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Sodium benzoate, a D-amino acid oxidase inhibitor, improved short-term memory in patients with mild cognitive impairment in a randomized, double-blind, placebo-controlled clinical trial
No full text[[abstract]]BackgroundPrevious studies have found that sodium benzoate (the pivotal D-amino acid oxidase [DAO] inhibitor) improved cognitive function in patients with mild Alzheimer disease; however, its efficacy for mild cognitive impairment (MCI) (especially its core feature, impaired short-term memory) remains uncertain. The aim of this study was to evaluate the efficacy and safety of sodium benzoate in treating amnestic MCI (aMCI).MethodsThis study was a randomized, double-blind, placebo-controlled clinical trial conducted in a major medical center in Taiwan. Eighty-two patients with aMCI were recruited for 24-week treatment of 250 to 1500 mg/day of sodium benzoate or placebo. Overall, cognitive function was measured by Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), and short-term memory was evaluated by the 'recall of test instructions' item in the ADAS-cog. The generalized estimating equation was applied to compare the two groups in efficacy.ResultsCompared with placebo, sodium benzoate therapy, displayed a trend, albeit statistically insignificant, in improving overall cognitive function (P = 0.082), and significantly improved short-term memory (P = 0.044). Both benzoate and placebo were well tolerated and benzoate therapy produced no additional side effect.ConclusionsWith the moderate sample size of the current study, treatment using sodium benzoate, a DAO inhibitor, showed promise in improving cognition, especially short-term memory, in patients with aMCI. Of note, while the ADAS-cog total score has been regarded as insensitive in measuring aMCI, its 'recall of test instructions' item may be a more sensitive and clinically feasible tool. Further larger studies are warranted to confirm the preliminary finding
Urban-rural disparity for socioeconomic inequality regarding PM2.5 exposure
No full text[[abstract]]Background Socioeconomic inequality in air pollution exposure poses a significant public health challenge, yet little is known about how such disparities vary across levels of urbanization. This study aims to examine the association between socioeconomic status (SES) and PM(2.5 )exposure in Taiwan from an urban-rural perspective. Methods This ecological study used township-level data from 2011 to 2020. PM(2.5 )exposure estimates were generated using land-use regression and Ordinary Kriging models. Socioeconomic position was assessed using multiple SES indicators, including educational attainment. Inequality was quantified using the Slope Index of Inequality (SII) and the Relative Index of Inequality (RII). Results PM(2.5 )concentrations were highest in metropolitan core areas and lowest in remote townships. Townships with higher SES experienced greater PM(2.5 )exposure. SII and RII for the proportion of individuals with higher education showed a consistent increase over the study period, indicating worsening socioeconomic inequality. However, inequality patterns differed between urban and rural areas. Conclusions Substantial urban-rural disparities in PM(2.5 )exposure and socioeconomic inequality were observed. The worsening trends highlight the need for immediate policy interventions to protect vulnerable populations and further research to identify and address pollution sources
Oncogenic role of fumarate hydratase in breast cancer: Metabolic reprogramming and mechanistic insights
No full text[[abstract]]Breast cancer remains the most prevalent malignancy among women globally, with its complexity linked to genetic variations and metabolic alterations within tumor cells. This study investigates the role of fumarate hydratase (FH), a key enzyme in the tricarboxylic acid (TCA) cycle, in breast cancer progression. Our findings reveal that FH mRNA and protein levels are significantly upregulated in breast cancer tissues and correlate with poor patient prognosis and aggressive tumor characteristics. Using in vitro and in vivo models, we demonstrate that FH overexpression enhances breast cancer cell proliferation, migration, and invasion through metabolic reprogramming and by increasing reactive oxygen species (ROS) production. Furthermore, we identify matrix metalloproteinase 1 (MMP1) as a downstream effector of FH, linked to p21 downregulation, elucidating a novel regulatory pathway influencing tumor behavior. Interestingly, unlike its tumor-suppressing role in other cancer types, this study highlights FH's oncogenic potential in breast cancer. Our results suggest that FH enhances cancer cell viability and aggressiveness via both catalytic and non-catalytic mechanisms. This work not only underscores the metabolic adaptations of breast cancer cells but also proposes FH as a potential biomarker and therapeutic target for breast cancer management
Using large language models for efficient cancer registry coding in the real hospital setting: A feasibility study
No full text[[abstract]]The primary challenge in reporting cancer cases lies in the labor-intensive and time-consuming process of manually reviewing numerous reports. Current methods predominantly rely on rule-based approaches or custom-supervised learning models, which predict diagnostic codes based on a single pathology report per patient. Although these methods show promising evaluation results, their biased outcomes in controlled settings may hinder adaption to real-world reporting workflows. In this feasibility study, we focused on lung cancer as a test case and developed an agentic retrieval-augmented generation (RAG) system to evaluate the potential of publicly available large language models (LLMs) for cancer registry coding. Our findings demonstrate that: (1) directly applying publicly available LLMs without fine-tuning is feasible for cancer registry coding; and (2) prompt engineering can significantly enhance the capability of pre-trained LLMs in cancer registry coding. The off-the-shelf LLM, combined with our proposed system architecture and basic prompts, achieved a macro-averaged F-score of 0.637 when evaluated on testing data consisting of patients' medical reports spanning 1.5 years since their first visit. By employing chain of thought (CoT) reasoning and our proposed coding item grouping, the system outperformed the baseline by 0.187 in terms of the macro-averaged F-score. These findings demonstrate the great potential of leveraging LLMs with prompt engineering for cancer registry coding. Our system could offer cancer registrars a promising reference tool to enhance their daily workflow, improving efficiency and accuracy in cancer case reporting
Psychopathologies and quality of life in mental and functional disorders associated with persistent somatic symptoms
No full text[[abstract]]BACKGROUND: Persistent somatic symptoms (PSS) are a central diagnostic feature of several mental and functional disorders. However, only several studies simultaneously considered disorders from different systems. The purpose of this study was to explore the coexisting status of these diagnoses and to analyze the relationship between diagnoses and various psychopathologies, as well as quality of life (QOL). METHODS: We recruited participants from psychosomatic clinics and neighboring communities of a hospital. All individuals underwent semi-structured interviews covering functional and mental disorder diagnoses and completed self-administered scales measuring somatic distress, health anxiety, depression, anxiety, and QOL. The relationships between diagnoses, psychopathologies, and QOL were explored. RESULTS: This cross-sectional study included 502 individuals (mean age 44.54 years, 38.8 % males). Among the various diagnoses with PSS, the DSM-IV's undifferentiated somatoform disorder (USD) and DSM-5's somatic symptom disorder (SSD) were the most common. SSD had a high comorbidity rate with generalized anxiety disorder (GAD), major depressive disorder (MDD), and panic disorder. The diagnosis most strongly associated with the severity of somatic distress and health anxiety was the DSM-IV USD and DSM-5 SSD, respectively. MDD, GAD, panic disorder, and adjustment disorder had significant associations with various psychopathologies and QOL. Among the diagnoses with PSS, the DSM-IV USD had the highest correlation with QOL, primarily in the overall and physical domains. LIMITATIONS: The clinical sample was collected from psychosomatic clinics and cannot represent other medical settings. CONCLUSION: DSM-IV USD and DSM-5 SSD were the diagnoses with PSS most extensively and significantly associated with psychopathologies and QOL
Macrophage activation determines muscle wasting in pancreatic cancer
No full text[[abstract]]The contribution of non-cancer tumoral microenvironment to cachexia is vastly unclear. Despite advances in understanding the signals involved in cancer cachexia progression, the exact time point of cachexia onset remains unpredictable. The transgenic Kras(LSL-G12D/+);Trp53(flox/flox);Pdx1-Cre (KP(2)C) GEMM is a clinically relevant model, with the timing of cancer cachexia progression from the pre-cachectic, early-onset, to severe cachexia showed that the onset of cachexia was associated with differences in muscle wasting. The exact cell-of-origin in different types of non-cancer cells in the tumoral microenvironment and the circulating blood, which drives cachexia, remains unclear. Production of potent pro-cachectic substances that induce skeletal muscle wasting also requires mechanistic analysis. This study analyzed the PBMC and the mouse-derived syngeneic transplants (MDSTs) of KP(2)C GEMM in recipient mice and pinpoints the cell-type changes with the timing of cachexia (>10% weight loss) by conducting single-cell expression analysis of cell-type-specific gene expression determinants of cachexia. Single-cell RNA sequencing analysis identified signals in high-quality, specific cell types of PBMC (29,615 cells) and MDST (23,151 cells). The scRNA-seq data identified differentially expressed chitinase 3 like 1 (CHI3L1 encoded by mouse Chi3l1) and chitinase-like 3 (CHI3L3, encoded by Chil3) and that macrophages are significant mediators of early-onset muscle wasting in tumor-bearing mice. C2C12 myoblasts treated with the CHI3L1 recombinant protein suppressed myotube formation and upregulated mRNA expression of Hdac3, Tlr9, Irf3, Tbk1, and Nfkb1. Skeletal muscle-specific conditional Hdac3 knockout in tumor-bearing mice decreased muscle wasting via CHI3L1-HDAC3 signaling. An anti-CHI3L1 monoclonal antibody was administered to target these macrophage populations, and the treatment resulted in suppressed tumor growth, metastatic progression, and protected body weight. Our results support the role of pancreatic tumor-associated macrophages in mediating skeletal muscle wasting and provide a clinically relevant mechanism of progression from the pre-cachectic state to the cachexia onset
Targeting SARS-CoV-2 RNA-dependent RNA polymerase with the coumarin derivative BPR2-D2: Evidence from cell-based and enzymatic studies
No full text[[abstract]]The rapid mutation rate of SARS-CoV-2 highlights the urgent need for continuous drug development to enhance both efficacy and safety. BPR2-D2, an angular coumarin derivative, has previously shown notable anti-influenza activity and broad-spectrum inhibitory effects against RNA viruses. In this study, we found that BPR2-D2 exhibits potent antiviral activity against multiple SARS-CoV-2 variants, including several variants of concern, at nanomolar concentrations. Notably, BPR2-D2 effectively disrupted viral RNA and protein synthesis in infected cells while mitigating pro-inflammatory cytokines triggered by viral replication. Our investigation of SARS-CoV-2 RdRp activity employed in silico analyses, including molecular docking, dynamic simulations, and binding free energy calculations. BPR2-D2 demonstrated superior binding affinity to the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 compared to remdesivir. Additionally, it exhibited an increased synergistic inhibitory activity against the viral enzyme when combined with remdesivir. Both cell-based and in vitro enzyme-based RdRp reporter assays validated BPR2-D2's capacity to inhibit SARS-CoV-2 RdRp activity. The potential synergistic interaction between BPR2-D2 and remdesivir was investigated using cell-based combination assays. The results revealed a synergistic effect in reducing SARS-CoV-2 RNA synthesis, consistent with the in silico analysis. Collectively, these findings suggest that BPR2-D2, a repurposed small-molecule compound, effectively inhibits SARS-CoV-2 by modulating its RdRp function. This positions BPR2-D2 as a promising novel antiviral agent, while also providing insights into the complex molecular mechanisms underlying viral replication
Cardiovascular-kidney-metabolic syndrome and all-cause and cardiovascular mortality: A retrospective cohort study
No full text[[abstract]]BACKGROUND: The American Heart Association recently issued guidelines introducing the concept of cardiovascular-kidney-metabolic (CKM) syndrome to emphasize the importance of multidisciplinary approaches to prevention, risk stratification, and treatment for these diseases. This study assessed the prevalence of CKM syndrome stages and the mortality risk associated with its components in a large Asian cohort. METHODS AND FINDINGS: We analyzed a retrospective cohort of 515,602 participants aged ≥20 years from a health screening program conducted between 1996 and 2017 in Taiwan. We assessed the associations of all-cause mortality, cardiovascular disease (CVD) mortality, and cause-specific mortality with CKM stages and its components-hypertension, diabetes mellitus, chronic kidney disease (CKD), metabolic syndrome, and hyperlipidemia. All participants were followed for a median of 16.5 years (interquartile range: 11.5, 21.2 years). Multivariate Cox proportional hazards models, adjusted for age, sex, educational level, smoking status, alcohol drinking status, and physical activity groups, were used to calculate hazard ratios (HRs). We used Chiang's life table method to estimate years of life lost due to each CKM component. Among all participants, 257,535 (49.9%) were female. The majority of participants (n = 368,578 participants, (71.5%)) met criteria for CKM syndrome, with prevalence rates of 19.5%, 46.3%, 1.9%, and 3.8% for stages 1, 2, 3, and 4, respectively. CKM syndrome was associated with higher risks of all-cause mortality (HR: 1.33; 95% confidence interval, CI: 1.28, 1.39), CVD mortality (HR: 2.81; 95% CI: 2.45, 3.22), and incident end-stage kidney disease (ESKD) (HR: 10.15; 95% CI: 7.54, 13.67). Each additional CKM component was associated with a 22% increase in the risk of all-cause mortality (HR: 1.22; 95% CI: 1.21, 1.23), a 37% increase in the risk of CVD mortality (HR: 1.37; 95% CI: 1.35, 1.40) compared with those without any CKM components. In addition, each additional component reduced average life expectancy by 3 years. The population-attributable fractions of CKM syndrome were 18.7% (95% CI: 15.8, 21.7) for all-cause mortality and 55.0% (95% CI: 49.0, 60.4) for CVD mortality. We estimated that failing to include CKD in CKM syndrome could result in the missed attribution of 11% of CVD deaths. The primary limitation is that our analysis relied on baseline measurements only, without accounting for longitudinal changes. CONCLUSIONS: In the large cohort study, the prevalence of CKM syndrome and its components were associated with risks of all-cause mortality, CVD mortality, and ESKD. These findings highlight the clinical need for integrated care within CKM health
Russell's viper envenomation: The challenge of diagnosis
No full text[[abstract]]Russell's viper envenomation is rare in Taiwan, and its typical clinical presentations, including consumption coagulopathy, acute renal failure, haemolysis, and increased capillary permeability, have been reported in the literature as case reports or series. Here, we report a case with an atypical presentation, and suspected to be a Russell's viper bite due to the distinct distribution characteristics of the snake and some progressive clinical signs/symptoms. He returned to health successfully after the correct antivenom was administered, and envenomation was ultimately confirmed by venom detection in the patient's serum and urine samples
[[alternative]]Storage media for preservation of corneal tissue
No full text[[abstract]]本發明公開了一種角膜器官保存組合物，該組合物包含有效量之已緩衝、已平衡且營養的電解質水溶液、聚-γ-麩胺酸及阿魏酸，可維持角膜組織細胞的完整性並可存活超過14天