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Questioning skills is one of competencies required by teachers in dealing with the 21st-Century challenges. The purpose of this study was profiling biology teacher candidates’ questioning skills in Pekanbaru. The subjects of the research were the students, in three institutions, who were taking Zoology course. The total number of the subjects were 278 students selected using purposive random sampling. The instrument used was test contained of five items which instructed students to make questions related to five objects. The results showed that the teacher candidates’ question level in three institution were low-level question (more than 50% in C1-C3 level). The questions posed were dominance in the level of memorizing, understanding, applying, and analyzing. They were not accustomed to asking questions with the evaluating and creating levels. The systematic of question was dominated as a divergent question, while the question area asked was dominated in the physiology (32.93%) and morphology (32.14%) concept. The information gained from this study can be consideration point for further research.

Hepatitis E is an RNA virus causing chronic diseases with detrimental effects, such as liver cancer and cirrhosis. Various biochemical tests exist for its diagnosis, but low sensitivity and cross-reactivity led the focus toward improved serological methods: immunoglobulin-based and enzyme immunodetection. This study aims to determine the effectiveness of improved enzyme immunodetection methods in hepatitis E virus laboratory diagnosis compared with other diagnostic methods. A systematic literature review was conducted over secondary source databases: Google Scholar, Web of Science, Springer, ScienceDirect, and PubMed. The study followed a Preferred Reporting of Items for Systematic Reviews and Meta-Analysis checklist for conducting the systematic review. Abstracted and full)text peer-reviewed articles were selected, published in English in 2015-2022. The study employed keywords and set publication dates to search for the most relevant articles. However, these studies were assessed using the risk of bias tools: the Cochrane Risk of Bias for randomized controlled design and the Newcastle-Ottawa Scale for non-randomized controlled design. Critical Appraisal Skills Programme checklist was also used to assess the quality of the studies that cannot be assessed by the Cochrane risk of bias tool and Newcastle-Ottawa Scale. After the selection, the data were synthesized using a qualitative approach to present the results. About 10 articles were identified, including randomized, cohort, qualitative, and diagnostic studies. They found the specificity of an immunoassay to achieve a significantly high specificity (98.3%) and sensitivity (89.5%) for immunoglobulin G-based hepatitis E virus detection. However, they reported that immunoglobulin G and immunoglobulin M detection in the suspected hepatitis E virus patients and exposed groups gave potential results for detecting hepatitis E virus. The method was found as efficient as can be designed as non-invasive and with low risks and challenges. The results showed that the improved enzyme immune-detective method can assist in providing a reliable, easily accessible, and error-free hepatitis E virus diagnostic method. Thus, future research must focus on exploiting these methods and strategies. [ABSTRACT FROM AUTHOR]

The Penata Island, also called the Fishermen’s Contact Village, exemplifies the Indonesian people’s characters in general. These characters are preserved to this day in the village to reflect social behavior of the people as native culture of Indonesia, such as helping each other, a sense of community life, and work discipline. When they have problem, they are able to resolve it wisely through community leaders. When the problem is not resolved, it will be taken to the police and resolved through other legal ways. From the results of this study, the researcher saw a few things that have not been done properly, for example, the fishermen have yet to perform the five-time prayers. Some of them are involved in gambling and liquor-drinking, though it is a restricted case that does not have any influence on behavior patterns of the community members in general especially with regard to the practice of Islamic religious teachings.

Since suppressor/enhancer of Lin-12-like (SEL1L) was cloned in 1997, various pieces of evidence from lower species suggest it plays a significant role in protein degradation via the ubiquitin-proteasome system. The relevance of SEL1L in many aspects of malignant transformation and tumorigenic events has been the subject of research, which has shown compelling in vitro and in vivo findings relating its altered expression to changes in tumor aggressiveness. The Endoplasmic Reticulum (ER) in tumor cells is crucial for preserving cellular proteostasis by inducing the unfolded protein response (UPR), a stress response. A crucial component of the UPR is ER-associated degradation (ERAD), which guards against ER stress-induced apoptosis and the removal of unfolded or misfolded proteins by the ubiquitin-proteasome system. As a protein stabilizer of HMG-CoA reductase degradation protein 1 (HRD1), one of the main components of ERAD, SEL1L plays an important role in ER homeostasis. Notably, the expression levels of these two proteins fluctuate independently in various cancer types, yet changes in their expression affect the levels of other associated proteins during cancer pathogenesis. Recent studies have also outlined the function of SEL1L in cancer medication resistance. This review explores the value of targeting SEL1L as a novel treatment approach for cancer, focusing on the molecular processes of SEL1L and its involvement in cancer etiology., (© 2024 International Federation for Cell Biology.)

The EGF receptors (EGFRs) signaling pathway is essential for tumorigenesis and progression of cancer. Emerging evidence suggests that miRNAs are essential regulators of EGF signaling, influencing various pathway components and tumor behavior. This article discusses the underlying mechanisms and clinical implications of miRNA-mediated regulation of EGF signaling in cancer. miRNAs utilize multiple mechanisms to exert their regulatory effects on EGF signaling. They can target EGF ligands, including EGF and TGF-directly, inhibiting their expression and secretion. In addition, miRNAs can modulate EGF signaling indirectly by targeting EGF receptors, downstream signaling molecules, and transcription factors implicated in regulating the EGF pathway. These miRNAs can disrupt the delicate equilibrium of EGF signaling, resulting in aberrant activation and fostering tumor cell proliferation, survival, angiogenesis, and metastasis. The dysregulation of the expression of specific miRNAs has been linked to clinical outcomes in numerous types of cancer. Specific profiles of miRNA expression have been identified as prognostic markers, reflecting tumor characteristics, invasiveness, metastatic potential, and therapeutic response. These miRNAs can serve as potential therapeutic targets for interventions that modulate EGF signaling and improve patient outcomes. Understanding the intricate relationship between miRNAs and EGF signaling in cancer can transform cancer diagnosis, prognosis, and treatment. The identification of specific miRNAs involved in the regulation of the EGF pathway opens the door to the development of targeted therapies and personalized medicine approaches. In addition, miRNA-based interventions promise to overcome therapeutic resistance and improve the efficacy of existing treatments. miRNAs are crucial regulators of EGF signaling in cancer, affecting tumor behavior and clinical outcomes. Further research is required to decipher the complex network of miRNA-mediated EGF signaling regulation and translate these findings into clinically applicable strategies for enhanced cancer treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) posed significant health problems and deaths. There are various challenges in the management of HCC, including the late detection or diagnosis. The ongoing diagnostic method in HCC also hinders the detection on the early stages of the disease, thus biomarkers need to be explored further for HCC detection. Serum alpha fetoprotein (AFP) and Midkine (MDK) are two proteins which might be the biomarker of choice in the detection of HCC. This meta-analysis aims to analyze the accuracy of Midkine and AFP in the detection of HCC., Methods: The systematic review and meta-analysis was conducted by adhering to the Preferred Reporting System for Systematic Review and Meta-Analysis (PRISMA) guidelines. We conduct literature screening and selection followed by quality assessment from various databases such as PubMed, MEDLINE, SpringerLink, ProQuest, EBSCOhost, Cochrane, and EMBASE. The included studies were then extracted and analyzed cumulatively using MedCalc and MetaDTA with forest plot and ROC curve as outcome., Results: 12 studies were included in this study. The AFP biomarker yields sensitivity value of 62.5% (97.5% CI 0.442 - 0.778) and specificity value of 95% (97.5% CI 0.842 - 0.986), while the Midkine biomarker denotes sensitivity value of 91.6% (97.5% CI 0.83 - 0.961) and specificity value of 82.2% (97.5% CI 0.83 - 0.96)., Conclusions: Both AFP and MDK are proven to be a good diagnostic tool or biomarker in the detection of HCC. The use of both in combination should provide high quality diagnostic marker for HCC suspected patients. Further studies on this should be conducted., Competing Interests: The authors declare that there is no conflicts of interest., (© The Author(s).)

Introduction : Hepatocellular carcinoma (HCC) is a leading global cause of cancer-related deaths. Thermal ablation techniques, especially radiofrequency ablation (RFA) and microwave ablation (MWA), have become pivotal treatments for HCC. This systematic review and meta-analysis aim to compare these modalities, highlighting their efficacy, strengths, and limitations in treating HCC. Methods : A comprehensive literature search was conducted across major databases (PubMed, MEDLINE, Springer, ProQuest, EBSCOhost, Cochrane, and EMBASE) targeting studies on hepatocellular carcinoma with RFA and MWA. Heterogeneity analyses and pooled outcomes using random-effect models with were evaluated to compare both thermal ablation methods. Results : Nine studies, which consists of 368 patients underwent RFA and 387 patients underwent MWA, were included in review. The findings showed no significant differences in pooled analysis of volume of ablation, complete ablation rate, local tumor progression, survival rates, major complications, and adverse events. Subgroup analysis showed significantly higher risk of local tumor progression in RFA in African populations. Conclusion : No statistically significant difference was seen between outcomes across studies. MWA may offer a potential for longer therapeutic response with comparable risk of complications and adverse outcomes., (© 2024 Imelda Rey et al., published by Sciendo.)

Objective: This systematic review aimed to compare the efficacy and safety of regorafenib and nivolumab, two FDA-approved second-line treatments for unresectable Hepatocellular Carcinoma (HCC)., Methods: Literature comparing the efficacy and safety of regorafenib and nivolumab in unresectable HCC patients was systematically searched across seven databases, including: PubMed, SCOPUS, Cochrane Database of Systematic Reviews, ScienceDirect, EBSCOhost, EMBASE, and ProQuest, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The search was done on April 2nd, 2023. Study quality and risk of bias were assessed using the Agency for Healthcare Research and Quality (AHRQ) and ROBINS-1 tools. The selected studies were included in the qualitative data synthesis., Results: Three trials found that HCC patients taking nivolumab had statistically insignificantly longer OS, TTP, and progression-free survival than those on regorafenib. Nivolumab increased ORR, with largely partial responses, and mixed DCR, with little statistical significance. All three studies showed that nivolumab had fewer side effects and improved tolerance., Discussion: Three retrospective cohort studies with a total of 383 regorafenib-receiving cohorts and 230 nivolumab-receiving cohorts were included in the qualitative analysis. Nivolumab was found to be superior in regards of longer overall survival, longer time to progression, higher objective response rate, and lower adverse event occurrence. However, statistical significance was not achieved in most of the parameters., Conclusions: The use of nivolumab is preferable as the second-line systemic therapy for unresectable HCC. More high-quality studies are urgently needed to generate quantitative analysis, and to encourage the formation of guidelines for second-line systemic therapy., (Copyright © 2024 Darmadi. This article is available under a Creative Commons License (Attribution 4.0 International).)

Long noncoding RNAs (lncRNAs) are a category of noncoding RNAs characterized by their length, often exceeding 200 nucleotides. There is a growing body of data that indicate the significant involvement of lncRNAs in a wide range of disorders, including cancer. lncRNA H19 was among the initial lncRNAs to be identified and is transcribed from the H19 gene. The H19 lncRNA exhibits significant upregulation in a diverse range of human malignancies, such as breast, colorectal, pancreatic, glioma, and gastric cancer. Moreover, the overexpression of H19 is frequently associated with a worse prognosis among individuals diagnosed with cancer. H19 has been shown to have a role in facilitating several cellular processes, including cell proliferation, invasion, migration, epithelial-mesenchymal transition, metastasis, and apoptosis. This article summarizes the aberrant upregulation of H19 in human malignancies, indicating promising avenues for future investigations on cancer diagnostics and therapeutic interventions., (© 2024 John Wiley & Sons Ltd.)

Individuals with inflammatory bowel disease (IBD) have been reported to be at an increased risk of infertility and sexual dysfunction. Although the relationship between them remains unclear, IBD severity is suspected to affect hormone levels and fertility. To analyze the impact of IBD severity on semen parameters and sex hormone levels in ulcerative colitis-type IBD (UC-IBD), we conducted a cross-sectional study involving 120 patients with UC-IBD in Adam Malik General Hospital, Medan, Indonesia. The patients were classified into three groups based on the Mayo score for UC, followed by a comparison of various semen and hormone parameters among these groups. In addition to the cross-sectional analysis, a simple correlation test was conducted irrespective of the patient grouping. Sperm concentration, motility, and morphology were found to decline significantly with an increase in IBD severity. Without classifying patients with IBD into subgroups, the Mayo score showed negative correlations with sperm concentration ( r = -0.375, P < 0.0001), rapid progressive motility ( r = -0.660, P < 0.0001), free testosterone ( r = -0.732, P < 0.0001), and total testosterone ( r = -0.721, P < 0.0001), and positive correlations with immotile sperm ( r = 0.660, P < 0.0001), abnormal morphology ( r = 0.657, P < 0.0001), and sex hormone-binding globulin (SHBG; r = 0.278, P = 0.002). Sperm concentration, motility, and morphology declined significantly with the severity of IBD. This study suggests a significant negative impact of IBD severity on semen quality and sex hormones., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Background: This study aims to determine the factors affecting HBV DNA suppression in chronic hepatitis B patients with tenofovir disoproxil fumarate (TDF). Methods: A case-control was carried out from October 2021 to August 2022 on 182 chronic hepatitis B patients who had TDF therapy regularly for 24 weeks at H. Adam Malik and USU Hospitals in Medan, Indonesia. The history of the samples was obtained, followed by physical examination, and blood collection. CTLA-4 polymorphism examination was carried out using real-time PCR, while the serum CTLA-4 levels were assessed with ELISA. Results:  The CTLA-4 -1661G>A polymorphism, genotype GG+AG, increased 1.52 times risk of not achieving HBV DNA suppression to TDF compared to genotype AA (p=0.041). High CTLA-4 levels increased 2.28 times risk, high HBV DNA levels increased 2.09 times risk, low ALT levels increased 1.95 times risk of not achieving HBV DNA suppression (p= 0.009, 0.026, 0.036, respectively). There was no relationship between gender, age, ethnicity, obesity, baseline AST, HBeAg, genotype, liver fibrosis and HBV DNA suppression after 24 weeks of treatment (p>0.05). Conclusions: The levels of CTLA-4, HBV DNA, ALT, and CTLA-4 -1661G>A polymorphism have a potential relationship with the suppression of HBV DNA in chronic hepatitis B patients with TDF., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Darmadi D et al.)

Introduction: Coronavirus disease-2019 (COVID-19) is still a global health problem nowadays. A particular COVID-19 patients develop severe symptoms. Some biomarkers can be used to determine disease severity and improve outcome. Homocysteine is one of the novel biomarkers. The objective of this study is to determine the role of serum homocysteine level in stratifying severity of COVID-19., Methods: A cross-sectional study was conducted in Medan, Indonesia from May to December 2021. Subjects were obtained using consecutive sampling method. Inclusion criteria was COVID-19 patients aged 18 years or older and willing to participate in the study. Patients with malignancy, chronic kidney disease, thyroid disease, coronary heart disease, and who consume several medications including cholestyramine, metformin, methotrexate, fibrate, and contraceptive pill, were excluded. Data regarding demographic, laboratory, and biomarker were gathered from each subject. Statistical analyses were conducted at 95% confidence interval., Results: A total of 100 patients were enrolled. Most subjects were males (59%) and from Batak ethnicity (64%). Twenty percent subjects had severe COVID-19. The levels of serum high-sensitivity C-reactive protein (hs-CRP), D dimer, homocysteine, and procalcitonin were significantly higher in severe COVID-19 subjects. D dimer had the highest sensitivity (91.7%) and specificity (94.7%) in stratifying severe COVID-19, followed by hs-CRP (91.7% and 85.5%, respectively), homocysteine (87.5% and 78.9%, respectively), and procalcitonin (58.3% and 74.0%, respectively)., Conclusion: Homocysteine can be used as a biomarker to determine COVID-19 severity., (© 2023 Jelita Siregar et al., published by Sciendo.)

Backgroud: Immune impairment, marked by increased expression of cytotoxic T lymphocyte antigen (CTLA)-4, promotes the disease progression of chronic hepatitis B., Objective: This study aimed to determine the association between serum CTLA-4 level and disease progression in patients with chronic hepatitis B., Methods: A cross-sectional study was conducted at Haji Adam Malik General Hospital Medan, Indonesia between October 2021 to September 2022. A total of 150 participants were enrolled. Patients aged 18 years or older with evidence of chronic hepatitis B, HBV-related liver cirrhosis, and HBV-related hepatocellular carcinoma (HCC) were enrolled. Exclusion criteria were history of chronic hepatotoxic drug consumption, underlying liver abnormalities other than HBV infection, and liver injury due to metastasized malignancy from other sites. Serum CTLA-4 level was determined from serum using human CTLA-4 enzyme linked immunosorbent assay kit., Results: Most participants were males and aged between 40 and 60 years. Serum CTLA-4 level was positively associated with chronic hepatitis B progression (P<0.001). Serum CTLA-4 level was negatively correlated with serum platelet (P<0.001) and albumin levels (P<0.001) but positively correlated with serum ALT (P=0.045) and total bilirubin levels (P<0.001)., Conclusions: Serum CTLA-4 level is associated with disease progression in patients with chronic hepatitis B., Competing Interests: authors declare that there are no conflicts of interest., (© 2023 Darmadi Darmadi, Dharma Lindarto, Jelita Siregar, Tri Widyawati, Muhammad Rusda, Mustafa Mahmud Amin, Fauzi Yusuf, Putri Chairani Eyanoer, Masrul Lubis, Imelda Rey.)

The phenomenon of the Industrial Revolution 4.0 currently emphasizes rapid technological advances. There is a need for innovation in technology development to package the current learning process more effectively, one of which is the development of learning media which is an important part of the learning process and is certainly directed at meaningful learning that encourages students to develop 21st Century skills as an urgency in the field of education. This study aims to 1) Develop interactive learning media with an articulate storyline based on a case method on cellular respiration material. 2) Look at students' responses to the interactive learning media articulate storyline based on the case method on cellular respiration material in training students' problem-solving skills. This research is a Research and Development (R & D). The development model in this study uses the Analysis, Design, Development, Implementation, and Evaluation (ADDIE) model, this research was carried out until the Development stage. The instruments used in this study were an open questionnaire sheet, material aspect validation sheet, media aspect validation sheet and pedagogic aspect validation sheet. The analytical technique used is descriptive qualitative analysis technique and quantitative analysis by finding the average score obtained from the validator's assessment and looking at the criteria. The results of this study obtained a very valid interactive learning media with a score of 3.9 material expert validators in the very valid category, 3.69 media expert validators in the very valid category, pedagogical expert validators of 3.47 in the valid category. It can be concluded that the articulate storyline interactive learning media based on the case method developed can improve students' problem-solving abilities., Competing Interests: Dominikus David Biondi Situmorang has the position to declare himself as a member of the journal's Editorial Team as an Associate Editor. However, this article has been handled by another unidentified Associate Editor and reviewed by the Reviewers in an objective and double-blind manner, according to applicable regulations from Elsevier, Heliyon, and Cell Press., (© 2023 The Authors.)

Introduction: This study aims to investigate the relationship between Neutrophil- Lymphocyte Ratio (NLR), Platelet-Lymphocyte Ratio (PLR) with Erectile Dysfunction (ED) and Peyronie's disease (PD)., Methods: We conducted a meta-analysis of the observational study by searching for the appropriate keywords in eight databases. The risk of publication bias of the included studies was assessed by Egger's test and Kendall's t. The data extraction was carried out for each study and analysed using Revman 5.0., Results: There were eleven eligible studies out of the 411 studies retrieved. Eight studies were conducted on cases of erectile dysfunction, and three studies on Peyronie's disease. There was a significant relationship between NLR, PLR and ED (SMD: 0.59, 95% CI: 0.33-0.85 and SMD: 0.64, 95% CI: 0.13-1.16, respectively). The same was also found for PD. The active phase of PD tended to have higher NLR (SMD: 0.68, 95% CI: 0.43-0.92) and PLR (SMD: 0.27, 95% CI: 0.06-0.49) compared to the chronic phase. No publication bias was found in both ED and PD studies., Conclusions: NLR and PLR indicate an ongoing inflammatory process in both ED and PD. These findings can be used as markers of treatment and prognosis of both diseases in sexual health care.

Background : The rate of infertility is increasing day by day. According to studies conducted worldwide, 30 million men are diagnosed with infertility. Cases of infertility are often associated with a failure to become male in society. Procreation and gender roles are often closely linked so that infertile men are often considered the second sex. Sometimes, this condition makes men question their masculinity. Methods : We performed a systematic review and metasynthesis with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline procedure on qualitative studies on ten databases exploring the experience of infertile men and their association with masculinity. Results : Twenty-four studies matched our question, and there are two major themes with eight subthemes that were obtained from the results of the metasynthesis of these studies. The impact of this gender issue is huge on men's health and their social interactions. As a result, gender issues provide a space for debate and a burden on men. Sometimes, men develop mental health problems. The topic of masculinity and infertility is at odds with feminism and is susceptible to the societal stigma that results from the hegemonic conception of masculinity. Interestingly, the men must accept reality and follow the treatment process for infertility, although it affects their psychological well-being. Conclusions : These findings provide insight for physicians, as treating infertility requires a multidisciplinary team that does not only address procreation issues. Social issues related to gender roles often bring patients into harmful and dangerous conditions. To address the gender issue in men globally in several dimensions, however, a large study in various populations is still required., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Pakpahan C et al.)

Increased lipid levels sometimes not only affect sexual function but also are considered to harm semen quality. It is often a suspicion that elevated lipids are a factor in infertility. We conduct a systematic review. Articles that met the criteria were identified according to The Preferred Reporting Items for Systematic Review and Meta-analysis of recommendations in the PubMed, ProQuest, EBSCO, Web of Science Wiley Online, Springer Link, Scopus, and Science Direct databases with no time restriction for publication. Seven studies are eligible for qualitative analysis from nine studies that have the potential to be assessed. These studies measure the correlation of serum lipids (VLDL, HDL, LDL, triglycerides, total cholesterol, free cholesterol, phospholipids, free fatty acids) with semen parameters (concentration, motility, morphology, DNA fragmentation index). Although not all studies consistently report that lipids impact semen quality, this review suspects that lipids have a significant impact on sperm quality. This study implies that it is necessary to maintain lipid levels to maintain sperm quality and quality of life. However, further investigation with an observational cohort study design needs to be carried out to assess the effect of lipids on semen quality more precisely for the promotion of reproductive health care., (© 2022. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Introduction: Hypogonadism and inflammato-ry bowel disease (IBD) are often associated. This association may influence sexual and reproductive function in IBD, including sperm profile and sex steroid hormones., Patients and Methods: This study included 59 IBD patients diagnosed with ulcerative colitis type IBD. Anamnesis was carried out regarding the history of the disease, along with a history of rectal bleeding. Evaluation proceeded with sperm and hormone examination if the patient agreed., Results: Progressive motility sperm, immotile sperm, and normal sperm were found to be significantly different between the rectal bleeding groups. In grade 3 (more significant bleeding) progressive sperm (24.81 ± 5.85, p < 0.0001) and normal sperm (6.33 ± 12.56, p = 0.0003) rates tended to be lower, while immotile sperm tended to be higher (44.48 ± 11.21, p < 0.0001). Testosterone and free testosterone levels were also reported to be significantly different between groups, where grade 3 had lower levels 255.9 ± 30.08, p = 0.014 and 4.645 ± 0.5, p = 0.002 respectively., Conclusions: Our study shows that the degree of rectal bleeding influences sperm motility and morphology, as well as testosterone and free testosterone levels. These results can concern managing IBD patients to fulfill reproductive health care.

Objective: The purpose of this study was to examine the sex lives of male cirrhotic patients organic factors affect them., Method: We did an observational study of 220 cirrhotic men's satisfaction with their sexual lives. Assessment of sex satisfaction was carried out using the New Sexual Satisfaction Scale. The frequency of intercourse and masturbation was estimated. Then, the levels of albumin, total bilirubin, vitamin D, and sex steroids were examined. Ascites and sarcopenia subgroups of our patients were stratified., Results: Along with sex steroids, albumin, total bilirubin, and vitamin D all had an impact on how satisfying sex was (r = 0.22), (r = 0.24), and (r = -0.17) affected sex satisfaction. There were strong positive correlations between vitamin D (r = 0.33), albumin (r = 0.59), and free testosterone, along with a negative correlation between total bilirubin (r = -0.63) and free testosterone. An imbalance in sex steroid levels was observed, leading to decreased frequency of intercourse(p < 0.0001), weakened erections(p < 0.0001), and reduced quality of orgasm (p < 0.0001). Significant new sex behavior changes were found, such as an increase in masturbation. Physical limitations such as ascites and sarcopenia also impacted the decreasing sex life., Conclusion: The sex life of cirrhotic men is affected. The decrease in the frequency of intercourse and sexual satisfaction is noticeable in male patients and leads to increased masturbation. Free Testosterone, vitamin D, albumin, and bilirubin play role in their sex life. In addition, ascites and sarcopenia not only affect their sex life but also hamper the quality of their well-being., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Darmadi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Tenofovir disoproxil fumarate (TDF) is a first-line nucleotide analog (NA) drug for hepatitis B therapy. Long-term NA therapy increases peripheral T cell levels to enhance antiviral response, while CTLA-4 inhibits the activation., Objective: This study analyzed the interaction between TDF and CTLA-4 through molecular docking., Methods: Target protein and ligand data mining were performed, and proteins were prepared by removing water molecules in the Discovery Studio 2019 software. The energy minimization was performed on ligands using Pyrx v.0.9.8 software. Protein-ligand docking was performed using Autodock Vina integrated with Pyrx v.09.8. Meanwhile, the docking of proteins was accomplished using the Haddock server. The BioVia Discovery Studio 2019 software visualized the interaction between the compound and the docked protein. Molecular dynamics simulations were carried out using the YASARA Dynamic program developed by Biosciences GmbH., Results: TDF ligand has good and stable inhibitory activity against the CTLA-4/B7-1 and CTLA4/B7-2 complexes. TDF docking has been shown to initiate conformational changes, indicating the ligand's inhibitory activity. The significant conformational changes based on superimposition results were shown by the CTLA-4/TDF/B7-2 and CTLA-4/B7-1/TDF complexes. TDF in all ligands undergoes bonding and displacement of binding sites., Conclusion: Treatment with TDF was predicted to have inhibitory activity against CTLA-4, especially in its complex form with B7-1 and B7-2., Competing Interests: None declared., (© 2023 Darmadi Darmadi, Dharma Lindarto, Jelita Siregar, Tri Widyawati, Muhammad Rusda, Mustafa Mahmud Amin, Fauzi Yusuf, Putri Chairani Eyanoer, Masrul Lubis, Imelda Rey.)

Background: The incidence of liver cancer is increased worldwide with 75%-85% diagnosed as hepatocellular carcinoma (HCC). Current practice has low sensitivity limitations to diagnose the early stages of HCC, thus urging the need for a biomarker with higher sensitivity to detect HCC, specifically in the early stage. This study aimed to determine the association between midkine levels and progressiveness of hepatocellular carcinoma (HCC), according to tumor size, Barcelona Clinic Liver Cancer (BCLC), and presence of portal venous thrombosis. Methods: This cross-sectional study involved 100 patients in Adam Malik General Hospital diagnosed with HCC, collected with a consecutive sampling method, whose diagnoses were confirmed by findings of hypervascular on arterial phase imaging and portal vein or delayed phase washout triple-phase CT Scan. Samples are later categorized according to Barcelona Clinic Liver Cancer (BCLC) stages, tumor size, and presence of portal venous thrombosis. Blood samples were drawn to measure serum midkine using ELISA. Kruskal-Wallis and Mann-Whitney U tests were conducted to determine the difference of midkine levels based on tumor size, BCLC staging, and presence of portal venous thrombosis. Results: Serum midkine level shows a significant difference over tumor size (p=0.014), no significant difference found compared to BCLC stages and presence of portal venous thrombosis. Conclusion: Serum midkine levels are associated with the tumor size of HCC, thus helping physicians determine treatment plans., (© 2022 Darmadi Darmadi et al., published by Sciendo.)

Background: Gastric cancer is the fifth most common malignancy and the third highest cancer-related mortality worldwide after lung and colorectal cancers. The gastric carcinogenesis is started with precancerous lesion. Prompt diagnosis and management of gastric precancerous lesion may prevent disease progression. Midkine is a growth factor associated with various cancers and proposed as a marker for detecting gastric precancerous lesion., Objective: The aim of the study is to determine the association between serum midkine level and gastric precancerous lesion in patients with gastritis., Methods: A cross sectional study was conducted at Haji Adam Malik general hospital. Subjects were obtained by consecutive sampling. Inclusion criteria were patients aged 18 years or older, diagnosed with gastritis from gastroscopy and histopathology results, and willing to cooperate in the study. Each subjects underwent interview and endoscopic examination. Serum midkine level was determined using enzyme-linked immunosorbent assay (ELISA) method. Chi square, receiver operating characteristic (ROC) curve, and logistic regression tests were applied., Results: A total of 160 subjects were enrolled with 29.4% had gastric precancerous lesion. Serum midkine level was associated with gastric premalignant lesion. Cut off point for serum midkine level was 252 pg/mL with area under the curve of 0.816 (p<0.001). It's sensitivity, specificity, and accuracy in diagnosing gastric precancerous lesion were 74.5%, 71.7%, and 72.5%, respectively. Helicobacter pylori infection, high serum midkine level, heavy alcohol drinker, and family history of gastric cancer were risk factors for gastric precancerous lesion., Conclusion: Serum midkine level is associated with gastric premalignant lesion in patients with gastritis and has good diagnostic values., (© 2022 Jelita Siregar, Darmadi Darmadi, Ratna Akbari Ganie.)

The signs of aging in humans can often be detected through a decrease in bone mass density (BMD). The decrease in BMD as a risk of osteoporosis is often only seen in women, but not in men, even though men also have a risk of osteoporosis which can affect their well-being. We conducted study searches through databases such as PubMed, EBSCO, ProQuest, Willey Online, Science Direct, and SAGE. We performed analysis on four types of Vitamin D receptor polymorphisms: BsmI, ApaI, FokI, and TaqI from 14 potential studies involving men. We found that several genetic analysis models of BsmI and FokI significantly affected BMD in men: BB vs bb in whole body BMD (SMD = 0.43, 95% CI = [0.12-0.75], p = 0.0008, BB vs Bb in whole body BMD (SMD = -1.38, 95% CI = [-1.87 to 0.88], p < 0.00001), and FF+Ff vs ff spine BMD (SMD = 0.59, 95% CI = 0.13-1.05], p = 0.001), even after adjusting for comorbidities as confounding variables. The present meta-analysis showed that BsmI and FokI polymorphisms of the VDR gene were correlated with decreased BMD in men which may contribute to the aging process and well-being., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Since thousands of years ago, oral sex has become part of sexual behavior among humans. Oral sex is considered taboo. Its taboo does not lie in the behavior, but its expression is deemed inappropriate. As technology becomes more sophisticated, human rights also stand out, leading to the disclosure of the practice in the 21 st century. The oral sex that is discussed on a large scale in media encourages people to express it as feedback whether within right or not. It all depends on the value of each people. We found that this sexual behavior is found everywhere regardless of religion, culture, and race. Pop culture influences this behavior so much, it can be seen from music, movies, and television programs that provoke oral sex. Many motivations underlying this behavior include getting sexual pleasure for the sake of living well-being. But it is undeniable that this behavior is still controversial. It could be at risk of causing disease and, on the other hand, is reported to provide many benefits.  According to our theory, oral sex is not a new behavior crossing boundaries. It is just an old behavior that surfaces because of the factors that support it. This behavior, which is still considered taboo, has its disadvantages such as sexually transmitted disease but has also benefits such as preventing preeclampsia., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Pakpahan C et al.)

Background: Coronavirus disease (COVID-19) remains a global health problem. COVID-19 patients with severe pneumonia have a higher risk for critical illness, mostly complicated by acute respiratory distress syndrome. The inflammatory response is critical, and the cytokine storm increases the severity of COVID-19. Many factors could be associated with a cytokine storm but they are incompletely understood. This study presents characteristics of COVID-19 patients and explore the clinical and inflammatory parameters of severe and critically ill COVID-19 patients in the intensive care unit (ICU). Method: This cross-sectional study was conducted in all severe COVID-19 patients admitted to the ICU. Peripheral blood was taken for laboratory examination within 24 hours of admission. Haematologic parameters, serum electrolyte, renal function, liver function, pancreas enzyme, D-dimer, inflammatory cytokines interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, monocyte chemoattractant protein-1 (MCP-1), and C-reactive protein (CRP) were assessed in this study. Comparative analyses were done between sex, existing comorbidities, body mass index (BMI), and COVID-19 vaccination status. Results: A total of 80 subjects were included in the study. The most frequent comorbidities found among the subjects were obesity (36.35%) and diabetes (22.5%). Only 13.75% of subjects were vaccinated. Laboratory results indicated leucocytosis and neutrophilia, with a neutrophil-lymphocyte-ratio (NLR) of 7. The mean inflammatory findings (IL-6, IL-10, TNF-alpha, IFN-gamma, MCP-1), D-dimer, CRP, and lipase increased. Lipase levels were higher in men (p = 0.003) and in comorbidity groups. No significant differences were found among different BMI groups. Lipase, IL-6, and MCP-1 levels were significantly higher (p=0.019, <0.0001, and 0.03, respectively) in the non-vaccinated group. Conclusions: Most patients with severe COVID-19 have comorbidities and increased inflammatory markers., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Darmadi D et al.)

Background: The most common glomerular disease in children is nephrotic syndrome. Steroid-resistant nephrotic syndrome tends to have a worse disease course, which bears a significant risk of chronic kidney disease in children., Objective: To compare VEGF and neopterin levels between children with steroid-sensitive nephrotic syndrome (SSNS), steroid-resistant nephrotic syndrome (SRNS), and also healthy (control) children., Methods: This cross-sectional study was conducted at H. Adam Malik General Hospital, Indonesia from January to December 2018. There were 160 children aged 1 to 8 years with confirmed nephrotic syndrome and without end-stage renal disease and systemic diseases, divided into SSNS, SRNS, and control groups. Data regarding age, gender, urine albumin creatinine ratio (UACR), serum albumin, total cholesterol, urea, creatinine, VEGF, and neopterin levels were collected. A p-value of less than 0.05 is considered statistically significant., Results: There were no differences between groups in gender (p = 0.269) and age (p = 0.375), but there was significant difference of UACR, albumin level, total cholesterol level, and VEGF level between groups, (all p< 0.001). There was a moderate positive correlation between VEGF level and UACR (r(158) = 0.439, p< 0.001) and a moderate negative correlation between neopterin level and albumin level (r(158)= -0.312, p = 0.005)., Conclusion: There were no differences in serum VEGF and neopterin levels between steroid-sensitive and steroid-resistant nephrotic syndrome groups. Serum VEGF level was positively correlated with UACR while serum neopterin level was negatively correlated with serum albumin level., Competing Interests: There are no conflicts of interest., (© 2021 Riska Habriel Ruslie, Darmadi Darmadi, Gontar Alamsyah Siregar.)

What is new? Serum IL-12 level is associated with NAFLD severity. Elevation in serum IL-12 level is in line with more severe NAFLD based on BARD score and NAFLD fibrosis score. Positive correlation is observed between serum IL-12 level and BARD score. Introduction. Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. Lipid accumulation in the liver triggers inflammation and leads to NAFLD. Prolonged inflammation will worsen the disease progression. Pro-inflammatory cytokines, including interleukin (IL)-12, plays a role in the inflammatory process. This study aimed to determine the association between IL-12 and NAFLD severity. Methods. A cross-sectional study was conducted between January and July 2019 in Haji Adam Malik Hospital Medan, Indonesia. Subjects were patients aged 18 years or older diagnosed with NAFLD based on ultrasound. Exclusion criteria were excessive alcohol consumption, other primary liver diseases, malignancies, and cardio-metabolic disturbances. Serum IL-12 level was determined using an enzyme-linked immunosorbent assay method. The severity of NAFLD was assessed using the BARD score and NAFLD fibrosis score. Results. A total of 100 subjects were enrolled with male predominant. The mean age of subjects was 54.97 ± 8.85 years, and the most frequent comorbidity was obesity. Most subjects had mild to moderate disease progression. Serum IL-12 level was higher in more severe NAFLD based on ultrasound grading (P < 0.001), BARD score (P = 0.003), and NAFLD fibrosis score (P = 0.005). A positive correlation was observed between serum IL-12 level and BARD score (P < 0.001) with sufficient accuracy (AUC = 0.691, P = 0.014). Conclusion. Serum IL-12 level was associated with the severity of NAFLD. Higher serum IL-12 level was observed in more severe NAFLD progression., (© 2021 Darmadi Darmadi et al., published by Sciendo.)

Aim To compare oxidative stress state of children with nephrotic syndrome at the first week of treatment and in remission, and to predict malondialdehyde (MDA) level from routine laboratory tests. Methods This cross-sectional study involved 80 1-18 years old children with nephrotic syndrome, who were divided into two groups: initial group (40 children in the first week of therapy) and remission group (40 children in remission). Demographic characteristics of the patients were taken by a questionnaire. Laboratory tests were measured in the initial group; in the remission group negative or trace proteinuria was measured for three consecutive days. Serum urea, creatinine, albumin, total cholesterol, MDA, superoxide dismutase, glutathione peroxidase, and urine albuminto-creatinine ratio (UACR) were measured and compared between the groups. Albumin, total cholesterol, and UACR were subjected to predict high serum MDA using a mean of all patients' MDA level as a cutoff. Results There were higher albumin levels and lower UACR, total cholesterol, and MDA in the remission group compared to the initial group. Albumin and UACR showed good accuracy, and total cholesterol showed very good accuracy to predict serum MDA level more than 1.35 µmol/L. Conclusion Children with nephrotic syndrome in the first week of therapy showed a higher oxidative stress state than the children in remission. Serum albumin, serum total cholesterol, and UACR can predict serum MDA level with good accuracy., (Copyright© by the Medical Assotiation of Zenica-Doboj Canton.)

Objective: We aimed to determine the neem leaf extract's effect on Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-6 (IL-6) expressions in dextran sodium sulfate (DSS)-induced colitis rats., Materials and Methods: In the first phase of the study, colitis was induced by DSS administration in the case group and compared to the control group. In the second phase, 84 colitis rats were divided into groups I, II, and III receiving 7.8 mg/day of mesalazine, 100 mg/200 gm body weight, and 200 mg/200 gm body weight neem leaf extract, respectively., Results: TNF-α and IL-6 expressions were significantly increased in the case group compared to the control group. TNF-α and IL-6 expressions were decreasing in all groups receiving treatment. Group III showed an earlier decrease compared to group II. TNF-α and IL-6 expressions in group III were comparable with group I since the second week. This condition was observed in the 4th week between group II and group I., Conclusion: It can be concluded that neem leaf extract decreased the expression of TNF-α and IL-6 in DSS-induced colitis., Competing Interests: The authors declare that they have no conflict of interest., (Copyright: © Journal of Advanced Veterinary and Animal Research.)

Aim To determine the role of endothelin (ET)-1 in predicting hepatopulmonary syndrome (HPS) in patients with liver cirrhosis. Methods A cross sectional study involving 80 liver cirrhosis patients aged 18 years or older was conducted in Adam Malik General Hospital Medan, Indonesia between July 2017 and June 2018. HPS diagnosis was confirmed from the presence of liver cirrhosis, abnormal oxygenation, and intrapulmonary vascular dilatations (IPVD). ET-1 level was measured from serum sample using ELISA method. Patients with coexisting primary pulmonary pathology and intrinsic heart disease were active smokers, and those who declined to participate were excluded. Statistical analysis was conducted at 95% confidence interval. p<0.05 was considered significant. Results Majority the patients were male (56.3%) and had higher educational background (62.5%). Mean age of the patients was 51.3 (SD=12.6) years. The prevalence of HPS was 21.2%. The patients with HPS had higher ET-1 level compared to those without HPS (p<0.001). The patients with hepatic encephalopathy had 2.917 times higher risk for suffering from HPS, while the patients with Child Pugh score A had lower risk (0.738 times) for having HPS compared to subjects with Child Pugh score B and C. ET-1 level >187.5 mg/L had sensitivity and specificity for predicting HPS in subjects with liver cirrhosis of 82.35% and 81.25%, respectively. Conclusion ET-1 could be used as a promising marker for HPS in patients with liver cirrhosis. ET-1 level of >187.5 mg/l had a good accuracy in predicting HPS in liver cirrhosis patient., (Copyright© by the Medical Assotiation of Zenica-Doboj Canton.)