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BackgroundDaily and on-demand pre-exposure prophylaxis (PrEP) has been well demonstrated to effectively prevent HIV acquisition for men who have sex with men (MSM). More than half of the MSM PrEP users in Taiwan prefer on-demand PrEP; however, on-demand PrEP involves a complicated dosing regimen because it requires precoital and postcoital dosing and sex events are hard to anticipate. Although there are a growing number of mobile apps designed to improve access to HIV prevention services and HIV medication adherence, few mobile apps focus on adherence to PrEP or are designed to accommodate a complicated, on-demand PrEP dosing schedule. ObjectiveThe aim of this project is to evaluate the usability of a newly developed mobile app (UPrEPU) to assist MSM PrEP users to self-monitor their adherence to either daily or on-demand PrEP using a user-centered scheme. MethodsThis research will be conducted in 2 phases: app development and usability study. In the app development phase, we will first conduct formative research with end users and stakeholders through in-depth interviews; the results will provide PrEP users’ and PrEP navigators’ personas as material used in the app conceptualization stage. PrEP navigators are individuals in the health care system that help HIV-negative individuals who need assistance in accessing PrEP care. A low-fidelity prototype of the app feature will be formatted by applying a participatory design approach to engage PrEP users, designers, and app developers in the design process of the app. Then, a high-fidelity prototype of the app will be developed for the usability study and refined iteratively by the multidisciplinary team and new internal testers. Internal testers include the research team consisting of experts in public health, infectious disease, and industrial design and a close network of the research team that is taking PrEP. In the usability study phase, we will enroll 70 MSM PrEP users and follow them up for 4 months. Usability, feasibility, and effectiveness of adherence monitoring will be evaluated. ResultsRefinement of the UPrEPU app is currently ongoing. The usability study commenced in May 2020. ConclusionsThe UPrEPU app is one of the first apps designed to help MSM PrEP users to self-manage their PrEP schedule better regardless of dosing modes. With a design-thinking approach and adapting to the cultural context in Taiwan’s MSM population, this novel app will have substantial potential to be acceptable and feasible and contribute to the reduction of new HIV infections. Trial RegistrationClinicalTrials.gov NCT04248790; https://clinicaltrials.gov/ct2/show/NCT04248790 International Registered Report Identifier (IRRID)PRR1-10.2196/20360

Abstract This study aimed to investigate the effects of tea green leafhopper damage on the sensory quality and metabolite composition of Oriental Beauty by using tea leaves from different varieties of tea plants and processing factories. The results indicated that tea green leafhopper damage could reduce bitterness and increase the level of fruity aroma, which was related to the content changes of catechin components and alcohol substances. Furthermore, the tea green leafhopper salivary treatment experiment revealed that the decrease of catechin content and increase of theaflavin content were mainly influenced by the action of saliva and mechanical injury, and changes in volatile components such as linalool oxidation were responsible for the alteration in aroma. These findings provide a theoretical reference for the aroma formation and quality improvement of Oriental Beauty.

In response to public health emergencies, many regions have requisitioned daily travel hotels as temporary quarantine places. However, few previous studies examine this policy and reflect on the rationality of urban spatial resource allocation and utilization in terms of comfort during quarantine. This study uses a hybrid multi-attribute decision-making model, based on the collection of 438 pieces of evaluation data about the comfort of isolation hotels in Guangzhou, to build an evaluation framework for the comfort of the quarantine environment. Then, this study uses the ANP-V technique to complete the performance evaluation of selected cases and combines the epidemic spread data in Guangzhou to explore the rationality and improvement strategies of local government epidemic prevention resource allocation and utilization. Based on the results of this study, local decision-makers can optimize the allocation of future epidemic prevention resources and minimize the negative impact on personal health during the emergency period.

Abstract Background There is an urgent clinical need for developing novel immunoprophylaxis and immunotherapy strategies against Staphylococcus aureus (S. aureus). In our previous work, immunization with a tetra-branched multiple antigenic peptide, named MAP2-3 that mimics lipoteichoic acid, a cell wall component of S. aureus, successfully induced a humoral immune response and protected BALB/c mice against S. aureus systemic infection. In this study, we further investigated whether vaccination with MAP2-3 can elicit immunologic memory. Methods BALB/c mice were immunized with MAP2-3 five times. After one month of the last vaccination, mice were challenged with heat-killed S. aureus via intraperitoneal injection. After a 7-day inoculation, the percentage of plasma cells, memory B cells, effector memory T cells, and follicular helper T cells were detected by flow cytometry. The levels of IL-6, IL-21, IL-2, and IFN-γ were measured by real-time PCR and ELISA. Flow cytometry results were compared by using one-way ANOVA or Mann-Whitney test, real-time PCR results were compared by using one-way ANOVA, and ELISA results were compared by using one-way ANOVA or student’s t-test. Results The percentage of plasma cells and memory B cells in the spleen and bone marrow from the MAP2-3 immunized mice was significantly higher than that from the control mice. The percentage of effector memory T cells in spleens and lymphoid nodes as well as follicular helper T cells in spleens from the MAP2-3 immunized mice were also higher. Moreover, the levels of IL-6 and IL-21, two critical cytokines for the development of memory B cells, were significantly higher in the isolated splenocytes from immunized mice after lipoteichoic acid stimulation. Conclusions Immunization with MAP2-3 can efficiently induce memory B cells and memory T cells.

Sungrazing comets, known for their proximity to the Sun, are traditionally classified into broad groups like Kreutz, Marsden, Kracht, Meyer, and non-group comets. While existing methods successfully categorize these groups, finer distinctions within the Kreutz subgroup remain a challenge. In this study, we introduce an automated classification technique using the densitybased spatial clustering of applications with noise (DBSCAN) algorithm to categorize sungrazing comets. Our method extends traditional classifications by finely categorizing the Kreutz subgroup into four distinct subgroups based on a comprehensive range of orbital parameters, providing critical insights into the origins and dynamics of these comets. Corroborative analyses validate the accuracy and effectiveness of our method, offering a more efficient framework for understanding the categorization of sungrazing comets.

Among civilization diseases, the number of individuals suffering from type 2 diabetes (T2DM) is expected to increase to more than a billion in less than 20 years, which is associated with, e.g., populational aging, poor diet, sedentary lifestyle, genetic predispositions, and immunological factors. T2DM affects many organs and is characterized by insulin resistance, high glucose levels, and adipocyte dysfunction, which are related to senescence. Although this type of cellular aging has beneficial biological functions, it can also act unfavorable since senescent adipocytes resist apoptosis, enhance cytokine secretion, downregulate cell identity genes, and acquire the senescence-associated secretory phenotype that renders a more oxidative environment. Opposing T2DM is possible via a wide variety of senotherapies, including senolytics and senomorphics; nevertheless, further research is advised to expand therapeutic possibilities and benefits. Consequences that ought to be deeply researched include secretory phenotype, chronic inflammation, increasing insulin resistance, as well as impairment of adipogenesis and functioning of adipocyte cells. Herein, despite reviewing T2DM and fat tissue senescence, we summarized the latest adipocyte-related anti-diabetes solutions and suggested further research directions.

Abstract Background Osimertinib is regarded as a promising third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for advanced non-squamous non-small cell lung cancer (NSCLC) patients who developed T790M. However the adverse effects, primarily fatigue, remain an overwhelming deficiency of Osimertinib, hindering it from achieving adequate clinical efficacy for such NSCLC. Ganoderma lucidum has been used for thousands of years in China to combat fatigue, while Ganoderma Lucidum spores powder (GLSP) is the main active ingredient. The aim of this study is to investigate whether GLSP is sufficiently effective and safe in improving fatigue and synergizing with Osimertinib in non-squamous NSCLC patients with EGFR mutant. Method/design A total of 140 participants will be randomly assigned to receive either de-walled GSLP or placebo for a duration of 56 days. The primary outcome measure is the fatigue score associated with EGFR-TKI adverse reactions at week 8, evaluated by the Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Patients (QLQ-C30). Secondary outcomes include evaluation of treatment effectiveness, assessment of quality of life (QoL), and exploration of immune indicators and gut microbiota relationships. Following enrollment, visits are scheduled biweekly until week 12. Trial registration China Clinical Trial Registry ChiCTR2300072786. Registrated on June 25, 2023.

Abstract Biliverdin, a bile pigment hydrolyzed from heme by heme oxygenase (HO), serves multiple functions in the human body, including antioxidant, anti-inflammatory, and immune response inhibitory activities. Biliverdin has great potential as a clinical drug; however, no economic and efficient production method is available currently. Therefore, the production of biliverdin by the biotransformation of exogenous heme using recombinant HO-expressing yeast cells was studied in this research. First, the heme oxygenase-1 gene (HO1) encoding the inducible plastidic isozyme from Arabidopsis thaliana, with the plastid transport peptide sequence removed, was recombined into Pichia pastoris GS115 cells. This resulted in the construction of a recombinant P. pastoris GS115-HO1 strain that expressed active HO1 in the cytoplasm. After that, the concentration of the inducer methanol, the induction culture time, the pH of the medium, and the concentration of sorbitol supplied in the medium were optimized, resulting in a significant improvement in the yield of HO1. Subsequently, the whole cells of GS115-HO1 were employed as catalysts to convert heme chloride (hemin) into biliverdin. The results showed that the yield of biliverdin was 132 mg/L when hemin was added to the culture of GS115-HO1 and incubated for 4 h at 30 °C. The findings of this study have laid a good foundation for future applications of this method for the economical production of biliverdin. Graphical Abstract

Melanoma is rare in Taiwan. Asian melanoma is distinct from Western melanoma because acral and mucosal melanoma accounts for the majority of melanoma cases, leading to distinct tumor behaviors and genetic profiling. With consideration of the clinical guidelines in Western countries, Taiwanese experts developed a local clinical practice consensus guideline. This consensus includes diagnosis, staging, and surgical and systemic treatment, based only on clinical evidence, local epidemiology, and available resources evaluated by experts in Taiwan. This consensus emphasizes the importance of surgical management, particularly for sentinel lymph node biopsies. In addition, molecular testing for BRAF is mandatory for patients before systemic treatment. Furthermore, immunotherapy and targeted therapy are prioritized for systemic treatment. This consensus aimed to assist clinicians in Taiwan in diagnosing and treating patients according to available evidence.

Abstract Background Established associated factors for DDH include female sex, breech presentation, family history, congenital malformations, oligohydramnios, and maternal hyperthyroidism. However, evidence for environmental factors that may contribute to DDH is limited and inconsistent. Methods A systematic review of medical literature was conducted to collect data on environmental factors, including latitude, longitude, average yearly precipitation, average yearly temperature, minimum monthly temperature, and maximum monthly temperature, from all institutions that published articles on DDH. Univariate linear regression analysis was used to examine the correlation between environmental factors and DDH incidence, while multiple regression analysis was conducted to identify significant associated factors for DDH incidence. Results Data from a total of 93 unique manuscripts were analyzed, revealing a significant negative correlation between DDH incidence and temperature, including average yearly temperature (r = -0.27, p = 0.008), minimum monthly temperature (r = -0.28, p = 0.006), and maximum monthly temperature (r = -0.23, p = 0.029). Additionally, there was a significant positive correlation between DDH incidence and latitude (r = 0.27, p = 0.009), and a significant negative correlation between DDH incidence and average yearly precipitation (r = -0.29, p = 0.004). In the final multiple regression analysis, temperature, including average yearly temperature, minimum monthly temperature, and maximum monthly temperature, were identified as significant associated factors for DDH incidence. Conclusion The findings of this study suggest an association between cold weather and DDH incidence. Further research should explore the link between cold weather and DDH incidence, offering insights into potential interventions for cold climates.

Abstract Background Plasmodium malariae was always neglected compared with P. falciparum and P. vivax. In the present study, we aimed to describe the epidemiology of reported cases infected with P. malariae in the past decade to raise awareness of the potential threat of this malaria parasite in China. Methods Individual data of malaria cases infected with P. malariae reported in China in the past decade were collected via the China Information System for Disease Control and Prevention and Parasitic Diseases Information Reporting Management System, to explore their epidemiological characteristics. Pearson Chi-square tests or Fisher’s Exact Test was used in the statistical analysis. Results From 2013 to 2022, a total of 581 P. malariae cases were reported in China, and mainly concentrated in 20–59 years old group (P

Increasing wheat yield is a long-term goal for wheat breeders around the world. Exploiting elite genetic resources and dissecting the genetic basis of important agronomic traits in wheat are the necessary methods for high-yield wheat breeding. This study evaluated nine crucial agronomic traits found in a natural population of 156 wheat varieties and 77 landraces from Sichuan, China in seven environments over two years. The results of this investigation of agronomic traits showed that the landraces had more tillers and higher kernel numbers per spike (KNS), while the breeding varieties had higher thousand-kernel weight (TKW) and kernel weight per spike (KWS). The generalized heritability (H2) values of the nine agronomic traits varied from 0.74 to 0.95. Structure analysis suggested that the natural population could be divided into three groups using 43 198 single nucleotide polymorphism (SNP) markers from the wheat 55K SNP chip. A total of 67 quantitative trait loci (QTLs) were identified by the genome-wide association study (GWAS) analysis based on the Q+K method of a mixed linear model. Three important QTLs were analyzed in this study. Four haplotypes of QFTN.sicau-7BL.1 for fertile tillers number (FTN), three haplotypes of QKNS.sicau-1AL.2 for KNS, and four haplotypes of QTKW.sicau-3BS.1 for TKW were detected. FTN-Hap2, KNS-Hap1, and TKW-Hap2 were excellent haplotypes for each QTL based on the yield performance of 42 varieties in regional trials from 2002 to 2013. The varieties with all three haplotypes showed the highest yield compared to those with either two haplotypes or one haplotype. In addition, the KASP-AX-108866053 marker of QTL QKNS.sicau-1AL.2 was successfully distinguished between three haplotypes (or alleles) in 63 varieties based on the number of kernels per spike in regional trials between 2018 and 2021. These genetic loci and reliable makers can be applied in marker-assisted selection or map-based gene cloning for the genetic improvement of wheat yield.