Coreference based event-argument relation extraction on biomedical text

This paper presents a new approach to exploit coreference information for extracting event-argument (E-A) relations from biomedical documents. This approach has two advantages: (1) it can extract a large number of valuable E-A relations based on the concept of salience in discourse; (2) it enables us to identify E-A relations over sentence boundaries (cross-links) using transitivity of coreference relations. We propose two coreference-based models: a pipeline based on Support Vector Machine (SVM) classifiers, and a joint Markov Logic Network (MLN). We show the effectiveness of these models on a biomedical event corpus. Both models outperform the systems that do not use coreference information. When the two proposed models are compared to each other, joint MLN outperforms pipeline SVM with gold coreference information

Microstructured organic cavities with high-reflective flat reflectors fabricated by using a nanoimprint-bonding process

The integration of photonic microstructure into organic microcavities represents an effective strategy for manipulating eigenstates of cavity or polariton modes. However, well-established fabrication processes for microstructured organic microcavities are still lacking. In this study, we propose a nanoimprint-bonding process as a novel fabrication method for microstructured organic microcavities. This process relies on a UV nanoimprint technique utilizing two different photopolymer resins, enabling the independent fabrication of highly reflective reflectors and photonic microstructures without compromising the accuracy of each. The resulting organic microcavities demonstrate spatially localized photonic modes within dot structures and their nonlinear responses on the pumping fluence. Furthermore, a highly precise photonic band is confirmed within a honeycomb lattice structure, which is owing to the high quality factor of the cavity achievable with the nanoimprint-bonding process. Additionally, a topological edge state is also observable within a zigzag lattice structure. These results highlight the significant potential of our fabrication method for advancing organic-based photonic devices, including lasers and polariton devices

1250nm帯モード同期クロム・フォルステライトレーザーを光源とした第2高調波発生光顕微鏡によるヒト顔皮膚の老化性真皮コラーゲン構造変化のその場観察

In vivo visualization of human skin aging is demonstrated using a Cr:Forsterite (Cr:F) laser-based, collagen-sensitive second harmonic generation (SHG) microscope. The deep penetration into human skin, as well as the specific sensitivity to collagen molecules, achieved by this microscope enables us to clearly visualize age-related structural changes of collagen fiber in the reticular dermis. Here we investigated intrinsic aging and/or photoaging in the male facial skin. Young subjects show dense distributions of thin collagen fibers, whereas elderly subjects show coarse distributions of thick collagen fibers. Furthermore, a comparison of SHG images between young and elderly subjects with and without a recent life history of excessive sun exposure show that a combination of photoaging with intrinsic aging significantly accelerates skin aging. We also perform image analysis based on two-dimensional Fourier transformation of the SHG images and extracted an aging parameter for human skin. The in vivo collagen-sensitive SHG microscope will be a powerful tool in fields such as cosmeceutical sciences and anti-aging dermatology.博士（医学）・乙第1311号・平成25年5月29

Anti-NF-κB peptide derived from nuclear acidic protein attenuates ovariectomyinduced osteoporosis in mice

NF-κB is a transcription factor that is activated with aging. It plays a key role in the development of osteoporosis by promoting osteoclast differentiation and inhibiting osteoblast differentiation. In this study, we developed a small anti-NF-κB peptide called 6A-8R from a nuclear acidic protein (also known as macromolecular translocation inhibitor II, Zn2+-binding protein, or parathymosin) that inhibits transcriptional activity of NF-κB without altering its nuclear translocation and binding to DNA. Intraperitoneal injection of 6A-8R attenuated ovariectomy-induced osteoporosis in mice by inhibiting osteoclast differentiation, promoting osteoblast differentiation, and inhibiting sclerostin production by osteocytes in vivo with no apparent side effects. Conversely, in vitro, 6A-8R inhibited osteoclast differentiation by inhibiting NF-κB transcriptional activity, promoted osteoblast differentiation by promoting Smad1 phosphorylation, and inhibited sclerostin expression in osteocytes by inhibiting myocyte enhancer factors 2C and 2D. These findings suggest that 6A-8R has the potential to be an antiosteoporotic therapeutic agent with uncoupling properties.Takami K., Okamoto K., Etani Y., et al. Anti-NF-κB peptide derived from nuclear acidic protein attenuates ovariectomyinduced osteoporosis in mice. JCI Insight 8, e171962 (2023); https://doi.org/10.1172/jci.insight.171962

An investigation of the differential therapeutic effects of romosozumab on postmenopausal osteoporosis patients with or without rheumatoid arthritis complications: a case–control study

The version of record of this article, first published in Osteoporosis International, is available online at Publisher’s website: https://doi.org/10.1007/s00198-024-07019-2Summary: The impact of ROMO on the width of anabolic windows and the increase in BMD was reduced in the RA group compared to the non-RA group, and this reduction was associated with correlations to RA-related factors. Purpose: To investigate the effects of romosozumab (ROMO) in postmenopausal osteoporosis, with and without comorbid rheumatoid arthritis (RA). Methods: In this retrospective, case-controlled, multicenter study, 171 postmenopausal patients who did not receive oral glucocorticoid, comprising 59 in the RA group and 121 in the non-RA group, received uninterrupted ROMO treatment for 12 months. Propensity score matching was employed to ensure comparability in clinical backgrounds, resulting in 41 patients in each group. Baseline characteristics were as follows: overall (mean age, 76.3 years; T-score of lumbar spine (LS), − 3.0; 45.1% were treatment-naive for osteoporosis); RA group (anti-cyclic citrullinated peptide antibody (ACPA) positivity, 80.5%; titer, 206.2 U/ml; clinical disease activity index (CDAI), 13.6; health assessment questionnaire disability index (HAQ-DI), 0.9). Bone mineral density (BMD) and serum bone turnover markers were monitored over a 12-month period. Results: The rate of increase in the bone formation marker, PINP, and the rates of decrease in the bone resorption marker, TRACP-5b, exhibited a trend toward smaller changes in the RA group compared to the non-RA group, implying a smaller anabolic window. After 12 months, the RA group displayed lower BMD increases in the LS (9.1% vs. 12.6%; P = 0.013) and total hip (2.4% vs. 4.8%; P = 0.025) compared to the non-RA group. Multiple regression analysis in the all RA group (n = 59) for the association between RA-specific factors and 12-month BMD changes revealed negative correlations between ACPA titer and LS BMD and between HAQ-DI and femoral neck BMD. Conclusions: The efficacy of ROMO may be attenuated by RA-related factors

Outcomes after stepwise ablation for persistent atrial fibrillation in patients with heart failure

AbstractBackgroundThere is limited data regarding the outcomes after stepwise ablation for persistent atrial fibrillation (AF) in patients with heart failure (HF).Methods and resultsPatients without structural heart disease undergoing stepwise ablation for persistent AF (continuous AF≤1 year) were studied (n=108; age, 61±10 years) and 32 patients had a history of HF. The HF patients were further grouped on the basis of left ventricular ejection fraction (LVEF)≤45% (n=15) and >45% (n=17). During a median follow-up period of 2.2 years, repeated ablations were necessary in 65 patients. The proportion of patients that were arrhythmia free 1 year after the last ablation was 67% in patients with LVEF≤45%, 86% in LVEF>45%, and 91% in no HF (p=0.0009). In patients with LVEF≤45%, the AF burden was reduced to less than one paroxysmal episode per month, and patients with and without recurrences both showed significant increases in LVEF over the follow-up period (38±7% to 60±10% and 37±6% to 53±10%, respectively).ConclusionsHF patients with LVEF≤45% had lower chances to remain free from arrhythmias after stepwise ablation for persistent AF than those with LVEF>45%. Nevertheless, LVEF also improved in patients with recurrences, reflecting the observed reduction in AF burden and emphasizing the benefits of ablation

Basic fibroblast growth factor promotes meniscus regeneration through the cultivation of synovial mesenchymal stem cells via the CXCL6–CXCR2 pathway

Objective: To investigate the efficacy of basic fibroblast growth factor (bFGF) in promoting meniscus regeneration by cultivating synovial mesenchymal stem cells (SMSCs) and to validate the underlying mechanisms. Methods: Human SMSCs were collected from patients with osteoarthritis. Eight-week-old nude rats underwent hemi-meniscectomy, and SMSCs in pellet form, either with or without bFGF (1.0 × 106 cells per pellet), were implanted at the site of meniscus defects. Rats were divided into the control (no transplantation), FGF (−) (pellet without bFGF), and FGF (+) (pellet with bFGF) groups. Different examinations, including assessment of the regenerated meniscus area, histological scoring of the regenerated meniscus and cartilage, meniscus indentation test, and immunohistochemistry analysis, were performed at 4 and 8 weeks after surgery. Results: Transplanted SMSCs adhered to the regenerative meniscus. Compared with the control group, the FGF (+) group had larger regenerated meniscus areas, superior histological scores of the meniscus and cartilage, and better meniscus mechanical properties. RNA sequencing of SMSCs revealed that the gene expression of chemokines that bind to CXCR2 was upregulated by bFGF. Furthermore, conditioned medium derived from SMSCs cultivated with bFGF exhibited enhanced cell migration, proliferation, and chondrogenic differentiation, which were specifically inhibited by CXCR2 or CXCL6 inhibitors. Conclusion: SMSCs cultured with bFGF promoted the expression of CXCL6. This mechanism may enhance cell migration, proliferation, and chondrogenic differentiation, thereby resulting in superior meniscus regeneration and cartilage preservation.Goshima A., Etani Y., Hirao M., et al. Basic fibroblast growth factor promotes meniscus regeneration through the cultivation of synovial mesenchymal stem cells via the CXCL6–CXCR2 pathway. Osteoarthritis and Cartilage , (2023); https://doi.org/10.1016/j.joca.2023.07.010

Effects of a trauma center on early mortality after trauma in a regional city in Japan: a population-based study

Background: Although the effects of the trauma center(TC) were researched in several studies, there have been few studies on changes in the regional mortality due to the implementation of a TC.An emergency medical center (EMC) and TC were implemented at Nagasaki University Hospital (NUH) for the first time in the Nagasaki medical region of Japan in April 2010 and October 2011, respectively, and they have cooperated with each other in treating trauma patients. The purpose of this study was to investigate the effects on the early mortality at population level of a TC working in cooperation with an EMC. Methods: This is a retrospective study using standardized regional data (ambulance service record) in Nagasaki medical region from April 2007 through March 2017. We included 19,045 trauma patients directly transported from the scene. The outcome measures were prognosis for one week. To examine the association between the implementation of the EMC and TC and mortality at a region, we fit adjusted logistic regression models. Results: The number of patients of each fiscal year increased from 1492 in 2007 to 2101 in 2016.The number of all patients transported to NUH decreased until 2009 to 70, but increased after implementation of the EMC and TC. Overall mortality of all patients in the region improved from 2.3% in 2007 to 1.0% in 2016.In multivariate logistic regression model, odds ratio of death was significantly smaller at 2013 and thereafter if the data from 2007 to 2011 was taken as reference. Conclusions: Implementation of the EMC and TC was associated with early mortality in trauma patients directly transported from the scene by ambulance. Our analysis suggested that the implementation of EMC and TC contributed to the improvement of the early mortality at a regional city with 500000 populations. Level of evidence: Level III

Amino acid influx via LAT1 regulates iron demand and sensitivity to PPMX-T003 of aggressive natural killer cell leukemia

Yanagiya R., Miyatake Y., Watanabe N., et al. Amino acid influx via LAT1 regulates iron demand and sensitivity to PPMX-T003 of aggressive natural killer cell leukemia. Leukemia , (2024); 10.1038/s41375-024-02296-6.Aggressive natural killer cell leukemia (ANKL) is a rare hematological malignancy with a fulminant clinical course. Our previous study revealed that ANKL cells proliferate predominantly in the liver sinusoids and strongly depend on transferrin supplementation. In addition, we demonstrated that liver-resident ANKL cells are sensitive to PPMX-T003, an anti-human transferrin receptor 1 inhibitory antibody, whereas spleen-resident ANKL cells are resistant to transferrin receptor 1 inhibition. However, the microenvironmental factors that regulate the iron dependency of ANKL cells remain unclear. In this study, we first revealed that the anti-neoplastic effect of PPMX-T003 was characterized by DNA double-strand breaks in a DNA replication-dependent manner, similar to conventional cytotoxic agents. We also found that the influx of extracellular amino acids via LAT1 stimulated sensitivity to PPMX-T003. Taken together, we discovered that the amount of extracellular amino acid influx through LAT1 was the key environmental factor determining the iron dependency of ANKL cells via adjustment of their mTOR/Myc activity, which provides a good explanation for the different sensitivity to PPMX-T003 between liver- and spleen-resident ANKL cells, as the liver sinusoid contains abundant amino acids absorbed from the gut. (Figure presented.