Sistem Pakar Untuk Membantu Dalam Mendiagnosa Penyakit Paru Basa (Efusi Pleura) Menggunakan Metode Rule Based Expert System

Indonesia sebagai suatu negara tropis dan tingkat kelembaban yang cukup tinggi memiliki salah satu masalah kesehatan yang cukup serius disebabkan oleh penyakit paru basah, salah satu varian penyakit ini yaitu Tuberkulosis merupakan salah satu penyakit infeksi terpenting setelah malaria. Untuk dapat menjadi seseorang yang benar-benar dapat dikatakan seorang Pakar dibidang tertentu (dalam hal ini adalah Dokter ahli/Spesialis) memerlukan waktu yang sangat lama untuk mempelajari berbagai pengetahuan dasar yang diperlukan, kondisi-kondisi khusus yang diperoleh dari pengalaman praktik, serta biaya yang tidak sedikit. Apalagi di Indonesia saat ini untuk memperoleh gelar seorang dokter ahli/spesialis memerlukan waktu yang sangat lama (+/- 12 Tahun) karena waktu pendidikan yang diperlukan untuk menjadi dokter umum adalah (+/- 6 tahun), kemudian harus tugas praktek terlebih dahulu selama 2-3 tahun, kemudian barulah dapat mengambil dokter spesialis dengan jangka waktu pendidikan sekitar 3-4 tahun. Tetapi hal ini dengan semakin berkembangnya teknologi perangkat lunak dalam bidang komputer, khususnya dibidang Sistem Pakar (Expert System) maka pengetahuan seorang Pakar dapat kita masukkan secara lengkap kedalam suatu perangkat lunak yang kita buat dengan metode-metode tertentu. Tujuan tugas akhir ini adalah mengaplikasikan sistem pakar berbasis aturan (rule based expert system) dalam lingkup tertentu yaitu pengidentifikasian penyakit paru basah dengan menggunakan metode backward chaining. Sebelum melakukan perancangan sistem pakar, terlebih dahulu dilakukan pengumpulan data dan informasi serta pemahaman cara kerja seorang pakar, setelah itu membuat suatu pohon keputusan yang menggambarkan cara kerja seorang pakar dalam menganalisa masalah dan mengambil keputusan. Langkah selanjutnya adalah merancang suatu basis pengetahuan (Knowledge base) berupa sistem berbasis aturan (Rule based expert system) yang akan merepresentasikan pengetahuan yang ada pada pohon pengambil keputusan tersebut. Sistem pakar ini menggunakan teori kepastian (Certainty Factor) untuk menangani fakta-fakta dan aturan-aturan yang tidak tepat dan tidak pasti. Ketidakpastian merupakan suatu masalah karena dapat menghambat kita dalam membuat keputusan yang terbaik dan bahkan mungkin menyebabkan kita membuat keputusan yang merugikan. Sumber-sumber ketidakpastian dalam sistem pakar meliputi: • Ketidakpastian bukti-bukti • Penggunaan bahasa yang kurang dimengerti • Latar belakang pendidikan seseoran

MANFAAT ELECTRONIC WORD OF MOUTH PADA KEPUTUSAN PEMBELIAN (STUDI KASUS: @AFTERGLOW.THELABEL)

Electronic word of mouth (e-WOM) is a word of mouth marketing done with orally and in writing, distributed through electronic media, and containing consumer experiences when purchasing products. This study aims to look at the benefits of e-WOM on consumer purchasing decisions, especially the @afterglow.thelabel, the role of e-WOM in increasing sales of the @afterglow.thelabel, and the form of marketing communication strategies undertaken by @afterglow.thelabel to get a positive e-WOM. The method used in this research is descriptive qualitative with a constructive paradigm. The method of data collection was done by semi-structured interviews and using data triangulation for the validity of the data. It was found that e-WOM is useful and plays a role in consumer purchasing decisions @afterglow.thelabel

Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis

Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-offunction mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n¼40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC

Ampullary cancers harbor ELF3 tumor suppressor gene mutations and exhibit frequent WNT dysregulation

The ampulla of Vater is a complex cellular environment from which adenocarcinomas arise to form a group of histopathologically heterogenous tumors. To evaluate the molecular features of these tumors, 98 ampullary adenocarcinomas were evaluated and compared to 44 distal bile duct and 18 duodenal adenocarcinomas. Genomic analyses revealed mutations in the WNT signaling pathway among half of the patients and in all three adenocarcinomas irrespective of their origin and histological morphology. These tumors were characterized by a high frequency of inactivating mutations of ELF3, a high rate of microsatellite instability, and common focal deletions and amplifications, suggesting common attributes in the molecular pathogenesis are at play in these tumors. The high frequency of WNT pathway activating mutation, coupled with small-molecule inhibitors of β-catenin in clinical trials, suggests future treatment decisions for these patients may be guided by genomic analysis

Somatic point mutation calling in low cellularity tumors

Somatic mutation calling from next-generation sequencing data remains a challenge due to the difficulties of distinguishing true somatic events from artifacts arising from PCR, sequencing errors or mis-mapping. Tumor cellularity or purity, sub-clonality and copy number changes also confound the identification of true somatic events against a background of germline variants. We have developed a heuristic strategy and software (http://www.qcmg.org/bioinformatics/qsnp/) for somatic mutation calling in samples with low tumor content and we show the superior sensitivity and precision of our approach using a previously sequenced cell line, a series of tumor/normal admixtures, and 3,253 putative somatic SNVs verified on an orthogonal platform.Karin S. Kassahn, Oliver Holmes, Katia Nones, Ann-Marie Patch, David K. Miller, Angelika N. Christ, Ivon Harliwong, Timothy J. Bruxner, Qinying Xu, Matthew Anderson, Scott Wood, Conrad Leonard, Darrin Taylor, Felicity Newell, Sarah Song, Senel Idrisoglu, Craig Nourse, Ehsan Nourbakhsh, Suzanne Manning, Shivangi Wani, Anita Steptoe, Marina Pajic, Mark J. Cowley, Mark Pinese, David K. Chang, Anthony J. Gill, Amber L. Johns, Jianmin Wu, Peter J. Wilson, Lynn Fink, Andrew V. Biankin, Nicola Waddell, Sean M. Grimmond, John V. Pearso

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe