The deubiquitinase USP5 prevents accumulation of protein aggregates in cardiomyocytes.

Protein homeostasis is crucial for maintaining cardiomyocyte (CM) function. Disruption of proteostasis results in accumulation of protein aggregates causing cardiac pathologies such as hypertrophy, dilated cardiomyopathy (DCM), and heart failure. Here, we identify ubiquitin-specific peptidase 5 (USP5) as a critical determinant of protein quality control (PQC) in CM.

Sensitivity of magnetohydrodynamic simulations of Joule-heated conductors to the vaporization curve in equations of state.

Magnetohydrodynamic (MHD) simulations of electrically exploded aluminum and copper rods demonstrate a technique to validate equations of state (EOS) for rapidly Joule-heated conductors. The balance of internal and magnetic forces at the conductor-insulator interface drives the metal there along the vaporization phase boundary. Variations between critical points and vaporization curves in existing models predict differing densities and temperatures in MHD simulations for these models.

An interdisciplinary course on evolution and sustainability increases acceptance of evolutionary theory and increases understanding of interdisciplinary application of evolutionary theory.

Background: Although evolutionary theory is foundational and integrative in modern biology, there remains widespread lack of acceptance among U.S. residents.

Diagnosis and treatment of MPN in real life: exploratory and retrospective chart review including 960 MPN patients diagnosed with ET or MF in Germany.

Purpose: The WHO 2016 re-classification of myeloproliferative neoplasms resulted in a separation of essential thrombocythemia (ET) from the pre-fibrotic and fibrotic (overt) phases of primary myelofibrosis (MF). This study reports on a chart review conducted to evaluate the real life approach regarding clinical characteristics, diagnostic assessment, risk stratification and treatment decisions for MPN patients classified as ET or MF after implementation of the WHO 2016 classification.

Methods: In this retrospective chart review, 31 office-based hematologists/oncologists and primary care centers in Germany participated between April 2021 and May 2022.

FOLFIRINOX or gemcitabine/nab-paclitaxel in advanced pancreatic adenocarcinoma: A novel validated prognostic score to facilitate treatment decision-making in real-world.

There is no prospective, randomised head-to-head trial comparing first-line FOLFIRINOX and gemcitabine/nab-paclitaxel in advanced pancreatic cancer. We assess real-world effectiveness and quality of life (QoL) of both regimens using a new prognostic score. This analysis includes 1540 patients with advanced pancreatic cancer from the prospective, clinical cohort study Tumour Registry Pancreatic Cancer separated into learning (n = 1027) and validation sample (n = 513).

An Active Learning Intervention Based on Evaluating Alternative Hypotheses Increases Scientific Literacy of Controlled Experiments in Introductory Biology.

Scientific education provides a set of tools to make sense of a complex world by teasing out complicated cause-and-effect relationships, such as the elimination of effects of confounding factors in controlled experiments. There is evidence that depth of understanding of controlled experiments is lacking among undergraduate science students despite exposure to controlled experiments in courses. To examine the understanding of controlled experiments, we developed a two-tiered assessment that includes closed-ended and open-ended questions, with three types of questions, i.

Aberrant Expression of and Cell Death Induction by Engagement of the MHC-II Chaperone CD74 in Anaplastic Large Cell Lymphoma (ALCL).

In 50-60% of cases, systemic anaplastic large cell lymphoma (ALCL) is characterized by the t(2;5)(p23;q35) or one of its variants, considered to be causative for anaplastic lymphoma kinase (ALK)-positive (ALK) ALCL. Key pathogenic events in ALK-negative (ALK) ALCL are less well defined. We have previously shown that deregulation of oncogenic genes surrounding the chromosomal breakpoints on 2p and 5q is a unifying feature of both ALK and ALK ALCL and predisposes for occurrence of t(2;5).

Non-vitamin K Antagonist Oral Anticoagulants (NOAC) as an Alternative Treatment Option in Tumor-Related Venous Thromboembolism.

Background: The risk of venous thromboembolism (VTE) is 4 to 7 times higher in cancer patients than in the normal population. Moreover, cancer patients who take anticoagulants suffer more frequently from hemorrhagic complications and VTE recurrences. Patients often find low-molecular-weight heparin (LMWH) treatment unpleasant; approximately 20% stop taking LMWH during the first six months of treatment.

Direct oral anticoagulants for the treatment of venous thromboembolism in cancer patients: Potential for drug-drug interactions.

Patients with cancer are at high risk of developing venous thromboembolism (VTE). Although the recommended low molecular weight heparins (LMWHs) are more effective than vitamin K antagonists in treating VTE in patients with cancer, they have limitations and contraindications. Direct oral anticoagulants (DOACs) circumvent some of these limitations.

Inactivation of the putative ubiquitin-E3 ligase PDLIM2 in classical Hodgkin and anaplastic large cell lymphoma.

Apart from its unique histopathological appearance with rare tumor cells embedded in an inflammatory background of bystander cells, classical Hodgkin lymphoma (cHL) is characterized by an unusual activation of a broad range of signaling pathways involved in cellular activation. This includes constitutive high-level activity of nuclear factor-κB (NF-κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), activator protein-1 (AP-1) and interferon regulatory factor (IRF) transcription factors (TFs) that are physiologically only transiently activated. Here, we demonstrate that inactivation of the putative ubiquitin E3-ligase PDLIM2 contributes to this TF activation.

Osteopontin in cerebrospinal fluid as diagnostic biomarker for central nervous system lymphoma.

Central nervous system lymphoma (CNSL) is diagnostically challenging. The identification of reliable and easy to measure biomarkers is desirable to facilitate diagnosis. Here, we evaluated the value of cerebrospinal fluid (CSF) osteopontin (OPN) as a diagnostic biomarker for CNSL.

[Protestant clergymen among Hahnemann's clientele. Patient histories in letters].

As part of the research project, developments in the history of science and in the regional and ecclesiastic history of the late feudal petty state of Köthen-Anhalt have been assessed and numerous documents of the Nagel and Mühlenbein family histories examined that place the transcribed patient letters of the two Protestant clergymen within the context of the Hahnemann Archives. These findings complement and extend previous insights into Hahnemann's Köthen clientele, especially when it comes to the structure and milieu of the local clerical elite. Inspired by the interpretive methods of sequential textual analysis, form and content of the letters of the two clergymen and their relatives were also investigated as methodically structured lines of communication.

Diagnosis, prevention, and management of bleeding episodes in Philadelphia-negative myeloproliferative neoplasms: recommendations by the Hemostasis Working Party of the German Society of Hematology and Medical Oncology (DGHO) and the Society of Thrombosis and Hemostasis Research (GTH).

Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPN) comprise a heterogeneous group of chronic hematologic malignancies. The quality of life, morbidity, and mortality of patients with MPN are primarily affected by disease-related symptoms, thromboembolic and hemorrhagic complications, and progression to myelofibrosis and acute leukemia. Major bleeding represents a common and important complication in MPN, and the incidence of such bleeding events will become even more relevant in the future due to the increasing disease prevalence and survival of MPN patients.

Prognostic impact of B-cell lymphoma 6 in primary CNS lymphoma.

Background: We investigated the prognostic significance of B-cell differentiation status and common B-cell differentiation markers in a post hoc analysis of 119 patients with primary CNS lymphoma (PCNSL) homogeneously receiving high-dose methotrexate (HDMTX)-based chemotherapy within the prospective G-PCNSL-SG1 trial.

Methods: We evaluated protein expression of B-cell lymphoma 2 (BCL2), BCL6, CD10, and multiple myeloma oncogene 1/interferon regulatory factor 4 (MUM1/IRF4) by immunohistochemistry and analyzed the association with survival.

Results: The median follow-up of all patients was 67.

Prophylaxis and management of venous thromboembolism in patients with myeloproliferative neoplasms: consensus statement of the Haemostasis Working Party of the German Society of Hematology and Oncology (DGHO), the Austrian Society of Hematology and Oncology (ÖGHO) and Society of Thrombosis and Haemostasis Research (GTH e.V.).

Patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) like polycythemia vera and essential thrombocythemia are at increased risk of arterial and venous thrombosis. Strategies of prevention may consist of platelet aggregation inhibitors and/or cytoreductive agents depending on the underlying disease and the individual risk. Clinical evidence for management of acute venous thromboembolic events in MPN patients is limited.

Mapping of transcription factor motifs in active chromatin identifies IRF5 as key regulator in classical Hodgkin lymphoma.

Deregulated transcription factor (TF) activities are commonly observed in hematopoietic malignancies. Understanding tumorigenesis therefore requires determining the function and hierarchical role of individual TFs. To identify TFs central to lymphomagenesis, we identified lymphoma type-specific accessible chromatin by global mapping of DNaseI hypersensitive sites and analyzed enriched TF-binding motifs in these regions.

Complex and non-redundant signals from individual odor receptors that underlie chemotaxis behavior in Drosophila melanogaster larvae.

The rules by which odor receptors encode odors and allow behavior are still largely unexplored. Although large data sets of electrophysiological responses of receptors to odors have been generated, few hypotheses have been tested with behavioral assays. We use a data set on odor responses of Drosophila larval odor receptors coupled with chemotaxis behavioral assays to examine rules of odor coding.

Prognostic impact of intraocular involvement in primary CNS lymphoma: experience from the G-PCNSL-SG1 trial.

The impact of intraocular involvement (IOL) in primary CNS lymphoma (PCNSL) has not been sufficiently evaluated. Here, we present the analysis of IOL in the only completed randomized phase III trial in PCNSL. The G-PCNSL-SG1 study evaluated the role of whole-brain radiotherapy in primary therapy of PCNSL.

Nuclear factor of activated T cells regulates the expression of interleukin-4 in Th2 cells in an all-or-none fashion.

Th2 memory lymphocytes have imprinted their Il4 genes epigenetically for expression in dependence of T cell receptor restimulation. However, in a given restimulation, not all Th cells with a memory for IL-4 expression express IL-4. Here, we show that in reactivated Th2 cells, the transcription factors NFATc2, NF-kB p65, c-Maf, p300, Brg1, STAT6, and GATA-3 assemble at the Il4 promoter in Th2 cells expressing IL-4 but not in Th2 cells not expressing it.

R-split-CHOP chemotherapy for elderly patients with diffuse large B-cell lymphoma.

Objectives: Chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab (R-CHOP) is the standard of care for patients with diffuse large B-cell lymphoma (DLBCL). However, management of elderly patients is challenging as critical comorbidities often account for increased number of treatment-related complications.

Patients And Methods: In the past 8 yrs, we have treated elderly patients with a full-dose R-CHOP regimen by splitting the administration of cyclophosphamide and doxorubicin over 2 days (R-split-CHOP) to reduce peak plasma level.

[Prophylaxis and treatment of venous thromboembolism in cancer patients. Clinical value of low-molecular-weight heparins].

Venous thromboembolism (VTE) is a common complication in patients with cancer. Because of their improved subcutaneous bioavailability and reliable antithrombotic efficiency low-molecular-weight heparins (LMWH) are preferably used for prevention and treatment of cancer-related VTE. Thromboprophylaxis with LMWH is well established in patients undergoing cancer surgery and hospitalized cancer patients, while outpatient prophylaxis remains contentious.

Brentuximab vedotin (SGN-35) in patients with transplant-naive relapsed/refractory Hodgkin lymphoma.

Only limited data are available on the role of brentuximab vedotin (SGN-35) in transplant-naive relapsed or refractory patients with Hodgkin lymphoma (HL). We thus retrospectively analyzed 14 patients with primary refractory or relapsed HL who were treated with brentuximab vedotin as single agent in a named patient program, who had not received prior high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) due to refractory disease (n = 9), comorbidity (n = 4) and unknown reasons (n = 1). Brentuximab vedotin resulted in an overall response rate of 71% (10/14) with five complete responses (CRs).

The tumour suppressor p53 is frequently nonfunctional in Sézary syndrome.

Background: Primary cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group with Sézary syndrome (SS) as one of the most aggressive variants. Recently, we identified a loss of E2A as a recurrent event in SS, which enhanced proliferation via upregulation of the proto-oncogene MYC. MYC-induced transformation usually requires deleterious alterations of key apoptotic genes including p53; however, p53 functionality and mutation status in SS are unclear.