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This paper surveys the current state of knowledge regarding large-scale meteorological patterns (LSMPs) associated with short-duration (less than 1 week) extreme precipitation events over North America. In contrast to teleconnections, which are typically defined based on the characteristic spatial variations of a meteorological field or on the remote circulation response to a known forcing, LSMPs are defined relative to the occurrence of a specific phenomenon—here, extreme precipitation—and with an emphasis on the synoptic scales that have a primary influence in individual events, have medium-range weather predictability, and are well-resolved in both weather and climate models. For the LSMP relationship with extreme precipitation, we consider the previous literature with respect to definitions and data, dynamical mechanisms, model representation, and climate change trends. There is considerable uncertainty in identifying extremes based on existing observational precipitation data and some limitations in analyzing the associated LSMPs in reanalysis data. Many different definitions of “extreme” are in use, making it difficult to directly compare different studies. Dynamically, several types of meteorological systems—extratropical cyclones, tropical cyclones, mesoscale convective systems, and mesohighs—and several mechanisms—fronts, atmospheric rivers, and orographic ascent—have been shown to be important aspects of extreme precipitation LSMPs. The extreme precipitation is often realized through mesoscale processes organized, enhanced, or triggered by the LSMP. Understanding of model representation, trends, and projections for LSMPs is at an early stage, although some promising analysis techniques have been identified and the LSMP perspective is useful for evaluating the model dynamics associated with extremes.

To assess the anthropogenic influence on the summer 2013 heat wave in Korea, this study employed a fraction of attributable risk (FAR) approach to three Atmospheric General Circulation Models (AGCMs) with a large ensemble simulation, participating in the C20C+ Detection and Attribution Project. Monthly and daily temperatures were compared between two experiments. The real world (ALL) experiments were simulated under the observed variations in sea surface temperature, sea ice, greenhouse gas, and aerosol concentrations, while the counterfactual world (NAT) experiments were performed under adjusted boundary conditions by removing anthropogenic warming and with preindustrial levels of greenhouse gases and aerosols. Results from the three AGCMs consistently show that anthropogenic influences had an important role in the extreme heat event over Korea, increasing the chance of the occurrence of extreme warming in summer mean temperature as observed in 2013 by at least 20 times, which supports results from the Coupled Model Intercomparison Project Phase 5 (CMIP5) coupled GCMs (CGCMs). A comparison of individual CMIP5 CGCMs suggests that inter-model difference in FAR values is highly correlated with the amplitude of surface warming centered over Korea, which is also supported by the three AGCMs. Further analysis of individual forcing experiments suggests that the inter-model difference in the regional surface warming is closely linked to the model's response to the aerosol forcing, with stronger influence than that of greenhouse gas forcing. Anthropogenic influences also result in a 5–6 times greater likelihood of extreme daily heat events as observed in 2013, which supports a robust mean-extreme relation in the attribution of extreme heat waves. Generally good agreement between AGCM and CGCM results increases the robustness of the conclusion of anthropogenic influences on the summer 2013 Korean heat wave.

Recent studies have detected anthropogenic influences due to increases in greenhouse gases on extreme temperature changes during the latter half of the twentieth century at global and regional scales. Most of the studies, however, were based on a limited number of climate models and also separation of anthropogenic influence from natural factors due to changes in solar and volcanic activities remains challenging at regional scales. Here, the authors conduct optimal fingerprinting analyses using 12 climate models integrated under anthropogenic-only forcing or natural plus anthropogenic forcing. The authors compare observed and simulated changes in annual extreme temperature indices of coldest night and day (TNn and TXn) and warmest night and day (TNx and TXx) from 1951 to 2000. Spatial domains from global mean to continental and subcontinental regions are considered and standardization of indices is employed for better intercomparisons between regions and indices. The anthropogenic signal is detected in global and northern continental means of all four indices, albeit less robustly for TXx, which is consistent with previous findings. The detected anthropogenic signals are also found to be separable from natural forcing influence at the global scale and to a lesser extent at continental and subcontinental scales. Detection occurs more frequently in TNx and TNn than in other indices, particularly at smaller scales, supporting previous studies based on different methods. A combined detection analysis of daytime and nighttime temperature extremes suggests potential applicability to a multivariable assessment. © 2013 American Meteorological Society.

J Oral Pathol Med (2009) 38: 792-800Background: Although N(1)-guanyl-1,7,-diamineoheptane (GC7), an inhibitor of deoxyhypusine synthase, has been shown to inhibit cell growth, the mechanism of its action is not completely understood. In this study, we investigated the mechanisms of the effects of GC7 on cell growth, differentiation and apoptosis in relation to adenosine monophosphate-activated protein kinase (AMPK) activation, as AMPK is known to be a possible target for cancer treatment. Methods: The effects of GC7 on the growth of immortalized human oral keratinocytes (IHOK) and primary oral cancer cells (HN4), was investigated using MTT assay, Western blotting, cell cycle analysis, DNA fragmentation and expression of apoptotic pathway proteins. Results: N(1)-guanyl-1,7,-diamineoheptane inhibited cell proliferation in a time- and dose-dependent manner in IHOK and HN4 cells. GC7 treatment decreased the expression of differentiation markers, such as involucrin, CK13 and CK19. The major mechanism of growth inhibition by GC7 treatment was induction of apoptosis, which is supported by sub-G(1) phase arrest, annexin V-FITC staining and DNA fragmentation analysis. GC7 treatment increased the cytosolic level of cytochrome c and resulted in caspase-3 activation. GC7 treatment also resulted in a strong activation of AMPK. Furthermore, specific AMPK activator blocked the GC7-induced growth inhibition effect, as well as apoptosis. Conclusion: These results demonstrate that GC7 blocks immortalized and malignant keratinocyte cell proliferation and differentiation by inducing apoptosis through the mitochondrial and AMPK pathways. On the basis of these observations, we propose that a strategy combining GC7 and AMPK inhibition could be developed into a novel chemotherapeutic modality in oral cancer. [ABSTRACT FROM AUTHOR]

Lemierre's syndrome is an uncommon septic thrombophlebitis of the internal jugular vein. The authors present the case of a 52-year-old woman with literature review. She developed flu-like symptoms and fever, and then painful swelling of the left side of her neck and left arm. Contrast-enhanced computed tomography of the neck revealed thrombosis in the left internal jugular vein, subclavian vein, and brachiocephalic vein and diffuse soft tissue inflammation around the veins. No microorganism was identified in the blood and venous thrombus, which was obtained by percutaneous aspiration thrombectomy. Systemic antibiotics and anticoagulation therapy achieved complete resolution of the symptoms. Recanalization of the thrombosed veins with no residual thrombi was observed on duplex scanning after 3 months. No pulmonary embolism or other metastatic infection was observed. Clinical suspicion seems to be essential to make an accurate diagnosis during the early stage of the disease, which is critical to obtain a successful outcome for Lemierre's syndrome. [ABSTRACT FROM AUTHOR]

Background: The goals of this study were to determine the effective bolus dose of alfentanil required for successful tracheal intubation during inhalation induction using sevoflurane 5% without neuromuscular block in children, and whether nitrous oxide reduces these doses.Methods: Fifty paediatric patients, aged 3-10 yr, were randomly assigned to one of the two groups. Subjects received either sevoflurane 5% in oxygen 100% (O(2) group, n=25) or sevoflurane 5% in oxygen 40% and nitrous oxide 60% (N(2)O group, n=25) through a face mask. One minute after inhalation induction, a predetermined dose of alfentanil was injected over 15 s. The alfentanil dose was determined using Dixon's up-and-down method, starting from alfentanil 14 microg kg(-1). The trachea was intubated 3 min after inducing anaesthesia.Results: The ED(50) [95% confidence interval (CI)] of alfentanil for successful tracheal intubation was 11.5 (9.9-13.1) and 8.6 (7.4-9.8) microg kg(-1) in the O(2) and N(2)O groups, respectively. The ED(50) of the N(2)O group was significantly lower than that of the O(2) group (P=0.0146)(.) From isotonic regression, 50% effective dose (ED(50)) (95% CI) of alfentanil in the O(2) and N(2)O groups was 11.4 (9.9-13.0) and 6.5 (5.0-8.1) microg kg(-1), respectively.Conclusions: The effective bolus dose of alfentanil for successful tracheal intubation was 11.5 microg kg(-1) in 50% of children during inhalation induction using sevoflurane 5% without neuromuscular blocking agent. Addition of nitrous oxide 60% in oxygen reduced the effective alfentanil dose by 25%. [ABSTRACT FROM AUTHOR]

Confinement of reactants within nanoscale spaces of low-dimensional materials has been shown to provide reorientation of strained reactants or stabilization of unstable reactants for synthesis of molecules and tuning of chemical reactivity. While few studies have reported chemistry within zero-dimensional pores and one-dimensional nanotubes, organic reactions in confined spaces between two-dimensional materials have yet to be explored. Here, we demonstrate that reactants confined between atomically thin sheets of graphene or hexagonal boron nitride experience pressures as high as 7 gigapascal, which allows the propagation of solvent-free organic reactions that ordinarily do not occur under standard conditions. Specifically, we show that cyclodehydrogenation of hexaphenylbenzene without catalysts as a proof of concept and oxidative polymerization of dopamine into sheet-like crystalline structure are enabled by the effective high pressure experienced by the reactants between the graphene layers. Our results demonstrate a facile, general approach for performing high-pressure chemistry based on confinement of reactants within two-dimensional materials.

Background: Remimazolam is not only associated with a lower incidence of respiratory depression than propofol but also in itself has the risk of respiratory depression., Objective: We investigated respiratory depression following remimazolam infusion, targeting different effect-site concentrations using target-controlled infusion., Design: A prospective, double-blind, randomised controlled study., Setting: Tertiary hospital, Suwon, South Korea, from April 2022 to November 2022., Participants: One hundred and seven patients scheduled for general anaesthesia were randomised into three groups targeting remimazolam effect-site concentrations of 500 (RMZ-500) ( n  = 36), 1000 (RMZ-1000) ( n  = 35) and 1500 ng ml -1 (RMZ-1500) ( n  = 36)., Interventions: Remimazolam was solely infused for 10 min according to target effect-site concentrations. According to the degree of SpO 2 decrease, oxygen desaturations were managed with the following respiratory supports: jaw-thrust for SpO 2 less than 97%, 100% oxygen delivery for SpO 2 less than 93% and assisted ventilation for SpO 2 less than 90%., Main Outcome Measures: The incidence of each respiratory support, along with respiratory variables (at baseline, 5 min and 10 min after remimazolam infusion) and loss of consciousness were observed for 10 min after remimazolam target-controlled infusion., Results: Both RMZ-1000 and RMZ-1500 required more frequent respiratory support than RMZ-500 (both P  < 0.001), with nearly identical frequencies between RMZ-1000 and RMZ-1500. In terms of respiratory support, the incidence of assisted ventilation was significantly lower in RMZ-500 (2.8%) than RMZ-1000 (48.6%) and RMZ-1500 (50%) ( P  < 0.001). RMZ-1000 and RMZ-1500 achieved loss of consciousness in all patients; RMZ-500 only achieved loss of consciousness in 86.1% of patients ( P  = 0.010). In patients who maintained spontaneous respiration, tidal volume decreased by 41 to 48% and respiratory rate increased by 118 to 158% at 5 and 10 min, significantly compared to baseline in all groups ( P  < 0.001)., Conclusions: Remimazolam infusion, like that of other benzodiazepines, led to respiratory depression, which was more prominent at higher target effect-site concentrations. Therefore, appropriate countermeasures should be developed to prevent oxygen desaturation., Trial Registration: CRIS ( https://cris.nih.go.kr ), identifier: KCT0006952., (Copyright © 2024 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Adventitial cystic disease (ACD), a rare vascular disease characterized by mucus accumulation in the adventitia of blood vessels, typically affects the popliteal artery. We present the case of a 61-year-old female diagnosed with ACD in 2018 who was initially treated with endovascular stenting and percutaneous aspiration of the cyst. The patient, who had been asymptomatic for 5 years, developed a stent fracture and pseudoaneurysm requiring surgical intervention. Despite initial successful treatment, complications such as stent fracture and recurrence can occur; therefore, surgical treatment is recommended to optimize outcomes in patients with ACD. Endovascular treatment and cyst aspiration should only be considered in cases with high surgical risk. After treatment, long-term follow-up and individualized management strategies are important to monitor ACD recurrence.

Traumatic ureteral injuries account for fewer than 1% of traumatic urologic injuries, and those caused by blunt trauma are even rarer than those caused by penetrating trauma. The symptoms associated with ureteral injury may be subtle, with or without hematuria, making it difficult to diagnose. We report the case of a 31-year-old man with a delayed diagnosis of proximal ureter injury after abdominal blunt trauma sustained in a motorcycle traffic accident. The patient underwent emergency laparotomy on admission for liver injury, mesenteric injury, and resultant hemoperitoneum. On postoperative day 6, he underwent angioembolization for suspected remnant intra-abdominal bleeding. Persistent symptoms of flank pain and leukocytosis led to follow-up imaging studies that revealed proximal ureter injury, and the patient underwent unilateral nephrectomy. This case stresses the importance of clinical suspicion for genitourinary injuries in the presence of abdominal trauma.

Climate models indicate that dry extremes will be exacerbated in many regions of the world 1,2 . However, confidence in the magnitude and timing of these projected changes remains low 3,4 , leaving societies largely unprepared 5,6 . Here we show that constraining model projections with observations using a newly proposed emergent constraint (EC) reduces the uncertainty in predictions of a core drought indicator, the longest annual dry spell (LAD), by 10-26% globally. Our EC-corrected projections reveal that the increase in LAD will be 42-44% greater, on average, than 'mid-range' or 'high-end' future forcing scenarios currently indicate. These results imply that by the end of this century, the global mean land-only LAD could be 10 days longer than currently expected. Using two generations of climate models, we further uncover global regions for which historical LAD biases affect the magnitude of projected LAD increases, and we explore the role of land-atmosphere feedbacks therein. Our findings reveal regions with potentially higher- and earlier-than-expected drought risks for societies and ecosystems, and they point to possible mechanisms underlying the biases in the current generation of climate models., (© 2024. The Author(s).)

Background: Venoactive drugs (VADs) based on Vitis vinifera extract are widely used in Korea. However, studies on the clinical effects and head-to-head comparisons with other groups of VADs are limited. This trial aimed to evaluate whether Vitis vinifera seed extract was noninferior to the micronized purified flavonoid fraction (MPFF) in relieving venous symptoms and improving quality of life in patients with chronic venous disease., Methods: In this double-blind prospective randomized trial, patients from 13 hospitals, who were diagnosed with venous incompetence by duplex ultrasound and classified as clinical class 1, 2, or 3 in the Clinical, Etiological, Anatomical, and Pathophysiological classifications were enrolled. The primary outcome was the change in the Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-20) score at 8 weeks from baseline. Secondary outcomes included changes in the Aberdeen Varicose Vein Questionnaire, visual analog scale, and Venous Clinical Severity Score at 4 and 8 weeks from baseline. Moreover, the change in leg circumferences was measured at 8 weeks and compared to baseline., Results: In total, 303 patients were enrolled and randomly assigned to receive either Vitis vinifera seed extract (n = 154) or MPFF (n = 149). The CIVIQ-20 scores at 8 weeks were significantly reduced compared to those at baseline in both groups. No significant intergroup difference in the change of CIVIQ-20 at 8 weeks from baseline was observed (-8.31 ± 14.63 vs. -10.35 ± 14.38, P = 0.29, 95% confidence interval -1.65 to 5.72). The lower limit of the 95% confidence interval was within the predefined noninferiority margin of 6.9. Furthermore, the Aberdeen Varicose Vein Questionnaire, visual analog scale, and Venous Clinical Severity Score scores significantly decreased at 4 and 8 weeks after randomization compared with baseline in both groups. No significant differences were observed in the reduction of each score between groups. The calf circumference measured at 8 weeks was significantly reduced compared to that at baseline in patients receiving Vitis vinifera seed extract., Conclusions: Vitis vinifera seed extract was noninferior to MPFF in relieving venous symptoms and improving the quality of life in patients with chronic venous disease., (Copyright © 2024. Published by Elsevier Inc.)

Background: The rapid increase of minimally invasive surgery and the shortened training period for surgical residents has resulted in limited opportunities to acquire proficiency in open surgical techniques, such as vascular anastomosis. However, vascular anastomosis remains an essential skill in every surgery for bleeding control. This study aimed to validate the effectiveness of surgical education model for vascular anastomosis and assess the impact on the comprehension, skill, and confidence of surgical residents in performing vascular anastomosis., Methods: A total of 21 surgical residents with first to third years of experience at Seoul National University Hospital participated in a 4-week vascular anastomosis training program. The program included an educational lecture and the performance of an end-to-side anastomosis on a procedural model, with evaluations being conducted using the Objective Structured Assessment of Technical Skills (OSATS) and the End-Product Rating Score (EPRS) in pretraining and posttraining surveys., Results: Significant improvement was observed in the OSATS score (from 9.22 ± 2.4 in week 1 to 12.87 ± 3.1 in week 4; P < 0.001) and the EPRS score (from 12.47 ± 4.1 in week 1 to 17.57 ± 2.2 in week 4; P < 0.001). Additionally, the surgical performance time significantly decreased from 20.99 ± 4.6 min to 16.33 ± 4.2 min (P = 0.019) CONCLUSIONS: Simulator training of in vitro vascular anastomosis, when accompanied by expert-led instruction, can effectively enhance the surgical proficiency, confidence, and overall surgical outcomes of residents, as inferred from the observed improvements in OSATS and EPRS scores. The results suggest that integration of this training model into surgical curricula could be a promising strategy for enhancing vascular surgical training., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Kidney transplantation is a widely used treatment for end-stage kidney disease. Nevertheless, the incidence of acute kidney injury (AKI) in deceased donors poses a potential hazard because it significantly increases the risk of delayed graft function and potentially exerts an influence on the kidney allograft outcome. It is crucial to develop a diagnostic model capable of assessing the existence and severity of AKI in renal grafts. However, no suitable kidney injury markers have been developed thus far., Methods: We evaluated the efficacy of the molecular probe NPO-B, which selectively responds to cysteine, as a new diagnostic tool for kidney injury. We used an in vitro model using ischemia/reperfusion injury human kidney-2 cells and an in vivo ischemia/reperfusion injury mouse model. Additionally, cysteine was investigated using urine samples from deceased donors and living donors to assess the applicability of detection techniques to humans., Results: This study confirmed that the NPO-B probe effectively identified and visualized the severity of kidney injury by detecting cysteine in both in vitro and in vivo models. We observed that the fluorescence intensity of urine samples measured using NPO-B from the deceased donors who are at a high risk of renal injury was significantly stronger than that of the living donors., Conclusions: If implemented in clinical practice, this new diagnostic tool using NPO-B can potentially enhance the success rate of kidney transplantation by accurately determining the extent of AKI in renal grafts., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Machines have continually developed with the needs of daily life and industrial applications. While the careful design of molecular-scale devices often displays enhanced properties along with mechanical movements, controlling mechanics within solid-state molecular structures remains a significant challenge. Here, we explore the distinct mechanical properties of zeolitic imidazolate frameworks (ZIFs)-frameworks that contain hidden mechanical components. Using a combination of experimental and theoretical approaches, we uncover the machine-like capabilities of ZIFs, wherein connected composite building units operate similarly to a mechanical linkage system. Importantly, this research suggests that certain ZIF subunits act as core mechanical components, paving an innovative view for the future design of solid-state molecular machines., (© 2024 Wiley-VCH GmbH.)

Senescent cells increase in many tissues with age and induce age-related pathologies, including osteoarthritis (OA). Senescent chondrocytes (SnCs) are found in OA cartilage, and the clearance of those chondrocytes prevents OA progression. However, targeting SnCs is challenging due to the absence of a senescent chondrocyte-specific marker. Therefore, we used flow cytometry to screen and select senescent chondrocyte surface markers and cross-validated with published transcriptomic data. Chondrocytes expressing dipeptidyl peptidase-4 (DPP-4), the selected senescent chondrocyte-specific marker, had multiple senescence phenotypes, such as increased senescence-associated-galactosidase, p16, p21, and senescence-associated secretory phenotype expression, and showed OA chondrocyte phenotypes. To examine the effects of DPP-4 inhibition on DPP-4+ SnCs, sitagliptin, a DPP-4 inhibitor, was treated in vitro. As a result, DPP-4 inhibition selectively eliminates DPP-4+ SnCs without affecting DPP-4- chondrocytes. To assess in vivo therapeutic efficacy of targeting DPP-4+ SnCs, three known senolytics (ABT263, 17DMAG, and metformin) and sitagliptin were comparatively verified in a DMM-induced rat OA model. Sitagliptin treatment specifically and effectively eliminated DPP-4+ SnCs, compared to the other three senolytics. Furthermore, Intra-articular sitagliptin injection to the rat OA model increased collagen type II and proteoglycan expression and physical functions and decreased cartilage destruction, subchondral bone plate thickness and MMP13 expression, leading to the amelioration of OA phenotypes. Collectively, OARSI score was lowest in the sitagliptin treatment group. Taken together, we verified DPP-4 as a surface marker for SnCs and suggested that the selective targeting of DPP-4+ chondrocytes could be a promising strategy to prevent OA progression., (© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

A quantitative understanding of the roles of rainfall and pollutant concentrations in wet deposition is important because they critically influence terrestrial and aquatic ecosystems. However, their relative contributions to wet deposition, which vary across regions, have not yet been identified. We propose two methods that quantitatively separate the contributions of rain and pollutant concentrations to wet deposition: one is based on simplified equations describing the wet scavenging of pollutants and the other is based on random forest models employing SHapley Additive exPlanations. Three-dimensional long-term air quality simulations from 2003 to 2019 are used as inputs for both the physics-based and machine learning models. Remarkably, the results drawn from the explainable machine learning model are consistent with those from the physics-based approach: overall, rain is a more important limiting factor than pollutant concentrations and the relative contribution of rain is larger than that of pollutants by up to a factor of 3-4 in polluted regions. In polluted regions, pollutant concentrations can remain relatively high even in the presence of precipitation owing to continuous and intense emissions; therefore, wet deposition is limited by rainfall. The contribution of rainfall is larger by 1.5-2.5 than that of pollutant concentrations in regions even with low emissions and this considerably large role of rain suggests that regional or transboundary pollutant transport plays a key role in modulating wet deposition. However, in very remote regions, once the rainfall amount exceeds a certain value, rainfall no longer contributes to increasing wet deposition because atmospheric pollutants are readily removed by rain. So, the contributions of the two factors are comparable in pristine regions. Our results can serve as a basis for explaining interannual variations in wet deposition and for future projections of wet deposition under emission control plans and climate change scenarios across regions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Unlike western countries, which have reported distinct decreases in incidence of ruptured abdominal aortic aneurysm (rAAA) over the last few decades, epidemiologic studies in Korea have not shown significant changes in incidence or mortality of rAAA. The purpose of this study was to analyze the changes in rAAA treatment outcomes and various associated risk factors over the past 2 decades., Methods: A 20-year retrospective multicenter review for rAAA cases from the period of January 2000 to December 2020 was undertaken. Preoperative, intraoperative and postoperative clinical data were extracted for patients diagnosed with rAAA. For analysis, outcomes from the early era, defined as patients treated between January 1, 2000, and December 31, 2010, were compared with outcomes from the late era, defined as patients treated between January 1, 2011, and December 31, 2020., Results: The total in-hospital mortality was 34.1% in the early era compared to 44.8% in the late era. Patients in the late era were older than those in the early era (75.2 ± 10.3 years vs. 70.3 ± 8.9 years; P = 0.009). Treatment with rAAA endovascular aneurysm repair increased from 2.3% in early to 13.8% in late era (P = 0.031). In the early era, more patients were operated by experienced surgeons than the late era (78.1% vs. 45.9%; P = 0.002). The emergency room to operating room time did not show improvement over the 20 years., Conclusions: The results indicate that mortality rate of rAAA in Korea has not changed over the last 2 decades. The study suggests the need for national preventive strategies, improved systemic coordination, and potential centralization of vascular services to enhance survival rates for rAAA., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A general formulation of the strong coupling between photons confined in a cavity and molecular electronic states is developed for the state-interaction state-average spin-restricted ensemble-referenced Kohn-Sham method. The light-matter interaction is included in the Jaynes-Cummings model, which requires the derivation and implementation of the analytical derivatives of the transition dipole moments between the molecular electronic states. The developed formalism is tested in the simulations of the nonadiabatic dynamics in the polaritonic states resulting from the strong coupling between the cavity photon mode and the ground and excited states of the penta-2,4-dieniminium cation, also known as PSB3. Comparison with the field-free simulations of the excited-state decay dynamics in PSB3 reveals that the light-matter coupling can considerably alter the decay dynamics by increasing the excited state lifetime and hindering photochemically induced torsion about the C=C double bonds of PSB3. The necessity of obtaining analytical transition dipole gradients for the accurate propagation of the dynamics is underlined., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Molecular discovery is central to the field of chemical informatics. Although optimization approaches have been developed that target-specific molecular properties in combination with machine learning techniques, optimization using databases of limited size is challenging for efficient molecular design. We present a molecular design method with a Gaussian process regression model and a graph-based genetic algorithm (GB-GA) from a data set comprising a small number of compounds by introducing mutation probability control in the genetic algorithm to enhance the optimization capability and speed up the convergence to the optimal solution. In addition, we propose reducing the number of parameters in the conventional GB-GA focusing on efficient molecular design from a small database. We generated a target-specific database by combining active learning and iterative design in the evolutionary methodologies and chose Gaussian process regression as the prediction model for molecular properties. We show that the proposed scheme is more efficient for optimization toward the target properties from goal-directed benchmarks with several drug-like molecules compared to the conventional GB-GA method. Finally, we provide a demonstration whereby we designed D-luciferin analogues with near-infrared fluorescence for bioimaging, which is desirable for effective in vivo light sources, from a small-size data set.

Molecules that violate Hund's rule and possess negative singlet-triplet gaps (Δ E ST ) have been actively studied for their potential usage in organic light emitting diodes without the need for thermal activation. However, the weak oscillator strength from the symmetry of such molecules has been recognized as their shortcoming for their application in optoelectronic devices. A group of molecules with a common structural motif involving the original molecule with an inverted gap having branches consisting of conjugated molecules of varied structures and extent of conjugation have been predicted to have desirable oscillator strength, but only few detailed and comprehensive studies regarding the form of excited states and the reason behind the improved oscillator strength have been carried out. We show in this work a series of analyses that suggest that the increase of oscillator strength is correlated with the nature of the excited state changing from a localized excitation to a delocalized excitation involving the central molecule and the branches. The resulting oscillator strength thus depends on the energetic matching of the branching molecule and the central molecule, rather than solely the oscillator strength of the central molecule. From the Δ E ST inversion point of view, the static correlation with low-lying doubly excited configurations, the key mechanism behind the inversion in the localized excited state, weakens as the excited states delocalize. As a consequence, the dynamic correlation has a more decisive effect in determining the singlet-triplet gap.

Friend Leukemia Virus Integration 1 (FLI-1) is a member of E26 transformation-specific family of transcription factors that participates in hematopoietic and vascular endothelial cell development. Immunohistochemical detection of FLI-1 has been widely used to diagnose vascular tumors or, more evidently, Ewing's sarcoma. However, the expression pattern of FLI-1 in hematolymphoid neoplasms remains unclear. Therefore, in this study, we aimed to investigate the expression of FLI-1 in these tumors, focusing on high-grade lesions, which presents a diagnostic challenge by mimicking Ewing's sarcoma. We evaluated the expression FLI-1 in various types of lymphoid and plasmacytic tumors, including 27 plasmablastic lymphomas, 229 diffuse large B-cell lymphomas, 22 precursor T- or B-lymphoblastic lymphomas, 24 angioimmunoblastic-type nodal T-follicular helper cell lymphomas, 52 peripheral T-cell lymphomas, NOS, 18 Burkitt lymphomas, 18 non-gastric lymphomas of mucosa-associated lymphoid tissue, 38 chronic lymphocytic leukemia/small lymphocytic lymphomas, 15 mantle cell lymphomas, 23 gastric MALT lymphomas, 50 plasma cell myelomas, and 38 follicular lymphomas. We calculated the H-scores of FLI-1 immunostaining, ranging from 0 to 200, and used the scores to analyze the clinicopathological significance of FLI-1 statistically. FLI-1 was expressed to varying degrees in all types of hematological tumors. FLI-1 expression was detected in 84.1% of patients (466/554). FLI-1 was highly expressed in precursor T- or B-lymphoblastic lymphomas. Follicular lymphomas exhibited low FLI-1 expression. In plasmablastic lymphoma, 85.2% of the patients were focally positive for FLI-1. FLI-1 expression did not correlate with clinicopathological variables, such as demographic data or disease stage, in patients with plasmablastic lymphoma and diffuse large B-cell lymphoma. However, FLI-1 overexpression was associated with poorer overall survival in patients with plasmablastic lymphoma. This study demonstrates that FLI-1 is expressed in various hematolymphoid neoplasms. FLI-1 expression can lead to diagnostic confusion, especially in small blue round cell tumors, such as lymphoblastic lymphoma, plasmablastic lymphoma, and plasma cell myeloma, when distinguishing tumors positive for CD99 and CD56 without CD3, CD20, or CD45. Our findings also suggested the possibility of FLI-1 as a potential prognostic biomarker for plasmablastic lymphoma., (© 2024. The Author(s).)

Origami, known as paper folding has become a fascinating research topic recently. Origami-inspired materials often establish mechanical properties that are difficult to achieve in conventional materials. However, the materials based on origami tessellation at the molecular level have been significantly underexplored. Herein, we report a two-dimensional (2D) porphyrinic metal-organic framework (MOF), self-assembled from Zn nodes and flexible porphyrin linkers, displaying folding motions based on origami tessellation. A combined experimental and theoretical investigation demonstrated the origami mechanism of the 2D porphyrinic MOF, whereby the flexible linker acts as a pivoting point. The discovery of the 2D tessellation hidden in the 2D MOF unveils origami mechanics at the molecular level., (© 2023. The Author(s).)

Objective: Arteriovenous fistulas (AVFs) are considered the first choice for venous access in end-stage renal disease patients, however, they are also known to have a high primary failure rate (early thrombosis and maturation failure). Of these, the outcome of thrombosed immature AVFs is not well known. This study aimed to investigate the outcome of AVFs with early thrombosis., Methods: Patients who underwent AVF creation from January 2009 to December 2019 at Seoul National University Hospital or Seoul Metropolitan Government - Seoul National University Boramae Medical Center were retrospectively reviewed. Patients who received salvage operations due to early thrombosis within 30 days after access creation were analyzed., Results: During the study period, a total of 45 patients (radiocephalic 26; brachiocephalic 19) developed early thrombosis and underwent salvage operations. The median age of patients was 61.0 (54.5-69.5) years, and 51.1% were male. The first salvage operation was performed on the median 1.0 (0.0-4.5) day after AVF creation. The most common cause for early thrombosis was venous stenosis (64.4%) and followed by poor arterial inflow (28.9%), especially in radiocephalic AVFs. About 20 AVFs were salvaged to maturation (46.5%). Post-salvage primary patency and secondary patency at 1 year was 72.6% and 100%. In a multivariate logistic regression, significant risk factors for maturation failures were minimum venous outflow diameter ⩽2.5 mm (OR, 4.433; 95% CI, 1.039-18.921; p  = 0.044) and lower in patients with hypertension (OR, 0.064; 95% CI, 0.006-0.637; p  = 0.019)., Conclusions: Thrombosed immature AVFs are associated with a high failure rate after salvage operation. However, if the salvage operation is successfully performed, it is associated with an acceptable 1-year outcome., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This research explores the alteration of metal-organic frameworks (MOFs) using a method called postsynthetic metal exchange. We focus on the shift from a Zn-based MOF containing a [Zn 4 O(COO) 6 ] secondary building unit (SBU) of octahedral site symmetry (ANT-1(Zn)) to a Fe-based one with a [Fe 3 III O(COO) 6 ] + SBU of trigonal prismatic site symmetry (ANT-1(Fe)). The symmetry-mismatched SBU transformation cleverly maintains the MOF's overall structure by adjusting the conformation of the flexible 1,3,5-benzenetribenzoate linker to alleviate the framework strain. The process triggers a decrease in the framework volume and pore size alongside a change in the framework's charge. These alterations influence the MOF's ability to adsorb gas and dye. During the transformation, core-shell MOFs (ANT-1(Zn@Fe)) are formed as intermediate products, demonstrating unique gas sorption traits and adjusted dye adsorption preferences due to the structural modifications at the core-shell interface. Heteronuclear clusters, located at the framework interfaces, enhance the heat of CO 2 adsorption. Furthermore, they also influence the selectivity of the dye size. This research provides valuable insights into fabricating novel MOFs with unique properties by modifying the SBU of a MOF with flexible organic linkers from one site symmetry to another.

Background: The casual relationship between the role of cholecystectomy and functional gastrointestinal disorders (FGIDs) are a controversial clinical challenge. This study aimed to investigate: (1) the overlap of FGIDs before cholecystectomy and its long-term outcome after surgery in patients with symptomatic cholelithiasis, and (2) the incidence of new-onset FGIDs after cholecystectomy., Methods: Patients with symptomatic gallstone disease who underwent elective, laparoscopic cholecystectomy were prospectively enrolled. Healthy populations who underwent medical check-ups were selected as age- and sex-matched controls. Questionnaires regarding sociodemographic characteristics, gastrointestinal symptoms and a somatization symptom checklist (SSC) were completed at baseline and 12 months thereafter., Results: The prevalence of all FGID symptoms before cholecystectomy were significantly higher in the group of patients with symptomatic cholecystolithiasis compared to the control group. In cholecystectomy group, the preoperative FGID symptoms improved after surgery, except for chronic diarrhea. Compared to the controls, the new-onset FGIDs, including functional dyspepsia (14.8% vs. 6.9%; p = 0.040), functional diarrhea (6.6% vs. 0.2%; p < 0.001), and chronic abdominal pain (11.9% vs. 4.4%; p = 0.024), were more common at 1 year after cholecystectomy. Somatization was independent predictors of new-onset dyspepsia and abdominal pain, while newly occurring diarrhea was not realted to somatization., Conclusion: Overlap of FGIDs was common in patients with symptomatic cholelithiasis before surgery and at follow-up 1 year after cholecystectomy. Furthermore, new-onset FGIDs could be occurred after cholecystectomy. Therefore, a delicate diagnostic approaches and appropriate treatments about co-existent FGIDs should be given in patients with cholelithiasis before and after cholecystectomy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chang, Jung, Moon, Kim, Shim, Jung and Min.)

Tacrolimus intra-patient variability (IPV) is a novel predictive marker for long-term kidney transplantation outcomes. We examined the association between IPV and calcineurin inhibitor (CNI) nephrotoxicity and the impact of pharmacogenes on CNI nephrotoxicity and IPV. Among kidney transplant recipients at our hospital between January 2013 and December 2015, the records of 80 patients who underwent 1-year protocol renal allograft biopsy and agreed to donate blood samples for genetic analysis were retrospectively reviewed. The cohort was divided into the low and high IPV groups based on a coefficient variability cutoff value (26.5%). In multivariate analysis, the IPV group was involved in determining CNI nephrotoxicity (HR 4.55; 95% CI 0.05-0.95; p = 0.043). The 5-year graft survival was superior in the low IPV group than in the high IPV group (100% vs 92.4% respectively, p = 0.044). Analysis of the time above therapeutic range (TATR) showed higher CNI nephrotoxicity in the high IPV with high TATR group than in the low IPV with low TATR group (35.7% versus 6.7%, p = 0.003). Genetic analysis discovered that CYP3A4 polymorphism (rs2837159) was associated with CNI nephrotoxicity (HR 28.23; 95% CI 2.2-355.9; p = 0.01). In conclusion, high IPV and CYP3A4 polymorphisms (rs2837159) are associated with CNI nephrotoxicity., (© 2023. Springer Nature Limited.)

According to twenty-first century climate-model projections, greenhouse warming will intensify rainfall variability and extremes across the globe 1-4 . However, verifying this prediction using observations has remained a substantial challenge owing to large natural rainfall fluctuations at regional scales 3,4 . Here we show that deep learning successfully detects the emerging climate-change signals in daily precipitation fields during the observed record. We trained a convolutional neural network (CNN) 5 with daily precipitation fields and annual global mean surface air temperature data obtained from an ensemble of present-day and future climate-model simulations 6 . After applying the algorithm to the observational record, we found that the daily precipitation data represented an excellent predictor for the observed planetary warming, as they showed a clear deviation from natural variability since the mid-2010s. Furthermore, we analysed the deep-learning model with an explainable framework and observed that the precipitation variability of the weather timescale (period less than 10 days) over the tropical eastern Pacific and mid-latitude storm-track regions was most sensitive to anthropogenic warming. Our results highlight that, although the long-term shifts in annual mean precipitation remain indiscernible from the natural background variability, the impact of global warming on daily hydrological fluctuations has already emerged., (© 2023. The Author(s).)

Radical nephrectomy with tumor thrombectomy for advanced renal cell carcinoma is an oncologically relevant approach that can achieve long-term survival even in the presence of distant metastases. However, the surgical techniques pose significant challenges. The objective of this clinical review was to present technical recommendations for tumor thrombectomy in the vena cava to facilitate surgical treatment. Transesophageal echocardiography is required to prepare for this procedure. Cardiopulmonary bypass should be considered when the tumor thrombus has invaded the cardiac chamber and clamping is not feasible because of the inability to milk the intracardiac chamber thrombus in the caudal direction. Prior to performing a cavotomy, it is crucial to clamp the contralateral renal vein and infrarenal and suprahepatic inferior vena cava (IVC). If the suprahepatic IVC is separated from the surrounding tissue, it can be gently pulled down toward the patient's leg until the lower margin of the atrium becomes visible. Subsequently, the tumor thrombus should be carefully pulled downward to a position where it can be clamped. Implementing the Pringle maneuver to reduce blood flow from the hepatic veins to the IVC during IVC cavotomy is simpler than clamping the hepatic veins. Sequential clamping is a two-stage method of dividing thrombectomy by clamping the IVC twice, first suprahepatically and then midretrohepatically. This sequential clamping technique helps minimize hypotension status and the Pringle maneuver time compared to single clamping. Additionally, a spiral cavotomy can decrease the degree of primary closure narrowing. The oncological prognoses of patients can be improved by incorporating these technical recommendations.

Atypical variceal bleeding, which primarily stems from extrahepatic portal vein obstruction (EHPVO), is a severe complication of pancreatic hepatobiliary surgery. This review provides insights into this condition's incidence, diagnosis, and management strategies. The treatment modalities for atypical variceal bleeding resulting from EHPVO range from endoscopic intervention to surgical procedures, including direct variceal ligation and shunt surgery. Here, we discuss the efficacy and potential limitations of each treatment approach. Additionally, we explored the utility and therapeutic advantages of the meso-Rex shunt, a particularly promising surgical technique for mitigating the hemodynamic and metabolic impacts of EHPVO.

A poleward shift of the Hadley cell (HC) edge in a warming climate, which contributes to the expansion of drought-prone subtropical regions, has been widely documented. The question addressed here is whether this shift is reversible with CO 2 removal. By conducting large-ensemble experiments where CO 2 concentrations are systematically increased and then decreased to the present-day level, we show that the poleward-shifted HC edge in a warming climate does not return to its present-day state when CO 2 concentrations are reduced. While the Southern Hemisphere HC edge remains poleward of its present-day state, the Northern Hemisphere HC edge ends up farther equatorward of its present-day state. Such hemispherically asymmetric HC edge changes are closely associated with the changes in vertical wind shear in the subtropical atmosphere, which result from the long adjustment time of the ocean response to CO 2 removal. Our findings suggest that CO 2 removal may not guarantee the recovery of the subtropical dryness associated with the HC changes.

Background: For patients with telangiectasia or reticular veins (CEAP [clinical, etiologic, anatomic, pathophysiologic] class C1), less invasive endovenous (EV) treatments have emerged. However, no prospective studies have compared compression stockings (CSs) and EV ablation treatment for C1 symptomatic refluxing saphenous veins. The present prospective study compared the therapeutic results of the two treatment modalities., Methods: From June 2020 to December 2021, 46 patients with telangiectasia or reticular veins (<3 mm; class C1) with axial saphenous reflux and venous congestion symptoms were prospectively enrolled. The patients were assigned to CS (n = 21) or EV treatment (n = 25), according to patient preference. Complications, clinical improvement scales (eg, the venous clinical severity score [VCSS]), and quality of life, including the Aberdeen varicose vein symptom severity score (AVSS) and venous insufficiency epidemiological and economic study - quality of life/symptoms (VEINES-QOL/Sym), were evaluated and compared between the two groups at 1, 3, and 6 months after treatment., Results: No major complications occurred in either group. The median VCSS was 2.0 (interquartile range [IQR], 1.0-2.0), 1.0 (IQR, 0.5-2.0), 1.0 (IQR 0.0-1.0), and 0.0 (IQR 0.0-1.0) at baseline and 1, 3, and 6 months after treatment in the CS group, respectively. The corresponding VCSSs were 3.0 (IQR, 1.0-3.0), 1.0 (IQR, 0.0-1.0), 0.0 (IQR, 0.0-0.0), and 0.0 (IQR, 0.0-0.0) in the EV group. The median AVSS was 4.4 (IQR, 3.0-5.5), 2.1 (IQR, 1.3-4.6), 1.0 (IQR, 0.0-2.8), and 0.0 (IQR, 0.0-1.8) at baseline and 1, 3, and 6 months after treatment in the CS group, respectively. The corresponding scores were 6.2 (IQR, 3.8-12.3), 1.6 (IQR, 0.6-2.8), 0.0 (IQR, 0.0-2.6), and 0.0 (IQR, 0.0-0.4) in the EV group. The mean VEINES-QOL/Sym score was 92.7 ± 8.1, 100.4 ± 7.3, 104.3 ± 8.2, and 106.0 ± 9.7 in the CS group at baseline and 1, 3, and 6 months after treatment, respectively. The corresponding scores were 83.6 ± 8.0, 102.9 ± 6.6, 107.9 ± 3.9, and 109.6 ± 3.7 in the EV group. Both groups showed considerable improvement in the VCSS, AVSS, and VEIN-SYM/QOL scores, and no significant between-group differences were observed for ≤6 months. Among the severely symptomatic patients (pretreatment VEINES-QOL/Sym score ≤90), the EV group exhibited more marked improvement (P = .029 for the VCSS and P = .030 for the VEINES-QOL/Sym score)., Conclusions: Both CSs and EV treatment provided clinical and quality of life improvement in symptomatic C1 patients with refluxing saphenous veins, with no significant between-group differences. However, a subgroup analysis revealed that EV treatment provided statistically significant improvement in the severe symptomatic C1 group., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Convective extreme El Niño (CEE) events, characterized by strong convective events in the eastern Pacific, are known to have a direct link to anomalous climate conditions worldwide, and it has been reported that CEE will occur more frequently under greenhouse warming. Here, using a set of CO 2 ramp-up and ramp-down ensemble experiments, we show that frequency and maximum intensity of CEE events increase further in the ramp-down period from the ramp-up period. These changes in CEE are associated with the southward shift of the intertropical convergence zone and intensified nonlinear rainfall response to sea surface temperature change in the ramp-down period. The increasing frequency of CEE has substantial impacts on regional abnormal events and contributed considerably to regional mean climate changes to the CO 2 forcings.