Mycobacterium marinum cutanous infection misdiagnosed as sporotrichosis in a patient with systemic lupus erythematosus: A case report.

Mycobacterium marinum(M. marinum ), a slow-growing bacterium in freshwater and seawater, can cause cutanous and extracutaneous infections. A fisher-woman with systemic lupus erythematosus (SLE) presented with chronic polymorphic rashes in a lymphangitic pattern was initially misdiagnosed as sporotrichosis. The final diagnosis of M. marinum and Candida dubliniensis co-infection was confirmed based on the skin histopathology, pustule culture, MetaCAP sequencing and effective antibiotic combination treatments.

Ask Questions with Double Hints: Visual Question Generation with Answer-awareness and Region-reference.

The visual question generation (VQG) task aims to generate human-like questions from an image and potentially other side information (e.g. answer type). Previous works on VQG fall in two aspects: i) They suffer from one image to many questions mapping problem, which leads to the failure of generating referential and meaningful questions from an image. ii) They fail to model complex implicit relations among the visual objects in an image and also overlook potential interactions between the side information and image. To address these limitations, we first propose a novel learning paradigm to generate visual questions with answer-awareness and region-reference. Concretely, we aim to ask the right visual questions with Double Hints - textual answers and visual regions of interests, which could effectively mitigate the existing one-to-many mapping issue. Particularly, we develop a simple methodology to self-learn the visual hints without introducing any additional human annotations. Furthermore, to capture these sophisticated relationships, we propose a new double-hints guided Graph-to-Sequence learning framework, which first models them as a dynamic graph and learns the implicit topology end-to-end, and then utilizes a graph-to-sequence model to generate the questions with double hints. Experimental results demonstrate the priority of our proposed method.

Central memory CD4+ T cells play a protective role against immune checkpoint inhibitor-associated myocarditis.

AIMS: The widespread use of immune checkpoint inhibitors (ICIs) has demonstrated significant survival benefits for cancer patients and also carry the risk of immune-related adverse events (irAEs). ICIs-associated myocarditis is a rare and serious adverse event with a high mortality rate. Here, we explored the mechanism underlying ICIs-associated myocarditis. METHODS AND RESULTS: Using the peripheral blood of patients with ICIs therapy and ICIs treated mice with transplanted tumors, we dissect the immune cell subsets and inflammatory factors associated with myocarditis. Compared to the control group, patients with myocarditis after ICIs therapy showed an increase in NK cells and myeloid cells in peripheral blood, while T cells significantly decreased. Among T cells, there was an imbalance of CD4/CD8 ratio in the peripheral blood of myocarditis patients, with a significant decrease in central memory CD4+ T (CD4+ TCM) cells. RNA-Seq revealed that CD4+ TCM cells in myocarditis patients were an immunosuppressive cell subset, which highly express the immunosuppressive factor IL4I1. To elucidate the potential mechanism of the decrease in CD4+ TCM cells, protein array was performed and revealed that several inflammatory factors gradually increased with the severity of myocarditis in the myocarditis group, such as IL-1B/CXCL13/CXCL9, while the myocardial protective factor IL-15 decreased. Correlation analysis indicated a positive correlation between IL-15 and CD4+ TCM cells, with high expression of IL-15 receptor IL15RA. Furthermore, in vivo studies using an anti-PDL1 antibody in a mouse tumor model indicated a reduction in CD4+ TCM cells and an increase in CD8+ TEMRA cells, alongside evidence of cardiac fibrosis. Conversely, combining anti-PDL1 antibody treatment with IL-15 led to a resurgence of CD4+ TCM cells, a reduction in CD8+ TEMRA cells, and a mitigated risk of cardiac fibrosis. CONCLUSIONS: Our data highlight CD4+ TCM cells as a crucial role in cardiac protection during ICIs therapy. IL-15, IL4I1 and CD4+ TCM cells can serve as therapeutic targets to reduce ICIs-associated myocarditis in cancer patients.

Clinical Value of the Quantitative Flow Ratio to Predict Long-term Target Vessel Failure in Patients with In-stent Restenosis after Drug-coated Balloon Angioplasty.

OBJECTIVE: The study sought to investigate the clinical predictive value of quantitative flow ratio (QFR) for the long-term target vessel failure (TVF) outcome in patients with in-stent restenosis (ISR) by using drug-coated balloon (DCB) treatment after a long-term follow-up. METHODS: This was a retrospective study. A total of 186 patients who underwent DCB angioplasty for ISR in two hospitals from March 2014 to September 2019 were enrolled. The QFR of the entire target vessel was measured offline. The primary endpoint was TVF, including target vessel-cardiac death (TV-CD), target vessel-myocardial infarction (TV-MI), and clinically driven-target vessel revascularization (CD-TVR). RESULTS: The follow-up time was 3.09±1.53 years, and 50 patients had TVF. The QFR immediately after percutaneous coronary intervention (PCI) was significantly lower in the TVF group than in the no-TVF group. Multivariable Cox regression analysis indicated that the QFR immediately after PCI was an excellent predictor for TVF after the long-term follow-up [hazard ratio (HR): 5.15×10-5 (6.13×10-8-0.043); P<0.01]. Receiver-operating characteristic (ROC) curve analysis demonstrated that the optimal cut-off value of the QFR immediately after PCI for predicting the long-term TVF was 0.925 (area under the curve: 0.886, 95% confidence interval: 0.834-0.938; sensitivity: 83.40%, specificity: 88.00; P<0.01). In addition, QFR≤0.925 post-PCI was strongly correlated with the TVF, including TV-MI and CD-TVR (P<0.01). CONCLUSION: The QFR immediately after PCI showed a high predictive value of TVF after a long-term follow-up in ISR patients who underwent DCB angioplasty. A lower QFR immediately after PCI was associated with a worse TVF outcome.

Artificial Intelligence-Assisted Prescription Determination for Orthokeratology Lens Fitting: From Algorithm to Clinical Practice.

OBJECTIVES: To explore the potential of artificial intelligence (AI) to assist prescription determination for orthokeratology (OK) lenses. METHODS: Artificial intelligence algorithm development followed by a real-world trial. A total of 11,502 OK lenses fitting records collected from seven clinical environments covering major brands. Records were randomly divided in a three-way data split. Cross-validation was used to identify the most accurate algorithm, followed by an evaluation using an independent test data set. An online AI-assisted system was implemented and assessed in a real-world trial involving four junior and three senior clinicians. RESULTS: The primary outcome measure was the algorithm's accuracy (ACC). The ACC of the best performance of algorithms to predict the targeted reduction amplitude, lens diameter, and alignment curve of the prescription was 0.80, 0.82, and 0.83, respectively. With the assistance of the AI system, the number of trials required to determine the final prescription significantly decreased for six of the seven participating clinicians (all P <0.01). This reduction was more significant among junior clinicians compared with consultants (0.76±0.60 vs. 0.32±0.60, P <0.001). Junior clinicians achieved clinical outcomes comparable to their seniors, as 93.96% (140/149) and 94.44% (119/126), respectively, of the eyes fitted achieved unaided visual acuity no worse than 0.8 ( P =0.864). CONCLUSIONS: AI can improve prescription efficiency and reduce discrepancies in clinical outcomes among clinicians with differing levels of experience. Embedment of AI in practice should ultimately help lessen the medical burden and improve service quality for myopia boom emerging worldwide.

Dual-level strategy for quantitative kinetics for the reaction between ethylene and hydroxyl radical.

The atmospheric reactions are mainly initiated by hydroxyl radical (OH). Here, we choose the C2H4 + OH reaction as a model reaction for other reactions of OH with alkenes. We use the GMM(P).L//CCSD(T)-F12a/cc-pVTZ-F12 theoretical method as the benchmark results close to the approximation of CCSDTQ(P)/CBS accuracy to investigate the C2H4 + OH reaction. The rate constants for the C2H4 + OH reaction at high-pressure limit were calculated by using the dual-level strategy. It integrates the transition state theory rate constant calculated by GMM(P).L//CCSD(T)-F12a/cc-pVTZ-F12 with the canonical variational transition state theory containing small-curvature tunneling (CVT/SCT) calculated by using the M11-L functional method with the MG3S basis set. The rate constants of C2H4 + OH at different pressures were obtained by using both the system-specific quantum Rice-Ramsperger-Kassel (SS-QRRK) theory and master equation method. The calculated results uncover that both the calculated rate constants at different pressures and temperatures are quantitatively consistent with the values obtained by the experimental measurements in the C2H4 + OH reaction. We find that the post-CCSD(T) contributions to the barrier height for the C2H4 + OH reaction are significant with the calculated value of -0.38 kcal/mol. We also find that the rate determining step is only dominated by the tight transition state under atmospheric conditions, whereas previous investigations indicated that the rate constants were controlled by both the loose and tight transition states in the C2H4 + OH reaction. The present findings unravel that it is an important factor for the effect of torsional anharmonicity on quantitative kinetics.

Quantitative kinetics reveal that reactions of HO2 are a significant sink for aldehydes in the atmosphere and may initiate the formation of highly oxygenated molecules via autoxidation.

Large aldehydes are widespread in the atmosphere and their oxidation leads to secondary organic aerosols. The current understanding of their chemical transformation processes is limited to hydroxyl radical (OH) oxidation during daytime and nitrate radical (NO3) oxidation during nighttime. Here, we report quantitative kinetics calculations of the reactions of hexanal (C5H11CHO), pentanal (C4H9CHO), and butanal (C3H7CHO) with hydroperoxyl radical (HO2) at atmospheric temperatures and pressures. We find that neither tunneling nor multistructural torsion anharmonicity should be neglected in computing these rate constants; strong anharmonicity at the transition states is also important. We find rate constants for the three reactions in the range 3.2-7.7 × 10-14 cm3 molecule-1 s-1 at 298 K and 1 atm, showing that the HO2 reactions can be competitive with OH and NO3 oxidation under some conditions relevant to the atmosphere. Our findings reveal that HO2-initiated oxidation of large aldehydes may be responsible for the formation of highly oxygenated molecules via autoxidation. We augment the theoretic studies with laboratory flow-tube experiments using an iodide-adduct time-of-flight chemical ionization mass spectrometer to confirm the theoretical predictions of peroxy radicals and the autoxidation pathway. We find that the adduct from HO2 + C5H11CHO undergoes a fast unimolecular 1,7-hydrogen shift with a rate constant of 0.45 s-1. We suggest that the HO2 reactions make significant contributions to the sink of aldehydes.

A Systematic review of the factors that affect soccer players' short-passing ability-based on the Loughborough Soccer Passing Test.

OBJECTIVE: This study synthesizes evidence from the Loughborough Passing Test to evaluate the short-passing ability of soccer players and summarizes the reported variables that affect this ability to provide support for the development and improvement of short-passing abilities in soccer players. METHODS: In this systematic review using the PRISMA guidelines, a comprehensive search was conducted in Web of Science, PubMed, and EBSCOhost from inception to July 2023 to identify relevant articles from the accessible literature. Only studies that used the Loughborough test to assess athletes' short-passing ability were included. The quality of the included studies was independently assessed by two reviewers using the PEDro scale, and two authors independently completed the data extraction. RESULTS: Based on the type of intervention or influencing factor, ten studies investigated training, nine studies investigated fatigue, nine studies investigated supplement intake, and five studies investigated other factors. CONCLUSION: Evidence indicates that fitness training, small-sided games training, and warm-up training have positive effects on athletes' short-passing ability, high-intensity special-position training and water intake have no discernible impact, mental and muscular exhaustion have a significantly negative effect, and the effect of nutritional ergogenic aid intake is not yet clear. Future research should examine more elements that can affect soccer players' short-passing ability. TRIAL REGISTRATION: https://inplasy.com/ ., identifier: INPLASY20237.

Exploration of factors affecting hemodynamic stability following pheochromocytoma resection - cohort study.

Purpose: Surgery is the only way to cure pheochromocytoma; however, postoperative hemodynamic instability is one of the main causes of serious complications and even death. This study's findings provide some guidance for improved clinical management. Patients and methods: This study was to investigate the factors leading to postoperative hemodynamic instability in the postoperative pathology indicated pheochromocytoma from May 2016 to May 2022. They were divided into two groups according to whether vasoactive drugs were used for a median number of days or more postoperatively. The factors affecting the postoperative hemodynamics in the perioperative period (preoperative, intraoperative, and postoperative) were then evaluated. Results: The median number of days requiring vasoactive drug support postoperatively was three in 234 patients, while 118 (50.4%) patients required vasoactive drug support for three days or more postoperatively. The results of the multivariate analysis indicated more preoperative colloid use (odds ratio [OR]=1.834, confidence interval [CI]:1.265-2.659, P=0.001), intraoperative use of vasoactive drug (OR=4.174, CI:1.882-9.258, P<0.001), and more postoperative crystalloid solution input per unit of body weight per day (ml/kg/d) (OR=1.087, CI:1.062-1.112, P<0.001) were risk factors for predicting postoperative hemodynamic instability. The optimal cutoff point of postoperative crystalloid use were 42.37 ml/kg/d. Conclusion: Hemodynamic instability is a key issue for consideration in the perioperative period of pheochromocytoma. The amount of preoperative colloid use, the need for intraoperative vasoactive drugs, and postoperative crystalloid solution are risk factors for predicting postoperative hemodynamic instability (registration number: ChiCT2300071166).

Increased serum SGLT2 and its potential diagnostic and prognostic value in patients with acute ischemic stroke.

BACKGROUND: Recently acquired data suggests that sodium-glucose cotransporter-2 (SGLT2) may be a therapeutic target for cerebral ischemia. The specific impact of SGLT2 in acute ischemic stroke (AIS) remains unknown. We aimed to explore the levels of SGLT2 in AIS patients and its association with functional prognosis. METHODS: In this study, 132 AIS patients and 44 healthy controls were recruited prospectively to determine serum SGLT2 levels. Logistic regression analysis was employed to assess the association between serum SGLT2 level and stroke risk as well as 3-month outcome. Receiver operating characteristic (ROC) curves were utilized to evaluate predictive values for blood biomarkers. RESULTS: Serum SGLT2 levels were significantly higher (P =.000) in AIS patients (47.1 (interquartile range [IQR]: 42.4-50.9) ng/mL) than healthy controls (35.7 (IQR: 28.6-39.5) ng/mL). The optimal SGLT2 cutoff point for diagnosing AIS was 39.55 ng/mL, with a sensitivity of 90.2 % and specificity of 77.3 %. Serum levels of SGLT2 were negatively correlated with the onset time of AIS (linear fit R2 = 0.056, P =.006), but were not associated with National Institutes of Health Stroke Scale (NIHSS) scores (r = 0.007, P >.05) and lesion volume (r = -0.151, P >.05). SGLT2 was not remarkably different between patients with unfavorable and favorable outcomes (46.7 (IQR: 41.9-49.6) ng/mL vs 47.6 (IQR: 42.5-51.9) ng/mL; P =.321). CONCLUSIONS: The serum SGLT2 concentration may be a potential biomarker for the diagnosis of AIS. However, it does not exhibit any association with disease severity or functional prognosis.

Reactive aldehyde chemistry explains the missing source of hydroxyl radicals.

Hydroxyl radicals (OH) determine the tropospheric self-cleansing capacity, thus regulating air quality and climate. However, the state-of-the-art mechanisms still underestimate OH at low nitrogen oxide and high volatile organic compound regimes even considering the latest isoprene chemistry. Here we propose that the reactive aldehyde chemistry, especially the autoxidation of carbonyl organic peroxy radicals (R(CO)O2) derived from higher aldehydes, is a noteworthy OH regeneration mechanism that overwhelms the contribution of the isoprene autoxidation, the latter has been proved to largely contribute to the missing OH source under high isoprene condition. As diagnosed by the quantum chemical calculations, the R(CO)O2 radicals undergo fast H-migration to produce unsaturated hydroperoxyl-carbonyls that generate OH through rapid photolysis. This chemistry could explain almost all unknown OH sources in areas rich in both natural and anthropogenic emissions in the warm seasons, and may increasingly impact the global self-cleansing capacity in a future low nitrogen oxide society under carbon neutrality scenarios.

Rapid Atmospheric Reactions between Criegee Intermediates and Hypochlorous Acid.

Hypochlorous acid (HOCl) is a paramount compound in the atmosphere due to its significant contribution to both tropospheric oxidation capacity and ozone depletion. The main removal routes for HOCl are photolysis and the reaction with OH during the daytime, while these processes are unimportant during the nighttime. Here, we report the rapid reactions of Criegee intermediates (CH2OO and anti/syn-CH3CHOO) with HOCl by using high-level quantum chemical methods as the benchmark; their accuracy is close to coupled cluster theory with single, double, and triple excitations and quasiperturbative connected quadruple excitations with a complete basis limit by extrapolation [CCSDT(Q)/CBS]. Their rate constants have been calculated by using a dual-level strategy; this combines conventional transition state theory calculated at the benchmark level with variational transition state theory with small-curvature tunneling by a validated density functional method. We find that the introduction of the methyl group into Criegee intermediates not only affects their reactivities but also exerts a remarkable influence on anharmonicity. The calculated results uncover that anharmonicity increases the rate constants of CH2OO + HOCl by a factor of 18-5, while it is of minor importance in the anti/syn-CH3CHOO + HOCl reaction at 190-350 K. The present findings reveal that the loose transition state for anti-CH3CHOO and HOCl is a rate-determining step at 190-350 K. We also find that the reaction of Criegee intermediates with HOCl contributes significantly to the sink of HOCl during the nighttime in the atmosphere.

In quest of China sports lottery development path to common prosperity in 2035.

OBJECTIVES: The China sports lottery contributes to sports and welfare causes. This study aims to construct a macro forecasting model supporting its sustained growth aligned with Vision 2035. METHODS: The modeling employed a distributional regression. Sales data of the China sports lottery from 2011 to 2022 were chosen as the response variable, alongside various macro- and event-level explanatory factors. RESULTS: A gamma distribution best fit the data. In the stable model spanning 2011-2019, urbanization, population dynamics, and FIFA emerged as significant contributors (Chi-square p < 0.05) to the location shift parameter. These three factors retained their significance in the 2011-2022 shock model, where shock itself notably impacted sales (p < 0.001). Utilizing the shock model, we simulated the trajectory of the China sports lottery up to 2035. China's demographics changes are poised to create structural headwinds starting in 2026, leading to an anticipated decline in sales driven by population shifts from 2032 onward. However, the FIFA effect is projected to continue fortifying this sector. CONCLUSIONS: Beyond offering original insights into the sales trajectory until 2035, specifically concerning new urbanization, negative population growth, and the FIFA effect, this macro forecasting framework can assist in addressing the policy priority of balancing growth with risk mitigation. We recommend policymakers connect market development with mass sports, potentially garnering a dual boost from the growing population of older consumers and the inherent benefits of a "FIFA (mass sports)" effect. A people-centered approach to the China sports lottery could significantly contribute to the long-range objectives of achieving common prosperity outlined in Vision 2035.

Mechanism of the Visible-Light-Promoted C(sp3)-H Oxidation via Uranyl Photocatalysis.

Uranyl cation, as an emerging photocatalyst, has been successfully applied to synthetic chemistry in recent years and displayed remarkable catalytic ability under visible light. However, the molecular-level reaction mechanisms of uranyl photocatalysis are unclear. Here, we explore the mechanism of the stepwise benzylic C-H oxygenation of typical alkyl-substituted aromatics (i.e., toluene, ethylbenzene, and cumene) via uranyl photocatalysis using theoretical and experimental methods. Theoretical calculation results show that the most favorable reaction path for uranyl photocatalytic oxidation is as follows: first, hydrogen atom transfer (HAT) from the benzyl position to form a carbon radical ([R•]), then oxygen addition ([R•] + O2 → [ROO•]), then radical-radical combination ([ROO•] + [R•] → [ROOR] → 2[RO•]), and eventually [RO•] reduction to produce alcohols, of which 2° alcohol would further be oxidized to ketones and 1° would be stepwise-oxygenated to acids. The results of the designed verification experiments and the capture of reactive intermediates were consistent with those of theoretical calculations and the previously reported research that the active benzylic C-H would be stepwise-oxygenated in the presence of uranyl. This work deepens our understanding of the HAT mechanism of uranyl photocatalysis and provides important theoretical support for the relevant application of uranyl photocatalysts in organic transformation.

Ammonolysis of Glyoxal at the Air-Water Nanodroplet Interface.

The reactions of glyoxal (CHO)2 ) with amines in cloud processes contribute to the formation of brown carbon and oligomer particles in the atmosphere. However, their molecular mechanisms remain unknown. Herein, we investigate the ammonolysis mechanisms of glyoxal with amines at the air-water nanodroplet interface. We identified three and two distinct pathways for the ammonolysis of glyoxal with dimethylamine and methylamine by using metadynamics simulations at the air-water nanodroplet interface, respectively. Notably, the stepwise pathways mediated by the water dimer for the reactions of glyoxal with dimethylamine and methylamine display the lowest free energy barriers of 3.6 and 4.9 kcal ⋅ mol-1 , respectively. These results showed that the air-water nanodroplet ammonolysis reactions of glyoxal with dimethylamine and methylamine were more feasible and occurred at faster rates than the corresponding gas phase ammonolysis, the OH+(CHO)2 reaction, and the aqueous phase reaction of glyoxal, leading to the dominant removal of glyoxal. Our results provide new and important insight into the reactions between carbonyl compounds and amines, which are crucial in forming nitrogen-containing aerosol particles.

Quantitative kinetics of the atmospheric reaction between isocyanic acid and hydroxyl radicals: post-CCSD(T) contribution, anharmonicity, recrossing effects, torsional anharmonicity, and tunneling.

Hydroxyl radicals (OH) are the most important atmospheric oxidant, initiating atmospheric reactions for the chemical transformation of volatile organic compounds. Here, we choose the HNCO + OH reaction as a prototype reaction because it contains the fundamental reaction processes for OH radicals: H-abstraction reaction by OH and OH addition reaction. However, its kinetics are unknown under atmospheric conditions. We investigate the reaction of HNCO with OH by using the GMM(P).L method close to the accuracy of single, double, triple, and quadruple excitations and noniterative quintuple excitations with a complete basis set (CCSDTQ(P)/CBS) as benchmark results and a dual-level strategy for kinetics calculations. The calculated rate constant of HNCO + OH is in good agreement with the experimental data available at the temperatures between 620 and 2500 K. We find that the rate constant cannot be correctly obtained by using experimental data to extrapolate the atmospheric temperature ranges. We find that the post-CCSD(T) contribution is very large for the barrier height with the value of -0.85 kcal mol-1 for the H-abstraction reaction, while the previous investigations were done up to the CCSD(T) level. Moreover, we also find that recrossing effects, tunneling, torsional anharmonicity, and anharmonicity are important for obtaining quantitative kinetics in the OH + HNCO reaction.

Hydroxyapatite-based nano-drug delivery system for nicotinamide mononucleotide (NMN): significantly enhancing NMN bioavailability and replenishing in vivo nicotinamide adenine dinucleotide (NAD+) levels.

OBJECTIVES: This study addresses the bioavailability challenges associated with oral nicotinamide mononucleotide (NMN) administration by introducing an innovative NMN formulation incorporated with hydroxyapatite (NMN-HAP). METHODS: The NMN-HAP was developed using a wet chemical precipitation and physical adsorption method. To assess its superiority over conventional free NMN, we examined NMN, nicotinamide adenine dinucleotide (NAD+), and nicotinamide riboside (NR) levels in mouse plasma and tissues following oral administration of NMN-HAP. KEY FINDINGS: NMN-HAP nanoparticles demonstrated a rod-shaped morphology, with an average size of ~50 nm, along with encapsulation efficiency and drug loading capacity exceeding 40%. In vitro, drug release results indicated that NMN-HAP exhibited significantly lower release compared with free NMN. In vivo studies showed that NMN-HAP extended circulation time, improved bioavailability compared with free NMN, and elevated plasma levels of NMN, NAD+, and NR. Moreover, NMN-HAP administration displayed tissue-specific distribution with a substantial accumulation of NMN, NAD+, and NR in the brain and liver. CONCLUSION: NMN-HAP represents an ideal formulation for enhancing NMN bioavailability, enabling tissue-specific delivery, and ultimately elevating in vivo NAD+ levels. Considering HAP's biocompatible nature and versatile characteristics, we anticipate that this system has significant potential for various future applications.

Association of immune checkpoint inhibitors therapy with arterial thromboembolic events in cancer patients: A retrospective cohort study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have emerged as a standard treatment for various malignancies. However, research indicates blocking the immune checkpoint pathway may exacerbate atherosclerotic lesions. OBJECTIVES: We aimed to investigate whether ICI therapy increases the risk of arterial thromboembolic events (ATEs). METHODS: A retrospective cohort study was conducted on patients with histologically confirmed cancer at our institution between 2018 and 2021, using the propensity score matching method. The primary endpoint was ATEs occurrence, comprising acute coronary syndrome, stroke/transient ischemic attack, and peripheral arterial thromboembolism. Subgroup analyses assessed whether the ICI treatment effect on ATEs varied over time by limiting the maximum follow-up duration. Logistic regression analysis identified ATE risk factors in ICI-treated patients. RESULTS: Overall, the ICI group (n = 2877) demonstrated an ATEs risk 2.01 times higher than the non-ICI group (RR, 2.01 [95% CI (1.61-2.51)]; p < 0.001). Subgroup analysis revealed no significant increase in ATEs risk for ICI-treated patients within 1 year (Limited to a max 9-month follow-up, p = 0.075). However, ATEs risk in the ICI group rose by 41% at 1 year (p = 0.010) and 97% at 4 years (p ≤ 0.001). Age, diabetes, hypertension, peripheral atherosclerosis, atrial fibrillation, chronic ischemic heart disease, distant cancer metastasis, and ICI treatment cycles contributed to ATEs risk elevation in ICI-treated patients. CONCLUSION: ICI-treated patients may exhibit a higher risk of ATEs, especially after 1 year of treatment.

Kinetics of Sulfur Trioxide Reaction with Water Vapor to Form Atmospheric Sulfuric Acid.

Although experimental methods can be used to obtain the quantitative kinetics of atmospheric reactions, experimental data are often limited to a narrow temperature range. The reaction of SO3 with water vapor is important for elucidating the formation of sulfuric acid in the atmosphere; however, the kinetics is uncertain at low temperatures. Here, we calculate rate constants for reactions of sulfur trioxide with two water molecules. We consider two mechanisms: the SO3···H2O + H2O reaction and the SO3 + (H2O)2 reaction. We find that beyond-CCSD(T) contributions to the barrier heights are very large, and multidimensional tunneling, unusually large anharmonicity of high-frequency modes, and torsional anharmonicity are important for obtaining quantitative kinetics. We find that at lower temperatures, the formation of the termolecular precursor complexes, which is often neglected, is rate-limiting compared to passage through the tight transition states. Our calculations show that the SO3···H2O + H2O mechanism is more important than the SO3 + (H2O)2 mechanism at 5-50 km altitudes. We find that the rate ratio between SO3···H2O + H2O and SO3 + (H2O)2 is greater than 20 at altitudes between 10 and 35 km, where the concentration of SO3 is very high.

Unimolecular Reactions of E-Glycolaldehyde Oxide and Its Reactions with One and Two Water Molecules.

The kinetics of Criegee intermediates are important for atmospheric modeling. However, the quantitative kinetics of Criegee intermediates are still very limited, especially for those with hydroxy groups. Here, we calculate rate constants for the unimolecular reaction of E-glycolaldehyde oxide [E-hydroxyethanal oxide, E-(CH2OH)CHOO], for its reactions with H2O and (H2O)2, and for the reaction of the E-(CH2OH)CHOO…H2O complex with H2O. For the highest level of electronic structure, we use W3X-L//CCSD(T)-F12a/cc-pVDZ-F12 for the unimolecular reaction and the reaction with water and W3X-L//DF-CCSD(T)-F12b/jun-cc-pVDZ for the reaction with 2 water molecules. For the dynamics, we use a dual-level strategy that combines conventional transition state theory with the highest level of electronic structure and multistructural canonical variational transition state theory with small-curvature tunneling with a validated density functional for the electronic structure. This dynamical treatment includes high-frequency anharmonicity, torsional anharmonicity, recrossing effects, and tunneling. We find that the unimolecular reaction of E-(CH2OH)CHOO depends on both temperature and pressure. The calculated results show that E-(CH2OH)CHOO…H2O + H2O is the dominant entrance channel, while previous investigations only considered Criegee intermediates + (H2O)2. In addition, we find that the atmospheric lifetime of E-(CH2OH)CHOO with respect to 2 water molecules is particularly short with a value of 1.71 × 10-6 s at 0 km, which is about 2 orders of magnitude shorter than those usually assumed for Criegee intermediate reactions with water dimer. We also find that the OH group in E-(CH2OH)CHOO enhances its reactivity.