Single-cell multi-omic analysis of fibrolamellar carcinoma reveals rewired cell-to-cell communication patterns and unique vulnerabilities.

Fibrolamellar carcinoma (FLC) is a rare malignancy disproportionately affecting adolescents and young adults with no standard of care. FLC is characterized by thick stroma, which has long suggested an important role of the tumor microenvironment. Over the past decade, several studies have revealed aberrant markers and pathways in FLC.

Transcriptional reprogramming primes CD8+ T cells toward exhaustion in Myalgic encephalomyelitis/chronic fatigue syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME) is a severe, debilitating disease, with substantial evidence pointing to immune dysregulation as a key contributor to pathophysiology. To characterize the gene regulatory state underlying T cell dysregulation in ME, we performed multiomic analysis across T cell subsets by integrating single-cell RNA-seq, RNA-seq, and ATAC-seq and further analyzed CD8+ T cell subpopulations following symptom provocation. Specific subsets of CD8+ T cells, as well as certain innate T cells, displayed the most pronounced dysregulation in ME.

Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious and poorly understood disease. To understand immune dysregulation in ME/CFS, we use single-cell RNA sequencing (scRNA-seq) to examine immune cells in patient and control cohorts. Postexertional malaise (PEM), an exacerbation of symptoms following strenuous exercise, is a characteristic symptom of ME/CFS.

Parallel evolution of ancient, pleiotropic enhancers underlies butterfly wing pattern mimicry.

Color pattern mimicry in butterflies is a classic case study of complex trait adaptation via selection on a few large effect genes. Association studies have linked color pattern variation to a handful of noncoding regions, yet the presumptive cis-regulatory elements (CREs) that control color patterning remain unknown. Here we combine chromatin assays, DNA sequence associations, and genome editing to functionally characterize 5 cis-regulatory elements of the color pattern gene We were surprised to find that the cis-regulatory architecture of is characterized by pleiotropy and regulatory fragility, where deletion of individual cis-regulatory elements has broad effects on both color pattern and wing vein development.

Chromatin conformation remains stable upon extensive transcriptional changes driven by heat shock.

Heat shock (HS) initiates rapid, extensive, and evolutionarily conserved changes in transcription that are accompanied by chromatin decondensation and nucleosome loss at HS loci. Here we have employed in situ Hi-C to determine how heat stress affects long-range chromatin conformation in human and cells. We found that compartments and topologically associating domains (TADs) remain unchanged by an acute HS.

Screening for depression in young Indigenous people: building on a unique community initiative.

Gurriny Yealamucka Health Service Aboriginal Corporation (GYHSAC) is an Indigenous community-controlled health organisation providing comprehensive primary care to the people of Yarrabah in far north Queensland, Australia. GYHSAC conducts an annual Young Person's Health Check (YPC) for people aged 15-25 years based on the Medical Benefits Schedule Item 715. However, the YPC is constantly evolving to meet the needs of the community, and in 2016, in response to concerns about psychological risk among Indigenous youth, GYHSAC teamed up with James Cook University to trial an adapted PHQ-9 depression screening tool (aPHQ-9) as part of the YPC.

Trajectories of loneliness during childhood and adolescence: predictors and health outcomes.

The present study employed latent growth mixture modeling to discern distinct trajectories of loneliness using data collected at 2-year intervals from age 7-17 years (N = 586) and examine whether measures taken at age 5 years were good predictors of group membership. Four loneliness trajectory classes were identified: (1) low stable (37% of the sample), (2) moderate decliners (23%), (3) moderate increasers (18%), and (4) relatively high stable (22%). Predictors at age 5 years for the high stable trajectory were low trust beliefs, low trusting, low peer acceptance, parent reported negative reactivity, an internalizing attribution style, low self-worth, and passivity during observed play.

The separateness of social and emotional loneliness in childhood.

Background: Much of the childhood loneliness research is misleading because it confounds objective and subjective measures of loneliness. The overall aim of this research was to examine the relationship between social isolation and emotional loneliness.

Method: Three extreme groups were identified in a sample of 640 4-9-year-old children.

The RHSET service as a regional resource: what price support?

The Rural Health Support, Education and Training (RHSET) advisory service has been a valuable tool for rural and remote organisations wishing to submit applications for health and human service grants. It has enhanced the concept of access and equity for groups in rural and remote areas. Support and networking have been strong factors in the service, which has overcome the limitations of inadequate travel and time resources for part-time project officers providing assistance to organisations seeking grants.

Children's understanding of number words.

This research notes gives details of an atypical response to a 'give a number' task by a 34-month-old child. The child clearly demonstrated that he understood the word 'two' to refer to an object rather than to a quantity. This incident offers support to Fuson's (1988) theory of the functionally specific initial acquisition of number word meanings and suggests that Gelman & Meck's (1983) 'principles first' account of the development of counting gives insufficient weight to the role of language and social interaction in the development of early number understanding.

Sibling quarrels and maternal intervention: individual differences in understanding and aggression.

Individual differences in the nature and frequency of conflict behaviour between 18-24 month old children and their older siblings were investigated in a sample of 43 sibling pairs observed at home with their mothers. By 24 months, relatively mature behaviour such as conciliation, teasing, reference to social rules and justification for prohibition were observed. These behaviours were correlated with maternal and sibling reference to social rules and feelings 6 months earlier; physical aggression was correlated with earlier sibling physical aggression and maternal involvement.