The increased risk of exposure to fine particulate matter for depression incidence is mediated by elevated TNF-R1: The healthy aging longitudinal study

[[abstract]]BACKGROUND: Depression among older adults is an important public health issue, and air and noise pollution have been found to contribute to exacerbation of depressive symptoms. This study examined the association of exposure to air and noise pollutants with clinically-newly-diagnosed depressive disorder. The mediating role of individual pro-inflammatory markers was explored. METHODS: We linked National Health Insurance claim data with 2998 healthy community-dwellers aged 55 and above who participated in the Healthy Aging Longitudinal Study between 2009 and 2013. Newly diagnosed depressive disorder was identified using diagnostic codes from the medical claim data. Pollutants were estimated using nationwide land use regression, including PM(2.5) and PM(10), carbon monoxide, ozone, nitrogen dioxide, sulfur dioxide, and road traffic noise. Cox proportional hazard models were employed to examine the association between pollutants and newly developed depressive disorders. The mediating effect of serum pro-inflammatory biomarkers on the relationship was examined. RESULTS: Among the 2998 participants, 209 had newly diagnosed depressive disorders. In adjusted Cox proportional hazard models, one interquartile range increase in PM(2.5) (8.53 µg/m(3)) was associated with a 17.5% increased hazard of developing depressive disorders. Other air pollutants and road traffic noise were not linearly associated with depressive disorder incidence. Levels of serum tumor necrosis factor receptor 1 mediated the relationship between PM(2.5) and survival time to newly onset depressive disorder. CONCLUSION: PM(2.5) is related to an increased risk of newly developed depressive disorder among middle-aged and older adults, and the association is partially mediated by the pro-inflammatory marker TNF-R1

Real-world use and treatment outcomes of ceftazidime-avibactam in gram-negative bacterial infection in Taiwan: A multicenter retrospective study

[[abstract]]Objectives: Ceftazidime-avibactam (CAZ-AVI) has been launched in Asian countries for five years, but local real-world data about patient characteristics, efficacy, and safety of CAZ-AVI is limited. We conducted a multicenter, retrospective study to investigate the clinical characteristics, microbiology, and outcomes of patients treated with CAZ-AVI for Gram-negative bacterial infection in Taiwan. Methods: This investigation was conducted as a multicenter retrospective cohort study involving five medical centers in Taiwan. Adult patients with documented/suspected Gram-negative bacterial infection and received >= 24 hours of CAZ-AVI were eligible for study cohort enrollment. In-hospital mortality was defined as the primary outcome, while symptom resolution or significant improvement, considered the secondary outcome, was defined as clinical success. Results: Among the 472 patients treated by CAZ-AVI, 46.2 % (218/472) had respiratory tract infections, 22.0 % (104/472) had complicated urinary tract infections, 14.0 % (66/472) had complicated intra-abdominal infections, and 10.0 % (47/472) had primary bacteremia. Most patients receiving ceftazidime/avibactam in Taiwan are old (mean: 70.6 years old), have a high SOFA score (mean 8.4), and have a high Charlson Comorbidity Index score (345/472, 73.1 %>= 4). 90 % of CAZ-AVI were used as targeted therapy for pathogens, including Klebsiella pneumoniae (64.4 %, 304/472), Pseudomonas aeruginosa (17.8 %, 84/472), Escherichia coli (8.3 %, 39/472), and Enterobacter spp. (2.3 %, 11/472). The overall clinical success rate is 58.1 % (274/472). The in-hospital mortality rate is 41.1 % (194/472). Conclusions: Most patients receiving CAZ-AVI as targeted therapy in Taiwan with characteristics of older age, high SOFA scores, and high CCI scores. Receiving immunomodulators, higher SOFA score, and Enterobacter spp. infections were the significant factors associated with in-hospital mortality, whereas early initiating CAZ-AVI treatment and CAZ-AVI monotherapy are associated with better outcome

Neurofilament light chain and cognitive function among OSA patients

[[abstract]]Introduction: Obstructive Sleep apnea (OSA) is characterized by intermittent hypoxia during sleep, leading to cognitive impairment. Neurofilament light chain (NFL) is a biomarker for brain nerve damage, it's level increased in peripheral blood in neurodegenerative diseases. The increase in NfL has been hypothesized to be related with sleep loss, sleep architecture change, and intermittent hypoxia. Methods: We recruited 18 adult patients with OSA between October 2023 and December 2023. The patients underwent in-laboratory polysomnographic studies, a smart-phone based psychomotor vigilance test (PVT), and blood test for level of NFL. Endotypic traits including arousal threshold, upper airway collapsibility, loop gain, and upper airway muscle compensation, hypoxic burden, apnea and hypopnea duration were generated using polysomnographic signals. We examined the correlation between PVT results and blood NFL level. We further used multivariate linear regression model to examine the association between endotypic traits of OSA with blood NFL level. Results: The study participants had an average apnea-hypopnea index (AHI) 49.3 ± 27.5/h, and NFL 10.5 ± 8.4 pg/mL. We observed a negative relationship between mean reciprocal reaction time in PVT and NFL level (r = _0.79, p < 0.001). After adjustment for age, sex, and body-mass index, AHI was positively associated with NFL level (β = 0.17, 95% confidence interval = 0.04–0.30, p = 0.02). However, endotypic traits were not associated with NFL level. After additional adjustment for AHI, the proportion of slow-wave sleep was negatively associated with NFL level, whereas rapid-eye movement sleep was positively associated with NFL. Conclusions: NFL level is correlated with worse attention performance among OSA patients. Our findings did not observe an association between hypoxic burden of OSA and neurodegeneration biomarker. Instead, slow-wave sleep deprivation is associated with neurodegeneration in OSA patients

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

[[alternative]]The method of the preparation of fused multicyclic compounds

[[abstract]]本發明公開了一種製備喹唑啉（quinazoline）式（I）化合物之方法，特別為一種以公斤量級規模製備之方法： 於本文中定義 B, D, W, Z, R 1, R 2及 n

Development of pd-loaded hf-based metal-organic framework as a dual-modal contrast agent for photoacoustic imaging and computed tomography

[[abstract]]Noninvasive cancer imaging significantly improves diagnostics by providing comprehensive structural and functional information about tumors. Herein, we explored palladium nanoparticles loaded hafnium-based metal-organic framework (MOF) (Hf-EDB), i.e., Pd@Hf-EDB as an efficient dual modal contrast agent for computed tomography (CT) and photoacoustic imaging (PAI). The synergistic collaborations between (i) high-Z element Hf-based MOF with superior X-rays absorbing capabilities, (ii) H2EDB linkers with special pi-donation and pi-acceptor characteristics capable of strongly anchoring noble metals, and (iii) Pd nanoparticles with broad absorption in the UV to near-infrared (NIR) regions due to strong interband transition are ideal for implementation in CT and PAI. The successful synthesis of Pd@Hf-EDB nanoparticles was confirmed through morphology, crystallinity, and compositional characterizations using X-ray diffraction, SEM, TEM, DLS, and EDS. Soft X-ray tomography verified cellular uptake via phagocytosis of Pd@Hf-EDB by BxPC-3 tumor cells. In-vitro experiments revealed superior CT imaging performance of Pd@Hf-EDB over traditional molecular contrast agents like Iohexol. Broad absorption range in the UV-vis/NIR regions and superior PAI capabilities of Pd@Hf-EDB relative to gold nanorods are reported. Furthermore, the in vivo xenograft model demonstrated significant contrast enhancements near the tumor, highlighting the excellent PAI and CT capabilities of the synthesized Pd@Hf-EDB

Cisd1 synergizes with Cisd2 to modulate protein processing by maintaining mitochondrial and ER homeostasis

[[abstract]]Connection and crosstalk among the organelles critically contribute to cellular functions. Destruction of any kind of organelle is likely to induce a series of intracellular disorders and finally lead to cell death. Because of its subcellular locations, CDGSH iron-sulfur domain-containing protein 1 (Cisd1) and Cisd2 have functions that are related to maintaining mitochondria and ER homeostasis. As previous reports have shown, Cisd2 knockout mice have a decreased body weight and poor survival rate, and the primary defects were conducted in skeletal muscle. Our previous findings indicated that Cisd1 deletion causes a range of skeletal muscle defects in mice with Cisd2 deficiency, including mitochondrial degeneration, endoplasmic reticulum (ER) stress, and alteration of protein process, as well as programmed cell death. In Cisd1 and Cisd2 deficient condition, the whole of the protein biosynthesis was damaged, including translation, modification, transport, and degradation. Changes in the immune response, redox regulation, and metabolism were also present in Cisd1 and Cisd2 double knockout mice. Overall, we have demonstrated that Cisd1 and Cisd2 knockout have a synergistic effect on skeletal muscles, and that Cisd2 plays a more critical role than Cisd1. These synergistic effects impact signaling regulation and interrupt the crosstalk and homeostasis of organelles. This creates severe disorders in various tissues and organs

Prenatal and childhood infections and risk of epilepsy

[[abstract]]Infections in utero and early childhood are associated with an increased epilepsy risk; however, confounding by familial predisposition has not been adequately accounted for in previous studies. We aimed to assess the epilepsy risk attributable to infections in utero and early childhood by performing population-based and sibling-comparison analyses to account for residual and unmeasured familial confounding factors. This nationwide birth cohort study included 2,609,289 individuals born 2001-2016 in Taiwan. Maternal infection during pregnancy and early childhood infection during the first year of life were defined. Maternal pre-pregnancy infection was used as negative control. In the population analyses, offspring exposed to any maternal infection during pregnancy had an increased epilepsy risk (hazard ratio (HR) = 1.36, 95% confidence interval (CI):1.27-1.45). However, the association with maternal infection was attenuated to the null (HR = 1.11, 95% CI:0.98-1.27), except for maternal infection in sepsis (HR = 2.54, 95% CI:1.74-3.70) and central nervous system (HR = 24.59, 95% CI:3.28-184.23), in the sibling analyses. The association of maternal pre-pregnancy infection with offspring epilepsy was observed in the population analyses, but not in the sibling analyses. Individuals exposed to childhood infection had an increased epilepsy risk (HR = 1.49, 95% CI:1.45-1.54) in the population analyses; the association was still observed in the sibling analyses (HR = 1.31, 95% CI:1.23-1.40). The association between maternal infection during pregnancy and epilepsy risk in the offspring appears largely because of familial confounding factors. Infections during early childhood may play a causal role in the subsequent epilepsy risk

Effectiveness of full mRNA vaccinations to prevent COVID-19 among immunocompromised patients receiving tixagevimab-cilgavimab as pre-exposure prophylaxis

[[abstract]]Pre-exposure prophylaxis with monoclonal antibodies (mAbs) offers protection against COVID-19 in immunocompromised patients. To attest full vaccinations, defined by ≥ 3-dose mRNA vaccines, providing additional protection effect on mAbs against COVID-19, we retrospectively compared the breakthrough SARS-CoV-2 infection rates between adult immunocompromised patients with and without full vaccinations before receiving prophylactic tixagevimab-cilgavimab during the Omicron BA.5 dominant period. Among 148 patients, most (96.6 %) had hematologic malignancies. Fifty-nine (39.9 %) patients received full vaccinations before tixagevimab-cilgavimab. Overall, 19 (12.8 %) patients have breakthrough infections, and only three of them had full vaccinations. By a multivariable logistic regression model, receipt of full vaccinations was the only independent factor associated with prevention of breakthrough infections (adjusted odds ratio, 0.26 [95 % CI, 0.07–0.95]). The Kaplan–Meier estimate showed a lesser trend of breakthrough infections with those receiving full vaccinations (P = 0.08). Our study underscores the importance of full vaccinations among immunocompromised patients receiving pre-exposure prophylactic mAbs against COVID-19

[[alternative]]Method and composition for treating hepatocellular carcinoma without viral infection by controlling the lipid homeostasis

[[abstract]]本發明係提供一種用於治療無肝炎病毒感染病史之肝細胞癌(HCC)患者的方法與組成物。本發明特別是關於一種透過基因工程技術標靶調控與控制體內脂質平衡相關基因，尤其是藉由調控CD36的增幅或與ABCG4的缺失，來治療非因B型肝炎病毒及/或C型肝炎病毒感染引起之肝細胞癌(NBNC-HCC)患者的方法