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The article in the Annals of Hematology discusses a case study of a 77-year-old man diagnosed with acute monocytic leukemia. The patient had a complex karyotype with various chromosomal abnormalities, including a KMT2A:ARHGEF12 fusion gene. Optical Genome Mapping (OGM) was used to identify the fusion gene, which was missed by traditional cytogenetic and molecular analyses. The rare KMT2A:ARHGEF12 fusion is associated with poor prognosis in hematological malignancies, highlighting the importance of advanced genetic technologies for accurate diagnosis and potential targeted therapies. [Extracted from the article]

Although there is evidence of a significant rise of neuroendocrine neoplasms (NENs) incidence, current treatments are largely insufficient due to somewhat poor knowledge of these tumours. Despite showing differentiated features, NENs exhibit therapeutic resistance to most common treatments, similar to other cancers in many instances. Molecular mechanisms responsible for this resistance phenomenon are badly understood. We aimed at identifying signalling partners responsible of acquired resistance to treatments in order to develop novel therapeutic strategies. We engineered QGP-1 cells resistant to current leading treatments, the chemotherapeutic agent oxaliplatin and the mTor inhibitor everolimus. Cells were chronically exposed to the drugs and assessed for acquired resistance by viability assay. We used microarray-based kinomics to obtain highthroughput kinase activity profiles from drug sensitive vs resistant cells and identified 'hit' kinases hyperactivated in drug-resistant cells, including kinases from FGFR family, cyclin-dependant kinases and PKCs in oxaliplatin-resistant (R-Ox) QGP-1 cells. We then validated these 'hit' kinases and observed that ERK signalling is specifically enhanced in QGP-1 R-Ox cells. Finally, we assessed drug-resistant cells sensitivity to pharmacological inhibition of 'hit' kinases or their signalling partners. We found that FGFR inhibition markedly decreased ERK signalling and cell viability in QGP-1 R-Ox cells. These results suggest that the FGFR/ERK axis is hyperactivated in response to oxaliplatin-based chemotherapeutic strategy. Thus, this sensitive approach, based on the study of kinome activity, allows identifying potential candidates involved in drug resistance in NENs and may be used to broadly investigate markers of NENs therapeutic response. [ABSTRACT FROM AUTHOR]

Pegvisomant (PEG), an antagonist of growth hormone (GH)-receptor (GHR), normalizes insulin-like growth factor 1 (IGF1) oversecretion in most acromegalic patients unresponsive to somatostatin analogs (SSAs) and/or uncontrolled by transsphenoidal surgery. The residual GH-secreting tumor is therefore exposed to the action of circulating PEG. However, the biological effect of PEG at the pituitary level remains unknown. To assess the impact of PEG in vitro on the hormonal secretion (GH and prolactin (PRL)), proliferation and cellular viability of eight human GH-secreting tumors in primary cultures and of the rat somatolactotroph cell line GH4C1. We found that the mRNA expression levels of GHR were characterized in 31 human GH-secreting adenomas (0.086 copy/copy β-Gus) and the GHR was identified by immunocytochemistry staining. In 5/8 adenomas, a dose-dependent inhibition of GH secretion was observed under PEG with a maximum of 38.2 ± 17% at 1 μg/mL (P < 0.0001 vs control). A dose-dependent inhibition of PRL secretion occurred in three mixed GH/PRL adenomas under PEG with a maximum of 52.8 ± 11.5% at 10 μg/mL (P < 0.0001 vs control). No impact on proliferation of either human primary tumors or GH4C1 cell line was observed. We conclude that PEG inhibits the secretion of GH and PRL in primary cultures of human GH(/PRL)-secreting pituitary adenomas without effect on cell viability or cell proliferation. [ABSTRACT FROM AUTHOR]

To test the role of wtPIT-1 (PITWT) or PIT-1 (R271W) (PIT271) in somatolactotroph cells, we established, using inducible lentiviral vectors, sublines of GH4C1 somatotroph cells that allow the blockade of the expression of endogenous PIT-1 and/or the expression of PITWT or PIT271, a dominant negative mutant of PIT-1 responsible for Combined Pituitary Hormone Deficiency in patients. Blocking expression of endogenous PIT-1 induced a marked decrease of cell proliferation. Overexpressing PITWT twofold led also to a dose-dependent decrease of cell proliferation that was accompanied by cell death. Expression of PIT271 induced a strong dose-dependent decrease of cell proliferation accompanied by a very pronounced cell death. These actions of PIT271 are independent of its interaction/competition with endogenous PIT-1, as they were unchanged when expression of endogenous PIT-1 was blocked. All these actions are specific for somatolactotroph cells, and could not be observed in heterologous cells. Cell death induced by PITWT or by PIT271 was accompanied by DNA fragmentation, but was not inhibited by inhibitors of caspases, autophagy or necrosis, suggesting that this cell death is a caspase-independent apoptosis. Altogether, our results indicate that under normal conditions PIT-1 is important for the maintenance of cell proliferation, while when expressed at supra-normal levels it induces cell death. Through this dual action, PIT-1 may play a role in the expansion/regression cycles of pituitary lactotroph population during and after lactation. Our results also demonstrate that the so-called “dominant-negative” action of PIT271 is independent of its competition with PIT-1 or a blockade of the actions of the latter, and are actions specific to this mutant variant of PIT-1. [ABSTRACT FROM AUTHOR]

Unforeseen forces are at work in higher education today. The purpose of this article is to explore the issues involved in the changing landscape. Decisions are and will be made that impact the intellectual property rights of faculty. It is important to be cognizant of the factors involved and alert to possible ramifications. The basics of the copyright law and their application in our traditional, face-to-face classrooms will be examined. The picture changes when online delivery is considered. The results of a simple survey of faculty regarding their expectations of copyright ownership will be shared. Issues that may make a difference and additional factors involved in Massive Open Online Courses will then be discussed. In some cases, existing policies of colleges and universities are being applied to these issues at least for the time being. A sample will be provided. The role of our professional organizations and unions will play a role in the ultimate decisions. Their relevant policies and recommendations will also be discussed. [ABSTRACT FROM AUTHOR]

Universities stand for truth and knowledge. Academic integrity is the ideal we hold up to our students and ourselves. It's based on respect for the work we do and respect for the work of others. The current state of academic dishonesty on campus is a threat to the morality of the students, the integrity of their grades, and the reputation of our institutions of higher education. This article explores issues surrounding academic integrity with an eye toward considering what can be done. It discusses the breadth and types of cheating (including plagiarism), the impact of technology, ways to prevent or limit its occurrence, and ways faculty might respond when it occurs. The discussion is enriched by the results of two surveys about academic integrity conducted in late 2012 and early 2013-one of faculty and one of students. Results reveal and compare the concerns and suggestions of both groups. [ABSTRACT FROM AUTHOR]

"Cloud computing" refers to the use of computing resources on the Internet instead of on individual personal computers. The field is expanding and has significant potential value for educators. This is discussed with a focus on four main functions: file storage, file synchronization, document creation, and collaboration-each of which has applications for educators. Cloud-based application suites such as Google Apps, Zoho, and Microsoft Office 365 are important tools. In addition, web-based tools such as Google Scholar and Zotero can enhance the learning and research experience. This discussion is enriched by the results of a survey of 80 faculty members delivered in May 2011. The respondents fell into two groups-those who currently use cloud computing and those who do not. Results reveal the areas of interest, future projections, and the concerns of both groups. [ABSTRACT FROM AUTHOR]

Forty percent of somatotroph tumors harbor recurrent activating GNAS mutations, historically called the gsp oncogene. In gsp-negative somatotroph tumors, GNAS expression itself is highly variable; those with GNAS overexpression most resemble phenotypically those carrying the gsp oncogene. GNAS is monoallelically expressed in the normal pituitary due to methylation-based imprinting. We hypothesize that changes in GNAS imprinting of gsp-negative tumors affect GNAS expression levels and tumorigenesis. We characterized the GNAS locus in two independent somatotroph tumor cohorts: one of 23 tumors previously published (PMID: 31883967) and classified by pan-genomic analysis, and a second with 82 tumors. Multi-omics analysis of the first cohort identified a significant difference between gsp-negative and gsp-positive tumors in the methylation index at the known differentially methylated region (DMR) of the GNAS A/B transcript promoter, which was confirmed in the larger series of 82 tumors. GNAS allelic expression was analyzed using a polymorphic Fok1 cleavage site in 32 heterozygous gsp-negative tumors. GNAS expression was significantly reduced in the 14 tumors with relaxed GNAS imprinting and biallelic expression, compared to 18 tumors with monoallelic expression. Tumors with relaxed GNAS imprinting showed significantly lower SSTR2 and AIP expression levels. Altered A/B DMR methylation was found exclusively in gsp-negative somatotroph tumors. 43% of gsp-negative tumors showed GNAS imprinting relaxation, which correlated with lower GNAS, SSTR2 and AIP expression, indicating lower sensitivity to somatostatin analogues and potentially aggressive behavior. [ABSTRACT FROM AUTHOR]