Chemical synthesis of oligodeoxyribonucleotides containing the Dewar valence isomer of the (6–4) photoproduct and their use in (6–4) photolyase studies

The pyrimidine(6–4)pyrimidone photoproduct, a major UV lesion formed between adjacent pyrimidine bases, is transformed to its Dewar valence isomer upon exposure to UVA/UVB light. We have synthesized a phosphoramidite building block of the Dewar photoproduct formed at the thymidylyl(3′–5′)thymidine site and incorporated it into oligodeoxyribonucleotides. The diastereoisomers of the partially protected dinucleoside monophosphate bearing the (6–4) photoproduct, which were caused by the chirality of the phosphorus atom, were separated by reversed-phase chromatography, and the (6–4) photoproduct was converted to the Dewar photoproduct by irradiation of each isomer with Pyrex-filtered light from a high-pressure mercury lamp. The Dewar photoproduct was stable under both acidic and alkaline conditions at room temperature. After characterization of the isomerized base moiety by NMR spectroscopy, a phosphoramidite building block was synthesized in three steps. Although the ordinary method could be used for the oligonucleotide synthesis, benzimidazolium triflate as an alternative activator yielded better results. The oligonucleotides were used for the analysis of the reaction and the binding of Xenopus (6–4) photolyase. Although the affinity of this enzyme for the Dewar photoproduct-containing duplex was reportedly similar to that for the (6–4) photoproduct-containing substrate, the results suggested a difference in the binding mode

Radial Transport Characteristics of Fast Ions Due to Energetic-Particle Modes inside the Last Closed-Flux Surface in the Compact Helical System

The internal behavior of fast ions interacting with magnetohydrodynamic bursts excited by energetic ions has been experimentally investigated in the compact helical system. The resonant convective oscillation of fast ions was identified inside the last closed-flux surface during an energetic-particle mode (EPM) burst. The phase difference between the fast-ion oscillation and the EPM, indicating the coupling strength between them, remains a certain value during the EPM burst and drives an anomalous transport of fast ions

Predictors of Survival in Patients With Ischemic Stroke and Active Cancer: A Prospective, Multicenter, Observational Study

BACKGROUND: Limited data exist on the prognostic factors for patients with ischemic stroke and active cancer. METHODS AND RESULTS: We conducted a prospective, multicenter, observational study in Japan, including patients with acute ischemic stroke and active cancer, to investigate the prognostic factors. We followed up the patients for 1 year after stroke onset. The patients were divided into 2 groups according to cryptogenic stroke and known causes (small-vessel occlusion, large-artery atherosclerosis, cardioembolism, and other determined cause), and survival was compared. The hazard ratios (HRs) and 95% CIs for mortality were calculated using Cox regression models. We identified 135 eligible patients (39% women; median age, 75 years). Of these patients, 51% had distant metastasis. A total of 65 (48%) and 70 (52%) patients had cryptogenic stroke and known causes, respectively. Patients with cryptogenic stroke had significantly shorter survival than those with known causes (HR [95% CI], 3.11 [1.82–5.32]). The multivariable Cox regression analysis revealed that distant metastasis, plasma D-dimer levels, venous thromboembolism (either deep venous thrombosis or pulmonary embolism) complications at stroke onset were independent predictors of mortality after adjusting for potential confounders. Cryptogenic stroke was associated with prognosis in univariable analysis but was not significant in multivariable analysis. The plasma D-dimer levels stratified the prognosis of patients with ischemic stroke and active cancer. CONCLUSIONS: The prognosis of patients with acute ischemic stroke and active cancer varied considerably depending on stroke mechanism, distant metastasis, and coagulation abnormalities. The present study confirmed that coagulation abnormalities were crucial in determining the prognosis of such patients.Gon Y., Sakaguchi M., Yamagami H., et al. Predictors of Survival in Patients With Ischemic Stroke and Active Cancer: A Prospective, Multicenter, Observational Study. Journal of the American Heart Association 12, e029618 (2023); https://doi.org/10.1161/JAHA.123.029618

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

BACKGROUND: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study\u27s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p\u3c0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p\u3c0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction

Characteristics of sustainable OSS projects: a theoretical and empirical study

CHASE '15 : the Eighth International Workshop on Cooperative and Human Aspects of Software Engineering, May 16-24, 2015, Florence, ItalyHow can we attract developers? What can we do to incentivize developers to write code? We started the study by introducing the population pyramid visualization to software development communities, called software population pyramids, and found a typical pattern in shapes. This pattern comes from the differences in attracting coding contributors and discussion contributors. To understand the causes of the differences, we then build game-theoretical models of the contribution situation. Based on these results, we again analyzed the projects empirically to support the outcome of the models, and found empirical evidence. The answers to the initial questions are clear. To incentivize developers to code, the projects should prepare documents, or the projects or third parties should hire developers, and these are what sustainable projects in GitHub did in reality. In addition, making innovations to reduce the writing costs can also have an impact in attracting coding contributors

Validation of an algorithm that determines stroke diagnostic code accuracy in a Japanese hospital-based cancer registry using electronic medical records

Abstract Background This study aimed to validate an algorithm that determines stroke diagnostic code accuracy, in a hospital-based cancer registry, using electronic medical records (EMRs) in Japan. Methods The subjects were 27,932 patients enrolled in the hospital-based cancer registry of Osaka University Hospital, between January 1, 2007 and December 31, 2015. The ICD-10 (international classification of diseases, 10th revision) diagnostic codes for stroke were extracted from the EMR database. Specifically, subarachnoid hemorrhage (I60); intracerebral hemorrhage (I61); cerebral infarction (I63); and other transient cerebral ischemic attacks and related syndromes and transient cerebral ischemic attack (unspecified) (G458 and G459), respectively. Diagnostic codes, both “definite” and “suspected,” and brain imaging information were extracted from the database. We set the algorithm with the combination of the diagnostic code and/or the brain imaging information, and manually reviewed the presence or absence of the acute cerebrovascular disease with medical charts. Results A total of 2654 diagnostic codes, 1991 “definite” and 663 “suspected,” were identified. After excluding duplicates, the numbers of “definite” and “suspected” diagnostic codes were 912 and 228, respectively. The proportion of the presence of the disease in the “definite” diagnostic code was 22%; this raised 51% with the combination of the diagnostic code and the use of brain imaging information. When adding the interval of when brain imaging was performed (within 30 days and within 1 day) to the diagnostic code, the proportion increased to 84% and 90%, respectively. In the algorithm of “definite” diagnostic code, history of stroke was the most common in the diagnostic code, but in the algorithm of “definite” diagnostic code and the use of brain imaging within 1 day, stroke mimics was the most frequent. Conclusions Combining the diagnostic code and clinical examination improved the proportion of the presence of disease in the diagnostic code and achieved appropriate accuracy for research. Clinical research using EMRs require outcome validation prior to conducting a study