bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression and subcellular localization of Discoidin Domain Receptor 1 (DDR1) define prostate cancer aggressiveness
Authors: Bonfil R. Daniel , Chen Wei , Vranic Semir , Sohail Anjum , Shi Dongping , Jang Hyejeong , Kim Hyeong-Reh , Prunotto Marco , Fridman Rafael
Published: September 2021

Background

The Discoidin Domain Receptor 1 (DDR1) is one of the two members of a unique family of receptor tyrosine kinase receptors that signal in response to collagen, which has been implicated in cancer progression. Here, we examined the expression of DDR1 in prostate cancer (PCa), and assessed its potential value as a prognostic marker, as a function of grade, stage and other clinicopathologic parameters.

Methods

We investigated the association between the expression level and subcellular localization of DDR1 protein and PCa aggressiveness by immunohistochemistry, using tissue microarrays (TMAs) encompassing 200 cases of PCa with various Gleason scores (GS) and pathologic stages with matched normal tissue, and a highly specific monoclonal antibody.

Results

DDR1 was found to be localized in the membrane, cytoplasm, and nuclear compartments of both normal and cancerous prostate epithelial cells. Analyses of DDR1 expression in low GS (≤ 7[3 + 4]) vs high GS (≥ 7[4 + 3]) tissues showed no differences in nuclear or cytoplasmic DDR1in either cancerous or adjacent normal tissue cores. However, relative to normal-matched tissue, the percentage of cases with higher membranous DDR1 expression was significantly lower in high vs. low GS cancers. Although nuclear localization of DDR1 was consistently detected in our tissue samples and also in cultured human PCa and normal prostate-derived cell lines, its presence in that site could not be associated with disease aggressiveness. No associations between DDR1 expression and overall survival or biochemical recurrence were found in this cohort of patients.

Conclusion

The data obtained through multivariate logistic regression model analysis suggest that the level of membranous DDR1 expression status may represent a potential biomarker of utility for better determination of PCa aggressiveness.
Reducing stiffness of shock-absorbing pylon amplifies prosthesis energy loss and redistributes joint mechanical work during walking
Authors: Maun Jenny Anne , Gard Steven A. , Major Matthew J. , Takahashi Kota Z.
Published: September 2021

Background

A shock-absorbing pylon (SAP) is a modular prosthetic component designed to attenuate impact forces, which unlike traditional pylons that are rigid, can compress to absorb, return, or dissipate energy. Previous studies found that walking with a SAP improved lower-limb prosthesis users’ comfort and residual limb pain. While longitudinal stiffness of a SAP has been shown to affect gait kinematics, kinetics, and work done by the entire lower limb, the energetic contributions from the prosthesis and the intact joints have not been examined. The purpose of this study was to determine the effects of SAP stiffness and walking speed on the mechanical work contributions of the prosthesis (i.e., all components distal to socket), knee, and hip in individuals with a transtibial amputation.

Methods

Twelve participants with unilateral transtibial amputation walked overground at their customary (1.22 ± 0.18 ms−1) and fast speeds (1.53 ± 0.29 ms−1) under four different levels of SAP stiffness. Power and mechanical work profiles of the leg joints and components distal to the socket were quantified. The effects of SAP stiffness and walking speed on positive and negative work were analyzed using two-factor (stiffness and speed) repeated-measure ANOVAs (α = 0.05).

Results

Faster walking significantly increased mechanical work from the SAP-integrated prosthesis (p < 0.001). Reducing SAP stiffness increased the magnitude of prosthesis negative work (energy absorption) during early stance (p = 0.045) by as much as 0.027 Jkg−1, without affecting the positive work (energy return) during late stance (p = 0.159), suggesting a damping effect. This energy loss was partially offset by an increase in residual hip positive work (as much as 0.012 Jkg−1) during late stance (p = 0.045). Reducing SAP stiffness also reduced the magnitude of negative work on the contralateral sound limb during early stance by 11–17% (p = 0.001).

Conclusions

Reducing SAP stiffness and faster walking amplified the prostheses damping effect, which redistributed the mechanical work, both in magnitude and timing, within the residual joints and sound limb. With its capacity to absorb and dissipate energy, future studies are warranted to determine whether SAPs can provide additional user benefit for locomotor tasks that require greater attenuation of impact forces (e.g., load carriage) or energy dissipation (e.g., downhill walking).
Revisiting genetic artifacts on DNA methylation microarrays exposes novel biological implications
Authors: Planterose Jiménez Benjamin , Kayser Manfred , Vidaki Athina
Published: September 2021

Background

Illumina DNA methylation microarrays enable epigenome-wide analysis vastly used for the discovery of novel DNA methylation variation in health and disease. However, the microarrays’ probe design cannot fully consider the vast human genetic diversity, leading to genetic artifacts. Distinguishing genuine from artifactual genetic influence is of particular relevance in the study of DNA methylation heritability and methylation quantitative trait loci. But despite its importance, current strategies to account for genetic artifacts are lagging due to a limited mechanistic understanding on how such artifacts operate.

Results

To address this, we develop and benchmark UMtools, an R-package containing novel methods for the quantification and qualification of genetic artifacts based on fluorescence intensity signals. With our approach, we model and validate known SNPs/indels on a genetically controlled dataset of monozygotic twins, and we estimate minor allele frequency from DNA methylation data and empirically detect variants not included in dbSNP. Moreover, we identify examples where genetic artifacts interact with each other or with imprinting, X-inactivation, or tissue-specific regulation. Finally, we propose a novel strategy based on co-methylation that can discern between genetic artifacts and genuine genomic influence.

Conclusions

We provide an atlas to navigate through the huge diversity of genetic artifacts encountered on DNA methylation microarrays. Overall, our study sets the ground for a paradigm shift in the study of the genetic component of epigenetic variation in DNA methylation microarrays.
Chromatin accessibility and regulatory vocabulary across indicine cattle tissues
Authors: Alexandre Pâmela A. , Naval-Sánchez Marina , Menzies Moira , Nguyen Loan T. , Porto-Neto Laercio R. , Fortes Marina R. S. , Reverter Antonio
Published: September 2021

Background

Spatiotemporal changes in the chromatin accessibility landscape are essential to cell differentiation, development, health, and disease. The quest of identifying regulatory elements in open chromatin regions across different tissues and developmental stages is led by large international collaborative efforts mostly focusing on model organisms, such as ENCODE. Recently, the Functional Annotation of Animal Genomes (FAANG) has been established to unravel the regulatory elements in non-model organisms, including cattle. Now, we can transition from prediction to validation by experimentally identifying the regulatory elements in tropical indicine cattle. The identification of regulatory elements, their annotation and comparison with the taurine counterpart, holds high promise to link regulatory regions to adaptability traits and improve animal productivity and welfare.

Results

We generate open chromatin profiles for liver, muscle, and hypothalamus of indicine cattle through ATAC-seq. Using robust methods for motif discovery, motif enrichment and transcription factor binding sites, we identify potential master regulators of the epigenomic profile in these three tissues, namely HNF4, MEF2, and SOX factors, respectively. Integration with transcriptomic data allows us to confirm some of their target genes. Finally, by comparing our results with Bos taurus data we identify potential indicine-specific open chromatin regions and overlaps with indicine selective sweeps.

Conclusions

Our findings provide insights into the identification and analysis of regulatory elements in non-model organisms, the evolution of regulatory elements within two cattle subspecies as well as having an immediate impact on the animal genetics community in particular for a relevant productive species such as tropical cattle.
Response and oil degradation activities of a northeast Atlantic bacterial community to biogenic and synthetic surfactants
Authors: Nikolova Christina N. , Ijaz Umer Zeeshan , Magill Clayton , Kleindienst Sara , Joye Samantha B. , Gutierrez Tony
Published: September 2021

Background

Biosurfactants are naturally derived products that play a similar role to synthetic dispersants in oil spill response but are easily biodegradable and less toxic. Using a combination of analytical chemistry, 16S rRNA amplicon sequencing and simulation-based approaches, this study investigated the microbial community dynamics, ecological drivers, functional diversity and robustness, and oil biodegradation potential of a northeast Atlantic marine microbial community to crude oil when exposed to rhamnolipid or synthetic dispersant Finasol OSR52.

Results

Psychrophilic Colwellia and Oleispira dominated the community in both the rhamnolipid and Finasol OSR52 treatments initially but later community structure across treatments diverged significantly: Rhodobacteraceae and Vibrio dominated the Finasol-amended treatment, whereas Colwellia, Oleispira, and later Cycloclasticus and Alcanivorax, dominated the rhamnolipid-amended treatment. Key aromatic hydrocarbon-degrading bacteria, like Cycloclasticus, was not observed in the Finasol treatment but it was abundant in the oil-only and rhamnolipid-amended treatments. Overall, Finasol had a significant negative impact on the community diversity, weakened the taxa-functional robustness of the community, and caused a stronger environmental filtering, more so than oil-only and rhamnolipid-amended oil treatments. Rhamnolipid-amended and oil-only treatments had the highest functional diversity, however, the overall oil biodegradation was greater in the Finasol treatment, but aromatic biodegradation was highest in the rhamnolipid treatment.

Conclusion

Overall, the natural marine microbial community in the northeast Atlantic responded differently to crude oil dispersed with either synthetic or biogenic surfactants over time, but oil degradation was more enhanced by the synthetic dispersant. Collectively, our results advance the understanding of how rhamnolipid biosurfactants and synthetic dispersant Finasol affect the natural marine microbial community in the FSC, supporting their potential application in oil spills.
A nonparametric probabilistic method to enhance PGD solutions with data-driven approach, application to the automated tape placement process
Authors: Ghnatios Chady , Barasinski Anais
Published: September 2021

A nonparametric method assessing the error and variability margins in solutions depicted in a separated form using experimental results is illustrated in this work. The method assess the total variability of the solution including the modeling error and the truncation error when experimental results are available. The illustrated method is based on the use of the PGD separated form solutions, enriched by transforming a part of the PGD basis vectors into probabilistic one. The constructed probabilistic vectors are restricted to the physical solution’s Stiefel manifold. The result is a real-time parametric PGD solution enhanced with the solution variability and the confidence intervals.
Behavioural and energetic consequences of competition among three overwintering swan (Cygnus spp.) species
Authors: Wood Kevin A. , Newth Julia L. , Hilton Geoff M. , Rees Eileen C.
Published: September 2021

Background

Winter numbers of the northwest European population of Bewick’s Swans (Cygnus columbianus bewickii) declined recently by c. 40%. During the same period, numbers of two sympatric and ecologically-similar congeners, the Mute Swan (Cygnus olor) and Whooper Swan (Cygnus cygnus) showed increases or stability. It has been suggested that these opposing population trends could have a causal relationship, as Mute and Whooper Swans are larger and competitively dominant to Bewick’s Swans in foraging situations. If so, effects of competition of Mute and Whooper Swans on Bewick’s Swans should be detectable as measurable impacts on behaviour and energetics.

Methods

Here, we studied the diurnal behaviour and energetics of 1083 focal adults and first-winter juveniles (“cygnets”) of the three swan species on their winter grounds in eastern England. We analysed video recordings to derive time-activity budgets and these, together with estimates of energy gain and expenditure, were analysed to determine whether individual Bewick’s Swans altered the time spent on key behaviours when sharing feeding habitat with other swan species, and any consequences for their energy expenditure and net energy gain.

Results

All three swan species spent a small proportion of their total time (0.011) on aggressive interactions, and these were predominantly intraspecific (≥ 0.714). Mixed-effects models indicated that sharing feeding habitat with higher densities of Mute and Whooper Swans increased the likelihood of engaging in aggression for cygnet Bewick’s Swans, but not for adults. Higher levels of interspecific competition decreased the time spent by Bewick’s Swan cygnets on foraging, whilst adults showed the opposite pattern. When among low densities of conspecifics (< c. 200 individuals/km2), individual Bewick’s Swans spent more time on vigilance in the presence of higher densities of Mute and Whooper Swans, whilst individuals within higher density Bewick’s Swan flocks showed the opposite pattern. Crucially, we found no evidence that greater numbers of interspecific competitors affected the net energy gain of either adult or cygnet Bewick’s Swans.

Conclusions

We found no evidence that Bewick’s Swan net energy gain was affected by sharing agricultural feeding habitat with larger congeners during winter. This was despite some impacts on the aggression, foraging and vigilance behaviours of Bewick’s Swans, especially among cygnets. It is unlikely therefore that competition between Bewick’s Swans and either Mute or Whooper Swans at arable sites in winter has contributed to the observed decline in Bewick’s Swan numbers. Further research is needed, however, to test for competition in other parts of the flyway, including migratory stopover sites and breeding areas.
The migration ban policy cycle: a comparative analysis of restrictions on the emigration of women domestic workers
Authors: Shivakoti Richa , Henderson Sophie , Withers Matt
Published: September 2021

Policies banning women domestic workers from migrating overseas have long been imposed by labour-sending states in the Indo-Pacific region. This article presents the complexities surrounding such bans by developing an overarching model of a migration ban policy cycle, which provides a theoretical framework for understanding the circumstances under which migration bans arise and play out. It examines the history of migration bans for four prominent labour-sending states – Indonesia, Nepal, the Philippines and Sri Lanka - to assess the causes, outcomes and extent of regional convergence of these policies. In doing so, we uncover two prominent policy narratives. The first involves labour diplomacy, where countries employ bans to negotiate superior working conditions and rights for migrant workers. The second concerns paternalist states as ‘protector’, where states are primarily motivated to reaffirm traditional gender norms. We conclude that migration bans have been most effective, both in curbing departures and achieving desired outcomes, when they are primarily motivated by labour issues and not gender politics. Nevertheless, even when used as a form of diplomatic negotiation, migration bans heighten the vulnerability of domestic workers to exploitation by pushing them into irregular pathways fraught with risk.
Concentrations and pharmacokinetic parameters of MRI and SPECT hepatobiliary agents in rat liver compartments
Authors: Pastor Catherine M. , Joly Florian , Vilgrain Valérie , Millet Philippe
Published: September 2021

Background

In hepatobiliary imaging, systems detect the total amount of agents originating from extracellular space, bile canaliculi, and hepatocytes. They add in situ concentration of each compartment corrected by its respective volume ratio to provide liver concentrations. In vivo contribution of each compartment to liver concentration is inaccessible. Our aim was to quantify the compartmental distribution of two hepatobiliary agents in an ex vivo model and determine how their liver extraction ratios and cholestasis (livers lacking canalicular transporters) might modify it.

Methods

We perfused labelled gadobenate dimeglumine (Bopta, 200 μM, 7% liver extraction ratio) and mebrofenin (Meb, 64 μM, 94% liver extraction ratio) in normal (n = 18) and cholestatic (n = 6) rat livers. We quantified liver concentrations with a gamma counter placed over livers. Concentrations in hepatocytes and bile canaliculi were calculated. Mann-Whitney and Kruskal-Wallis tests were used.

Results

Hepatocyte concentrations were 2,043 ± 333 μM (Meb) versus 360 ± 69 μM (Bopta, p < 0.001). Meb extracellular concentrations did not contribute to liver concentrations (1.3 ± 0.3%). The contribution of Bopta extracellular concentration was 12.4 ± 1.9% (p < 0.001 versus Meb). Contribution of canaliculi was similar for both agents (16%). Cholestatic livers had no Bopta in canaliculi but their hepatocyte concentrations increased in comparison to normal livers.

Conclusion

Hepatocyte concentrations are correlated to liver extraction ratios of hepatobiliary agents. When Bopta is not present in canaliculi of cholestatic livers, hepatocyte concentrations increase in comparison to normal livers. This new understanding extends the interpretation of clinical liver images.
A Framework of College Student Buy-in to Evidence-Based Teaching Practices in STEM: The Roles of Trust and Growth Mindset
Authors: Wang Cong , Cavanagh Andrew J. , Bauer Melanie , Reeves Philip M. , Gill Julia C. , Chen Xinnian , Hanauer David I. , Graham Mark J.
Published: September 2021

This investigation tests a college science, technology, engineering, and mathematics (STEM) student buy-in framework and contributes to understanding the social and cognitive factors influencing students in evidence-based teaching contexts. Students’ level of commitment to instructors’ teaching practices can be key to attaining many desired student outcomes of undergraduate STEM education reform.
Student-Authored Scientist Spotlights: Investigating the Impacts of Engaging Undergraduates as Developers of Inclusive Curriculum through a Service-Learning Course
Authors: Aranda Maurina L. , Diaz Michelle , Mena Lorenzo Gastelum , Ortiz Jocelyn I. , Rivera-Nolan Christian , Sanchez Daniela C. , Sanchez Melissa J. , Upchurch Allison M. , Williams Carleigh S. , Boorstin Stephanie N. , Cardoso Laura M. , Dominguez Matthew , Elias Sarah , Lopez Elmer E. , Ramirez Ruby E. , Romero Paola Juliet , Tigress Falina Nicole , Wilson Jenee Alexandra , Winstead Ryan , Cantley Jason T. , Chen Joseph C. , Fuse Megumi , Goldman Michael A. , Govindan Brinda , Ingmire Peter , Knight Jonathan D. , Pasion Sally G. , Pennings Pleuni S. , Sehgal Ravinder N. M. , de Vera Patricia Tiongco , Kelley Loretta , Schinske Jeffrey N. , Riggs Blake , Burrus Laura W. , Tanner Kimberly D.
Published: September 2021

The impact of student-authored Scientist Spotlights was investigated within the context of a service-learning course engaging students in STEM curricular reform efforts. Student-authored Scientists Spotlights significantly shifted peers’ perceptions of scientists across all demographic groups, as well as student authors’ own relatability to and stereotypes about scientists.
Evaluating health disparities in access to genomic testing for metastatic non-small cell lung cancer patients.
Authors: Yoon Brian , Weeraratne Dilhan , Arriaga Yull Edwin , Huang Hu , Osterman Travis John
Published: September 2021

113

Background: Over the past decade, genomic testing has become standard of care for metastatic non-small cell lung cancer (NSCLC). These tests qualify patients for additional anti-cancer therapies and should be performed in all patients. Small scale studies at the institutional level have revealed that there may be disparities in genomic testing in NSCLC and not all patients may have similar access to care. In this study, we use the IBM Explorys Electronic Health Record (EHR) database to conduct a nationwide retrospective, observational study to understand how gender, race, insurance type, and spoken language impacts the rate of genomic testing in metastatic NSCLC patients. Methods: From Jan 1st, 2015 to Dec 31st, 2020, the IBM Explorys EHR database comprised 128,119 lung cancer patients using the SNOMED-CT concept of Primary Malignant Neoplasm of the Lung (CID 93880001). As structured staging information was not available, metastatic NSCLC patients were imputed by removing patients who received thoracic surgeries (presumably stage I or II) and those who received radiation therapy (presumably stage III). Following imputation, 120,470 patients with metastatic NSCLC were queried for testing for EGFR, ALK, ROS1, and/or RET. Odds ratios and chi-squared tests were computed for gender, race, insurance type, and spoken language comparing patients that received genomics testing to those who did not. Results: Genomic testing was taken significantly more by male patients (OR: 1.35, p<0.0001), and by Caucasian patients (OR: 1.39, p<0.0001). Compared to the public insurance plans, the genomic testing was significantly more in patients with private insurance plans (OR: 2.48, p<0.0001) and self-pay patients (OR: 2.84, p<0.0001). Patients speaking English as their first language significantly less likely took genomic testing (OR: 0.81, p<0.05). Conclusions: This study aims to identify gaps in health disparities in gender, race/ethnicity, and insurance type for genomic testing that should be standard practice. Future investigation and attention to this issue appears necessary to begin moving from documenting disparities, to understanding them, and ultimately to reducing them.[Table: see text]
Patient- and provider-level predictors of mortality among patients with metastatic renal cell carcinoma receiving oral anticancer agents.
Authors: Spees Lisa , Dinan Michaela Ann , Jackson Bradford E. , Baggett Christopher , Wilson Lauren E. , Greiner Melissa A. , Kaye Deborah , Zhang Tian , George Daniel J. , Scales Charles D. , Pritchard Jessica , Leapman Michael S. , Gross Cary Philip , Wheeler Stephanie B.
Published: September 2021

116

Background: It is important to understand how emerging new therapies, such as oral anti-cancer agents (OAAs), diffuse across and can improve outcomes within real-world populations, which include age groups and racial groups not well-represented in clinical trials, such as people older than age 65 and Black patients. Our objectives were to examine whether disparities in mortality persist among patients with metastatic renal cell carcinoma (mRCC) receiving OAAs and whether these disparities may be partially explained by patient’s clinical characteristics or provider-level factors. Methods: We used linked state cancer registry data and multi-payer claims data to identify patients with mRCC who were diagnosed in 2004 through 2015 and had initiated an OAA and survived ≥ 90 days after initiating. Provider data were obtained from North Carolina Health Professions Data System and the National Plan & Provider Enumeration System. A patient’s modal provider was the provider most frequently on claims with a diagnosis code of RCC or metastatic cancer between 2 months prior to and 3 months following the index date. We estimated hazard ratios (HR) and corresponding 95% confidence limits (CL) using Cox proportional hazard models to evaluate which patient demographics, patient clinical characteristics, and provider-level factors were associated with 2-year all-cause mortality. Results: The cohort included 207 patients with mRCC. In unadjusted analyses, public insurance (Medicaid or Medicare), de novo metastatic diagnosis, frailty, polypharmacy, and a visit to a skilled nursing facility were associated with increased all-cause mortality. In multivariable models, clinical variables such as frailty (HR: 1.36, 95% CL: 1.11-1.67) and de novo metastatic diagnosis (HR: 2.63, 95%CL: 1.67-4.16) were associated with higher all-cause mortality. Additionally, Medicare-insured patients continued to have higher all-cause mortality compared to privately insured patients (HR: 2.35, 95% CL: 1.32-4.18). None of the provider-level covariates (i.e., specialization, experience, volume, or practice location) investigated were associated with all-cause mortality. Conclusions: Even when adjusting for age, frailty, and comorbidities, Medicare-insured patient had lower overall survival than privately-insured patients. Patient survival did not differ based on modal provider’s characteristics.
Analysis of racial disparities in time to treatment initiation and survival among patients with advanced cancers.
Authors: Zyczynski Teresa Maria , Smith Cardinale B. , Zhang Ying , Hao Yi
Published: September 2021

127

Background: Racial disparities in cancer care have received increased attention in recent years. One previously identified disparity is in the time to treatment initiation (TTI) – a factor closely associated with outcomes. While most research in the US to date has focused on the Medicaid and Medicare populations, this study examined disparities between different racial/ethnic groups in TTI and overall survival (OS) among patients with cancer managed in the community setting. Methods: Using the Flatiron Health electronic health record database, patients diagnosed with advanced non-small cell lung cancer (aNSCLC), metastatic colorectal cancer (mCRC), metastatic breast cancer (mBC), multiple myeloma (MM), advanced gastroesophageal cancer (aGastric), advanced urothelial cancer (aUL), metastatic renal cell carcinoma (mRCC) or advanced melanoma (aMel) and treated with first-line (1L) therapy, with ≥1 month of follow-up during 2014-2019, were included. Patient characteristics, TTI and outcomes were compared across race/ethnicity groups classified as White, Black, Asian and Hispanic/Latino/Other (Other). Results: A total of 81,543 patients were evaluated (37% aNSCLC, 19% mCRC, 15% mBC, 8% MM, 6% aGastric, 5.2% aUL, 5.0% mRCC and 4.1% aMel); 67% were White, 9% Black, 3% Asian and 11% Other. Overall, TTI was similar across race/ethnicity groups (median range 1.1–1.2 months), and 44% of all patients received treatment ≤30 days post-diagnosis. Overall Survival (months). Median OS varied by tumor and race/ethnicity groups (Table). However, multivariate Cox proportional hazards analysis showed that Asian patients had better OS than Black patients in many cancers (hazard ratio [HR] 0.8 aNSCLC, 0.75 mBC, 0.63 aGastric, 0.59 aUL, 0.81 mCRC, 0.68 mRCC), while White patients had better survival than Black patients in mBC (HR 0.8) and aGastric (HR 0.87). Conclusions: In this real-word analysis, TTI did not differ by race/ethnicity group for any of the cancers examined. However, some differences in OS emerged on multivariate analysis – this was longer in Asian than Black patients in aNSCLC, mBC, mCRC, aGastric, aUL and mRCC, and longer in White than Black patients in mBC and aGastric. Given the small sample size in some groups, further analyses are needed to determine the influence of race/ethnicity on cancer care and outcomes.[Table: see text]
The impact of COVID-19 on breast cancer care: Delays in screening.
Authors: Dhahri Amina , Tegene Teshome
Published: September 2021

130

Background: Breast cancer (BC) screening is an integral part of cancer prevention. COVID-19 posed multiple obstacles on ensuring continuity of cancer care. The short and long-term outcomes of the pandemic on BC screening is unknown. The purpose of this study is to examine the challenges the pandemic has on mammogram completion using a granular measure of social economic deprivation: Area deprivation index (ADI). Methods: A Retrospective cohort study was conducted at an academic hospital system at the epicenter of COVID-19 pandemic comparing BC screening rates during the year of 2019 (pre-COVID19) and 2020 (COVID-19). For the year 2020, only charts between January-February and July-December were reviewed. March-June period was avoided as the USA declared a national emergency and the American Cancer Society recommended to temporarily pause cancer screening. The outcome variable was mammogram completion. The predictor variables were: COVID-19 period, race, insurance, age and ADI. ADI is a validated dataset that ranks census block groups based on socioeconomic deprivation (SED). Chi-square and Wilcoxon rank sum test were used to compare categorical and continuous variables by receipt of mammography. A multivariate logistic regression was used for associations between mammogram completion and the predictor variables. Results: A total of 694 patients were deemed eligible for BC screening in the year of 2019 (394) and 2020 (300). During the follow up period, only 106 and 30 patients from the pre-COVID-19 and COVID-19 cohorts underwent BC screening, respectively. During the pandemic, 30/30 patients who completed their screening were African Americans and had a high SED. In a multivariable analysis, COVID-19 period is associated with 79% lower odds of mammogram completion (OR 0.21; 95% CI 0.13, 0.35). ADI and race were not associated with higher screening rates. Medicaid status is associated with higher odds of mammogram completion (OR 1.97; 95% CI 1.12, 3.47). Conclusions: COVID-19 caused significant disruption in BC screening. In an area with high SED and high COVID-19 infection rates, private insurance holders and white patients had low rates mammogram completion. One potential explanation is that these patients sought care elsewhere. [Table: see text]
Preference-weighted quality of life: Findings from the Selenium and Vitamin E Cancer Prevention Trial (SELECT).
Authors: Rock Matthew , Vaidya Riha , Till Cathee , Unger Joseph M. , Hershman Dawn L. , Maeng Daniel , Krouse Robert S.
Published: September 2021

144

Background: The differences in preference-weighted health-related quality of life (HRQOL) among racial and ethnic groups have been previously reported. The Selenium and Vitamin E Cancer Prevention Trial (SELECT) enrolled 35,533 men aged 50 years and older, among whom 20% were minorities. HRQOL, using the SF-36V, was examined for a subset of participants. Using these survey data, we examined the preference-weighted HRQOL differences across the racial/ethnic categories included in SELECT. Methods: SELECT participants who completed the SF-36V at baseline, and subsequently in at least one of years 1, 3, and 5 were included. We used the SF-6D to calculate an HRQOL score ranging between 0 (worst possible) and 1 (best possible) for every participant using data from the SF-36V. We modeled the association of race/ethnicity with SF-6D scores using a linear mixed model adjusting for demographic and clinical characteristics. Results: At baseline, 9,691 men were eligible for analysis. Hispanic and non-Hispanic white participants had higher unadjusted mean SF-6D scores than non-Hispanic Black participants at baseline and every subsequent time point (p<0.05; Table). Non-Hispanic white participants had lower mean scores than Hispanic participants at every time point after baseline. After adjusting for demographic and clinical characteristics there are statistically significant differences in HRQOL among all three groups. In particular, Hispanic participants had higher scores than white participants by.074 (p<.001),.076 (p<.001), and.039 (p<.001) in years 1, 3, and 5 after baseline. Conversely, compared to non-Hispanic White participants, non-Hispanic Black participants had lower scores by.009 (p=.004) and.008 (p=.02) in years 1 and 3 after baseline. Conclusions: In this sample of men enrolled in a prostate cancer chemoprevention trial, preference-weighted HRQOL using the SF-6D was higher for Hispanic men than for white and Black men, and lower for Black men than for white men. Understanding how individuals belonging to different racial and/or ethnic categories view their own HRQOL is necessary not only for delivering culturally competent care but also for conducting accurate cost effectiveness analyses of new interventions and programs. Further research that includes a sample with women, reports on more categories of race/ethnicity, and explores underlying potential cultural and social differences is necessary. [Table: see text]
Mobile app and wearable sensor-based patient and caregiver physical function and reported outcomes: A survey on oncologists’ current practices and preferences on data delivery.
Authors: Neeman Elad , Kubo Ai , Kurtovich Elaine , Aghaee Sara , Ramsey Maya , Yunis Reem , Kolevska Tatjana , Liu Raymond , Oakley-Girvan Ingrid
Published: September 2021

174

Background: Patient-reported outcomes and wearable sensor measures of physical function can predict important outcomes in oncology. However, mobile and wearable-sensor apps collect vast information from patients and caregivers; indiscriminate reporting may increase provider burden and reduce data reliance. This study aimed to assess medical oncologists’ current practices in utilizing such information, and their data delivery preferences. Methods: Cross-sectional survey delivered by email to all Kaiser Permanente Northern California medical oncologists, February-March 2021. Results: Thirty-eight oncologists (30% of 127) responded to the survey. Most agreed that to reduce adverse events (AEs) it is important for the oncologist to know about the following measures: 1) patient/caregiver-reported physical symptoms (92% responded either very important or essential); 2) patient/caregiver-reported physical function (87%); and 3) objective measures of gait/balance (55%) and physical activity (50%) obtained from wearable sensors. Similarly, most respondents strongly consider these data when making decisions related to treatment intent, dosage, or visit frequency. All respondents routinely rely on information from caregivers, and in case of a discrepancy, more rely on the caregiver’s report (45%) than the patient’s report (8%), and some seek additional objective information (26%). Most respondents indicated that they prefer to receive electronic information on physical function and symptoms only for “critical values” and/or to have the information accessible “as needed” in the electronic chart, but not actively delivered to them (Table). Conclusions: Oncologists believe that patient/caregiver reports of symptoms and physical function can predict AEs, and strongly rely on them in clinical decision making. The majority of respondents would like to have access to physical function/symptoms data from mobile/wearable apps, with more providers wishing to receive information prior to a visit and/or in case of “critical values”. These findings may inform future implementations of mobile/wearable technologies to track symptoms and function of cancer patients.[Table: see text]
“The waiting is the worst”: Development of a next day access (NDA) program for patients with cancer.
Authors: Mougalian Sarah Schellhorn , Shomsky Lisa , Major Campos Maureen , Chiang Anne C.
Published: September 2021

205

Background: Delays in access to treatment can cause anxiety and distress in patients with cancer. Time to treatment is increasing nationally, with retrospective analyses showing worse outcomes in patients with longer times to treatment initiation. It is critical to implement interventions that enhance navigation, improve access to cancer care, and eliminate operational and cultural barriers to prompt establishment of care and subsequent treatment initiation. We piloted a program for oncologic consultation within 1 business day in two subspecialty clinics and two network sites within our NCI designated comprehensive cancer center. Methods: Each pilot team created an implementation plan, with algorithms defining patients “eligible” for NDA. Generally, patients with a diagnosis or findings suggestive of cancer were eligible; full records were not required prior to the NDA visit. Interventions included adjusting physician templates and use of specific scripting to set expectations for patients prior to NDA visit. An institutional dashboard was created to display metrics--including new patient volume, % NDA visits, and reasons for non-utilization. Plan-Do-Study-Act cycles were completed every 2 weeks to assess data input/validity and address challenges. Patients seen via NDA completed a brief anonymous survey regarding their experience. Results: In 7 months, a total of 3107 new patients were seen across the 4 pilot sites, 900 (29.8%) of whom met “next day appropriate” criteria, and 370 (12%) of whom were seen via NDA. Uptake of NDA appointments was higher in patients with breast cancer. NDA patient satisfaction was extremely high, with 96% indicating that expectations were met or exceeded. Over half (56%) responded that a timely appointment was important when choosing a cancer center. The most common reasons patients were not seen via NDA included: specific provider requested (41%), specific date requested (23%), unavailable next day appointment (6%). Cultural barriers, particularly from treating physicians, included feeling that NDA appointments were inefficient with incomplete data, less time for clinical review, and increased burden due to last minute new patients; operational challenges included insufficient staffing and ensuring complete/accurate data collection. During 12/2019 – 2/2020, median time to first visit ranged from 17 to 36 days; median time to first visit decreased in 3 of the 4 pilot sites to 6-20 days 1 year later. Conclusions: Overall, 12% of patients were seen via NDA Success of this pilot required extensive effort to address change management and perceived barriers. Deployment in other disease teams and community sites is underway.[Table: see text]
Health-system specialty pharmacy impact on oral chemotherapy outcomes.
Authors: Sheikh Tehsinabanu , Wu Cindy , Kalfayan Niree , Sakamoto Leanne , Shane Rita
Published: September 2021

240

Background: Oral chemotherapy usage has grown significantly over the years as it provides a more convenient and less invasive administrative option for patients.In 2019, 89% of large hospitals owned and operated their own Health System Specialty Pharmacies (HSSP)1.Pharmacist-led medication therapy management services are crucial to provide patient education, monitoring of medication adherence and adverse effect management. With the current vertical integration of health plans and pharmacy benefit managers (PBMs) increasing their dominance over specialty dispensing channels, HSSP are often excluded from specialty networks. The objective of this study is to compare outcomes of oncology patients filling their oral chemotherapy at Cedars Sinai Medical Center (CSMC) Specialty Pharmacy versus those who are filling their medications at outside specialty pharmacies (OSP). Methods: Electronic health records were used to conduct a retrospective chart review of patients started on oral chemotherapy at CSMC between January 2019 to January 2021. Primary endpoints included time to treatment (TTT) and proportion of days covered (PDC). Secondary endpoints included drug-related problems (DRPs) and treatment-related ED visits and hospitalizations. DRPs were categorized by severity and type of intervention. Results: There were 100 patients included in the study: CSMC group (n = 50) and OSP group (n = 50). Patients in the CMSC group had significantly shorter TTT compared to OSP group (4 days vs. 9.5 days, respectively [P < 0.0026]), as well as a higher PDC (99.5% vs 91%, respectively [P < 0.0005]). Pharmacists identified and resolved 31 DRPs in CSMC arm with 19 DRPs categorized as serious and 1 DRP categorized as life-threatening. For the OSP group, 23 preventable DRPs were identified with 12 DRPs categorized as serious and 1 DRP categorized as life-threatening. There were no treatment-related ED visits or hospitalizations in either group. Conclusions: Patients filling their oral chemotherapy at CSMC Specialty Pharmacy had significantly quicker TTT and higher adherence rates as measured by PDC. Numerous DRPs were identified for OSP patients; potential pharmacist-interventions could have led to optimized and safer medication therapy if filled at a HSSP. Continued research comparing treatment outcomes and interventions made between HSSP and OSP can create a strong argument for health plans and PBMs to consider inclusion of HSSPs into their specialty networks. References: Pedersen CA, Schneider PJ, Ganio MC, Scheckelhoff DJ. ASHP national survey of pharmacy practice in hospital settings: Prescribing and transcribing—2019. American Journal of Health-System Pharmacy. 2020;77(13):1026-1050. doi:10.1093/ajhp/zxaa104
Health-related quality of life outcomes in adults with nonmuscle-invasive bladder cancer receiving a mitomycin-containing reverse thermal gel as a primary treatment (Optima II: Phase 2b, single-arm, open-label trial).
Authors: Stover Angela M. , Basak Ramsankar , Mueller Dana , Smith Angela B.
Published: September 2021

270

Background: The standard of care for low-grade non‐muscle‐invasive bladder cancer (LG NMIBC) is transurethral resection of the bladder tumor, which can worsen health‐related quality of life (HRQOL). The “OPTimized Instillation of Mitomycin for Bladder Cancer Treatment” (Optima II, clinicaltrials.gov: NCT03558503) is a Phase 2b, open label, single arm, multicenter trial evaluating a nonsurgical alternative as a primary treatment. Patients receive six weekly instillations of UGN-102, a mitomycin-containing reverse thermal gel with a sustained release time of up to 8 hours. We report on HRQOL changes between baseline and the primary endpoint of 3 months. Methods: A total of 63 patients enrolled in the Optima II trial at 20 sites in the U.S. and 2 sites in Israel between October 2018 and October 2020. Of the 63 patients enrolled, 44 were in the HRQOL cohort and completed a quarterly questionnaire. The QLQ-NMIBC24 has six subscales (urinary symptoms, malaise, future health worries, bloating and flatulence, sexual functioning, and male sexual problems) and five single items (intravesical treatment issues, sexual intimacy, worry about contaminating partner, sexual enjoyment, and female sexual problems) assessed with 24 items. Items were rescaled to 0-100 and reverse-coded so that higher scores indicate worse symptom burden. Longitudinal score changes were evaluated using the Sign test. We examined demographic and clinical characteristics associated with HRQOL change scores with regression modeling. A p-value of ≤0.01 was used. Results: The HRQOL cohort was 61% men, 57% age 65+, and 89% non-Hispanic White. Clinically, most LG NMIBC patients had multiple tumors (88%) with prior NMIBC episodes (77%), and two or more prior transurethral resection of bladder procedures (TURBT) (85%). Approximately half (55%) had their most recent TURBT surgery within 12 months of trial enrollment. No patients had missing HRQOL data at baseline or the primary end point of 3 months. The chemoablative reverse thermal gel used as a primary treatment did not cause decrements in patient-reported urinary symptoms, bloating/ flatulence, malaise, fever, general health, or future health worries. Sexual function mildly worsened between baseline and 3 months, and abated by 6 months. Demographic and clinical characteristics were not correlated with HRQOL change scores. By 3 months, 31/44 (70%) LG NMIBC patients achieved a complete response (negative endoscopic examination, cytology, and for-cause biopsy) and 0 experienced a recurrence. By 12 months, 8/44 (18%) patients had a recurrence. Conclusions: Adults with LG NMIBC in a Phase 2b trial who received a mitomycin-containing reverse thermal gel with sustained release maintained their HRQOL through 3 months. A Phase 3 trial is warranted. Clinical trial information: NCT03558503.
Assessing oncology patient and provider telehealth experience.
Authors: Eng Kelly , Donohue Caitlin C. , Wagner Andrew J. , Dougherty David W. , Salehi Elahi , Lowenstein Carol , Gundersen Daniel A. , Lederman Ruth , Kadish Sarah
Published: September 2021

284

Background: Due to COVID-19, telehealth volume at our comprehensive cancer center rose from less than 5% of exam visits to over 25% in April 2020. We sought to understand the experience of telehealth and compare it to in-person experiences for patients and providers (physicians, nurse practitioners, and physician assistants) to identify areas for improvement. Methods: A multidisciplinary team adapted our existing patient satisfaction survey to incorporate telehealth, defined as phone and video exam visits. A technology section was created to assess aspects unique to telehealth. Questions about the patient-provider experience were the same for telehealth and in-person visits. A provider experience survey was conducted during a two-week period in May and June 2020. The provider survey aligned questions with the patient survey to compare the perceptions of the provider-patient interaction. Results: Patient experience scores for in-person and telehealth visits were comparable, with a slightly higher mean score for in-person visits. The mean scores for patient perception of care given at our cancer center was 97.5 (n=11,969) and 96.9 (n=4670) and the likelihood to recommend was 97.8 (n=12,072) and 97.4 (n=4,398) for in-person and telehealth, respectively, between June and December 2020. Patient feedback prioritized addressing technical barriers. We implemented several interventions and increased the telehealth technology section mean scores from 93.2 (n=1,095) to 95.2 (n=700) between June and December 2020. When comparing the percent of respondents scoring good or very good, provider scores showed sizable gaps between in-person and telehealth experiences on all questions (see table). The question “degree to which the care team was well coordinated” had the largest difference between in-person and telehealth scores for both patients and providers. Several interventions to adapt staffing and workflows have been implemented to improve care telehealth coordination. Conclusions: While patients reported similar satisfaction between in-person and telehealth visits, increasing coordination remains vital to improving the experience for both patients and providers. Furthermore, understanding the gap in the provider experience between in-person and telehealth is critical for successful adoption of telehealth as a long-term strategy for healthcare delivery.[Table: see text]