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Abstract Reliable prediction of aviation’s environmental impact, including the effect of nitrogen oxides on ozone, is vital for effective mitigation against its contribution to global warming. Estimating this climate impact however, in terms of the short-term ozone instantaneous radiative forcing, requires computationally-expensive chemistry-climate model simulations that limit practical applications such as climate-optimised planning. Existing surrogates neglect the large uncertainties in their predictions due to unknown environmental conditions and missing features. Relative to these surrogates, we propose a high-accuracy probabilistic surrogate that not only provides mean predictions but also quantifies heteroscedastic uncertainties in climate impact estimates. Our model is trained on one of the most comprehensive chemistry-climate model datasets for aviation-induced nitrogen oxide impacts on ozone. Leveraging feature selection techniques, we identify essential predictors that are readily available from weather forecasts to facilitate the implementation therein. We show that our surrogate model is more accurate than homoscedastic models and easily outperforms existing linear surrogates. We then predict the climate impact of a frequently-flown flight in the European Union, and discuss limitations of our approach.

Abstract Purpose To determine the ability of CO2-enhanced angiography to detect active diverticular bleeding that is not detected by iodinated contrast medium (ICM)-enhanced angiography and its impact on clinical outcomes when used to confirm embolization, particularly the risks of rebleeding and ischemic complications. Materials and methods We retrospectively identified a cohort of patients with colonic diverticular bleeding who underwent catheter angiography between August 2008 and May 2023 at our institution. We divided them according to whether they underwent CO2 angiography following a negative ICM angiography study or to confirm hemostasis post-embolization (the CO2 angiography group) or ICM angiography alone in the absence of active bleeding or for confirmation of hemostasis post-embolization (the ICM angiography group). The ability to detect active colonic diverticular bleeding and clinical outcomes were compared between the two groups. Results There were 31 patients in the ICM angiography group and 29 in the CO2 angiography group. The rate of detection of active bleeding by CO2 angiography that was not identified by ICM angiography was 48%. The rebleeding rate was 23% in the ICM angiography group and 6.9% in the CO2 angiography group. Among the patients who underwent TAE, the ischemic complications rate was 7.1% in the ICM angiography group and 4.5% in the CO2 angiography group. Conclusions CO2 angiography may detect active diverticular bleeding that is not detectable by ICM angiography and appears to be associated with a lower rebleeding rate. Level of evidence IV. Graphical Abstract

Abstract In complex systems, it’s crucial to uncover latent mechanisms and their context-dependent relationships. This is especially true in medical research, where identifying unknown cancer mechanisms and their impact on phenomena like drug resistance is vital. Directly observing these mechanisms is challenging due to measurement complexities, leading to an approach that infers latent mechanisms from observed variable distributions. Despite machine learning advancements enabling sophisticated generative models, their black-box nature complicates the interpretation of complex latent mechanisms. A promising method for understanding these mechanisms involves estimating latent factors through linear projection, though there’s no assurance that inferences made under specific conditions will remain valid across contexts. We propose a novel solution, suggesting data, even from systems appearing complex, can often be explained by sparse dependencies among a few common latent factors, regardless of the situation. This simplification allows for modeling that yields significant insights across diverse fields. We demonstrate this with datasets from finance, where we capture societal trends from stock price movements, and medicine, where we uncover new insights into cancer drug resistance through gene expression analysis.

Abstract Here we report the effects of low-intensity pulsed ultrasound (LIPUS) on symptoms in peripheral arterial disease patients with Buerger disease. A double-blinded and randomized study with active and inactive LIPUS was conducted. We assessed symptoms in leg circulation during a 24-week period of LIPUS irradiation in 12 patients with Buerger disease. Twelve patients without LIPUS irradiation served as controls. The pain intensity on visual analog score was significantly decreased after 24-week LIPUS treatment. Skin perfusion pressure was significantly increased in patients who received LIPUS treatment. There was no significant difference in symptoms and perfusion parameters in the control group. No severe adverse effects were observed in any of the patients who underwent LIPUS treatment. LIPUS is noninvasive, safe and effective option for improving symptoms in patients with Buerger disease.

Abstract Background Current guidelines recommend the use of mechanical circulatory support (MCS) for patients with cardiogenic shock that is refractory to medical therapy. Bleeding is the most common complication of MCS. Transarterial embolization (TAE) is often performed to treat this complication, because it is a less invasive hemostatic procedure. However, the TAE option needs to be carefully considered during MCS, as the access route may be limited during MCS. Case presentation A man in his 70 s was diagnosed with acute myocardial infarction and underwent percutaneous coronary intervention via venoarterial extracorporeal membrane oxygenation (VA-ECMO) and Impella. During treatment in the intensive care unit, he suffered damage to a branch of the internal thoracic artery during a cardiac drainage procedure, which was subsequently treated via emergency TAE. An ECMO return cannula and an Impella sheath were inserted into the patient’s right and left femoral arteries, respectively. An approach from the left brachial artery was selected, and the left internal thoracic artery was embolized. Subsequently, the patient required re-intervention to treat re-bleeding from another artery. Because it was difficult to target the target artery from the brachial one, owing to interference from the Impella catheter, the ECMO circuit near the return cannula was punctured and a guiding sheath was inserted. The ECMO flow and the patient’s blood pressure decreased following placement of this guiding sheath. We were thus able to maintain the patient’s blood pressure by increasing the infusion fluids and Impella flow, and embolize the target artery using a gelatin sponge to achieve hemostasis. Conclusion When TAE is difficult to perform during MCS using an approach from the upper extremities, a lower extremity approach with a sheath inserted into the ECMO circuit may represent a viable alternative.

Abstract Necrophilic behavior (attempted copulation with corpses) has been scarcely reported in non-human primates, especially in the wild. Here is the first case of necrophilic behavior observed in wild stump-tailed macaques in Thailand. Six groups of total N > 460 individuals have been identified and habituated. The corpse of an adult female was found and directly observed for 2 days and by camera trap for 3 days. The cause of death could not be identified, but no prominent physical injury was detected. Within 3 days of the observation, three different males attempted copulation with the corpse. Noteworthy for this observation was that not only males in the group of the dead female but also males from different groups interacted with the corpse. Taken together, these observations suggest that some cues emanating from the corpse coupled with a nonresistant/passive orientation may have triggered these responses in the males. Given that necrophiliac responses have been scarcely reported in non-human primates, our findings provide new insight into these behaviors and to comparative thanatology in general.

Abstract Background We aimed to compare the hydrodynamic values of carbon dioxide (CO2) and iodine contrast media for bleeding detection using an in vitro model. Materials and methods We created a bleeding model with large and small wounds in simulated blood vessels. We connected a syringe to the bleeding model and the blood pressure transducer, filling the circuit with CO2 and iodine contrast media. The syringe’s piston was pressed, and the flow rate and intravascular pressure of the CO2 and iodine contrast media leaking from the bleeding model were measured. We compared each leaked contrast medium’s volume, sphere-equivalent diameter, and sphere-equivalent area. These values were analyzed to compare the visibility of the leakage objectively. Results At a constant flow rate, the intravascular pressure required for the model to leak was lower for the CO2 than that for the iodine contrast medium. The CO2 contrast medium leakage volume, equivalent circle diameter, and equivalent circle area were greater than those of the iodine one. These values indicate higher CO2 visibility during fluoroscopy. Conclusions In the bleeding model, a CO2 contrast medium may be more prone to leakage than the iodine one in large and small wounds. Regarding visibility, a CO2 contrast medium may be more likely to detect leakage than an iodine one.

Abstract Background We developed a bleeding risk scoring system (BRSS) using prophylactic anticoagulation therapy to comprehensively assess the risk of venous thromboembolism (VTE) in trauma patients. This study evaluated the usefulness of this system in trauma patients, with a focus on minimizing the rate of bleeding events associated with prophylactic anticoagulation therapy. Methods We retrospectively evaluated the efficacy of BRSS in trauma patients who received prophylactic anticoagulation therapy for VTE at the Kitasato University Hospital Emergency and Critical Care Center between April 1, 2015, and August 31, 2020. To compare the incidence of bleeding events, patients were divided into two groups: one group using the BRSS (BRSS group) and another group not using the BRSS (non-BRSS group). Results A total of 94 patients were enrolled in this study, with 70 and 24 patients assigned to the non-BRSS and BRSS groups, respectively. The major bleeding event rates were not significantly different between the two groups (BRSS group, 4.2%; non-BRSS group, 5.7%; p = 1.000). However, minor bleeding events were significantly reduced in the BRSS group (4.2% vs.27.1%; p = 0.020). Multivariate logistic regression analysis showed that BRSS was not an independent influencing factor of major bleeding events (odds ratio, 0.660; 95% confidence interval: 0.067-6.47; p = 0.721). Multivariate logistic regression analysis showed that BRSS was an independent influencing factor of minor bleeding events (odds ratio, 0.119; 95% confidence interval: 0.015-0.97; p = 0.047). The incidence of VTE did not differ significantly between groups (BRSS group, 4.2%; non-BRSS group, 8.6%; p = 0.674). Conclusions BRSS may be a useful tool for reducing the incidence of minor bleeding events during the initial prophylactic anticoagulation therapy in trauma patients. There are several limitations of this study that need to be addressed in future research.

Abstract The purpose of this study was to evaluate the effects of administration of overnight 1 mg dexamethasone on vascular function in patients with nonfunctioning adrenal adenomas (NFA). Flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) were measured to assess vascular function in 22 patients with NFA who had hypertension and/or diabetes mellitus (DM) and 272 patients without adrenal incidentalomas who had hypertension and/or DM (control patients with hypertension and/or DM). FMD and NID were measured in the morning before and after administration of 1 mg of dexamethasone at 2300 h in 18 patients with NFA. There were no significant differences in FMD and NID between control patients with hypertension and/or DM and patients with NFA who had hypertension and/or DM (3.4 ± 2.8% vs. 2.9 ± 1.9% and 11.5 ± 5.7% vs. 11.4 ± 4.3%, P = 0.46, and P = 0.99, respectively). There were no significant differences in vascular function between control patients with hypertension and/or DM and patients with NFA who had hypertension and/or DM even after adjustment for cardiovascular risk factors. Overnight 1 mg dexamethasone increased FMD from 2.4 ± 1.9% to 5.3 ± 3.2% (P

Background: Zinc plays an important role in sepsis; however, the effectiveness of zinc supplementation and the appropriate dose remain unclear. This study aimed to verify the effectiveness of zinc supplementation and the appropriate dose in patients with sepsis. Methods: This single-center retrospective observational study included 247 patients with sepsis from 1 April 2015 to 31 March 2023 who were receiving ventilatory management. The patients were divided into three groups according to the zinc supplementation dose: p = 0.36). No statistically significant differences were observed in the length of intensive care unit (ICU) stay (p = 0.06). A higher supplementation dose corresponded with a statistically significant increase in blood zinc concentration in the first week (38.5 ± 16.6 µg/dL, 58.8 ± 19.7 µg/dL, 74.2 ± 22.5 µg/dL, respectively; p < 0.01) but not in the second or third weeks (p = 0.08, 0.19, respectively). Conclusions: Zinc supplementation did not reduce the mortality rate or length of ICU stay or contribute to an increased serum zinc concentration. High-dose zinc supplementation may not be effective during acute sepsis.

Abstract Background The number of elderly patients with ulcerative colitis (UC) has been increasing worldwide. Complications are common in elderly patients who undergo colonoscopy, raising doubts about whether colonoscopy should be performed in the same way in this age group as in younger patients. The aim of this study was to determine the safety of full bowel preparation and colonoscopy in elderly patients with UC. Methods We retrospectively reviewed a cohort of patients with UC who had visited any of the 12 hospitals and were registered in our inflammatory bowel disease database. We compared complications associated with colonoscopy and bowel preparation and relapse of UC after colonoscopy in 133 patients aged ≥65 years with UC (the elderly group) and 116 randomly selected patients aged

Abstract Adult T‐cell leukaemia/lymphoma (ATL) remains incurable. The NF‐κB and interferon regulatory factor 4 (IRF4) signalling pathways are among the critical survival pathways for the progression of ATL. TGF‐β‐activated kinase 1 (TAK1), an IκB kinase‐activating kinase, triggers the activation of NF‐κB. The resorcylic acid lactone LL‐Z1640‐2 is a potent irreversible inhibitor of TAK1/extracellular signal‐regulated kinase 2 (ERK2). We herein examined the therapeutic efficacy of LL‐Z1640‐2 against ATL. LL‐Z1640‐2 effectively suppressed the in vivo growth of ATL cells. It induced in vitro apoptosis and inhibited the nuclear translocation of p65/RelA in ATL cells. The knockdown of IRF4 strongly induced ATL cell death while downregulating MYC. LL‐Z1640‐2 as well as the NF‐κB inhibitor BAY11‐7082 decreased the expression of IRF4 and MYC at the protein and mRNA levels, indicating the suppression of the NF‐κB‐IRF4‐MYC axis. The treatment with LL‐Z1640‐2 also mitigated the phosphorylation of p38 MAPK along with the expression of CC chemokine receptor 4. Furthermore, the inhibition of STAT3/5 potentiated the cytotoxic activity of LL‐Z1640‐2 against IL‐2‐responsive ATL cells in the presence of IL‐2. Therefore, LL‐Z1640‐2 appears to be an effective treatment for ATL. Further studies are needed to develop more potent compounds that retain the active motifs of LL‐Z1640‐2.