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CARI score ≥3 demonstrated moderate discrimination (c-statistic 0.79, optimism-corrected c-statistic 0.77) with appropriate calibration. QTc ≥480 ms was associated with a 5-fold increase in the risk of CA/VAs. The CARI score may identify patients at higher risk of these events. Whether heightened perioperative cardiac surveillance, avoidance of QT prolonging medications, or beta blockers could mitigate the risk of CA/VAs in this population merits further study.Background and aim Very early-onset inflammatory bowel disease is defined as inflammatory bowel disease diagnosed before 6 years of age. Very early-onset inflammatory bowel disease has various differential diagnoses, including primary immunodeficiency disorders, and is known to be resistant to conventional treatment. Therefore, global attention is required to manage this challenging condition. We conducted a retrospective epidemiological survey of the number of patients, final diagnosis, and examinations performed to diagnose very early-onset inflammatory bowel disease in Japan. Methods A primary questionnaire about the number of very early-onset bowel disease cases and its diagnosis was administered to 630 pediatric facilities nationwide in Japan. A secondary survey about the examinations performed to achieve diagnosis was sent to the facilities that responded to the first survey. Results The answering rate was 92.2% (581/630 facilities); 81 facilities had 225 very early-onset bowel disease patients undergoing their care during the past 68 months. Twenty-six patients (11.6%) were diagnosed with immunodeficiency-associated inflammatory bowel disease. The answering rate of the secondary survey was 70.4% (57/81 facilities). Colonoscopy, esophagogastroduodenoscopy, and small bowel imaging were performed for 99.4%, 67.5%, and 28.8% of patients, respectively. Genetic analysis was performed for 26.9% (43/160 patients) of patients, and 51.2% (22/43) of patients were diagnosed with immunodeficiency-associated inflammatory bowel disease. Conclusions Approximately 40 patients are diagnosed yearly in Japan. Imaging studies, especially for small bowel lesions, can be challenging for this unique group of patients. However, a comprehensive approach including immunological and genetic analyses appears useful for diagnosing immunodeficiency-associated inflammatory bowel disease.2020 is a leap year. That means that we have one day extra and, if the Olympic games had survived the corona crisis, we would all be watching television and ask the eternal question whether Olympic records will for ever be broken and broken again, or that there are limits to human biology1 . In this article we ask the same question, but rather than discussing aspects of Citius, Altius, and Fortius of athletes we will discuss them for macromolecules. It is remarkable how many parallels can be found between Olympic records in these two seemingly different worlds. People involved in structure validation and re-refinement try to make us believe that most aspects of macromolecular structures can be caught by a number that has some constant value with little variation around it. We will show here that the PDB2 databank proves this idea to be wrong. In the protein structure world, it holds for many that "participating is more important than winning", but some, fortunately, still go for the record books.Two types of Fe(III) polynuclear iron(III) 1D-chain coordination compounds of the general formula [Fe (L)(tvp)]BPh4 nSolv, where L = dianion of N,N'-ethylenebis (benzoylacetylacetone)2,2'-imine (bzacen), tvp = 1,2-di(4-pyridyl)ethylene were synthesized and studied by the electron paramagnetic resonance (EPR) and magnetic susceptibility methods in the temperature range (100-300) К. Two types of spin-variable complexes are formed depending on the time of precipitation of the complexes from the same solution leading to differently solvated species. They have different characteristics of the local ligand field and the spin transition behavior. Apoptosis antagonist The thermodynamic parameters of spin transitions were determined from the temperature dependence of the EPR signals integral intensity. The energy levels splitting values obtained by analyzing g-factors of low-spin Fe(III) centers evidenced not only on the crucial role of low-symmetry distortions on the principal possibility of spin-crossover processes, but also on the temperature peculiarities of spin transitions.Recent studies have revealed that metabolic reprogramming is closely associated with epithelial-mesenchymal transition (EMT) during cancer progression. Aldolase A (ALDOA) is a key glycolytic enzyme that is highly expressed in several types of cancer. In this study, we found that ALDOA is highly expressed in uterine cervical adenocarcinoma and that high ALDOA expression promotes EMT to increase malignant potentials, such as metastasis and invasiveness, in cervical adenocarcinoma cells. In human surgical specimens, ALDOA was highly expressed in cervical adenocarcinoma and high ALDOA expression was correlated with lymph node metastasis, lymphovascular infiltration, and short overall survival. Suppression of ALDOA expression significantly reduced cell growth, migration, and invasiveness of cervical cancer cells. Aldolase A expression was partially regulated by hypoxia-inducible factor-1α (HIF-1α). Shotgun proteome analysis revealed that cell-cell adhesion-related proteins were significantly increased in ALDOA-overexpressing cells. Interestingly, overexpression of ALDOA caused severe morphological changes, including a cuboidal-to-spindle shape shift and reduced microvilli formation, coincident with modulation of the expression of typical EMT-related proteins. Overexpression of ALDOA increased migration and invasion in vitro. Furthermore, overexpression of ALDOA induced HIF-1α, suggesting a positive feedback loop between ALDOA and HIF-1α. In conclusion, ALDOA is overexpressed in cervical adenocarcinoma and contributes to malignant potentials of tumor cells through modulation of HIF-1α signaling. The feedback loop between ALDOA and HIF-1α could become a therapeutic target to improve the prognosis of this malignancy.