ARID1A orchestrates SWI/SNF-mediated sequential binding of transcription factors with ARID1A loss driving pre-memory B cell fate and lymphomagenesis.

ARID1A, a subunit of the canonical BAF nucleosome remodeling complex, is commonly mutated in lymphomas. We show that ARID1A orchestrates B cell fate during the germinal center (GC) response, facilitating cooperative and sequential binding of PU.1 and NF-kB at crucial genes for cytokine and CD40 signaling.

Integrative genomic analysis identifies unique immune environments associated with immunotherapy response in diffuse large B cell lymphoma.

Most diffuse large B-cell lymphoma (DLBCL) patients treated with bispecific antibodies (BsAb) or chimeric antigen receptor (CAR) T cells fail to achieve durable treatment responses, underscoring the need for a deeper understanding of mechanisms that regulate the immune environment and response to treatment. Here, an integrative, multi-omic approach was employed to characterize DLBCL immune environments, which effectively segregated DLBCLs into four quadrants - termed DLBCL-immune quadrants (IQ) - defined by cell-of-origin and immune-related gene set expression scores. Recurrent genomic alterations were enriched in each IQ, suggesting that lymphoma cell-intrinsic alterations contribute to orchestrating unique DLBCL immune environments.

An inducible Cd79b mutation confers ibrutinib sensitivity in mouse models of Myd88-driven diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma and constitutes a highly heterogenous disease. Recent comprehensive genomic profiling revealed the identity of numerous molecularly defined DLBCL subtypes, including a cluster which is characterized by recurrent aberrations in MYD88, CD79B, and BCL2, as well as various lesions promoting a block in plasma cell differentiation, including PRDM1, TBL1XR1, and SPIB. Here, we generated a series of autochthonous mouse models to mimic this DLBCL cluster and specifically focused on the impact of Cd79b mutations in this setting.

Profile identification and characterization of risk perceptions and preventive behaviors during the COVID-19 pandemic: A latent profile analysis.

In a public health crisis, communication plays a vital role in making sure policies and recommendations from the government level get disseminated accurately to its people and is only considered as effective when the public accepts, supports, complies to, and engages in policies or behaves as per governments' recommendations. Adopting the multivariate audience segmentation strategy for health communication, this study uses a data-driven analytical method to (1) identify audience segments of public health crisis communication in Singapore based on knowledge, risk perception, emotional responses, and preventive behaviors; and (2) characterize each audience segment according to demographic factors, personality traits, information processing styles, and health information preferences. Results ( = 2033) from a web-based questionnaire executed in August 2021 have identified three audience segments: the ( = 650), the ( = 142), and the ( = 1,241).

mutation yields supercompetitive B cells primed for malignant transformation.

Multicellular life requires altruistic cooperation between cells. The adaptive immune system is a notable exception, wherein germinal center B cells compete vigorously for limiting positive selection signals. Studying primary human lymphomas and developing new mouse models, we found that mutations affecting disrupt a critical immune gatekeeper mechanism that strictly limits B cell fitness during antibody affinity maturation.

Distinct Genetically Determined Origins of Myd88/BCL2-Driven Aggressive Lymphoma Rationalize Targeted Therapeutic Intervention Strategies.

Unlabelled: Genomic profiling revealed the identity of at least 5 subtypes of diffuse large B-cell lymphoma (DLBCL), including the MCD/C5 cluster characterized by aberrations in MYD88, BCL2, PRDM1, and/or SPIB. We generated mouse models harboring B cell-specific Prdm1 or Spib aberrations on the background of oncogenic Myd88 and Bcl2 lesions. We deployed whole-exome sequencing, transcriptome, flow-cytometry, and mass cytometry analyses to demonstrate that Prdm1- or Spib-altered lymphomas display molecular features consistent with prememory B cells and light-zone B cells, whereas lymphomas lacking these alterations were enriched for late light-zone and plasmablast-associated gene sets.

An Aged/Autoimmune B-cell Program Defines the Early Transformation of Extranodal Lymphomas.

Unlabelled: A third of patients with diffuse large B-cell lymphoma (DLBCL) present with extranodal dissemination, which is associated with inferior clinical outcomes. MYD88L265P is a hallmark extranodal DLBCL mutation that supports lymphoma proliferation. Yet extranodal lymphomagenesis and the role of MYD88L265P in transformation remain mostly unknown.

Interprofessional learning in a student-run dental clinic: The effect on attitudes of students in oral healthcare.

The purpose of this study was to gain insight into change in attitudes held by students in oral healthcare about interprofessional learning and collaboration after one year of work in a student-run dental clinic (SRDC). Third- and fourth-year bachelor of dental hygiene students (n = 221) and first- and second-year master of dentistry students (n = 203) participated in baseline and follow-up measurements and completed 570 questionnaires. The Readiness for Interprofessional Learning Scale (RIPLS) was used to measure changes in attitudes toward Interprofessional Education (IPE) during participation in the SRDC.

Durable remissions following combined targeted therapy in patients with CLL harboring TP53 deletions and/or mutations.

Fifty-one of 189 evaluable patients from 3 prospective phase 2 trials evaluating a sequential targeted treatment had high-risk chronic lymphocytic leukemia (CLL) with a 17p deletion, TP53 mutation, or both. Twenty-seven patients started treatment with bendamustine debulking before induction and maintenance treatment, which was ibrutinib/ofatumumab (IO) in 21 patients, ibrutinib/obinutuzumab (IG) in 13, and venetoclax/obinutuzumab (AG) in 17. The primary end point was overall response rate after 8 months of induction treatment, which was 81%, 100%, and 94% for IO, IG, and AG, respectively.

Attitudes and Knowledge of European Medical Students and Early Graduates about Vaccination and Self-Reported Vaccination Coverage-Multinational Cross-Sectional Survey.

Vaccination is one of the most useful preventive interventions in healthcare. The purpose of our study was to gain overview of the opinions, knowledge, and engagement in vaccination practices among medical students (MS) and junior doctors (JD) in Europe. The survey was distributed from March 2016 until August 2016 via the e-mail and social media of the European Medical Students' Association.

An Autochthonous Mouse Model of Myd88- and BCL2-Driven Diffuse Large B-cell Lymphoma Reveals Actionable Molecular Vulnerabilities.

Based on gene expression profiles, diffuse large B cell lymphoma (DLBCL) is sub-divided into germinal center B cell-like (GCB) and activated B cell-like (ABC) DLBCL. Two of the most common genomic aberrations in ABC-DLBCL are mutations in , as well as copy number gains. Here, we employ immune phenotyping, RNA-Seq and whole exome sequencing to characterize a and -driven mouse model of ABC-DLBCL.

Activation of Mirror Neuron Regions Is Altered in Developmental Coordination Disorder (DCD)-Neurophysiological Evidence Using an Action Observation Paradigm.

Children with Developmental Coordination Disorder (DCD) have difficulty performing and learning motor skills. Automatic activation of the mirror neuron system (MNS) during action observation and its coupling to the motor output system are important neurophysiological processes that underpin observational motor learning. In the present study, we tested the hypothesis that MNS function is disrupted in children with DCD by using sensitive electroencephalography (EEG)-based measures of MNS activation during action observation.

An Analysis of the Presence and Composition of OutLists at United States, Canadian, and European Medical Institutions.

Sexual and gender minority (SGM) medical students and physicians are exposed to bias in professional contexts. One strategy for promoting SGM visibility and inclusion within medicine is the development of institutional OutLists, which are online, opt-in lists of SGM-identified individuals affiliated with an academic institution. We present the first quantitative evaluation of publicly accessible OutLists at medical institutions in the United States, Canada, and Europe.

Performance of the AsperGenius® PCR assay for detecting azole resistant Aspergillus fumigatus in BAL fluids from allogeneic HSCT recipients: A prospective cohort study from Essen, West Germany.

In this study a commercially available multiplex real-time PCR (AsperGenius®) was evaluated for its efficacy in detecting Aspergillus fumigatus and azole resistance markers in comparison with conventional culture methods and galactomannan (GM) testing from BAL fluids in allogeneic HSCT recipients. Between January 2015 and May 2017 100 allogeneic HSCT recipients with pulmonary infiltrates and suspicion of invasive fungal infection were recruited to the study from a tertiary care center in Germany. BAL fluid was routinely assessed using the following diagnostic tests: AsperGenius® PCR assay, GM testing (cut-off: 1.

Surveillance of Myelodysplastic Syndrome via Migration Analyses of Blood Neutrophils: A Potential Prognostic Tool.

Autonomous migration is a central characteristic of immune cells, and changes in this function have been correlated to the progression and severity of diseases. Hence, the identification of pathologically altered leukocyte migration patterns might be a promising approach for disease surveillance and prognostic scoring. However, because of the lack of standardized and robust assays, migration patterns have not been clinically exploited so far.

Light chain monoclonal gammopathy of undetermined significance is characterized by a high disappearance rate and low risk of progression on longitudinal analysis.

We determined the 10-year progression rate of light chain monoclonal gammopathy of undetermined significance (LCMGUS) and investigated potential associations with cancer utilizing the German population-based Heinz Nixdorf Recall Study. The Heinz Nixdorf Recall Study comprises 4814 men and women aged 45-75 years. Serum samples from baseline (2000-2003) and five-year (2006-2008) and 10-year (2011-2015) follow-up examinations were screened for monoclonal free light chains (FLC).

Associations Between Personality Disorder Characteristics, Psychological Symptoms, and Sexual Functioning in Young Women.

Background: Recently, the etiology of sexual dysfunctions in women has been approached from different angles. In clinical practice and in previous studies, it has been observed that women with sexual problems experience anxiety problems and express more rigid and perfectionistic personality traits than women without these problems.

Aim: To investigate whether personality disorder characteristics according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) and psychological symptoms are associated with sexual problems in women.

Exact p-values for pairwise comparison of Friedman rank sums, with application to comparing classifiers.

Background: The Friedman rank sum test is a widely-used nonparametric method in computational biology. In addition to examining the overall null hypothesis of no significant difference among any of the rank sums, it is typically of interest to conduct pairwise comparison tests. Current approaches to such tests rely on large-sample approximations, due to the numerical complexity of computing the exact distribution.