Fabrication of Large-Area Mullite–Cordierite Composite Substrates for Semiconductor Probe Cards and Enhancement of Their Reliability

This work aims to fabricate a large-area ceramic substrate for the application of probe cards. Mullite (M) and cordierite (C), which both have a low thermal expansion coefficient, excellent resistance to thermal shock, and high durability, were selected as starting powders. The mullite–cordierite composites were produced through different composition ratios of starting powders (M:C = 100:0, M:C = 90:10, M:C = 70:30, M:C = 50:50, M:C = 30:70, and M:C = 0:100). The effects of composition ratio and sintering temperature on the density, porosity, thermal expansion coefficient, and flexural strength of the mullite–cordierite composite pellets were investigated. The results showed that the mullite–cordierite composite pellet containing 70 wt% mullite and 30 wt% cordierite sintered at 1350 °C performed exceptionally well. Based on these findings, a large-area mullite–cordierite composite substrate with a diameter of 320 mm for use in semiconductor probe cards was successfully fabricated. Additionally, the changes in sheet resistance and flexural strength were measured to determine the effect of the environmental tests on the large-area substrate such as damp heat and thermal shock. The results indicated that the mullite–cordierite composite substrate was extremely reliable and durable.     

Intralymphatic Histiocytosis Associated with Osteoarthritis: A Case Report

Intralymphatic histiocytosis (ILH) is a rare cutaneous condition with uncertain pathogenesis. It is characterized by dilated lymphatic vessels that contain histiocytes within their lumina. Although the etiology of ILH remains unknown, it has been associated with various inflammatory and neoplastic diseases, such as rheumatoid arthritis (RA), reaction to metal joint implants and Merkel cell carcinoma, breast cancer and colon cancer. An 83-year-old female presented with an erythematous patch on the left forearm that had appeared six months previous. She had suffered from osteoarthritis (OA) and the cutaneous lesion was located in the vicinity of the affected joint. Skin biopsy from the lesion showed dilated dermal vessels and some ectatic vessels that contained many mononuclear histiocytes. Based on the clinical and histopathological findings, we diagnosed her with ILH with OA. Two sessions of intralesional triamcinolone acetonide injection (5 mg/ml) were administered to treat the skin lesion, which gradually improved over a period of a few months. We here report a rare case of ILH associated with degenerative OA.     

Metabolic Dysfunction-Associated Fatty Liver Disease Predicts Long-term Mortality and Cardiovascular Disease

Background/AimsWe investigated the effect of metabolic dysfunction-associated fatty liver disease (MAFLD) on future mortality and cardiovascular disease (CVD) using a prospective community-based cohort study.MethodsIndividuals from two community-based cohorts who were 40 to 70 years old were prospectively followed for 16 years. MAFLD was defined as a high fatty liver index (FLI ≥60) plus one of the following conditions overweight/obesity (body mass index ≥23 kg/m²), type 2 diabetes mellitus, or ≥2 metabolic risk abnormalities. Nonalcoholic fatty liver disease (NAFLD) was defined as FLI ≥60 without any secondary cause of hepatic steatosis.ResultsAmong 8,919 subjects (age 52.2±8.9 years, 47.7% of males), 1,509 (16.9%) had MAFLD. During the median follow-up of 15.7 years, MAFLD independently predicted overall mortality after adjustment for confounders (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.05 to 1.69) but NAFLD did not (HR, 1.20; 95% CI, 0.94 to 1.53). MAFLD also predicted CVD after adjustment for age, sex, and body mass index (HR, 1.35; 95% CI, 1.13 to 1.62), which lost its statistical significance by further adjustments. Stratified analysis indicated that metabolic dysfunction contributed to mortality (HR, 1.51; 95% CI, 1.21 to 1.89) and CVD (HR, 1.27; 95% CI, 1.02 to 1.59). Among metabolic dysfunctions used for defining MAFLD, type 2 diabetes mellitus in MAFLD increased the risk of both mortality (HR, 2.07; 95% CI, 1.52 to 2.81) and CVD (HR, 1.42; 95% CI, 1.09 to 1.85).ConclusionsMAFLD independently increased overall mortality. Heterogeneity in mortality and CVD risk of subjects with MAFLD may be determined by the accompanying metabolic dysfunctions.     

Safety,tolerability, and pharmacokinetics of single and multiple topical ophthalmic administration of imatinib mesylate in healthy subjects

For the long‐term efficacy of dry eye disease treatment, relieving underlying inflammation is necessary. Imatinib mesylate is a novel ophthalmic formulation of imatinib mesylate, which is expected to alleviate inflammation by inhibiting the discoidin domain receptor 1 activity. This study aims to evaluate the safety and pharmacokinetics of imatinib mesylate in healthy subjects. A randomized, double‐blind, placebo‐controlled study was conducted. In a single ascending dose, 16 subjects received a single eye drop of imatinib mesylate 0.1%, 0.3%, or matching placebo. In the multiple ascending dose (MAD), subjects received multiple eye drops of imatinib mesylate 0.1%, 0.3%, or matching placebo once daily for 7 days. Safety and tolerability were assessed by ophthalmic examination, including the visual analog scale (VAS) to monitor the burning sensation in the eyes. A total of four treatment‐emergent adverse events (TEAEs) occurred during the study. All TEAEs were mildly severe with no serious cases. VAS results in the 0.1% MAD group exhibited highest score of two points, whereas it was less than one point in others. Insignificant difference between the imatinib mesylate and placebo groups in the VAS results was seen. After a single dose administration of imatinib mesylate 0.1%, all plasma concentrations were below the lower limit of quantification. The peak plasma concentrations of imatinib were less than 0.54 µg/L in all groups. In conclusion, a single and multiple topical ophthalmic administration of imatinib mesylate was well‐tolerated in healthy subjects. Because there was minimal systemic exposure to imatinib, the adverse effect in the body seems to be insignificant.