Impaired health-related quality of life due to elevated risk of developing diabetes: A cross-sectional study in Indonesia.

BACKGROUND: This study investigated the association between elevated risk of developing diabetes and impaired health-related quality of life (HRQoL) in the Indonesian population. METHODS: A cross-sectional study was conducted on 1,336 Indonesians from the general population who had no previous diagnosis of diabetes. Utility score to represent HRQoL was measured using the EuroQol 5-dimension, while the risk for developing diabetes was determined using the Finnish Diabetes Risk Score (FINDRISC) instrument. All participants underwent a blood glucose test after fasting for 8 hours. The association between FINDRISC score and HRQoL adjusted for covariates was analysed using multivariate Tobit regression models. Minimal clinically important differences were used to facilitate interpretation of minimal changes in utility score that could be observed. RESULTS: The median (interquartile range) of the overall FINDRISC score was 6 (7), while the mean (95% confidence intervals) of the EQ-5D utility score was 0.93 (0.93-0.94). Once adjusted for clinical parameters and socio-demographic characteristics, participants with a higher FINDRISC score showed a significantly lower HRQoL. No significant association was detected between fasting blood glucose level categories and HRQoL. A difference of 4-5 points in the FINDRISC score was considered to reflect meaningful change in HRQoL in clinical practice. CONCLUSION: An elevated risk of developing diabetes is associated with a lower HRQoL. Therefore, attention should be paid not only to patients who have already been diagnosed with diabetes, but also to members of the general population who demonstrate an elevated risk of developing diabetes. This approach will assist in preventing the onset of diabetes and any further deterioration of HRQoL in this segment of the Indonesian population.

Genetic Association Studies of MICB and PLCE1 with Severity of Dengue in Indonesian and Taiwanese Populations.

Dengue is an arboviral disease that has spread globally and become a major public health concern. A small proportion of patients may progress from symptomatic dengue fever (DF) to dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Findings from a previous genome-wide association study (GWAS) demonstrated that variations in the major histocompatibility complex (MHC) class I chain-related B (MICB) and the phospholipase C epsilon 1 (PLCE1) genes were related to DSS in a Vietnamese population. This study investigated associations of variations in MICB (rs3132468) and PLCE1 (rs3740360, rs3765524) with dengue severity and thrombocytopenia in both the Indonesian and Taiwanese populations. We sampled 160 patients from the Indonesian population and 273 patients from the Taiwanese population. None of the patients had DSS in the Taiwanese population. Based on age demographics, we found that dengue is more prevalent among younger individuals in the Indonesian population, whereas it has a greater impact on adults in the Taiwanese population. Our results showed the association between MICB rs3132468 and DSS. In addition, an association was identified between PLCE1 rs3740360 and DHF in secondary dengue in Indonesian patients. However, there is no association of MICB or PLCE1 variants with thrombocytopenia. This study highlights the value of genetic testing, which might be included in the clinical pathway for specific patients who can be protected from severe dengue.

The knowledge mapping of HIV/AIDS in Indonesians living on six major islands using the Indonesian version of the HIV-KQ-18 instrument.

Indonesia's total number of HIV/AIDS cases is still high. Inadequate knowledge about the risk of HIV infection will influence HIV prevention and therapy. This study aimed to map the level of HIV-related knowledge among Indonesians living on six major islands in Indonesia and investigate the relationship between socio-demographic characteristics and HIV/AIDS knowledge. This cross-sectional study used the Bahasa Indonesia version of the HIV Knowledge Questionnaire-18 items (HIV-KQ-18) Instrument. Data collection was done online through the Google form application. A total of 5,364 participants were recruited. The participants from Java had the highest degree of HIV/AIDS knowledge, which was 12.5% higher than participants from Sumatra, Kalimantan, Sulawesi, Papua, and Maluku. Linear regression showed that region, educational level, monthly expenditure, occupation, background in health sciences, and workshop attendance were significantly correlated with HIV knowledge. Participants typically understand that "HIV/AIDS transmission" only happens when sex partners are changed. Additionally, the government still needs improvement in HIV/AIDS education, particularly in the HIV incubation period, HIV transmission from pregnant women to the fetus, and condom use as one method of protection. There are disparities in HIV/AIDS knowledge levels among the major islands of Indonesia. Based on these findings, the government's health promotion program to increase public awareness of HIV/AIDS must be implemented vigorously. Additionally, in line with our research findings, it is essential to broaden the scope of HIV/AIDS education and promotion materials.

Mapping EORTC-QLQ-C30 onto EQ-5D-5L Index in Indonesian Cancer Patients.

OBJECTIVE: This study aims to develop a mapping algorithm for EORTC QLQ-C30 to EQ-5D-5L which can produce utility values in patients with cancer. METHODS: We used a cross sectional study design with 300 cancer patients. The research instruments used were EORTC QLQ-C30 and EQ-5D-5L. Data were collected by interviewing cancer patients who were hospitalized in the Kasuari Installation of Dr Kariadi Hospital Semarang, Indonesia. The Ordinary Least Squares (OLS) regression method was used to predict the utility value of EQ-5D-5L. This study uses two models to predict utility values, namely model 1 with all domains, and model 2 with domains that affect the EQ-5D-5L. The predictive power of regression on the model is evaluated by calculating the mean absolute error (MAE) and root mean square error (RMSE) values. RESULT: The highest score in the functional domain is the 'emotional function' domain (mean: 85.89; SD: 16.04) and the highest symptom domain is 'weakness' (mean: 36.21; SD:21.69). The predicted utility values of models 1 and 2 are 0.683. The mean absolute error (MAE) and root mean square error (RMSE) values of model 1 are 0.128 and 0.173, while in model 2 the MAE and RMSE values obtained are 0.125 and 0.168. CONCLUSION: The development of the mapping algorithm from the EORTC QLQ-C30 to EQ-5D-5L instrument shows a predictive value of utility in a sample of patients with cancer at Dr. Kariadi Hospital, Semarang, Indonesia. The utility prediction in both model is similar, however model 2 involves fewer domains and symptoms.
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Cross-cultural adaptation and psychometric properties of the Indonesian version for quality of life among breast cancer patients.

Background: Breast cancer is one of the most important health problems worldwide. Quality of life (QoL) is an important indicator to evaluate symptoms in cancer patients, including those with breast cancer. Culturally suitable, valid, reliable, and appropriate instruments to measure the QoL of breast cancer patients are needed, which is still rare in Indonesia. This study aimed to translate the EORTC QLQ-BR45 instrument into Indonesian and evaluate its psychometrics. Methods: A cross-sectional study was performed on 635 patients conveniently selected from the oncology department in referral hospital. The first phase of this study involved translation of the existing EORTC QLQ-BR45 into Indonesian, and in the second phase, we evaluated its psychometric properties. Construct validity was evaluated using confirmatory factor analysis (CFA). Criterion validity was examined according to the association between disease stage and Karnofsky Performance Scale (KPS). Results: A total of 635 (99.00%) completed the EORTC QLQ-BR45 successfully. The instrument indicated good readability and high content validity. All Cronbach's alpha coefficients were satisfactory (overall value, 0.87). For construct validity, patients with KPS ≥80% did better than those with KPS ≤70% as did two multi-item scales in functional scales (body image and breast satisfaction) and five multi-item scales in symptom scales (systemic therapy side effects, endocrine therapy, and arm, breast, and endocrine sexual symptoms). Body image score of late-stage patients was significantly higher. CFA indicated that the nine-factor structure of the Indonesian EORTC QLQ-BR45 was a good fit for the data. Conclusion: The Indonesian EORTC QLQ-BR45 questionnaire is reliable and valid with good psychometric properties, thus can be used for breast cancer patients in Indonesia.

Determinants of quality of life among people with HIV and tuberculosis in an underserved area in Indonesia: a cross-sectional study.

Introduction: human immunodeficiency virus (HIV) and tuberculosis (TB) remain global health problems and impose a substantial reduction in people´s quality of life (QoL). This study aimed to assess and compare the QoL in HIV and TB patients and factors associated with QoL between those groups. Methods: a cross-sectional study was conducted at a hospital clinic in Jayapura, Indonesia, between December 2022 and March 2023. Those who were aged above 18 years, diagnosed with HIV or TB infection, have been taking HIV or TB medications for at least 3 months, and provided informed consent were eligible to participate. Patients´ QoL was measured using the Bahasa Indonesia version of a validated 26-item World Health Organization Quality of Life - Brief (WHOQOL-BREF) questionnaire. Results: a total of 365 patients with HIV and 125 with TB were included. The majority of participants were Papuan (75.9%) and aged 20 - 65 years (92.9%). More than half of the participants were female (56.5%), employed (50.8%), married (65.5%), and had family support (64.9%). Education level and social support were predictors of poor physical health in the HIV group, while ethnicity was a predictor in the TB group. Patients´ age was associated with poor psychological health in HIV, whereas sex was the associated factor in TB patients. Ethnicity was the only predictor of poor social relationships in those with TB. Whereas patients´ age was a predictor of poor environmental health in the HIV group, marital status, and education were predictors in the TB group. Finally, only social support was associated with poor general QoL in TB patients. Conclusion: tuberculosis (TB) patients had poorer QoL than those with HIV. There is a need for more awareness to support those receiving TB treatment. In addition, further research is needed to understand in more detail the determinants of patients with drug-resistant TB, TB with HIV, and drug-resistant TB-HIV, to ensure that interventions are designed to help them.

Identification of Hub Genes and Potential Biomarkers for Childhood Asthma by Utilizing an Established Bioinformatic Analysis Approach.

Childhood asthma represents a heterogeneous disease resulting from the interaction between genetic factors and environmental exposures. Currently, finding reliable biomarkers is necessary for the clinical management of childhood asthma. However, only a few biomarkers are being used in clinical practice in the pediatric population. In the long run, new biomarkers for asthma in children are required and would help direct therapy approaches. This study aims to identify potential childhood asthma biomarkers using a genetic-driven biomarkers approach. Herein, childhood asthma-associated Single Nucleotide Polymorphisms (SNPs) were utilized from the GWAS database to drive and facilitate the biomarker of childhood asthma. We uncovered 466 childhood asthma-associated loci by extending to proximal SNPs based on r2 > 0.8 in Asian populations and utilizing HaploReg version 4.1 to determine 393 childhood asthma risk genes. Next, the functional roles of these genes were subsequently investigated using Gene Ontology (GO) term enrichment analysis, a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and a protein−protein interaction (PPI) network. MCODE and CytoHubba are two Cytoscape plugins utilized to find biomarker genes from functional networks created using childhood asthma risk genes. Intriguingly, 10 hub genes (IL6, IL4, IL2, IL13, PTPRC, IL5, IL33, TBX21, IL2RA, and STAT6) were successfully identified and may have been identified to play a potential role in the pathogenesis of childhood asthma. Among 10 hub genes, we strongly suggest IL6 and IL4 as prospective childhood asthma biomarkers since both of these biomarkers achieved a high systemic score in Cytohubba's MCC algorithm. In summary, this study offers a valuable genetic-driven biomarker approach to facilitate the potential biomarkers for asthma in children.

Integration of genomic variants and bioinformatic-based approach to drive drug repurposing for multiple sclerosis.

Multiple sclerosis (MS) is a chronic autoimmune disease in the central nervous system (CNS) marked by inflammation, demyelination, and axonal loss. Currently available MS medication is limited, thereby calling for a strategy to accelerate new drug discovery. One of the strategies to discover new drugs is to utilize old drugs for new indications, an approach known as drug repurposing. Herein, we first identified 421 MS-associated SNPs from the Genome-Wide Association Study (GWAS) catalog (p-value < 5 × 10-8), and a total of 427 risk genes associated with MS using HaploReg version 4.1 under the criterion r2 > 0.8. MS risk genes were then prioritized using bioinformatics analysis to identify biological MS risk genes. The prioritization was performed based on six defined categories of functional annotations, namely missense mutation, cis-expression quantitative trait locus (cis-eQTL), molecular pathway analysis, protein-protein interaction (PPI), genes overlap with knockout mouse phenotype, and primary immunodeficiency (PID). A total of 144 biological MS risk genes were found and mapped into 194 genes within an expanded PPI network. According to the DrugBank and the Therapeutic Target Database, 27 genes within the list targeted by 68 new candidate drugs were identified. Importantly, the power of our approach is confirmed with the identification of a known approved drug (dimethyl fumarate) for MS. Based on additional data from ClinicalTrials.gov, eight drugs targeting eight distinct genes are prioritized with clinical evidence for MS disease treatment. Notably, CD80 and CD86 pathways are promising targets for MS drug repurposing. Using in silico drug repurposing, we identified belatacept as a promising MS drug candidate. Overall, this study emphasized the integration of functional genomic variants and bioinformatic-based approach that reveal important biological insights for MS and drive drug repurposing efforts for the treatment of this devastating disease.

Genomic variants-driven drug repurposing for tuberculosis by utilizing the established bioinformatic-based approach.

A major challenge in translating genomic variants of Tuberculosis (TB) into clinical implementation is to integrate the disease-associated variants and facilitate drug discovery through the concept of genomic-driven drug repurposing. Here, we utilized two established genomic databases, namely a Genome-Wide Association Study (GWAS) and a Phenome-Wide Association Study (PheWAS) to identify the genomic variants associated with TB disease and further utilize them for drug-targeted genes. We evaluated 3.425 genomic variants associated with TB disease which overlapped with 200 TB-associated genes. To prioritize the biological TB risk genes, we devised an in-silico pipeline and leveraged an established bioinformatics method based on six functional annotations (missense mutation, cis-eQTL, biological process, cellular component, molecular function, and KEGG molecular pathway analysis). Interestingly, based on the six functional annotations that we applied, we discovered that 14 biological TB risk genes are strongly linked to the deregulation of the biological TB risk genes. Hence, we demonstrated that 12 drug target genes overlapped with 40 drugs for other indications and further suggested that the drugs may be repurposed for the treatment of TB. We highlighted that CD44, CCR5, CXCR4, and C3 are highly promising proposed TB targets since they are connected to SELP and HLA-B, which are biological TB risk genes with high systemic scores on functional annotations. In sum, the current study shed light on the genomic variants involved in TB pathogenesis as the biological TB risk genes and provided empirical evidence that the genomics of TB may contribute to drug discovery.

The use of genomic variants to drive drug repurposing for chronic hepatitis B.

Background: One of the main challenges in personalized medicine is to establish and apply a large number of variants from genomic databases into clinical diagnostics and further facilitate genome-driven drug repurposing. By utilizing biological chronic hepatitis B infection (CHB) risk genes, our study proposed a systematic approach to use genomic variants to drive drug repurposing for CHB. Method: The genomic variants were retrieved from the Genome-Wide Association Study (GWAS) and Phenome-Wide Association Study (PheWAS) databases. Then, the biological CHB risk genes crucial for CHB progression were prioritized based on the scoring system devised with five strict functional annotation criteria. A score of ≥ 2 were categorized as the biological CHB risk genes and further shed light on drug target genes for CHB treatments. Overlapping druggable targets were identified using two drug databases (DrugBank and Drug-Gene Interaction Database (DGIdb)). Results: A total of 44 biological CHB risk genes were screened based on the scoring system from five functional annotation criteria. Interestingly, we found 6 druggable targets that overlapped with 18 drugs with status of undergoing clinical trials for CHB, and 9 druggable targets that overlapped with 20 drugs undergoing preclinical investigations for CHB. Eight druggable targets were identified, overlapping with 25 drugs that can potentially be repurposed for CHB. Notably, CD40 and HLA-DPB1 were identified as promising targets for CHB drug repurposing based on the target scores. Conclusion: Through the integration of genomic variants and a bioinformatic approach, our findings suggested the plausibility of CHB genomic variant-driven drug repurposing for CHB.

Translation and performance of the Finnish Diabetes Risk Score for detecting undiagnosed diabetes and dysglycaemia in the Indonesian population.

A diabetes risk score cannot directly be translated and applied in different populations, and its performance should be evaluated in the target population. This study aimed to translate the Finnish Diabetes Risk Score (FINDRISC) instrument and compare its performance with the modified version for detecting undiagnosed type 2 diabetes mellitus (T2DM) and dysglycaemia among the Indonesian adult population. Forward and backward translations were performed and followed by cultural adaptation. In total, 1,403 participants were recruited. The FINDRISC-Bahasa Indonesia (FINDRISC-BI) was scored according to the original FINDRISC instrument, while a Modified FINDRISC-BI was analyzed using a specific body mass index and waist circumference classification for Indonesians. The area under the receiver operating characteristic curve, sensitivity, specificity, and the optimal cut-offs of both instruments were estimated. The area under the receiver operating characteristic curve for detecting undiagnosed T2DM was 0.73 (0.67-0.78) for the FINDRISC-BI with an optimal cut-off score of ≥9 (sensitivity = 63.0%; specificity = 67.3%) and 0.72 (0.67-0.78) for the Modified FINDRISC-BI with an optimal cut-off score of ≥11 (sensitivity = 59.8%; specificity = 74.9%). The area under the receiver operating characteristic curve for detecting dysglycaemia was 0.72 (0.69-0.75) for the FINDRISC-BI instrument with an optimal cut-off score of ≥8 (sensitivity = 66.4%; specificity = 67.0%), and 0.72 (0.69-0.75) for the Modified FINDRISC-BI instrument with an optimal cut-off score ≥9 (sensitivity = 63.8%; specificity = 67.6%). The Indonesian version of the FINDRISC instrument has acceptable diagnostic accuracy for screening people with undiagnosed T2DM or dysglycaemia in Indonesia. Modifying the body mass index and waist circumference classifications in the Modified FINDRISC-BI results in a similar diagnostic accuracy; however, the Modified FINDRISC-BI has a higher optimal cut-off point than the FINDRISC-BI. People with an above optimal cut-off score are suggested to take a further blood glucose test.

Translation and Validation of the Indonesian Version of the Adverse Drug Reaction Severity Level Instruments in Colorectal Cancer Patients.

Introduction: Assessment of the severity of adverse drug reaction (ADR) is very rare in Indonesia. The severity of ADR can describe how serious this affects the clinical condition of the patient. In Indonesia, there are no instruments used to measure the severity of ADR. Purpose: This study aims to translate, pilot test, and validate Hartwig instruments for measuring the severity of ADR in colorectal cancer patients in Indonesia. Patients and Methods: The translation method was used forward-backward technique from English to Indonesian, then being retranslated from Indonesia to English. The instrument of Indonesian version was used to assess the severity of ADR as the effect of chemotherapy. The assessment was conducted to 10 colorectal cancer patients by 30 health workers. The test validity was done based on content validity ratio (CVR) and content validity index (CVI); meanwhile, the test reliability was based on intraclass coefficient correlation (ICC). Results: All of the results of CVR present a value of >0.33, while the range of CVI moves between 0.8 to 1.0, which declares that the instrument is valid. The satisfactory alpha value for reliability is 0.996 with signification of 0.197 (p > 0.05) based on ANOVA analysis. Meanwhile, the ICC value of 0.896 indicates a good reliability among raters. Conclusion: Indonesian version of Hartwig Instrument can be applied in measuring the severity of ADR caused by chemotherapy in colorectal cancer patients.

Dynamic Changes of Platelet and Factors Related Dengue Haemorrhagic Fever: A Retrospective Study in Indonesian.

Dengue is a viral infection caused by the dengue virus (DENV). Dengue infection is a self-limited acute febrile illness caused by four serotypes of DENV (DENV-1~4). Early recognition of high-risk patients would be helpful to reduce mortality rates and prevent severe dengue. Our study aimed to identify factors related to dengue hemorrhagic fever (DHF) based on admission-day data, and further to understand the distribution of biochemical laboratory data in dengue patients. This retrospective study was conducted in hospitals in Yogyakarta city, Indonesia, and involved febrile patients who were admitted to the hospital with a diagnosis of dengue during 2018 and 2020. Logistic regression models were used to identify variables related to DHF. In this study, 1087 patients were included as suspected dengue patients, among them 468 had dengue fever (DF) and 619 had DHF. Over half of the DHF patients were males (55.9%) with an average age of 17.9 years, and with a secondary infection (71.3%). By a multivariate analysis, on-admission laboratory data of thrombocytopenia and hemoglobin showed significant association with DHF. Furthermore, DHF patients had significantly prolonged hospitalizations compared to DF patients. In conclusion, on-admission platelet counts and hemoglobin laboratory data are useful as predictors of DHF especially for suspected dengue patients with the limitations of diagnostic tests.

Adaptation and validation of the HIV Knowledge Questionnaire-18 for the general population of Indonesia.

BACKGROUND: Despite a global decline in new HIV/AIDS cases in low-middle countries, cases are increasing in Indonesia. Low knowledge about the disease among the general population is one of the major factors responsible for this trend. Indonesia does not have a validated instrument to assess HIV/AIDS knowledge. The HIV Knowledge Questionnaire-18 (HIV-KQ-18) has been translated into several languages and is one of the most extensively used instruments for assessing HIV/AIDS knowledge. This paper describes the process of adapting and validating the HIV-KQ-18, an instrument to assess the level of HIV/AIDS knowledge in the general population of Indonesia. METHODS: In the adaptation phase, feedback for the initial Bahasa Indonesia version was gathered from two HIV activists, an obstetrician, two general practitioners, and 60 pilot participants. At the validation stage, we distributed the instrument link via Google Form to 6 major regions in Indonesia. Validity was measured using known-group validity and construct validity. The construct validity was assessed using an exploratory factor analysis (EFA) with a polychoric correlation matrix. Cronbach's alpha was used to analyze the internal consistency. RESULTS: Based on the findings in the adaptation phase, additional descriptions (namely synonyms or examples) were added to 6 items to make them more understandable. In the validation phase, 1,249 participants were recruited. The a priori hypothesis in known-group validity was supported. We also found three items that did not meet the construct validity. Based on the acceleration factor approach to interpret the scree tree in the factor analysis, using only two factors was preferable. Cronbach's alpha values were 0.75 and 0.71 representing good internal reliability. CONCLUSION: The HIV-KQ-18 Bahasa Indonesia is considered a valid and reliable instrument to assess the level of HIV/AIDS knowledge in Indonesia.

Geographic Characteristics of Various Cancers in Yogyakarta Province, Indonesia: A Spatial Analysis at the Community Level.

BACKGROUND: Cancer remains a significant public health problem in Indonesia and worldwide. Yogyakarta Province has the largest number of cancer cases in Indonesia. Maps of the distribution of cancer cases are useful tools for stratification of cancer risk and for selective prevention strategies. The aim of this study was to determine the spatial distribution of cancer cases in Yogyakarta Province. METHODS: Cancer patient data registered by the Yogyakarta Provincial Health Office during 2019-2020 were analysed in this study (n=9,933). To evaluate cancer pattern distributions, ArcGIS 10.2 and Excel 2016 software were used. RESULTS: The mean participant age (± standard deviation) was 55.08 ± 15.46 years, and 79.40% were female. Breast and cervical cancer were the most frequently diagnosed, and the majority of patients were located in Sleman district. The incidence of all cancer types varied by county-level. The majority of cancer patients lived below the poverty line. Cancer screening rates were low, and screening was limited to breast and cervical cancer. CONCLUSION: Various types of cancers were identified in Yogyakarta, Indonesia; of them, breast and cervical cancer predominated. Most of the cancer patients were from Sleman district and economically poor areas. Geospatial techniques are useful for identifying environmental factors related to cancer and improving cancer control strategies and resource allocation.

Identification of Druggable Genes for Asthma by Integrated Genomic Network Analysis.

Asthma is a common and heterogeneous disease characterized by chronic airway inflammation. Currently, the two main types of asthma medicines are inhaled corticosteroids and long-acting ß2-adrenoceptor agonists (LABAs). In addition, biological drugs provide another therapeutic option, especially for patients with severe asthma. However, these drugs were less effective in preventing severe asthma exacerbation, and other drug options are still limited. Herein, we extracted asthma-associated single nucleotide polymorphisms (SNPs) from the genome-wide association studies (GWAS) and phenome-wide association studies (PheWAS) catalog and prioritized candidate genes through five functional annotations. Genes enriched in more than two categories were defined as "biological asthma risk genes." Then, DrugBank was used to match target genes with FDA-approved medications and identify candidate drugs for asthma. We discovered 139 biological asthma risk genes and identified 64 drugs targeting 22 of these genes. Seven of them were approved for asthma, including reslizumab, mepolizumab, theophylline, dyphylline, aminophylline, oxtriphylline, and enprofylline. We also found 17 drugs with clinical or preclinical evidence in treating asthma. In addition, eleven of the 40 candidate drugs were further identified as promising asthma therapy. Noteworthy, IL6R is considered a target for asthma drug repurposing based on its high target scores. Through in silico drug repurposing approach, we identified sarilumab and satralizumab as the most promising drug for asthma treatment.

Drug Repurposing for Atopic Dermatitis by Integration of Gene Networking and Genomic Information.

Atopic Dermatitis (AD) is a chronic and relapsing skin disease. The medications for treating AD are still limited, most of them are topical corticosteroid creams or antibiotics. The current study attempted to discover potential AD treatments by integrating a gene network and genomic analytic approaches. Herein, the Single Nucleotide Polymorphism (SNPs) associated with AD were extracted from the GWAS catalog. We identified 70 AD-associated loci, and then 94 AD risk genes were found by extending to proximal SNPs based on r2 > 0.8 in Asian populations using HaploReg v4.1. Next, we prioritized the AD risk genes using in silico pipelines of bioinformatic analysis based on six functional annotations to identify biological AD risk genes. Finally, we expanded them according to the molecular interactions using the STRING database to find the drug target genes. Our analysis showed 27 biological AD risk genes, and they were mapped to 76 drug target genes. According to DrugBank and Therapeutic Target Database, 25 drug target genes overlapping with 53 drugs were identified. Importantly, dupilumab, which is approved for AD, was successfully identified in this bioinformatic analysis. Furthermore, ten drugs were found to be potentially useful for AD with clinical or preclinical evidence. In particular, we identified filgotinub and fedratinib, targeting gene JAK1, as potential drugs for AD. Furthermore, four monoclonal antibody drugs (lebrikizumab, tralokinumab, tocilizumab, and canakinumab) were successfully identified as promising for AD repurposing. In sum, the results showed the feasibility of gene networking and genomic information as a potential drug discovery resource.

The knowledge of COVID-19 treatments, behaviors, and attitudes of providing the information on COVID-19 treatments: Perspectives of pharmacy students.

BACKGROUND: Increasing community awareness about the transmission and treatment of COVID-19 will stop the spread of the virus. Pharmacy students are the potential facilitator to give community education about COVID-19 treatment. The objective of this study is to evaluate the pharmacy students' knowledge of COVID-19 treatment, behavior, and attitude of providing the information about COVID-19 treatment. MATERIALS AND METHODS: We conducted cross-sectional study, recruiting 429 pharmacy students from three schools of pharmacy in Indonesia. The questionnaire about the knowledge of COVID-19 treatment, behavior, and attitude of providing the information on COVID-19 treatment met the validity and reliability criteria. We defined the proportion of knowledge, behavior, and attitude of the students using SPSS® version 22. RESULTS: Most of the students are in the earlier years (46.63%), female (84.15%), find the information about COVID-19 from many sources of media (85.08%) including scientific articles and know information about COVID-19 transmission around their life area (76.46%). The students' knowledge about antiviral and plasma convalescent is good (>70%), the positive behaviors are related to the COVID-19 treatment information regarding to the antiviral and the provision of Vitamin C (>50%), and the positive attitude are related to giving information about the use of avigan®, plasma convalescent, chloroquine, hydroxychloroquine, and immunomodulator (>50%). CONCLUSIONS: As a future pharmacist, the knowledge of pharmacy students about COVID-19 treatment needs to be improved since earlier years. Furthermore, using the good knowledge about COVID-19 treatment, the positive behavior and attitude of providing information of the students, the community behavior and attitude will be improved. The high year students have a tendency for the good knowledge and positive behavior and attitude of providing the information.

Genetic Association of the Functional WDR4 Gene in Male Fertility.

Infertility is one of the important problems in the modern world. Male infertility is characterized by several clinical manifestations, including low sperm production (oligozoospermia), reduced sperm motility (asthenozoospermia), and abnormal sperm morphology (teratozoospermia). WDR4, known as Wuho, controls fertility in Drosophila. However, it is unclear whether WDR4 is associated with clinical manifestations of male fertility in human. Here, we attempted to determine the physiological functions of WDR4 gene. Two cohorts were applied to address this question. The first cohort was the general population from Taiwan Biobank. Genomic profiles from 68,948 individuals and 87 common physiological traits were applied for phenome-wide association studies (PheWAS). The second cohort comprised patients with male infertility from Wan Fang Hospital, Taipei Medical University. In total, 81 male participants were recruited for the genetic association study. Clinical records including gender, age, total testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total sperm number, sperm motility, and sperm morphology were collected. In the first cohort, results from PheWAS exhibited no associations between WDR4 genetic variants and 87 common physiological traits. In the second cohort, a total of four tagging single-nucleotide polymorphisms (tSNPs) from WDR4 gene (rs2298666, rs465663, rs2248490, and rs3746939) were selected for genotyping. We found that SNP rs465663 solely associated with asthenozoospermia. Functional annotations through the GTEx portal revealed the correlation between TT or TC genotype and low expression of WDR4. Furthermore, we used mouse embryonic fibroblasts cells from mwdr4 heterozygous (+/‒) mice for functional validation by western blotting. Indeed, low expression of WDR4 contributed to ROS-induced DNA fragmentation. In conclusion, our results suggest a critical role of WDR4 gene variant as well as protein expression in asthenozoospermia.

The role of genetic polymorphisms in STIM1 and ORAI1 for erythropoietin resistance in patients with renal failure.

ABSTRACT: Anemia is a common complication in patients with renal failure. While erythropoietin is commonly used to treat anemia, some patients exhibit a poor response to erythropoietin. Since store-operated calcium channel (SOC) signaling is one of the erythropoietin activated pathways, we aimed to investigate the association between the genetic polymorphisms of SOC signaling pathway and erythropoietin resistance in patients with renal failure.Four tagging single nucleotide polymorphisms in STIM1 and five in ORAI1 were selected in this study. Genotyping was performed with the TaqMan Allelic Discrimination assay and the association of individual tagging single nucleotide polymorphisms with erythropoietin resistance was analyzed by multivariable adjusted random intercepts model.194 patients were enrolled in this study. The mean age of participants is 68 years, and 56% were men. The mean erythropoietin resistance index was 9.04 ±â€Š4.51 U/Kg/week/g/dL. We found that patients with the AA genotype of rs1561876 in STIM1, and the CC or CT genotypes of rs6486795 in ORAI1, were associated with increased risk of erythropoietin resistance. Functional annotation of expression quantitative trait loci revealed that the AA genotype of rs1561876 in STIM1 has a relatively lower expression of ribonucleotide reductase catalytic subunit M1 in skeletal muscle, while the CC genotype of rs6486795 in ORAI1 has a relatively higher expression of ORAI1 in the whole blood and thyroid.Overall, we demonstrate a significant association between erythropoietin resistance and genetic polymorphisms of STIM1 and ORAI1. Annotation prediction revealed the importance of SOC-mediated calcium signaling for erythropoietin resistance.