Somatic evolution of marine transmissible leukemias in the common cockle, Cerastoderma edule.

Transmissible cancers are malignant cell lineages that spread clonally between individuals. Several such cancers, termed bivalve transmissible neoplasia (BTN), induce leukemia-like disease in marine bivalves. This is the case of BTN lineages affecting the common cockle, Cerastoderma edule, which inhabits the Atlantic coasts of Europe and northwest Africa. To investigate the evolution of cockle BTN, we collected 6,854 cockles, diagnosed 390 BTN tumors, generated a reference genome and assessed genomic variation across 61 tumors. Our analyses confirmed the existence of two BTN lineages with hemocytic origins. Mitochondrial variation revealed mitochondrial capture and host co-infection events. Mutational analyses identified lineage-specific signatures, one of which likely reflects DNA alkylation. Cytogenetic and copy number analyses uncovered pervasive genomic instability, with whole-genome duplication, oncogene amplification and alkylation-repair suppression as likely drivers. Satellite DNA distributions suggested ancient clonal origins. Our study illuminates long-term cancer evolution under the sea and reveals tolerance of extreme instability in neoplastic genomes.

Increasing digital mental health reach and uptake via youth partnerships.

Youth in the United States are facing an unprecedented mental health crisis. Yet, brick-and-mortar mental healthcare, such as face-to-face therapy, is overwhelmingly inaccessible to youth despite research advances in youth mental health. Digital Mental Health tools (DMH), the use of technologies to deliver mental health assessments and interventions, may help to increase mental healthcare accessibility. However, for a variety of reasons, evidence-based DMH have not been successful in reaching youth in real-world settings, particularly those who are most encumbered with access barriers to mental healthcare. This Comment therefore focuses on increasing DMH reach and uptake by young people, particularly among minoritized youth, by engaging in community-based youth partnerships. This idea recognizes and grows from decades' worth of community-based participatory research and youth partnerships successfully conducted by other disciplines (e.g., social work, public health, urban planning, education). Increasing uptake and engagement is an issue that is unlikely to be solved by adult-driven theory and design. As such, we emphasize the necessity of reframing youth input into DMH design and deployment from one-time participants to integral community-based partners. Indeed, recognizing and valuing their expertise to equitably address DMH implementation challenges, youth should help to pose the very questions that they will help to answer throughout the design and implementation planning for DMH moving forward.

The evolution of two transmissible cancers in Tasmanian devils.

Tasmanian devils have spawned two transmissible cancer lineages, named devil facial tumor 1 (DFT1) and devil facial tumor 2 (DFT2). We investigated the genetic diversity and evolution of these clones by analyzing 78 DFT1 and 41 DFT2 genomes relative to a newly assembled, chromosome-level reference. Time-resolved phylogenetic trees reveal that DFT1 first emerged in 1986 (1982 to 1989) and DFT2 in 2011 (2009 to 2012). Subclone analysis documents transmission of heterogeneous cell populations. DFT2 has faster mutation rates than DFT1 across all variant classes, including substitutions, indels, rearrangements, transposable element insertions, and copy number alterations, and we identify a hypermutated DFT1 lineage with defective DNA mismatch repair. Several loci show plausible evidence of positive selection in DFT1 or DFT2, including loss of chromosome Y and inactivation of MGA, but none are common to both cancers. This study reveals the parallel long-term evolution of two transmissible cancers inhabiting a common niche in Tasmanian devils.

Temporal discounting modifies the effect of microtemporal hedonic hunger on food consumption: An ecological momentary assessment study.

INTRODUCTION: Steeper delay discounting, or preference for small rewards sooner versus larger rewards later, has been linked to disinhibited eating and obesity. The overconsumption of food may also be motivated by hedonic hunger, or the drive to consume foods for pleasure rather than energy need. The present study hypothesized that hedonic hunger would modify the relation between temporal discounting and palatable food consumption. METHODS: Seventeen adolescents between the ages of 13-18 (M = 15.12,SD = 1.80) completed a temporal discounting measure at baseline followed by daily ecological momentary assessments of food intake (e.g., self-reported servings of sweet, starchy, fatty, fast foods) and hedonic hunger for 20 days on a mobile phone. Multilevel models examined between-person (BP) and within-person (WP) hedonic hunger, monetary temporal discounting, and their interactions, on food consumption. RESULTS: The models for sweet, starchy, and fast food consumption had significant interactions between WP hedonic hunger and temporal discounting. For each of these interactions, those with average-or-lower temporal discounting rates were at less risk of consuming sweet, starchy, and fast foods when hedonic hunger was higher than typical while those with high rates of discounting were at higher risk of consuming these types of foods when hedonic hunger was elevated. CONCLUSION: Increases in daily hedonic hunger may confer risk for sweet, starchy, and fast food consumption. However, preference for larger rewards later may serve as a protective factor against consumption of these palatable foods. Future studies should further investigate this and other reward-driven processes that may influence food consumption.

Micro-scale pedestrian streetscapes and physical activity in Hispanic/Latino adults: Results from HCHS/SOL.

We examined associations of micro-scale environment attributes (e.g., sidewalks, street crossings) with three physical activity (PA) measures among Hispanic/Latino adults (n = 1776) living in San Diego County, CA. Systematic observation was used to quantify micro-scale environment attributes near each participant's home. Total PA was assessed with accelerometers, and PA for transportation and recreation were assessed by validated self-report. Although several statistically significant interactions between individual and neighborhood characteristics were identified, there was little evidence micro-scale attributes were related to PA. An important limitation was restricted environmental variability for this sample which lived in a small area of a single county.

Location-specific psychosocial and environmental correlates of physical activity and sedentary time in young adolescents: preliminary evidence for location-specific approaches from a cross-sectional observational study.

BACKGROUND: A better understanding of the extent to which psychosocial and environmental correlates of physical activity are specific to locations would inform intervention optimization. PURPOSE: To investigate cross-sectional associations of location-general and location-specific variables with physical activity and sedentary time in three common locations adolescents spend time. METHODS: Adolescents (N = 472,Mage = 14.1,SD = 1.5) wore an accelerometer and global positioning systems (GPS) tracker and self-reported on psychosocial (e.g., self-efficacy) and environmental (e.g., equipment) factors relevant to physical activity and sedentary time. We categorized each survey item based on whether it was specific to a location to generate psychosocial and environmental indices that were location-general or specific to either school, non-school, or home location. Physical activity (MVPA) and sedentary time were based on time/location match to home, school, or all "other" locations. Mixed-effects models investigated the relation of each index with location-specific activity. RESULTS: The location-general and non-school physical activity psychosocial indices were related to greater MVPA at school and "other" locations. The school physical activity environment index was related to greater MVPA and less sedentary time at school. The home activity environment index was related to greater MVPA at home. The non-school sedentary psychosocial index was related to less sedentary time at home. Interactions among indices revealed adolescents with low support on one index benefited (i.e., exhibited more optimal behavior) from high support on another index (e.g., higher scores on the location-general PA psychosocial index moderated lower scores on the home PA environment index). Concurrent high support on two indices did not provide additional benefit. CONCLUSIONS: No psychosocial or environment indices, including location-general indices, were related to activity in all locations. Most of the location-specific indices were associated with activity in the matching location(s). These findings provide preliminary evidence that psychosocial and environmental correlates of activity are location specific. Future studies should further develop location-specific measures and evaluate these constructs and whether interventions may be optimized by targeting location-specific psychosocial and environmental variables across multiple locations.

Sex disparity in oronasal presentations of canine transmissible venereal tumour.

BACKGROUND: The canine transmissible venereal tumour (CTVT) is a contagious cancer spread by the direct transfer of living cancer cells. CTVT usually spreads during mating, manifesting as genital tumours. However, oronasal CTVT is also occasionally observed, and presumably arises through oronasal contact with genital CTVT tumours during sniffing and licking. METHODS: Given that sniffing and licking transmission behaviours may differ between sexes, we investigated whether oronasal CTVT shows sex disparity. RESULTS: Twenty-seven of 32 (84%) primary oronasal tumours in a CTVT tumour database occurred in males. In addition, 53 of 65 (82%) primary oronasal CTVT tumours reported in the published literature involved male hosts. These findings suggest that male dogs are at four to five times greater risk of developing primary oronasal CTVT than females. This disparity may be due to sex differences in licking and sniffing activity, perhaps also influenced by sex differences in CTVT accessibility for these behaviours. CONCLUSION: Although oronasal CTVT is rare, it should be considered as a possible diagnosis for oronasal tumours, particularly in male dogs.

The development of a clinical algorithm for the diagnosis of tumours in the parapharyngeal space. A systematic review.

INTRODUCTION: Parapharyngeal space (PPS) is defined as a deep space, located around the upper pharynx, in the shape of an inverted pyramid. Primary tumours in this region are rare, accounting for 0.5% of head and neck neoplasms, and most are benign. The objective of this study is to propose a new study algorithm based on a systematic review and our experience. MATERIALS AND METHODS: A cross-sectional and analytical study was carried out through review of the clinical records of our hospital. Patients with tumours of the parapharyngeal space operated from January 2010 to December 2019 and a systematic review of Pubmed studies from the last 5 years were included. We considered clinical signs, diagnostic methods, presumptive diagnosis and histopathological findings. Statistical analysis was performed with STATA v.14 software. RESULTS: 53 of our cases and 1392 from the review were included. The clinical algorithm showed a sensitivity of 76.4% and a specificity of 96.3%, with an AUC of 0.57 for diagnosis. DISCUSSION: Complementary radiological examinations are essential in the topographic diagnosis of the tumour. Angio-MRI links the tissue of origin of the tumours and provides the highest diagnostic certainty. FNA has some disadvantages in PPS, but it is useful in some patients. CONCLUSION: The proposed algorithm contributes to obtaining excellent results in the management of these tumours because it turned out to be effective in diagnosis, and this enables improved surgical planning.

Somatic mutation rates scale with lifespan across mammals.

The rates and patterns of somatic mutation in normal tissues are largely unknown outside of humans1-7. Comparative analyses can shed light on the diversity of mutagenesis across species, and on long-standing hypotheses about the evolution of somatic mutation rates and their role in cancer and ageing. Here we performed whole-genome sequencing of 208 intestinal crypts from 56 individuals to study the landscape of somatic mutation across 16 mammalian species. We found that somatic mutagenesis was dominated by seemingly endogenous mutational processes in all species, including 5-methylcytosine deamination and oxidative damage. With some differences, mutational signatures in other species resembled those described in humans8, although the relative contribution of each signature varied across species. Notably, the somatic mutation rate per year varied greatly across species and exhibited a strong inverse relationship with species lifespan, with no other life-history trait studied showing a comparable association. Despite widely different life histories among the species we examined-including variation of around 30-fold in lifespan and around 40,000-fold in body mass-the somatic mutation burden at the end of lifespan varied only by a factor of around 3. These data unveil common mutational processes across mammals, and suggest that somatic mutation rates are evolutionarily constrained and may be a contributing factor in ageing.

Ultrasound-guided Drainage vs Surgical Drainage of Deep Neck Space Abscesses: A Randomized Controlled Trial.

INTRODUCTION: The most common cause of deep neck infections is dental infection. They are diagnosed with physical examination, imaging studies, ultrasound, or computed tomography. Surgical drainage of collections should always be performed early in a classical or percutaneous way, depending on the case. The aim of the study was to compare ultrasound-guided percutaneous drainage techniques vs. surgical drainage in deep cervical abscesses of odontogenic origin in a controlled and randomized trial. METHODS: A randomized controlled clinical trial was performed from January 2015 to December 2019. Hospital stay was evaluated as an efficiency variable. Epidemiological and secondary variable data (tumour, trismus, fever, pain), leukocytosis, cosmetic result comparing both techniques were analysed. Statistical analysis was carried out with STATA v 14.0. RESULTS: 128 patients were analysed, 51 women and 77 men. Average age 27.3 (SD = 10.13). The percutaneous group had a mean hospital stay of 3.03 (SD = 2.86) days and the surgical group 5.46 (SD = 2.96). The P-value was <.001. Cosmetic results showed differences favouring the percutaneous drainage group. None of the other variables showed statistically significant results. DISCUSSION: Surgical treatment (cervicotomy and debridement) should be undertaken early with evidence of extensive collection in deep spaces. Minimally invasive image-guided procedures are an alternative. These can be performed in well-located, unilocular collections, without compromising of the patient's airway. Percutaneous drainage and suction techniques if necessary, serially, or drainage placement may be performed. CONCLUSIONS: Ultrasound-guided and serially guided percutaneous drainage is the best therapeutic option in patients with mild and/or moderate dental infections.

Searching for transmissible cancers among the mussels of Europe.

Transmissible cancers are infectious malignant cell clones that spread among individuals through transfer of living cancer cells. Several such clones have been identified in various species of marine bivalve molluscs, including mussels, clams and cockles. These parasitic cell lineages cause a leukaemia-like disease called disseminated neoplasia, and are presumed to pass between hosts by ingestion of water-borne cancer cells during filter feeding. Although occasional cases of transmissible cancer had previously been identified in mussels of the genus Mytilus in Europe, the number of distinct clones affecting these animals, and their prevalence, was unknown. In this issue of Molecular Ecology, Hammel et al. (2021) present findings from a large-scale screen for transmissible cancer across 5907 European Mytilus mussels. Using a genotyping approach, Hammel et al. searched for signal of genetic chimerism, which can arise due to infection by transmissible cancer cells. The screen detected a previously identified globally distributed mussel transmissible cancer at very low prevalence, and found no evidence of additional contagious clones. A parallel histological screen additionally revealed low prevalence of a nontransmissible form of disseminated neoplasia. By quantifying the burden of disseminated neoplasia in European mussel populations, this study provides strong foundations for future work investigating the origins, evolution and impacts of transmissible cancers in mussels.

As cancer grows old.

Mutations trace the evolution of an ancient tumor lineage.

Aberrant integration of Hepatitis B virus DNA promotes major restructuring of human hepatocellular carcinoma genome architecture.

Most cancers are characterized by the somatic acquisition of genomic rearrangements during tumour evolution that eventually drive the oncogenesis. Here, using multiplatform sequencing technologies, we identify and characterize a remarkable mutational mechanism in human hepatocellular carcinoma caused by Hepatitis B virus, by which DNA molecules from the virus are inserted into the tumour genome causing dramatic changes in its configuration, including non-homologous chromosomal fusions, dicentric chromosomes and megabase-size telomeric deletions. This aberrant mutational mechanism, present in at least 8% of all HCC tumours, can provide the driver rearrangements that a cancer clone requires to survive and grow, including loss of relevant tumour suppressor genes. Most of these events are clonal and occur early during liver cancer evolution. Real-time timing estimation reveals some HBV-mediated rearrangements occur as early as two decades before cancer diagnosis. Overall, these data underscore the importance of characterising liver cancer genomes for patterns of HBV integration.

Meta-Analysis of Adherence Promotion Interventions in Pediatric Asthma.

BACKGROUND: Youth with asthma commonly have suboptimal adherence to inhaled corticosteroids (ICS). It is critical to systematically evaluate the effectiveness of ICS adherence promotion interventions and discern which techniques are most effective. OBJECTIVE: This study aims to (1) quantify the extent to which interventions improve ICS adherence in pediatric asthma, (2) explore differences in effect size estimates based on intervention and study characteristics, and (3) characterize the risk of bias across interventions. METHODS: We conducted literature searches across five databases. Included studies quantitatively measured ICS adherence as an intervention outcome among youth (<18 years old) diagnosed with asthma and were published after 1997. We analyzed aggregate effect sizes and moderator variables using random-effects models and characterized risk of bias using the Cochrane Collaboration tool. RESULTS: Thirty-three unique studies met inclusion criteria. At post-intervention, the aggregate effect size for pediatric ICS adherence promotion interventions was small but significant (n = 33, g = 0.39, 95% confidence interval [CI] = 0.24-0.54); however, the aggregate effect size at follow-up was not statistically significant (n = 6, g = 0.38, 95% CI = -0.08 to 0.83). Method of adherence measurement and intervention format were significant moderators. Most interventions had a high risk of performance bias and an unclear risk of bias in one or more domains. CONCLUSIONS: ICS adherence promotion interventions are effective among youth with asthma. Additional longitudinal research is needed to quantify a more precise measure of intervention effectiveness over time, and moderators of intervention effectiveness should be reassessed as the literature base expands.

Ultrasound-guided drainage vs surgical drainage of deep neck space abscesses: A randomized controlled trial. / Drenaje percutáneo ecoguiado vs. drenaje quirúrgico en abscesos cervicales profundos de origen odontógeno. Ensayo clínico controlado y aleatorizado.

INTRODUCTION: The most common cause of deep neck infections is dental infection. They are diagnosed with physical examination, imaging studies, ultrasound, or computed tomography. Surgical drainage of collections should always be performed early in a classical or percutaneous way, depending on the case. The aim of the study was to compare ultrasound-guided percutaneous drainage techniques vs. surgical drainage in deep cervical abscesses of odontogenic origin in a controlled and randomized trial. METHODS: A randomized controlled clinical trial was performed from January 2015 to December 2019. Hospital stay was evaluated as an efficiency variable. Epidemiological and secondary variable data (tumour, trismus, fever, pain), leukocytosis, cosmetic result comparing both techniques were analysed. Statistical analysis was carried out with STATA v 14.0. RESULTS: 128 patients were analysed, 51 women and 77 men. Average age 27.3 (SD = 10.13). The percutaneous group had a mean hospital stay of 3.03 (SD = 2.86) days and the surgical group 5.46 (SD = 2.96). The p-value was <.001. Cosmetic results showed differences favouring the percutaneous drainage group. None of the other variables showed statistically significant results. DISCUSSION: Surgical treatment (cervicotomy and debridement) should be undertaken early with evidence of extensive collection in deep spaces. Minimally invasive image-guided procedures are an alternative. These can be performed in well-located, unilocular collections, without compromising of the patient's airway. Percutaneous drainage and suction techniques if necessary, serially, or drainage placement may be performed. CONCLUSIONS: Ultrasound-guided and serially guided percutaneous drainage is the best therapeutic option in patients with mild and/or moderate dental infections.

LigaSure™ haemorrhoidectomy and the risk of postoperative bleeding.

AIM: LigaSure™ is an electro-surgical device that has increasingly been utilized in haemorrhoid surgery. However, recent literature has highlighted a possible increased risk of delayed postoperative bleeding following LigaSure haemorrhoidectomy (LH). We aim to evaluate the rates of postoperative bleeding following LigaSure compared to Ferguson (closed) haemorrhoidectomy (FH). METHODS: A retrospective cohort study was undertaken at our single academic safety-net county hospital from August 2016 through July 2019 evaluating patients who received FH or LH. Patient demographics, surgical data, postoperative emergency department visit for pain or bleeding within 30 days and resulting transfusion requirement, and rates of readmission and interventions within 30 days were collected. RESULTS: Sixty-one FH and 66 LH patients were identified. The groups had no difference in demographics. The LH group and FH group had similar rates of postoperative emergency department visits (29% vs. 23%, P = 0.454), as well as visits for bleeding (20% vs. 11%, P = 0.204). The average operating time was also significantly shorter with LH (14.5 min vs. 24.9 min, P ≤ 0.001). On multivariate analysis, male sex (OR 7.28, 95% CI 1.88-28.25) and haemorrhoid grade ≤2 (OR 4.64, 95% CI 1.31-16.49) were significantly associated with postoperative bleeding on multivariate analysis. Use of LH was not independently associated with postoperative bleeding risk (OR 1.89, 95% CI 0.70-5.11). CONCLUSIONS: LH and FH have similar risks for postoperative bleeding and other complications. Male sex and haemorrhoid Grades 1 or 2 may be associated with increased postoperative bleeding risk. Excisional haemorrhoidectomy should be undertaken with caution for male patients with lower internal haemorrhoid grades.

The development of a clinical algorithm for the diagnosis of tumours in the parapharyngeal space. A systematic review. / Desarrollo de algoritmo clínico para el diagnóstico de tumores del espacio parafaríngeo. Revisión sistemática.

INTRODUCTION: Parapharyngeal space (PPS) is defined as a deep space, located around the upper pharynx, in the shape of an inverted pyramid. Primary tumours in this region are rare, accounting for 0.5% of head and neck neoplasms, and most are benign. The objective of this study is to propose a new study algorithm based on a systematic review and our experience. MATERIALS AND METHODS: A cross-sectional and analytical study was carried out through review of the clinical records of our hospital. Patients with tumours of the parapharyngeal space operated from January 2010 to December 2019 and a systematic review of Pubmed studies from the last 5years were included. We considered clinical signs, diagnostic methods, presumptive diagnosis and histopathological findings. Statistical analysis was performed with STATA v.14 software. RESULTS: 53 of our cases and 1392 from the review were included. The clinical algorithm showed a sensitivity of 76.4% and a specificity of 96.3%, with an AUC of 0.57 for diagnosis. DISCUSSION: Complementary radiological examinations are essential in the topographic diagnosis of the tumour. Angio-MRI links the tissue of origin of the tumours and provides the highest diagnostic certainty. FNA has some disadvantages in PPS, but it is useful in some patients. CONCLUSION: The proposed algorithm contributes to obtaining excellent results in the management of these tumours because it turned out to be effective in diagnosis, and this enables improved surgical planning.

Somatic mutation landscapes at single-molecule resolution.

Somatic mutations drive the development of cancer and may contribute to ageing and other diseases1,2. Despite their importance, the difficulty of detecting mutations that are only present in single cells or small clones has limited our knowledge of somatic mutagenesis to a minority of tissues. Here, to overcome these limitations, we developed nanorate sequencing (NanoSeq), a duplex sequencing protocol with error rates of less than five errors per billion base pairs in single DNA molecules from cell populations. This rate is two orders of magnitude lower than typical somatic mutation loads, enabling the study of somatic mutations in any tissue independently of clonality. We used this single-molecule sensitivity to study somatic mutations in non-dividing cells across several tissues, comparing stem cells to differentiated cells and studying mutagenesis in the absence of cell division. Differentiated cells in blood and colon displayed remarkably similar mutation loads and signatures to their corresponding stem cells, despite mature blood cells having undergone considerably more divisions. We then characterized the mutational landscape of post-mitotic neurons and polyclonal smooth muscle, confirming that neurons accumulate somatic mutations at a constant rate throughout life without cell division, with similar rates to mitotically active tissues. Together, our results suggest that mutational processes that are independent of cell division are important contributors to somatic mutagenesis. We anticipate that the ability to reliably detect mutations in single DNA molecules could transform our understanding of somatic mutagenesis and enable non-invasive studies on large-scale cohorts.

Adaptive mHealth Intervention for Adolescent Physical Activity Promotion.

OBJECTIVE: The present nonrandomized controlled trial aimed to evaluate feasibility, acceptability, and preliminary efficacy of a tailored text message intervention for increasing adolescent physical activity, as compared with passive monitoring. METHODS: Forty adolescents (13-18 years old) received either a tailored text messaging intervention (Network Underwritten Dynamic Goals Engine [NUDGE]; N = 20), or participated in an attention-control condition (N = 20), for 20 days. Physical activity was measured for all participants via continuous accelerometry. Frequency analyses were conducted on program usage and satisfaction ratings to evaluate feasibility and acceptability, and multilevel models were used to evaluate the efficacy hypotheses. RESULTS: The vast majority of participants (90%) reported being very or mostly satisfied with the NUDGE program and rated their enjoyment as above average. The intervention group was estimated to spend an average of 20.84 more minutes per day in moderate-to-vigorous physical activity relative to the attention-control group (ß = 20.84, SE = 8.19). Exploratory analyses revealed that the intervention group also engaged in 82 fewer minutes of sedentary time per day on average, although this effect was not significant due to the large variability in sedentary time (ß = -81.98, SE = 46.86). CONCLUSIONS: The NUDGE tailored text messaging intervention was feasible, acceptable, and efficacious in increasing physical activity in this sample. Findings warrant additional evaluation of NUDGE as both a standalone physical activity intervention or as part of a multicomponent package.