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Understanding the aberrant transcriptional landscape of neuroblastoma is necessary to provide insight to the underlying influences of the initiation, progression and persistence of this developmental cancer. Here, we present chromatin immunoprecipitation sequencing (ChIP-Seq) data for the oncogenic transcription factors, MYCN and MYC, as well as regulatory histone marks H3K4me1, H3K4me3, H3K27Ac, and H3K27me3 in ten commonly used human neuroblastoma-derived cell line models. In addition, for all of the profiled cell lines we provide ATAC-Seq as a measure of open chromatin. We validate specificity of global MYCN occupancy in MYCN amplified cell lines and functional redundancy of MYC occupancy in MYCN non-amplified cell lines. Finally, we show with H3K27Ac ChIP-Seq that these cell lines retain expression of key neuroblastoma super-enhancers (SE). We anticipate this dataset, coupled with available transcriptomic profiling on the same cell lines, will enable the discovery of novel gene regulatory mechanisms in neuroblastoma.

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.

Depressive symptoms are prevalent among people with type 2 diabetes (T2D) and, even at low severity levels, are associated with worse diabetes outcomes. Carbohydrate restriction is an effective treatment for T2D but its long-term impacts on depressive symptoms are unclear. In the current study we explored changes in depressive symptoms over 2 years among 262 primarily non-depressed T2D patients participating in a continuous remote care intervention emphasizing carbohydrate restriction. Subclinical depressive symptoms decreased over the first 10 weeks and reductions were maintained out to 2 years. Increased frequency of blood ketone levels indicative of adherence to low carbohydrate eating predicted decreases in depressive symptoms. Concerns have been raised with recommending restrictive diets due to potential negative impacts on quality-of-life factors such as mood; however, results of the current study support positive rather than negative long-term impacts of closely monitored carbohydrate restriction on depressive symptoms., Author(s): Rebecca N. Adams [sup.1] , Shaminie J. Athinarayanan [sup.1] , Amy L. McKenzie [sup.1] , Sarah J. Hallberg [sup.1] [sup.2] , James P. McCarter [sup.3] [sup.4] , Stephen D. [...]

We thank Vorland et al [...].

A routine measurement in heart examination is that of the heart wall thickness. This study investigated whether histology can be used to estimate heart wall thickness measured in a post-mortem examination, and therefore assess the utility of this method in the post-mortem report peer review process. This study compared 30 consecutive adult heart measurements (left and right free wall thickness and interventricular wall thickness). It showed that heart wall thickness measurements on histology slides were non-repeatable, non-reproducible, and unreliable, with overall poor to moderate intraclass correlation coefficient (<0.60, p < 0.05). The 95% confidence interval in the difference between histology and post-mortem examination was 1–3.5 mm for left ventricle and interventricular wall thickness, and −1–0.5 mm for the right ventricle. This study showed limited utility in using histology in estimating heart wall thickness. However, in instances where histology was the only modality available to estimate heart wall, marking where the measurements were taken, citing the confidence intervals, and noting the limitations thereof is recommended. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite the emergence of several approved targeted and immune therapies for melanoma, clinical management continues to present challenges. These include resistance to clinically available treatments and lower response rates for late-stage and metastatic disease, translating to less favourable survival. Additionally, approved immunotherapies are not directed specifically against cancer cells. New treatments are therefore required to improve outcomes. One such approach entails therapeutics targeting molecules on the cancer cell surface but less frequently or lowly expressed in normal tissues. Chondroitin sulfate proteoglycan 4 (CSPG4) is a transmembrane protein overexpressed in solid tumours, including melanoma, with restricted expression in normal tissues, potentially fulfilling key criteria as a promising therapeutic target. Here, we describe the known functions of CSPG4 in healthy states and in melanoma. We review different approaches designed to activate the patient's immune system to target CSPG4-expressing melanomas, and we discuss how such interventions could be translated into clinical practice. Immunotherapies, including checkpoint inhibitor antibodies, have precipitated significant improvements in clinical outcomes for melanoma. However, approximately half of patients do not benefit from approved treatments. Additionally, apart from Tebentafusp, which is approved for the treatment of uveal melanoma, there is a lack of immunotherapies directly focused on melanoma cells. This is partly due to few available targets, especially those expressed on the cancer cell surface. Chondroitin sulfate proteoglycan 4 (CSPG4) is a cell surface molecule overexpressed in human melanoma, with restricted distribution and low expression in non-malignant tissues and involved in several cancer-promoting and dissemination pathways. Here, we summarize the current understanding of the expression and functional significance of CSPG4 in health and melanoma, and we outline immunotherapeutic strategies. These include monoclonal antibodies, antibody–drug conjugates (ADCs), chimeric-antigen receptor (CAR) T cells, and other strategies such as anti-idiotypic and mimotope vaccines to raise immune responses against CSPG4-expressing melanomas. Several showed promising functions in preclinical models of melanoma, yet few have reached clinical testing, and none are approved for therapeutic use. Obstacles preventing that progress include limited knowledge of CSPG4 function in human cancer and a lack of in vivo models that adequately represent patient immune responses and human melanoma biology. Despite several challenges, immunotherapy directed to CSPG4-expressing melanoma harbors significant potential to transform the treatment landscape. [ABSTRACT FROM AUTHOR]

Maternal vaccination is a safe and effective means of preventing infection in pregnant women, their fetuses, and infants after birth. Several vaccines are routinely administered in pregnancy as a valuable part of prenatal care with supporting recommendations from national and international health organizations. Fears concerning vaccine safety in pregnancy are pervasive despite sufficient available safety data to support their use, leading to underutilization of maternal immunization. Despite this hesitancy, the field of maternal vaccination is evolving to include more vaccines in the routine prenatal vaccination schedule, including the new RSV vaccine. This review discusses the currently recommended vaccines in pregnancy, evidence for their use, and an overview of ongoing clinical trials investigating prospective vaccines for pregnant women. [ABSTRACT FROM AUTHOR]

This study involved a randomized, controlled, single-blind 12-month treatment study of a comprehensive nutritional and dietary intervention. Participants were 67 children and adults with autism spectrum disorder (ASD) ages 3-58 years from Arizona and 50 non-sibling neurotypical controls of similar age and gender. Treatment began with a special vitamin/mineral supplement, and additional treatments were added sequentially, including essential fatty acids, Epsom salt baths, carnitine, digestive enzymes, and a healthy gluten-free, casein-free, soy-free (HGCSF) diet. There was a significant improvement in nonverbal intellectual ability in the treatment group compared to the non-treatment group (+6.7 ± 11 IQ points vs. -0.6 ± 11 IQ points, p = 0.009) based on a blinded clinical assessment. Based on semi-blinded assessment, the treatment group, compared to the non-treatment group, had significantly greater improvement in autism symptoms and developmental age. The treatment group had significantly greater increases in EPA, DHA, carnitine, and vitamins A, B2, B5, B6, B12, folic acid, and Coenzyme Q10. The positive results of this study suggest that a comprehensive nutritional and dietary intervention is effective at improving nutritional status, non-verbal IQ, autism symptoms, and other symptoms in most individuals with ASD. Parents reported that the vitamin/mineral supplements, essential fatty acids, and HGCSF diet were the most beneficial.

Despite the success of immunotherapies for melanoma in recent years, there remains a significant proportion of patients who do not yet derive benefit from available treatments. Immunotherapies currently licensed for clinical use target the adaptive immune system, focussing on Tcell interactions and functions. However, the most prevalent immune cells within the tumor microenvironment (TME) of melanoma are macrophages, a diverse immune cell subset displaying high plasticity, to which no current therapies are yet directly targeted. Macrophages have been shown not only to activate the adaptive immune response, and enhance cancer cell killing, but, when influenced by factors within the TME of melanoma, these cells also promote melanoma tumorigenesis and metastasis. We present a review of the most up-to-date literatureavailable on PubMed, focussing on studies from within the last 10 years. We also include data from ongoing and recent clinical trials targeting macrophages in melanoma listed on clinicaltrials.gov. Understanding the multifaceted role of macrophages in melanoma, including their interactions with immune and cancer cells, the influence of current therapies on macrophage phenotype and functions and how macrophages could be targeted with novel treatment approaches, are all critical for improving outcomes for patients with melanoma. [ABSTRACT FROM AUTHOR]

Objectives Myeloid/lymphoid neoplasms with FGFR1 rearrangement are a rare group of neoplasms that share features of eosinophilia and lineage promiscuity. First, we described a challenging case of acute leukemia with lineage switch and cytogenetically cryptic FGFR1. Second, we aimed to systemically review this phenomenon in published literature. Methods A 68-year-old man with a history of chemotherapy exposure presented with acute leukemia of myeloid lineage without eosinophilia or 8p11 abnormalities on karyotyping. Over a refractory and relapsing course, the blast phenotype shifted to B lymphoid. Results Fluorescence in situ hybridization identified a cytogenetically cryptic FGFR1 rearrangement, likely a paracentric inversion. We identified 26 published cases of FGFR1 -rearranged acute leukemia with ambiguous, mixed, or switching lineage. Although there was variability in the partner gene, anatomical location of different phenotypes, and timing of lineage switch, the prognosis was consistently poor in the absence of novel therapy. Conclusions Ours is the only reported case of FGFR1 -rearranged neoplasms with a disease sequence of acute myeloid leukemia transforming to B-cell acute lymphoblastic leukemia and 1 of only 3 reported cases with cytogenetically cryptic FGFR1 rearrangement. Fluorescence in situ hybridization testing for FGFR1 rearrangement should be a standard investigation in leukemia of mixed or switching lineage. [ABSTRACT FROM AUTHOR]

This article finds the subject of how to articulate the promotion of spiritual well-being by chaplains to be one of complementary, not competing, forms of presence. Chaplains are called upon to be attentive to another's story and, crucially, to their own, but this study also argues for the use of presence in other forms, such as to challenge a pervading narrative of organizational culture or to provide a formational learning opportunity. These need not be opposite sides of a coin; they are perhaps more like diverse limbs of a growing tree. This article articulates each area as attentive presence, transformational presence, formational presence and informed presence. It outlines a critical reflection on what the author is beginning to understand of her own nascent role in Scottish healthcare chaplaincy and concludes by wondering what is required to nourish its roots. [ABSTRACT FROM AUTHOR]

This issue features five original articles, all pertinent to international chaplains and their health and social care colleagues. If there is an overarching theme, it is the role of the chaplain. All the studies answer, in one way or another, the "proverbial" question "What do chaplains do?" by exploring different perspectives, such as spiritual assessment, spiritual intervention, the patient experience of chaplaincy, and the organization of healthcare chaplaincy. [ABSTRACT FROM AUTHOR]

Background: As life expectancy and morbidity related to chronic disease increase, the baby boomers will be called upon to provide care to aging members of their family or to be care recipients themselves. Purpose: Through the theoretical lens of the life course perspective, this review of the literature provides insight into what characteristics of baby boomers separate them from previous caregiving cohorts and how these characteristics will affect family caregiving. Methods: A systematic process to identify literature was completed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Results: Findings suggest multiple emerging trends related to caregiving, including (1) increasing use of digital technology for information gathering and support, (2) more diversity among caregivers and care recipients, (3) strained finances and loss of entitlements, (4) more complex care and care management, (5) demand for public policies related to caregiving, and (6) balancing work, family, chronic disease, and caregiving. Discussion: Examining the literature related to family caregiving and baby boomers through a life course perspective offers a unique and more complete understanding of emerging trends related to chronic disease management. Translation to Health Education Practice: These emerging trends offer health educators implications for strategies and best practices intended to support those involved in family caregiving.

Cancer patients have high rates of persistent and disabling symptoms. Evidence suggests that social constraints (e.g., avoidance and criticism) negatively impact symptoms, but pathways linking these variables have yet to be identified. This study examined whether cancer-related loneliness (i.e., feeling socially disconnected related to having cancer) mediated the relationships between social constraints and symptoms (i.e., pain interference, fatigue, sleep disturbance, and cognitive complaints) in patients with various cancers (N = 182). Patients (51% female, mean age = 59) were recruited from the Indiana Cancer Registry and completed questionnaires assessing social constraints, cancer-related loneliness, and symptoms. Structural equation modeling was used to evaluate the hypothesized relationships among variables. The model demonstrated good fit. Consistent with our hypothesis, cancer-related loneliness mediated the relationships between social constraints and each symptom. Findings suggest that addressing cancer-related loneliness in symptom management interventions may mitigate the negative impact of social constraints on outcomes., Author(s): Rebecca N. Adams [sup.1] , Catherine E. Mosher [sup.2] , Joseph G. Winger [sup.3] , Rafat Abonour [sup.4] , Kurt Kroenke [sup.4] [sup.5] [sup.6] Author Affiliations: (Aff1) 0000000419368956, grid.168010.e, [...]

Background: Despite the multitude of available resources, family caregivers of those with chronic disease continually underutilize support services to cope with the demands of caregiving. Several studies have linked self-identification as a caregiver to the increased likelihood of support service use. Purpose: The present study reviewed the literature related to the development of family caregiver identity. Methods: After a systematic process to locate literature was completed, content analysis was conducted to determine major themes related to the development of caregiving identity. Results: Findings suggest that there are multiple factors related to the development of family caregiver identity, including role engulfment and reversal, loss of shared identity, family obligation and gender norming, extension of the former role, and development of a master identity. Discussion: Considering the role of identity in human behavior, health professionals can address the underutilization of support services by family caregivers of those with chronic disease by understanding the influences on the development of caregiver identity. Translation to Health Education Practice: This literature review will assist health educators in addressing the underutilization of support services by family caregivers of those with chronic disease.

B cells are known to contribute to the anti-tumor immune response, especially in immunogenic tumors such as melanoma, yet humoral immunity has not been characterized in these cancers to detail. Here we show comprehensive phenotyping in samples of circulating and tumor-resident B cells as well as serum antibodies in melanoma patients. Memory B cells are enriched in tumors compared to blood in paired samples and feature distinct antibody repertoires, linked to specific isotypes. Tumor-associated B cells undergo clonal expansion, class switch recombination, somatic hypermutation and receptor revision. Compared with blood, tumor-associated B cells produce antibodies with proportionally higher levels of unproductive sequences and distinct complementarity determining region 3 properties. The observed features are signs of affinity maturation and polyreactivity and suggest an active and aberrant autoimmune-like reaction in the tumor microenvironment. Consistent with this, tumor-derived antibodies are polyreactive and characterized by autoantigen recognition. Serum antibodies show reactivity to antigens attributed to autoimmune diseases and cancer, and their levels are higher in patients with active disease compared to post-resection state. Our findings thus reveal B cell lineage dysregulation with distinct antibody repertoire and specificity, alongside clonally-expanded tumor-infiltrating B cells with autoimmune-like features, shaping the humoral immune response in melanoma. B cells are playing an active role in shaping the tumour immune microenvironment and the anti-tumour immune response in melanomas. Here authors show that intra-tumoral B cells are aberrantly activated and produce antibodies that are potentially autoreactive. [ABSTRACT FROM AUTHOR]

Research has shown that task-based computer-mediated communication (CMC) can foster attention to linguistic form in ways that may promote language learning (c.f., Blake, 2000; Smith, 2003, 2005). However, relatively little research has investigated how differences in the way that tasks are used in CMC settings influence learning opportunities during the task. In an attempt to shed light on the manner in which second language (L2) writing may contribute to L2 development, this chapter presents an empirical study of how two implementation features (degree of task structure and provision of language support) of a writing group task in simultaneous text-CMC influenced learner attention to linguistic form. The analysis draws on data from text chat performance and post-task group interviews to illustrate how aspects of task implementation in a technology-enhanced learning environment may promote attention to language expression and encourage collaborative work on language errors during writing task performance. (Contains 2 figures, 6 tables, and 3 examples.)

Research on interactional feedback has typically focused on feedback learners receive from native speakers (i.e., NS-learner contexts). However, for many second language (L2) learners, the majority of their opportunities to engage in interaction occur with other learners (i.e., learner-learner contexts). The literature has suggested that feedback in learner-learner interaction contexts differs from that found in NS-learner contexts in the quantity of feedback moves (e.g., Mackey, Oliver, & Leeman, 2003), types of feedback used (Pica, Lincoln-Porter, Paninos, & Linnell, 1996), and narrowness of linguistic foci (Toth, 2008). The current study examines how learners provide each other with two types of input-providing feedback, recasts (implicit feedback), and explicit corrections (explicit feedback), in order to investigate how different types of feedback and responses to feedback promote learning of English past tense and locatives. Findings suggest a limited evidence for a relationship between implicit feedback, modified output, and L2 learning, and evidence for a negative effect of explicit corrections from peers. These findings indicate that the role of feedback and modified output in learning may be different in learner-learner interactions than has been found in NS-learner interactions.

This article presents the authors' reply to Beniko Mason and Stephen Krashen's comments on their recent article published in "TESOL Quarterly." Mason and Krashen have provided an interesting reinterpretation of the authors' results and have also brought up several valid points regarding the efficiency of vocabulary learning from instruction, especially with regard to attrition. Here, the authors respond to several of the points made by Mason and Krashen. (Contains 1 figure.)

This study examines the relationship between learners' production of modified output and their working memory (WM) capacity. The task-based interactions of 42 college-level, native English-speaking learners of Spanish as a foreign language were examined. A relationship was found between learners' WM test scores and their tendency to modify output. Specifically, greater processing capacity was related to greater production of modified output during interaction.

This study compares integrated and isolated form-focused instruction for vocabulary development in an English as a second language (ESL) reading lesson. Two classes of ESL learners (N = 20) from a university preparation academic English course were involved in the study. Each class did two reading treatments in which they read an article and studied vocabulary from that article. In one of the treatments participants were taught the words in isolation prior to reading the article, and in the other the vocabulary instruction was integrated with reading the article. Paribakht and Wesche's (1997) vocabulary knowledge scale was used as the instrument to measure learning and retention gains for words taught in isolated instruction, in integrated instruction, and words acquired incidentally. Statistical analysis showed both types of instruction led to more learning and retention of vocabulary knowledge than incidental exposure alone. Although retention rates were similar for isolated and integrated instruction, there was a trend for isolated instruction to lead to higher rates of learning. (Contains 6 tables, 6 figures and 2 footnotes.)

While "Where the Wild Things Are" may be Maurice Sendak's most popular book, "In the Night Kitchen" is arguably the greater work. Though his journey in "Wild Things" shares many of the elements of Mickey's adventure in "Night Kitchen"--swinging between the protagonist's initiatory verbal assertions and silent, completely pictorial spreads that indicate his eventual dominance over his environment--Max's story is ultimately only a narrative of the self. "Where the Wild Things Are" is a beautiful exploration of how Max (the maximum boy) is able to use an imaginative journey to create an individual personality that fills the world around him. But Mickey must confront something more than merely a projection of his own desires. Mickey, unlike Max, is diminutive in his fantasy world, and his adventure is a true dream shaped willy-nilly by his lived experience, not a daydream tailored to defend the ego. The story told as Mickey learns to navigate the Night Kitchen is essentially a social narrative--more realistic, more challenging, and with greater overall dividends than Max's adventure. We can see this in the ways "In the Night Kitchen" combines four sorts of ingredients--Sendak's own life, the psychology of dreaming, popular culture, and the immigrant experience--into a subtle, captivating tale of the self and society.