bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nationally representative estimates of the participation of cancer patients in clinical research studies according to the commission on cancer.
Authors: Unger Joseph M. , Fleury Mark 
Published: September 2021

74 Background: The successful conduct of cancer clinical trials hinges on the willingness of patients to participate. The rate of adult clinical trial participation has been regarded as being < 5%. However, national estimates of trial participation are nearly two decades old, and no evidence based on original data sources has been examined for many years. Moreover, studies about trial participation have focused solely on enrollment to treatment trials, which does not reflect the willingness of patients to contribute to other key elements of clinical research, such as quality of life or biorepository studies. We determined inclusive, contemporary estimates of clinical trial participation for adults with cancer using a national sample of data from 1,200 institutions. Methods: The data were from the Commission on Cancer (CoC), a consortium of cancer-related organizations providing accreditation for both academic and community cancer care facilities across the U.S. CoC enrollment data represent 70% of all cases of cancer diagnosed each year. Deidentified, institution-level aggregate counts of annual enrollment to treatment, biorepository, diagnostic, economic, genetic, prevention, quality of life, registry, and screening studies were examined. Overall, study-type estimates for the period 2013-2017 were estimated. Multiple imputation by chained equations was used to account for missing data, with summary estimates calculated separately by type of program (e.g., NCI-designated cancer programs) and pooled. Results: Across the entire U.S. system, the estimated participation rate to cancer treatment trials was 6.3%. Enrollment to treatment trials was highest at NCI-designated comprehensive cancer centers (18.9%), while for community cancer programs (CCPs) and comprehensive CCPs, treatment trial rates were 4.4% and 3.6%, respectively. Nearly 1 in 7 patients participated in biorepository studies (13.4%), including 39.4% at NCI cancer centers. Patients participated in a wide variety of other study types, including registry (8.1%), prevention (6.4%), genetic (3.6%), quality of life (2.9%), economic (2.7%), diagnostic (2.7%), and screening studies (1.8%). At least 25.4% of adult cancer patients were estimated to participate in one or more cancer clinical research studies. Conclusions: In a first-time use of nationally representative enrollment data from the CoC, enrollment to cancer treatment trials was 6.3%, higher than historical estimates of < 5%. Patients participated in a diverse set of other study types, and taken together, at least one quarter of patients participated in a study. Contributions of adult patients with cancer to clinical research is much more comprehensive than previously understood.
Abrogation of survival disparity between insured and uninsured individuals after the USPSTF's 2012 prostate-specific antigen-based prostate cancer screening recommendation.
Authors: Kim Isaac Elijah , Kim Daniel D. , Kim Sinae , Singer Eric A. , Jang Thomas L. , Ghodoussipour Saum , Aron Monish , Kim Isaac Yi 
Published: September 2021

77 Background: In 2012, the U.S. Preventive Services Task Force (USPSTF) recommended against prostate-specific antigen (PSA)-based screening for prostate cancer. Studies have found that insured patients with prostate cancer have better outcomes than uninsured patients. We examined the recommendation’s effects on survival disparities based on insurance status as well as socioeconomic quintile, marital status, and housing (urban/rural). Methods: Using the SEER18 database, we examined prostate cancer-specific survival (PCSS) based on diagnostic time period and one of four factors: insurance status, socioeconomic quintile, marital status, and housing (urban/rural). The SEER-designated socioeconomic quintile was based on variables including median household income and education index. Patients were designated as belonging to the pre-USPSTF era if diagnosed in 2010-2012 or post-USPSTF era if diagnosed in 2014-2016. Disparities were measured with the Cox proportional hazards model. Results: We identified 282,994 patients diagnosed with prostate cancer. During the pre-USPSTF era, uninsured patients experienced worse PCSS compared to insured patients (adjusted HR 1.29, 95% CI 1.06-1.58, p = 0.01). This survival disparity narrowed during the post-USPSTF era as a result of decreased PCSS among insured patients combined with unchanged PCSS among uninsured patients. Moreover, the survival disparity was no longer observed during the post-USPSTF era (aHR 0.91, 95% CI 0.61-1.38, p = 0.67). The survival disparity based on socioeconomic quintile also narrowed but remained significant. In contrast, the survival disparity based on marital status widened, while housing status was not associated with survival disparities in either era. Conclusions: From the pre- to the post-USPSTF era, insured patients with prostate cancer observed a significant decrease in survival that made their survival outcomes similar to that of uninsured patients. Although the underlying reasons are not clear, the USPSTF’s 2012 PSA screening recommendation may have hindered insured patients from being regularly screened for prostate cancer and selectively led to worse outcomes for insured patients without improving the survival of uninsured patients.[Table: see text]
Association of rurality and race with surgical treatment and outcomes for nonmetastatic colon cancer.
Authors: Ramkumar Niveditta , Colla Carrie , Wang Qianfei , O'Malley James , Wong Sandra L. , Brooks Gabriel A. 
Published: September 2021

78 Background: Rural cancer patients face limited access to care due to greater travel distance and lack of specialty cancer care. Little is known about the intersection of rurality with well-documented racial disparities in colon cancer treatment and outcomes. Methods: We used fee-for-service Medicare claims to study patients age 65+ diagnosed with incident colon cancer without evidence of metastases who underwent cancer-directed surgery between 04/01/2016 and 09/30/2018. The primary exposure wasrurality of patient’s residence categorized as metropolitan (metro), micropolitan, and small town/rural. Outcomes were non-elective surgery (emergency department visit or transfer within 2 days prior to surgery), receipt of minimally invasive surgery (laparoscopic or robotic), 90-day surgical complications, and 90-day mortality. Logistic regression adjusted for patient demographics, cancer side (right vs left), comorbidities, and Area Deprivation Index. We assessed effect modification by race/ethnicity. Results: Of 57,710 patients with incident non-metastatic colon cancer, 37,691 (65%) underwent surgery. In this surgical cohort, small town/rural and micropolitan residents were more likely to be older, white, and Medicare-Medicaid dual-eligible than metro residents. After risk adjustment, patients in small town/rural areas had higher odds of non-elective surgery (OR =1.24, 95% CI:1.13-1.36) and lower odds of minimally invasive surgery (OR = 0.75, 95% CI:0.71-0.80) than patients living in metro areas. Similar results were seen for micropolitan areas. White rural patients had lower mortality than white urban patients, whereas black rural patients had higher mortality than black metro patients (see Table). Increasing area deprivation was associated with higher odds of non-elective surgery, surgical complications and mortality, and lower odds of minimally invasive surgery, even after adjusting for race and rurality. Conclusions: Small town/rural-residing Medicare beneficiaries undergoing surgery for non-metastatic colon cancer were less likely to receive optimal surgical management and had worse outcomes, especially among non-white patients. The compounded effect of rurality, race/ethnicity, and social deprivation should be incorporated in developing policies and interventions to improve care for rural cancer patients.[Table: see text]
Improving hematology/oncology clinical research recruitment via universal prescreening: The VA Connecticut (VACT) Cancer Center experience.
Authors: Xiang Jenny Jing , Roy Alicia , Summers Christine , Delvy Monica , O'Donovan Jessica Lee , Christensen John , Perry Lydia , Connery Donna , Rose Michal G. , Chao Herta H. 
Published: September 2021

79 Background: Patient-trial matching is a critical step in clinical research recruitment that requires extensive review of clinical data and trial requirements. Prescreening, defined as identifying potentially eligible patients using select eligibility criteria, may streamline the process and increase study enrollment. We describe the real-world experience of implementing a standardized, universal clinical research prescreening protocol within a VA cancer center and its impact on research enrollment. Methods: An IRB approved prescreening protocol was implemented at the VACT Cancer Center in March 2017. All patients with a suspected or confirmed diagnosis of cancer are identified through tumor boards, oncology consults, and clinic lists. Research coordinators perform chart review and manually enter patient demographics, cancer type and stage, and treatment history into a REDCap (Research Electronic Data Capture) database. All clinical trials and their eligibility criteria are also entered into REDCap and updated regularly. REDCap generates real time lists of potential research studies for each patient based on his/her recorded data. The primary oncologist is alerted to a patient’s potential eligibility prior to upcoming clinic visits and thus can plan to discuss clinical research enrollment as appropriate. Results: From March 2017 to December 2020, a total of 2548 unique patients were prescreened into REDCAP. The mean age was 71.5 years, 97.5% were male, and 15.5% were African American. 32.57 % patients had genitourinary cancer, 17.15% had lung cancer, and 46.15% were undergoing malignancy workup. 1412 patients were potentially eligible after prescreening and 556 patients were ultimately enrolled in studies. The number of patients enrolled on therapeutic clinical trials increased after the implementation of the prescreening protocol (35 in 2017, 64 in 2018, 78 in 2019, and 55 in 2020 despite the COVID19 pandemic). Biorepository study enrollment increased from 8 in 2019 to 15 in 2020. The prescreening protocol also enabled 200 patients to be enrolled onto a lung nodule liquid biopsy study from 2017 to 2019. Our prescreening process captured 98.57% of lung cancer patients entered into the cancer registry during the same time period. Conclusions: Universal prescreening streamlined research recruitment operations and was associated with yearly increases in clinical research enrollment at a VA cancer center. Our protocol identified most new lung cancer patients, suggesting that, at least for this malignancy, potential study patients were not missed. The protocol was integral in our program becoming the top accruing VA site for NCI’s National Clinical Trial Network (NCTN) studies since 2019.
Disaggregating Pacific Islanders and major Asian subpopulations to reveal hidden breast cancer disparities.
Authors: Taparra Kekoa , Dee Edward Christopher , Dao Dyda , Patel Rohan , Santos Patricia Mae G. , Chino Fumiko 
Published: September 2021

80 Background: The Asian American, Native Hawaiian, and Other Pacific Islander (AA/NHPI) population is the fastest growing and most socioeconomically heterogeneous racial/ethnic group in the US. AA/NHPI breast cancer outcomes are often reported as superior to Non-Hispanic Whites (NHW) however evidence suggests aggregating AA/NHPI masks disparities among subpopulations. As NHPI is often ignored as one of five official US races, this study aims to disaggregate AA and NHPI to unmask breast cancer disparities. Methods: An IRB exempt, retrospective cohort study using the National Cancer Database was conducted for women diagnosed with breast cancer in 2004-2016. AA and NHPI patients were compared with the majority NHW group. AA was separated into pertinent geographical origins: East Asian (EA; Chinese, Japanese, Korean), South Asian (SA; Indian, Pakistani), and Southeast Asian (SEA; Filipino, Vietnamese, Laotian, Hmong, Cambodian). Descriptive statistics were used. Logistic and Cox proportional hazard regressions assessed adjusted Odds Ratios (aORs) and adjusted Hazards Ratios (aHR), respectively, with 95% confidence intervals (95%CI). Analyses were adjusted for patient factors (age, insurance, income, rural/urban, education, hospital region, hospital distance, Deyo comorbidity score) and cancer characteristics (grade, stage, metastases, diagnosis year, hormone status). Results: Of 2,073,822 women there were 28,311 EA, 13,259 SA, 21,645 SEA, 5,375 NHPI, and 2,005,232 NHW. The median age was 62 years with median 66 month follow-up. Compared to NHW (9.6%), presentation with late-stage disease (Stage III/IV) was higher in NHPI (12%), SA (12%), and SEA (11%), but not EA (7.5%). On adjusted analysis (Table), EA was the only group with a statistical difference from NHW with aOR=0.85 (95%CI=0.76-0.94). Kaplan-Meier test for overall survival (OS) showed differences between ethnic/racial groups with NHPI having worse OS than AA subpopulations (p<0.0001). On adjusted analysis (Table), all AA subpopulations had lower risk of death compared to NHW: EA (aHR=0.69; 95%CI=0.64-0.74), SA (aHR=0.65; 95CI=0.59-0.71), and SEA (aHR=0.78; 95%CI=0.73-0.84) however the NHPI group had a greater risk of death (aHR=1.14; 95%CI=1.02-1.28). Conclusions: NHPI women with breast cancer have worse outcomes compared to NHW. This is masked by superior AA outcomes when aggregated. The continual improper aggregation of AA with NHPI downplays NHPI cancer disparities. Proper disaggregation of NHPI from AA warrants greater attention.[Table: see text]
The association of access to systemic therapy and overall survival in metastatic bladder cancer in Russia: An analysis of URRU register.
Authors: Petkau Vladislav , Alekseeva Galina , Zukov Ruslan , Mazhbich Mikhail , Statsenko Galina , Vladimirova Liubov Yu , Novikova Olga , Semenov Andrey , Zaitsev Igor , Gurina Ludmila , Tsimafeyeu Ilya 
Published: September 2021

88 Background: Social, economic and community disadvantages are well-described for metastatic bladder cancer (mBC) in different geographical regions. For the first time in Russian Federation we investigated treatment options and survival disparities for patients with mBC including urothelial cancer in URRU register. Methods: Patients were retrospectively identified at 9 cancer centers in southern, central, and eastern regions of Russia (Astrakhan, Ekaterinburg, Ivanovo, Khabarovsk, Krasnoyarsk, Moscow, Omsk, Rostov-on-Don, Vladivostok). Patients were included in the study if histologically confirmed mBC was diagnosed between January 2017 and January 2018 and they had at least one visit to the cancer center during the follow-up period. Anonymised data were collected by online registry. The outcomes of interest were overall survival (OS), patient characteristics and treatment patterns. Results: 246 adult patients were included in the study for analysis. Mean number of patients in one region per year was 31. All patients had metastatic disease. Median age at diagnosis of mBC was 72 (37-99) years (with 60.6% of patients aged ≥70 years). Patients were predominantly male (75%), histological subtype of BC (urothelial carcinoma, etc.) was determined in 70.32%. 92 (37.4%) patients received systemic therapy for mBC. Despite the approved checkpoint inhibitors for mBC in 2017-2018 in Russia the main treatment option was chemotherapy (n=70; 76%). Multivariate analysis by adjusting demographic and cancer variables showed that non-receipt of systemic therapy was independently associated with higher odds of death (Odds Ratio=3.1, confidence interval (CI)=1.89 to 5.18). Median OS (21 months; 95% CI 17.38-24.62) of patients who received systemic therapy was significantly longer than that of patients who did not received the therapy (3 months; 95% CI 1.79-4.22; p<0.0001). Patients receiving immunotherapy had better survival outcomes comparing to chemotherapy (median OS 34.5 vs. 18 months, p=0.003). Conclusions: In Russia only one third of patients with mBC received systemic therapy for metastatic disease which affected OS. Consistent with other studies these results indicate that patients should have access to novel therapies.
Interdisciplinary clinician perspectives on an embedded palliative oncology model in pediatric cancer care.
Authors: Salek Marta , Woods Cameka , Gattuso Jami S. , Mandrell Belinda Neal , Baker Justin N. , Kaye Erica 
Published: September 2021

9 Background: Integration of palliative care into cancer care is recognized as best practice by international oncology and pediatrics organizations. However, optimal strategies for integration of pediatric palliative care (PPC) within cancer care remain understudied. While the majority of PPC provision for cancer patients occurs through subspeciality consultation, growing evidence suggests that models embedding PPC within cancer care have the potential to improve quality of care. Embedded models rely on partnerships with multidisciplinary clinicians, whose perspectives regarding this model are not well known. Methods: We conducted 25 focus groups with 175 clinicians in an academic pediatric cancer center, with groups stratified by discipline (physicians, advance practice providers (APPs), nurses, psychosocial providers) and by care team (hematologic malignancy, bone marrow transplant, solid tumor, brain tumor). Focus groups were led by trained research facilitators and audio-recorded for subsequent targeted content analysis to identify clinician perspectives regarding embedded PPC models. Results: Across 4 physician, 5 APP, 12 nurse, and 4 psychosocial focus groups, 25 physicians, 30 APPs, 71 nurses, and 49 psychosocial providers participated, respectively. When asked to describe features of an “ideal” PPC model, physicians, APPs, and nurses predominantly discussed care delivery and identified early integration of PPC into cancer care as a core feature of an ideal model. Physicians, nurses, and psychosocial providers also emphasized the importance of having a formalized, structured care model. The need for collaboration was the dominant theme for psychosocial providers. Clinicians in all disciplines identified potential benefits from an embedded model, including access to PPC across care settings, normalization of PPC integration, and emphasis on collaboration, teamwork, communication, and earlier PPC involvement. Physicians, APPs, and nurses anticipated similar challenges with an embedded model, including possible reticence of oncology providers and inadequate PPC staffing. Nurses, APPs, and psychosocial providers also voiced concern about potential lack of clarity in delegation of roles and responsibilities between PPC and oncology providers. Conclusions: Pediatric oncology multidisciplinary providers recognize the potential value of an embedded model for integration of PPC in the care of children with cancer. Though providers at times identified similar themes with respect to ideal PPC provision and the benefits and challenges to an embedded model, some identified priorities varied by discipline. These findings highlight the importance of integrating varied interdisciplinary perspectives when developing an embedded care model to align with priorities of diverse pediatric cancer stakeholders.
The Cortisol Response of Male and Female Choroidal Endothelial Cells: Implications for Central Serous Chorioretinopathy
Authors: Brinks Joost , van Dijk Elon H C , Kiełbasa Szymon M , Mei Hailiang , van der Veen Isa , Peters Hendrika A B , Sips Hetty C M , Notenboom Robbert G E , Quax Paul H A , Boon Camiel J F , Meijer Onno C 
Published: September 2021

Abstract

Context
Central serous chorioretinopathy (CSC) is a severe ocular disease characterized by fluid accumulation under the retina and abnormalities in the underlying vascular layer, the choroid. CSC has a striking prevalence in males of 80% to 90% of total patients. Corticosteroids are the most pronounced extrinsic risk factor for CSC. Choroidal endothelial cells (CECs) are important for the vascular integrity of the choroid, but the effects of corticosteroid effects in these cells are unknown.

Objective
We aimed to reveal the potential steroidal contribution to CSC.

Method
We characterized the expression of the glucocorticoid, mineralocorticoid, and androgen receptor in the human choroid using immunohistochemistry. Using RNA-sequencing, we describe the cortisol response in human CECs derived from 5 male and 5 female postmortem donors.

Results
The glucocorticoid receptor was highly expressed in the human choroid, whereas no to minimal expression of the mineralocorticoid and androgen receptors was observed. The extensive transcriptional response to cortisol in human primary cultured CECs showed interindividual differences but very few sex differences. Several highly regulated genes such as ZBTB16 (log2 fold change males 7.9; females 6.2) provide strong links to choroidal vascular regulation.

Conclusions
The glucocorticoid receptor predominantly mediates the response to cortisol in human CECs. Interindividual differences are an important determinant regarding the cortisol response in human cultured CECs, whereas intrinsic sex differences appear less pronounced. The marked response of particular target genes in endothelial cells to cortisol, such as ZBTB16, warrants further investigation into their potential role in the pathophysiology of CSC and other vascular conditions.
Regulation of cell quiescence–proliferation balance by Ca2+–CaMKK–Akt signaling
Authors: Xin Yi , Guan Jian , Li Yingxiang , Duan Cunming 
Published: September 2021

ABSTRACT
Compared with our extensive understanding of the cell cycle, we have limited knowledge of how the cell quiescence–proliferation decision is regulated. Using a zebrafish epithelial model, we report a novel signaling mechanism governing the cell quiescence–proliferation decision. Zebrafish Ca2+-transporting epithelial cells, or ionocytes, maintain high cytoplasmic Ca2+ concentration ([Ca2+]c) due to the expression of Trpv6. Genetic deletion or pharmacological inhibition of Trpv6, or reduction of external Ca2+ concentration, lowered the [Ca2+]c and reactivated these cells. The ionocyte reactivation was attenuated by chelating intracellular Ca2+ and inhibiting calmodulin (CaM), suggesting involvement of a Ca2+ and CaM-dependent mechanism. Long-term imaging studies showed that after an initial decrease, [Ca2+]c gradually returned to the basal levels. There was a concomitant decease in endoplasmic reticulum (ER) Ca2+ levels. Lowering the ER Ca2+ store content or inhibiting ryanodine receptors impaired ionocyte reactivation. Further analyses suggest that CaM-dependent protein kinase kinase (CaMKK) is a key molecular link between Ca2+ and Akt signaling. Genetic deletion or inhibition of CaMKK abolished cell reactivation, which could be rescued by expression of a constitutively active Akt. These results suggest that the quiescence–proliferation decision in zebrafish ionocytes is regulated by Trpv6-mediated Ca2+ and CaMKK–Akt signaling.