Model development was based on previous work done by Umegaki et al. [ 7]. Briefly, possible variables were derived by using methods developed by Umegaki et al., but with modifications. First, patients in the Umegaki model are all admitted to the ICU, whereas in our dataset not all patients were admitted to the ICU but all patients received MV. Among the demographic variables, age was defined as a continuous variable. Among the clinical factors, hospital admission categories were derived from the administrative data. Scheduled-admission patients were those admitted through a reservation provided during their previous hospital visit. Unscheduled or ambulance admissions were categorized as emergency admissions. Emergency admission included admissions direct to the hospital, by referral from other hospitals, or from the scene of the precipitating event or accident. Scheduled admission was used as a reference value for hospital admissions in the multivariate analysis. “Reasons for ICU admission” in the study by Umegaki et al. was replaced by “Reasons for starting MV.” “Patients who underwent surgery on the day of initiation of MV”, or “patients who began MV within 7 days after surgery” were replaced as “patients who underwent MV in relation to surgery.” Among these patients, those who underwent surgery on the day of hospital admission or the following day were defined as having had “emergency surgery,” whereas those who did not undergo emergency surgery were defined as having had “scheduled surgery.” All other patients were considered to have been admitted for medical reasons.

Inhibition of glycolytic and TCA cycle‐related enzymes. (A) Recombinant human GAPDH treated with 100 and 250μM GP‐2250 for 30 and 60min, followed by GAPDH enzyme activity assay. (B) Inhibition of GAPDH activity in Panc Tul and BxPC3 cells following incubation with GP‐2250 (500μM) for 24h. The GAPDH inhibitor DMF, 100μM, was included as control. (C) Human recombinant hexokinase 2 (HK2) incubated with 250 and 500μM GP‐2250 for 60min. Formation of NADH was measured every 5min. (D) Inhibition of hexokinase 2 (HK2)activity in Panc Tul and BxPC3 cells following incubation with GP‐2250 (250, 500 and 1000μM) for 24h. (E) Inhibition of alpha‐ketoglutarate dehydrogenase (αKGDH) following treatment of Panc Tul and BxPC3 cells for 24h with GP‐2250 (250, 500 and 1000μM). (F) Inhibition of pyruvate dehydrogenase (PDH) following treatment of Panc Tul and BxPC3 cells for 24h with GP‐2250 (250 and 500μM). Concentrations of GP‐2250 ranging from 100 to 1000μM were used in the cellular assays of GAPDH, HK2, αKGDH and PDH, Shown are the results of the lowest effective concentrations, respectively. * p≤0.05, significant; ** p≤0.01, highly significant; *** p≤0.001, extremely significant. DMF, dimethylfumarate; GAPDH, glyceraldehyde‐3‐phosphate‐dehydrogenase; HK2, hexokinase 2; NADH, nicotinamide adenine dinucleotide+hydrogen; NC, negative control; U, untreated. Carson SS, Cox CE, Holmes GM, et al. The changing epidemiology of mechanical ventilation: a population-based study. J Intensive Care Med. 2006;21(3):173–82.

Stock Glass

Shen H. Y., Zhao H. H., Yang J., Zhao J., Yan L., Chou L. J., Song H. L., New J. Chem., 2022, 46, 3095 Takeda K, Wada A, Yamamoto K, Moriyama Y, Aoki K (1989) Conformational change of bovine serum albumin by heat treatment. J Protein Chem 8:653–659 A reduction of the transcriptional activity of NF‐κB was apparent in both Panc Tul and BxPC3 cell lines by the change in expression of cyclin D1 and Bcl2. This is testimony to the functional relevance of NF‐kB inhibition by GP‐2250. The expression of cyclin D1, the driver of cell cycle progression, was reduced by GP‐2250 (Figure 5). This finding is in line with the previously shown reduction of the rate of cell proliferation by GP‐2250. 1 The expression of the anti‐apoptotic protein Bcl2 was likewise reduced by GP‐2250 (Figure 6). Thus, by inhibiting NF‐κB, GP‐2250 is able to disrupt tumour progression in a two‐pronged manner, by reducing the rate of cell proliferation and promoting apoptosis. Meng D. L., Zhang M. D., Si D. H., Mao M. J., Hou Y., Huang Y. B., Cao R., Angew. Chem. Int. Ed., 2021, 60, 25485 Chang G. G., Ma X. C., Zhang Y. X., Wang L. Y., Tian G., Liu J. W., Wu J., Hu Z. Y., Yang X. Y., Chen B. L., Adv. Mater., 2019, 31, 1904969

Fischer M, Georges J (1997) Use of thermal lens spectrometry for the investigation of dimerization equilibria of rhodamine 6G in water and aqueous micellar solutions. Spectrochim Acta A Mol Biomol Spectrosc 53:1419–1430 Kemnitz K, Yoshihara K (1991) Entropy-driven dimerization of xanthene dyes in nonpolar solution and temperature-dependent fluorescence decay of dimers. J Phys Chem 95:6095–6104Representative western blot (A) and quantitative analysis (B) of regulatory proteins in Panc TuI (A) and BxPC3 (B) cells. pACC: Time‐dependent increase of ACC‐1 phosphorylation at Ser79 and of Raptor at Ser792 following incubation of Panc Tul (250μM GP‐2250) and BxPC3 (500μM GP‐2250). pRaptor: Time‐dependent Raptor phosphorylation at Ser 792 in PancTul and BxPc3 cells incubated with 500 and 1000μM GP‐2250. p53: Time‐dependent increase of protein level of p53 in Panc Tul and BxPC3 cells (500μM GP‐2250). Akt and mTor: Time‐dependent decrease of the protein level of Akt and mTor at 1000μM GP‐2250 in Panc TuI and BxPC3 cells. Bcl2: Time‐dependent downregulation of protein level of Bcl2 following incubation of Panc Tul and BxPC3 cells (500μM GP‐2250). ß‐Actin/HSP‐90 used as internal controls. Hannagan R. T., Giannakakis G., Flytzani-Stephanopoulos M., Sykes E. C. H., Chem. Rev., 2020, 120, 12044 Sirio CA, Tajimi K, Taenaka N, et al. A cross-cultural comparison of critical care delivery: Japan and the United States. Chest. 2002;121:539–48.

Hemmer E, Benayas A, Legare F, Vetrone F (2016) Exploiting the biological windows: current perspectives on fluorescent bioprobes emitting above 1000 nm. Nanoscale Horiz 1:168–184 We compared patients on MV who were treated at least once in ICUs (ICU group) and those who never stayed in ICUs (non-ICU group). Patients whose treatment was started in non-ICU settings and who were then transferred to ICUs were counted in the ICU group, regardless of whether they started MV before or after ICU admission. “MV” includes both intubated MV and acute-phase non-invasive MV with partial arterial pressure of oxygen (PaO 2) < 300 mmHg or partial arterial pressure of carbon dioxide (PaCO 2) > 45 mmHg. “ICU” was defined here as “officially certified ICU” in accordance with Japanese government insurance policy. The criteria for an officially certified ICU include staffing of the unit with at least one physician in-house 24 hourly and with nurses at a ratio of one nurse to two patients; in addition, a certified ICU must be fully equipped with hardware to resuscitate critically ill patients. In Japan there are many quasi-ICU units that treat severely ill patients and function similar to ICUs but not officially certified. These quasi-ICUs were counted among non-ICUs. Duke GJ, Santamaria J, Shann F, et al. Critical care outcome prediction equation (COPE) for adult intensive care. Crit Care Resusc. 2008;10:35–41. Zhu J, Li J-J, Zhao J-W (2009) Spectral characters of rhodamine B as a multi-information fluorescence probe for bovine serum albumins. Sensors Actuators B Chem 138:9–13IBM System/360 Component Description IBM 2250 Display Unit Model 2 IBM 2840 Display Control Model 1 GA27-2702-0.