A practical algorithmic approach to mature aggressive B cell lymphoma diagnosis in the double/triple hit era. Selecting cases, matching clinical benefit. A position paper from the Italian Group of Haematopathology (G.I.E.)

An accurate diagnosis of clinically distinct subgroups of aggressive mature B cell lymphomas is crucial for the choice of proper treatment. Presently, precise recognition of these disorders relies on the combination of morphological, immunophenotypical, and cytogenetic/molecular features. The diagnostic workup in such situations implies the application of costly and time-consuming analyses, which are not always required, since an intensified treatment option is reasonably reserved to fit patients. The Italian Group of Haematopathology proposes herein a practical algorithm for the diagnosis of aggressive mature B cell lymphomas based on a stepwise approach, aimed to select cases deserving molecular analysis, in order to optimize time and resources still assuring the optimal management for any patient

Blastic plasmacytoid dendritic cell neoplasm: Genomics mark epigenetic dysregulation as a primary therapeutic target

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy for which there is still no effective B therapy. In order to identify genetic alterations useful for a new treatment design, we used whole-exome sequencing to analyze 14 BPDCN patients and the patient-derived CAL-1 cell line. The functional enrichment analysis of mutational data reported the epigenetic regulatory program to be the most significantly undermined (P<0.0001). In particular, twenty-five epigenetic modifiers were found mutated (e.g. ASXL1, TET2, SUZ12, ARID1A, PHF2, CHD8); ASXL1 was the most frequently affected (28.6% of cases). To evaluate the impact of the identified epigenetic mutations at the gene-expression and Histone H3 lysine 27 trimethylation/acetylation levels, we performed additional RNA and pathology tissue-chromatin immunoprecipitation sequencing experiments. The patients displayed enrichment in gene signatures regulated by methylation and modifiable by decitabine administration, shared common H3K27-acetylated regions, and had a set of cell-cycle genes aberrantly up-regulated and marked by promoter acetylation. Collectively, the integration of sequencing data showed the potential of a therapy based on epigenetic agents. Through the adoption of a preclinical BPDCN mouse model, established by CAL-1 cell line xenografting, we demonstrated the efficacy of the combination of the epigenetic drugs 5’-azacytidine and decitabine in controlling disease progression in vivo

a study to discover novel tumor-specific mutations

Background Splenic marginal zone lymphoma (SMZL) is an indolent B-cell non- Hodgkin lymphoma and represents the most common primary malignancy of the spleen. Its precise molecular pathogenesis is still unknown and specific molecular markers for diagnosis or possible targets for causal therapies are lacking. Methods We performed whole exome sequencing (WES) and copy number analysis from laser-microdissected tumor cells of two primary SMZL discovery cases. Selected somatic single nucleotide variants (SNVs) were analyzed using pyrosequencing and Sanger sequencing in an independent validation cohort. Results Overall, 25 nonsynonymous somatic SNVs were identified, including known mutations in the NOTCH2 and MYD88 genes. Twenty-three of the mutations have not been associated with SMZL before. Many of these seem to be subclonal. Screening of 24 additional SMZL for mutations at the same positions found mutated in the WES approach revealed no recurrence of mutations for ZNF608 and PDE10A, whereas the MYD88 L265P missense mutation was identified in 15 % of cases. An analysis of the NOTCH2 PEST domain and the whole coding region of the transcription factor SMYD1 in eight cases identified no additional case with a NOTCH2 mutation, but two additional cases with SMYD1 alterations. Conclusions In this first WES approach from microdissected SMZL tissue we confirmed known mutations and discovered new somatic variants. Recurrence of MYD88 mutations in SMZL was validated, but NOTCH2 PEST domain mutations were relatively rare (10 % of cases). Recurrent mutations in the transcription factor SMYD1 have not been described in SMZL before and warrant further investigation

Using a Servitized Business Model to Facilitate Adoption of Electric Vehicles for the Chinese Private Car Market

The automobile industry is facing a technological shift from internal combustion engines to battery driven electric vehicles, a shift called electrification. Since 2015, when it surpassed the U.S. market, the Chinese market has been the world’s largest electric vehicle market. Electrification gives rise to a new set of consumer anxieties, primarily related to battery charging and range, but also price. In addition to the ongoing electrification, the automobile industry is also subject to a servitization trend, meaning that manufacturers are integrating a higher level of services in their offers. Further, innovative leasing and car pool related offers are rapidly emerging on the Chinese electric vehicle market. These trends suggest that car manufacturers need to develop new innovative business models to facilitate technology adoption and stay competitive. This study investigates characteristics of servitized business models and how servitized business models can be used to overcome the obstacles concerning diffusion of electric vehicles on the Chinese market. The report’s theoretical framework and findings are therefore structured based on the business model framework provided by Chesbrough and Rosenbloom (2002). Through interviews with researchers and industry representatives, and by studying market reports for the Chinese EV market, the study maps the components and attributes of a servitized business model from the perspective of the Chinese electric vehicle market. By doing this, it contributes to the theoretical field of servitization in B2C industries. It is found that the Chinese electric vehicle market is rapidly growing, but consumer anxieties and preferences are continuously changing. The study concludes that several attributes of servitized business models, such as more agile development and closer customer relationships, could facilitate adoption of electric vehicles on the Chinese automobile market. Thus, to implement and benefit from a servitized business model, it is concluded that manufacturing companies must develop capabilities for gaining and acting on consumer insights. One way of doing this is by increasing the number of customer touch points, either physical or digital, throughout the usage life cycle

Acquisition of The Spanish Preterite and Imperfect By Non-Native Students in A Traditional Classroom Vs. A Hybrid Setting

High school students learning Spanish often struggle with the acquisition of the past tense. Spanish requires differentiation between aspects (preterite and imperfect) of the past tense; a linguistic contrast that does not exist in English. While this has been researched for years in Second Language Acquisition (SLA), the increasing availability of technology offers a new angle from which to explore students’ ability to master this concept. In the 2020-2021 school year, the presence of the Novel Coronavirus (COVID-19) forced schools to overhaul and adapt the learning environment during a pandemic in which a fully traditional in-person model was not a feasible option. The Hononegah High School district adopted a hybrid environment in which students split their class time with equal time learning in person and remotely from home. This change in environment offered the opportunity to compare data on the success of past tense aspect acquisition of students in a traditional learning environment with the hybrid environment.In this study, data from a recognition quiz, oral production narrative task, and an in-class writing narrative task were studied in order to compare overall accuracy between in-person and hybrid groups. Results from the tasks were used to attempt to determine how the difference in instructional delivery affects the acquisition and production of the Spanish past tense. More detailed analysis was conducted on the 2020-2021 students’ use of preterite and imperfect forms, as student responses were unavailable from the 2019-2020 group. Previous research has shown that students prefer the present and preterite tenses in production tasks, but this was not the case for the 2020-2021 students. Students in the hybrid classroom environment performed with a similar level of accuracy as students in the traditional setting on all tasks, except for the oral production task, on which the in-person students performed better

Whole exome sequencing of microdissected splenic marginal zone lymphoma: a study to discover novel tumor-specific mutations

BACKGROUND: Splenic marginal zone lymphoma (SMZL) is an indolent B-cell non-Hodgkin lymphoma and represents the most common primary malignancy of the spleen. Its precise molecular pathogenesis is still unknown and specific molecular markers for diagnosis or possible targets for causal therapies are lacking. METHODS: We performed whole exome sequencing (WES) and copy number analysis from laser-microdissected tumor cells of two primary SMZL discovery cases. Selected somatic single nucleotide variants (SNVs) were analyzed using pyrosequencing and Sanger sequencing in an independent validation cohort. RESULTS: Overall, 25 nonsynonymous somatic SNVs were identified, including known mutations in the NOTCH2 and MYD88 genes. Twenty-three of the mutations have not been associated with SMZL before. Many of these seem to be subclonal. Screening of 24 additional SMZL for mutations at the same positions found mutated in the WES approach revealed no recurrence of mutations for ZNF608 and PDE10A, whereas the MYD88 L265P missense mutation was identified in 15 % of cases. An analysis of the NOTCH2 PEST domain and the whole coding region of the transcription factor SMYD1 in eight cases identified no additional case with a NOTCH2 mutation, but two additional cases with SMYD1 alterations. CONCLUSIONS: In this first WES approach from microdissected SMZL tissue we confirmed known mutations and discovered new somatic variants. Recurrence of MYD88 mutations in SMZL was validated, but NOTCH2 PEST domain mutations were relatively rare (10 % of cases). Recurrent mutations in the transcription factor SMYD1 have not been described in SMZL before and warrant further investigatio

What factors influence training opportunities for older workers? Three factorial surveys exploring the attitudes of HR professionals

The core research questions addressed in this paper are: what factors influence HR professionals in deciding whether to approve training proposals for older workers? What kind of training are they more likely to recommend for older employees and in which organizational contexts? We administered three factorial surveys to 66 HR professionals in Italy. Participants made specific training decisions based on profiles of hypothetical older workers. Multilevel analyses indicated that access to training decreases strongly with age, while highly-skilled older employees with low absenteeism rates are more likely to enjoy training opportunities. In addition, older workers displaying positive performance are more likely to receive training than older workers who perform poorly, suggesting that training late in working life may serve as a reward for good performance rather than as a means of enhancing productivity. The older the HR professional evaluating training proposals, the higher the probability that older workers will be recommended for training. keywords: training; older workers; HR professionals; factorial survey; multilevel model