Exploring novel immunotherapy biomarker candidates induced by cancer deformation

by Se Min Kim, Namu Park, Hye Bin Park, JuKyung Lee, Changho Chun, Kyung Hoon Kim, Jong Seob Choi, Hyung Jin Kim, Sekyu Choi, Jung Hyun Lee

Triple-negative breast cancer (TNBC) demands urgent attention for the development of effective treatment strategies due to its aggressiveness and limited therapeutic options [1]. This research is primarily focused on identifying new biomarkers vital for immunotherapy, with the aim of developing tailored treatments specifically for TNBC, such as those targeting the PD-1/PD-L1 pathway. To achieve this, the study places a strong emphasis on investigating Ig genes, a characteristic of immune checkpoint inhibitors, particularly genes expressing Ig-like domains with altered expression levels induced by "cancer deformation," a condition associated with cancer malignancy. Human cells can express approximately 800 Ig family genes, yet only a few Ig genes, including PD-1 and PD-L1, have been developed into immunotherapy drugs thus far. Therefore, we investigated the Ig genes that were either upregulated or downregulated by the artificial metastatic environment in TNBC cell line. As a result, we confirmed the upregulation of approximately 13 Ig genes and validated them using qPCR. In summary, our study proposes an approach for identifying new biomarkers applicable to future immunotherapies aimed at addressing challenging cases of TNBC where conventional treatments fall short.

Predictive value of CD86 for the occurrence of sepsis (Sepsis-3) in patients with infection

by Dan lv, Keji Zhang, Changqing Zhu, Xinhui Xu, Hao Gong, Li Liu

This prospective observational study explored the predictive value of CD86 in the early diagnosis of sepsis in the emergency department. The primary endpoint was the factors associated with a diagnosis of sepsis. The secondary endpoint was the factors associated with mortality among patients with sepsis. It enrolled inpatients with infection or high clinical suspicion of infection in the emergency department of a tertiary Hospital between September 2019 and June 2021. The patients were divided into the sepsis and non-sepsis groups according to the Sepsis-3 standard. The non-sepsis group included 56 patients, and the sepsis group included 65 patients (19 of whom ultimately died). The multivariable analysis showed that CD86% (odds ratio [OR] = 1.22, 95% confidence interval [CI]: 1.04–1.44, P = 0.015), platelet count (OR = 0.99, 95%CI: 0.986–0.997, P = 0.001), interleukin-10 (OR = 1.01, 95%CI: 1.004–1.025, P = 0.009), and procalcitonin (OR = 1.17, 95%CI: 1.01–1.37, P = 0.043) were independent risk factors for sepsis, while human leukocyte antigen (HLA%) (OR = 0.96, 05%CI: 0.935–0.995, P = 0.022), respiratory rate (OR = 1.16, 95%CI: 1.03–1.30, P = 0.014), and platelet count (OR = 1.01, 95%CI: 1.002–1.016, P = 0.016) were independent risk factors for death in patients with sepsis. The model for sepsis (CD86%, platelets, interleukin-10, and procalcitonin) and the model for death (HLA%, respiratory rate, and platelets) had an area under the curve (AUC) of 0.870 and 0.843, respectively. CD86% in the first 24 h after admission for acute infection was independently associated with the occurrence of sepsis in the emergency department.

Transcriptome and machine learning analysis of the impact of COVID-19 on mitochondria and multiorgan damage

by Yu-Yu Chang, An-Chi Wei

The effects of coronavirus disease 2019 (COVID-19) primarily concern the respiratory tract and lungs; however, studies have shown that all organs are susceptible to infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 may involve multiorgan damage from direct viral invasion through angiotensin-converting enzyme 2 (ACE2), through inflammatory cytokine storms, or through other secondary pathways. This study involved the analysis of publicly accessible transcriptome data from the Gene Expression Omnibus (GEO) database for identifying significant differentially expressed genes related to COVID-19 and an investigation relating to the pathways associated with mitochondrial, cardiac, hepatic, and renal toxicity in COVID-19. Significant differentially expressed genes were identified and ranked by statistical approaches, and the genes derived by biological meaning were ranked by feature importance; both were utilized as machine learning features for verification. Sample set selection for machine learning was based on the performance, sample size, imbalanced data state, and overfitting assessment. Machine learning served as a verification tool by facilitating the testing of biological hypotheses by incorporating gene list adjustment. A subsequent in-depth study for gene and pathway network analysis was conducted to explore whether COVID-19 is associated with cardiac, hepatic, and renal impairments via mitochondrial infection. The analysis showed that potential cardiac, hepatic, and renal impairments in COVID-19 are associated with ACE2, inflammatory cytokine storms, and mitochondrial pathways, suggesting potential medical interventions for COVID-19-induced multiorgan damage.

Physiological changes of microalga <i>Dunaliella parva</i> under the treatment of PEG, CaCl₂

by Qiman Zou, Limei Huang, Jinghui Gu, Bingbing Pang, Changhua Shang

Carotenoids are antioxidants, which reduce various chronic diseases of human, and have many industrial applications. The halophilic Dunaliella parva (D. parva) is rich in carotenoids. The compounds CaCl₂ and PEG are the popular metabolic enhancers. To further enhance carotenogenesis, D. parva was treated with two compounds polyethylene glycol (PEG) and CaCl₂. Application of CaCl₂ and PEG enhanced the carotenoids contents and the antioxidant activities of carotenoids compared to control group (no treatment of CaCl₂ or PEG). The highest carotenoids contents were obtained by treating D. parva with 40 ppm CaCl₂ (3.11 mg/g dry weight, DW) and 80 ppm PEG (2.78 mg/g DW) compared with control group (1.96 mg/g DW). When D. parva was treated with 40 ppm CaCl₂ and 80 ppm PEG, protein contents reached the highest values (90.28 mg/g DW and 89.57 mg/g DW) compared to that of control group (73.42 mg/g DW). The antioxidant activities of carotenoids samples were determined. Generally, the antioxidant activities of carotenoids from D. parva treated with PEG and CaCl₂ were superior to that of control group. The antioxidant activities of carotenoids mainly contained reducing power, hydroxyl radical scavenging activity and superoxide radical scavenging activity. The reducing powers of carotenoids extracts from 20 ppm CaCl₂ group (2.07%/mg carotenoids) and 120 ppm PEG group (1.59%/mg carotenoids) were significantly higher than that of control group (2 group (70.33%/mg carotenoids) and 80 ppm PEG group (65.94%/mg carotenoids) were significantly higher than that of control group (D. parva.

Can digital transformation reduce corporate stock price crashes?

by Xing Zhao, Xiangqian Li, Changman Ren

Purpose

The purpose of this paper is to study the impact of enterprises’ digital transformation on the risk of stock price crashes, but also to study the mediating role of enterprises’ financialization and accounting conservatism in the enterprises’ digital transformation on stock price crash risk.

Design/methodology/approach

Based on the data of 2,599 listed companies in China from 2010 to 2019, this paper constructs indicators of enterprise digital transformation through word frequency analysis method, and uses fixed-effects model and mediated-effects model to explore the impact and mechanism of enterprise digital transformation on the stock price crash risk.

Findings

This study shows that firms’ digital transformation reduces the risk of stock price crashes and that financialization of firms and accounting conservatism play a significant mediating effect between enterprises’ digital transformation and the risk of stock price crashes.

Originality/value

This study enriches the study of stock price crash risk by including digital transformation in the field of stock price crash research, and it examines the mediating roles of financialization of enterprises and accounting conservatism, which provides a new explanatory mechanism to the study of the correlation between digital transformation of enterprises and the risk of stock price crash.

A non-socially-sensitive predictive model of prostate cancer for Asian males with benign prostatic hyperplasia: A multi-site cross-sectional case-control study

by Heng-Jui Chang, Sin-Hua Moi, Yu-Jiun Chan, Tzuo-Yun Lan

Background

Benign prostatic hyperplasia (BPH) is common in aging Asian males and is associated with an excess risk of developing prostate cancer (PCa). However, discussions about socially-sensitive experiences such as sexual activity, which can significantly predict PCa risk, may be considered stigmatized in Asian culture. This study aimed to develop a predictive model for PCa risk in Asian males with BPH using non-socially-sensitive information.

Methods

A cross-sectional case-control study, with PCa patients as the cases and remaining as the controls, was conducted on a cohort of Taiwanese males with BPH from four medical institutions. Patients who met the inclusion criteria were enrolled, excluding those aged over 86 years or who had received human papillomavirus (HPV) vaccination. Non-socially-sensitive variables such as obesity, occupational exposure, HPV infection, and PCa family history score (FH score) were included in a fully adjusted logistic regression model, and depicted using a nomogram.

Results

Among 236 BPH patients, 45.3% had PCa. Obesity, occupational exposure, HPV infection, and family history of PCa were significantly associated with PCa risk. The FH score (OR = 1.89, 95% CI = 1.03–3.47, P = 0.041) had the highest impact, followed by HPV infection (OR = 1.47, 95% CI = 1.03–2.11, P = 0.034), occupational exposure (OR = 1.32, 95% CI = 1.15–1.51, P P = 0.005). The nomogram accurately depicted the predictive risk, and the model demonstrated robust performance compared to individual factors. In addition, the subgroup analysis results showed elderly age group could obtain more favorable predictive performance in our proposed model (AUC = 0.712).

Conclusion

This non-socially-sensitive predictive model for PCa risk in Taiwanese males with BPH integrates multiple factors that could provide acceptable PCa risk-predictive performance, especially for elderly BPH patients over 70 years, aiding clinical decision-making and early cancer detection.

Electroacupuncture attenuates inflammatory pain via peripheral cannabinoid receptor type 1 signaling pathway in mice

by Tsung-Jung Ho, Ching-Fang Lin, Jhong-Kuei Chen, Yen-Lun Kung, Li-Kung Wu, Chen-Ying Chang Chien, Chun-Ping Huang

Pain is strongly associated with neuro-immune activation. Thus, the emerging role of the endocannabinoid system in neuro-inflammation is important. Acupuncture has been used for over 2500 years and is widely accepted for the management of pain. Our study aimed to investigate the effects of electroacupuncture on the regulation of cannabinoid receptor type 1 within the peripheral nervous system. Inflammatory pain was induced by injecting Complete Freund’s adjuvant to induce mechanical and thermal hyperalgesia. Electroacupuncture significantly attenuated the mechanical and thermal sensitivities, and AM251, a cannabinoid receptor type 1 antagonist, eliminated these effects. Dual immunofluorescence staining demonstrated that electroacupuncture elevated expression of cannabinoid receptor type 1, co-localized with Nav 1.8. Furthermore, electroacupuncture significantly reduced levels of Nav 1.8 and COX-2 by western blot analysis, but not vice versa as AM251 treatment. Our data indicate that electroacupuncture mediates antinociceptive effects through peripheral endocannabinoid system signaling pathway and provide evidence that electroacupuncture is beneficial for pain treatment.

Traumatic brain injury and risk of heart failure and coronary heart disease: A nationwide population-based cohort study

by Ching-Hui Huang, Chao-Tung Yang, Chia-Chu Chang

Background

This study examined the long-term risks of heart failure (HF) and coronary heart disease (CHD) following traumatic brain injury (TBI), focusing on gender differences.

Methods

Data from Taiwan’s National Health Insurance Research Database included 29,570 TBI patients and 118,280 matched controls based on propensity scores.

Results

The TBI cohort had higher incidences of CHD and HF (9.76 vs. 9.07 per 1000 person-years; 4.40 vs. 3.88 per 1000 person-years). Adjusted analyses showed a significantly higher risk of HF in the TBI group (adjusted hazard ratio = 1.08, 95% CI = 1.01–1.17, P = 0.031). The increased CHD risk in the TBI cohort became insignificant after adjustment. Subgroup analysis by gender revealed higher HF risk in men (aHR = 1.14, 95% CI = 1.03–1.25, P = 0.010) and higher CHD risk in women under 50 (aHR = 1.32, 95% CI = 1.15–1.52, P Conclusion

Our results suggest that TBI increases the risk of HF and CHD in this nationwide cohort of Taiwanese citizens. Gender influences the risks differently, with men at higher HF risk and younger women at higher CHD risk. Beta-blockers have a neutral effect on HF and CHD risk.

Applying the reference values of real-ear-to-coupler-difference for deaf and hard-of-hearing children in Taiwan: Cautions and considerations

by Chun-Yi Lin, Yi-ping Chang, Ying-Chuan Julie Ma

Measurement of real-ear-to-coupler differentials (RECDs) is a critical part of the hearing aid (HA) verification process. This study examines the validity of reference RECD values preset by the HA analyzer, Audioscan RM500, for deaf-and-hard-of-hearing (DHH) children in Taiwan. RECD measurements were performed on 658 ears of DHH children. A linear mixed model was used to analyze the reference and measured RECD values. The findings revealed slight disparities between normative RECD values from North America and those observed in Taiwanese DHH children. While generally small (less than 5 dB), these differences imply potential challenges in achieving optimal HA fitting in specific scenarios. Therefore, we recommend individualized RECD/REM measurements for cases of poor auditory performance, certain frequency ranges, or notable variations in ear canal volume. From a clinical perspective, while broadly applicable, the use of North American RECD normative data in Taiwan requires cautious consideration of potential minor variations. This study contributes to current knowledge by affirming the use of a Western RECD database for Taiwanese DHH children. However, we underscore the ongoing importance of individualized HA fitting strategies, particularly for cases with stagnant intervention progress. While built-in RECD reference values can offer preliminary fitting guidance, especially in busy clinical settings, our study sheds light on the circumstances where caution is essential. Audiologists can efficiently allocate their time and effort by focusing on personalized RECD measurements for cases exhibiting suboptimal intervention outcomes, thereby effectively optimizing HA gain settings.

Understanding health literacy of deaf persons with hypertension in South Korea: A cross-sectional study

by Gi Won Choi, Sun Ju Chang, Hee Jung Kim, Ha Na Jeong

Background

Health literacy is strongly associated with health inequality among persons with deafness, and hypertension (HTN) is the most prevalent chronic disease among persons with deafness in South Korea. Despite its importance, research regarding the health literacy levels of persons with deafness with HTN in South Korea is lacking. This study aimed to comprehensively assess the health literacy levels of persons with deafness with HTN in South Korea, including linguistic, functional, and internet health literacy.

Methods

In this descriptive cross-sectional study, 95 persons with deafness with HTN were recruited through facilities associated with the deaf community. From August 2022 to February 2023, data were collected through face-to-face surveys attended by a sign language interpreter and online surveys. The data were analyzed using descriptive statistics and Spearman’s correlation.

Results

Approximately 62.1% of the participants exhibited a linguistic health literacy level corresponding to less than that of middle school students, and the total percentage correct of functional health literacy was 17.9%. Each domain of internet health literacy was low. Significant correlations were found between some aspects of health literacy.

Conclusions

The study’s findings highlight the low health literacy levels across various facets among persons with deafness with HTN in South Korea. Based on these findings, several strategies are suggested for developing HTN self-management interventions for persons with deafness. This study contributes to the foundational understanding of health literacy among persons with deafness with HTN in South Korea and provides valuable insights and guidance for developing HTN self-management interventions.

Impact of PARP inhibitor maintenance therapy in newly diagnosed advanced epithelial ovarian cancer: A meta-analysis

by Banghyun Lee, Suk-Joon Chang, Byung Su Kwon, Joo-Hyuk Son, Myong Cheol Lim, Yun Hwan Kim, Shin-Wha Lee, Chel Hun Choi, Kyung Jin Eoh, Jung-Yun Lee, Dong Hoon Suh, Yong Beom Kim

Objectives

This meta-analysis was undertaken to systematically evaluate the effects of poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy on the survival of newly diagnosed advanced epithelial ovarian cancer (EOC) patients.

Methods/Materials

A systematic literature search revealed 3,227 studies. A subsequent selection process identified seven suitable randomized studies that assessed the survival outcomes in newly diagnosed advanced EOC patients administered PARPi (n = 1921; the PARPi group) or placebo (n = 1150; the placebo group). The survival outcomes were compared with respect to the PARPi treatment regardless of bevacizumab maintenance therapy. All adverse events ≥ grade 3 were analyzed. Review Manager Version 5.4.1 software was used for the meta-analysis.

Results

The two-year progression-free survival (PFS) was significantly better in the PARPi group than the placebo (Hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.41 to 0.68). Furthermore, patients in the PARPi group with the BRCA1/2 mutation (BRCAm), BRCA wild type, homologous-recombination deficiency (HRD), or HRD without BRCAm, but not with homologous-recombination proficiency had a significantly better two-year PFS than the patients in the placebo group. The five-year overall survival (OS) was comparable in the two groups, but patients in the PARPi group with BRCAm had a significantly better five-year OS than those in the placebo group (HR, 0.57; 95% CI, 0.44 to 0.74). In addition, the adverse event rate (≥ grade 3) was significantly higher in the PARPi group than in the placebo group (HR, 2.94; 95% CI, 1.13 to 7.63).

Conclusions

In patients with newly diagnosed advanced EOC, PARPi maintenance therapy was significantly more effective in terms of survival than no PARPi treatment. However, the risk of serious adverse events was higher for patients who received PARPi maintenance therapy.

Randomized clinical trial to compare the efficacy of self-expanding bare metal nitinol stent and balloon angioplasty alone for below-the-knee lesions following successful balloon angioplasty: 1-year clinical outcomes

by Jihun Ahn, HyeYon Yu, Seung-Woon Rha, Byoung Geol Choi, Dong Oh Kang, Cheol Ung Choi, Sangho Park, Jon Seo, Kichang Kim, Minung Kim, Yong Hoon Kim, Yong Seong Seo

This prospective, multicenter, randomized study aimed to compare the 1-year clinical outcomes after primary stenting with self-expanding bare metal nitinol stent (SENS) and plain old balloon angioplasty (POBA) in patients with critical limb ischemia (CLI) and below-the-knee (BTK) lesions. Overall, 119 patients with CLI and BTK lesions were randomized to POBA alone (POBA group, 61 patients) or primary stenting with SENS (stenting group, 58 patients) after achieving acceptable POBA results in target BTK lesions. Clinical outcomes including amputation and revascularization rates were prospectively compared for 1 year. After 1 year, similar incidence rates of individual clinical endpoints, including cardiac death (6.5% vs. 5.1%, p > 0.999), myocardial infarction (1.6% vs. 0.0%, p > 0.999), repeat revascularization (19.6% vs. 18.9%, p = 0.922), target lesion revascularization (13.1% vs. 17.2%, p = 0.530), and amputation (4.9% vs. 0.0%, p = 0.244), were observed. POBA appeared to have acceptable treatment outcomes compared with primary stenting with SENS after 1 year in CLI patients with BTK lesions undergoing percutaneous transluminal angioplasty (PTA).

Metabolic profiling of <i>Mytilus coruscus</i> mantle in response of shell repairing under acute acidification

by Xiaojun Fan, Ying Wang, Changsheng Tang, Xiaolin Zhang, Jianyu He, Isabella Buttino, Xiaojun Yan, Zhi Liao

Mytilus coruscus is an economically important marine bivalve mollusk found in the Yangtze River estuary, which experiences dramatic pH fluctuations due to seasonal freshwater input and suffer from shell fracture or injury in the natural environment. In this study, we used intact-shell and damaged-shell M. coruscus and performed metabolomic analysis, free amino acids analysis, calcium-positive staining, and intracellular calcium level tests in the mantle to investigate whether the mantle-specific metabolites can be induced by acute sea-water acidification and understand how the mantle responds to acute acidification during the shell repair process. We observed that both shell damage and acute acidification induced alterations in phospholipids, amino acids, nucleotides, organic acids, benzenoids, and their analogs and derivatives. Glycylproline, spicamycin, and 2-aminoheptanoic acid (2-AHA) are explicitly induced by shell damage. Betaine, aspartate, and oxidized glutathione are specifically induced by acute acidification. Our results show different metabolic patterns in the mussel mantle in response to different stressors, which can help elucidate the shell repair process under ocean acidification. furthermore, metabolic processes related to energy supply, cell function, signal transduction, and amino acid synthesis are disturbed by shell damage and/or acute acidification, indicating that both shell damage and acute acidification increased energy consumption, and disturb phospholipid synthesis, osmotic regulation, and redox balance. Free amino acid analysis and enzymatic activity assays partially confirmed our findings, highlighting the adaptation of M. coruscus to dramatic pH fluctuations in the Yangtze River estuary.