The outcome of patients with anaplastic gliomas varies considerably. Whether a molecular classification of anaplastic gliomas based on large-scale genomic or epigenomic analyses is superior to ...histopathology for reflecting distinct biological groups, predicting outcomes and guiding therapy decisions has yet to be determined. Epigenome-wide DNA methylation analysis, using a platform which also allows the detection of copy-number aberrations, was performed in a cohort of 228 patients with anaplastic gliomas (astrocytomas, oligoastrocytomas, and oligodendrogliomas), including 115 patients of the NOA-04 trial. We further compared these tumors with a group of 55 glioblastomas. Unsupervised clustering of DNA methylation patterns revealed two main groups correlated with
IDH
status: CpG island methylator phenotype (CIMP) positive (77.5 %) or negative (22.5 %). CIMP
pos
(
IDH
mutant) tumors showed a further separation based on copy-number status of chromosome arms 1p and 19q. CIMP
neg
(
IDH
wild type) tumors showed hallmark copy-number alterations of glioblastomas, and clustered together with CIMP
neg
glioblastomas without forming separate groups based on WHO grade. Notably, there was no molecular evidence for a distinct biological entity representing anaplastic oligoastrocytoma. Tumor classification based on CIMP and 1p/19q status was significantly associated with survival, allowing a better prediction of outcome than the current histopathological classification: patients with CIMP
pos
tumors with 1p/19q codeletion (CIMP-codel) had the best prognosis, followed by patients with CIMP
pos
tumors but intact 1p/19q status (CIMP-non-codel). Patients with CIMP
neg
anaplastic gliomas (GBM-like) had the worst prognosis. Collectively, our data suggest that anaplastic gliomas can be grouped by
IDH
and 1p/19q status into three molecular groups that show clear links to underlying biology and a significant association with clinical outcome in a prospective trial cohort.
How can we tailor assistance systems, such as recommender systems or decision support systems, to consumers’ individual shopping motives? How can companies unobtrusively identify shopping motives ...without explicit user input? We demonstrate that eye movement data allow building reliable prediction models for identifying goal-directed and exploratory shopping motives. Our approach is validated in a real supermarket and in an immersive virtual reality supermarket. Several managerial implications of using gaze-based classification of information search behavior are discussed: First, the advent of virtual shopping environments makes using our approach straightforward as eye movement data are readily available in next-generation virtual reality devices. Virtual environments can be adapted to individual needs once shopping motives are identified and can be used to generate more emotionally engaging customer experiences. Second, identifying exploratory behavior offers opportunities for marketers to adapt marketing communication and interaction processes. Personalizing the shopping experience and profiling customers’ needs based on eye movement data promises to further increase conversion rates and customer satisfaction. Third, eye movement-based recommender systems do not need to interrupt consumers and thus do not take away attention from the purchase process. Finally, our paper outlines the technological basis of our approach and discusses the practical relevance of individual predictors.
Classifying information search behavior helps tailor recommender systems to individual customers’ shopping motives. But how can we identify these motives without requiring users to exert too much effort? Our research goal is to demonstrate that eye tracking can be used at the point of sale to do so. We focus on two frequently investigated shopping motives: goal-directed and exploratory search. To train and test a prediction model, we conducted two eye-tracking experiments in front of supermarket shelves. The first experiment was carried out in immersive virtual reality; the second, in physical reality—in other words, as a field study in a real supermarket. We conducted a virtual reality study, because recently launched virtual shopping environments suggest that there is great interest in using this technology as a retail channel. Our empirical results show that support vector machines allow the correct classification of search motives with 80% accuracy in virtual reality and 85% accuracy in physical reality. Our findings also imply that eye movements allow shopping motives to be identified relatively early in the search process: our models achieve 70% prediction accuracy after only 15 seconds in virtual reality and 75% in physical reality. Applying an ensemble method increases the prediction accuracy substantially, to about 90%. Consequently, the approach that we propose could be used for the satisfiable classification of consumers in practice. Furthermore, both environments’ best predictor variables overlap substantially. This finding provides evidence that in virtual reality, information search behavior might be similar to the one used in physical reality. Finally, we also discuss managerial implications for retailers and companies that are planning to use our technology to personalize a consumer assistance system.
Neurons form transiently stable assemblies that may underlie cognitive functions, including memory formation. In most brain regions, coherent activity is organized by network oscillations that ...involve sparse firing within a well-defined minority of cells. Despite extensive work on the underlying cellular mechanisms, a fundamental question remains unsolved: how are participating neurons distinguished from the majority of nonparticipators? We used physiological and modeling techniques to analyze neuronal activity in mouse hippocampal slices during spontaneously occurring high-frequency network oscillations. Network-entrained action potentials were exclusively observed in a defined subset of pyramidal cells, yielding a strict distinction between participating and nonparticipating neurons. These spikes had unique properties, because they were generated in the axon without prior depolarization of the soma. GABAA receptors had a dual role in pyramidal cell recruitment. First, the sparse occurrence of entrained spikes was accomplished by intense perisomatic inhibition. Second, antidromic spike generation was facilitated by tonic effects of GABA in remote axonal compartments. Ectopic spike generation together with strong somatodendritic inhibition may provide a cellular mechanism for the definition of oscillating assemblies.
Function and dysfunction of endothelial cells are regulated by a multitude of factors. Endothelial cell research often requires in vitro cell culture experiments. Hence, various culture media ...specifically designed to promote endothelial cell growth are available. These strikingly differ in their composition: complex media contain endothelial cell growth supplement (ECGS), an extract produced of bovine brain with undefined amounts of biologically active compounds, whilst defined media contain selected growth factors in defined concentrations. We here compared the effect of seven purchasable endothelial cell culture media on colony outgrowth, proliferation, viability, in vitro angiogenesis and phenotype of mature primary human endothelial cells using feto-placental endothelial cells isolated from chorionic arteries (fpEC). The effect of media on colony outgrowth was additionally tested on umbilical cord blood-derived endothelial progenitor cells (ECFCs). Outgrowth, purity, proliferation and viability differed between media. Outgrowth of fpEC and ECFCs was best in a defined medium containing EGF, FGF2 and VEGF. By contrast, established fpEC isolations proliferated best in complex media containing ECGS, heparin and ascorbic acid. Also viability of cells was higher in complex media. In vitro angiogenesis was most intense in a defined medium containing the highest number of individual growth factors. FACS analysis of surface markers for endothelial cell subtypes revealed that endothelial phenotype of fpEC was unaffected by media composition. Our data demonstrate the fundamental effect of endothelial cell culture media on primary cell isolation success and behaviour. Whether the composition of supplements is suitable also for individual experiments needs to be tested specifically.
Purpose
Research on the impact of family cancer caregiving is primarily dyadic in focus. How caregiving affects the larger family system is less understood, yet knowing this is vital to developing ...supportive resources for caregivers, patients, and their families. To better understand how blood cancer caregiving impacts the family system, we explored the experiences of adult child caregivers of diagnosed parents and parent caregivers of diagnosed children.
Methods
We conducted semi-structured interviews with 39 midlife parent and adult child caregivers of patients with leukemia or lymphoma. Using a family systems theory lens, we conducted a thematic analysis using the constant comparative method to identify how caregiving impacts the larger family system.
Results
Caregivers ranged from age 30 to 64 (
M
= 43). They described four ways that caregiving impacted themselves and the larger family system: (1)
disruption of home life
, (2)
emotional (dis)connection
, (3)
juggling competing roles
, and (4)
developing resiliency and intimacy
. Perspectives within each category differed based on their relational role to the patient or in the broader family.
Conclusions
Themes identify ways to provide support to both caregiver types. Support care resources could help families navigate gains and losses impacting the family system after a blood cancer diagnosis. Both caregiver types described experiencing (and/or their family experiencing) a loss in relational connection, feeling alone, and members distancing themselves. Both caregiver types also described gains in family functioning, like strengthened bonds and togetherness. Findings validate the need for family-centered support with key areas to address for healthy family functioning.
Survivorship care often refers to continued healthcare after cancer treatment. Jacobsen and colleagues advocated to expand this to include patients on extended treatments and maintenance/prophylactic ...therapies, recognizing the care continuum as more complex. Transitions of care for individuals diagnosed with a blood cancer can be complicated. We sought to better understand blood cancer caregivers' experiences as their diagnosed family member encountered "survivorship transitions" across the continuum.
We conducted semi-structured interviews with adults caring for a parent or a child with a blood cancer. Caregivers were segmented into survivorship groups based on two transitional contexts: (1) when patients transitioned to a new line of therapy (active treatment or maintenance therapy); (2) when patients ended treatment. We conducted a thematic analysis and triangulated findings to compare transitional experiences.
Caregivers in both groups reported experiencing a "new normal," which included personal, relational, and environmental adjustments. Caregivers in the treatment transitions group (n = 23) also described uncertainty challenges (e.g., losing their "safety net") and disrupted expectations (e.g., feeling "caught off guard" by challenges). Whereas caregivers in the end-of-treatment transitions group (n = 15) described relief coupled with worry (e.g., feeling hopeful yet worried).
Survivorship transitions for caregivers are riddled with challenges that include difficult readjustments, uncertainty/worry, and unmet expectations. While there seems to be a cohesive experience of "survivorship transitions," each transition group revealed nuanced distinctions.
Tailored supportive resources are needed for caregivers throughout survivorship transitions.
The proportion of cancer patients who participate in clinical trials (CTs) remains low, despite an understanding of barriers to enrollment. The barrier of rural residence is relevant to Veterans, who ...more commonly live in rural areas than non-Veterans. In this exploratory study, we aimed to examine geographic factors that could impede CT enrollment and to improve access to CTs for Veterans.
To assess the influence of rurality on the availability of CTs, we performed simulated searches using The Leukemia & Lymphoma Society's Clinical Trial Support Center (LLS CTSC) database. The LLS CTSC provides free CT education and navigation. In the second part of this study, we offered Veterans with blood cancers who received care at the Durham, Salem, Clarksburg, Sioux Falls, and Houston Veterans Administration (VA) Medical Centers referral to the LLS CTSC.
In simulated searches, we found significantly lower numbers of CTs open to enrollment in rural areas, compared to urban areas. In actual referrals, 33 Veterans were referred to the LLS CTSC, of which 15 (45%) lived in rural areas. Three Veterans enrolled in CTs. Patients declined referral or did not enroll in CTs for various reasons, including a desire to maintain care within the VA and/or to initiate therapy quickly.
We identified "clinical trial deserts," which might hinder access and reduce CT participation for rural Veterans. Referral to the LLS CTSC promoted CT education and enrollment among a highly rural cohort of Veterans receiving care in the VA system.
Maternal overweight in pregnancy alters the metabolic environment and generates chronic low-grade inflammation. This affects fetal development and programs the offspring's health for developing ...cardiovascular and metabolic disease later in life. MME (membrane-metalloendopeptidase, neprilysin) cleaves various peptides regulating vascular tone. Endothelial cells express membrane-bound and soluble MME. In adults, the metabolic environment of overweight and obesity upregulates endothelial and circulating MME. We here hypothesized that maternal overweight increases MME in the feto-placental endothelium. We used primary feto-placental endothelial cells (fpEC) isolated from placentas after normal vs. overweight pregnancies and determined MME mRNA, protein, and release. Additionally, soluble cord blood MME was analyzed. The effect of oxygen and tumor necrosis factor α (TNFα) on MME protein in fpEC was investigated in vitro. Maternal overweight reduced MME mRNA (-39.9%,
< 0.05), protein (-42.5%,
= 0.02), and MME release from fpEC (-64.7%,
= 0.02). Both cellular and released MME protein negatively correlated with maternal pre-pregnancy BMI. Similarly, cord blood MME was negatively associated with pre-pregnancy BMI (
= -0.42,
= 0.02). However, hypoxia and TNFα, potential negative regulators of MME expression, did not affect MME protein. Reduction of MME protein in fpEC and in cord blood may alter the balance of vasoactive peptides. Our study highlights the fetal susceptibility to maternal metabolism and inflammatory state.
Objective
We examined the effects of the family communication environment (conversation orientation) on adult child caregivers' burden and clinical interactions and if the effects are mediated by ...openness to communicate about cancer, avoidant cancer communication, and social support (SS).
Method
Caregivers of a parent diagnosed with a blood cancer (N = 121) completed an online survey of validated measures of conversation orientation (i.e., the extent to which families openly communicate), SS, cancer openness, avoidance, caregiver burden, clinical communication skills, and quality of clinical interactions (QCI).
Results
Conversation orientation had significant indirect effects on caregiver burden, mediated by SS (β = −0.11, p < 0.001), as well as cancer openness and avoidance (β = −0.07, p < 0.001). Conversation orientation also had significant indirect effects on caregivers' communication skills with a parent's clinician, mediated by avoidance (β = 0.08, p < 0.01) and SS (β = 0.06, p < 0.001). Finally, conversation orientation had significant indirect effects on caregivers' QCI mediated by avoidance (β = 0.71, p < 0.05).
Conclusions
Adult child caregivers whose families communicate more openly exhibit less caregiver burden and report better clinical interaction skills and perceived quality of the clinical interaction. Avoidance emerged as a key mediating factor. Caregivers from less open communication environments may benefit from interventions that help them navigate challenging but critical caregiving conversations.
Introduction
Despite the importance of clinical trial participation among cancer patients, few participate—and even fewer patients from ethnic and racial minoritized groups. It is unclear whether ...suggested approaches to increase accrual are successful. We conducted a scoping review to identify evidence‐based approaches to increase participation in cancer treatment clinical trials that demonstrated clear increases in accrual. Notably, more stringent than other published reviews, only those studies with comparison data to measure a difference in accrual rates were included.
Methods
We searched PubMed/MEDLINE, Embase, CINAHL, and Web of Science for English‐language articles published from January 1, 2012, to August 8, 2022. Studies were included if they were conducted in the United States, described single or multicomponent interventions, and provided data to measure accrual relative to baseline levels or that compared accrual rates with other interventions.
Results
Sixteen articles were included: six with interventions addressing patient barriers, two addressing provider barriers, seven describing institutional change, and one describing policy change. Key themes emerged, such as a focus on patient education, cultural competency, and building the capacity of clinics. Few studies provide comparative accrual data, making it difficult to identify with certainty any effective, evidence‐based approaches for increasing accrual. Some patient‐ and system‐level interventions studies showed modest increases in accrual primarily through pre‐post measurement.
Conclusion
Despite an extensive body of literature about the barriers that impede cancer treatment trial accrual, along with numerous recommendations for how to overcome these barriers, results reveal surprisingly little evidence published in the last 10 years on interventions that increase accrual relative to baseline levels or compared with other interventions. As clinical trials are a primary vehicle through which we improve cancer care, it is critical that evidence‐based approaches are used to inform all efforts to increase accrual. Strategies for increasing participation in cancer clinical trials must be developed and rigorously evaluated so that these strategies can be disseminated, participation in trials can increase and become more equitable, and trial results can become more generalizable.
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