bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiplicity of negative-energy solutions for singular-superlinear Schrödinger equations with indefinite-sign potential
Authors: Alves Ricardo Lima , Santos Carlos Alberto , Silva Kaye 
Published: April 2021

We are concerned with the multiplicity of positive solutions for the singular superlinear and subcritical Schrödinger equation [Formula: see text] beyond the Nehari extremal value, as defined in [Y. Il’yasov, On extreme values of Nehari manifold via nonlinear Rayleigh’s quotient, Topol. Methods Nonlinear Anal. 49 (2017) 683–714], when the potential [Formula: see text] may change its sign, [Formula: see text], [Formula: see text] is a positive continuous function, [Formula: see text] and [Formula: see text] is a real parameter. The main difficulties come from the non-differentiability of the energy functional and the fact that the intersection of the boundaries of the connected components of the Nehari set is non-empty. We overcome these difficulties by exploring topological structures of that boundary to build non-empty sets whose boundaries have empty intersection and minimizing over them by controlling the energy level.
Drug-Wide Association Study (DWAS): Challenges and Opportunities
Authors: Wang Youjin , Gadalla Shahinaz M. 
Published: April 2021

Abstract
Cancer risk associations with commonly prescribed medications have been mainly evaluated in hypothesis-driven studies that focus on one drug at a time. Agnostic drug-wide association studies (DWAS) offer an alternative approach to simultaneously evaluate associations between a large number of drugs with one or more cancers using large-scale electronic health records. Although cancer DWAS approaches are promising, a number of challenges limit their applicability. This includes the high likelihood of false positivity; lack of biological considerations; and methodological shortcomings, such as inability to tightly control for confounders. As such, the value of DWAS is currently restricted to hypothesis generation with detected signals needing further evaluation. In this commentary, we discuss those challenges in more detail and summarize the approaches to overcome them by using published cancer DWAS studies, including the accompanied article by Støer and colleagues. Despite current concerns, DWAS future is filled with opportunities for developing innovative analytic methods and techniques that incorporate pharmacology, epidemiology, cancer biology, and genetics.
See related article by Støer et al., p. 682
Breast Tissue Composition—Why It Matters and How Can We Measure It More Accurately in Epidemiology Studies
Authors: Oskar Sabine , Kehm Rebecca , Terry Mary Beth 
Published: April 2021

Abstract
Early-life body size has been consistently associated with breast cancer risk. The direction of the association changes over time, with high birth weight, smaller adolescent body size, and adult weight gain all increasing breast cancer risk. There is also a clear positive association between larger body size and increased breast adipose tissue measured by mammograms, but less is known about how body size changes across life stages affect stromal and epithelial breast tissue. Using breast tissue slides from women with benign breast disease, Oh and colleagues applied machine learning methods to evaluate body size across the life course and adipose, epithelial, and stromal tissue concentrations in adulthood. They found consistent patterns for higher adipose and lower stromal tissue concentrations with larger childhood and adult body size at age 18 years. They reported lower levels of epithelial tissue with larger body size at 18 years, but not at other time periods. Additional studies examining how body size at different life stages may affect breast tissue composition will be important. Noninvasive methods that can provide measures of breast tissue composition may offer potential ways forward to ensure generalizability, and repeated measurements by life stage.
See related article by Oh et al., p. 608
Improving the Process of Screening for Medical Financial Hardship in Oncology Practice
Authors: Yabroff K. Robin , Bradley Cathy J. , Shih Ya-Chen Tina 
Published: April 2021

Abstract
Medical financial hardship, including problems paying medical bills, distress, and forgoing care because of cost, is increasingly common among patients receiving cancer treatment and cancer survivors across the economic spectrum. Little is known, however, about provider practices for identifying patients who experience financial hardship and the strategies for mitigating hardship and addressing patient needs. In this editorial, we discuss a study of practices within the NCI Community Oncology Research Program. McLouth and colleagues found disparities in the use of screening and financial navigation and reliance on inadequate screening methods. To address these disparities, we emphasize the importance of comprehensive and ongoing financial hardship screening throughout the course of cancer treatment and survivorship care, as well as the necessity of accompanying counseling, navigation, and referrals. We also recommend key attributes of screening tools and a process for systematic implementation within clinical practice. With adverse health and economic consequences of the COVID-19 pandemic disproportionately affecting people who are racial or ethnic minorities, uninsured or underinsured, or living in poverty, the need to address medical financial hardship is more urgent than ever, to ensure that all people have an equal opportunity for high quality cancer treatment and survival.
See related article by McLouth et al., p. 669
Breast Cancer Surgery Experiences and Outcomes in Sex and Gender Minority Individuals: A Systematic Review
Authors: Arthur EK , Ridgway E , Lee CN 
Published: April 2021

Abstract
Purpose of the study: The purpose of this study was to summarize and critique contemporary research describing the experiences and outcomes of sex and gender minority (SGM) individuals with breast cancer surgery through systematic literature review. Methods: We performed a comprehensive search using keywords and subject headings to elicit studies that addressed experiences and outcomes of SGM breast cancer survivors in PubMed, Embase, CINAHL, PsycINFO, and LGBT Life. Studies were included if (1) participants were breast cancer survivors who identified as sexual and gender minority (SGM) women or transgender men; (2) one or more of the following were reported: experiences, preferences, or needs related to breast cancer care or surgical treatment decision-making, as well as interactions with healthcare providers and support persons; (3) they were published in English; and (4) they were published in the last 20 years. Covidence® was used to document the inclusion/exclusion process. Included studies were assessed using The Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Qualitative Research. The authors performed thematic content analysis to identify emergent themes. Results: The search yielded 115 records, and seven studies were included in the final critical appraisal. All studies were qualitative with sample sizes ranging n=10–81, and quality scores ranged 6–8 out of 10. Studies were performed in the U.S. and Canada, and included sexual and gender diverse individuals. Major themes were identified: 1) surgical decision-making, 2) experiences of the post-surgical body, 3) information and support seeking, and 4) interactions with healthcare providers. Subthemes are explored, including body image vs. function, gender policing and politicizing of the body, and intersectionality. Conclusions: SGM breast cancer survivors have unique experiences of healthcare access, decision-making, and quality of life in survivorship. Researchers and clinicians must consider SGM breast cancer survivors' personal values and preferences for treatment, as well as their support network. Culturally sensitive healthcare provider interactions are critical for reducing health disparities in cancer care access and quality of life outcomes.
Circulating Inflammatory Proteins Associated with Dementia Risk in Older Adult Cancer Survivors in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Ugoji CC , Walker KA , Dean LT , Gross AL , Ballantyne CM , Butler K , Hoogeveen RC , Joshu C , Mosley TH , Prizment A , Sharrett AR , Tin A , Coresh J , Platz EA 
Published: April 2021

Abstract
Background Inflammation is linked to cognitive impairment (CI) in cancer survivors. But its role in survivors who develop dementia is unclear. Methods We evaluated dementia risk per log2 increase in 580 inflammatory proteins in 391 dementia-free long-term (&gt;5 yrs) older adult survivors of prostate, breast, colorectal, endometrial and bladder cancers in ARIC. Plasma inflammatory proteins were measured at visit 5 (2011–13) using SomaScan, an aptamer-based assay. Participants were followed through visit 6 (2016–17). We adjusted for age, sex, race, years since cancer diagnosis, ApoE4, renal function, anti-inflammatory drug use and cancer/CVD shared risk factors. We also investigated proteins associated with dementia in 196 prostate and 135 breast cancer survivors, accounting for multiple testing by Bonferroni correction and false discovery rate Q-values. Results Survivors were 20% Black, 54% male, mean age of 76yrs, median time since diagnosis of 12yrs. 67 dementia cases occurred in 1780 person-yrs. After FDR correction, 73 proteins were statistically significantly associated with dementia risk. TMEM87B, CD9, RAF1, IL21sR and FGF7 showed the strongest positive association, with HR:3.4–3.8 per Δlog2. LAIR1, IL36B, FGFR3, FLRT3 and LSAMP showed the strongest inverse association, HR:0.1–0.2. Only syntaxin12 (STX12) was significant after Bonferroni correction, HR:2.2. Associations of some inflammatory proteins with dementia were cancer site-specific. In breast cancer survivors, IL6, HMGA2, IFN-GR1, SAP, TNFRSF1a, TNFRSF14, and TNFAIP3, were associated with dementia. STX12 and RAF1 were significantly associated (q &lt;0.05) with dementia in all, prostate, and breast cancer survivors. Conclusion Inflammatory proteins were associated with dementia in older adult cancer survivors, including STX12 (enriched in brain, linked to WNT signaling loss, exerts CNS effects) and RAF1 (regulates MAPK/ERK pathway, previously identified in dementia etiology). Inflammatory proteins previously associated with CI, including TNF proteins/receptors, were associated with dementia in breast cancer survivors. If confirmed, these proteins may warrant evaluation as potential biomarkers for dementia risk screening, and possibly preventive/therapeutic targets in cancer survivors. Funding: NHLBI, NCI, NPCR
Early-life Exposures and Age at Breast Development in the Sister Study Cohort
Authors: Goldberg M , D'Aloisio AA , O'Brien KM , Zhao S , Sandler DP 
Published: April 2021

Abstract
Purpose: Early age at breast development (thelarche) has been associated with increased breast cancer risk. Average age at thelarche has declined over time, but there are few established risk factors for early thelarche. We examined associations between pre- and postnatal exposures and age at thelarche in a U.S. cohort of women born between 1928 and 1974. Methods: Breast cancer-free women ages 35–74 years who had a sister diagnosed with breast cancer were enrolled in the Sister Study from 2003–2009 (N = 50,884). At enrollment, participants reported their age at thelarche, which we categorized as early (≤10 years), average (11–13 years), and late (≥14 years), as well as information on early-life exposures. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for early and late thelarche relative to average age at thelarche using polytomous logistic regression for each early-life exposure, adjusted for birth cohort, race/ethnicity and family income level in childhood. We examined modification by birth cohort, race/ethnicity, family income, relative weight at age 10, and extent of breast cancer family history through stratification. Results: Early thelarche was more common in recent birth cohorts and among non-Hispanic Black and Hispanic women. Early thelarche (≤10 years) was associated with multiple prenatal exposures: gestational hypertensive disorder (OR = 1.25, 95% CI, 1.09–1.43), maternal diethylstilbestrol (DES) use (OR = 1.23, 95% CI, 1.04–1.45), maternal smoking during pregnancy (OR = 1.20, 95% CI, 1.13–1.27), and young maternal age (OR 1.30, 95% CI, 1.16–1.47 for &lt;20 vs 25–29 years). Being firstborn was also associated with early thelarche (OR = 1.25, 95% CI, 1.17–1.33). Low birthweight (&lt;2500 vs 2500–3999g) was suggestively associated with both early (OR = 1.06, 95% CI, 0.96–1.17) and late (OR = 1.15, 95% CI, 1.05–1.25) thelarche, as was use of soy formula in infancy (Early: OR = 1.10, 95% CI, 0.93–1.30; Late: OR = 1.07, 95% CI, 0.92–1.25). Patterns were generally similar across strata of modifiers of interest. Conclusion: Associations between pre- and postnatal exposures and age at thelarche suggest that the early-life environment may influence breast development and therefore may also affect breast cancer risk by altering the timing of pubertal breast development.
Ethnic Disparities in Methotrexate Neurotoxicity among Children and Adolescents with Acute Lymphoblastic Leukemia
Authors: Scheurer ME , Brown AL , Taylor OA , Bernhardt MB , Dreyer ZA , Brackett J , Mitby PA , Hooke MC , Moore IM , Hockenberry MJ , Rabin KR , Lupo PJ 
Published: April 2021

Abstract
Purpose of study: To identify factors related to the increased risk of neurotoxicity in children with acute lymphoblastic leukemia (ALL) after treatment with the antifolate agent methotrexate (MTX), a critical component of curative protocols. Methods: We analyzed the incidence of and factors associated with acute MTX neurotoxicity (neurologic episode within 14d of dose that resulted in treatment modification) in a multi-site study of 280 (48% Latino) newly diagnosed (between 2012–2017) patients treated on recent pediatric ALL protocols. We examined the effects of genetic ancestry and single nucleotide variants in a subset of 190 patients with genotype data. Results: MTX neurotoxicity occurred in 22% of Latino compared to 7% of non- Latino patients; a nearly 2.5-fold increased risk after accounting for other clinical and demographic factors. Patients with neurotoxicity received fewer total MTX doses, and their risk for relapse was 2-fold higher than patients who did not experience neurotoxicity. We also found that 42% of our Latino patients who experienced a first neurotoxic event went on to have additional events, compared to only 21% of non-Latino patients. The proportion of genetic variation that co-segregates with Native American ancestry was overrepresented in individuals with MTX-related neurotoxicity (mean = 35%) vs without neurotoxicity (mean = 23%, p = 0.025). In multivariable models accounting for sex, age at diagnosis, and treatment risk group, every 10% increase in the proportion of Native American genetic ancestry was associated with a 16% increase in neurotoxicity incidence (HR = 1.16; 95% CI: 1.02–1.32). Our data also suggest that Latinos are at higher risk for first (OR = 3.51, p = 0.02) and subsequent (OR = 6.10, p = 0.04) neurotoxic events associated with a missense variant in TCF12, which is more common in admixed Latino (23%) compared to European (3%) or African (&lt;1%) populations. Conclusions: MTX neurotoxicity is more common among Latino children and adolescents with ALL, compromises treatment efficacy, and may contribute to disparities in ALL relapse and survival. Our findings to date highlight that differences in inherited genetic variation, which segregate with ancestry, likely contribute to disparities in the incidence of treatment-related neurotoxicity.
Historical Housing Discrimination, Indicators of Disinvestment, and Breast Cancer Outcomes Nearly a Century Later
Authors: Plascak JJ , Roy J , Stroup AM , Beyer K , Rundle AG , Mooney SJ , Jacob G , Llanos AAM 
Published: April 2021

Abstract
Purpose: We investigated associations between 1930's era records of mortgage lending discrimination (i.e., “redlining”), a present-day indicator of disinvestment (i.e., residential physical disorder), and tumor clinicopathologic features (stage, grade, subtype) and survival among women diagnosed with breast cancer in New Jersey. Methods: Historical, Home Owners' Loan Corporation (HOLC) data were recently geocoded from the University of Richmond's Digital Scholarship Lab. Risk grades of ‘A'/‘Best', ‘B'/‘Still Desirable', ‘C'/‘Definitely Declining', and ‘D'/‘Hazardous' – available for six metropolitan areas of New Jersey – were collapsed into C/D (‘redlined') and A/B (‘not redlined') for analyses. Sociodemographics (age, race, ethnicity, geocoded residential address, date of diagnosis), tumor features (stage at diagnosis, grade, subtype), and vital status (cause and date of death) were ascertained from the New Jersey State Cancer Registry for all primary, histologically-confirmed, invasive breast cancer cases diagnosed between 2008 and 2017, among female residents of a HOLC-graded area, who were ≥ 20 years at diagnosis (N = 11,980). Residential physical disorder was estimated based on residential address at diagnosis using spatial prediction models of virtually audited Google Street View scenes of 6,132 locations. Logistic regression models of tumor features and accelerated failure time models of survival time to BrCa-specific death (follow-up through 2019) were built to investigate associations with redlining and physical disorder, while controlling for covariates. Results: There were 1,215 BrCa-specific deaths, a median follow-up time of 5.1 years, and a 5-year survival of 89.6%. Living in a historically redlined neighborhood was associated with higher odds of late-stage and high-grade tumors. Living in a non-redlined neighborhood was associated with a 47.5% (95% CI: 20.1, 79.8) longer survival time in low physical disorder areas. This survival benefit decreased as physical disorder increased. Conclusions: Historical racial housing discrimination might interact with present-day measures of disinvestment to influence BrCa survival. Future studies should collect more comprehensive data including potential confounders and residential history.
Impact of COVID-19 Pandemic on Healthcare Delivery, Behavioral Outcomes, and Financial Stress in 1,253 Individuals with Cancer at Huntsman Cancer Institute (HCI)
Authors: Peoples AR , Himbert C , Hathaway CA , Kirchhoff AC , Ose J , Lin T , Colman H , Jones KB , Akerley WL , Grossman D , Hunt JP , Penedo FJ , Siegel EM , Ulrich CM , Tworoger SS 
Published: April 2021

Abstract
Purpose: The COVID-19 pandemic has substantially changed social practices, economic stability, and access to medical care that may significantly affect cancer patients, especially those undergoing active treatment. We characterized the pandemic's influence on healthcare delivery, behavioral health, and financial stress in cancer patients. Methods: We included data from N = 1,253 adult cancer patients, who visited HCI in the last 4 years, consented to the Total Cancer Care study, and completed a COVID-19 survey as part of the COPES consortium. The survey was administered between Aug and Sept 2020 and included questions on change/cancellation of medical visits, change in exercise and alcohol consumption, daily life, social interactions, and financial stress since March 2020. Results: The cohort's mean age was 60.4 (19–92) years, with 54% female, 68% non-Hispanic White, 41% retired, 43% employed full or part-time, and 24% living in rural counties. Among the 27% of patients who reported receiving current treatment at HCI, 30% had to change or cancel a medical visit due to the pandemic, with 2% reported a change/cancellation in a biopsy, surgery, radiotherapy, and chemotherapy; 5% reported a change/cancellation in imaging; and 3% and 23% reported a change/cancellation in cancer screening and doctor's visit, respectively. 18% rescheduled an appointment to a telehealth visit. Changes in exercise habits due to the pandemic were common (47%), with 10% no longer exercising regularly, 21% exercising less, and 11% exercising more than before. 5% reported increased alcohol consumption, while 6% reported a decrease. Most patients (84%) experienced a change in their daily lives (ranging from somewhat to a lot of change). 69% had fewer social interactions, and 49% reported financial stress due to the pandemic, with 11% reporting being quite a bit/very much financially stressed. Conclusions: These findings suggest that within approximately the first 6 months, the COVID-19 pandemic had a substantial impact on cancer patients' lives, with adverse effects on health behaviors and financial stress. Healthcare delivery continued for essential cancer care but was disrupted for other services, such as cancer screening. Further analyses are underway. Funding: U01CA206110 and R01CA211705.
Implementation of QI Coaching Versus Physician Communication Training for Improving HPV Vaccination in Primary Care: A Randomized Implementation Trial
Authors: Grabert BK , Kurtzman R , Heisler-MacKinnon J , Leeman J , Bjork A , Alton Dailey S , Brewer NT , Gilkey MB 
Published: April 2021

Abstract
Purpose of study: Health departments (HDs) are at the forefront of efforts to improve HPV vaccine uptake in the US. Most notably, HD staff routinely conduct in-person quality improvement (QI) coaching to help primary care clinics improve their vaccine delivery systems. Some HDs also engage outside experts to conduct remote physician communication training to help vaccine prescribers recommend HPV vaccine more effectively. To guide future HD programming, we sought to understand the implementation strengths and challenges of QI coaching and physician communication training. Methods: In a cluster randomized trial, we allocated 855 primary care clinics in 3 geographically-diverse US states to receive: 1) QI coaching; 2) physician communication training; or 3) both interventions combined. In each arm, we assessed adoption (or the % of clinics receiving the allocated intervention out of those invited), contacts per clinic (mean number of contacts needed to successfully schedule one clinic), reach (median number of total staff and prescriber participants per clinic), and delivery cost. Results: More clinics adopted QI coaching than communication training or the combined intervention (63% vs 16% and 12%, both p&lt;.05). Recruiting clinics into QI coaching sessions required fewer contacts than communication training or the combined intervention (mean = 4.7 vs 29.0 and 40.4, both p&lt;.05). In contrast, communication training and the combined intervention reached more total staff per clinic than QI coaching (median = 5 and 5 vs 2, both p&lt;.05), including more prescribers per clinic (2 and 2 vs 0, both p&lt;.05). QI coaching cost $439 per clinic on average, including costs incurred from follow up ($129/clinic), session preparation ($73/clinic), and travel ($69/clinic). Communication training cost $1,287 per clinic, with most cost incurred from clinic recruitment ($653/clinic). Conclusions: QI coaching was lower cost and had higher adoption, but remote communication training achieved higher reach, including to highly influential vaccine prescribers. Thus, communication training is a promising intervention for improving HPV vaccine delivery, although care will be needed to overcome substantial challenges to clinic recruitment.