Search

Nowadays, polyurethane (PU) foam has successfully replaced various engineering materials in many applications due to its many advantages in mechanical and thermal properties. In various applications, PU foam must be formed into various 3-dimensional models according to user requirements by utilizing CAM software and CNC milling machining to manufacture a product. Thus, the selection of cutting parameters in the milling machining process in terms of the nature and character of the material and cutting tools is essential and significantly influences the geometric structure and surface roughness of the PU foam products produced. Based on the review of this article, several machining parameters must be appropriately considered, including spindle rotation speed, depth of cut, cutting tool selection, and feed rate. Vibration will increase as the spindle rotation speed increases, which brings cutting tools but results in better surface quality. Continuous chip formation can be achieved by selecting the proper cut depth and producing low surface roughness values. Selecting suitable cutting tools and geometries that match the material characteristics can reduce the risk of material damage during the machining process, thereby reducing the surface roughness value. Finally, a low cutting rate will minimize surface roughness but increase the risk of cutting-edge wear.

Elisna Syahruddin,1,2 Laksmi Wulandari,3 Nunuk Sri Muktiati,4 Ana Rima,5 Noni Soeroso,6 Sabrina Ermayanti,7 Michael Levi,8 Heriawaty Hidajat,2 Grace Widjajahakim,8 Ahmad Rusdan Handoyo Utomo9 1Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Indonesia; 2Department of Pulmonology, Persahabatan Hospital, Jakarta, Indonesia; 3Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Airlangga – Soetomo Hospital, Surabaya, Indonesia; 4Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Brawijaya – Saiful Anwar General Hospital, Malang, Indonesia; 5Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Sebelas Maret, Dr. Moewardi General Hospital, Surakarta, Indonesia; 6Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, University of Sumatera Utara, Adam Malik General Hospital, Medan, Indonesia; 7Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Andalas University, M. Djamil Hospital, Padang, Indonesia; 8Kalbe Genomics Laboratory, Division of Molecular Pathology Testing Service, PT Bifarma Adiluhung, 9Stem Cell and Cancer Institute, Cancer Diagnostic Research Division, PT Kalbe Farma Tbk, Jakarta, Indonesia Purpose: We aimed to evaluate the distribution of individual epidermal growth factor receptor (EGFR) mutation subtypes found in routine cytological specimens.Patients and methods: A retrospective audit was performed on EGFR testing results of 1,874 consecutive cytological samples of newly diagnosed or treatment-naïve Indonesian lung cancer patients (years 2015–2016). Testing was performed by ISO15189 accredited central laboratory.Results: Overall test failure rate was 5.1%, with the highest failure (7.1%) observed in pleural effusion and lowest (1.6%) in needle aspiration samples. EGFR mutation frequency was 44.4%. Tyrosine kinase inhibitor (TKI)-sensitive common EGFR mutations (ins/dels exon 19, L858R) and uncommon mutations (G719X, T790M, L861Q) contributed 57.1% and 29%, respectively. Approximately 13.9% of mutation-positive patients carried a mixture of common and uncommon mutations. Women had higher EGFR mutation rate (52.9%) vs men (39.1%; p

The prevalence of stunting in Indonesian children under five years of age is about 20%. Chronic maternal malnutrition contributes to the risk of stunting by affecting global DNA methylation. In the present study, we aimed to evaluate the levels of 5-methyl-cytosine (5mC), as a surrogate marker of global DNA methylation, in buccal swabs and its potential association with risk of stunting and cognitive performance. The levels of 5mC were measured using the enzyme-linked immunosorbent assay. The Wechsler Preschool and Primary Scale of Intelligence was used to measure cognitive functions. Buccal swab DNA samples and anthropometric data were collected from a total of 231 children aged zero to five years. In this cross-sectional cohort, the prevalence of stunting was 37% in 138 children aged zero to two years and 30% in 93 children aged > two years. The univariable analysis revealed that the levels of 5mC in buccal swab DNA were significantly lower in severely stunted children (median, 2.84; interquartile range [IQR], 2.39-4.62; P -value, 0.0314) and in children of a younger age (median, 2.81; IQR 2.53-4.62, P- value, 0.0001) than in normal (median, 3.75; IQR, 2.80-4.74) and older children (median, 4.01, IQR, 3.39-4.87), respectively. We also found that the average cognitive scores tended to be low in boys and stunted children, although the differences were not statistically significant. Furthermore, levels of 5mC found in buccal and mouthwash DNA were not associated with cognitive scores.

Whole-genome sequencing (WGS) has played a significant role in understanding the epidemiology and biology of SARS-CoV-2 virus. Here, we investigate the use of SARS-CoV-2 WGS in Southeast and East Asian countries as a genomic surveillance during the COVID-19 pandemic. Nottingham-Indonesia Collaboration for Clinical Research and Training (NICCRAT) initiative has facilitated collaboration between the University of Nottingham and a team in the Research Center for Biotechnology, National Research and Innovation Agency (BRIN), to carry out a small number of SARS-CoV-2 WGS in Indonesia using Oxford Nanopore Technology (ONT). Analyses of SARS- CoV-2 genomes deposited on GISAID reveal the importance of clinical and demographic metadata collection and the importance of open access and data sharing. Lineage and phylogenetic analyses of two periods defined by the Delta variant outbreak reveal that: (1) B.1.466.2 variants were the most predominant in Indonesia before the Delta variant outbreak, having a unique spike gene mutation N439K at more than 98% frequency, (2) Delta variants AY.23 sub-lineage took over after June 2021, and (3) the highest rate of virus transmissions between Indonesia and other countries was through interactions with Singapore and Japan, two neighbouring countries with a high degree of access and travels to and from Indonesia.

<b>Background and Objective:</b> Two Indonesian lactic acid bacteria of<i> L. plantarum </i>I IA-1A5 and <i>L. acidophilus </i>IIA-2B4 were previously isolated from beef with some functional probiotic properties. Nevertheless, the possibility of these strains to have anticancer activity remains unknown. Current study aimed to evaluate the inhibitory properties of intra-and extracellular protein extracts of these two strains against cervical cancer HeLa cells. <b>Materials and Methods:</b> The intracellular and extracellular proteins extract from <i>L. plantarum </i>IIA-1A5 and <i>L. acidophilus </i>IIA-2B4 were collected and designated as IP-LP, IP-LA, EP-LP and EP-LA, respectively. The effect of these extracts on the viability and morphology of HeLa cells were observed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and confocal microscopy, respectively. <b>Results:</b> Both IP-LP and IP-LA inhibited HeLa cells in a concentration-dependent manner, with IC<sub>50</sub> values of 352.62 and 120.97 μg mL<sup>1</sup>, respectively. Meanwhile, the inhibition activity was also observed for EP-LP and EP-LA, <i>albeit</i> very low. The inhibition effect was also confirmed by morphological analysis under confocal electron microscopy which showed the changes in the cell shapes and numbers. <b>Conclusion:</b> Altogether, for the first time this study proposed that the probiotic isolated from Indonesian beef are promising to inhibit cancer cell lines.

The outbreak of coronaviruses (CoVs) presents an enormous threat to humans. To date, no new therapeutic drugs or vaccines licensed to treat human coronaviruses remain undiscovered. This mini-review briefly reports the number of potential plants widely distributed in Indonesia for further research and development as anti-SARS-CoV-2 agents and the critical targets for SARS-CoV-2 therapy, such as angiotensin-converting enzyme 2 (ACE-2) receptor, spike protein, 3-chymotrypsin-like protease (3CL pro ), papain-like protease (PL pro ), RNA-dependent RNA polymerase (RdRp), helicase, and serine protease. Indonesia is rich in medicinal plants (herbal); it also has a long history of using plants to treat various hereditary diseases. However, since SARS-CoV-2 is a new disease, it has no history of plant-based treatment anywhere in the world. This mini-review describes natural products from several Indonesian plants that contain compounds that could potentially prevent or reduce SARS-CoV-2 infection, act as potential targeted therapy, and provide new therapeutic strategies to develop SARS-CoV-2 countermeasures., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

Introduction: the objective was to evaluate the impact of IDH1 R132H mutation, MGMT methylation and PD-L1 expression in high grade glioma that received standard therapy (surgery, radiation and chemotherapy) to overall survival (OS)., Methods: this is a retrospective study of 35 high grade glioma cases. Genotyping of IDH1 gene alteration on the mutation hotspot R132 (Sanger sequencing method with Applied Biosystems 3500 Genetic Analyzer), EZ DNA Methylation-Gold kit (Zymo Research) is used to study the methylation, Cell line BT549 (ATCC HTB-122) and HCT-116 (ATCC CCL-247) were used as unmethylated control and partially methylated control respectively. Anti-human PD-L1 antibody clone E1L3N ® from Cell Signalling Technology (USA) and Rabbit XP ® were used to see PDL-1 expression., Results: anaplastic astrocytoma cases had more MGMT promoter methylation (50%) than glioblastoma multiforme (GBM) (20%), more IDH1 R132H mutation (42%) than GBM (4.3%). Immunohistochemistry tumor proportion score method (TPS) identified 17% and 8.7% were PD-L1 positive in AA and GBM groups, respectively. Cases with IDH1 R132H mutation and MGMT methylation still showed better OS although with high PD-L1 expression., Conclusion: IDH1 R132H mutation and MGMT methylation were good prognostic markers. High expression of PD-L1 apparently might not indicate poor overall survival in the presence of IDH1 R132 mutation and MGMT methylation., Competing Interests: The authors declare no competing interests., (Copyright: Julius July et al.)

Background: Tumor cells express programmed death ligand-1 (PD-L1) through several biological processes, thereby having different clinical significance depending on the underlying mechanism of expression. Currently, mechanisms leading to PDL1 gene expression in colorectal cancer (CRC) are not fully understood., Methods: We investigated 98 Indonesia CRC patients to determine PD-L1 protein expressions and their correlations with PD-L1 gene copy number status, tumor infiltrating lymphocytes (TILs), tumor mutational profile, as well as clinicopathologic features., Results: Our investigation demonstrated that 18% of patients positively expressed PD-L1. Further analysis on PD-L1 copy number revealed that all PD-L1+ tumors had normal copy number, indicating that the expression of PD-L1 was not a consequence of genetic amplification of PD-L1. From TILs analysis, there was a significant increase of CD8 in all tumor cells expressing PD-L1 (P=0.0051), indicating that the inducible PD-L1 expression was the prominent mechanism occurred in CRC. Furthermore, the expression of PD-L1 in this CRC population was significantly associated with high frequency of MSI compared to the remainder PD-L1- tumors (P=0.0001), suggesting the natural immunogenicity of tumors via MSI status plays role in attracting immune response. On the other hand, p53 mutations which were frequently observed within Indonesian CRCs (76.5%), they were not associated with PD-L1 expression (p=0.1108), as well as KRAS gene (29.6%; p=0.5772) and BRAF gene mutations (5%; p=0.2171)., Conclusion: Our study demonstrated that PD-L1 expressions in CRC were predominantly found as a consequence of infiltrating CD8 T lymphocytes that in part arise in the setting of microsatellite instability. Taken together, our findings further support the role of adaptive immune resistance to drive PD-L1 induction in tumor microenvironment and may provide important rationale for strategy implementation of immunotherapy for CRC cases., .

Background: Defining the presence of BCR-ABL transcript in suspected myeloproliferative neoplasm is essential in establishing chronic myeloid leukemia. In the absence of BCR-ABL, the conventional diagnostic algorithm recommends JAK2 V617F mutation testing to support diagnosis of other MPN diseases such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis. In certain cases of thrombocythemia, simultaneous upfront testing of both BCR-ABL and JAK2 may be desirable. We wanted to test the feasibility of multiplex detection of BCR-ABL transcript variants and JAK2 V617F mutation simultaneously using the reverse transcriptase polymerase chain reaction (RT-PCR)-based reverse dot-blot hybridization (RDB) method., Material and Methods: Separate biotinylated RT-PCR primers were designed to amplify specific BCR-ABL transcripts and JAK2 V617F mutant alleles. Specific hybridization of RT-PCR products with arrays of membrane-bound probes followed by colorimetric development would allow simultaneous visualization of BCR-ABL and/or JAK2 mutant transcripts in a given specimen. To validate the RDB method, we used cDNA specimens previously referred to our laboratory for routine clinical testing of BCR-ABL and/or JAK2., Results: The limit of detection or analytical sensitivity of the RDB method using cDNA specimens was 0.5% and 6.25% in detecting BCR-ABL and JAK2 mutant transcripts, respectively. The diagnostic specificity and sensitivity to detect BCR-ABL and JAK2 were 100% and 92.3% (N = 38); and 100% and 100% (N = 27), respectively. RDB also detected BCR-ABL transcripts in 22% of JAK2 V617F mutation-positive samples (N = 14)., Conclusions: RT-PCR RDB is a promising qualitative multiplex method to detect BCR-ABL and JAK2 mutant transcripts simultaneously., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: K-RAS and recently N-RAS gene mutation testing are mandatory requirements prior to anti-epidermal growth factor receptor (EGFR) monoclonal antibody treatment of metastatic CRC. Mutation prevalence and distribution in Indonesian colorectal cancer (CRC) are not known., Methods: Combined methods of PCR high-resolution melt (HRM), restriction fragment length polymorphism (RFLP), and direct DNA sequencing were used to genotype exons 2, 3, and 4 of both K-RAS and N-RAS genes for routine clinical testing of CRC patients. Descriptive analytical review of 595 consecutive CRC patients (years 2013 to 2016) was performed to find associations between gene mutations and clinicopathologic features., Results: This retrospective study revealed overall K-RAS gene mutation in exon 2 (codon 12 and 13) rates being 34.9%. Women (42.5%), stages I and II (43.4%), and well and moderate differentiations (37.7%) had higher frequency of K-RAS exon 2 mutations than men (29%, p = 0.006), stages (III and IV 31.9%, p = 0.05), and poor differentiation (11.8%, p = 0.002), respectively. At later period (2015-2016), 121 of 595 patients were genotyped for the remaining exons 3 and 4 of K-RAS as well as exons 2, 3, and 4 of N-RAS mutations resulting in overall RAS mutation prevalence of 41%. Mucinous histology had highest frequency of N-RAS mutation., Conclusions: Combination of PCR HRM with either RFLP or direct DNA sequencing was useful to detect K-RAS exon 2 and extended RAS mutations, respectively. Frequency of all RAS mutations in stage IV Indonesian (41%) was similar among Asians (41-49%), which tend to be lower than western (55%) CRC.

Purpose: We sought to evaluate prevalence, age-adjusted distribution, and impact of single and multiple high- and low-risk human papillomavirus (HPV) subtypes and their associations with cervical lesions., Methods: Data were extracted from 11,224 women who underwent routine screening of HPV genotyping and liquid-based cytology co-testing. Fifteen high-risk (HR) and six low-risk (LR) HPV types were genotyped., Results: Overall HPV prevalence was 10.7 %, and young women (under 21 years old) harbored highest HPV infection rate (40.38 %). The rate declined in old women 9.49 % (age 30-49) and 6.89 % (age 50 and above). Normal cytology had lowest HPV (5.66 %) compared to low-grade (60.49 %), high-grade (71.96 %) squamous intraepithelial lesions (LSIL and HSIL) and squamous cell carcinoma SCC (86.9 %). LR HPV subtypes were absent in SCC and were consistently lower than HR HPV in LSIL (6.74 vs. 33.54 %) and HSIL (2.12 vs. 51.32 %). Multiple HPV infection was more frequent in young women under 30 years old (10 %) than older women (2 %) and in LSIL (20.2 %), HSIL (18.5 %) than SCC (4.4 %). HR HPV 52, 16, 18, and 58 were the most frequent subtypes in normal, LSIL, and HSIL. Greater or equal proportion of HPV 16, 18, 45, and 52 was found in SCC compared to normal cytology (SCC/normal ratios 4.8, 1.2, 1.6, and 1.7). While important in LSIL and HSIL, HPV58 was not detected in SCC., Conclusion: Taken together, identification of these HPV types, especially HPV 16, 18, 45, and 52, and their associated cervical lesions may improve cervical cancer preventive strategies in Indonesia.

Colorectal cancer is an emerging public health problem in Indonesia and currently ranks among the three highest cancers. Lack of a colonoscopy screening and lifestyle changes might contribute to it. In the last few decades, there is an increasing interest towards the contribution of genetic-environment interaction in colorectal carcinogenesis. Some studies have indicated that CRC might develop through several different pathways; the three major routes are chromosomal instability (CIN), microsatellite instability (MSI), and inflammatory pathways. An earlier study on clinical epidemiology of CRC in Indonesia showed that the majority of patients were diagnosed between 45 and 50 years old, with a mean age around 47 years old. Further studies showed that most young Indonesian cases of CRC do not have hereditary characteristics; however, the CRC did not follow the conventional pathways of sporadic CRC (the CIN) pathway. Rather, it is a mixed of MSI and inflammatory pathways. Immunohistochemical studies showed that the proportion of patients with negative mismatch repair proteins was 43.5% for MSH2 and 83.5% for MLH1. Along the sporadic colorectal carcinogenesis pathway, there was a specific role of cyclooxygenase-2 (COX-2) enzyme during the polyp formation. COX-2 expression was reported in about 80% CRC cases worldwide. However, our study found only 49% of COX-2 expression among the CRC patients. Interestingly, an inflammatory marker, the nucleus factor κB (NF-κB), was expressed in about 73.5% cases, in line with a previous study. More recently, KRAS has been used as a potential tumor marker to select treatment and its expression was reported to be as high as 30%-40% worldwide. However, we found that KRAS gene expression was only 16.3%. Our findings support that CRC patients in Indonesian might follow a distinct pathway, a hypothesis that deserves further exploration.

Pharmacogenetic is broadly understood as study or clinical testing of genetic variations that contribute to differing response to drugs. In cancer treatment, applications of pharmacogenetic cover three areas: avoidance of adverse drug reaction (ADR), selection of treatment options, and prediction of cancer recurrence. Patients with genetic variations in UGT1A1 and DPYD genes are hypersensitive to Irinotecan and 5-Fluorouracil (5FU) respectively. Therefore, the chance for the patients to suffer from ADR from using those drugs can be predicted a priori by simple genetic tests. Secondly, the efficacy of targeted therapy drugs such as Cetuximab and Erlotinib, or non- targeted agents such as temozolomide and nitrosourea has been influenced by the presence of certain genetic or epigenetic markers in tumors. Lastly, microarray analysis to evaluate 70-gene expression profile in breast cancer samples has been shown in recent studies to predict probability of breast cancer recurrence. Patients whose tumors have been determined to have low probability score based on the gene expression profile may omit chemotherapy altogether, avoiding unnecessary therapeutic side effects. In summary, pharmacogenetic tests help patients, their caregivers, and doctors in deciding the best treatment options with favorable chance of success, as well as saving overall treatment costs.

We have developed a universal system for temporal, spatial, and cell type-specific control of gene expression in mice that (1) integrates the advantages of tetracycline-controlled gene expression and Cre-recombinase-loxP site-mediated gene inactivation, and (2) simplifies schemes of animal crosses by combination of two control elements in a single transgene. Two transgenic strains were generated in which the cell type-specific control was provided by either the retinoblastoma gene promoter or the whey acidic protein promoter. Both promoters drive the expression of the reverse tetracycline-controlled transactivator (rtTA). Placed in cis configuration to the rtTA transcription unit, the rtTA-inducible promoter directs expression of Cre recombinase. In both strains crossed with cActXstopXLacZ reporter mice, which have a loxP-stop of transcription/translation-loxP-LacZ cassette driven by chicken beta-actin promoter, Cre-loxP-mediated DNA recombination leading to LacZ expression was accurately regulated in a temporal, spatial, and cell type-specific manner. This approach can be applied to establishment of analogous mouse strains with virtually any promoter as systems to control gene regulation in a variety of cell types.