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New interaction potentials were developed for molecular dynamics simulations to study the role of Mg and Ca in modifying the structure and properties of alkaline earth silicates and borates. Competition between the depolymerization of the silica network and the formation of new bonds between oxygen atoms and modifiers leads to the enhancement of the elastic moduli with increasing modifier content in alkaline earth silicate glasses. Compared with calcium silicate, the higher elastic moduli of magnesium silicate result from a higher connectivity of the overall glass network due to the incorporation of fourfold coordinated magnesium and a more rigid connection between oxygen atoms and modifiers. In contrast to the silicates, the effect of modifier on the elastic moduli of alkaline earth borates is dominated by the formation of fourfold coordinated boron (N4). Calcium borate with higher N4 shows a more rigid network structure and higher elastic moduli.

Examines the computational cost of solving the convection-diffusion equation using finite element discretization strategies and Krylov subspace-based iteration solution algorithms. Partial differential equations; Cost benefits from combined streamline and crosswind diffusion discretization compared to shock-capturing discretization; Advantages of a generalized minimal residual algorithm.

BACKGROUND: Combined mortality rates for pneumonia and influenza suggest that the 2 conditions represent the sixth leading cause of death in the United States. The total cost of pneumonia, including indirect costs, was estimated to be approximately $23 billion per year in 1994. OBJECTIVE: The objective of this study was to assess variables that may be significantly associated with the cost of treating patients hospitalized with community-acquired pneumonia (CAP). We also assessed the impact of treatment guidelines for management of CAP (developed by managed care plans) on total costs. METHODS: Patients in 3 managed care plans who were hospitalized with a primary or secondary diagnosis of CAP in Maryland and Washington, DC, between January 1, 1997, and April 30, 1997, or between January 1, 1998, and April 30, 1998, were identified based on International Classification of Diseases, Ninth Revision codes. Clinical data were abstracted from patients' medical charts by nurses, and billing data were acquired from these plans. A retrospective data analysis was carried out using billing data from 3 managed care plans and clinical data from hospitals associated with the plans. A multivariate regression model was developed using the natural logarithm of cost as the dependent variable. Independent variables that were studied included severity of illness, days in the intensive care unit (ICU), triage per guidelines, drug therapy per guidelines, mortality, and managed care plan identifiers. RESULTS: The charts of 569 patients were assessed. The mean age of the study sample was 75.3 years. ICU days (P < 0.001), mortality, and drug therapy (both P < 0.01) per guidelines significantly affected costs. As expected, an increase in the number of ICU days led to an increase in costs. However, patients who received drug therapy recommended by the guidelines had significantly lower costs than patients not treated according to the guidelines (P = 0.001). CONCLUSIONS: The findings of this study suggest that guidelines for CAP management, such as those developed by managed care plans, may help reduce costs by minimizing unnecessary ICU admissions and appropriately managing patients with CAP. [ABSTRACT FROM AUTHOR]

We investigated the effect of retropharyngeal nodal volumes (RNV) on distant metastasis in patients with advanced nasopharyngeal carcinoma (NPC). From February 2000 to June 2006, a total of 181 patients with biopsy-proven NPC, no distant metastasis, and available pre-treatment magnetic resonance imaging (MRI) were retrospectively reviewed. Most of the patients (95.6%) had stage III/IV diseases. The contour of retropharyngeal nodes 5mm was delineated on the axial slides of pre-treatment T2-weighted MRI without contrast enhancement. The RNV was calculated by the Eclipse[TM] treatment planning software. The primary end-points were subsequent distant failure rates and distant metastasis failure-free survival (DMFFS). The pre-treatment RNV in patients who developed distant failure was higher than in those without distant failure (P=0.0536). The distant failure rates between the patients with RNV > and 4.68cm(3) were 33.3% and 16.0%, respectively (P=0.0112). The rates of 7-year DMFFS in patients with RNV > and 4.68cm(3) were 66.4% and 83.5%, respectively (P=0.0043). Multivariate Cox analysis showed N-stage (P<0.001), gender (P=0.026), and RNV (P=0.088) were important predictors for DMFFS. We conclude that the RNV measured by MRI is a potential predictor of distant metastasis in patients with advanced NPC. [ABSTRACT FROM AUTHOR]

Engineering vascularized tissues remains a promising approach for treating ischemic cardiovascular diseases. The availability of 3D-bioprinted vascular grafts that induce therapeutic angiogenesis can help avoid necrosis and excision of ischemic tissues. Here, using a combination of living cells and biodegradable hydrogels, we fabricated 3D-printed biocompatible proangiogenic patches from endothelial cell-laden photo-crosslinked gelatin (EC-PCG) bioink and smooth muscle cell-encapsulated polyurethane (SMC-PU) bioink. Implantation of 3D-bioprinted proangiogenic patches in a mouse model showed that EC-PCG served as an angiogenic capillary bed, whereas patterned SMC-PU increased the density of microvessels. Moreover, the assembled patterns between EC-PCG and SMC-PU induced the geometrically guided generation of microvessels with blood perfusion. In a rodent model of hindlimb ischemia, the vascular patches rescued blood flow to distal tissues, prevented toe/foot necrosis, promoted muscle remodeling, and increased the capillary density, thereby improving the heat-escape behavior of ischemic animals. Thus, our 3D-printed vascular cell-laden bioinks constitute efficient and scalable biomaterials that facilitate the engineering of vascular patches capable of directing therapeutic angiogenesis for treating ischemic vascular diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Recruiting special populations to smoking cessation trials is challenging and approaches beyond in-clinic recruitment may be beneficial. This secondary analysis of data from a smoking cessation RCT for individuals with a history of cervical cancer or cervical intraepithelial neoplasia (CIN) explored differences associated with in-clinic vs. online recruitment., Aims and Methods: Participants were recruited from clinics within a university-based NCI-designated cancer center (n = 87) and online nationally via Facebook (n = 115). Baseline measures included sociodemographics, smoking history, and cancer or CIN history. Study retention and smoking abstinence were assessed 12 months post-baseline. Group differences in baseline characteristics were evaluated. Retention and abstinence were evaluated while controlling for group differences and predictors., Results: Participants recruited online (vs. in-clinic) had higher educational attainment (p = .01) and health literacy (p = .003). They were more likely to have CIN versus cancer, to be further from the time of diagnosis, and to have completed active treatment (p values < .001). While controlling for these group differences and independent predictors, retention was higher among participants recruited online (log-likelihood χ2(1) = 11.41, p < .001). There were no recruitment differences in self-reported (p = .90) or biochemically confirmed smoking abstinence (p = .18)., Conclusions: Compared to individuals recruited in-person, individuals recruited online were more educated, had higher health literacy, and presented with a different clinical profile (ie, more likely to have CIN vs. cancer and to have completed active treatment). There were few differences in participant characteristics between recruitment approaches, and no differences on any smoking-related variables. Online recruitment has the potential to improve enrollment of cancer survivors in smoking cessation trials., Implications: People with a history of CIN or cervical cancer recruited to a smoking cessation RCT online (vs. in-clinic) were more likely to have a diagnosis of CIN versus cancer and were more educated and health literate. Participants recruited online were more likely to be retained in the study and there were no differences in smoking abstinence rates at 12 months. Incorporating online recruitment increased the reach of tobacco treatment efforts to a larger and more diverse sample. This could reduce the burden of tobacco-related disease, improve CIN and cancer treatment outcomes, and reduce secondary malignancies and morbidity among this underserved group., (Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco 2024.)

The rising costs of cancer care and subsequent medical financial hardship for cancer survivors and families are well documented in the United States. Less attention has been paid to employment disruptions and loss of household income after a cancer diagnosis and during treatment, potentially resulting in lasting financial hardship, particularly for working-age adults not yet age-eligible for Medicare coverage and their families. In this article, the authors use a composite patient case to illustrate the adverse consequences of cancer diagnosis and treatment for employment, health insurance coverage, household income, and other aspects of financial hardship. They summarize existing research and provide nationally representative estimates of multiple aspects of financial hardship and health insurance coverage, benefit design, and employee benefits, such as paid sick leave, among working-age adults with a history of cancer and compare them with estimates among working-age adults without a history of cancer from the most recently available years of the National Health Interview Survey (2019-2021). Then, the authors identify opportunities for addressing employment and health insurance coverage challenges at multiple levels, including federal, state, and local policies; employers; cancer care delivery organizations; and nonprofit organizations. These efforts, when informed by research to identify best practices, can potentially help mitigate the financial hardship associated with cancer., (© 2024 The Authors. CA: A Cancer Journal for Clinicians published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Many genes with distinct molecular functions have been linked to genetically heterogeneous amyotrophic lateral sclerosis (ALS), including SuperOxide Dismutase 1 (SOD1) and Valosin-Containing Protein (VCP). SOD1 converts superoxide to oxygen and hydrogen peroxide. VCP acts as a chaperon to regulate protein degradation and synthesis and various other cellular responses. Although the functions of these two genes differ, in the current report we show that overexpression of wild-type VCP in mice enhances lifespan and maintains the size of neuromuscular junctions (NMJs) of both male and female SOD1G93A mice, a well-known ALS mouse model. Although VCP exerts multiple functions, its regulation of ER formation and consequent protein synthesis has been shown to play the most important role in controlling dendritic spine formation and social and memory behaviors. Given that SOD1 mutation results in protein accumulation and aggregation, it may direct VCP to the protein degradation pathway, thereby impairing protein synthesis. Since we previously showed that the protein synthesis defects caused by Vcp deficiency can be improved by leucine supplementation, to confirm the role of the VCP-protein synthesis pathway in SOD1-linked ALS, we applied leucine supplementation to SOD1G93A mice and, similar to Vcp overexpression, we found that it extends SOD1G93A mouse lifespan. In addition, the phenotypes of reduced muscle strength and fewer NMJs of SOD1G93A mice are also improved by leucine supplementation. These results support the existence of crosstalk between SOD1 and VCP and suggest a critical role for protein synthesis in ASL. Our study also implies a potential therapeutic treatment for ALS., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Inappropriate medication utilization among older adults is a pressing concern in the United States, owing to its high prevalence and the consequential detrimental impact it engenders. The adverse effects stemming from the inappropriate use of medication may be unequally borne by racial/ethnic minority populations, calling for greater efforts towards promoting equity in healthcare. The study objective was to assess the cost-effectiveness of Medication Therapy Management (MTM) services among Medicare beneficiaries and across racial/ethnic groups., Methods: Medicare administrative data from 2016 to 2017 linked to Area Health Resources Files were used to analyze Medicare fee-for-service patients aged 65 or above with continuous Parts A/B/D coverage. The intervention group included new MTM enrollees in 2017; the control group referred to patients who met the general MTM eligible criteria but did not enroll in 2016 or 2017. The 2 groups were matched using a propensity score method. Effectiveness was evaluated as the proportion of appropriate medication utilization based on performance measures developed by the Pharmacy Quality Alliance. Costs were computed as total healthcare costs from Medicare perspective. A multivariable net benefit regressions with a classic linear model and Bayesian analysis were utilized. Net benefit was calculated based on willingness-to-pay thresholds at various multiples of the gross domestic product in 2017. Three-way interaction terms among dummy variables for MTM enrollment, 2017, and racial/ethnic minority groups were incorporated in a difference-in-differences study design., Results: After adjusting for patient characteristics, the findings indicate that MTM receipt was associated with incremental net benefit among each race and ethnicity. For instance, the net benefit of MTM among the non-Hispanic White patients was $2498 (95% confidence interval = $1609, $3386) at a willingness-to-pay value of $59,908. The study found no significant difference in net benefits for MTM services between minority and White patients., Conclusion: The study provides evidence that MTM is a cost-effective tool for managing medication utilization among the Medicare population. However, MTM may not be cost-effective in reducing racial/ethnic disparities in medication utilization in the short term. Further research is needed to understand the long-term cost-effectiveness of MTM on racial/ethnic disparities., Competing Interests: The following potential conflicts of interest are disclosed. No potential conflict of interest was reported by Chi Chun Steve Tsang. Junling Wang received funding from AbbVie, Curo, Bristol Myers Squibb, Pfizer, and Pharmaceutical Research and Manufacturers of America (PhRMA); and serves as Co-Chair on the Value Assessment-Health Outcomes Research Advisory Committee of the PhRMA Foundation. Ya-Chen Tina Shih reported receiving institutional grants from the Health Care Service Corporation, Blue Cross and Blue Shield of Texas. She received consulting fees, travel support, and accommodations for serving on an advisory board for Sanofi; and is a member of the American Cancer Society Guideline Development Group., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Continuous tobacco use in patients with cancer is linked to substantial healthcare costs due to increased risks and complications, whereas quitting smoking leads to improved treatment outcomes and cost reductions. Addressing the need for empirical evidence on the economic impact of smoking cessation, this study examined the association between smoking cessation and healthcare cost utilization among a sample of 930 patients with cancer treated at The University of Texas MD Anderson Cancer Center's Tobacco Research and Treatment Program (TRTP). Applying conditional quantile regression and propensity scores to address confounding, our findings revealed that abstinence achieved through the TRTP significantly reduced the median cost during a 3-month period post-quitting by $1,095 [β = -$1,095, P = 0.007, 95% confidence interval (CI), = (-$1,886 to -$304)]. Sensitivity analysis corroborated these conclusions, showing a pronounced cost reduction when outlier data were excluded. The long-term accrued cost savings from smoking cessation could potentially offset the cost of participation in the TRTP program, underscoring its cost effectiveness. An important implication of this study is that by reducing smoking rates, healthcare systems can more efficiently allocate resources, enhance patient health outcomes, and lessen the overall cancer burden., Prevention Relevance: This study emphasizes the dual impact of smoking cessation programs in patients with cancer: quitting smoking and reducing healthcare costs. It highlights the importance of integrating cessation programs into cancer prevention strategies, ensuring both individual health benefits and broader, system-wide economic efficiencies. See related Spotlight, p. 197., (©2023 American Association for Cancer Research.)

In this study, the photoelectric properties of a complete series of GaS 1- x Se x (0 ≤ x ≤ 1) layered crystals are investigated. The photoconductivity spectra indicate a decreasing bandgap of GaS 1- x Se x as the Se composition x increases. Time-resolved photocurrent measurements reveal a significant improvement in the response of GaS 1- x Se x to light with increasing x . Frequency-dependent photocurrent measurements demonstrate that both pure GaS crystals and GaS 1- x Se x ternary alloy crystals exhibit a rapid decrease in photocurrents with increasing illumination frequency. Crystals with lower x exhibit a faster decrease in photocurrent. However, pure GaSe crystal maintains its photocurrent significantly even at high frequencies. Measurements for laser-power-dependent photoresponsivity and bias-voltage-dependent photoresponsivity also indicate an increase in the photoresponsivity of GaS 1- x Se x as x increases. Overall, the photoresponsive performance of GaS 1- x Se x is enhanced with increasing x , and pure GaSe exhibits the best performance. This result contradicts the findings of previous reports. Additionally, the inverse trends between bandgap and photoresponsivity with increasing x suggest that GaS 1- x Se x -based photodetectors could potentially offer a high response and wavelength-selectivity for UV and visible light detection. Thus, this work provides novel insights into the photoelectric characteristics of GaS 1- x Se x layered crystals and highlights their potential for optoelectronic applications.

Objectives: The Pathways to Wellness randomized controlled trial found that 2 behavioral interventions, mindfulness awareness practices and survivorship education, reduced depressive symptoms in younger breast cancer survivors (BCSs) compared with wait-list control. This secondary analysis examines whether the interventions led to reduced loss of work productivity among younger BCSs and whether such reductions were mediated by reductions in depressive symptoms., Methods: The Work Productivity and Activity Impairment scale was used to measure work productivity loss at 4 assessment time points. Correlates of productivity loss at enrollment were examined using multivariable linear regression. Differences in change over time in productivity loss between each intervention group and control were assessed using linear mixed models. Reduced depressive symptoms were tested as a mediator of reduced productivity loss., Results: Of 247 trial participants, 199 were employed and included in the analyses. At enrollment, higher productivity loss was associated with chemotherapy receipt (P = .003), younger age (P = .021), more severe cognitive problems (P = .002), higher musculoskeletal pain severity (P = .002), more depressive symptoms (P = .016), and higher fatigue severity (P = .033). The mindfulness intervention led to significantly less productivity loss compared with control at all 3 postintervention assessment points (all P < .05), with about 54% of the effect mediated by reduction in depressive symptoms. Survivorship education was not associated with reduced loss of productivity., Conclusions: These findings suggest that addressing depressive symptoms through behavioral interventions, such as mindfulness, may mitigate impacts on work productivity in younger BCSs., Competing Interests: Author Disclosures Conflict of Interest Disclosures for this article can be found here., (Copyright © 2024. Published by Elsevier Inc.)

Importance: The current method of BRCA testing for breast and ovarian cancer prevention, which is based on family history, often fails to identify many carriers of pathogenic variants. Population-based genetic testing offers a transformative approach in cancer prevention by allowing for proactive identification of any high-risk individuals and enabling early interventions., Objective: To assess the lifetime incremental effectiveness, costs, and cost-effectiveness of population-based multigene testing vs family history-based testing., Design, Setting, and Participants: This economic evaluation used a microsimulation model to assess the cost-effectiveness of multigene testing (BRCA1, BRCA2, and PALB2) for all women aged 30 to 35 years compared with the current standard of care that is family history based. Carriers of pathogenic variants were offered interventions, such as magnetic resonance imaging with or without mammography, chemoprevention, or risk-reducing mastectomy and salpingo-oophorectomy, to reduce cancer risk. A total of 2000 simulations were run on 1 000 000 women, using a lifetime time horizon and payer perspective, and costs were adjusted to 2022 US dollars. This study was conducted from September 1, 2020, to December 15, 2023., Main Outcomes and Measures: The main outcome measure was the incremental cost-effectiveness ratio (ICER), quantified as cost per quality-adjusted life-year (QALY) gained. Secondary outcomes included incremental cost, additional breast and ovarian cancer cases prevented, and excess deaths due to coronary heart disease (CHD)., Results: The study assessed 1 000 000 simulated women aged 30 to 35 years in the US. In the base case, population-based multigene testing was more cost-effective compared with family history-based testing, with an ICER of $55 548 per QALY (95% CI, $47 288-$65 850 per QALY). Population-based multigene testing would be able to prevent an additional 1338 cases of breast cancer and 663 cases of ovarian cancer, but it would also result in 69 cases of excess CHD and 10 excess CHD deaths per million women. The probabilistic sensitivity analyses show that the probability that population-based multigene testing is cost-effective was 100%. When the cost of the multigene test exceeded $825, population-based testing was no longer cost-effective (ICER, $100 005 per QALY; 95% CI, $87 601-$11 6323)., Conclusions and Relevance: In this economic analysis of population-based multigene testing, population-based testing was a more cost-effective strategy for the prevention of breast cancer and ovarian cancer when compared with the current family history-based testing strategy at the $100 000 per QALY willingness-to-pay threshold. These findings support the need for more comprehensive genetic testing strategies to identify pathogenic variant carriers and enable informed decision-making for personalized risk management.

Several compounds have been used for atherosclerosis treatment, including clinical trials; however, no anti-atherosclerotic drugs based on hemodynamic force-mediated atherogenesis have been discovered. Our previous studies demonstrated that "small mothers against decapentaplegic homolog 1/5" (Smad1/5) is a convergent signaling molecule for chemical [e.g., bone morphogenetic proteins (BMPs)] and mechanical (e.g., disturbed flow) stimulations and hence may serve as a promising hemodynamic-based target for anti-atherosclerosis drug development. The goal of this study was to develop a high-throughput screening (HTS) platform to identify potential compounds that can inhibit disturbed flow- and BMP-induced Smad1/5 activation and atherosclerosis. Through HTS using a Smad1/5 downstream target inhibitor of DNA binding 1 ( Id-1 ) as a luciferase reporter, we demonstrated that KU-55933 and Apicidin suppressed Id-1 expression in AD-293 cells. KU-55933 (10 μM), Apicidin (10 μM), and the combination of half doses of each [1/2(K + A)] inhibited disturbed flow- and BMP4-induced Smad1/5 activation in human vascular endothelial cells (ECs). KU-55933, Apicidin, and 1/2(K + A) treatments caused 50.6%, 47.4%, and 73.3% inhibitions of EC proliferation induced by disturbed flow, respectively, whereas EC inflammation was only suppressed by KU-55933 and 1/2(K + A), but not Apicidin alone. Administrations of KU-55933 and 1/2(K + A) to apolipoprotein E-deficient mice inhibited Smad1/5 activation in ECs in athero-susceptible regions, thereby suppressing endothelial proliferation and inflammation, with the attenuation of atherosclerotic lesions in these mice. A unique drug screening platform has been developed to demonstrate that KU-55933 and its combination with Apicidin are promising therapeutic compounds for atherosclerosis based on hemodynamic considerations., Competing Interests: Competing interests statement:The authors declare no competing interest.

It is of interest to health policy research to estimate the population-averaged longitudinal medical cost trajectory from initial cancer diagnosis to death, and understand how the trajectory curve is affected by patient characteristics. This research question leads to a number of statistical challenges because the longitudinal cost data are often non-normally distributed with skewness, zero-inflation, and heteroscedasticity. The trajectory is nonlinear, and its length and shape depend on survival, which are subject to censoring. Modeling the association between multiple patient characteristics and nonlinear cost trajectory curves of varying lengths should take into consideration parsimony, flexibility, and interpretation. We propose a novel longitudinal varying coefficient single-index model. Multiple patient characteristics are summarized in a single-index, representing a patient's overall propensity for healthcare use. The effects of this index on various segments of the cost trajectory depend on both time and survival, which is flexibly modeled by a bivariate varying coefficient function. The model is estimated by generalized estimating equations with an extended marginal mean structure to accommodate censored survival time as a covariate. We established the pointwise confidence interval of the varying coefficient and a test for the covariate effect. The numerical performance was extensively studied in simulations. We applied the proposed methodology to medical cost data of prostate cancer patients from the Surveillance, Epidemiology, and End Results-Medicare-Linked Database., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Biometric Society.)

Due to the widespread involvement of distributed collaboration triggered by COVID-19, it has become a new trend that has continued into the post-pandemic era. This study investigated collective performance within two collaborative environments (co-located and distancing settings) by assessing inter-brain synchrony patterns (IBS) among design collaborators using functional near-infrared spectroscopy. The preliminary study was conducted with three dyads who possessed 2-3 years of professional product design experience. Each dyad completed two designated design tasks in distinct settings. In the distributed condition, participants interacted through video conferencing in which they were allowed to communicate by verbalization and sketching using a shared digital whiteboard. To prevent the influences of different sketching tools on design outputs, we employed digital sketching for both environments. The interactions between collaborators were identified in three behaviors: verbal only, sketch only, and mixed communication (verbal and sketch). The consequences revealed a higher level of IBS when mixed communication took place in distributed conditions than in co-located conditions. Comparably, the occurrence of IBS increased when participants solely utilized sketching as the interaction approach within the co-located setting. A mixed communication method combining verbalization and sketching might lead to more coordinated cognitive processes when in physical isolation. Design collaborators are inclined to adjust their interaction behaviors in order to adapt to different design environments, strengthen the exchange of ideas, and construct design consensus. Overall, the present paper discussed the performance of virtual collaborative design based on a neurocognitive perspective, contributing valuable insights for the future intervention design that promotes effective virtual teamwork.

In this article, we present a flexible model for microbiome count data. We consider a quasi-likelihood framework, in which we do not make any assumptions on the distribution of the microbiome count except that its variance is an unknown but smooth function of the mean. By comparing our model to the negative binomial generalized linear model (GLM) and Poisson GLM in simulation studies, we show that our flexible quasi-likelihood method yields valid inferential results. Using a real microbiome study, we demonstrate the utility of our method by examining the relationship between adenomas and microbiota. We also provide an R package "fql" for the application of our method., (© 2023 John Wiley & Sons Ltd.)

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced melanoma, but racial disparities in melanoma outcomes continue. These inequities are not fully explained by individual factors. OBJECTIVE: To investigate the associations of neighborhood factors with the use of ICIs in metastatic melanoma. METHODS: We conducted a retrospective cohort study of commercially insured US adults with metastatic melanoma diagnosed between January 2011 and December 2020. We examined the associations between the county-level percentage of population from racial and ethnic minority groups and the time from metastatic melanoma diagnosis to initiating ICIs using Cox proportional hazards models adjusting for patient characteristics. RESULTS: We identified 4,052 patients with metastatic melanoma, of which 49% used ICIs. We found that the adoption of ICIs in a county declined with increasing minority quintile (quintile 1: 52.4%, quintile 2: 50.4%, quintile 3: 50.1%, quintile 4: 45.8%, and quintile 5: 44.7%). The delay in ICI initiation also went up as the percentage of minorities in a county increased (log-rank test P = 0.03). Compared with the lowest quintile, the adjusted hazard ratio of ICI initiation of the second, third, fourth, and highest minority quintile was 0.94 (95% CI = 0.81-1.08), 0.88 (95% CI = 0.76-1.02), 0.81 (95% CI = 0.68-0.97), and 0.77 (95% CI = 0.66-0.91), respectively. Secondary analysis revealed that the slower initiation was driven by the counties with the highest percentage of Hispanic population (hazard ratio = 0.74; 95% CI = 0.61-0.89) in both Cox models and sensitivity analyses. High-minority counties correlated with metro areas, higher poverty levels, and a greater number of medical oncologists. CONCLUSIONS: We found that patients with metastatic melanoma living in counties with higher proportion of minorities, particularly of Hispanic origin, are more likely to experience delays in ICI treatment. This study provides important population-level data on neighborhood-level disparity in medication use. More research is needed on the underlying provider- and system-level factors that directly contributed to the lower use of cancer medicines in high-minority areas, which can help inform the development of evidence-based medication use strategies that can improve health outcomes and equity.

Heterozygous mutations in the dual-specificity tyrosine phosphorylation-regulated kinase 1a (Dyrk1a) gene define a syndromic form of autism spectrum disorder. The synaptic and circuit mechanisms mediating DYRK1A functions in social cognition are unclear. Here, we identify a social experience-sensitive mechanism in hippocampal mossy fiber-parvalbumin interneuron (PV IN) synapses by which DYRK1A recruits feedforward inhibition of CA3 and CA2 to promote social recognition. We employ genetic epistasis logic to identify a cytoskeletal protein, ABLIM3, as a synaptic substrate of DYRK1A. We demonstrate that Ablim3 downregulation in dentate granule cells of adult heterozygous Dyrk1a mice is sufficient to restore PV IN-mediated inhibition of CA3 and CA2 and social recognition. Acute chemogenetic activation of PV INs in CA3/CA2 of adult heterozygous Dyrk1a mice also rescued social recognition. Together, these findings illustrate how targeting DYRK1A synaptic and circuit substrates as "enhancers of DYRK1A function" harbors the potential to reverse Dyrk1a haploinsufficiency-associated circuit and cognition impairments., Competing Interests: Declaration of interests A.S. is a named inventor on US Patent 10,287,580 (Methods for inhibition of Ablim3 to improve memory in aging, Alzheimer’s disease and PTSD)., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Cancer survivors with a disability are among the most vulnerable in health status and financial hardship, but no prior research has systematically examined how disability modifies health-care use and costs. This study examined the association between functional disability among cancer survivors and their health-care utilization and medical costs., Methods: We generated nationally representative estimates using the 2015-2019 Medical Expenditure Panel Survey. Outcomes included use of 6 service types (inpatient, outpatient, office-based physician, office-based nonphysician, emergency department, and prescription) and medical costs of aggregate services and by each of 6 service types. The primary independent variable was a categorical variable for the total number of functional disabilities. We employed multivariable generalized linear models and 2-part models, adjusting for sociodemographics and health conditions and accounting for survey design., Results: Among cancer survivors (n = 9359; weighted n = 21 046 285), 38.8% reported at least 1 disability. Compared with individuals without a disability, cancer survivors with 4 or more disabilities experienced longer hospital stays (adjusted average marginal effect = 1.14 days, 95% confidence interval [CI] = 0.55 to 1.73), more visits to an office-based physician (average marginal effect = 1.43 visits, 95% CI = 0.51 to 2.35), and a greater number of prescriptions (average marginal effect = 12.1 prescriptions, 95% CI = 9.27 to 15.0). Their total (average marginal effect = $9537, 95% CI = $5713 to $13 361) and out-of-pocket (average marginal effect = $639, 95% CI = $79 to $1199) medical costs for aggregate services were statistically significantly higher. By type, disability in independent living was most strongly associated with greater costs for aggregate services., Conclusions: Cancer survivors with a disability experienced greater health-care use and higher costs. Cancer survivorship planning for health care and financial stability should consider the patients' disability profile., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Telehealth restrictions were relaxed under the COVID-19 public health emergency. We examined telehealth use before and during the pandemic among patients with newly diagnosed cancers and the association between state policies and telehealth use., Methods: The study cohort was constructed from Optum's deidentified Clinformatics Data Mart and included patients with lymphoma, female breast cancer, colorectal cancer, prostate cancer, and lung cancer diagnosed between March 1, 2019, and March 31, 2021. We performed an interrupted time series analysis to examine the trend of cancer-related telehealth use within 1 month of diagnosis relative to the timing of the COVID-19 public health emergency and multivariable logistic regressions to examine factors-specifically, state parity laws and regulations on cross-state practice-associated with telehealth., Results: Of 110 461 patients, the rate of telehealth use peaked at 33.4% in April 2020, then decreased to 12% to 15% between September 2020 and March 2021. Among the 53 982 patients diagnosed since March 2020, telehealth use was statistically significantly lower for privately insured patients residing in states with coverage-only parity or no or unspecified parity than those in states with coverage and payment parity (adjusted rate = 20.2%, 19.1%, and 23.3%, respectively). The adjusted rate was lower for patients in states with cross-state telehealth policy limitations than for those in states without restrictions (14.9% vs 17.8%)., Conclusions: Telehealth use by patients diagnosed with cancer during the pandemic was higher among those living in states with more generous parity and less restrictive rules for cross-state practice. Policy makers contemplating whether to permanently relax certain telehealth policies must consider the impact on vulnerable patient populations who can benefit from telehealth., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Acute care (AC) visits by cancer patients are costly sources of healthcare resources and can exert a financial burden of oncology care both for individuals with cancer and healthcare systems. We sought to identify whether cancer patients who reported more severe initial financial toxicity (FT) burdens shouldered excess risks for acute care utilization., Methods: In 225 adult patients who participated in the Economic Strain and Resilience in Cancer (ENRICh) survey study of individuals receiving ambulatory cancer care between March and September 2019, we measured the baseline FT (a multidimensional score of 0-10 indicating the least to most severe global, material, and coping FT burdens). All AC visits, including emergency department (ED) and unplanned hospital admissions, within 1-year follow-up were identified. The association between the severity of FT and the total number of AC visits was tested using Poisson regression models., Results: A total of 18.6% ( n = 42) of patients had any AC visit, comprising 64.3% hospital admissions and 35.7% ED visits. Global FT burden was associated with the risk of repeat AC visits within 1-year follow-up (RR = 1.17, 95% CI 1.07-1.29, P < 0.001 for every unit increase), even after adjusting for sociodemographic and disease covariates. When examining subdimensions of FT, the burden of depleted FT coping resources (coping FT) was strongly associated with the risk of repeat AC visits (RR = 1.27, 95% CI 1.15-1.40, P < 0.001) while material FT burden showed a trend toward association (RR = 1.07, 95% CI 0.99-1.15, P = 0.07)., Conclusion: In this prospective study of acute oncology care utilization outcomes among adult cancer patients, FT was a predictor of a higher burden of acute care visits. Patients with severely depleted material and also practical and social coping resources were at particular risk for repeated visits. Future studies are needed to identify whether early FT screening and intervention efforts may help to mitigate urgent acute care utilization burdens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shi, Maldonado, Wu, Peterson, Chen, Diao, Volk, Giordano, Shih, Kaiser and Smith.)

Purpose: To evaluate the performance of a biopsy decision support algorithmic model, the intelligent-augmented breast cancer risk calculator (iBRISK), on a multicenter patient dataset., Materials and Methods: iBRISK was previously developed by applying deep learning to clinical risk factors and mammographic descriptors from 9700 patient records at the primary institution and validated using another 1078 patients. All patients were seen from March 2006 to December 2016. In this multicenter study, iBRISK was further assessed on an independent, retrospective dataset (January 2015-June 2019) from three major health care institutions in Texas, with Breast Imaging Reporting and Data System (BI-RADS) category 4 lesions. Data were dichotomized and trichotomized to measure precision in risk stratification and probability of malignancy (POM) estimation. iBRISK score was also evaluated as a continuous predictor of malignancy, and cost savings analysis was performed., Results: The iBRISK model's accuracy was 89.5%, area under the receiver operating characteristic curve (AUC) was 0.93 (95% CI: 0.92, 0.95), sensitivity was 100%, and specificity was 81%. A total of 4209 women (median age, 56 years [IQR, 45-65 years]) were included in the multicenter dataset. Only two of 1228 patients (0.16%) in the "low" POM group had malignant lesions, while in the "high" POM group, the malignancy rate was 85.9%. iBRISK score as a continuous predictor of malignancy yielded an AUC of 0.97 (95% CI: 0.97, 0.98). Estimated potential cost savings were more than $420 million., Conclusion: iBRISK demonstrated high sensitivity in the malignancy prediction of BI-RADS 4 lesions. iBRISK may safely obviate biopsies in up to 50% of patients in low or moderate POM groups and reduce biopsy-associated costs. Keywords: Mammography, Breast, Oncology, Biopsy/Needle Aspiration, Radiomics, Precision Mammography, AI-augmented Biopsy Decision Support Tool, Breast Cancer Risk Calculator, BI-RADS 4 Mammography Risk Stratification, Overbiopsy Reduction, Probability of Malignancy (POM) Assessment, Biopsy-based Positive Predictive Value (PPV3) Supplemental material is available for this article. Published under a CC BY 4.0 license.See also the commentary by McDonald and Conant in this issue., Competing Interests: Disclosures of conflicts of interest: C.F.E. No relevant relationships. T.H. No relevant relationships. T.A.P. No relevant relationships. V.K. Consultant fees from AstraZeneca, Daiichi, Seagen, Gilead, Novartis, Lilly, Pfizer, Genentech, and TerSera; payment or honoraria from AstraZeneca, Daiichi, Seagen, Gilead, Novartis, Lilly, and Genentech. M.E. No relevant relationships. E.B. No relevant relationships. P.M.O. No relevant relationships. K.A.K. No relevant relationships. H.S. No relevant relationships. L.W. No relevant relationships. J.E. No relevant relationships. Y.C.T.S. Research grants from the National Cancer Institute on topics unrelated to this manuscript. B.K. No relevant relationships. I.W.P. No relevant relationships. A.L.C. Grants or contracts from Novartis and Acrotech. K.K. No relevant relationships. D.S. No relevant relationships. W.T.Y. Research grant with Clarity sponsorship for “Evaluation of individual level breast cancer risk prediction in a cohort of patients with a personal history of breast cancer using a novel software as a medical device;” royalties or licenses from Elsevier. J.C.C. Support from the Breast Cancer Research Foundation (BCRF); philanthropic support from M. Neal and R. Neal; National Cancer Institute/National Institutes of Health grant number U01 CA268813; grants or contracts from the Cancer Prevention and Research Institute of Texas (grant no. RP220650); payment or honoraria from Duke and NUS Singapore (August 7, 2022); sole inventor on patent application number 10420838 entitled “Methods for treating cancer using iNOS-inhibitory compositions” held by Houston Methodist Hospital; participation on Merck Triple Negative Breast Cancer Advisory Board (December 13, 2022), Lilly Loxo Advisory Board (December 8, 2022), and BCRF Annual Meeting (October 26, 2022). S.T.C.W. No relevant relationships., (© 2023 by the Radiological Society of North America, Inc.)

Background: Financial toxicity (FT) reflects multi-dimensional personal economic hardships borne by cancer patients. It is unknown whether measures of FT-to date derived largely from English-speakers-adequately capture economic experiences and financial hardships of medically underserved low English proficiency US Hispanic cancer patients. We piloted a Spanish language FT instrument in this population., Methods: We piloted a Spanish version of the Economic Strain and Resilience in Cancer (ENRICh) FT measure using qualitative cognitive interviews and surveys in un-/under-insured or medically underserved, low English proficiency, Spanish-speaking Hispanics (UN-Spanish, n  = 23) receiving ambulatory oncology care at a public healthcare safety net hospital in the Houston metropolitan area. Exploratory analyses compared ENRICh FT scores amongst the UN-Spanish group to: (1) un-/under-insured English-speaking Hispanics (UN-English, n  = 23) from the same public facility and (2) insured English-speaking Hispanics (INS-English, n  = 31) from an academic comprehensive cancer center. Multivariable logistic models compared the outcome of severe FT (score > 6)., Results: UN-Spanish Hispanic participants reported high acceptability of the instrument (only 0% responded that the instrument was "very difficult to answer" and 4% that it was "very difficult to understand the questions"; 8% responded that it was "very difficult to remember resources used" and 8% that it was "very difficult to remember the burdens experienced"; and 4% responded that it was "very uncomfortable to respond"). Internal consistency of the FT measure was high (Cronbach's α  = 0.906). In qualitative responses, UN-Spanish Hispanics frequently identified a total lack of credit, savings, or income and food insecurity as aspects contributing to FT. UN-Spanish and UN-English Hispanic patients were younger, had lower education and income, resided in socioeconomically deprived neighborhoods and had more advanced cancer vs. INS-English Hispanics. There was a higher likelihood of severe FT in UN-Spanish (OR = 2.73, 95% CI 0.77-9.70; p  = 0.12) and UN-English (OR = 4.13, 95% CI 1.13-15.12; p  = 0.03) vs. INS-English Hispanics. A higher likelihood of severely depleted FT coping resources occurred in UN-Spanish (OR = 4.00, 95% CI 1.07-14.92; p  = 0.04) and UN-English (OR = 5.73, 95% CI 1.49-22.1; p  = 0.01) vs. INS-English. The likelihood of FT did not differ between UN-Spanish and UN-English in both models ( p  = 0.59 and p  = 0.62 respectively)., Conclusion: In medically underserved, uninsured Hispanic patients with cancer, comprehensive Spanish-language FT assessment in low English proficiency participants was feasible, acceptable, and internally consistent. Future studies employing tailored FT assessment and intervention should encompass the key privations and hardships in this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shi, McGinnis, Peterson, Taku, Chen, Yu, Wu, Mendoza, Shete, Ma, Volk, Giordano, Shih, Nguyen, Kaiser and Smith.)