The reliability and interobserver reproducibility of T2/FLAIR mismatch in the diagnosis of IDH-mutant astrocytomas

PURPOSE:The reliability and reproducibility of T2-weighted imaging/ fluid-attenuated inversion recovery (T2/FLAIR) mismatch were investigated in the diagnosis of isocitrate dehydrogenase (IDH) mutant astrocytoma between WHO grade II and III diffuse hemispheric gliomas.METHODS:WHO grade II and grade III diffuse hemispheric gliomas (n=133) treated in our institute were included in the study. Pathological findings and molecular markers of the cases were reviewed with the criteria of WHO 2016. The finding of mismatch between T2-weighted and FLAIR images in preoperative magnetic resonance imaging (MRI) of the cases was evaluated by two different radiologists. The readers reviewed MRIs independently, blinded to the histopathologic diagnosis or molecular subset of tumors. The cases were classified as IDH-mutant astrocytoma, oligodendroglioma and IDH-wildtype (IDH-wt) astrocytoma according to molecular and genetic features.RESULTS:T2/FLAIR mismatch positivity was observed in 46 patients (34.6%). T2/FLAIR mismatch positivity was observed in 42 of 75 IDH-mutant astrocytomas (56%) and 4 of 43 oligodendrogliomas (9.30%), while it was not seen among IDH-wt astrocytomas (0/15, 0%). The T2/FLAIR mismatch ratio was significantly different between IDH-mutant astrocytomas (WHO grade II and grade III) and oligodendrogliomas (chi-square, p <0.05). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of T2/FLAIR mismatch in predicting IDH-mutant astrocytomas were 58.7%, 90.7%, 91.7%, 61.4%, and 70.3% respectively. Radiologist 1 diagnosed T2/FLAIR mismatch in 48 of 133 cases (36.1%) and Radiologist 2 in 66 of 133 cases (49.6%). The interrater agreement for the T2/FLAIR mismatch sign was 0.61 (p <0.05), 95% CI (0.55, 0.67).CONCLUSION:T2/FLAIR mismatch appears to be an important MRI finding in distinguishing IDH-mutant astrocytomas from other diffuse hemispheric gliomas. However, it should be kept in mind that T2/FLAIR mismatch sign can be seen in a minority of oligodendrogliomas besides IDH-mutant astrocytomas

Tumor heterogeneity and tumor-microglia interactions in primary and recurrent IDH1-mutant gliomas

The isocitrate dehydrogenase (IDH) gene is recurrently mutated in adult diffuse gliomas. IDH-mutant gliomas are categorized into oligodendrogliomas and astrocytomas, each with unique pathological features. Here, we use single-nucleus RNA and ATAC sequencing to compare the molecular heterogeneity of these glioma subtypes. In addition to astrocyte-like, oligodendrocyte progenitor-like, and cycling tumor subpopulations, a tumor population enriched for ribosomal genes and translation elongation factors is primarily present in oligodendrogliomas. Longitudinal analysis of astrocytomas indicates that the proportion of tumor subpopulations remains stable in recurrent tumors. Analysis of tumor-associated microglia/macrophages (TAMs) reveals significant differences between oligodendrogliomas, with astrocytomas harboring inflammatory TAMs expressing phosphorylated STAT1, as confirmed by immunohistochemistry. Furthermore, inferred receptor-ligand interactions between tumor subpopulations and TAMs may contribute to TAM state diversity. Overall, our study sheds light on distinct tumor populations, TAM heterogeneity, TAM-tumor interactions in IDH-mutant glioma subtypes, and the relative stability of tumor subpopulations in recurrent astrocytomas

تطوير المواد الدراسية في تعليم مهارة الكتاب في برنامج الخاض لتعليم اللغة العربية في جامعة مولانا مالك ابراهم الإسلامية الحكومية مالانج

ABSTRAK Perkembangan Universitas Islam Negeri Maulana Malik Ibrahim Malang sebagai salah satu Perguruan Tinggi Islam yang berkembang pesat membutuhkan terobosan- terobosan yang handal. Salah satu hal penting yang tidak bisa dipisahkan adalah peranan penting dari PKPBA (Program Khusus Pengembangan Bahasa Arab). PKPBA sebagai sebuah unit pengembangan bahasa, telah berperan penting dalam membantu meningkatkan kemampuan berbahasa mahasiswa khususnya bahasa arab. Banyak dari mahasiswa yang pertama kali masuk PKPBA belum mengetahui bahasa Arab. Namun setelah belajar di PKPBA mereka mampu mengenal ilmu bahasa arab. Namun, tidak hanya berhenti pada mengetahui bahasa arab saja, program ini juga berupaya agar semua mahasiswa mampu untuk menguasai salah satu dari 4 ketrampilan bahasa yakni ketrampilan menulis. Tujuan dari peneliyian ini adalah untuk melengkapi proses pengembangan penyusunan materi ajar menulis dan mengetahui ke-efektifan materi yang dikembangkan. Penelitian ini menggunakan prosedur eksperimen dimana peneliti mendisain Pre-test dan Postest terhadap dua kelompok yakni kelompok eksperimen dan kelompok kontrol. Hasil penelitian ini adalah bahwa pembelajaran ketrampilan menulis dengan menggunakan buku ajar lebih efektif dari pada tanpa menggunakan buku ajar. Dengan indikasi bahwa t-test kelas eksperimen (J3) lebih efektif dengan indikasi bahwa t-test kelas kontrol adalah 3,4. dimana hasil ini lebih besar dari pada tingkat t-table 5% 2,059 dan tingkat 1% 2,787. Dari hasil ini menunjukan bahwa pengajaran menulis bahasa Arab efektif dengan menggunakan materi ajar yang telah disusun oleh peneliti. Hasil penelitian ini adalah: (1) Penyusunan materi ajar untuk PKPBA dimulai dengan membatasi tujuan pengajaran, kemudian menentukan pembagian materi sesuai dengan jumlah hari yang digunakan untuk pembelajaran dalam satu minggu. (2) Pembelajaran menulis bahasa Arab dengan menggunakan Materi ajar ini dinyatakan efektif. Dari hasil yang disebutkan diatas, sudah semestinya materi pengajaran menulis bahasa Arab dapat dimanfaatkan dengan benar dalam proses pengajaran, selain itu penulis berharap agar penelitian ini menjadi referensi untuk penelitian lanjutan yang berhubungan dengan penelitian ini sehingga dapat dikembangkan ke dalam desain materi ajar menulis untuk tingkat selanjutnya. ABSTRACT The expansion of State Islamic University Maulana Malik Ibrahim need some powerful breakthrough. One of the important things is the role of Intensive Arabic Program as unit for improving Arabic, have played an important for helping Arabic language improvement. Most of the students when the first time they enter to this Program, they haven’t yet Arabic knowledge. But after studying in this program for several months they could understand about Arabic. But is not enough in knowing the Arabic only, but this program also try to make all students are mastering one of these four skills, that is writing skill. This research aims at designing process of writing teaching material and finding out the effectiveness of writing teaching material using in Intensive Arabic Program of State Islamic University of Maulana Malik Ibrahim Malang. This research uses the experimental method that the researcher design pre-test and post-test for both groups (Experiment and Control group). This research reach the degree of t-test 3,4 this biggest than t-table at the level of 5% (2,059) and at the level 1% (2,787). This indicates that the use of writing Teaching Material in Arabic for improving writing skill is effective. And the result of this research are obtained bellow: (1) Preparing this teaching material process started by determining the goals, finding out the learning material based on the days in a week which used for teaching (2) The use of writing Teaching Material in Arabic for improving writing skill is effective. Based on these results, teaching material must be used as good as possible in teaching process. Besides, the researcher hopes that the research becomes the reference for further researchers which have a relation with this chapter and could be developed to other teaching material for advance grade

Oligosarcomas, IDH‑mutant are distinct and aggressive

Oligodendrogliomas are defined at the molecular level by the presence of an IDH mutation and codeletion of chromosomal arms 1p and 19q. In the past, case reports and small studies described gliomas with sarcomatous features arising from oligodendrogliomas, so called oligosarcomas. Here, we report a series of 24 IDH-mutant oligosarcomas from 23 patients forming a distinct methylation class. The tumors were recurrences from prior oligodendrogliomas or developed de novo. Precursor tumors of 12 oligosarcomas were histologically and molecularly indistinguishable from conventional oligodendrogliomas. Oligosarcoma tumor cells were embedded in a dense network of reticulin fibers, frequently showing p53 accumulation, positivity for SMA and CALD1, loss of OLIG2 and gain of H3K27 trimethylation (H3K27me3) as compared to primary lesions. In 5 oligosarcomas no 1p/19q codeletion was detectable, although it was present in the primary lesions. Copy number neutral LOH was determined as underlying mechanism. Oligosarcomas harbored an increased chromosomal copy number variation load with frequent CDKN2A/B deletions. Proteomic profiling demonstrated oligosarcomas to be highly distinct from conventional CNS WHO grade 3 oligodendrogliomas with consistent evidence for a smooth muscle differentiation. Expression of several tumor suppressors was reduced with NF1 being lost frequently. In contrast, oncogenic YAP1 was aberrantly overexpressed in oligosarcomas. Panel sequencing revealed mutations in NF1 and TP53 along with IDH1/2 and TERT promoter mutations. Survival of patients was significantly poorer for oligosarcomas as first recurrence than for grade 3 oligodendrogliomas as first recurrence. These results establish oligosarcomas as a distinct group of IDH-mutant gliomas differing from conventional oligodendrogliomas on the histologic, epigenetic, proteomic, molecular and clinical level. The diagnosis can be based on the combined presence of (a) sarcomatous histology, (b) IDH-mutation and (c) TERT promoter mutation and/or 1p/19q codeletion, or, in unresolved cases, on its characteristic DNA methylation profile