Changes in prostate-specific antigen kinetics during androgen-deprivation therapy as a predictor of response to abiraterone in chemonaïve patients with metastatic castration-resistant prostate cancer

Chung-Lin Lee,Ying-Hsu Chang,Chung-Yi Liu,Ming-Li Hsieh,Liang-Kang Huang,Yuan-Cheng Chu,Hung-Cheng Kan,Po-Hung Lin,Kai-Jie Yu,Cheng-Keng Chuang,Chun-Te Wu,See-Tong Pang,I-Hung Shao 대한비뇨의학회 2022 Investigative and Clinical Urology Vol.63 No.5

Purpose: Metastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis. Abiraterone acetate (AA), enzalutamide, and chemotherapy are first-line treatments for patients with mCRPC. This study examined prognostic factors for AA response in the form of prostate-specific antigen (PSA) kinetics throughout androgen-deprivation therapy (ADT) in chemonaïve patients with mCRPC. Materials and Methods: We retrospectively included data from 34 chemonaïve patients with mCRPC who had received AA at some point between January 2017 and December 2018. We separated patients into two study arms according to the decrease in PSA percentages after use of AA for 3 months. We correlated PSA kinetics parameters with response and compared the two study groups with respect to PSA kinetics. Results: The patients’ median age was 77 years. In the total group of patients, 64% had a response to AA, whereas 35% did not. The ratio of the PSA level at nadir to the level during ADT was significantly higher in the AA-sensitive group (19.78 vs. 1.03, p=0.019). Conclusions: Patients who experienced a dramatic change in PSA level during ADT were more likely to be resistant to AA after progression to mCRPC. Chemotherapy rather than AA might be more suitable as a first-line treatment for these patients.

Biomarkers in pursuit of precision medicine for acute kidney injury: hard to get rid of customs

( Kun-mo Lin ),( Ching-chun Su ),( Jui-yi Chen ),( Szu-yu Pan ),( Min-hsiang Chuang ),( Cheng-jui Lin ),( Chih-jen Wu ),( Heng-chih Pan ),( Vin-cent Wu ) 대한신장학회 2024 Kidney Research and Clinical Practice Vol.43 No.4

Traditional acute kidney injury (AKI) classifications, which are centered around semi-anatomical lines, can no longer capture the complexity of AKI. By employing strategies to identify predictive and prognostic enrichment targets, experts could gain a deeper comprehension of AKI’s pathophysiology, allowing for the development of treatment-specific targets and enhancing individualized care. Subphenotyping, which is enriched with AKI biomarkers, holds insights into distinct risk profiles and tailored treatment strategies that redefine AKI and contribute to improved clinical management. The utilization of biomarkers such as N-acetyl-β-D-glucosaminidase, tissue inhibitor of metalloprotease-2·insulin-like growth factor-binding protein 7, kidney injury molecule-1, and liver fatty acid-binding protein garnered significant attention as a means to predict subclinical AKI. Novel biomarkers offer promise in predicting persistent AKI, with urinary motif chemokine ligand 14 displaying significant sensitivity and specificity. Furthermore, they serve as predictive markers for weaning patients from acute dialysis and offer valuable insights into distinct AKI subgroups. The proposed management of AKI, which is encapsulated in a structured flowchart, bridges the gap between research and clinical practice. It streamlines the utilization of biomarkers and subphenotyping, promising a future in which AKI is swiftly identified and managed with unprecedented precision. Incorporating kidney biomarkers into strategies for early AKI detection and the initiation of AKI care bundles has proven to be more effective than using care bundles without these novel biomarkers. This comprehensive approach represents a significant stride toward precision medicine, enabling the identification of high-risk subphenotypes in patients with AKI.

BRCA1/2 mutation status in patients with metachronous breast and ovarian malignancies: clues towards the implementation of genetic counseling

Angel Chao,Yi-Hao Lin,Lan-Yan Yang,Ren-Chin Wu,Wei-Yang Chang,Pi-Yueh Chang,Shih-Cheng Chang,Chiao-Yun Lin,Huei-Jean Huang,Cheng-Tao Lin,Hung-Hsueh Chou,Kuan-Gen Huang,Wen-Ling Kuo,Ting-Chang Chang,Ch 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.3

Objective: The characteristics of patients with metachronous breast and ovarian malignancies and the pathogenic role of BRCA1/2 mutations remain poorly understood. We investigated these issues through a review of hospital records and nationwide Taiwanese registry data, followed by BRCA1/2 mutation analysis in hospital-based cases. Methods: We retrospectively retrieved consecutive clinical records of Taiwanese patients who presented with these malignancies to our hospital between 2001 and 2017. We also collected information from the Data Science Center of the Taiwan Cancer Registry (TCR) between 2007 and 2015. Next-generation sequencing and multiplex ligation-dependent probe amplification were used to identify BRCA1/2 mutations and large genomic rearrangements, respectively. When BRCA1/2 mutations were identified in index cases, pedigrees were reconstructed and genetic testing was offered to family members. Results: A total of 12,769 patients with breast cancer and 1,537 with ovarian cancer were retrieved from our hospital records. Of them, 28 had metachronous breast and ovarian malignancies. We also identified 113 cases from the TCR dataset. Eighteen hospital-based cases underwent BRCA1/2 sequencing and germline pathogenic mutations were detected in 7 patients (38.9%, 5 in BRCA1 and 2 in BRCA2). All BRCA1/2 mutation carriers had ovarian high-grade serous carcinomas. Of the 12 patients who were alive at the time of analysis, 5 were BRCA1/2 mutation carriers. All of them had family members with BRCA1/2-associated malignancies. Conclusions: Our results provide pilot evidence that BRCA1/2 mutations are common in Taiwanese patients with metachronous breast and ovarian malignancies, supporting the clinical utility of genetic counseling.

Prolyl endopeptidase remodels macrophage function as a novel transcriptional coregulator and inhibits fibrosis

Lin Shuang-Zhe,Wu Wei-Jie,Cheng Yu-Qing,Zhang Jian-Bin,Jiang Dai-Xi,Ren Tian-Yi,Ding Wen-Jin,Liu Mingxi,Chen Yuan-Wen,Fan Jian-Gao 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Macrophages are immune cells crucial for host defense and homeostasis maintenance, and their dysregulation is involved in multiple pathological conditions, such as liver fibrosis. The transcriptional regulation in macrophage is indispensable for fine-tuning of macrophage functions, but the details have not been fully elucidated. Prolyl endopeptidase (PREP) is a dipeptidyl peptidase with both proteolytic and non-proteolytic functions. In this study, we found that Prep knockout significantly contributed to transcriptomic alterations in quiescent and M1/M2-polarized bone marrow-derived macrophages (BMDMs), as well as aggravated fibrosis in an experimental nonalcoholic steatohepatitis (NASH) model. Mechanistically, PREP predominantly localized to the macrophage nuclei and functioned as a transcriptional coregulator. Using CUT&Tag and co-immunoprecipitation, we found that PREP was mainly distributed in active cis-regulatory genomic regions and physically interacted with the transcription factor PU.1. Among PREP-regulated downstream genes, genes encoding profibrotic cathepsin B and D were overexpressed in BMDMs and fibrotic liver tissue. Our results indicate that PREP in macrophages functions as a transcriptional coregulator that finely tunes macrophage functions, and plays a protective role against liver fibrosis pathogenesis.

Robust design on the arrangement of a sail and control planes for improvement of underwater Vehicle's maneuverability

Wu, Sheng-Ju,Lin, Chun-Cheng,Liu, Tsung-Lung,Su, I-Hsuan The Society of Naval Architects of Korea 2020 International Journal of Naval Architecture and Oc Vol.12 No.-

The purpose of this study is to discuss how to improve the maneuverability of lifting and diving for underwater vehicle's vertical motion. Therefore, to solve these problems, applied the 3-D numerical simulation, Taguchi's Design of Experiment (DOE), and intelligent parameter design methods, etc. We planned four steps as follows: firstly, we applied the 2-D flow simulation with NACA series, and then through the Taguchi's dynamic method to analyze the sensitivity (β). Secondly, take the data of pitching torque and total resistance from the Taguchi orthogonal array (L9), the ignal-to-noise ratio (SNR), and analysis each factorial contribution by ANOVA. Thirdly, used Radial Basis Function Network (RBFN) method to train the non-linear meta-modeling and found out the best factorial combination by Particle Swarm Optimization (PSO) and Weighted Percentage Reduction of Quality Loss (WPRQL). Finally, the application of the above methods gives the global optimum for multi-quality characteristics and the robust design configuration, including L/D is 9.4:1, the foreplane on the hull (Bow-2), and position of the sail is 0.25 Ls from the bow. The result shows that the total quality is improved by 86.03% in comparison with the original design.

Ginsenoside Rg1 supplementation clears senescence-associated β-galactosidase in exercising human skeletal muscle

Wu, Jinfu,Saovieng, Suchada,Cheng, I-Shiung,Liu, Tiemin,Hong, Shangyu,Lin, Chang-Yu,Su, I-Chen,Huang, Chih-Yang,Kuo, Chia-Hua The Korean Society of Ginseng 2019 Journal of Ginseng Research Vol.43 No.4

Background: Ginsenoside Rg1 has been shown to clear senescence-associated beta-galactosidase (SA-${\beta}$-gal) in cultured cells. It remains unknown whether Rg1 can influence SA-${\beta}$-gal in exercising human skeletal muscle. Methods: To examine SA-${\beta}$-gal change, 12 young men (age $21{\pm}0.2years$) were enrolled in a randomized double-blind placebo controlled crossover study, under two occasions: placebo (PLA) and Rg1 (5 mg) supplementations 1 h prior to a high-intensity cycling (70% $VO_{2max}$). Muscle samples were collected by multiple biopsies before and after cycling exercise (0 h and 3 h). To avoid potential effect of muscle biopsy on performance assessment, cycling time to exhaustion test (80% $VO_{2max}$) was conducted on another 12 participants (age $23{\pm}0.5years$) with the same experimental design. Results: No changes of SA-${\beta}$-gal were observed after cycling in the PLA trial. On the contrary, nine of the 12 participants showed complete elimination of SA-${\beta}$-gal in exercised muscle after cycling in the Rg1 trial (p < 0.05). Increases in apoptotic DNA fragmentation (PLA: +87% vs. Rg1: +133%, p < 0.05) and $CD68^+$ (PLA:+78% vs. Rg1:+121%, p = 0.17) occurred immediately after cycling in both trials. During the 3-h recovery, reverses in apoptotic nuclei content (PLA:+5% vs. Rg1 -32%, p < 0.01) and increases in inducible nitrate oxide synthase and interleukin 6 mRNA levels of exercised muscle were observed only in the Rg1 trial (p < 0.01). Conclusion: Rg1 supplementation effectively eliminates senescent cells in exercising human skeletal muscle and improves high-intensity endurance performance.

Analysis of the following effect of the natural enemies with Frankliniella intonsa in tea garden

Cheng Honghao,Chen Shiyan,Wu Xiaomeng,Xu Yue,Zhang Lin,Sun Jiazhao,Zhou Xiazhi,Zou Yunding,Bi Shoudong 한국곤충학회 2022 Entomological Research Vol.52 No.8

In order to reasonably protect and utilize natural enemies for comprehensive control of Frankliniella intonsa, a systematic investigation was conducted on F. i n t o n s a and natural enemies in tea gardens in Hefei, Anhui Province, and the spatial following effect of natural enemies on F. intonsa was studied. The semi-variogram of natural enemies and thrips was obtained by the geostatistics method, and the correlation degree between them was analyzed by the grey correlation degree analysis method. The higher the correlation degree between natural enemies and F. intonsa, the closer the relationship between natural enemies and F. intonsa was. In this study, we analyzed the relationship between 11 natural enemies of F. i n t o n s a in tea gardens from October 28, 2020 to November 20, 2020 and from August 22, 2021 to November 19, 2021. The top five natural enemies with the largest closeness index to F. intonsa in Huangshan Dayezhong tea garden are Oxyopes sertatus, Theridion octomaculatum, Plexippus setipes, Xysticus ephippiafus and Erigonidium graminicolum. The top five natural enemies with the largest closeness index to F. intonsa in Pingyang Tezao tea garden are Erigonidium graminicolum, Plexippus setipes, Xysticus ephippiafus, Oxyopes sertatus and Clubiona japonicola.Among the top five natural enemies in the two tea gardens, those in common are Oxyopes sertatus, Erigonidium graminicolum, Xysticus ephippiafus and Plexippus setipes. According to the summation of the closeness index and the sum of the serial numbers, the top five natural enemies closely related to the spatial following of F. intonsa in the tea gardens were Oxyopes sertatus, Plexippus setipes, Erigonidium graminicolum, Xysticus ephippiafus and Theridion octomaculatum. One of the factors closely related to the space of F. i n t o n s a in the same tea garden was the ratio of F. i n t o n s a to a certain natural enemy. The smaller the ratio was, the closer the following relationship was. The results of this study provide scientific basis for biological control and natural enemy protection of F. intonsa.

A novel regression prediction model for structural engineering applications

Lin, Jeng-Wen,Chen, Cheng-Wu,Hsu, Ting-Chang Techno-Press 2013 Structural Engineering and Mechanics, An Int'l Jou Vol.45 No.5

Recently, artificial intelligence tools are most used for structural engineering and mechanics. In order to predict reserve prices and prices of awards, this study proposed a novel regression prediction model by the intelligent Kalman filtering method. An artificial intelligent multiple regression model was established using categorized data and then a prediction model using intelligent Kalman filtering. The rather precise construction bid price model was selected for the purpose of increasing the probability to win bids in the simulation example.

Tissue Quality Comparison Between Heparinized Wet Suction and Dry Suction in Endoscopic Ultrasound-Fine Needle Biopsy of Solid Pancreatic Masses: A Randomized Crossover Study

Lin Meng-Ying,Wu Cheng-Lin,Su Yung-Yeh,Huang Chien-Jui,Chang Wei-Lun,Sheu Bor-Shyang 거트앤리버 소화기연관학회협의회 2023 Gut and Liver Vol.17 No.2

Background/Aims: A high-quality sample allows for next-generation sequencing and the administration of more tailored precision medicine treatments. We aimed to evaluate whether heparinized wet suction can obtain higher quality samples than the standard dry-suction method during endoscopic ultrasound (EUS)-guided biopsy of pancreatic masses. Methods: A prospective randomized crossover study was conducted. Patients with a solid pancreatic mass were randomly allocated to receive either heparinized wet suction first or dry suction first. For each method, two needle passes were made, followed by a switch to the other method for a total of four needle punctures. The primary outcome was the aggregated white tissue length. Histological blood contamination, diagnostic performance and adverse events were analyzed as secondary outcomes. In addition, the correlation between white tissue length and the extracted DNA amount was analyzed. Results: A total of 50 patients were enrolled, and 200 specimens were acquired (100 with heparinized wet suction and 100 with dry suction), with one minor bleeding event. The heparinized wet suction approach yielded specimens with longer aggregated white tissue length (11.07 mm vs 7.96 mm, p=0.001) and less blood contamination (p=0.008). A trend towards decreasing tissue quality was observed for the 2nd pass of the dry-suction method, leading to decreased diagnostic sensitivity and accuracy, although the accumulated diagnostic performance was comparable between the two suction methods. The amount of extracted DNA correlated positively to the white tissue length (p=0.001, Spearman̕s ρ=0.568). Conclusions: Heparinized wet suction for EUS tissue acquisition of solid pancreatic masses can yield longer, bloodless, DNA-rich tissue without increasing the incidence of adverse events (ClinicalTrials.gov. identifier NCT04707560).

Robust design on the arrangement of a sail and control planes for improvement of underwater Vehicle's maneuverability

Wu, Sheng-Ju,Lin, Chun-Cheng,Liu, Tsung-Lung,Su, I-Hsuan The Society of Naval Architects of Korea 2020 International Journal of Naval Architecture and Oc Vol.12 No.1

The purpose of this study is to discuss how to improve the maneuverability of lifting and diving for underwater vehicle's vertical motion. Therefore, to solve these problems, applied the 3-D numerical simulation, Taguchi's Design of Experiment (DOE), and intelligent parameter design methods, etc. We planned four steps as follows: firstly, we applied the 2-D flow simulation with NACA series, and then through the Taguchi's dynamic method to analyze the sensitivity (β). Secondly, take the data of pitching torque and total resistance from the Taguchi orthogonal array (L9), the ignal-to-noise ratio (SNR), and analysis each factorial contribution by ANOVA. Thirdly, used Radial Basis Function Network (RBFN) method to train the non-linear meta-modeling and found out the best factorial combination by Particle Swarm Optimization (PSO) and Weighted Percentage Reduction of Quality Loss (WPRQL). Finally, the application of the above methods gives the global optimum for multi-quality characteristics and the robust design configuration, including L/D is 9.4:1, the foreplane on the hull (Bow-2), and position of the sail is 0.25 Ls from the bow. The result shows that the total quality is improved by 86.03% in comparison with the original design.