Search Results (73)

Background: Solid organ transplant (SOT) recipients have an elevated risk of diabetes mellitus (DM). This study investigated the risk of posttransplant DM (PTDM) in a retrospective cohort study. Methods: We analyzed patients aged over 18 years who received an SOT between 2002 and 2013. Each patient was matched with four control individuals by age, sex, insured salary, urbanization level, Charlson’s comorbidity index (CCI), and year of inclusion in the study. After matching, the study comprised 6874 patients who underwent an SOT and 27,496 matched general patients as the comparison. The risk of DM among the SOT recipients was assessed using a Cox proportional hazards model after adjustment for all relevant variables. Results: The SOT cohort had a significantly higher risk of DM than general patients (adjusted hazard ratio [aHR], 1.61; 95% confidence interval [CI], 1.51–1.72). Kidney and liver recipients, respectively, had DM incidence rates 1.57 (95% CI, 1.46–1.70) and 1.73 (95% CI, 1.53–1.94) times that of the general patients. Conclusions: SOT recipients had an elevated risk of DM. Among various organ recipients, liver recipients had the highest PTDM risk. Kidney and liver recipients demonstrated the highest DM risk at 6 months after their SOT. The risk of PTDM following an SOT may result in long-term consequences. Hence, we advise the critical need for proper management to mitigate related complications after transplantation. Full article

Polyurethane foam (PUF) pads are widely used in semiconductor manufacturing, particularly for chemical mechanical polishing (CMP). This study prepares PUF composites with microcrystalline cellulose (MCC) and nanocrystalline cellulose (NCC) to improve CMP performance. MCC and NCC were characterized using scanning electron microscopy (SEM) and X-ray diffraction (XRD), showing average diameters of 129.7 ± 30.9 nm for MCC and 22.2 ± 6.7 nm for NCC, both with high crystallinity (ca. 89%). Prior to preparing composites, the study on the influence of the postbaked step on the PUF was monitored through Fourier-transform infrared spectroscopy (FTIR). After that, PUF was incorporated with MCC/NCC to afford two catalogs of polyurethane foam composites (i.e., PUFC-M and PUFC-N). These PUFCs were examined for their thermal and surface properties using a differential scanning calorimeter (DSC), thermogravimetric analysis (TGA), dynamic mechanical analyzer (DMA), and water contact angle (WCA) measurements. T_gs showed only slight changes but a notable increase in the 10% weight loss temperature (T_d10%) for PUFCs, rising from 277 °C for PUF to about 298 °C for PUFCs. The value of Tan δ dropped by up to 11%, indicating improved elasticity. Afterward, tensile and abrasion tests were conducted, and we acquired significant enhancements in the abrasion performance (e.g., from 1.04 mm/h for the PUF to 0.76 mm/h for a PUFC-N) of the PUFCs. Eventually, we prepared high-performance PUFCs and demonstrated their capability toward the practical CMP process. Full article

A novel five-surface phosphor-in-glass (FS-PiG) structure for high illumination and excellent color uniformity in large-view scale LEDs for sensor light source application is demonstrated. YAG phosphor (Y₃Al₅O₁₂:Ce³⁺) was uniformly mixed with ceramic and sintered at 680 °C to form a phosphor wafer. Sophisticated laser engraving was employed on the phosphor wafer to form saddle-shaped large-view scale FS-PiG LEDs. The performance of the FS-PiG LEDs exhibited an illumination of 401 lm, average color temperature (CCT) of 5488 K ± 110 K, and color coordinates (CIE) of (0.3179 ± 0.003, 0.3352 ± 0.003). In contrast to convention single-surface phosphor-in-glass (SS-PiG) LEDs, the performance exhibited an illumination of 380 lm, average CCT of 5830 K ± 758 K, and CIE of (0.3083 ± 0.07, 0.3172 ± 0.07). These indicated that the performance of the FS-PiG LEDs was higher than the SS-PiG LEDs for illumination, CCT, and CIE by 1.7, 7, and 23 times, respectively. Furthermore, the FS-PiG LEDs demonstrate a lower lumen loss of 2% and a reduced chromaticity shift of 5.4 × 10⁻³ under accelerated aging at 350 °C for 1008 h, owing to the high ceramic melting temperature of up to 510 °C. In this study, the proposed FS-PiG large-view scale LEDs with excellent optical performance and high reliability may be promising candidates to replace the conventional phosphor-in-organic silicone material used in high-power LEDs for the next generation of sensor light sources, display, and headlight applications. Full article

Diabetic retinopathy (DR), which can cause vision loss, may progress faster with poor glycemic control and oxidative stress. This study aims to examine how dietary patterns and glycemic control biomarkers relate to retinopathy risk in type 2 diabetes patients. In this study, we enrolled diabetic patients with retinopathy (DR) (n = 136) and without retinopathy (no DR) (n = 466) from a cohort of participants in the “Blood Pressure Control to Reduce the Risk of Type 2 Diabetic Nephropathy Study”. Hemoglobin A1c (HbA1c) and malondialdehyde were defined as elevated when their levels reached ≥8.5% and ≥2/3 (16.2 μm), respectively. Dietary data were collected by a food frequency questionnaire. Dietary patterns were identified by factor analysis. Elevated HbA1c was significantly correlated with increased risk of DR (OR: 2.12, 95% CI: 1.14–3.93, p = 0.017). In subjects with a high animal protein and processed food dietary pattern (≥highest tertile score) or a low vegetable intake pattern (<highest tertile score), elevated HbA1c was significantly associated with a 4.44-fold (95% CI: 1.34–14.68, p = 0.015), 3.96-fold (95% CI: 1.12–14.04, p = 0.033), and 2.57-fold (95% CI: 1.16–5.67, p = 0.020) increase in the risk of DR, respectively, compared to subjects with HbA1c levels < 8.5%. When stratifying subjects with a high animal protein pattern, higher MDA levels were significantly correlated with an increased risk of DR (OR: 2.93, 95% CI: 1.33–6.48, p = 0.008). Poor glycemic control increases the risk of retinopathy in patients with type 2 diabetes, and combined with diets low in vegetables and high in animal protein or processed food may exacerbate the risk of DR. The findings of this study should be further investigated in prospective studies. Full article

Screening for osteoporosis is crucial for early detection and prevention, yet it faces challenges due to the low accuracy of calcaneal quantitative ultrasound (QUS) and limited access to dual-energy X-ray absorptiometry (DXA) scans. Recent advances in AI offer a promising solution through opportunistic screening using existing medical images. This study aims to utilize deep learning techniques to develop a model that analyzes chest X-ray (CXR) images for osteoporosis screening. This study included the AI model development stage and the clinical validation stage. In the AI model development stage, the combined dataset of 5122 paired CXR images and DXA reports from the patients aged 20 to 98 years at a medical center was collected. The images were enhanced and filtered for hardware retention such as pedicle screws, bone cement, artificial intervertebral discs or severe deformity in target level of T12 and L1. The dataset was then separated into training, validating, and testing datasets for model training and performance validation. In the clinical validation stage, we collected 440 paired CXR images and DXA reports from both the TCVGH and Joy Clinic, including 304 pared data from TCVGH and 136 paired data from Joy Clinic. The pre-clinical test yielded an area under the curve (AUC) of 0.940, while the clinical validation showed an AUC of 0.946. Pearson’s correlation coefficient was 0.88. The model demonstrated an overall accuracy, sensitivity, and specificity of 89.0%, 88.7%, and 89.4%, respectively. This study proposes an AI model for opportunistic osteoporosis screening through CXR, demonstrating good performance and suggesting its potential for broad adoption in preliminary screening among high-risk populations. Full article

The purpose of this study was to investigate whether plasma biomarkers can help to diagnose, differentiate from Alzheimer disease (AD), and stage cognitive performance in patients with positron emission tomography (PET)-confirmed primary age-related tauopathy, termed tau-first cognitive proteinopathy (TCP) in this study. In this multi-center study, we enrolled 285 subjects with young-onset AD (YOAD; n = 55), late-onset AD (LOAD; n = 96), TCP (n = 44), and cognitively unimpaired controls (CTL; n = 90) and analyzed plasma Aβ42/Aβ40, pTau181, neurofilament light (NFL), and total-tau using single-molecule assays. Amyloid and tau centiloids reflected pathological burden, and hippocampal volume reflected structural integrity. Receiver operating characteristic curves and areas under the curves (AUCs) were used to determine the diagnostic accuracy of plasma biomarkers compared to hippocampal volume and amyloid and tau centiloids. The Mini-Mental State Examination score (MMSE) served as the major cognitive outcome. Logistic stepwise regression was used to assess the overall diagnostic accuracy, combining fluid and structural biomarkers and a stepwise linear regression model for the significant variables for MMSE. For TCP, tau centiloid reached the highest AUC for diagnosis (0.79), while pTau181 could differentiate TCP from YOAD (accuracy 0.775) and LOAD (accuracy 0.806). NFL reflected the clinical dementia rating in TCP, while pTau181 (rho = 0.3487, p = 0.03) and Aβ42/Aβ40 (rho = −0.36, p = 0.02) were significantly correlated with tau centiloid. Hippocampal volume (unstandardized β = 4.99, p = 0.01) outperformed all of the fluid biomarkers in predicting MMSE scores in the TCP group. Our results support the superiority of tau PET to diagnose TCP, pTau181 to differentiate TCP from YOAD or LOAD, and NFL for functional staging. Full article

It may be possible to enhance adults’ cognitive health and promote healthy aging through processing speed training using the Useful Field of View (UFOV) related activities and software. This study investigated the impact of utilizing UFOV on processing speed improvement in older adults in response to the growing global attention on cognitive health and aging issues. In this quasi-experimental study, 22 individuals (mean age ± SD = 71.9 ± 4.8) participated in the experimental group, and 20 community-based participants (mean age ± SD = 67.1 ± 4.8) were in the control group. The intervention involved ten sessions of UFOV training, each lasting 60 min, conducted twice a week for the experimental group while the control group engaged in volunteer service activities. Measurements of Counting Back, Fabrica, Double-Decision, and Hawkeye were administered to all participants before and after the intervention. The results showed significant improvements in the experimental group for the four measurements (p ≤ 0.01, 0.05, 0.001, 0.001) and non-significant gains in the control group (p ≥ 0.05) for all. Furthermore, mixed repeated-measures ANOVA analysis, with time 1 pre-test measures as the covariate, revealed significant interaction effects between time and group for all measurement indicators (p = 0.05, 0.01, 0.05) except for Fabrica (p > 0.05). In conclusion, these findings support the effectiveness of UFOV cognitive training interventions in enhancing specific cognitive abilities. Full article

Background and Aims: The impact of antibody responses following direct-acting antiviral (DAA) therapy in hepatitis C virus (HCV)-infected recipients before and after liver transplantation (LT) is still undetermined. Methods: In this observational cohort study, we aimed to explore the association between changes in anti-HCV antibody titers following pre-LT DAA therapy and allograft injury, including biliary complications (BCs) and acute cellular rejection (ACR). Results: A total of 153 cases were enrolled from January 2015 to February 2021. Serum anti-HCV antibody titers were assessed before and after (day 30) LT. Among all recipients, 31/153 (20.3%) had pre-LT DAA therapy (the DAA group) and 122/153 (79.7%) did not undergo pre-LT DAA therapy (the DAA-naïve group). A higher incidence of post-LT BCs was observed in the DAA group (p = 0.028). Compared with the DAA-naïve group, the DAA group had a significantly higher mean level of anti-HCV titer upregulation (p = 0.0024); furthermore, among the recipients with BCs (n = 28) and ACR (n = 41), those in the DAA group exhibited significantly higher mean levels of anti-HCV antibody titer upregulation (p < 0.005). Conclusions: In conclusion, we speculate that the upregulation of anti-HCV antibody titers, which might have been induced via the restoration of HCV-specific immune responses through pre-LT DAA therapy, was associated with post-LT allograft injury. Full article

Background and Objectives: Approximately 5–10% of all patients with metastatic colorectal cancer (mCRC) harbor a BRAF^V600E mutation. These patients exhibit distinct metastatic patterns, poor prognosis, and heterogenous survival outcomes. The findings from the TRIBE study indicated that the administration of FOLFOXIRI plus bevacizumab as first-line treatment extended the median duration of overall survival (OS). In this study, we explored the effects of UGT1A1 polymorphism on the outcomes of irinotecan dose escalation versus FOLFOXIRI plus bevacizumab in patients with BRAF^V600E-mutant mCRC. Materials and Methods: We retrospectively reviewed the medical records of 25 patients who had received a diagnosis of BRAF^V600E-mutant mCRC between October 2015 and August 2022. All patients underwent UGT1A1 genotyping before receiving bevacizumab plus FOLFIRI. The primary end point was progression-free survival (PFS), and secondary endpoints were OS and adverse events (AEs). The two treatment arms were compared in terms of 6-month PFS and 12-month OS. Results: Over a median follow-up duration of 15.0 (interquartile range, 10.0–30.5) months, no significant differences were noted between the treatment arms in severe AEs (SAEs), 6-month PFS, or 12-month OS (all p < 0.05). Regarding AEs, the FOLFIRI plus bevacizumab regimen was associated with a lower incidence of anorexia than was the FOLFOXIRI plus bevacizumab regimen (p = 0.042). Conclusions: Our findings indicate that FOLFIRI plus bevacizumab with irinotecan dose escalation is an effective first-line treatment regimen for patients with BRAF^V600E-mutant mCRC. This regimen leads to acceptable clinical outcomes with manageable AEs. However, the effects on survival and safety outcomes could only be speculated, and further studies are needed because of the sample size, the follow-up for the OS evaluation, and the non-uniformity in all the variables considered in the two groups. Full article

The protein disulfide isomerase (PDI) family is a group of thioredoxin endoplasmic reticulum (ER)-resident enzymes and molecular chaperones that play crucial roles in the correct folding of proteins. PDIs are upregulated in multiple cancer types and are considered a novel target for cancer therapy. In this study, we found that a potent pan-PDI inhibitor, E64FC26, significantly decreased the proliferation of pancreatic ductal adenocarcinoma (PDAC) cells. As expected, E64FC26 treatment increased ER stress and the unfolded protein response (UPR), as evidenced by upregulation of glucose-regulated protein, 78-kDa (GRP78), phosphorylated (p)-PKR-like ER kinase (PERK), and p-eukaryotic initiation factor 2α (eIF2α). Persistent ER stress was found to lead to apoptosis, ferroptosis, and autophagy, all of which are dependent on lysosomal functions. First, there was little cleaved caspase-3 in E64FC26-treated cells according to Western blotting, but a higher dose of E64FC26 was needed to induce caspase activity. Then, E64FC26-induced cell death could be reversed by adding the iron chelator, deferoxamine, and the reactive oxygen species scavengers, ferrostatin-1 and N-acetylcysteine. Furthermore, the autophagosome-specific marker, light chain 3B (LC3B)-II, increased, but the autolysosome marker, sequestosome 1 (SQSTM1)/p62, was not degraded in E64FC26-treated cells. Using the FUW mCherry-LC3 plasmid and acridine orange staining, we also discovered a lower number of acidic vesicles, such as autolysosomes and mature lysosomes, in E64FC26-treated cells. Finally, E64FC26 treatment increased the cathepsin L precursor (pre-CTSL) but decreased mature CTSL expression according to Western blotting, indicating a defective lysosome. These results suggested that the PDI inhibitor, E64FC26, might initially impede proper folding of proteins, and then induce ER stress and disrupt proteostasis, subsequently leading to lysosomal defects. Due to defective lysosomes, the extents of apoptosis and ferroptosis were limited, and fusion with autophagosomes was blocked in E64FC26-treated cells. Blockade of autolysosomal formation further led to the autophagic cell death of PDAC cells. Full article

Due to their diverse and unique physical properties, miktoarm star copolymers (μ-SCPs) have garnered significant attention. In our study, we employed α-monobomoisobutyryl-terminated polydimethylsiloxane (PDMS-Br) to carry out styrenics-assisted atom transfer radical coupling (SA ATRC) in the presence of 4-vinylbenzyl alcohol (VBA) at 0 °C. By achieving high coupling efficiency (χ_c = 0.95), we obtained mid-chain functionalized PDMS-VBA_m-PDMS polymers with benzylic alcohols. Interestingly, matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) analysis revealed the insertion of only two VBA coupling agents (m = 2). Subsequently, the PDMS-VBA₂-PDMS products underwent mid-chain extensions using ε-caprolactone (ε-CL) through ring-opening polymerization (ROP) with an efficient organo-catalyst at 40 °C, resulting in the synthesis of novel (PDMS)₂-μ-(PCL)₂ μ-SCPs. Eventually, novel (PDMS)₂-μ-(PCL)₂ μ-SCPs were obtained. The obtained PDMS-μ-PCL μ-SCPs were further subjected to examination of their solid-state self-assembly through small-angle X-ray scattering (SAXS) experiments. Notably, various nanostructures, including lamellae and hexagonally packed cylinders, were observed with a periodic size of approximately 15 nm. As a result, we successfully developed a simple and effective reaction combination (Є) strategy (i.e., SA ATRC-Є-ROP) for the synthesis of well-defined PDMS-μ-PCL μ-SCPs. This approach may open up new possibilities for fabricating nanostructures from siloxane-based materials. Full article

The co-occurrence of depression and obesity has become a significant public health concern worldwide. Recent studies have shown that metabolic dysfunction, which is commonly observed in obese individuals and is characterized by inflammation, insulin resistance, leptin resistance, and hypertension, is a critical risk factor for depression. This dysfunction may induce structural and functional changes in the brain, ultimately contributing to depression’s development. Given that obesity and depression mutually increase each other’s risk of development by 50–60%, there is a need for effective interventions that address both conditions. The comorbidity of depression with obesity and metabolic dysregulation is thought to be related to chronic low-grade inflammation, characterized by increased circulating levels of pro-inflammatory cytokines and C-reactive protein (CRP). As pharmacotherapy fails in at least 30–40% of cases to adequately treat major depressive disorder, a nutritional approach is emerging as a promising alternative. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are a promising dietary intervention that can reduce inflammatory biomarkers, particularly in patients with high levels of inflammation, including pregnant women with gestational diabetes, patients with type 2 diabetes mellitus, and overweight individuals with major depressive disorder. Further efforts directed at implementing these strategies in clinical practice could contribute to improved outcomes in patients with depression, comorbid obesity, and/or metabolic dysregulation. Full article

A hole array was fabricated via photolithography to wet the bottoms of holes using oxygen plasma. Amide-terminated silane, a water immiscible compound before hydrolysis, was evaporated for deposition on the plasma-treated hole template surface. The silane compound was hydrolyzed along the edges of circular sides of the hole bottom to form a ring of an initiator after halogenation. Poly(methacrylic acid) (PMAA) was grafted from the ring of the initiator to attract Ag clusters (AgCs) as AgC–PMAA hybrid ring (SPHR) arrays via alternate phase transition cycles. The SPHR arrays were modified with a Yersinia pestis antibody (abY) to detect the antigen of Yersinia pestis (agY) for plague diagnosis. The binding of the agY onto the abY-anchored SPHR array resulted in a geometrical change from a ring to a two-humped structure. The reflectance spectra could be used to analyze the AgC attachment and the agY binding onto the abY-anchored SPHR array. The linear range between the wavelength shift and agY concentration from 30 to 270 pg mL⁻¹ was established to obtain the detection limit of ~12.3 pg mL⁻¹. Our proposed method provides a novel pathway to efficiently fabricate a ring array with a scale of less than 100 nm, which demonstrates excellent performance in preclinical trials. Full article

Microglia-associated neuroinflammation is recognized as a critical factor in the pathogenesis of neurodegenerative diseases; however, there is no effective treatment for the blockage of neurodegenerative disease progression. In this study, the effect of nordalbergin, a coumarin isolated from the wood bark of Dalbergia sissoo, on lipopolysaccharide (LPS)-induced inflammatory responses was investigated using murine microglial BV2 cells. Cell viability was assessed using the MTT assay, whereas nitric oxide (NO) production was analyzed using the Griess reagent. Secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) was detected by the ELISA. The expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, mitogen-activated protein kinases (MAPKs) and NLRP3 inflammasome-related proteins was assessed by Western blot. The production of mitochondrial reactive oxygen species (ROS) and intracellular ROS was detected using flow cytometry. Our experimental results indicated that nordalbergin ≤20 µM suppressed NO, IL-6, TNF-α and IL-1β production; decreased iNOS and COX-2 expression; inhibited MAPKs activation; attenuated NLRP3 inflammasome activation; and reduced both intracellular and mitochondrial ROS production by LPS-stimulated BV2 cells in a dose-dependent manner. These results demonstrate that nordalbergin exhibits anti-inflammatory and anti-oxidative activities through inhibiting MAPK signaling pathway, NLRP3 inflammasome activation and ROS production, suggesting that nordalbergin might have the potential to inhibit neurodegenerative disease progression. Full article

This study aimed to investigate the regulatory role of Aldo-keto reductase family 1 member B1 (AKR1B1) in glioma cell proliferation through p38 MAPK activation to control Bcl-2/BAX/caspase-3 apoptosis signaling. AKR1B1 expression was quantified in normal human astrocytes, glioblastoma multiforme (GBM) cell lines, and normal tissues by using quantitative real-time polymerase chain reaction. The effects of AKR1B1 overexpression or knockdown and those of AKR1B1-induced p38 MAPK phosphorylation and a p38 MAPK inhibitor (SB203580) on glioma cell proliferation were determined using an MTT assay and Western blot, respectively. Furthermore, the AKR1B1 effect on BAX and Bcl-2 expression was examined in real-time by Western blot. A luminescence detection reagent was also utilized to identify the effect of AKR1B1 on caspase-3/7 activity. The early and late stages of AKR1B1-induced apoptosis were assessed by performing Annexin V-FITC/PI double-staining assays. AKR1B1 expression was significantly downregulated in glioma tissues and GBM cell lines (T98G and 8401). Glioma cell proliferation was inhibited by AKR1B1 overexpression but was slightly increased by AKR1B1 knockdown. Additionally, AKR1B1-induced p38 MAPK phosphorylation and SB203580 reversed AKR1B1′s inhibitory effect on glioma cell proliferation. AKR1B1 overexpression also inhibited Bcl-2 expression but increased BAX expression, whereas treatment with SB203580 reversed this phenomenon. Furthermore, AKR1B1 induced caspase-3/7 activity. The induction of early and late apoptosis by AKR1B1 was confirmed using an Annexin V-FITC/PI double-staining assay. In conclusion, AKR1B1 regulated glioma cell proliferation through the involvement of p38 MAPK-induced BAX/Bcl-2/caspase-3 apoptosis signaling. Therefore, AKR1B1 may serve as a new therapeutic target for glioma therapy development. Full article