Functional Signature of LRP4 Antibodies in Myasthenia Gravis.

Background And Objectives: Antibodies (Abs) specific for the low-density lipoprotein receptor-related protein 4 (LRP4) occur in up to 5% of patients with myasthenia gravis (MG). The objective of this study was to profile LRP4-Ab effector actions.

Methods: We evaluated the efficacy of LRP4-specific compared with AChR-specific IgG to induce Ab-dependent cellular phagocytosis (ADCP), Ab-dependent cellular cytotoxicity (ADCC), and Ab-dependent complement deposition (ADCD).

Protein arginine methyltransferase 1 regulates B cell fate after positive selection in the germinal center in mice.

Positively selected germinal center B cells (GCBC) can either resume proliferation and somatic hypermutation or differentiate. The mechanisms dictating these alternative cell fates are incompletely understood. We show that the protein arginine methyltransferase 1 (Prmt1) is upregulated in murine GCBC by Myc and mTORC-dependent signaling after positive selection.

Tempo-spatial patterns of PM measured using a portable particulate monitor around a mine complex in Canada's Arctic.

Mining activities in Canada's pristine Arctic (e.g., driving on unpacked roads, blasts, rock grinding, diesel combustion, and garbage incineration) could add local sources of airborne fine particulate matter with a diameter of < 2.

Erratum: The uracil-DNA glycosylase UNG protects the fitness of normal and cancer B cells expressing AID.

[This corrects the article DOI: 10.1093/narcan/zcaa019.].

The uracil-DNA glycosylase UNG protects the fitness of normal and cancer B cells expressing AID.

In B lymphocytes, the uracil N-glycosylase (UNG) excises genomic uracils made by activation-induced deaminase (AID), thus underpinning antibody gene diversification and oncogenic chromosomal translocations, but also initiating faithful DNA repair. mice develop B-cell lymphoma (BCL). However, since UNG has anti- and pro-oncogenic activities, its tumor suppressor relevance is unclear.

N-glycosylation analysis of mouse immunoglobulin G isolated from dried blood spots.

The association of immunoglobulin G (IgG) glycosylation changes with various human diseases and physiological conditions is well established. Since the mechanistical explanation of the regulation of IgG glycosylation and its functional role in these various states is still missing, the eyes of the biomedical community are now turned towards animal models, which enable intervention studies necessary for conclusions on causality. Mice are recognized and used as a good experimental model for human IgG glycosylation.

Factors Affecting Surgical Decisions in Newly Diagnosed Young Women with Early-Stage Breast Cancer.

Given that young women with breast cancer often have concerns and priorities attributable to their life stage, we conducted a series of interviews to better understanding the surgical decision-making experience among women diagnosed at age ≤40. Women spoke of how the potential effect of an extended recovery was affecting their decision and, in some cases, contributing to decisional conflict. Several women described their worry of leaving cancer cells behind; others cited the need for continued surveillance as a consideration.

'Why us?' Causal attributions of childhood cancer survivors, survivors' parents and community comparisons - a mixed methods analysis.

Introduction: Understanding the cause of their cancer is important for many cancer patients. Childhood cancer survivors'/survivors' parents' beliefs about cancer etiology are understudied. We aimed to assess survivors'/parents' beliefs about what causes childhood cancer, compared with beliefs in the community.

PRMT5 is essential for B cell development and germinal center dynamics.

Mechanisms regulating B cell development, activation, education in the germinal center (GC) and differentiation, underpin the humoral immune response. Protein arginine methyltransferase 5 (Prmt5), which catalyzes most symmetric dimethyl arginine protein modifications, is overexpressed in B cell lymphomas but its function in normal B cells is poorly defined. Here we show that Prmt5 is necessary for antibody responses and has essential but distinct functions in all proliferative B cell stages in mice.

The Avatar Acceptability Study: Survivor, Parent and Community Willingness to Use Patient-Derived Xenografts to Personalize Cancer Care.

Background: Using patient-derived xenografts (PDXs) to assess chemosensitivity to anti-cancer agents in real-time may improve cancer care by enabling individualized clinical decision-making. However, it is unknown whether this new approach will be met with acceptance by patients, family and community.

Methods: We used a cross-sectional structured survey to investigate PDX acceptability with 1550 individuals across Australia and New Zealand (648 survivors of adult and childhood cancer, versus 650 community comparisons; and 48 parents of childhood cancer survivors versus 204 community parents).

The multidisciplinary pediatric psycho-oncology workforce: A national report on supervision for staff and training opportunities.

Objective: This paper presents data on licensure/certification status, supervision of multidisciplinary pediatric psychosocial staff, and training opportunities in pediatric cancer programs in the United States, data that are critical to provide care aligned with the Standards of Psychosocial Care in Pediatric Cancer (Psychosocial Standards).

Methods: An online survey of psychosocial care consistent with the Psychosocial Standards was completed from a national sample of pediatric cancer programs (144/200). Licensure/certification status, availability and format of supervision for multidisciplinary staff (social workers, psychologists, psychiatrists, child life specialists/recreational therapists), and types and number of psychosocial trainees were reported.

"A change in perspective": Exploring the experiences of adolescents with hereditary tumor predisposition.

Background: Hereditary tumor predisposition syndromes (HTPSs) are being recognized more frequently in the etiology of pediatric cancer. Previous research indicates that disclosure of tumor susceptibility is a significant event in adolescents' lives. Insight into adolescents' adjustment to knowledge of their syndromes can guide healthcare delivery, particularly genetic counseling.

Protocol for the avatar acceptability study: a multiperspective cross-sectional study evaluating the acceptability of using patient-derived xenografts to guide personalised cancer care in Australia and New Zealand.

Introduction: Patient-derived xenografts (PDXs) have the potential to transform personalised cancer care, however, little is known about the acceptability of using PDXs to guide treatment decision-making. Given that patient and community preferences can influence satisfaction with care as well as the success of new technologies, we will evaluate the acceptability of PDXs in individuals affected by cancer and community comparisons.

Methods And Analysis: This comparative cross-sectional study will recruit 323 individuals affected by cancer (cancer survivors (of childhood or adult cancer) and parents of childhood cancer survivors) and 323 community comparisons (adults and parents).

Maternal perceptions of BRCA genetic counseling communication processes about disclosing cancer risk information to children and adult relatives.

Objectives: Using a novel measure, examine maternal perceptions of the process by which issues pertaining to family communication of BRCA test results are addressed during cancer genetic counseling.

Methods: After receiving BRCA results, mothers (N = 211) of minor-age children reported on their counseling experiences with providers using a communication process measure as well as other psychosocial variables.

Results: The novel Genetic Counseling Communication Process measure demonstrated good internal consistency of its 2 factors: patient-led communication (Cronbach's α = 0.

A licensing step links AID to transcription elongation for mutagenesis in B cells.

Activation-induced deaminase (AID) mutates the immunoglobulin (Ig) genes to initiate somatic hypermutation (SHM) and class switch recombination (CSR) in B cells, thus underpinning antibody responses. AID mutates a few hundred other loci, but most AID-occupied genes are spared. The mechanisms underlying productive deamination versus non-productive AID targeting are unclear.

Children and young people's understanding of inherited conditions and their attitudes towards genetic testing: A systematic review.

Children and young people are increasingly likely to receive information regarding inherited health risks relevant to their genetic relatives and themselves. We reviewed the literature to determine what children and young people (21 years and younger) understand about inherited conditions and their attitudes towards genetic testing. We screened 1815 abstracts to identify 20 studies representing the perspectives of 1811 children and young people between the ages of 6 and 21 years (1498 children or young people at general population-level risk from 9 studies, 313 affected/at risk from 15 studies).

"I don't want to take chances.": A qualitative exploration of surgical decision making in young breast cancer survivors.

Objective: Young women with unilateral breast cancer are increasingly choosing contralateral prophylactic mastectomy (CPM), despite its limited medical benefit for most women. The purpose of this study was to better understand this choice through a qualitative exploration of surgical decision-making in young survivors, including how issues particular to younger women affected their decision and the post-surgical experience.

Methods: Women age ≤ 40 years with stage 0 to III breast cancer, 1 to 3 years from diagnosis who had undergone breast cancer surgery were recruited to participate.

Strategies to facilitate shared decision-making about pediatric oncology clinical trial enrollment: A systematic review.

Objective: We conducted a systematic review to identify the strategies that have been recommended in the literature to facilitate shared decision-making regarding enrolment in pediatric oncology clinical trials.

Methods: We searched seven databases for peer-reviewed literature, published 1990-2017. Of 924 articles identified, 17 studies were eligible for the review.

Family history-taking practices and genetic confidence in primary and tertiary care providers for childhood cancer survivors.

Background: There is growing impetus for increased genetic screening in childhood cancer survivors. Family history-taking is a critical first step in determining survivors' suitability. However, the family history-taking practices of providers of pediatric oncology survivorship care and the confidence of these providers to discuss cancer risks to relatives are unknown.

ICAM1+ neutrophils promote chronic inflammation via ASPRV1 in B cell-dependent autoimmune encephalomyelitis.

Neutrophils contribute to demyelinating autoimmune diseases, yet their phenotype and functions have been elusive to date. Here, we demonstrate that ICAM1 surface expression distinguishes extra- from intravascular neutrophils in the mouse CNS during experimental autoimmune encephalomyelitis (EAE). Transcriptomic analysis of these 2 subpopulations indicated that neutrophils, once extravasated, acquire macrophage-like properties, including the potential for immunostimulation and MHC class II-mediated antigen presentation.

Family Communication, Risk Perception and Cancer Knowledge of Young Adults from BRCA1/2 Families: a Systematic Review.

Understanding challenges in familial communication of cancer risk has informed genetic service delivery. Parent-child interactions have received considerable attention, but few studies focus on young adulthood experiences within BRCA1/2 families. Young adults are approaching, or at a life stage where awareness of hereditary cancer risk is vital for informed choice of risk management options.

Parents' attitudes toward genetic testing of children for health conditions: A systematic review.

This review assessed parents' attitudes toward childhood genetic testing for health conditions, with a focus on perceived advantages and disadvantages. We also evaluated the factors that influence parents' attitudes toward childhood genetic testing. We searched Medline, Medline In-Process, EMBASE, PsycINFO, Social Work Abstracts and CINAHL.

Roles for APRIN (PDS5B) in homologous recombination and in ovarian cancer prediction.

APRIN (PDS5 cohesin associated factor B) interacts with both the cohesin complex and the BRCA2 tumor suppressor. How APRIN influences cohesion and DNA repair processes is not well understood. Here, we show that APRIN is recruited to DNA damage sites.