the ECs over East Asia. Meanwhile, precipitation shows a dipole pattern with significantly suppressed (enhanced) precipitation in northern and northeastern China, and slightly enhanced (suppressed) rainfall south of 40°N of East Asia, mainly over the East China Sea. Lake Baikal and its adjacent areas are occupied by a strong anticyclonic (cyclonic) circulation while the southeast coastal areas of China have a relatively weak cyclonic (anticyclonic) circulation accompanied with an anomalous northeasterly (southwesterly) wind to the southeast of the anticyclonic circulation, which is opposite to (coincident with) the atmospheric circulation anomalies that are associated with the second mode of the EASM. [ABSTRACT FROM AUTHOR]

Studying impacts of the CO 2 effect on potential evapotranspiration (PET) and offline drought indices from surface resistance perspective is significant for understanding and accessing droughts. This study comprehensively investigated impacts of the CO 2 effect on PET and Standardized Precipitation-Evapotranspiration Index (SPEI) over China during 1971–2010 based on two simulations with and without CO 2 effect, respectively. We found that the CO 2 effect led to decreased PET and increased SPEI , and decreased drought, which showed strong spatial variations with the greatest impact over northern China (excluding westernmost part for PET). Such spatial variations had functional relationships not only with CO 2 concentration but also climatological conditions, i.e., climatological wind speed (U) and slope of vapour pressure curve (s) for PET , but climatological U , s and precipitation (P) for SPEI. Further analyses implied that climatological U (climatological U and P) determined the spatial variations in the CO 2 effect-induced PET (SPEI) changes over China during 1971–2010. [ABSTRACT FROM AUTHOR]

• A probability-based index is calculated to represent concurrent heatwaves and droughts. • Physical mechanisms of concurrent heatwaves and droughts are recognized. • Independent predictors are used to construct a physical-empirical prediction model. Concurrent heatwaves and droughts that occur over northeastern China (NEC) bring severe threats to human lives and crop production. Despite the great efforts taken in previous studies, realistic prediction of these concurrent extreme events remains a challenge. In the present study, a probability-based index that simultaneously considers precipitation deficiency and high temperature is calculated to represent concurrent heatwaves and droughts in July–August over NEC. Based on this index, the characteristics of concurrent heatwaves and droughts over NEC in July–August are investigated using the year-to-year increment approach. The results indicate that the occurrence of concurrent heatwaves and droughts over NEC is closely related to the Polar-Eurasian teleconnection pattern and the Pacific-Japan teleconnection pattern. Further analyses indicate that the sea ice content in the Barents Sea in March ( SICBS ), the La Niña-like sea surface temperature (SST) in February ( SST-PC1 ), and the northwestern Siberia soil moisture in April ( SM ) are coincidently linked to the two teleconnection patterns mentioned above. Based on their corresponding physical mechanisms, these three independent predictors are chosen to construct a physical-empirical prediction model for the prediction of concurrent heatwaves and droughts over NEC. Results suggest that this physical-empirical prediction model performs well with a high correlation coefficient and a low root mean squared error between the observed and predicted concurrent heatwaves and droughts over NEC during the period of 1979–2018. Moreover, the cross-validation test and independent hindcasts both suggest that the physical-empirical model proposed in the present study with the three independent predictors has good prediction skills. [ABSTRACT FROM AUTHOR]

• Causes of the annual evapotranspiration (ET) and water yield trends over vegetated mainland China were investigated. • Vegetation and precipitation dominated ET trends over 55% and 32% of study area, respectively. • Human-distributed vegetation and natural vegetation combined explained water yield trends over 30% areas. • Vegetation (particularly for human-distributed vegetation) greening was crucial for the hydrological cycle changes. Quantifying the contributions of climate and vegetation to the dynamics of evapotranspiration (ET) and water yield (i.e., precipitation minus ET) will help us better understand the changes in the water budget. In this study, we identified the contributions of climate variables (including precipitation, radiation, temperature, and relative humidity), human-disturbed vegetation, and natural vegetation to the trends in annual ET and water yield over vegetated mainland China during 2001–2020, using a process-based terrestrial ecosystem model and a joint-solution method with multiple sensitivity numerical experiments. Results showed that 46% of the study area experienced significant (p <0.05) increases in ET, with an overall increase of 2.32 mm y−1. Meanwhile, the overall trend in water yield was 2.56 mm y−1 but insignificant. Spatially, vegetation and precipitation are the dominant factors for ET trends over 55% and 32% of vegetated mainland China, respectively. Over the regions where vegetation dominates the ET trends, nearly half of these regions are covered by human-disturbed vegetation (e.g., cropland or regions with land cover changes), suggesting that anthropogenic activities play a crucial role in the hydrological cycle there. Concerning the trends in water yield, precipitation is the dominant factor over 64% areas. Human-disturbed vegetation and natural vegetation play similar roles and combined can explain the water yield trends over 30% areas. Our study highlights the spatial variations in the mechanisms behind changes in the water budget over mainland China, particularly in regions covered by human-disturbed vegetation. This finding should be considered in the existing and future national ecological recovery policies to maximize its eco-hydrological benefits. [ABSTRACT FROM AUTHOR]

Background: Understanding the burden of aortic stenosis (AS) across diverse racial and ethnic populations is important to ensure equitable resource allocation. This study explored whether severe AS rate varies by race and ethnicity., Methods: The rates of severe AS, stratified by race and ethnicity, were calculated among 615,038 adults with a transthoracic echocardiogram. Logistic regression analysis was performed to identify factors associated with severe AS., Results: Severe AS rates ranged from 0.08% in adults < 50 years old to 3.8% in those ≥ 90 years old. Compared to non-Hispanic White and Asian American [adjusted odds ratio (aOR) = 0.47, 95% confidence interval (CI): 0.42-0.53] and non-Hispanic Black (aOR = 0.44, 95% CI: 0.39-0.50) patients were less likely to have severe AS, whereas Hispanic patients (aOR = 0.91, 95% CI: 0.87-0.98) had near similar likelihood. Age was the strongest risk factor for severe AS (compared to age < 50 years, aOR = 21.8, 95% CI: 17.8-26.6 for age 80-89 years, and aOR = 43.8, 95% 35.5-54.0 for age ≥ 90 years). Additional factors associated with severe AS included male sex (aOR = 1.38, 95% CI: 1.30-1.46) and diabetes (aOR = 1.23, 95% CI: 1.15-1.31)., Conclusions: Asian American and non-Hispanic Black adults had lower rates of severe AS compared to White and Hispanic patients. The rate of severe AS progressively increases with age in all racial and ethnic groups, with higher rates in men compared with women. With a demographic shift toward an aging and more diverse population, the burden of AS is anticipated to rise. Ensuring adequate allocation of resources to meet the evolving needs of a diverse population remains a shared health care imperative., Competing Interests: Conflict of Interests None declared

Background: Over the last decade, there has been growing interest in inverted classroom teaching (ICT) and its various forms within the education sector. Physiology is a core course that bridges basic and clinical medicine, and ICT in physiology has been sporadically practiced to different extents globally. However, students' and teachers' responses and feedback to ICT in physiology are diverse, and the effectiveness of a modified ICT model integrated into regular teaching practice in physiology courses is difficult to assess objectively and quantitatively., Objective: This study aimed to explore the current status and development direction of ICT in physiology in basic medical education using bibliometric visual analysis of the related literature., Methods: A bibliometric analysis of the ICT-related literature in physiology published between 2000 and 2023 was performed using CiteSpace, a bibliometric visualization tool, based on the Web of Science database. Moreover, an in-depth review was performed to summarize the application of ICT in physiology courses worldwide, along with identification of research hot spots and development trends., Results: A total of 42 studies were included for this bibliometric analysis, with the year 2013 marking the commencement of the field. University staff and doctors working at affiliated hospitals represent the core authors of this field, with several research teams forming cooperative relationships and developing research networks. The development of ICT in physiology could be divided into several stages: the introduction stage (2013-2014), extensive practice stage (2015-2019), and modification and growth stage (2020-2023). Gopalan C is the author with the highest citation count of 5 cited publications and has published 14 relevant papers since 2016, with a significant surge from 2019 to 2022. Author collaboration is generally limited in this field, and most academic work has been conducted in independent teams, with minimal cross-team communication. Authors from the United States published the highest number of papers related to ICT in physiology (18 in total, accounting for over 43% of the total papers), and their intermediary centrality was 0.24, indicating strong connections both within the country and internationally. Chinese authors ranked second, publishing 8 papers in the field, although their intermediary centrality was only 0.02, suggesting limited international influence and lower overall research quality. The topics of ICT in physiology research have been multifaceted, covering active learning, autonomous learning, student performance, teaching effect, blended teaching, and others., Conclusions: This bibliometric analysis and literature review provides a comprehensive overview of the history, development process, and future direction of the field of ICT in physiology. These findings can help to strengthen academic exchange and cooperation internationally, while promoting the diversification and effectiveness of ICT in physiology through building academic communities to jointly train emerging medical talents., (© Zonglin He, Botao Zhou, Haixiao Feng, Jian Bai, Yuechun Wang. Originally published in JMIR Medical Education (https://mededu.jmir.org).)

Recent rapid Arctic sea ice loss was documented as combined results from anthropogenic forcing and climate system internal variability. However, the role of internal variability is not well understood. Here, we propose that the Asian-Pacific Oscillation (APO), an intrinsic atmospheric mode featuring out-of-phase variations in upper-tropospheric temperatures between Asia and the North Pacific, is one driver for autumn sea ice variability in the eastern Arctic. The positive summer APO favors warming of the mid-latitude North Atlantic sea surface temperatures. This warming persists to autumn and in turn triggers strong anticyclonic anomalies over the Barents-Kara-Laptev Seas and weak lower-tropospheric cyclonic anomalies over the East Siberian Sea, enhancing moisture transport into the eastern Arctic. Such changes consequently increase lower-tropospheric humidity, downwelling longwave radiation, and surface air temperature in the eastern Arctic, thereby melting sea ice. Hence, a recent tendency of the summer APO towards the positive phase accelerates autumn sea ice loss in the eastern Arctic., (© 2024. The Author(s).)

The blood-brain barrier (BBB) is a remarkable and intricate barrier that controls the exchange of molecules between the bloodstream and the brain. Its role in maintaining the stability of the central nervous system cannot be overstated. Over the years, advancements in neuroscience and technology have enabled us to delve into the cellular and molecular components of the BBB, as well as its regulation. Yet, there is a scarcity of comprehensive reviews that follow a logical framework of structure-function-regulation, particularly focusing on the nuances of BBB regulation under both normal and pathological conditions. This review sets out to address this gap by taking a historical perspective on the discovery of the BBB and highlighting the major observations that led to its recognition as a distinct brain barrier. It explores the intricate cellular elements contributing to the formation of the BBB, including endothelial cells, pericytes, astrocytes, and neurons, emphasizing their collective role in upholding the integrity and functionality of the BBB. Furthermore, the review delves into the dynamic regulation of the BBB in physiological states, encompassing neural, humoral, and auto-regulatory mechanisms. By shedding light on these regulatory processes, a deeper understanding of the BBB's response to various physiological cues emerges. This review also investigates the disruption of the BBB integrity under diverse pathological conditions, such as ischemia, infection, and toxin exposure. It elucidates the underlying mechanisms that contribute to BBB dysfunction and explores potential therapeutic strategies that aim to restore the BBB integrity and function. Overall, this recapitulation provides valuable insights into the structure, functions, and regulation of the BBB. By integrating historical perspectives, cellular elements, regulatory mechanisms, and pathological implications, this review contributes to a more comprehensive understanding of the BBB and paves the way for future research and therapeutic interventions.

Background: CD27 is an immunological checkpoint gene, plays a critical function inInhibition or activation of cancer immunity. The CD27 / CD27L axis is its pathway of action. Therefore, our goal was to examine the predictive role of CD27 in the clinical prognosis of 33 cancer types and its functions in cancer progression, as well as explore the link between pan-cancer CD27 gene expression and immune infiltration. Methods: By comprehensive use of datasets and methods from TCGA, cBioPortal, GTEx, HPA, KM-plotter, Spearman, CellMinerTM, R packages and RT-qPCR, we delved deeper into the potential impact of the CD27 on cancer development. These include expression differences, immune infiltration, matrix infiltration, gene mutations, DNA methylation, signaling pathways, TMB, MSI, and prognosis. Also, we explored CD27 interactions with different drugs. Results: The results showed that, mutated CD27 was highly expressed in most cancers. The CD27 showed strong diagnostic value in 4 cancers and marked a positive prognosis for CESC, intracervical adenocarcinoma, HNSC, and endometrial cancer, and a poor prognosis for UVM. In addition, CD27 affects multiple immune and inflammatory signaling pathways and is positively correlated with immune cell infiltration, T cell differentiation, macrophage M1 polarization, stromal infiltration, and drug sensitivity. DNA methylation is involved in CD27 expression in cancer. Conclusion: CD27, which is mutated in cancers and appears widely highly expressed and altered tumor immune invasion and stromal invasion by affecting multiple immune-related and inflammation signaling pathways, plays a significant role in CESC, HNSC, UCEC and UVM, and may be used as a therapeutic target for related cancers., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background/objectives: There is currently no widely accepted approach to identify patients at increased risk for sporadic pancreatic cancer (PC). We aimed to compare the performance of two machine-learning models with a regression-based model in predicting pancreatic ductal adenocarcinoma (PDAC), the most common form of PC., Methods: This retrospective cohort study consisted of patients 50-84 years of age enrolled in either Kaiser Permanente Southern California (KPSC, model training, internal validation) or the Veterans Affairs (VA, external testing) between 2008 and 2017. The performance of random survival forests (RSF) and eXtreme gradient boosting (XGB) models were compared to that of COX proportional hazards regression (COX). Heterogeneity of the three models were assessed., Results: The KPSC and the VA cohorts consisted of 1.8 and 2.7 million patients with 1792 and 4582 incident PDAC cases within 18 months, respectively. Predictors selected into all three models included age, abdominal pain, weight change, and glycated hemoglobin (A1c). Additionally, RSF selected change in alanine transaminase (ALT), whereas the XGB and COX selected the rate of change in ALT. The COX model appeared to have lower AUC (KPSC: 0.737, 95% CI 0.710-0.764; VA: 0.706, 0.699-0.714), compared to those of RSF (KPSC: 0.767, 0.744-0.791; VA: 0.731, 0.724-0.739) and XGB (KPSC: 0.779, 0.755-0.802; VA: 0.742, 0.735-0.750). Among patients with top 5% predicted risk from all three models (N = 29,663), 117 developed PDAC, of which RSF, XGB and COX captured 84 (9 unique), 87 (4 unique), 87 (19 unique) cases, respectively., Conclusions: The three models complement each other, but each has unique contributions., Competing Interests: Declaration of competing interest The authors declare they have no conflict of interest for this study., (Copyright © 2023 IAP and EPC. All rights reserved.)

Introduction: There is currently no widely accepted approach to screening for pancreatic cancer (PC). We aimed to develop and validate a risk prediction model for pancreatic ductal adenocarcinoma (PDAC), the most common form of PC, across 2 health systems using electronic health records., Methods: This retrospective cohort study consisted of patients aged 50-84 years having at least 1 clinic-based visit over a 10-year study period at Kaiser Permanente Southern California (model training, internal validation) and the Veterans Affairs (VA, external testing). Random survival forests models were built to identify the most relevant predictors from >500 variables and to predict risk of PDAC within 18 months of cohort entry., Results: The Kaiser Permanente Southern California cohort consisted of 1.8 million patients (mean age 61.6) with 1,792 PDAC cases. The 18-month incidence rate of PDAC was 0.77 (95% confidence interval 0.73-0.80)/1,000 person-years. The final main model contained age, abdominal pain, weight change, HbA1c, and alanine transaminase change (c-index: mean = 0.77, SD = 0.02; calibration test: P value 0.4, SD 0.3). The final early detection model comprised the same features as those selected by the main model except for abdominal pain (c-index: 0.77 and SD 0.4; calibration test: P value 0.3 and SD 0.3). The VA testing cohort consisted of 2.7 million patients (mean age 66.1) with an 18-month incidence rate of 1.27 (1.23-1.30)/1,000 person-years. The recalibrated main and early detection models based on VA testing data sets achieved a mean c-index of 0.71 (SD 0.002) and 0.68 (SD 0.003), respectively., Discussion: Using widely available parameters in electronic health records, we developed and externally validated parsimonious machine learning-based models for detection of PC. These models may be suitable for real-time clinical application., (Copyright © 2022 by The American College of Gastroenterology.)