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Application of clinical department–specific AI-assisted coding using Taiwan diagnosis-related groups: Retrospective validation study
[[abstract]]Background: The accuracy of the ICD-10-CM (International Classification of Diseases, Tenth Revision, Clinical Modification) procedure coding system (PCS) is crucial for generating correct Taiwan diagnosis-related groups (DRGs), as coding errors can lead to financial losses for hospitals. Objective: The study aimed to determine the consistency between an artificial intelligence (AI)-assisted coding module and manual coding, as well as to identify clinical specialties suitable for implementing the developed AI-assisted coding module. Methods: This study examined the AI-assisted coding module from the perspective of health care professionals. The research period started in February 2023. The study excluded cases outside of Taiwan DRGs, those with incomplete medical records, and cases with Taiwan DRG disposals ICD-10 (International Statistical Classification of Diseases, Tenth Revision) PCS. Data collection was conducted through retrospective medical record review. The AI-assisted module was constructed using a hierarchical attention network. The verification of the Taiwan DRGs results from the AI-assisted coding model focused on the major diagnostic categories (MDCs). Statistical computations were conducted using SPSS version 19. Research variables consisted of categorical variables represented by MDC, and continuous variables were represented by the relative weight of Taiwan DRGs. Results: A total of 2632 discharge records meeting the research criteria were collected from February to April 2023. In terms of inferential statistics, κ statistics were used for MDC analysis. The infectious and parasitic diseases MDC, as well as the respiratory diseases MDC had κ values exceeding 0.8. Clinical inpatient specialties were statistically analyzed using the Wilcoxon signed rank test. There was not a difference in coding results between the 23 clinical departments, such as the Division of Cardiology, the Division of Nephrology, and the Department of Urology. Conclusions: For human coders, with the assistance of the ICD-10-CM AI-assisted coding system, work time is reduced. Additionally, strengthening knowledge in clinical documentation enables human coders to maximize their role. This positions them to become clinical documentation experts, preparing them for further career development. Future research will apply the same method to validate the ICD-10 AI-assisted coding module
Targeting CXCL7 reduced breast cancer progression and recurrence via reshaping dendritic cells in TME
[[abstract]]Immunokines shape the tumor microenvironment dictating the course of tumor dormancy and progression. Our recent study has identified CXCL7 as a key promoter of breast cancer advancement via FAK-MMP13 axis. In this study, targeting CXCL7 with neutralizing antibodies led to a significant decrease in xenograft growth and recurrence. Suppression of CXCL7 not only reduced tumor growth but also inhibited metastatic spread and the infiltration of CD11b-CD11c+ plasmacytoid dendritic cells (pDCs), a factor linked to early relapse and poor survival in ovarian cancer, within murine xenograft tumors. Administering CXCL7monoclonal antibodies post-surgery in mice effectively prevented tumor recurrence in an immunocompetent model. Serum CXCL7levels emerged as a reflective marker of tumor progression. This study highlights the pivotal role of CXCL7 in reshaping the immune landscape within the tumor microenvironment, thus influencing tumor progression. Combining CXCL7 immunotherapy with conventional treatments holds promise for combating breast cancer
Ulvan-based microneedles releasing curcumin to enhance X-ray radiotherapy on melanomabearing animal models
[[abstract]]Despite surgical removal, recurrence rates of melanoma remain high, implying the necessity of radiotherapy. We aim to develop soluble ulvan microneedles (UMN) containing curcumin-loaded micelles (Cur-m) to improve transdermal delivery and act asradiosensitizers during X-ray irradiation. Cur-m was prepared by Cur and Pluronic 123 at a 1:20 weight ratio, with a particle size of19.3 nm and encapsulation efficiency of 98.3%. The colony formation assay against B16F10 cell lines further presented either radioprotection or radio sensitization properties depending on the concentration of curcumin. Integration of Cur-m into ulvanmicroneedles resulted in Cur-UMN, which presented a 99.56% successful insertion rate on porcine skin. Upon insertion, Cur-UMN rapidly dissolved by 82.3% within 150 seconds, with Franz cell testing revealing 76.4% of curcumin permeation into the dermis within 4 hours. Moreover, Cur-UMN transfer and release of curcumin in animals was validated by thein vivo imaging system followed by X-ray radiotherapy. In conclusion, Cur-UMN effectively delivers curcumin as a radiosensitizer, eliminating radiation dosage while enhancing the therapeutic efficacy of melanoma.[Disclosure of COI by Responsible researcher] Lead presenter is the Responsible researcher
Tumor cell-derived ISG15 promotes fibroblast recruitment in oral squamous cell carcinoma via CD11a-dependent glycolytic reprogramming
[[abstract]]Cancer-associated fibroblast (CAF) recruitment and activation within the tumor microenvironment (TME) are increasingly acknowledged as drivers of oral squamous cell carcinoma (OSCC) tumor growth and metastasis. Therefore, the mechanisms underlying tumor cell and fibroblast crosstalk warrant further investigation. We discovered that ectopic interferon-stimulated gene 15 (ISG15) expression, which is a promising and novel oncoprotein biomarker elevated in a variety of cancers, enhanced OSCC growth and elevated collagen and alpha-smooth muscle actin (alpha-SMA) expression in ISG15-expressing tumors. Analysis of immunohistochemistry revealed high ISG15 expression in human oral tissues correlated with high expression of alpha-SMA and fibroblast activation protein (FAP). Fibroblast migration and recruitment by ISG15-expressing OSCC cells were confirmed by in vitro and in vivo experiments. Exogenous ISG15 induced fibroblast migration, morphological changes, and vimentin expression. Enrichment of glycolysis pathway genes, as well as increased glycolysis-related gene expression, glucose uptake, and lactate production were observed in ISG15-treated fibroblasts. Lactate release and fibroblast migration were blocked by a competitive inhibitor of glucose metabolism. Furthermore, the knockdown of integrin alpha L (ITGAL)/CD11a, a subunit of ISG15 receptor lymphocyte functional-associated antigen-1 (LFA-1), in immortalized fibroblasts diminished extracellular ISG15-mediated glycolysis and migration. Our findings suggest that ISG15 derived from OSCC cells interacts with fibroblasts through the LFA-1 receptor, leading to glycolytic reprogramming and promotion of fibroblast migration into the TME
Cellular sentinels: Empowering survival and immune defense in hematopoietic stem cell transplantation through mesenchymal stem cells and T lymphocytes
[[abstract]]Background Hematopoietic stem cell transplantation (HSCT) is a critical treatment for hematologic disorders such as leukemia, lymphoma, and specific immune deficiencies. Despite its efficacy, challenges such as engraftment failure and delayed neutrophil regeneration remain significant barriers. These complications lead to prolonged cytopenia, increased risks of infections and other complications, and elevated morbidity and mortality rates. While mesenchymal stem cells (MSCs) are known to play essential roles in supporting hematopoiesis, the precise mechanisms and interactions between MSCs and other cellular components in HSCT require further investigation.MethodsTo address these challenges, we explored the combined infusion of allotype-cord blood hematopoietic stem cells (HSCs) and activated T cells from the same donor along with third-party MSCs. The study assessed the effects of this triple-cell therapy on neutrophil differentiation and function ex vivo and in vivo. Using a respiratory infection model, we evaluated the accumulation of human neutrophils, cytokine secretion (IL-6 and IL-8), bacterial clearance, and overall survival compared to control groups.ResultsThe triple-cell therapy demonstrated a significant improvement in the differentiation of human HSCs into neutrophils both in ex vivo and in vivo. In the respiratory infection model, this approach resulted in enhanced accumulation of human neutrophils, increased secretion of IL-6 and IL-8, superior bacterial clearance, and reduced mortality rates compared to the control group. These findings highlight the synergistic interplay between allo-HSCs, MSCs, and activated T cells in promoting neutrophil production and function.ConclusionsOur study presents a novel therapeutic strategy combining allo-HSCs, activated T cells, and third-party MSCs to enhance neutrophil production and functionality post-transplantation. This approach not only accelerates neutrophil regeneration but also improves resistance to infections, offering a promising avenue to overcome engraftment challenges in HSCT
[[alternative]]Induction of LY6E regulates interleukin-1β production, potentially contributing to the immunopathogenesis of systemic lupus erythematosus
[[abstract]]Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the deposition of immune complexes (ICs) in various organs, especially the kidney, leading to lupus nephritis, one of the major and therapeutically challenging manifestations of SLE. Among the various cytokines induced in SLE, type I interferons (IFN-Is) play crucial roles in mediating immunopathogenesis, and anti-IFN-I treatment has been approved for SLE treatment. The uptake of ICs by macrophages results in macrophage activation, which initiates, triggers, and exaggerates immune responses in SLE. After observing the induction of an IFN-stimulated gene, LY6E, in monocytes from SLE patients, we demonstrated the colocalization of both LY6E and a macrophage marker in kidneys from pristane-induced lupus-prone mice and from patients with lupus nephritis. By studying mouse bone marrow-derived macrophages, we showed that LY6E regulated IFN-alpha- and IC-induced production and secretion of mature interleukin-1 beta (mIL-1 beta), foam cell formation and several mitochondria-associated mechanisms, such as the release of mitochondrial DNA (mtDNA) but not mitochondrial RNA (mtRNA) into the cytosol, the generation of mitochondrial reactive oxygen species (mtROS) and ROS, the activation of caspase 1, NLRP3, and the stimulator of interferon genes (STING) signaling pathway, and the activation of cytidine/uridine monophosphate kinase 2 (CMPK2), which were involved in LY6E-mediated immunomodulatory effects. In addition, synergistic effects of a combination of IL-1 beta and IFN-alpha and of IL-1 beta and ICs on the induction of the expression of IFN-stimulated genes were observed. In addition to revealing the proinflammatory roles and mechanisms of LY6E in macrophages, given that various subgroups of macrophages have been identified in the kidneys of patients with lupus nephritis, targeted treatment aimed at LY6E may be a potential therapeutic for lupus nephritis
[[alternative]]Taxane/anthracycline combinations reduced incidence of breast cancer recurrence in young women across molecular subtypes: A real-world evidence of Taiwan from 2011 to 2019 (vol 209, pg 647, 2024)
[[abstract]]In this article, Fig. 1 appeared incorrectly and has now been corrected in the original publication. For completeness and transparency, the correct and old incorrect versions are displayed below. The original article has been corrected. Incorrect Fig. 1: (Figure presented.) Correct Fig. 1: (Figure presented.) Flowchart of AYA early breast cancer patients. Note: AYA, adolescents and young adults at 15–39 ages
Sex-specific association of co-exposures to melamine and phthalates in children with their early renal injury
[[abstract]]Studies concerning the effect of co-exposure to melamine and phthalates on kidney function in children are rare. Thus, this study examines the above-mentioned relationship and their sex-different effect. Whether the exposure of the two chemicals from their mothers, when children were in the womb during the third trimester, affected renal injury markers in children afterwards is also examined. This study was from Taiwan Maternal and Infant Cohort Study cohort established in October 2012 to enroll third-trimester pregnant mothers up to May 2015. Their offspring were subsequently recruited between 2016 and 2020 as our study children. One-spot urine specimens were collected from both pregnant mothers (2012-2015) and study children (2016-2020) for the simultaneous measurement of melamine and 11 phthalate metabolites. Daily intakes of melamine and five phthalates, including DEHP (di-2-ethylhexylphthalate), DiBP (Dibutyl phthalate), DnBP (Di-n-butyl phthalate), BBzP (Butyl benzyl phthalate), and DEP (Diethyl phthalate), were estimated using a creatinine excretion-based model in both study children and their mothers. Two early markers of renal injury, microalbumin and N-acetylbeta-D-glucosaminidas (NAG), were measured in urine samples of study children (2016-2020). A total of 552 eligible children were studied, with a mean age of 4 years. We found that boys in the highest quartile of estimated melamine intake (>= 0.68 mu g/kg/day) had significantly higher urine ACR levels and in the highest quartile of estimated phthalate intake of DEHP (>= 5.36 mu g/kg/day), DEP (>= 0.89 mu g/kg/day), and DiBP (>= 1.19 mu g/kg/ day) had significantly higher urine NAG levels when compared to the combined three lowest quartile ones as comparison groups. No significant associations were found between their mothers' phthalates and melamine intake during the third trimester and urine ACR and NAG in children. We conclude that children (particularly boys) with high co-exposure of melamine and certain phthalate chemicals among children have increased early markers of kidney injury
Relationship between long-term exposure to fine particulate air pollution and colorectal cancer mortality in Taiwan
[[abstract]]The International Agency for Research on Cancer classified fine particulate matter (PM2.5) air pollution as carcinogenic to humans (Group I). Although PM2.5 exposure has been associated with lung cancer occurrence, few studies investigated this association with non-lung cancer. Colorectal cancer (CRC) is the third leading cause of cancer deaths both among men and women. In Taiwan, deaths attributed to CRC vary considerably across townships, suggesting involvement of the environment. The aim of this study was to examine the association between long-term ambient PM2.5 exposure and deaths attributed to CRC in 66 municipal areas across Taiwan. Annual PM2.5 levels were compared against age-standardized CRC mortality rates in male and female residents of these municipalities from 2012 to 2021. Annual PM2.5 levels of different municipalities were sub-divided into tertiles. Adjusted risk ratio (RR) was calculated by multiple regression analyses, controlling for municipal lung cancer deaths, urbanization level, annual average household income, and density of physicians in the municipal areas. For males, adjusted RRs for CRC death were 1.1 (95% CI = 1.05-1.15) for municipalities with PM2.5 levels ranging from 18.96 to 25.19 mu g/m3and 1.15 (95% CI = 1.1-1.21) for levels ranging from 25.2 to 29.48 mu g/m3, respectively, compared to those areas belonging to the lowest tertiles. Our analysis of trend suggested that risk of CRC-related death paralleled increases PM2.5 levels in males. For females, adjusted RRs were 1.18 (95% CI = 1.12-1.25) and 1.12 (95% CI = 1.06-1.19), respectively. Evidence indicated that long-term exposure to PM2.5 may elevate the risk of CRC-related death in both men and women in Taiwan
Recommendations and guidance for human papillomavirus (HPV) vaccination for adults in Taiwan
[[abstract]]Human papillomavirus (HPV) is the most prevalent viral infection globally, transmitted primarily through sexual or intimate skin-to-skin contact. Certain HPV types can cause anogenital warts and has the potential to cause cervical cancer, other anogenital, and oropharyngeal cancers. Adjuvanted, non-live, HPV recombinant vaccines, including the bivalent, quadrivalent, and 9-valent vaccines, are widely recommended for adolescents and young adults to prevent HPV infection and lower the incidence of HPV-related cancers. However, recommendations for adults aged 26 years or older have been lacking due to insufficient evidence until recently. The Working Group on Adult Immunization Practice of the Infectious Diseases Society of Taiwan (IDSTAIP working group) addressed this gap and drafted recommendations for HPV vaccination in adults using the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. These recommendations were then reviewed and revised by expert panels and endorsed by eight national medical societies. This document is positioned as a guidance to provide recommendations for HPV vaccination in adults, considering gender, age, immune status, and prior HPV vaccination history. Safety evaluations, dosing schedules, and special considerations regarding the occupational exposure of healthcare providers, based on potential modes of HPV transmission, are provided. In summary, a 3-dose HPV vaccination schedule is recommended for all adults through age 45 years, regardless of sex, to prevent genital warts, anogenital cancers, as well as oropharyngeal infections and cancers. This guidance serves to assist healthcare providers in facilitating shared decision-making but does not supersede clinical judgment in assessing individual risk and making specific recommendations