A novel therapeutic multiepitope vaccine based on oncoprotein E6 and E7 of HPV 16 and 18: An in silico approach.

Introduction: The current vaccine strategies to prevent cervical cancer are effective only for individuals unexposed to HPV, lacking therapeutic effects against pre-existing infections. Multiepitope vaccines, using an immunoinformatic approach, are promising against tumors and viral infections because of their high specificity, safety, and stability, as well as the cheap cost of development. Methods: This study employed computer-based immunoinformatic analysis to design therapeutic multiepitope vaccines against cervical cancer using oncoproteins E6 and E7 of HPV 16 and 18. Several immunoinformatic tools were applied to analyze potential vaccine constructs capable of stimulating immune responses against both oncoproteins. Results: The constructed vaccine exhibited antigenic, immunogenic, nonallergenic, nontoxic, stable, and soluble characteristics. Additionally, it effectively interacted with TLR2 and TLR4, showing high binding capacity. Computational analysis indicated the vaccine could induce immune responses through the elevation of cytokine levels after the third injection, antibody production, activation of memory B and T cells, and promotion of increased dendritic cell counts. Conclusion: The novel multiepitope vaccine based on E6 and E7 presented as a promising candidate for combating HPV infections and associated cervical cancer. Further in vitro and in vivo studies were essential to validate the efficacy and safety of the vaccine.

The Art of Bioimmunogenomics (BIGs) 5.0 in CAR-T Cell Therapy for Lymphoma Management.

Purpose: Lymphoma, the most predominant neoplastic disorder, is divided into Hodgkin and Non-Hodgkin Lymphoma classifications. Immunotherapeutic modalities have emerged as essential methodologies in combating lymphoid malignancies. Chimeric Antigen Receptor (CAR) T cells exhibit promising responses in chemotherapy-resistant B-cell non-Hodgkin lymphoma cases. Methods: This comprehensive review delineates the advancement of CAR-T cell therapy as an immunotherapeutic instrument, the selection of lymphoma antigens for CAR-T cell targeting, and the conceptualization, synthesis, and deployment of CAR-T cells. Furthermore, it encompasses the advantages and disadvantages of CAR-T cell therapy and the prospective horizons of CAR-T cells from a computational research perspective. In order to improve the design and functionality of artificial CARs, there is a need for TCR recognition investigation, followed by the implementation of a quality surveillance methodology. Results: Various lymphoma antigens are amenable to CAR-T cell targeting, such as CD19, CD20, CD22, CD30, the kappa light chain, and ROR1. A notable merit of CAR-T cell therapy is the augmentation of the immune system's capacity to generate tumoricidal activity in patients exhibiting chemotherapy-resistant lymphoma. Nevertheless, it also introduces manufacturing impediments that are laborious, technologically demanding, and financially burdensome. Physical, physicochemical, and physiological limitations further exacerbate the challenge of treating solid neoplasms with CAR-T cells. Conclusion: While the efficacy and safety of CAR-T cell immunotherapy remain subjects of fervent investigation, the promise of this cutting-edge technology offers valuable insights for the future evolution of lymphoma treatment management approaches. Moreover, CAR-T cell therapies potentially benefit patients, motivating regulatory bodies to foster international collaboration.

Novel prophylactic and therapeutic multi-epitope vaccine based on Ag85A, Ag85B, ESAT-6, and CFP-10 of Mycobacterium tuberculosis using an immunoinformatics approach.

BACKGROUND: Current tuberculosis (TB) control strategies face limitations, such as low antibiotic treatment compliance and a rise in multidrug resistance. Furthermore, the lack of a safe and effective vaccine compounds these challenges. The limited efficacy of existing vaccines against TB underscores the urgency for innovative strategies, such as immunoinformatics. Consequently, this study aimed to design a targeted multi-epitope vaccine against TB infection utilizing an immunoinformatics approach. METHODS: The multi-epitope vaccine targeted Ag85A, Ag85B, ESAT-6, and CFP-10 proteins. The design adopted various immunoinformatics tools for cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and linear B lymphocyte (LBL) epitope prediction, the assessment of vaccine characteristics, structure modeling, population coverage analysis, disulfide engineering, solubility prediction, molecular docking/dynamics with toll-like receptors (TLRs), codon optimization/cloning, and immune simulation. RESULTS: The multi-epitope vaccine, which was assembled using 12 CTL, 25 HTL, and 21 LBL epitopes associated with CpG adjuvants, showed promising characteristics. The immunoinformatics analysis confirmed the antigenicity, immunogenicity, and lack of allergenicity. Physicochemical evaluations indicated that the proteins were stable, thermostable, hydrophilic, and highly soluble. Docking simulations suggested high-affinity binding to TLRs, including TLR2, TLR4, and TLR9. In silico immune simulation predicted strong T cell (cytokine release) and B cell (immunoglobulin release) responses. CONCLUSION: This immunoinformatics-designed multi-epitope vaccine targeting Ag85A, Ag85B, ESAT-6, and CFP-10 proteins showed promising characteristics in terms of stability, immunogenicity, antigenicity, solubility, and predicted induction of humoral and adaptive immune responses. This suggests its potential as a prophylactic and therapeutic vaccine against TB.

Immunoinformatics approach for design novel multi-epitope prophylactic and therapeutic vaccine based on capsid proteins L1 and L2 and oncoproteins E6 and E7 of human papillomavirus 16 and human papillomavirus 18 against cervical cancer.

BACKGROUND: This study aimed to identify the optimal protein construction for designing a multi-epitope vaccine with both prophylactic and therapeutic effects against cervical cancer, utilizing an immunoinformatics approach. The construction process involved using capsid epitopes L1 and L2, as well as oncoproteins E5, E6, and E7 from human papillomavirus (HPV) types 16 and 18. METHODS: An experimental in silico analysis with an immunoinformatics approach was used to develop 2 multi-epitope vaccine constructs (A and B). Further analysis was then conducted to compare the constructs and select the one with the highest potential against cervical cancer. RESULTS: This study produced 2 antigenic, non-allergenic, and nontoxic multi-epitope vaccine constructs (A and B), which exhibited the ideal physicochemical properties for a vaccine. Further analysis revealed that construct B effectively induced both cellular and humoral immune responses. CONCLUSION: The multi-epitope vaccine construct B for HPV 16 and 18, designed for both prophylactic and therapeutic purposes, met the development criteria for a cervical cancer vaccine. However, these findings need to be validated through in vitro and in vivo experiments.

Genomic analysis reveals the association of KIT and MITF variants with the white spotting in swamp buffaloes.

BACKGROUND: Swamp-type buffaloes with varying degrees of white spotting are found exclusively in Tana Toraja, South Sulawesi, Indonesia, where spotted buffalo bulls are highly valued in accordance with the Torajan customs. The white spotting depigmentation is caused by the absence of melanocytes. However, the genetic variants that cause this phenotype have not been fully characterized. The objective of this study was to identify the genomic regions and variants responsible for this unique coat-color pattern. RESULTS: Genome-wide association study (GWAS) and selection signature analysis identified MITF as a key gene based on the whole-genome sequencing data of 28 solid and 39 spotted buffaloes, while KIT was also found to be involved in the development of this phenotype by a candidate gene approach. Alternative candidate mutations included, in addition to the previously reported nonsense mutation c.649 C > T (p.Arg217*) and splice donor mutation c.1179 + 2T > A in MITF, a nonsense mutation c.2028T > A (p.Tyr676*) in KIT. All these three mutations were located in the genomic regions that were highly conserved exclusively in Indonesian swamp buffaloes and they accounted largely (95%) for the manifestation of white spotting. Last but not the least, ADAMTS20 and TWIST2 may also contribute to the diversification of this coat-color pattern. CONCLUSIONS: The alternative mutations identified in this study affect, at least partially and independently, the development of melanocytes. The presence and persistence of such mutations may be explained by significant financial and social value of spotted buffaloes used in historical Rambu Solo ceremony in Tana Toraja, Indonesia. Several de novo spontaneous mutations have therefore been favored by traditional breeding for the spotted buffaloes.

Comparisons of automated machine learning (AutoML) in predicting whistleblowing of academic dishonesty with demographic and theory of planned behavior.

Machine learning has been very promising in solving real problems, but the implementation involved difficulties mainly for the inexpert data scientists. Therefore, this paper presents an automated machine learning (AutoML) to simplify and accelerate the modeling tasks. Focused on Python and RapidMiner rapid modeling tools, Tree-based Pipeline Optimization Tool (TPOT) and AutoModel were used. This paper presents a comprehensive comparison between these tools with regard to the prediction accuracy and Area Under Curve (AUC) in classifying real cases of whistleblowing academic dishonesty among undergraduate students of two universities in Indonesia. Additionally, the correlations weight from demographic and Theory of Planned Behavior (TOB) attributes in the different machine learning models are also discussed. All the machine learning algorithms from TPOT and AutoModel are considerable powerful to generate good accuracy level (between 70-93% of AUC) in classifying both cases of whistleblowing and non-whistleblowing on the hold-out samples from the testing process. Generally, based on the validation results of the prediction models, demographic attributes presented more importance than the TBP attributes. The findings of this study will be a great interest of many research scholars to conduct a more in-depth analysis on AutoML for many domains mainly in education and academic misconduct fields.•AutoML is the first of its kind to be empirically compared between TPOT and AutoModel in an application to predict academic dishonesty whistleblowing.•Besides accuracy performances of the AutoML, the proportion of the variance of each attribute from demographic and Theory of Planned Behavior (TPB) is also presented in the prediction models of academic dishonesty whistleblowing.•AutoML is a convenient and reproducible rapid modeling method of machine learning to be used in many kinds of prediction problem.

Self-Efficacy in Self-Care and Its Related Factors Among Patients with Coronary Heart Disease in Indonesia: A Rasch Analysis.

Background: Low self-efficacy (SE) can impact decreasing health status, poor self-care, and quality of life among patients with Coronary Heart Disease (CHD). Many factors can affect SE. However, studies on SE in CHD patients with Rasch Model analysis have not been carried out widely. Purpose: This study aims to identify the SE in self-care and its related factors that correlate SE among CHD patients. Patients and Methods: Cross-sectional study was conducted on 104 adult patients (≥18 years) diagnosed with CHD. Selection of the sample using convenience sampling technique with several predetermined criteria. SE was measured using the SEQ-CHDM questionnaire, with high validity and reliability results. Data were analyzed using the Rasch model and chi-square test. Results: The results showed that most respondents had a moderate SE (51.5%). Care units (p=0.003) and duration of illness (p=0.049) were significantly correlated to SE among patients with CHD. "Maintaining an ideal body weight" is the most challenging thing. On the other hand, stop smoking is the most confident thing to be performed by the respondents. Conclusion: We conclude that CHD patients in the acute care unit and patients with a duration of illness >6 months have a lower tendency for SE. Health interventions such as raising awareness about the disease, modifying health behavior, and immediately screening can improve patients' SE. Besides that, proper diagnosis and ongoing treatment are crucial to improving SE and CHD care outcomes.

Optimization of Ultrasonic-Assisted Extraction (UAE) Method Using Natural Deep Eutectic Solvent (NADES) to Increase Curcuminoid Yield from Curcuma longa L., Curcuma xanthorrhiza, and Curcuma mangga Val.

This study aims to optimize ultrasonic-assisted natural deep eutectic solvents (NADES) based extraction from C. longa. Choline chloride-lactic acid (CCLA-H2O = 1:1, b/v) was used to investigate the impact of various process parameters such as solvent's water content, solid loading, temperature, and extraction time. The optimal yield of 79.635 mg/g of C. longa was achieved from extraction in 20% water content NADES with a 4% solid loading in 35 °C temperature for 1 h. Peleg's model was used to describe the kinetics of the optimized ultrasonic-assisted extraction (UAE) method, and the results were found to be compatible with experimental data. The optimum conditions obtained from C. longa extraction were then used for the extraction of C. xanthorriza and C. mangga, which give yields of 2.056 and 31.322 mg/g, respectively. Furthermore, n-hexane was utilized as an anti-solvent in the separation process of curcuminoids extract from C. longa, C. xanthorriza, and C. mangga, which gave curcuminoid recovery of 39%, 0.74%, and 27%, respectively. Solidification of curcuminoids was also carried out using the crystallization method with n-hexane and isopropanol. However, the solution of CCLA and curcuminoids formed a homogeneous mixture with isopropanol. Hence, the curcuminoids could not be solidified due to the presence of NADES in the extract solution.

Development and psychometric evaluation of an instrument to assess Knowledge, Attitude and Practice of Family Caregivers at Preventing Pressure Injuries (KAP-PI) in Indonesian community-dwelling older adults.

BACKGROUND: The prevalence of pressure injuries among community-dwelling older adults in countries worldwide is still a serious problem. In Indonesia, older adults mostly rely on family members for (medical) care. Therefore, involving family members in the prevention and treatment of pressure injuries (PIs) could potentially decrease its prevalence rates. However, family members are usually not trained for such tasks. Hence, it is essential to first get more insight into the current state of affairs on family members' knowledge, attitude and actual practice of preventing PIs. Due to the lack of an existing instrument to measure knowledge, attitude and practice of family caregivers in preventing PIs, this study focuses on the development and evaluation of psychometric properties of such an instrument. METHODS: Three phases of instrument development and evaluation were used, including item generation, instrument construction and psychometric testing of the instrument. A total of 372 family caregivers of community-dwelling older adults who randomly selected participated in this study. Principal factor analysis, confirmatory factor analysis and Cronbach's alpha were performed to evaluate factor structure and internal consistency of the Knowledge, Attitude and Practice of Family Caregivers at Preventing Pressure Injuries (KAP-PI) instrument. RESULTS: The final version of the KAP-PI-instrument consists of a 12-item knowledge domain, a 9-item attitude domain, and a 12-item practice domain with Cronbach's Alpha values of 0.83, 0.93 and 0.89, respectively. The instrument appeared to be both reliable and valid. CONCLUSION: The KAP-PI instrument can be used in family nursing or community nursing practice, education, and research to assess knowledge, attitude and practice of pressure injury prevention of family caregivers.

Metabolome analysis and chemical profiling of Indonesian royal jellies as the raw material for cosmetic and bio-supplement products.

Royal jellies (RJs) possess moisturizing, emulsifying, and stabilizing properties, and several pharmacological activities have also been found to be present, which make them an ideal component for cosmetic and skin care products. However, despite the abundant efficacies, there is a lack of studies that explore the chemical composition of RJ using metabolome analysis. Furthermore, an evaluation of the chemical composition of Indonesian RJs collected from different regions has yet to be carried out. Therefore, the main objective of this study was to identify any differences in the chemical composition of such RJs. Chemical profiling was also carried out to enable more targeted utilization based on the actual compositions. Chemical profiling is also important given the rich Indonesian biodiversity and the high dependence of the RJ compositions on the botanical source. In this research, ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used as part of an untargeted metabolomics approach. From the chemical profiling, >30 compounds were identified across four RJ samples. The major constituents of the samples were found to be oligosaccharides, fatty acids, and adenosine monophosphate derivatives. Meanwhile, sucrose and planteose were found to be highest in the samples from Banjarnegara and Kediri, whereas dimethyloctanoic acid was found to be unique to the sample from Banjarnegara. It was also discovered that the RJs from Demak and Tuban contained more organic fatty acids and oligosaccharides than the other samples. Although the sample from Demak demonstrated good potential for use in the cosmetic, skin care, and bio-supplement industries, the higher abundance of fatty acids and oligosaccharides in the sample from Tuban indicated that it is perhaps the most suitable RJ for use in this field.

Understanding divergent domestication traits from the whole-genome sequencing of swamp- and river-buffalo populations.

Domesticated buffaloes have been integral to rice-paddy agro-ecosystems for millennia, yet relatively little is known about the buffalo genomics. Here, we sequenced and assembled reference genomes for both swamp and river buffaloes and we re-sequenced 230 individuals (132 swamp buffaloes and 98 river buffaloes) sampled from across Asia and Europe. Beyond the many actionable insights that our study revealed about the domestication, basic physiology and breeding of buffalo, we made the striking discovery that the divergent domestication traits between swamp and river buffaloes can be explained with recent selections of genes on social behavior, digestion metabolism, strengths and milk production.

Analysis of Tomato Carotenoids: Comparing Extraction and Chromatographic Methods.

Background: Tomatoes (Solanum lycopersicum) are an economically and nutritionally important crop colored by carotenoids such as lycopene and ß-carotene. Market diversification and interest in the health benefits of carotenoids has created the desire in plant, food, and nutritional scientists for improved extraction and quantification protocols that avoid the analytical bottlenecks caused by current methods. Objective: Our objective was to compare standard and rapid extraction as well as chromatographic separation methods for tomato carotenoids. Method: Comparison was based on accuracy and the ability to discriminate between alleles and genetic backgrounds. Estimates of the contribution to variance in the presence of genetic and environmental effects were further used for comparison. Selections of cherry and processing tomatoes with varying carotenoid profiles were assessed using both established extraction and HPLC-diode array detector (HPLC-DAD) methods and rapid extraction and ultra-HPLC-DAD (UHPLC-DAD) protocols. Results: Discrimination of alleles in samples extracted rapidly (<5 min/sample) was similar to samples extracted using a standard method (10 min/sample), although carotenoid concentrations were lower due to reduced extraction efficiency. Quantification by HPLC-DAD (21.5 min/sample) and UHPLC-DAD (4.2 min/sample) were comparable, but the UHPLC-DAD method could not separate all carotenoids and isomers of tangerine tomatoes. Random effects modeling indicated that extraction and chromatographic methods explained a small proportion of variance compared with genetic and environmental sources. Conclusions: The rapid extraction and UHPLC-DAD methods could enhance throughput for some applications compared with standard protocols.

The prevalence of pressure ulcers in community-dwelling older adults: A study in an Indonesian city.

The objectives of this study were to investigate the prevalence and the characteristics of pressure ulcers (PU) in community-dwelling older adults in Indonesia, including specific characteristics of the PU patients and their use of formal and informal care. A cross-sectional design was used for the study, with 325 participants aged 60 years or older, randomly chosen from the general community. The overall PU prevalence and the PU prevalence excluding category 1 were 10.8% (95% confidence interval [CI], 5.8-15.8) and 5.2% (95% CI 0.2-10.2), respectively. Category 1 PUs were mostly (34.3%) located on knees and toes, while category 2 and higher PUs were mostly (70.4%) located on the shoulder, sacrum, and hip. The main factors that contributed strongly to PUs among older adults in the community were the degree of physical activity, problems with sensory perception, and having a history of stroke. None of the participants with a PU received wound care or information about PUs from formal caregivers and only 11.4% received wound care from family caregivers. This study shows that pressure ulcers in community-dwelling older adults in Indonesia are a relevant and largely unaddressed problem. Developing an intervention program to manage the PU problem in the community is recommended.

Phylogenetic analysis of Aceh cattle breed of Indonesia through mitochondrial D-Loop region.

The objective of this research was to find the basic data on genetic diversity of mtDNA D-Loop in Aceh cattle and its association with Bhutanese, Chinese, and Indian cattle. There were sixty samples of DNA which had been sequenced; i.e. Banda Aceh (11), Saree (20), and Indrapuri (29). To the best of our knowledge this is the first published data on the complete mitochondrial D-Loop sequence of Aceh cattle. Results show that Aceh cattle have the closest relationship to Bos indicus and have been influenced by Bos taurus. The closest genetic ranges among Aceh cattle, Bhutanese, Chinese, Indian and Zebu were Aceh-Zebu (0.0138), Aceh-Bhutanese (0.0156), Aceh-Chinese (0.0190) and Aceh-Indian (0.0193). D-Loop mtDNA analyses showed that there were 27 haplotypes in which twenty-one samples spread in haplotype 1, two samples were in haplotype 2, and the other four haplotypes had various samples in the range of three to seventeen samples. One sample of Aceh cattle from Saree has a closest maternal genetic with B. taurus. One of the four mutations among the star-shaped clusters on median joining network was a new specific haploid-group in Aceh cattle. From this finding it could be assumed that Aceh cattle form a specific haplotype and it can be conclude that Aceh cattle are animal genetic resources from Aceh in Sumatera Island that have to be preserved.