Advancing mathematics by guiding human intuition with AI.

The practice of mathematics involves discovering patterns and using these to formulate and prove conjectures, resulting in theorems. Since the 1960s, mathematicians have used computers to assist in the discovery of patterns and formulation of conjectures1, most famously in the Birch and Swinnerton-Dyer conjecture2, a Millennium Prize Problem3. Here we provide examples of new fundamental results in pure mathematics that have been discovered with the assistance of machine learning-demonstrating a method by which machine learning can aid mathematicians in discovering new conjectures and theorems. We propose a process of using machine learning to discover potential patterns and relations between mathematical objects, understanding them with attribution techniques and using these observations to guide intuition and propose conjectures. We outline this machine-learning-guided framework and demonstrate its successful application to current research questions in distinct areas of pure mathematics, in each case showing how it led to meaningful mathematical contributions on important open problems: a new connection between the algebraic and geometric structure of knots, and a candidate algorithm predicted by the combinatorial invariance conjecture for symmetric groups4. Our work may serve as a model for collaboration between the fields of mathematics and artificial intelligence (AI) that can achieve surprising results by leveraging the respective strengths of mathematicians and machine learning.

Healthcare utilization disparities among children with high-risk neuroblastoma treated on Children's Oncology Group clinical trials.

INTRODUCTION: Disparities in relapse and survival from high-risk neuroblastoma (HRNBL) persist among children from historically marginalized groups even in highly standardized clinical trial settings. Research in other cancers has identified differential treatment toxicity as one potential underlying mechanism. Whether racial and ethnic disparities in treatment-associated toxicity exist in HRNBL is poorly understood. METHODS: This is a retrospective study utilizing a previously assembled merged cohort of children with HRNBL on Children's Oncology Group (COG) post-consolidation immunotherapy trials ANBL0032 and ANBL0931 at Pediatric Health Information System (PHIS) centers from 2005 to 2014. Race and ethnicity were categorized to reflect historically marginalized populations as Hispanic, non-Hispanic Black (NHB), non-Hispanic other (NHO), and non-Hispanic White (NHW). Associations between race-ethnicity and intensive care unit (ICU)-level care utilization as a proxy for treatment-associated toxicity were examined with log binomial regression and summarized as risk ratio (RR) and corresponding 95% confidence interval (CI). RESULTS: The analytic cohort included 370 children. Overall, 88 (23.8%) patients required ICU-level care for a median of 3.0 days (interquartile range [IQR]: 1.0-6.5 days). Hispanic children had nearly three times the risk of ICU-level care (RR 3.1, 95% CI: 2.1-4.5; fully adjusted RR [aRR] 2.5, 95% CI: 1.6-3.7) compared to NHW children and the highest percentage of children requiring cardiovascular-driven ICU-level care. CONCLUSION: Children of Hispanic ethnicity with HRNBL receiving clinical trial-delivered therapy were more likely to experience ICU-level care compared to NHW children. These data suggest that further investigation of treatment-related toxicity as a modifiable mechanism underlying outcome disparities is warranted.

Feasibility of oncology clinical trial-embedded evaluation of social determinants of health.

Social determinants of health (SDoH) are associated with stark disparities in cancer outcomes, but systematic SDoH data collection is virtually absent from oncology clinical trials. Trial-based SDoH data are essential to ensure representation of marginalized populations, contextualize outcome disparities, and identify health-equity intervention opportunities. We report the feasibility of a pediatric oncology multicenter therapeutic trial-embedded SDoH investigation. Among 448 trial participants, 392 (87.5%) opted-in to the embedded SDoH study; 375 (95.7%) completed baseline surveys, with high longitudinal response rates (88.9-93.1%) over 24 months. Trial-embedded SDoH data collection is feasible and acceptable and must be consistently included within future oncology trials.

Socioeconomic disparities in survival after high-risk neuroblastoma treatment with modern therapy.

BACKGROUND: Modern therapeutic advances in high-risk neuroblastoma have improved overall survival (OS), but it is unclear whether these survival gains have been equitable. This study examined the relationship between socioeconomic status (SES) and overall survival (OS) in children with high-risk neuroblastoma and whether SES-associated disparities have changed over time. PROCEDURE: In this population-based cohort study, children <18 years diagnosed with high-risk neuroblastoma (diagnosis at age ≥12 months with metastatic disease) from 1991 to 2015 were identified through the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Associations of county-level SES variables and OS were tested with univariate Cox proportional hazards regression. For a subcohort diagnosed after 2007, insurance status was examined as an individual-level SES variable. Multivariable regression analyses with treatment era and interaction terms were performed when SES variables reached near-significance (p ≤ .1) in univariate and bivariate modeling with treatment era. RESULTS: Among 1217 children, 2-year OS improved from 53.0 ± 3.4% in 1991-1998 to 76.9 ± 2.9% in 2011-2015 (p < .001). In univariate analyses, children in high-poverty counties (hazard ratio [HR] = 1.74, 95% confidence interval [CI] = 1.17-2.60, p = .007), and those with Medicaid (HR = 1.40, 95% CI = 1.05-1.86, p = .02) experienced an increased hazard of death. No interactions between treatment era and SES variables were statistically significant in multivariable analyses, indicating that differences in the OS between SES groups did not change over time. CONCLUSIONS: Survival disparities among children with high-risk neuroblastoma have not widened over time, suggesting equitable access to and benefit from therapeutic advances. However, children of low SES experience persistently inferior survival. Interventions to narrow this disparity are paramount.

PediCARE: Development of a poverty-targeted intervention for pediatric cancer.

BACKGROUND: Poverty is associated with inferior psychosocial outcomes, higher rates of relapse, and decreased overall survival in children with cancer. Despite this, there are few evidence-based, poverty-targeted interventions and none specific to pediatric oncology. To address this gap, we developed and refined the Pediatric Cancer Resource Equity (PediCARE) intervention, a household material hardship (HMH) targeted intervention providing transportation and groceries to pediatric oncology families. METHODS: This was a single-arm pilot study conducted at a single, large, tertiary pediatric cancer center. Newly diagnosed patients with HMH-exposure were directly assigned to receive PediCARE for a total of three months. Quantitative and qualitative approaches were used to evaluate its acceptability and to rapidly refine the intervention. RESULTS: Nine families (100% of those approached) consented to enrollment with no attrition over the three-month study period. Families were highly satisfied with the intervention and recommended participation to others. All of the families utilized the grocery delivery component of PediCARE, and seven utilized the transportation component. Qualitative participant feedback was used to rapidly refine the intervention including logistics of intervention delivery, and dose of intervention components. CONCLUSION: PediCARE, a poverty-targeted intervention, was highly acceptable to pediatric oncology families. The intervention was refined in real-time utilizing quantitative and qualitative feedback. Next steps include intervention evaluation in a randomized, controlled feasibility study.

Disparities in pediatric psychosocial oncology utilization.

BACKGROUND: Integratedbehavioral health models have been proposed as care delivery approaches to mitigate mental health disparities in primary care settings. However, these models have not yet been widely adopted or evaluated in pediatric oncology medical homes. METHODS: We conducted a retrospective cohort study of 394 children with newly diagnosed cancer at Dana-Farber/Boston Children's Cancer and Blood Disorders Center (DF/BCH) from April 2013 to January 2017. Baseline sociodemographic characteristics and psychiatry utilization outcomes at 12 months following diagnosis were abstracted from the medical record. The severity of household material hardship (HMH), a concrete poverty exposure, at diagnosis and race/ethnicity were characterized by parent report using the Psychosocial Assessment Tool 2.0 (PAT). Associations between sociodemographic characteristics and receipt of psychiatry consultation were assessed with multivariable logistic regression models. RESULTS: Among 394 children, 29% received a psychiatric consultation within 12 months postdiagnosis. Of these, 88% received a new psychiatric diagnosis, 76% received a psychopharmacologic recommendation, and 62% received a new behavioral intervention recommendation. In multivariable logistic regression adjusting for age, cancer diagnosis, and PAT total score, there was no statistically significant association between HMH severity or household income and psychiatry utilization. Children who identified as racial/ethnic minorities were significantly less likely to receive a psychiatry consultation (OR = 0.48, 95% CI = 0.27-0.84). CONCLUSIONS: In a pediatric oncology medical home with an integrated behavioral health model, socioeconomic status was not associated with disparate psychiatry utilization. However, there remained a profound racial/ethnic disparity in psychiatry utilization, highlighting the need for additional research and care delivery intervention.

Longitudinal analysis of quality-of-life outcomes in children during treatment for acute lymphoblastic leukemia: A report from the Children's Oncology Group AALL0932 trial.

BACKGROUND: Children with average-risk acute lymphoblastic leukemia (AR-ALL) face many challenges that can adversely affect their quality of life (QOL). However, to the authors' knowledge, patterns and predictors of QOL impairment during therapy have not been well characterized to date. METHODS: Patients with AR-ALL who were enrolled on the Children's Oncology Group AALL0932 trial were offered participation in this prospective cohort study if they were aged ≥4 years at the time of diagnosis and had an English-speaking parent. At approximately 2 months, 8 months, 17 months, 26 months, and 38 months (boys only) after diagnosis, parents completed the Pediatric Quality of Life Inventory Generic Core Scales Version 4.0 (PedsQL4.0) and McMaster Family Assessment Device instruments for QOL (physical, emotional, and social functioning) and family functioning, respectively. The proportions of individuals scoring in the impaired range (2 standard deviations below the population mean) were calculated at each time point. Longitudinal impairment patterns and predictors were examined. RESULTS: A total of 594 participants with AR-ALL were diagnosed at a mean age of 6.0 years (standard deviation, 1.6 years). At 2 months, a substantial proportion of participants had impaired scores for physical (36.5%; 95% confidence interval [95% CI], 32.3%-40.8%) and emotional (26.2%; 95% CI, 22.5%-30.2%) functioning compared with population norms of 2.3%. These elevations persisted at 26 months. Emotional impairment at 2 months (odds ratio, 3.4; 95% CI, 1.5-7.7) was found to significantly predict emotional impairment at 26 months. In repeated measures analysis with multivariate modeling, unhealthy family functioning (odds ratio, 1.5; 95% CI, 1.1-2.1) significantly predicted emotional impairment controlling for age and sex. QOL outcomes were similar between sexes at the end of therapy (26 months for girls and 38 months for boys). CONCLUSIONS: Many children with AR-ALL experience physical and emotional functioning impairment that begins early in treatment and persists. Early screening may identify high-risk patients who might benefit from family-based interventions. Cancer 2018;124:571-9. © 2017 American Cancer Society.

Long-term psychological and educational outcomes for survivors of neuroblastoma: A report from the Childhood Cancer Survivor Study.

BACKGROUND: Neuroblastoma survivors may be at elevated risk for psychological impairments because of their young age at diagnosis and neurotoxic treatment, but this is not well described. METHODS: A total of 859 ≥5-year survivors of neuroblastoma younger than 18 years (diagnosed in 1970-1999), who had a median age at diagnosis of 0.8 years (range: 0.0-7.3 years) and a median follow-up of 13.3 years (range: 8.0-17.9 years), were compared with 872 siblings of childhood cancer survivors who were younger than 18 years with the parent-reported Behavior Problem Index (BPI) for psychological functioning. Age- and sex-adjusted multivariate log-binomial models were used to identify factors associated with impairment in BPI domains (scores worse than the sibling 10th percentile). The impact of psychological impairment on educational outcomes was examined among survivors. RESULTS: Compared with siblings, neuroblastoma survivors had an increased prevalence of impairment in the domains of anxiety/depression (19% vs 14%; P = .003), headstrong behavior (19% vs 13%; P < .001), attention deficits (21% vs 13%; P < .001), peer conflict/social withdrawal (26% vs 17%; P < .001), and antisocial behavior (16% vs 12%; P = .01). Common treatment exposures (vincristine, cisplatin, and retinoic acid) were not associated with impairment. Having 2 or more chronic health conditions predicted impairment in 4 domains (P < .001). Specifically, pulmonary disease predicted impairment in all 5 domains (P ≤ .004). Endocrine disease (P ≤ .004) and peripheral neuropathy (P ≤ .02) each predicted impairment in 3 domains. Psychological impairment was associated with special education service usage and educational attainment less than college. CONCLUSIONS: Neuroblastoma survivors are at elevated risk for psychological impairment, which is associated with special education service usage and lower adult educational attainment. Those with chronic health conditions may represent a high-risk group for targeted screening and intervention. Cancer 2018. © 2018 American Cancer Society.

Feasibility of systematic poverty screening in a pediatric oncology referral center.

BACKGROUND: Based on the strong link between poverty and child health outcomes, both the American Academy of Pediatrics (AAP) and national pediatric oncology associations have advocated for routine clinical poverty screening. Systematic implementation of this recommendation in pediatric oncology is not yet standard, and feasibility data are needed. We report the feasibility of routine poverty screening in a pediatric oncology referral center and baseline poverty characteristics of this population. METHODS: From 2013 to 2017, 448 families with newly diagnosed pediatric cancer at Dana-Farber/Boston Children's Cancer and Blood Disorders Center were offered the Psychosocial Assessment Tool 2.0 (PAT) as part of routine care. The PAT includes a two-item screen for household material hardship (HMH). All families were asked about annual household income by a resource specialist. Data were abstracted with sociodemographic and child/disease characteristics. Descriptive statistics are reported. RESULTS: Four hundred and thirteen families completed the PAT (response rate 92%), of whom 394 (95%) completed specific questions assessing for HMH. Ninety-four percent of families who met with a resource specialist disclosed their annual household income. One quarter (27%) of families was ≤200% federal poverty level at diagnosis, and 44% of families endorsed at least one domain of HMH. The most frequent domains of HMH included housing (24%), utilities (20%), and transportation (20%). CONCLUSIONS: Systematic poverty screening per AAP and pediatric oncology psychosocial standards of care is feasible in routine cancer care. There is a high baseline incidence (44%) of HMH in at least one domain in families with newly diagnosed pediatric cancer who may benefit from early identification and resource intervention.

Physical activity barriers, preferences, and beliefs in childhood cancer patients.

PURPOSE: Childhood cancer patients report low physical activity levels despite the risk for long-term complications that may benefit from exercise. Research is lacking regarding exercise barriers, preferences, and beliefs among patients (1) on- and off-therapy and (2) across the age spectrum. METHODS: Cross-sectional study in the Yale Pediatric Hematology-Oncology Clinic (October 2013-October 2014). Participants were ≥ 4 years old, > 1 month after cancer diagnosis at < 20 years, not acutely ill, expected to live > 6 months, and received chemotherapy and/or radiation. Participants (or parents if < 13 years) completed a survey. RESULTS: The 162 patients (99% participated) were 34% children (4.0-12.9 years), 31% adolescents (13.0-17.9 years), and 35% adults (≥ 18 years). Most had leukemia/lymphoma (66%); 32% were on-therapy. On-therapy patients were more likely than off-therapy patients (73 vs. 48%; p = 0.003) to report ≥ 1 barrier related to physical complaints, such as "just too tired" (46 vs. 28%; p = 0.021) or "afraid" of injury (22 vs. 9%; p = 0.027). The majority preferred walking (73%), exercising at home (91%), exercising in the afternoon (79%), and a maximum travel time of 10-20 min (54%); preferences did not vary significantly by therapy status or age. Most respondents (94%) recognized the benefits of exercise after cancer, but 50% of on- vs. 12% of off-therapy patients believed "their cancer diagnosis made it unsafe to exercise regularly" (p < 0.001). CONCLUSIONS: Physical activity barriers pertaining to physical complaints and safety concerns were more pronounced in on-therapy childhood cancer patients but persisted off-therapy. Preferences and beliefs were relatively consistent. Our data can inform interventions in different patient subgroups.

Use of single-question screening for erectile dysfunction: a study of at-risk Asian men in primary health care.

This study assesses the validity of a single-question screener for erectile dysfunction (ED) in men at risk in comparison to a standard validated tool - the five-item version of the International Index of Erectile Function (IIEF-5). A total of 174 men with at least one risk factor for ED were studied, with 58.0% and 10.9% of the study respondents meeting the criteria for their erectile impairment by IIEF-5 and single-question screener respectively. Our results suggest that in spite of high feasibility, a simplified, single-question screener has low sensitivity in capturing ED prevalence, even in an at-risk population, within the Asian context.

A home-based physical activity intervention using activity trackers in survivors of childhood cancer: A pilot study.

BACKGROUND: Over 70% of childhood cancer survivors develop late complications from therapy, many of which can be mitigated by physical activity. Survivors engage in exercise at similar or lower rates than their sedentary healthy peers. We piloted a novel home-based exercise intervention with a motivational activity tracker. We evaluated (i) feasibility, (ii) impact on activity levels and physical fitness, and (iii) barriers, preferences, and beliefs regarding physical activity. METHODS: Childhood cancer survivors currently 15 years or older and not meeting the Centers for Disease Control and Prevention physical activity guidelines were enrolled and instructed to wear the Fitbit One, a 4.8 cm × 1.8 cm motivational activity tracker, daily for 6 months. Baseline and follow-up evaluations included self-report surveys, an Actigraph accelerometer for 7 days, and a VO2 maximum test by cardiac stress test. RESULTS: Nineteen participants were enrolled (13.4% participation rate) with a mean age of 24.3 ± 5.8 years (range 15-35). Four participants withdrew with a 79% retention rate. Participants wore the Fitbit an average of 19.0 ± 4.7 days per month during months 1-3 and 15.0 ± 7.9 days per month during months 4-6. Total weekly moderate to vigorous physical activity increased from 265.6 ± 117.0 to 301.4 ± 135.4 min and VO2 maximum increased from 25.7 ± 7.7 to 27.2 ± 7.4 ml/kg/min. These changes were not statistically significant (P = 0.47 and 0.30, respectively). Survey responses indicated no change in barriers, preferences, and beliefs regarding physical activity. CONCLUSIONS: This pilot study of a motivational activity tracker demonstrated feasibility as measured by participant retention, receptivity, and belief of utility. Future studies with a large sample size are needed to demonstrate the efficacy and sustainability of this intervention.

Experiences with the survivorship care plan in primary care providers of childhood cancer survivors: a mixed methods approach.

PURPOSE: Focusing on primary care providers (PCPs) of known childhood cancer survivors, we used a mixed methods approach to understand providers' experiences with the survivorship care plan (SCP), as well as preferences and barriers regarding survivorship care. METHODS: The SCP was sent to 202 eligible PCPs of patients attending a regional survivorship clinic. The PCPs then completed quantitative postal surveys. Sixteen PCPs underwent an additional qualitative interview. Provider characteristics were examined as potential predictors of experiences, preferences, and barriers regarding survivorship care. Grounded theory was utilized to analyze the qualitative data. RESULTS: Respondents (n=134) included 55% pediatricians, 23% internists, 20% family practitioners, and 2% obstetricians/gynecologists. Only 8% of PCPs preferred to have primary responsibility for survivorship care; 46% favored a specialized clinic. A minority of PCPs reported that they felt "very comfortable" using the SCP to guide surveillance (31%) or deliver all survivorship care (3%). Endorsed barriers included lack of knowledge/training (74%), not recalling or understanding the contents of the SCP (69%), and uncertainty about who is responsible for providing care (58%). Two distinct themes emerged from the qualitative interviews: a preference not to be responsible for survivorship care, and uncertain utility of the SCP. CONCLUSIONS: Our study suggests that PCPs of childhood cancer survivors generally felt uncomfortable using the SCP and providing survivorship care. Even with the availability of the SCP, the biggest barrier was lack of knowledge. Our data suggests that including PCPs in survivorship care will require additional educational opportunities and evaluation of more collaborative models of care delivery.

Soluble biglycan induces the production of ICAM-1 and MCP-1 in human aortic valve interstitial cells through TLR2/4 and the ERK1/2 pathway.

OBJECTIVE: Mononuclear cell infiltration in valvular tissue is one of the characteristics in calcific aortic valve disease. The inflammatory responses of aortic valve interstitial cells (AVICs) play an important role in valvular inflammation. However, it remains unclear what may evoke AVIC inflammatory responses. Accumulation of biglycan has been found in diseased aortic valve leaflets. Soluble biglycan can function as a danger-associated molecular pattern to induce the production of proinflammatory mediators in cultured macrophages. We tested the hypothesis that soluble biglycan induces AVIC production of proinflammatory mediators involved in mononuclear cell infiltration through Toll-like receptor (TLR)-dependent signaling pathways. METHODS: Human AVICs isolated from normal aortic valve leaflets were treated with specific siRNA and neutralizing antibody against TLR2 or TLR4 before biglycan stimulation. The production of ICAM-1 and MCP-1 was assessed. To determine the signaling pathway involved, phosphorylation of ERK1/2 and p38 MAPK was analyzed, and specific inhibitors of ERK1/2 and p38 MAPK were applied. RESULTS: Soluble biglycan induced ICAM-1 expression and MCP-1 release in human AVICs, but had no effect on IL-6 release. TLR4 blockade and knockdown reduced ICAM-1 and MCP-1 production induced by biglycan, while knockdown and neutralization of TLR2 resulted in greater suppression of the inflammatory responses. Biglycan induced the phosphorylation of ERK1/2 and p38 MAPK, but ICAM-1 and MCP-1 production was reduced only by inhibition of the ERK1/2 pathway. Further, inhibition of ERK1/2 attenuated NF-κB activation following biglycan treatment. CONCLUSIONS: Soluble biglycan induces the expression of ICAM-1 and MCP-1 in human AVICs through TLR2 and TLR4 and requires activation of the ERK1/2 pathway. AVIC inflammatory responses induced by soluble biglycan may contribute to the mechanism of chronic inflammation associated with calcific aortic valve disease.

Fostering Wonder Through the Arts and Humanities: Using Visual Thinking Strategies in Medical Education.

ABSTRACT: Philosophers and scientists alike argue that wonder-that emotion or state of consciousness in which one's attention is fixed on phenomena beyond one's comprehension-is the central virtue and driving force of all education. As in general education, wonder is central to all aspects of academic medicine's tripartite mission; a sense of wonder fuels the delivery of humanized patient care, sparks scientific discoveries, and supports engagement in lifelong learning. Despite its importance throughout medicine, developing a capacity for wonder among physicians has not been a stated goal of medical education, and innovative methods to foster a capacity for wonder have not been explored. There is a growing interest in the arts and humanities in medical education, and evidence suggests that these can support the development of a diverse array of clinically relevant skills and attitudes (including close observation, critical thinking, empathy, and tolerance for ambiguity) in medical learners across the learning continuum. However, even the potential of these methods to support a capacity for wonder has not yet been fully explored. In this article, the authors explore how one of the most widely used and studied arts-based learning activities in medical education, Visual Thinking Strategies, can help develop a capacity for wonder among physicians. They illustrate how Visual Thinking Strategies support the central elements of wonder-based pedagogy (i.e., exploration, improvisation, imagination, personal interest, and the ethos of educators) previously developed in education theory.

Household income and health-related quality of life in children receiving treatment for acute myeloid leukemia: Potential impact of selection bias in health equity research.

OBJECTIVE: Examine the influence of household income on health-related quality of life (HRQOL) among children with newly diagnosed acute myeloid leukemia (AML). DESIGN: Secondary analysis of data prospectively collected from pediatric patients receiving treatment for AML at 14 hospitals across the United States. EXPOSURE: Household income was self-reported on a demographic survey. The examined mediators included the acuity of presentation and treatment toxicity. OUTCOME: Caregiver proxy reported assessment of patient HRQOL from the Peds QL 4.0 survey. RESULT: Children with AML (n = 131) and caregivers were prospectively enrolled to complete PedsQL assessments. HRQOL scores were better for patients in the lowest versus highest income category (mean ± SD: 76.0 ± 14 household income <$25,000 vs. 59.9 ± 17 income ≥$75,000; adjusted mean difference: 11.2, 95% CI: 2.2-20.2). Seven percent of enrolled patients presented with high acuity (ICU-level care in the first 72 h), and 16% had high toxicity (any ICU-level care); there were no identifiable differences by income, refuting mediating roles in the association between income and HRQOL. Enrolled patients were less likely to be Black/African American (9.9% vs. 22.2%), more likely to be privately insured (50.4% vs. 40.7%), and more likely to have been treated on a clinical trial (26.7% vs. 18.5%) compared to eligible unenrolled patients not enrolled. Evaluations of potential selection bias on the association between income and HRQOL suggested differences in HRQOL may be smaller than observed or even in the opposing direction. CONCLUSIONS: While primary analyses suggested lower household income was associated with superior HRQOL, differential participation may have biased these results. Future studies should partner with patients/families to identify strategies for equitable participation in clinical research.

Visual attention to features and space in mice using reverse correlation.

Visual attention allows the brain to evoke behaviors based on the most important visual features. Mouse models offer immense potential to gain a circuit-level understanding of this phenomenon, yet how mice distribute attention across features and locations is not well understood. Here, we describe a new approach to address this limitation by training mice to detect weak vertical bars in a background of dynamic noise while spatial cues manipulate their attention. By adapting a reverse-correlation method from human studies, we linked behavioral decisions to stimulus features and locations. We show that mice deployed attention to a small rostral region of the visual field. Within this region, mice attended to multiple features (orientation, spatial frequency, contrast) that indicated the presence of weak vertical bars. This attentional tuning grew with training, multiplicatively scaled behavioral sensitivity, approached that of an ideal observer, and resembled the effects of attention in humans. Taken together, we demonstrate that mice can simultaneously attend to multiple features and locations of a visual stimulus.

Trends of Low Back Pain Research in Older and Working-Age Adults from 1993 to 2023: A Bibliometric Analysis.

Although the number of publications focusing on low back pain in older adults (LBP-O) and working-age adults (LBP-W) has been growing for decades, comparative research trends in these two populations, which may help to guide future investigation, have not been rigorously explored. This analysis aimed to describe publication patterns and trends of research targeting LBP-O and LBP-W over the last three decades. Peer-reviewed LBP-O and LBP-W articles published between 1993 and 2023 were retrieved from the Web of Science, which provided the details of annual publication volume, and prominent journals/countries/institutions. The relationship between the annual publication volumes and years was analyzed by Spearman correlation analysis. The hot topics and emerging trends were analyzed by VOSviewer and CiteSpace, respectively. A total of 4217 LBP-O-related and 50,559 LBP-W-related documents were included. The annual publication volumes of LBP-O and LBP-W articles increased over the years (r=0.995 to 0.998, p<0.001). The United States had the highest number of prominent institutions publishing relevant articles. The most prolific journal for LBP-O (5.4%) and LBP-W-related (6.1%) papers is the journal "Spine". Cognitive behavioral therapy, intervertebral disc (IVD) degeneration, physiotherapy, physical activity, and walking were the recent hot topics and physical activity was an emerging trend in LBP-O, while surgery and IVD degeneration (also a hot topic) were emerging trends in LBP-W. This study highlights the paucity of LBP-O-related research in the past. The United States and the journal Spine stand out in LBP research. The research trend of physical activity in LBP-O is consistent with the recognized importance of physical activity for older adults in general, and for managing LBP-O in particular. Conversely, the emerging trends of surgery and intervertebral disc degeneration in LBP-W research highlight a focus on the biomedical model of LBP despite LBP being a biopsychosocial condition.

Patient-reported neurocognitive function in adult survivors of childhood and adolescent osteosarcoma and Ewing sarcoma.

PURPOSE: Little is known regarding long-term neurocognitive outcomes in osteosarcoma and Ewing sarcoma (EWS) survivors despite potential risk factors. We evaluated associations among treatment exposures, chronic health conditions, and patient-reported neurocognitive outcomes in adult survivors of childhood osteosarcoma and EWS. METHODS: Five-year survivors of osteosarcoma (N = 604; median age 37.0 years) and EWS (N = 356; median age 35.0 years) diagnosed at < 21 years from 1970 to 1999, and 697 siblings completed the Childhood Cancer Survivor Study Neurocognitive Questionnaire and reported chronic health conditions, education, and employment. Prevalence of reported neurocognitive difficulties were compared between diagnostic groups and siblings. Modified Poisson regression identified factors associated with neurocognitive difficulties. RESULTS: Osteosarcoma and EWS survivors, vs. siblings, reported higher prevalences of difficulties with task efficiency (15.4% [P = 0.03] and 14.0% [P = 0.04] vs. 9.6%, respectively) and emotional regulation (18.0% [P < 0.0001] and 15.2% [P = 0.03] vs. 11.3%, respectively), adjusted for age, sex, and ethnicity/race. Osteosarcoma survivors reported greater memory difficulties vs. siblings (23.5% vs. 16.4% [P = 0.01]). Comorbid impairment (i.e., ≥ 2 neurocognitive domains) was more prevalent in osteosarcoma (20.0% [P < 0.001]) and EWS survivors (16.3% [P = 0.02]) vs. siblings (10.9%). Neurological conditions were associated with worse task efficiency (RR = 2.17; 95% CI = 1.21-3.88) and emotional regulation (RR = 1.88; 95% CI = 1.01-3.52), and respiratory conditions were associated with worse organization (RR = 2.60; 95% CI = 1.05-6.39) for EWS. Hearing impairment was associated with emotional regulation difficulties for osteosarcoma (RR = 1.98; 95% CI = 1.22-3.20). Patient report of cognitive difficulties was associated with employment but not educational attainment. CONCLUSIONS: Survivors of childhood osteosarcoma and EWS are at increased risk for reporting neurocognitive difficulties, which are associated with employment status and appear related to chronic health conditions that develop over time. IMPLICATIONS FOR CANCER SURVIVORS: Early screening, prevention, and treatment of chronic health conditions may improve/prevent long-term neurocognitive outcomes.