Putting bacteria on the cancer map.

In a study recently in Nature, Galeano Niño et al. use spatial profiling and single-cell RNA sequencing to delineate the spatial organization of microbiota in cancer. Their findings demonstrate that tumor-associated microbiota coalesce in micro-niches where they may mediate immune and epithelial oncogenic roles.

Longitudinal trajectories of suicidal ideation among child welfare-involved 7- to 12-year-old children.

BACKGROUND: Young children involved in the child welfare system (CWS) are at high risk for suicidal ideation (SI) at a time when overall rates of suicide death in this age group are rising. Yet risk factors for and changes in SI over time are poorly understood in this population. METHOD: We combined data from two large representative longitudinal studies of children involved in the United States CWS. We examined patterns of SI among children who were between ages 7 and 12 years at the initial survey wave (N = 2,186), assessed at three waves using a measure of SI in the past 2 weeks. We conducted a multinomial regression to understand the baseline demographic, child maltreatment, and mental health characteristics that distinguish the trajectories. RESULTS: There were eight different subgroups (Non-Ideators, Late Ideators, Boomerang Ideators, Delayed Ideators, Desisters, Boomerang Non-Ideators, Late Desisters, and Persisters). Differences in race, type of maltreatment, sex, and mental health symptoms were identified when comparing Persisters (SI at all three waves) to other groups. CONCLUSIONS: These findings can help researchers and practitioners to develop strategies for better identifying CWS-involved children who are in greatest need of suicide risk monitoring and intervention.

Striatal brain volume linked to severity of substance use in high-risk incarcerated youth.

Substance use disorders among juveniles are a major public health concern and are often intertwined with other psychosocial risk factors including antisocial behavior. Identifying etiological risks and mechanisms promoting substance use disorders remains a high priority for informing more focused interventions in high-risk populations. The present study examined brain gray matter structure in relation to substance use severity among n = 152 high-risk, incarcerated boys (aged 14-20). Substance use severity was positively associated with gray matter volume across several frontal/striatal brain regions including amygdala, pallidum, putamen, insula, and orbitofrontal cortex. Effects were apparent when using voxel-based-morphometric analysis, as well as in whole-brain, data-driven, network-based approaches (source-based morphometry). These findings support the hypothesis that elevated gray matter volume in striatal reward circuits may be an endogenous marker for vulnerability to severe substance use behaviors among youth.

Mixed Signals in Child and Adolescent Mental Health and Well-Being Indicators in the United States: A Call for Improvements to Population Health Monitoring.

Policy Points Social indicators of young peoples' conditions and circumstances, such as high school graduation, food insecurity, and smoking, are improving even as subjective indicators of mental health and well-being have been worsening. This divergence suggests policies targeting the social indicators may not have improved overall mental health and well-being. There are several plausible reasons for this seeming contradiction. Available data suggest the culpability of one or several common exposures poorly captured by existing social indicators. Resolving this disconnect requires significant investments in population-level data systems to support a more holistic, child-centric, and up-to-date understanding of young people's lives.

Automated patterns of head dynamics are associated with psychopathic traits in incarcerated women.

Men with elevated psychopathic traits have been characterized by unique patterns of nonverbal communication, including more fixed and focused head positions during clinical interviews, compared to men scoring low on measures of psychopathy. However, it is unclear whether similar patterns of head dynamics help characterize women scoring high on psychopathic traits. Here, we utilized an automated detection algorithm to assess head position and dynamics during a videotaped clinical interview (i.e., the Psychopathy Checklist - Revised [PCL-R]) in a sample of n = 213 incarcerated women. PCL-R Total, Factor 1 (i.e., interpersonal and affective psychopathic traits), and Factor 2 (i.e., lifestyle/behavioral and antisocial/developmental psychopathic traits) scores were associated with a pattern of head dynamics indicative of a rigid head position. The current study extends analyses of nonverbal behavior studies in men to women and highlights how individuals with elevated psychopathic traits demonstrate unique nonverbal behaviors relative to individuals who score low on psychopathic traits. The implications and clinical value of these findings are discussed.

Dashboards as Mechanisms for Community Empowerment: Developing a Prototype for Child and Adolescent Well-being in California.

CONTEXT: In recent years, stakeholders in public health have emphasized measuring young peoples' well-being as a more holistic and upstream approach to understanding their health and development. However, summarizing the available indicators of well-being in ways that strengthen ongoing policy and community efforts remains a challenge. PROGRAM: Our objective was to develop a measurement framework of young peoples' well-being that would be engaging and actionable to a broad and diverse set of stakeholders in California. IMPLEMENTATION: We began with a scan of the relevant literature documenting previous efforts to measure young peoples' well-being, both within the United States and internationally. Subsequently, we individually interviewed a set of key informants and then convened a multidisciplinary panel of experts to solicit feedback on our approach. Throughout this iterative and collaborative process, we developed and refined a measurement framework based on the information provided across these various sources. EVALUATION: Findings suggest data dashboards are a promising approach for presenting a parsimonious yet holistic picture of young peoples' well-being. Dashboards can highlight well-being's multidimensionality by categorizing indicators over different domains. Our framework organizes indicators over 5 types: child-centric, subjective well-being, contextual determinants, developmental, and equity-focused. The design and flexibility of dashboards can also highlight important gaps in data collection that are of interest to end users such as indicators not yet collected among the broader population. Furthermore, dashboards can include interactive features, such as selecting key data elements, that can help communities articulate priority areas for policy action, thereby generating momentum and enthusiasm for future iterations and improvements. DISCUSSION: Data dashboards are well suited for engaging a variety of stakeholders on complex multidimensional concepts such as young peoples' well-being. However, to fulfill their promise, they should be codesigned and codeveloped through an iterative process with the stakeholders and community members they intend to serve.

Iodination of PEGylated Polymers Counteracts the Inhibition of Fibrinogen Adsorption by PEG.

Poly(ethylene glycol), PEG, known to inhibit protein adsorption, is widely used on the surfaces of biomedical devices when biofilm formation is undesirable. Poly(desaminotyrosyl-tyrosine ethyl ester carbonate), PDTEC, PC for short, has been a promising coating polymer for insertion devices, and it has been anticipated that PEG plays a similar role if it is copolymerized with PC. Earlier studies show that no fibrinogen (Fg) is adsorbed onto PC polymers with PEG beyond the threshold weight percentage. This is attributed to the phase separation of PEG. Further, iodination of the PC units in the PC polymer, (I2PC), has been found to counteract this Fg-repulsive effect by PEG. In this study, we employ surface-sensitive X-ray techniques to demonstrate the surface affinity of Fg toward the air-water interface, particularly in the presence of self-assembled PC-based film, in which its constituent polymer units are assumed to be much more mobile as a free-standing film. Fg is found to form a Gibbs monolayer with its long axis parallel to the aqueous surface, thus maximizing its interactions with hydrophobic interfaces. It influences the amount of insoluble, surface-bound I2PC likely due to the desorption of the formed Fg-I2PC complex and/or the penetration of Fg onto the I2PC film. The results show that the phase behavior at the liquid-polymer interface shall be taken into account for the surface behavior of bulk polymers surrounded by tissue. The ability of PEG units rearranging into a protein-blocking layer, rather than its mere presence in the polymer, is the key to antifouling characteristics desired for polymeric coating on insertion devices.

Hybrid schwannoma-perineurioma frequently harbors VGLL3 rearrangement.

Benign peripheral nerve tumors include schwannoma, neurofibroma, and perineurioma, as well as a recently recognized group of tumors with dual patterns of differentiation. The molecular pathogenesis of these so-called "hybrid" tumors remains poorly understood. Following identification of a novel CHD7-VGLL3 fusion gene in a hybrid schwannoma-perineurioma, we evaluated an expanded cohort of this tumor-type-as well as tumors with VGLL3 rearrangement identified from a curated molecular database-to characterize the prevalence of fusion genes among these tumors. Eighteen tumors met the inclusion criteria for this study. RNA sequencing identified VGLL3 rearrangement in 14 of these cases; the partner genes included CHD7 (ten cases), CHD9 (two cases), and MAMLD1 (two cases). Two cases possessed altogether unrelated fusions, including: DST-BRAF and SQSTM1-CDX1 fusion genes. Finally, two cases lacked identifiable fusion products. These findings highlight the molecular diversity of these neoplasms, with frequent rearrangement of VGLL3. More importantly, despite their dual pattern of differentiation, our results reveal the pathogenesis of hybrid schwannoma-perineurioma is unrelated to conventional schwannoma and perineurioma, thereby implying this tumor represents an altogether pathologically distinct entity.

Optimal uses of pooled testing for COVID-19 incorporating imperfect test performance and pool dilution effect: An application to congregate settings in Los Angeles County.

INTRODUCTION: Pooled testing is a potentially efficient alternative strategy for COVID-19 testing in congregate settings. We evaluated the utility and cost-savings of pooled testing based on imperfect test performance and potential dilution effect due to pooling and created a practical calculator for online use. METHODS: We developed a 2-stage pooled testing model accounting for dilution. The model was applied to hypothetical scenarios of 100 specimens collected during a one-week time-horizon cycle for varying levels of COVID-19 prevalence and test sensitivity and specificity, and to 338 skilled nursing facilities (SNFs) in Los Angeles County (Los Angeles) (data collected and analyzed in 2020). RESULTS: Optimal pool sizes ranged from 1 to 12 in instances where there is a least one case in the batch of specimens. 40% of Los Angeles SNFs had more than one case triggering a response-testing strategy. The median number (minimum; maximum) of tests performed per facility were 56 (14; 356) for a pool size of 4, 64 (13; 429) for a pool size of 10, and 52 (11; 352) for an optimal pool size strategy among response-testing facilities. The median costs of tests in response-testing facilities were $8250 ($1100; $46,100), $6000 ($1340; $37,700), $6820 ($1260; $43,540), and $5960 ($1100; $37,380) when adopting individual testing, a pooled testing strategy using pool sizes of 4, 10, and optimal pool size, respectively. CONCLUSIONS: Pooled testing is an efficient strategy for congregate settings with a low prevalence of COVID-19. Dilution as a result of pooling can lead to erroneous false-negative results.

Trends in Health Equity Among Children in the United States, 1997-2018.

OBJECTIVES: Health equity is crucial to population health. To achieve this aim, extensive monitoring efforts beyond traditional disparities research are required. This analysis assesses trends in health equity for children from 1997 to 2018. METHODS: Health equity in a given year is calculated using a previously developed measure as the mean weighted departure of individual health from the best achievable level of health. This criterion is defined as the median health of the most socially privileged identifiable group: white, non-Latinx boys in upper-income households. Using more than 20 years of data from the National Health Interview Survey, we apply this methodology to six measures of child health: parent-reported health status, school days missed due to illness or injury in the past year, a strength and difficulties questionnaire score, emotional difficulties, a toddler mental health indicator score, and toddler depression. We separately calculate racial/ethnic and income disparities. Monte Carlo simulation is used to assess whether trends are statistically significant. RESULTS: Health equity among children increased gradually over the past 2 decades, with five of the six measures demonstrating upward trends. Improvements in health equity are stronger among younger children (age 0-3 and 4-7). Unlike previous work examining adults, both types of disparities narrowed over the study period. CONCLUSIONS FOR PRACTICE: Progress on health equity requires accountability to an objective metric. This analysis suggests some improvement over the past two decades, although these gains are under threat from potential decreases in government spending on programs affecting children and the COVID-19 pandemic.

The role of consolidation in learning context-dependent phonotactic patterns in speech and digital sequence production.

Speakers implicitly learn novel phonotactic patterns by producing strings of syllables. The learning is revealed in their speech errors. First-order patterns, such as "/f/ must be a syllable onset," can be distinguished from contingent, or second-order, patterns, such as "/f/ must be an onset if the vowel is /a/, but a coda if the vowel is /o/." A metaanalysis of 19 experiments clearly demonstrated that first-order patterns affect speech errors to a very great extent in a single experimental session, but second-order vowel-contingent patterns only affect errors on the second day of testing, suggesting the need for a consolidation period. Two experiments tested an analogue to these studies involving sequences of button pushes, with fingers as "consonants" and thumbs as "vowels." The button-push errors revealed two of the key speech-error findings: first-order patterns are learned quickly, but second-order thumb-contingent patterns are only strongly revealed in the errors on the second day of testing. The influence of computational complexity on the implicit learning of phonotactic patterns in speech production may be a general feature of sequence production.

Ewing-like sarcoma: An emerging family of round cell sarcomas.

Ewing-like sarcomas are an emerging subgroup of small round blue cell sarcomas that share various degrees of morphological, immunohistochemical, molecular, and clinical similarity with Ewing sarcoma. Despite these similarities, Ewing-like sarcomas lack the pathognomonic molecular hallmark of Ewing sarcoma: A translocation between a gene of the RNA-binding TET family (EWSR1 or FUS) with a gene of the ETS-transcription family ( FLI1, ERG, ETV1, ETV4, or FEV). Recently, increased use of modern molecular methods based on next-generation sequencing have enabled the identification of distinct subgroups within this previously uncharacterized group of Ewing-like sarcomas based on the discovery of novel molecular driving events. The focus of this review is to provide an update on the main subcategories of Ewing-like sarcomas discovered to date: CIC-rearranged sarcomas, BCOR-rearranged sarcomas, sarcomas with a rearrangement between EWSR1 and a non-ETS family gene, and the substantial fraction of tumors which remain uncharacterized by molecular methods. There is increasing evidence that these tumors represent stand-alone entities with unique characteristics rather than simply a subgroup of Ewing sarcoma; thus, the question of the best therapeutic approach for these often aggressive sarcomas remains of primary importance. Ultimately, large collaborative efforts will be necessary to better determine the characteristics of this rare, heterogeneous family of tumors.

Machine learning of brain gray matter differentiates sex in a large forensic sample.

Differences between males and females have been extensively documented in biological, psychological, and behavioral domains. Among these, sex differences in the rate and typology of antisocial behavior remains one of the most conspicuous and enduring patterns among humans. However, the nature and extent of sexual dimorphism in the brain among antisocial populations remains mostly unexplored. Here, we seek to understand sex differences in brain structure between incarcerated males and females in a large sample (n = 1,300) using machine learning. We apply source-based morphometry, a contemporary multivariate approach for quantifying gray matter measured with magnetic resonance imaging, and carry these parcellations forward using machine learning to classify sex. Models using components of brain gray matter volume and concentration were able to differentiate between males and females with greater than 93% generalizable accuracy. Highly differentiated components include orbitofrontal and frontopolar regions, proportionally larger in females, and anterior medial temporal regions proportionally larger in males. We also provide a complimentary analysis of a nonforensic healthy control sample and replicate our 93% sex discrimination. These findings demonstrate that the brains of males and females are highly distinguishable. Understanding sex differences in the brain has implications for elucidating variability in the incidence and progression of disease, psychopathology, and differences in psychological traits and behavior. The reliability of these differences confirms the importance of sex as a moderator of individual differences in brain structure and suggests future research should consider sex specific models.

Affective and interpersonal psychopathic traits associated with reduced corpus callosum volume among male inmates - RETRACTED.

BACKGROUND: Psychopathy is a personality disorder associated with severe emotional and interpersonal consequences and persistent antisocial behavior. Neurobiological models of psychopathy emphasize impairments in emotional processing, attention, and integration of information across large-scale neural networks in the brain. One of the largest integrative hubs in the brain is the corpus callosum (CC) - a large white matter structure that connects the two cerebral hemispheres. METHOD: The current study examines CC volume, measured via Freesurfer parcellation, in a large sample (n = 495) of incarcerated men who were assessed for psychopathic traits using the Hare Psychopathy Checklist-Revised (PCL-R). RESULTS: Psychopathy was associated with reduced volume across all five sub-regions of the CC. These relationships were primarily driven by the affective/interpersonal elements of psychopathy (PCL-R Factor 1), as no significant associations were found between the CC and the lifestyle/antisocial traits of psychopathy. The observed effects were not attributable to differences in substance use severity, age, IQ, or total brain volume. CONCLUSIONS: These findings align with suggestions that core psychopathic traits may be fostered by reduced integrative capacity across large-scale networks in the brain.

Comprehensive comparative economic evaluation of woody biomass energy from silvicultural fuel treatments.

Fuel treatments are used in overstocked, fire-prone forests to alter wildfire behavior and reduce fire risk. Some of the benefits they provide are not captured in markets, and therefore represent unaccounted environmental externalities that can lead to inefficient decision making. This study uses a replicable method to integrate market and nonmarket economic values into a comprehensive economic evaluation of fuel treatment and bioenergy production using a case study of ponderosa pine and mixed-conifer forests in Colorado's wildland-urban interface. Treatment costs and people's willingness to pay for better forest health, lower likelihood of wildfire, improved air quality, and expanded renewable energy production are incorporated into techno-economic analysis of biopower production. Results show that fuel treatments are likely to be undervalued when evaluated strictly on a financial basis. Under the standard practice of disposing of treatment residues through pile-burning, net present value (NPV) of fuel treatment on 138,034 ha over 20 years is -$275 million, without consideration of nonmarket benefits. If nonmarket benefits associated with forest health, wildfire likelihood and air quality are included, NPV improves to -$116 million. Without the consideration of nonmarket benefits, when treatment resides are used for biopower production, NPV is -$178 million, with net cost savings compared to pile burning attributable to reduced biomass disposal costs and electricity revenue. Accounting for additional air quality benefits and nonmarket value associated with renewable energy, the bioenergy scenario improves NPV to -$25 million, with 27.7% of outcomes having positive NPV. The impact of additional nonmarket values and potential revenues from timber harvest are discussed, and are likely to make mean NPV positive for this scenario.

Aberrant functional network connectivity in psychopathy from a large (N = 985) forensic sample.

Psychopathy is a personality disorder characterized by antisocial behavior, lack of remorse and empathy, and impaired decision making. The disproportionate amount of crime committed by psychopaths has severe emotional and economic impacts on society. Here we examine the neural correlates associated with psychopathy to improve early assessment and perhaps inform treatments for this condition. Previous resting-state functional magnetic resonance imaging (fMRI) studies in psychopathy have primarily focused on regions of interest. This study examines whole-brain functional connectivity and its association to psychopathic traits. Psychopathy was hypothesized to be characterized by aberrant functional network connectivity (FNC) in several limbic/paralimbic networks. Group-independent component and regression analyses were applied to a data set of resting-state fMRI from 985 incarcerated adult males. We identified resting-state networks (RSNs), estimated FNC between RSNs, and tested their association to psychopathy factors and total summary scores (Factor 1, interpersonal/affective; Factor 2, lifestyle/antisocial). Factor 1 scores showed both increased and reduced functional connectivity between RSNs from seven brain domains (sensorimotor, cerebellar, visual, salience, default mode, executive control, and attentional). Consistent with hypotheses, RSNs from the paralimbic system-insula, anterior and posterior cingulate cortex, amygdala, orbital frontal cortex, and superior temporal gyrus-were related to Factor 1 scores. No significant FNC associations were found with Factor 2 and total PCL-R scores. In summary, results suggest that the affective and interpersonal symptoms of psychopathy (Factor 1) are associated with aberrant connectivity in multiple brain networks, including paralimbic regions.

Psychopathic traits associated with abnormal hemodynamic activity in salience and default mode networks during auditory oddball task.

Psychopathy is a personality disorder accompanied by abnormalities in emotional processing and attention. Recent theoretical applications of network-based models of cognition have been used to explain the diverse range of abnormalities apparent in psychopathy. Still, the physiological basis for these abnormalities is not well understood. A significant body of work has examined psychopathy-related abnormalities in simple attention-based tasks, but these studies have largely been performed using electrocortical measures, such as event-related potentials (ERPs), and they often have been carried out among individuals with low levels of psychopathic traits. In this study, we examined neural activity during an auditory oddball task using functional magnetic resonance imaging (fMRI) during a simple auditory target detection (oddball) task among 168 incarcerated adult males, with psychopathic traits assessed via the Hare Psychopathy Checklist-Revised (PCL-R). Event-related contrasts demonstrated that the largest psychopathy-related effects were apparent between the frequent standard stimulus condition and a task-off, implicit baseline. Negative correlations with interpersonal-affective dimensions (Factor 1) of the PCL-R were apparent in regions comprising default mode and salience networks. These findings support models of psychopathy describing impaired integration across functional networks. They additionally corroborate reports which have implicated failures of efficient transition between default mode and task-positive networks. Finally, they demonstrate a neurophysiological basis for abnormal mobilization of attention and reduced engagement with stimuli that have little motivational significance among those with high psychopathic traits.

Reverse-engineering of graphene on metal surfaces: a case study of embedded ruthenium.

Using scanning tunneling microscopy, x-ray photoelectron spectroscopy, and x-ray absorption spectroscopy, we show that Ru forms metallic nanoislands on graphite, covered by a graphene monolayer. These islands are air-stable, contain 2-4 layers of Ru, and have diameters on the order of 10 nm. To produce these nanoislands two conditions must be met during synthesis. The graphite surface must be ion-bombarded, and subsequently held at an elevated temperature (1000-1180 K) during Ru deposition. A coincidence lattice forms between the graphene overlayer and the Ru island top. Its characteristics-coincidence lattice constant, corrugation amplitude, and variation of carbon lattice appearance within the unit cell-closely resemble the well-established characteristics of single-layer graphene on the (0001) surface of bulk Ru. Quantitative analysis of the graphene lattice in relation to the coincidence lattice on the island tops show that the two-dimensional lattice constant of the underlying metal equals that of bulk Ru(0001), within experimental error. The embedded Ru islands are energetically favored over on-top (adsorbed) islands, based on density-functional-theory calculations for Ru films with 1-3 Ru layers. We propose a formation mechanism in which Ru atoms intercalate via defects that act as entry portals to the carbon galleries, followed by nucleation and growth in the galleries. In this model, high deposition temperature is necessary to prevent blockage of entry portals.

Aggressive embryonal rhabdomyosarcoma in a 3-month-old boy: A clinical and molecular analysis.

Rhabdomyosarcoma (RMS) represents the most common soft tissue sarcoma in the pediatric age group. While RMS has been traditionally classified on the basis of its histological appearance (with embryonal and alveolar being most common), it is now clear that the PAX-FOXO1 fusion product drives prognosis. We report here a case of pelvic embryonal RMS in a 3-month-old male who was subsequently found to have developed brain metastases during the course of chemotherapy. Cytogenetic analysis of the brain metastases at the time of autopsy as well as next-generation sequencing analysis revealed a reciprocal translocation involving the SH3 domain containing ring finger 3 gene (SH3RF3, on chromosome 2q13) and the Lipase C gene (LIPC, on chromosome 15q21.3). Due to the poor quality of the pretreatment and postresection samples, cytogenetics and NGS analysis looking for the presence of this balanced translocation in these specimens could not be performed. To the authors' knowledge, this translocation has never been described in RMS. Further studies are needed to determine the biological and clinical implications of this novel translocation.

Cost and performance tradeoffs between mail and internet survey modes in a nonmarket valuation study.

Using the results of a choice modeling survey, internet, mail-only and mixed internet and mail survey modes were examined with regards to their cost-effectiveness, representativeness, and willingness to pay (WTP). The topical focus of the study was biomass energy generation preferences of the residents of Montana, Colorado and Arizona, USA. Compared to the mail and mixed mode samples, the internet-only mode produced a sample of respondents that was younger, more likely to have a college degree, and more likely to have a household income of at least $100,000 per year. However, observed differences in the characteristics of the collected sample did not result in significant differences in estimates of WTP. The internet survey mode was the most cost-effective method of collecting the target sample size of 400 responses. Sensitivity analysis showed that as the target number of responses increased the cost advantage of internet over the mail-only and mixed mode surveys increased because of the low marginal cost associated with extending additional invitations.