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Patient-Derived Organoids (PDO) and Xenografts (PDX) are the current gold standards for patient derived models of cancer (PDMC). Nevertheless, how patient tumor cells evolve in these models and the impact on drug response remains unclear. Herein, we compared the transcriptomic and chromatin accessibility landscapes of six matched sets of colorectal cancer (CRC) PDO, PDX, PDO-derived PDX (PDOX), and original patient tumors (PT) and discovered two major remodeling axes. The first axis delineates PDX and PDO from PT, and the second axis distinguishes PDX and PDO. PDOX were more similar to PDX than they were to PDO, indicating that the growth environment is a driving force for chromatin adaptation. Using bivariate genomic footprinting analysis, we identified transcription factors (TF) that differentially bind to open chromatins between matched PDO and PDOX. Among them, KLF14 and EGR2 footprints were enriched in all six PDOX relative to matched PDO, and silencing of KLF14 or EGR2 promoted tumor growth. Furthermore, EPHA4, a shared downstream target gene of KLF14 and EGR2, altered tumor sensitivity to MEK inhibitor treatment. Altogether, patient-derived CRC cells undergo both common and distinct chromatin remodeling in PDO and PDX/PDOX, driven largely by their respective microenvironments, which results in differences in growth and drug sensitivity and needs to be taken into consideration when interpreting their ability to predict clinical outcome.

Despite steady increases in homelessness in the U.S., only recently has research on transportation needs and use for persons experiencing homelessness (PEH) been the focus of research endeavours. Moreover, limited research has identified how the geographic relocation of homeless community services and resources impacts the transportation needs of PEH and how this process affects access to health and social services. To fill this gap in the literature, using a community-engaged research approach, we conducted a qualitative research study in which 24 professionals working in planning, transportation, local government, and the homelessness services sector were engaged in in-depth, semi-structured interviews. We examined participant perspectives on how PEH transportation needs and use changed after three new emergency shelters replaced a centralised one, and how access to health and social services was impacted. Data were organised into three overarching categories: (1) Changes in transportation need and use following decentralisation; (2) Impact of transportation changes on PEH access to services; and (3) Recommendations for improving transportation access. Findings suggest the need to offer PEH transportation on demand, provide education on transportation and system navigation, and increase transportation-related funding for homeless service providers and PEH to ensure transportation costs are not a barrier to healthcare and social services.

Ecological forecasting has vast potential to support environmental decision making with repeated, testable predictions across management-relevant timescales and locations. Yet resource managers rarely use co-designed forecasting systems or embed them in decision making. Although prediction of planned management outcomes is particularly important for biological invasions to optimize when and where resources should be allocated, spatial-temporal models of spread typically have not been openly shared, iteratively updated, or interactive to facilitate exploration of management actions. We describe a species-agnostic, open-source framework - called the Pest or Pathogen Spread (PoPS) Forecasting Platform - for co-designing near-term iterative forecasts of biological invasions. Two case studies are presented to demonstrate that iterative calibration yields higher forecast skill than using only the earliest-available data to predict future spread. The PoPS framework is a primary example of an ecological forecasting system that has been both scientifically improved and optimized for real-world decision making through sustained participation and use by management stakeholders.

During the COVID-19 pandemic, members of the African American Medical Librarians Alliance (AAMLA) Caucus of the Medical Library Association formed a weekly virtual forum known as the “Chat & Chew.” The purpose of these weekly check-ins was to build community and provide support amidst a series of unprecedented health crises adversely affecting Black Americans, including the coronavirus pandemic and the long-standing issue of police killings and brutality. In coming together for these weekly check-ins, group participants benefited by actively practicing self-care and exchanging ideas and information with colleagues across the country. Each gathering incorporated various presentations and discussions, including topics related to self-care and wellness, microaggressions and stigmatization in the workplace, virtual technologies, plant care, book discussions, and opportunities to engage in diversity, equity, and inclusion work. This chapter provides successes for member engagement and best practices that made the program sustainable throughout 2020 and beyond.

Mucopolysaccharidosis (MPS) IIIB is a neuropathic lysosomal storage disease characterized by the deficient activity of a lysosomal enzyme obligate for the degradation of the glycosaminoglycan (GAG) heparan sulfate (HS). The pathogenesis of neurodegeneration in MPS IIIB is incompletely understood. Large animal models are attractive for pathogenesis and therapeutic studies due to their larger size, outbred genetics, longer lifespan, and naturally occurring MPS IIIB disease. However, the temporospatial development of neuropathologic changes has not been reported for canine MPS IIIB. Here we describe lesions in 8 brain regions, cervical spinal cord, and dorsal root ganglion (DRG) in a canine model of MPS IIIB that includes dogs aged from 2 to 26 months of age. Pathological changes in the brain included early microscopic vacuolation of glial cells initially observed at 2 months, and vacuolation of neurons initially observed at 10 months. Inclusions within affected cells variably stained positively with PAS and LFB stains. Quantitative immunohistochemistry demonstrated increased glial expression of GFAP and Iba1 in dogs with MPS IIIB compared to age-matched controls at all time points, suggesting neuroinflammation occurs early in disease. Loss of Purkinje cells was initially observed at 10 months and was pronounced in 18- and 26-month-old dogs with MPS IIIB. Our results support the dog as a replicative model of MPS IIIB neurologic lesions and detail the pathologic and neuroinflammatory changes in the spinal cord and DRG of MPS IIIB-affected dogs.

Background It has been reported that many hospitals in the United States have fragmented and ineffective ordering, administration, documentation, and evaluation/monitoring of nutrition therapies. This paper reports on a project to investigate if perceived hospital staff awareness and documentation of nutrition support therapies (NSTs) improves by including them as part of the medication administration record (MAR). Methods Surveys were conducted with nursing staff, physicians, and dietitians before and after adding NSTs to the MAR to evaluate the perceived impact on the outcome of interest. The outcomes of interest include nurses' perception of ease of finding information, awareness of an order, and ability to assess administration and documentation and dietitian, nurse, and physician staff perceptions of impact of intervention on aspects of the nutrition care process. Results After adding NST to the MAR, nursing staff perceived improvement in knowing that their patient had an oral nutritional supplement (ONS) order (P = .01), when and how much product was last administered (P = .01), and documentation of the type of product consumed (P = .01) and volume of product consumed (P = .01). The majority of dietitian and nurses surveyed reported perceived improvement in placing and finding ONS orders, in administration of ONS, in ability to evaluate patient nutrition status, and in ONS intake and a positive impact on clinical practice. Conclusion Inclusion of NST in the MAR presents an innovative solution to enhance staff awareness of ordered therapies and perception of improved documentation of nutrition interventions for hospitalized patients.

Pulmonary vein stenosis (PVS) is an increasingly recognized disease in infants and young children. Controversy exists regarding the best management of this disease. The hallmarks of PVS include recurrence, upstream progression, and spread to previously unaffected pulmonary veins. This review highlights invasive and medical therapies for pediatric patients with primary and secondary PVS. Catheter-based therapies for PVS are the mainstay of anatomic, large-vessel therapy. Angioplasty and stenting both have a role in the anatomic management of PVS. Repeated transcatheter interventions have been shown to improve survival. Surgical PVS intervention is an important element to PVS therapy. Primary (medical) therapy is increasingly recognized as an important element to PVS treatment. New anti-proliferative therapies have proven to be a useful adjunct to invasive therapies. Congenital and acquired PVS are progressive diseases that pose a growing challenge for cardiologists. Surgical and transcatheter interventions in most cases have early success but are only temporizing solutions in the face of myofibroblastic proliferation. More recent studies focusing on benefits of immunomodulatory therapy have paved the way for the use of primary treatment alongside the anatomic therapy.

Ecological forecasts will be best suited to inform intervention strategies if they are accessible to a diversity of decision-makers. Researchers are developing intuitive forecasting interfaces to guide stakeholders through the development of intervention strategies and visualization of results. Yet, few studies to date have evaluated how user interface design facilitates the coordinated, cross-boundary management required for controlling biological invasions. We used a participatory approach to develop complementary tangible and online interfaces for collaboratively forecasting biological invasions and devising control strategies. A diverse group of stakeholders evaluated both systems in the real-world context of controlling sudden oak death, an emerging forest disease killing millions of trees in California and Oregon. Our findings suggest that while both interfaces encouraged adaptive experimentation, tangible interfaces are particularly well suited to support collaborative decision-making. Reflecting on the strengths of both systems, we suggest workbench-style interfaces that support simultaneous interactions and dynamic geospatial visualizations.

Coping Power (CP) is an evidence-based preventive intervention for youth with disruptive behavior problems. This study examined whether Mindful Coping Power (MCP), a novel adaptation which integrates mindfulness into CP, enhances program effects on children’s reactive aggression and self-regulation. A pilot randomized design was utilized to estimate the effect sizes for MCP versus CP in a sample of 102 child participants (fifth grade students, predominantly low-middle income, 87% Black). MCP produced significantly greater improvement in children’s self-reported dysregulation (emotional, behavioral, cognitive) than CP, including children’s perceived anger modulation. Small to moderate effects favoring MCP were also observed for improvements in child-reported inhibitory control and breath awareness and parent-reported child attentional capacity and social skills. MCP did not yield a differential effect on teacher-rated reactive aggression. CP produced a stronger effect than MCP on parent-reported externalizing behavior problems. Although MCP did not enhance program effects on children’s reactive aggression as expected, it did have enhancing effects on children’s internal, embodied experiences (self-regulation, anger modulation, breath awareness). Future studies are needed to compare MCP and CP in a large scale, controlled efficacy trial and to examine whether MCP-produced improvements in children’s internal experiences lead to improvements in their observable behavior over time.

Although cognitive-behavioral interventions have reduced the risk of substance use, little is known about moderating factors in children with disruptive behaviors. This study examined whether aggressive preadolescents’ inhibitory control and intervention engagement moderates the effect of group versus individual delivery on their substance use. Following screening for aggression in 4th grade, 360 children were randomly assigned to receive the Coping Power intervention in either group or individual formats. The sample was primarily African American (78%) and male (65%). Assessments were made of children’s self-reported substance use from preintervention through a six-year follow-up after intervention, parent-reported inhibitory control at preintervention, and observed behavioral engagement in the group intervention. Multilevel growth modeling found lower increases in substance use slopes for children with low inhibitory control receiving individual intervention, and for children with higher inhibitory control receiving group intervention. Children with low inhibitory control but who displayed more positive behavioral engagement in the group sessions had slower increases in their substance use than did similar children without positive engagement. Aggressive children’s level of inhibitory control can lead to tailoring of group versus individual delivery of intervention. Children’s positive behavioral engagement in group sessions is a protective factor for children with low inhibitory control.

Universal prevention approaches have significantly reduced children's conduct problems and aggressive behavior in the school setting, but it has not been clear whether the effects generalize into children's behavior in home and community settings in later elementary school years. The present study examined this issue using a classroom-randomized design, with 1030 students in 70 fourth and fifth grade Italian classes. The intervention model is the Coping Power Universal and the classroom teachers delivered it. Coping Power Universal produced a significant reduction in both parents' and teachers' rated conduct problems, relative to control classes, indicating that universal prevention can produce significant reductions in children's conduct problems that generalize into the home and community settings. The intervention also increased children's prosocial behaviors in school and home settings. The Coping Power Universal is a short intervention model that is believed to be a useful strategy for children's behavioral problems in the broad population.

We present evidence that variability in the STEREO‐A Heliospheric Imager (HI) data is correlated with in situ solar wind speed estimates from WIND, STEREO‐A, and STEREO‐B. For 2008–2012, we compute the variability in HI differenced images in a plane‐of‐sky shell between 20 to 22.5 solar radii and, for a range of position angles, compare daily means of HI variability and in situ solar wind speed estimates. We show that the HI variability data and in situ solar wind speeds have similar temporal autocorrelation functions. Carrington rotation periodicities are well documented for in situ solar wind speeds, but, to our knowledge, this is the first time they have been presented in statistics computed from HI images. In situ solar wind speeds from STEREO‐A, STEREO‐B, and WIND are all are correlated with the HI variability, with a lag that varies in a manner consistent with the longitudinal separation of the in situ monitor and the HI instrument. Unlike many approaches to processing HI observations, our method requires no manual feature tracking; it is automated, is quick to compute, and does not suffer the subjective biases associated with manual classifications. These results suggest we could possibly estimate solar wind speeds in the low heliosphere directly from HI observations. This motivates further investigation, as this could be a significant asset to the space weather forecasting community; it might provide an independent observational constraint on heliospheric solar wind forecasts, through, for example, data assimilation. Finally, these results are another argument for the potential utility of including a HI on an operational space weather mission.

Images of coronal mass ejections (CMEs) from the Heliospheric Imager (HI) instruments on board the STEREO spacecraft frequently contain rich structure. Here, we present analysis of the Earth-directed CME launched on 12 December 2008 in which we intepret the revealed structure as projections of separate discrete sections of the physical boundary of the CME. By comparing the relative position of the outer and inner 'ghost' fronts seen in the STEREO HI1 cameras with the positions of features determined from three CME models we show that the two fronts seen in the images correspond to the expected position of the flank and nose of the CME where the background solar wind is uniform. In contrast, the flank of the CME observed expanding into a structured background solar wind results in the elongation between the two fronts being greater than expected. This is consistent with the CME flank distorting in the presence of a high-speed solar wind stream. Further work is required to consolidate these results. The presence of a shock for this event was ruled out by consideration of the low CME speed and by studying in-situ spacecraft data. The CME flank crossing the Thomson sphere was also ruled out as a cause of the ghost fronts. Ghost fronts could provide information about the longitudinal shape of the CME independent of geometric models. This technique could subsequently be used to improve space weather forecast models through techniques such as data assimilation.

Models that are both spatially and temporally dynamic are needed to forecast where and when non-native pests and pathogens are likely to spread, to provide advance information for natural resource managers. The potential US range of the invasive spotted lanternfly (SLF, Lycorma delicatula) has been modeled, but until now, when it could reach the West Coast’s multi-billion-dollar fruit industry has been unknown. We used process-based modeling to forecast the spread of SLF assuming no treatments to control populations occur. We found that SLF has a low probability of first reaching the grape-producing counties of California by 2027 and a high probability by 2033. Our study demonstrates the importance of spatio-temporal modeling for predicting the spread of invasive species to serve as an early alert for growers and other decision makers to prepare for impending risks of SLF invasion. It also provides a baseline for comparing future control options.