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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.

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]