Improving communication and promoting social inclusion for hearing-impaired users: Usability evaluation and design recommendations for assistive mobile applications.

This study examines the usability of communication-assistive applications for hearing-impaired users, with a focus on enhancing user experience and promoting social inclusion. Although such applications have been developed and evaluated previously, interface designs that consider the intimacy needs of hearing-impaired users remain under-explored. We performed a comprehensive usability evaluation employing a mixed-method approach, which involved hearing-impaired individuals as well as field experts. The findings revealed areas for improvement in the design, validated the feasibility of implementing these applications, and emphasized the importance of incorporating the unique needs and preferences of hearing-impaired users. Furthermore, this paper discusses the importance of introducing guidelines and evaluation scales for the "Design for Emotion and Life Knowledge" levels to facilitate smooth and effective human-computer interactions. Such measures will promote the development of intelligent assistive technologies that reflect the qualitative needs of people with disabilities and contribute to social rights for hearing-impaired users. With the growing demands of artificial-intelligence-powered assistive technologies, the inclusion of individuals with disabilities in the design and research process is anticipated to increase. In future, studies should be conducted to blend the culturally shared experiences and emotional bonds expressed by users (having mild-to-severe hearing impairment) with the design and development process of assistive devices or services.

Discovery of a peripheral 5HT2A antagonist as a clinical candidate for metabolic dysfunction-associated steatohepatitis.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is currently the leading cause of chronic liver disease worldwide. Metabolic Dysfunction-Associated Steatohepatitis (MASH), an advanced form of MASLD, can progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Based on recent findings by our team that liver 5HT2A knockout male mice suppressed steatosis and reduced fibrosis-related gene expression, we developed a peripheral 5HT2A antagonist, compound 11c for MASH. It shows good in vitro activity, stability, and in vivo pharmacokinetics (PK) in rats and dogs. Compound 11c also shows good in vivo efficacy in a diet-induced obesity (DIO) male mice model and in a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) male mice model, effectively improving histologic features of MASH and fibrosis. According to the tissue distribution study using [14C]-labeled 11c, the compound was determined to be a peripheral 5HT2A antagonist. Collectively, first-in-class compound 11c shows promise as a therapeutic agent for the treatment of MASLD and MASH.

Synthesis and biological evaluation of xanthine derivatives with phenacyl group as tryptophan hydroxylase 1 (TPH1) inhibitors for obesity and fatty liver disease.

Tryptophan hydroxylase 1 (TPH1) has emerged as a target for the treatment of metabolic diseases including obesity and fatty liver disease. A series of xanthine derivatives were synthesized and evaluated for their TPH1 inhibition. Among the synthesized compounds, compound 40 showed good in vitro activity and liver microsomal stability. Docking studies revealed that compound 40 showed better binding to TPH1 via key intermolecular interactions involving the xanthine scaffold, imidazo-thiazolyl ring, and hydroxyl-containing phenacyl moiety. In addition, compound 40 effectively suppressed the adipocyte differentiation of 3 T3-L1 cells.

Optical and Electrical Characterization of Visible Parylene Films.

Poly-dichloro-para-xylylene (parylene-C) film is formed through a chemical vapor deposition process, where monomeric gases are polymerized on the target surface at room temperature and are used as transparent insulating coating films. The thin parylene-C films exhibit uniform conformal layers even when deposited on substrates or surfaces with fine cracks, structures, and bumps. However, the film is highly transparent in the visible range (transmittance > 90%); thus, it is difficult to visually identify, inspect the coating process and check for any defects when used as an insulation film. Some reports have demonstrated the deposition of visible (hazy) parylene films through the control of the vaporization or pyrolysis of the parylene-C powder and sublimed dimers, respectively. Even though these films have been applied as device substrates and light extraction layers in organic light-emitting diodes (OLEDs), their optical and electrical characteristics have not been extensively explored, especially for their applications as insulation coatings. In this study, the characteristics of visible parylene films produced by tuning the ratio of dimer to monomer gases via the adjustments of the pyrolysis temperature are analyzed with electrical and optical methods. Parylene-C films deposited within the pyrolysis temperature of 400−700 °C exhibited a haze range of 10−90%. A relative reflectance of 18.8% at 550 nm of the visible light region was achieved in the visible parylene film deposited with a pyrolysis temperature of 400 °C. Resistivity in the order of 1010 Ω cm was achieved for the visible parylene films measured with the transmission line measurement (TLM) method. The films can be applied in advanced insulation coatings for various optical systems and electronic devices.

The Effect of Reactive Sputtering on the Microstructure of Parylene-C.

Sputtering technique involves the use of plasma that locally heats surfaces of substrates during the deposition of atoms or molecules. This modifies the microstructure by increasing crystallinity and the adhesive properties of the substrate. In this study, the effect of sputtering on the microstructure of parylene-C was investigated in an aluminum nitride (AlN)-rich plasma environment. The sputtering process was carried out for 30, 45, 90 and 120 min on a 5 µm thick parylene-C film. Topography and morphology analyses were conducted on the parylene-C/AlN bilayers. Based on the experimental data, the results showed that the crystallinity of parylene-C/AlN bilayers was increased after 30 min of sputtering and remained saturated for 120 min. A scratch-resistance test conducted on the bilayers depicted that a higher force is required to delaminate the bilayers on top of the substrate. Thus, the adhesion properties of parylene-C/AlN bilayers were improved on glass substrate by about 17% during the variation of sputtering time.

Identification of New Non-BBB Permeable Tryptophan Hydroxylase Inhibitors for Treating Obesity and Fatty Liver Disease.

Serotonin (5-hydroxytryptophan) is a hormone that regulates emotions in the central nervous system. However, serotonin in the peripheral system is associated with obesity and fatty liver disease. Because serotonin cannot cross the blood-brain barrier (BBB), we focused on identifying new tryptophan hydroxylase type I (TPH1) inhibitors that act only in peripheral tissues for treating obesity and fatty liver disease without affecting the central nervous system. Structural optimization inspired by para-chlorophenylalanine (pCPA) resulted in the identification of a series of oxyphenylalanine and heterocyclic phenylalanine derivatives as TPH1 inhibitors. Among these compounds, compound 18i with an IC50 value of 37 nM was the most active in vitro. Additionally, compound 18i showed good liver microsomal stability and did not significantly inhibit CYP and Herg. Furthermore, this TPH1 inhibitor was able to actively interact with the peripheral system without penetrating the BBB. Compound 18i and its prodrug reduced body weight gain in mammals and decreased in vivo fat accumulation.

Synthesis and biological evaluation of tyrosine derivatives as peripheral 5HT2A receptor antagonists for nonalcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD), attributed to excessive fat accumulation in the liver, is reportedly prevalent worldwide. NAFLD is one of the leading causes of chronic liver disease, including non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatic cellular carcinoma (HCC). The peripheral roles of serotonin (5-hydroxytryptamine, 5HT) were found to regulate hepatic lipid metabolism. Among serotonin receptor subtypes, 5HT2A receptor is known to regulate hepatic lipid metabolism. Hepatic lipid accumulation and hepatic triglyceride (TG) were reduced in liver-specific 5HT2A receptor knockout (5HT2A receptor LKO) mice upon high-fat diet (HFD) feeding. In the present study, we explored a series of new peripherally acting 5HT2A receptor antagonists. Compound 14a displayed good in vitro activity, with an IC50 value of 0.17 nM. Compound 14a exhibited good microsomal stability, no significant CYP and hERG inhibition, and 5HT receptor subtype selectivity. The brain-to-plasma ratio of 14a was below the lower limit of quantification, indicating limited blood-brain barrier (BBB) penetration. HFD-fed 14a treated mice showed decreased liver steatosis and lobular inflammation. These results demonstrate the potential of newly synthesized peripheral 5HT2A receptor antagonists for treating NAFLD.

Peripheral Selective Oxadiazolylphenyl Alanine Derivatives as Tryptophan Hydroxylase 1 Inhibitors for Obesity and Fatty Liver Disease.

Tryptophan hydroxylase 1 (TPH1) has been recently suggested as a promising therapeutic target for treating obesity and fatty liver disease. A new series of 1,2,4-oxadiazolylphenyl alanine derivatives were identified as TPH1 inhibitors. Among them, compound 23a was the most active in vitro, with an IC50 (half-maximal inhibitory concentration) value of 42 nM, showed good liver microsomal stability, and showed no significant inhibition of CYP and hERG. Compound 23a inhibited TPH1 in the peripheral tissue with limited BBB penetration. In high-fat diet-fed mice, 23a reduced body weight gain, body fat, and hepatic lipid accumulation. Also, 23a improved glucose intolerance and energy expenditure. Taken together, compound 23a shows promise as a therapeutic agent for the treatment of obesity and fatty liver diseases.

Outcoupling efficiency enhancement of a bottom-emitting OLED with a visible parylene film.

We have investigated an effective and a single-step chemical vapor deposition (CVD) method to achieve conformal visible poly-dichloro-para-xylylene (parylene C) film for light extraction enhancement in bottom-emitting organic light-emitting diodes (OLEDs) at room temperature. We report that sublimed parylene dimers pyrolyzed between 400 °C and 500 °C resulted in visible parylene films with tunable transmittance and haze, exhibiting light scattering properties due to the formation of uniformly distributed dimer crystals. We achieved a novel conformal visible parylene film with total transmittance and high haze of 79.5% and 93.6%, respectively. It is observed that the outcoupling efficiency of the OLEDs employing the visible parylene film is enhanced up to 45.8%. Additionally, the OLED with the visible parylene light extraction film shows limited angle-dependency of emission spectrum over viewing angles. The single-step room temperature fabrication process of this conformal outcoupling film paves the way to achieving commercial high-performance OLEDs.

Design, Synthesis, and Biological Evaluation of New Peripheral 5HT2A Antagonists for Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent worldwide, causing serious liver complications, including nonalcoholic steatohepatitis. Recent findings suggest that peripheral serotonin (5-hydroxytryptamine, 5HT) regulates energy homeostasis, including hepatic lipid metabolism. More specifically, liver-specific 5HT2A knockout mice exhibit alleviated hepatic lipid accumulation and hepatic steatosis. Here, structural modifications of pimavanserin (CNS drug), a 5HT2A antagonist approved for Parkinson's disease, led us to synthesize new peripherally acting 5HT2A antagonists. Among the synthesized compounds, compound 14a showed good in vitro activity, good liver microsomal stability, 5HT subtype selectivity, and no significant inhibition of CYP and hERG. The in vitro and in vivo blood-brain barrier permeability study proved that 14a acts peripherally. Compound 14a decreased the liver weight and hepatic lipid accumulation in high-fat-diet-induced obesity mice. Our study suggests new therapeutic possibilities for peripheral 5HT2A antagonists in NAFLD.