Association between carotid plaque progression and persistent endothelial dysfunction in an infarct-related coronary artery in STEMI survivors.

Persistent coronary endothelial dysfunction predicts future adverse events; however, performing multiple invasive endothelial function tests is difficult in actual clinical practice. This study examined the association between carotid plaque progression and persistent coronary endothelial dysfunction using serial assessments of the coronary vasomotor response to acetylcholine (ACh) in the infarct-related artery (IRA) among patients with ST-elevation acute myocardial infarction (STEMI). This study included 169 consecutive patients with a first STEMI due to the left anterior descending coronary artery (LAD) occlusion who underwent successful percutaneous coronary intervention. The vasomotor response to ACh in the LAD was measured within two weeks after acute myocardial infarction (AMI) (first test) and repeated at six months (second test) after AMI. Ultrasonography of the bilateral common carotid artery and internal carotid artery was performed during the acute phase, and the thickest intima-media thickness (IMT) of either artery was measured as the maximum IMT. After six months, the IMT at the site of maximal IMT was re-measured to determine the carotid plaque progression. Finally, 87 STEMI patients analyzed. At 6 months, 25 patients (28.7%) showed carotid plaque progression. In a multivariable analysis, carotid plaque progression was identified as an independent predictor of persistent coronary endothelial dysfunction, both in terms of coronary diameter response [odd ratio (OR) 3.22, 95% confidence interval (95% CI) 1.13-9.15, p = 0.03] and coronary flow response [OR 2.65, 95% CI 1.01-7.00, p = 0.04]. Independently, carotid plaque progression is linked to persistent endothelial dysfunction in the IRA among STEMI survivors.

Survey on large language model annotation of cellular senescence from figures in review articles.

This study evaluated large language models (LLMs), particularly the GPT-4 with vision (GPT-4 V) and GPT-4 Turbo, for annotating biomedical figures, focusing on cellular senescence. We assessed the ability of LLMs to categorize and annotate complex biomedical images to enhance their accuracy and efficiency. Our experiments employed prompt engineering with figures from review articles, achieving more than 70% accuracy for label extraction and approximately 80% accuracy for node-type classification. Challenges were noted in the correct annotation of the relationship between directionality and inhibitory processes, which were exacerbated as the number of nodes increased. Using figure legends was a more precise identification of sources and targets than using captions, but sometimes lacked pathway details. This study underscores the potential of LLMs in decoding biological mechanisms from text and outlines avenues for improving inhibitory relationship representations in biomedical informatics.

Probability of normal tissue complications for hematologic and gastrointestinal toxicity in postoperative whole pelvic radiotherapy for gynecologic malignancies using intensity-modulated proton therapy with robust optimization.

This retrospective treatment-planning study was conducted to determine whether intensity-modulated proton therapy with robust optimization (ro-IMPT) reduces the risk of acute hematologic toxicity (H-T) and acute and late gastrointestinal toxicity (GI-T) in postoperative whole pelvic radiotherapy for gynecologic malignancies when compared with three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated X-ray (IMXT) and single-field optimization proton beam (SFO-PBT) therapies. All plans were created for 13 gynecologic-malignancy patients. The prescribed dose was 45 GyE in 25 fractions for 95% planning target volume in 3D-CRT, IMXT and SFO-PBT plans and for 99% clinical target volume (CTV) in ro-IMPT plans. The normal tissue complication probability (NTCP) of each toxicity was used as an in silico surrogate marker. Median estimated NTCP values for acute H-T and acute and late GI-T were 0.20, 0.94 and 0.58 × 10-1 in 3D-CRT; 0.19, 0.65 and 0.24 × 10-1 in IMXT; 0.04, 0.74 and 0.19 × 10-1 in SFO-PBT; and 0.06, 0.66 and 0.15 × 10-1 in ro-IMPT, respectively. Compared with 3D-CRT and IMXT plans, the ro-IMPT plan demonstrated significant reduction in acute H-T and late GI-T. The risk of acute GI-T in ro-IMPT plan is equivalent with IMXT plan. The ro-IMPT plan demonstrated potential clinical benefits for reducing the risk of acute H-T and late GI-T in the treatment of gynecologic malignances by reducing the dose to the bone marrow and bowel bag while maintaining adequate dose coverage to the CTV. Our results indicated that ro-IMPT may reduce acute H-T and late GI-T risk with potentially improving outcomes for postoperative gynecologic-malignancy patients with concurrent chemotherapy.

Pretransfer Aspirin Administration and Its Impact on Angiographic Outcomes for Patients with ST-Elevation Myocardial Infarction.

Although guidelines recommend early aspirin administration after diagnosis of ST-elevation myocardial infarction (STEMI), the decision of pretransfer aspirin administration is at the discretion of the primary physicians. Therefore, this study aimed to determine whether pretransfer aspirin administration was associated with better angiographical outcomes in patients with STEMI. This study compared the angiographic findings of thrombolysis in myocardial infarction (TIMI) flow grade in the infarct-related artery before percutaneous coronary intervention (PCI) between patients who received pretransfer aspirin and those who did not. In total, 28 patients (11.2%) were administered aspirin before transfer and 219 (88.8%) were administered aspirin upon arrival at the hospital. Propensity score matching yielded 135 patients [27 patients (20%) who were administered aspirin before transfer and 108 patients (80%) who were administered aspirin upon arrival at the hospital]. Patients who received pretransfer aspirin had a higher rate of TIMI-3 flow before PCI compared to those who did not receive pretransfer aspirin [8 (28.6%) versus 15 (6.8%), P < 0.01, in all study patients; 8 (26.6%) versus 7 (6.5%), P < 0.01, in propensity-score-matched patients]. Multivariable logistic regression analysis revealed that pretransfer aspirin administration was significantly associated with the presence of TIMI-3 flow before PCI, independent of age, gender, transfer time, and statin use (OR: 5.43, 95% CI: 1.94-15.2, P < 0.01, in all study patients; OR: 6.17, 95% CI: 1.86-20.46, P < 0.01, in propensity-score-matched patients). Pretransfer aspirin administration could lead to the early restoration of coronary blood flow in patients with STEMI, supporting its active use in STEMI care.

Using the PubAnnotation ecosystem to perform agile text mining on Genomics & Informatics: a tutorial review.

The prototype version of the full-text corpus of Genomics & Informatics has recently been archived in a GitHub repository. The full-text publications of volumes 10 through 17 are also directly downloadable from PubMed Central (PMC) as XML files. During the Biomedical Linked Annotation Hackathon 6 (BLAH6), we experimented with converting, annotating, and updating 301 PMC full-text articles of Genomics & Informatics using PubAnnotation, a system that provides a convenient way to add PMC publications based on PMCID. Thus, this review aims to provide a tutorial overview of practicing the iterative task of named entity recognition with the PubAnnotation/PubDictionaries/TextAE ecosystem. We also describe developing a conversion tool between the Genia tagger output and the JSON format of PubAnnotation during the hackathon.

open-japanese-mesh: assigning MeSH UIDs to Japanese medical terms via open Japanese-English glossaries.

The Medical Subject Headings (MeSH) system is a controlled vocabulary for indexing biomedical documents that is used for document retrieval and other natural language processing purposes. However, although the original English MeSH is freely available, its Japanese translation has a restricted license. We attempted to create an open alternative, and for this purpose we made a script for assigning MeSH UIDs to Japanese medical terms using Japanese-English glossaries. From the MeSpEn glossary and MEDUTX dictionary, we generated a 12,457-word Japanese-MeSH dictionary.

Visualizing redox orbitals and their potentials in advanced lithium-ion battery materials using high-resolution x-ray Compton scattering.

Reduction-oxidation (redox) reactions are the key processes that underlie the batteries powering smartphones, laptops, and electric cars. A redox process involves transfer of electrons between two species. For example, in a lithium-ion battery, current is generated when conduction electrons from the lithium anode are transferred to the redox orbitals of the cathode material. The ability to visualize or image the redox orbitals and how these orbitals evolve under lithiation and delithiation processes is thus of great fundamental and practical interest for understanding the workings of battery materials. We show that inelastic scattering spectroscopy using high-energy x-ray photons (Compton scattering) can yield faithful momentum space images of the redox orbitals by considering lithium iron phosphate (LiFePO4 or LFP) as an exemplar cathode battery material. Our analysis reveals a new link between voltage and the localization of transition metal 3d orbitals and provides insight into the puzzling mechanism of potential shift and how it is connected to the modification of the bond between the transition metal and oxygen atoms. Our study thus opens a novel spectroscopic pathway for improving the performance of battery materials.

Educational Activity for the Radiation Emergency System in the Northern Part of Japan: Meeting Report on "The 3rd Educational Symposium on Radiation and Health (ESRAH) by Young Scientists in 2016".

In the northern part of Japan, close cooperation is essential in preparing for any possible emergency response to radiation accidents because several facilities, such as the Low-Level Radioactive Waste Disposal Facility, the MOX Fuel Fabrication Plant and the Vitrified Waste Storage Center, exist in Rokkasho Village (Aomori Prefecture). After the accident at Fukushima Daiichi Nuclear Power Plant in 2011, special attention should be given to the relationship between radiation and human health, as well as establishing a system for managing with a radiation emergency. In the area of Hokkaido and Aomori prefectures in Japan, since 2008 an exchange meeting between Hokkaido University and Hirosaki University has been held every year to have opportunities to discuss radiation effects on human health and to collect the latest news on monitoring environmental radiation. This meeting was elevated to an international meeting in 2014 titled "Educational Symposium on Radiation and Health (ESRAH) by Young Scientists". The 3rd ESRAH meeting took place in 2016, with the theme "Investigating Radiation Impact on the Environmental and Health". Here we report the meeting findings on the continuing educational efforts after the Fukushima incident, what was accomplished in terms of building a community educational approaches, and future goals.

Effect of enhanced expression of connexin 43 on sunitinib-induced cytotoxicity in mesothelioma cells.

Connexin (Cx) makes up a type of intercellular channel called gap junction (GJ). GJ plays a regulatory role in cellular physiology. The Cx expression level is often decreased in cancer cells compared to that in healthy ones, and the restoration of its expression has been shown to exert antiproliferative effects. This work aims to evaluate the effect of the restoration of connexin 43 (Cx43) (the most ubiquitous Cx subtype) expression on sunitinib (SU)-induced cytotoxicity in malignant mesothelioma (MM) cells. Increased Cx43 expression in an MM cell line (H28) improved the ability of SU to inhibit receptor tyrosine kinase (RTK) signaling. Moreover, higher Cx43 expression promoted SU-induced apoptosis. The cell viability test revealed that Cx43 enhanced the cytotoxic effect of SU in a GJ-independent manner. The effect of Cx43 on a proapoptotic factor, Bax, was then investigated. The interaction between Cx43 and Bax was confirmed by immunoprecipitation. Furthermore, higher Cx43 expression increased the production of a cleaved (active) form of Bax during SU-induced apoptosis with no alteration in total Bax expression. These findings indicate that Cx43 most likely increases sensitivity to SU in H28 through direct interaction with Bax. In conclusion, we found that Cx43 overcame the chemoresistance of MM cells.

New 2-aryl-1,4-naphthoquinone-1-oxime methyl ether compound induces microtubule depolymerization and subsequent apoptosis.

In this study, we describe the antitumor activity of QO-1, one of the new 2-aryl-1,4-naphthoquinone-1-oxime methyl ether derivatives. QO-1 is a derivative of macarpine, a natural occurring product from Rutaceae plant. It could potently inhibit cell growth when tested on 19 cancer cell lines. To investigate its mechanism, two cell lines (HeLa and MCF-7) sensitive to QO-1 were selected. Based on flow cytometry, it was found to induce G(2)/M-phase arrest. Moreover, it could cause microtubule depolymerization both in vitro and in vivo. On the other hand, QO-1 activated spindle assembly checkpoint (SAC) proteins. Expression of Bub1, one of the SAC, was gradually increased, reaching a peak after 16 - 20 h, and then gradually decreased. Instead, QO-1 increased the sub-G(1) population, which suggested a cell death population. Actually, expression of Bcl-2 family proteins and activation of caspase-3/7 were evidences of apoptosis. Consistent with these results, cells with DNA fragmentation and multinucleated cells were increased time-dependently after QO-1 exposure. In conclusion, QO-1 has promising antitumor effects via microtubule depolymerization.

A demethylating agent enhances chemosensitivity to vinblastine in a xenograft model of renal cell carcinoma.

Renal cell carcinoma (RCC) is resistant to chemo-therapy partly due to the overexpression of the P-glycoprotein. Several tumor suppressor genes have been reported to be silenced by hypermethylation of the promoter region in RCC. We recently reported that the in vitro cytotoxicity of vinblastine (VBL) was enhanced by pre-treatment with the demethylating agent, 5-aza-2'-deoxycytidine (Aza), in the RCC cell line, Caki-1. In this study, we investigated the combined effect of Aza and VBL in a Caki-1 xenograft model and in other RCC cell lines in vitro. In the xenograft model, tumor volume and weight were significantly suppressed in the co-treatment group, compared to the control, and the expressions of P-glycoprotein, Bcl-2 and cyclin B1 were reduced. Thus, this combined effect could be mediated by the accumulation of intracellular VBL and the enhancement of apoptosis and cell cycle arrest. More-over, the cytotoxicity of VBL was enhanced in vitro in three RCC cell lines by Aza treatment. These findings suggest that the combination treatment with Aza and VBL is effective against RCC.

2-Aryl-1,4-naphthoquinone-1-oxime methyl ethers: their cytotoxic activity.

Preliminary examination for the structure-activity relationship of quinone monooxime derivatives on cytotoxicity against HeLa S3 cell and further trials using eight different cell lines suggested that 2-aryl-6,7-methylenedioxy-1,4-naphthoquinone-1-oxime methyl ethers, carrying 2-methoxy-4,5-methylenedioxyphenyl, 7-methoxy-2-methylbenzofuran-4-yl, and 2-methoxycarbonyl-3,4-dimethoxyphenyl as the 2-aryl substituent, were potential candidates for anti-cancer drugs.

Enhanced effect of connexin 43 on cisplatin-induced cytotoxicity in mesothelioma cells.

The expression levels of connexin (Cx) proteins, which are gap junction (GJ) components, are often decreased in many cancers, and restoring their levels has been shown to have antitumor effects. Previously, dysfunctional gap junctional intercellular communication (GJIC) has been observed in several malignant mesotheliomas (MMs), and among the many Cx proteins, Cx43 is prominently expressed in nontumorigenic mesothelial tissues. Therefore, we investigated whether Cx43 upregulation has an antitumor effect on an MM cell line (H28 cell), especially with regard to drug resistance. After treatment with the chemotherapeutic agent cisplatin (CDDP), MM cell viability significantly decreased, and apoptosis induction was observed in Cx43-transfected clones. A specific GJIC inhibitor could not abrogate this effect. On the other hand, the Src protein is known to phosphorylate Cx43, which results in GJIC inhibition. This suggests that Src activity might also be regulated by the hyperexpression of Cx43. In fact, the Src protein level was decreased in Cx43-transfected clones. Moreover, Src inhibition reinforced CDDP cytotoxicity in parental H28 cells. These data suggest that Cx43 could improve the resistance to CDDP in a GJIC-independent manner, which may be partly mediated by the suppression of Src activity.