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Quantum computing promises to provide the next step up in computational power for diverse application areas. In this review, we examine the science behind the quantum hype, and the breakthroughs required to achieve true quantum advantage in real world applications. Areas that are likely to have the greatest impact on high performance computing (HPC) include simulation of quantum systems, optimization, and machine learning. We draw our examples from electronic structure calculations and computational fluid dynamics which account for a large fraction of current scientific and engineering use of HPC. Potential challenges include encoding and decoding classical data for quantum devices, and mismatched clock speeds between classical and quantum processors. Even a modest quantum enhancement to current classical techniques would have far-reaching impacts in areas such as weather forecasting, aerospace engineering, and the design of 'green' materials for sustainable development. This requires significant effort from the computational science, engineering and quantum computing communities working together., (Creative Commons Attribution license.)

Background: Epstein Barr virus positive (EBV+) immunodeficiency-associated lymphoproliferative disorders (IA-LPD) are heterogeneous diseases with variable treatment strategies that are not well-defined., Case Presentation: A 68-year-old woman with systemic lupus erythematosus developed EBV+ B-cell polymorphic lymphoproliferative disease (LPD). Positron emission tomography computed tomography (PET/CT) showed a large nasopharyngeal mass, multiple pulmonary lesions, splenomegaly and disseminated lymphadenopathy. Plasma EBV DNA was grossly elevated to 1.5 × 10 4 IU/mL. There were three paraproteins. Treatment with O-CHOP (obinutuzumab, cyclophosphamide, adriamycin, vincristine, prednisolone) led to undetectable plasma EBV DNA, suggesting eradiation of the EBV-positive malignant clone. However, radiologic abnormalities were still present on PET/CT, and paraprotein persisted. A nasopharyngeal re-biopsy showed infiltration with EBV-negative plasma cells. On treatment with lenalidomide, she finally achieved complete metabolic response. Molecular analysis showed that the EBV+ B-cell LPD and the EBV- plasma cell lesion exhibited identical immunoglobulin gene rearrangements. Next generation sequencing revealed that the EBV+ B-LPD showed mutation in only one gene ( TP53 ), a profile typical of EBV-driven lymphoid neoplasms. However, the EBV- plasma cell lesion showed mutations in five genes ( TP53 , SF3B1 , STAT5B , CD79B and CRKL ), suggesting that these mutations instead of EBV infection were the oncogenic driver., Conclusion: The presence of both EBV+ and EBV- lesions, which showed different mutational profiles, indicated clonal heterogeneity that might be of biologic and therapeutic significance.

Immunoglobulin G4-related disease (IgG4-RD) has rarely been associated with lymphoid neoplasms, the spectrum of which remains unclear. B-cell lymphoid neoplasms (LN) associated with IgG4-RD diagnosed in a 4-year period were analysed. There were five men and three women at a median age of 76.5 (52-90) years; three with synchronous IgG4-RD and LN; three with IgG4-RD preceding LN by 2, 3, and 22 years; and two with LN preceding IgG4-RD by 2.5 and 7 years. All patients presented with disseminated lymphadenopathy. Monoclonal gammopathy of undetermined significance (MGUS)/smouldering multiple myeloma (SMM) was found in three patients, all with an IgGκ paraprotein. Levels of IgGκ and IgG4 correlated. Diffuse large B-cell lymphoma (DLBCL) was found in three patients, with one case showing co-existing lymphoma and IgG4-RD in the same lymph node biopsy. The remaining two cases were marginal zone lymphoma (MZL) developing in a lacrimal gland previously involved by IgG4-RD; and nodular lymphocyte predominant Hodgkin lymphoma (NLP-HL) diagnosed in a lymph node with concomitant IgG4-RD. Low-dose continuous prednisolone was given for MGUS/SMM, with both monoclonal IgGκ and IgG4 responding. Combination chemotherapy was given for DLBCL, with two patients achieving complete response and one patient dying from refractory lymphoma. The patient with MZL refused treatment, whereas the case of NLP-HL responded completely to chemotherapy. Our findings together with previous observations suggest that IgG4-RD has an increased risk of B-cell neoplasms. Patients with IgG4-RD presenting with lymphadenopathy require vigorous investigations to exclude lymphoid neoplasms., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with respect to outcome. Features of the tumor microenvironment (TME) are associated with prognosis when assessed by gene expression profiling. However, it is uncertain whether assessment of the microenvironment can add prognostic information to the most relevant and clinically well-established molecular subgroups when analyzed by immunohistochemistry (IHC)., Patients and Methods: We carried out a histopathologic analysis of biomarkers related to TME in a very large cohort (n = 455) of DLBCL treated in prospective trials and correlated with clinicopathologic and molecular data, including chromosomal rearrangements and gene expression profiles for cell-of-origin and TME., Results: The content of PD1+, FoxP3+ and CD8+, as well as vessel density, was not associated with outcome. However, we found a low content of CD68+ macrophages to be associated with inferior progression-free survival (PFS) and overall survival (OS; P = 0.023 and 0.040, respectively) at both univariable and multivariable analyses, adjusted for the factors of the International Prognostic Index (IPI), MYC break and BCL2/MYC and BCL6/MYC double-hit status. The subgroup of PDL1+ macrophages was not associated with survival. Instead, secreted protein acidic and cysteine rich (SPARC)-positive macrophages were identified as the subtype of macrophages most associated with survival. SPARC-positive macrophages and stromal cells directly correlated with favorable PFS and OS (both, P[log rank] <0.001, P[trend] < 0.001). The association of SPARC with prognosis was independent of the factors of the IPI, MYC double-/triple-hit status, Bcl2/c-myc double expression, cell-of-origin subtype and a recently published gene expression signature [lymphoma-associated macrophage interaction signature (LAMIS)]., Conclusions: SPARC expression in the TME detected by a single IHC staining with fair-to-good interobserver reproducibility is a powerful prognostic parameter. Thus SPARC expression is a strong candidate for risk assessment in DLBCL in daily practice., Competing Interests: Disclosure GAC received travel support/congress support from Novartis (not related to work); VP received travel support/congress support from AbbVie, Amgen, BMS, Gilead and Roche (not related to work); WK received grants from Amgen, Regeneron, and Takeda (not related to work). All remaining authors have declared no conflicts of interest., (Copyright © 2021 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

Introduction : Natural killer (NK)/T-cell lymphomas are aggressive malignancies that present predominantly in nasal and adjacent sites (nasal subtype), occasionally in skin, gastrointestinal tract and other tissues (non-nasal), and rarely as disseminated disease with a leukemic phase (aggressive NK-cell leukemia, or leukemia/lymphoma, subtype). Areas covered : The diagnosis and treatment of NK/T-cell lymphoma are discussed, based on a PubMed literature search. The diagnostic criteria for NK/T-cell lymphoma are highlighted, followed by an update of the diagnostic and prognostic importance (on presentation, at interim and end-of-treatment) of plasma EBV DNA as a surrogate biomarker of lymphoma load. Prognostic models based on clinicopathologic features and EBV DNA load are discussed. For stage I/II NK/T-cell lymphomas, combined chemotherapy, and radiotherapy gives the best results, with their concomitant or sequential administration equally efficacious. For stage III/IV NK/T-cell lymphoma, chemotherapy is the mainstay of treatment. Conventional anthracycline-based regimens for B-cell lymphomas are ineffective. Recommended regimens combine L-asparaginase with other drugs not affected by P-glycoprotein. For relapsed/refractory patients, immune checkpoint blockade with antibodies against programmed cell death protein 1 has shown much promise. Expert opinion : Current strategies result in durable remissions in a significant proportion of NK/T-cell lymphomas. Immune checkpoint inhibition and other novel approaches are promising for relapsed/refractory cases.

Background: Inadequate patient education and preparation for office-based procedures often leads to delayed care, poor patient satisfaction, and increased costs to the health care system. We developed and deployed a mobile health (mHealth) reminder and education program for patients scheduled for transrectal prostate biopsy., Objective: We aimed to evaluate the impact of an mHealth reminder and education program on appointment cancellation rates, communication frequency, and patient satisfaction., Methods: We developed a text message (SMS, short message service)-based program with seven reminders containing links to Web-based content and surveys sent over an 18-day period (14 days before through 3 days after prostate biopsy). Messages contained educational content, reminders, and readiness questionnaires. Demographic information, appointment cancellations or change data, and patient/provider communication events were collected for 6 months before and after launching the intervention. Patient satisfaction was evaluated in the postintervention cohort., Results: The preintervention (n=473) and postintervention (n=359) cohorts were composed of men of similar median age and racial/ethnic distribution living a similar distance from clinic. The postintervention cohort had significantly fewer canceled or rescheduled appointments (33.8% vs 21.2%, P<.001) and fewer same-day cancellations (3.8% vs 0.5%, P<.001). There was a significant increase in preprocedural telephone calls (0.6 vs 0.8 calls per patient, P=.02) in the postintervention cohort, but not a detectable change in postprocedural calls. The mean satisfaction with the program was 4.5 out of 5 (SD 0.9)., Conclusions: An mHealth periprocedural outreach program significantly lowered appointment cancellation and rescheduling and was associated with high patient satisfaction scores with a slight increase in preprocedural telephone calls. This led to fewer underused procedure appointments and high patient satisfaction., (©Ashwin S Balakrishnan, Hao G Nguyen, Katsuto Shinohara, Reuben Au Yeung, Peter R Carroll, Anobel Y Odisho. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 02.06.2019.)

The new recently described provisional lymphoma category Burkitt-like lymphoma with 11q aberration comprises cases similar to Burkitt lymphoma (BL) on morphological, immunophenotypic and gene-expression levels but lacking the IG- MYC translocation. They are characterized by a peculiar imbalance pattern on chromosome 11, but the landscape of mutations is not yet described. Thus, we investigated 15 MYC -negative Burkitt-like lymphoma with 11q aberration (mnBLL,11q,) cases by copy-number analysis and whole-exome sequencing. We refined the regions of 11q imbalance and identified the INO80 complex-associated gene NFRKB as a positional candidate in 11q24.3. Next to recurrent gains in 12q13.11-q24.32 and 7q34-qter as well as losses in 13q32.3-q34, we identified 47 genes recurrently affected by protein-changing mutations (each ≥3 of 15 cases). Strikingly, we did not detect recurrent mutations in genes of the ID3-TCF3 axis or the SWI/SNF complex that are frequently altered in BL, or in genes frequently mutated in germinal center-derived B-cell lymphomas like KMT2D or CREBBP An exception is GNA13 , which was mutated in 7 of 15 cases. We conclude that the genomic landscape of mnBLL,11q, differs from that of BL both at the chromosomal and mutational levels. Our findings implicate that mnBLL,11q, is a lymphoma category distinct from BL at the molecular level., (© 2019 by The American Society of Hematology.)

Natural killer (NK)/T-cell lymphomas failing L-asparaginse regimens have no known salvage and are almost invariably fatal. Seven male patients with NK/T-cell lymphoma (median age, 49 years; range, 31-68 years) for whom a median of 2 (range, 1-5) regimens (including l-asparaginase regimens and allogeneic hematopoietic stem-cell transplantation [HSCT] in 2 cases) failed were treated with the anti-programmed death 1 (PD1) antibody pembrolizumab. All patients responded, according to various clinical, radiologic (positron emission tomography), morphologic, and molecular (circulating Epstein-Barr virus [EBV] DNA) criteria. Two patients achieved complete response (CR) in all parameters. Three patients achieved clinical and radiologic CRs, with two having molecular remission (undetectable EBV DNA) but minimal EBV-encoded RNA-positive cells in lesions comprising predominantly CD3 + CD4 + and CD3 + CD8 + T cells (which ultimately disappeared, suggesting they represented pseudoprogression) and one having detectable EBV DNA despite morphologic CR. Two patients achieved partial response (PR). After a median of 7 (range, 2-13) cycles of pembrolizumab and a follow-up of a median of 6 (range, 2-10) months, all five CR patients were still in remission. The only adverse event was grade 2 skin graft-versus-host disease in one patient with previous allogeneic HSCT. Expression of the PD1 ligand was strong in 4 patients (3 achieving CR) and weak in 1 (achieving PR). PD1 blockade with pembrolizumab was a potent strategy for NK/T-cell lymphomas failing l-asparaginase regimens., (© 2017 by The American Society of Hematology.)