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Background Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer that most commonly occurs in ultraviolet-exposed body sites. The epidemiology of MCC in different geographies and populations is not well characterized. Objectives The objective of this systematic review is to summarize evidence on the incidence, mortality and survival rates of MCC from population-based studies. Methods We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from database inception to 6 June 2023. No geographic, age or date exclusions were applied. We included population-based studies of MCC that reported the incidence, survival or mortality rate, and also considered systematic reviews. A data-charting form was created and validated to identify variables to extract. Two reviewers then independently charted the data for each included study with patient characteristics, and estimates of incidence rate, mortality rate, and survival rate and assessed the quality of included studies using the Joanna Briggs Institute Checklist for Prevalence studies, Newcastle–Ottawa Scale and Assessment of Multiple Systematic Reviews. We abstracted age-, sex-, stage- and race-stratified outcomes, and synthesized comparisons between strata narratively and using vote counting. We assessed the certainty of evidence for those comparisons using the Grading of Recommendations, Assessments, Developments and Evaluations framework. Results We identified 11 472 citations, of which 52 studies from 24 countries met our inclusion criteria. Stage I and the head and neck were the most frequently reported stage and location at diagnosis. The incidence of MCC is increasing over time (high certainty), with the highest reported incidences reported in southern hemisphere countries [Australia (2.5 per 100 000); New Zealand (0.96 per 100 000) (high certainty)]. Male patients generally had higher incidence rates compared with female patients (high certainty), although there were some variations over time periods. Survival rates varied, with lower survival and/or higher mortality associated with male sex (moderate certainty), higher stage at diagnosis (moderate-to-high certainty), older age (moderate certainty), and immunosuppression (low-to-moderate certainty). Conclusions MCC is increasing in incidence and may increase further given the ageing population of many countries. The prognosis of MCC is poor, particularly for male patients, those who are immunosuppressed, and patients diagnosed at higher stages or at an older age. [ABSTRACT FROM AUTHOR]

Abstract Inadequate delivery of oxygen to organisms during development can lead to cell dysfunction/death and life-long disabilities. Although the susceptibility of developing cells to low oxygen conditions changes with maturation, the cellular and molecular pathways that govern responses to low oxygen are incompletely understood. Here we show that developing Caenorhabditis elegans are substantially more sensitive to anoxia than adult animals and that this sensitivity is controlled by nervous system generated hormones (e.g., neuropeptides). A screen of neuropeptide genes identified and validated nlp-40 and its receptor aex-2 as a key regulator of anoxic survival in developing worms. The survival-promoting action of impaired neuropeptide signaling does not rely on five known stress resistance pathways and is specific to anoxic insult. Together, these data highlight a novel cell non-autonomous pathway that regulates the susceptibility of developing organisms to anoxia. Graphical abstract fx1 Highlights • Developing C. elegans lacking neuropeptide signaling survive anoxic stress better. • This effect does not rely on canonical stress resistance pathways. • Neurons, not other tissues, are the source of the neuropeptides underlying survival. • We employed a directed screen of worm neuropeptides to identify candidates. • The screen suggests nlp-40 partially accounts for anoxic survival phenotype. [ABSTRACT FROM AUTHOR]

This article documents the experiences of three early career academics trying to establish a network of early career academics (ECAs) in a middle-ranked university in Australia. The changing context of academia means that ECAs face considerable challenges in understanding and negotiating effective career paths. Some of the issues encountered include insecure employment arrangements; unclear and shifting expectations; heavy workloads and competing demands; and conflicting experiences around the collegiate culture of academia. As research and teaching institutions, universities must ensure the ongoing development of new academics. While there is a growing interest in exploring the issues confronted by new academics, much remains to be done to better understand, and improve, the pathways of academic development. To this end we reflect on our efforts to establish an ECA network that aimed to enhance professional development, facilitate an improved research culture and establish an informal peer support network. We did so through establishing an online presence for sharing information, hosting a series of professional development seminars and hosting a 2.5 day writing retreat. Our experiences suggest that, while efforts to enhance the capacity of ECAs are worthwhile, the very same pressures that our network was attempting to address were simultaneously creating barriers to ECA involvement in the network and its activities. [ABSTRACT FROM PUBLISHER]

The current incarnation of 'reality TV' in Australia has a strong focus on the portrayal of everyday life. Although based on 'real' situations or people, there is a clear tension between ideas of authenticity and performance. As a global phenomenon, 'reality' formats are produced for local audiences by highlighting aspects of the national culture and identity, with format popularity directly linked to identification and affirmation of the spectacle of 'reality'. This paper will analyse the use of popular Australian myth in 'reality' formats by charting narrative and character construction as an 'illusory everyday', with reference to Bondi Rescue (Cordell Jigsaw). The paper will examine the representation of Australian identity through both myth and construction in 'reality TV' as the perpetuation of a cultural simulation. Implications for research on the genre and the industry are also discussed. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The current study aimed to investigate the difference in the levels of core beliefs between eating disordered women and those who showed milder forms of symptomatology. Methods: Thirty-five eating disordered women, 16 symptomatic dieters, 39 normal dieters and 34 non-clinical comparison women completed questionnaires measuring eating symptomatology (Eating Disorders Inventory [EDI]), core beliefs (Young Schema Questionnaire [YSQ]), depression (The Beck Depression Inventory-II [BDI-II]) and self-esteem (Rosenberg Self-Esteem Inventory [RSE]). Results: With the exception of Entitlement beliefs, there were significant differences in the levels of core beliefs across all four groups. In particular, symptomatic dieters and eating disordered women differed on 8 YSQ subscales despite showing very similar level of eating symptomatology. Discussion: The current findings lend support to the discontinuity model that suggests that there are fundamental differences between women with a clinical eating disorder and those with milder eating psychopathology. The clinical and research implications of the present results were discussed. [Copyright &y& Elsevier]

SINE-VNTR-Alu (SVA) retrotransposons are a subclass of transposable elements (TEs) that exist only in primate genomes. TE insertions can be co-opted as cis-regulatory elements (CREs); however, the regulatory potential of SVAs has predominantly been demonstrated using bioinformatic approaches and reporter gene assays. The objective of this study was to demonstrate SVA cis-regulatory activity by CRISPR (clustered regularly interspaced short palindromic repeats) deletion and subsequent measurement of direct effects on local gene expression. We identified a region on chromosome 17 that was enriched with human-specific SVAs. Comparative gene expression analysis at this region revealed co-expression of TRPV1 and TRPV3 in multiple human tissues, which was not observed in mouse, highlighting key regulatory differences between the two species. Furthermore, the intergenic region between TRPV1 and TRPV3 coding sequences contained a human specific SVA insertion located upstream of the TRPV3 promoter and downstream of the 3′ end of TRPV1, highlighting this SVA as a candidate to study its potential cis-regulatory activity on both genes. Firstly, we generated SVA reporter gene constructs and demonstrated their transcriptional regulatory activity in HEK293 cells. We then devised a dual-targeting CRISPR strategy to facilitate the deletion of this entire SVA sequence and generated edited HEK293 clonal cell lines containing homozygous and heterozygous SVA deletions. In edited homozygous ∆SVA clones, we observed a significant decrease in both TRPV1 and TRPV3 mRNA expression, compared to unedited HEK293. In addition, we also observed an increase in the variability of mRNA expression levels in heterozygous ∆SVA clones. Overall, in edited HEK293 with SVA deletions, we observed a disruption to the co-expression of TRPV1 and TRPV3. Here we provide an example of a human specific SVA with cis-regulatory activity in situ, supporting the role of SVA retrotransposons as contributors to species-specific gene expression. [ABSTRACT FROM AUTHOR]

The article focuses on the detection and management of the Eastern raccoon rabies virus variant (RRVV) in Omaha, Nebraska, following a rabid kitten's death. Topics include the coordinated response by public health agencies, the implementation of enhanced surveillance efforts, and a wildlife vaccination campaign to prevent further rabies transmission.

Influenza A virus (IAV) increases presentation of class I human leukocyte antigen (HLA) proteins that limit antiviral responses mediated by natural killer (NK) cells, but molecular mechanisms have not yet been fully elucidated. We observed that infection with A/Fort Monmouth/1/1947 (H1N1) IAV significantly increased presentation of HLA-B, -C and -E on lung epithelial cells. Virus entry was not sufficient to induce HLA upregulation because UV-inactivated virus had no effect. Aberrant internally-deleted viral RNAs (vRNAs) known as mini viral RNAs (mvRNAs) and defective interfering RNAs (DI RNAs) expressed from an IAV minireplicon were sufficient to induce HLA upregulation. These defective RNAs bind to retinoic acid-inducible gene-I (RIG-I) and initiate mitochondrial antiviral signaling (MAVS) protein-dependent antiviral interferon (IFN) responses. Indeed, MAVS was required for HLA upregulation in response to IAV infection or ectopic mvRNA/DI RNA expression. The effect was partially due to paracrine signalling, as we observed that IAV infection or mvRNA/DI RNA-expression stimulated production of IFN-β and IFN-λ, and conditioned media from these cells elicited a modest increase in HLA surface levels in naïve epithelial cells. HLA upregulation in response to aberrant viral RNAs could be prevented by the Janus kinase (JAK) inhibitor ruxolitinib. While HLA upregulation would seem to be advantageous to the virus, it is kept in check by the viral non-structural 1 (NS1) protein; we determined that NS1 limits cell-intrinsic and paracrine mechanisms of HLA upregulation. Taken together, our findings indicate that aberrant IAV RNAs stimulate HLA presentation, which may aid viral evasion of innate immunity. IMPORTANCE Human leukocyte antigens (HLA) are cell surface proteins that regulate innate and adaptive immune responses to viral infection by engaging with receptors on immune cells. Many viruses have evolved ways to evade host immune responses by modulating HLA expression and/or processing. Here, we provide evidence that aberrant RNA products of influenza virus genome replication can trigger RIG-I/MAVS-dependent remodeling of the cell surface, increasing surface presentation of HLA proteins known to inhibit the activation of an immune cell known as a natural killer (NK) cell. While this HLA upregulation would seem to be advantageous to the virus, it is kept in check by the viral non-structural 1 (NS1) protein, which limits RIG-I activation and interferon production by the infected cell. [ABSTRACT FROM AUTHOR]

Background: A resuscitation plan is a medically authorised order to use or withhold resuscitation interventions. Absence of appropriate resuscitation orders exposes patients to the risk of invasive medical interventions that may be of questionable benefit depending on individual circumstances. Aims: To describe among junior doctors: (i) self‐reported confidence discussing and completing resuscitation plans; (ii) knowledge of resuscitation policy including whether resuscitation plans are legally enforceable and key triggers for completion; and (iii) the factors associated with higher knowledge of triggers for completing resuscitation plans. Methods: A cross‐sectional survey was conducted at five hospitals. Junior doctors on clinical rotation were approached at scheduled training sessions, before or after ward rounds or at change of rotation orientation days and provided with a pen‐and‐paper survey. Results: A total of 118 junior doctors participated. Most felt confident discussing (79%; n = 92) and documenting (87%; n = 102) resuscitation plans with patients. However, only 45% (n = 52) of doctors correctly identified that resuscitation plans are legally enforceable medical orders. On average, doctors correctly identified 6.8 (standard deviation = 1.8) out of 10 triggers for completing a resuscitation plan. Doctors aged >30 years were four times more likely to have high knowledge of triggers for completing resuscitation plans (odds ratio 4.28 (95% confidence interval 1.54–11.89); P = 0.0053). Conclusion: Most junior doctors feel confident discussing and documenting resuscitation plans. There is a need to improve knowledge about legal obligations to follow completed resuscitation plans, and about when resuscitation plans should be completed to ensure they are completed with patients who are most at risk. [ABSTRACT FROM AUTHOR]

Background: Punctate palmoplantar keratoderma type 1 (PPPK1) presents in late childhood to adulthood with multiple small discrete hyperkeratotic papules on palms and soles. PPPK1 is an autosomal dominant skin disease caused by AAGAB mutations. It has been suggested that PPPK1 may be associated with an increased predisposition to systemic malignancies. Objectives: To evaluate the presence of AAGAB mutations in Canadian families with PPPK1 and the possible increased predisposition to systemic malignancies. Methods: Eighteen unrelated Canadian families with PPPK1 were recruited for this study. Genomic DNA was extracted from saliva and PCR amplification was performed for all AAGAB exons and exon/intron junctions. PCR products were sequenced and analyzed for mutations. A family history of malignancy was obtained from the index case and, when possible, from other family members. Results: We have identified 5 heterozygous AAGAB loss of function mutations in 11 families. The mutation c.370 C>T, p.Arg124* was the most prevalent and was identified in 6 families. A splice site mutation, c.451+3delAAGT, was identified in 2 families. The other mutations c.473delG, p.Gly158Glufs*0; c.550-551insAAT, p.Gly183*; and c.505-506 dupAA, p.Asn169Lysfs*6 were each identified in 1 family. Different cancers were reported in 11 families (Table 1 and Supplemental Figure S1). Conclusions: AAGAB mutations were found in 11 of 18 families with PPPK1. In some families there appears to be an association with cancer. [ABSTRACT FROM AUTHOR]