bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparative study of the linear and colour-flavour-locked equation of states for compact objects
Authors: Thirukkanesh S. , Kaisavelu Anand , Govender Megan 
Published: March 2020

AbstractIn this work we present a general framework for obtaining exact solutions to the Einstein field equations describing strange stars obeying a colour-flavour-locked (CFL) equation of state. Starting off with a spherically symmetric metric in isotropic coordinates describing the interior of the star, we impose a CFL equation of state to reduce the problem to a single-generating function of the gravitational potentials. Our approach leads to an infinite class of solutions of the field equations. In order to test the physical viability of our solutions, we subscribe a particular model to stringent stability tests. In particular, we show that a linear equation of state described by the MIT Bag model mimics the CFL equation of state describing strange stars with interacting quark matter. This is an interesting result which connects the more robust and mathematically tractable linear equation of state to the fundamental physics describing nuclear matter in the quark regime.
A platform for semiautomated voluntary training of common marmosets for behavioral neuroscience
Authors: Walker Jeffrey D. , Pirschel Friederice , Gidmark Nicholas , MacLean Jason N. , Hatsopoulos Nicholas G. 
Published: March 2020

Generally behavioral neuroscience studies of the common marmoset employ adaptations of well-established training methods used with macaque monkeys. However, in many cases these approaches do not readily generalize to marmosets indicating a need for alternatives. Here we present the development of one such alternate: a platform for semiautomated, voluntary in-home cage behavioral training that allows for the study of naturalistic behaviors. We describe the design and production of a modular behavioral training apparatus using CAD software and digital fabrication. We demonstrate that this apparatus permits voluntary behavioral training and data collection throughout the marmoset’s waking hours with little experimenter intervention. Furthermore, we demonstrate the use of this apparatus to reconstruct the kinematics of the marmoset’s upper limb movement during natural foraging behavior. NEW & NOTEWORTHY The study of marmosets in neuroscience has grown rapidly and presents unique challenges. We address those challenges with an innovative platform for semiautomated, voluntary training that allows marmosets to train throughout their waking hours with minimal experimenter intervention. We describe the use of this platform to capture upper limb kinematics during foraging and to expand the opportunities for behavioral training beyond the limits of traditional training sessions. This flexible platform can easily incorporate other tasks.
Auto-antibodies to p53 and the Subsequent Development of Colorectal Cancer in a United States Prospective Cohort Consortium
Authors: Butt J , Blot WJ , Visvanathan K , Le Marchand L , Chen Y , Sesso HD , Wassertheil-Smoller S , Ho GYF , Tinker LE , Potter JD , Song M , Berndt S , Waterboer T , Pawlita M , Epplein M 
Published: March 2020

Abstract
Auto-antibodies to tumor suppressor p53 are found in a subset of colorectal cancer (CRC) patients. A prospective cohort study in the US (Cancer Prevention Study II) has recently reported a statistically significant 1.8-fold increased odds for the development of CRC based on pre-diagnostic sero-positivity for p53; the magnitude of this association decreased with longer time-span between blood sampling and diagnosis. In the present study, we sought to examine this association in a large US CRC cohort consortium to evaluate the potential utility of p53 auto-antibodies as an early CRC detection biomarker. Methods: Antibody responses to p53 were measured in pre-diagnostic blood samples of 3,702 incident CRC cases (median [range] follow-up: 7.3 years [0–40 years]) and an equal number of controls, matched by age, race, and sex, from 9 US prospective cohorts. The association of sero-positivity to p53 with CRC risk, overall and by time between blood draw and diagnosis, was determined by conditional logistic regression. Results: Overall, 5% of controls and 7% of cases were sero-positive to p53, resulting in a statistically significant 33% increased CRC risk (OR: 1.33; 95% CI: 1.09, 1.61). The association was strongest for CRC diagnoses within 2 years after blood draw (OR: 2.73; 95% CI: 1.67, 4.45), with 15% sero-positive cases compared to 6% sero-positive controls. The number of sero-positive cases decreased with longer follow-up time (2–&lt;5 years: 9%; 5–&lt;10 years: 6%; ≥10 years: 3%) down to a proportion similar to that in controls resulting in the absence of an association of p53 sero-positivity with CRC risk after more than 5 years between blood draw and CRC diagnosis. Conclusion: In this large consortium of prospective cohorts, we found that pre-diagnostic sero-positivity to the tumor suppressor p53 was statistically significantly associated with a 2.7-fold increased risk of a subsequent CRC diagnosis within 2 years after blood draw, replicating the findings of the one previous cohort study examining this association. The findings suggest that while p53 sero-positivity may not be a useful predictor of long-term CRC risk, p53 auto-antibodies might be considered as part of a marker panel for early detection of this cancer.
Accelerometer-measured Physical Activity and Breast Cancer Incidence in the WHI OPACH Study
Authors: Parada H , Bellettiere J , Evenson KR , LaMonte MJ , LaCroix AZ 
Published: March 2020

Abstract
To examine the associations between accelerometer-measured physical activity (PA) and breast cancer incidence among a cohort of postmenopausal women. Methods: This longitudinal study included 6,382 women (mean age 79 ± 6 years; 49.4% non-Hispanic white, 33.7% non-Hispanic Black, 16.9% Hispanic) without a history of breast cancer who participated in the Women's Health Initiative (WHI) Objective Physical Activity and Cardiovascular Health (OPACH) Study. During 2012–2013, participants wore an ActiGraph GT3X+ accelerometer at the hip for up to 7 days. Accelerometer intensity counts were specially calibrated to PA in older women. The resulting data were used to compute minutes per day spent in total PA, light intensity PA (e.g., usual walking), and moderate-to-vigorous PA (MVPA; e.g., brisk walking). Physician-adjudicated first diagnosis of in situ (n = 18) or invasive (n = 103) breast cancer was ascertained over a median follow-up of 5.6 years. We used multivariable Cox regression to estimate covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for tertiles and one-standard deviation (SD) unit increments of PA exposures in association with breast cancer incidence. We examined effect measure modification by age, race/ethnicity, body mass index (BMI), and smoking history. Results: The highest (vs. lowest) tertile of total PA was associated with a breast cancer incidence HR of 0.67 (95% CI = 0.43–1.05) and this association was more pronounced for MVPA (HR = 0.61, 95% CI = 0.38–1.00) than for light PA (HR = 0.81, 95% CI = 0.53–1.26). In BMI-stratified analyses, HRs for total (PInteraction = 0.04) and light PA (PInteraction = 0.01), but not MVPA (PInteraction = 0.79), were stronger among women with BMI ≥ 30 kg/m2 (n cancer events = 48; total PA HRper one-SD = 0.69, 95% CI = 0.50–0.96; light PA HR = 0.69, 95% CI = 0.50–0.95) than among women with BMI &lt; 30 kg/m2 (n cancer events = 73; total PA HRper one-SD = 1.07, 95% CI = 0.84–1.38; light PA HR = 1.13, 95% CI = 0.89–1.44). Age, race/ethnicity, and cigarette smoking history did not strongly modify these associations (PInteraction's ≥ 0.16). Conclusions: Engaging in high levels of PA may play a beneficial role in the prevention of breast cancer in older women, and in particular among postmenopausal women with BMI ≥ 30 kg/m2.
PSA Testing and Prostate Cancer Incidence Following the 2012 Update to the U.S. Preventive Services Task Force Prostate Cancer Screening Recommendation: Implications for Racial/Ethnic Disparities
Authors: Kensler KH , Pernar CH , Mahal BA , Nguyen PL , Trinh QD , Kibel AS , Rebbeck TR 
Published: March 2020

Abstract
The 2012 U.S. Preventive Services Task Force (USPSTF) recommendation against prostate specific antigen (PSA) testing led to a decrease in prostate cancer screening, but its impact on prostate cancer racial/ethnic disparities remains unclear. Methods: The proportion of men ages 40–74 years who received a routine PSA test in the past year was estimated over time in the Behavioral Risk Factor Surveillance System (BRFSS; 2012–2018) and the National Health Interview Survey (NHIS; 2005–2018). Screening trends by race/ethnicity were evaluated using logistic regression models to estimate odds ratios (ORs) of screening adjusting for socioeconomic and healthcare-related factors. Prostate cancer incidence rates and rate ratios (IRRs) by race/ethnicity were estimated in the Surveillance, Epidemiology and End Results (SEER) registry data over time (2004–2016). Results: In the 2012 BRFSS, PSA testing rates were highest among non-Hispanic white (NHW) men (32.3%), followed by non-Hispanic black (NHB; 30.3%), Hispanic (21.8%), and Asian/Pacific Islander men (17.7%). The absolute screening frequency declined by 9.5% overall from 2012 to 2018, with a greater decline among NHB (11.6%) than NHW men (9.3%). Adjusting for socioeconomic and healthcare-related factors, the relative decline was greater among NHB (OR per year = 0.86, 95% CI 0.84–0.88) than NHW men (OR = 0.89, 95% CI 0.89–0.90; p-het. = 0.005), driven by a steeper drop among NHB men ages 40–54. In the NHIS, the 2012 update was associated with a 35% decrease in the odds of screening (OR = 0.65, 95% CI 0.51–0.82), though there was no annual change since 2012 (OR = 1.00, 95% CI 0.98–1.03). Trends in the NHIS did not differ by race/ethnicity. The NHB:NHW IRR for total prostate cancer increased from 1.73 in 2011 to 1.87 in 2012 and has remained elevated, driven by differences in the incidence of localized tumors. Disparity IRRs have been consistent since 2012 for other racial/ethnic populations. Conclusions: Although the frequency of prostate cancer screening varies by race/ethnicity, the impact of the 2012 USPSTF recommendation against PSA testing on screening trends did not robustly differ by race/ethnicity. Following 2012, there was a modest increase in the disparity for localized prostate cancer incidence between NHB and NHW men.
Abnormal Stool Blood Tests and Colorectal Cancer Mortality in a Large United States Cohort
Authors: San Miguel Y , Demb J , Martinez ME , Gupta S , May F 
Published: March 2020

Abstract
Our aim was to examine the association between fatal colorectal cancer (CRC) and time to colonoscopy among individuals who underwent diagnostic colonoscopy after abnormal stool blood test (SBT) in a cohort of United States Veterans. Methods: We performed a cohort study of Veterans aged 50–75 years, with an abnormal SBT using the Veterans Health Administration's (VA) national electronic health record data during the years 1999 and 2010. Colonoscopy receipt was ascertained using current procedural terminology codes after abnormal SBT. The study outcome, CRC death, was defined through National Death Index cause-specific mortality data. We followed patients through CRC-related death, other death, or until December 31, 2015. Multivariable Cox proportional hazards modeling was used to generate CRC-specific mortality hazard ratios (HRs) and 95% confidence intervals (CI) for 3-month colonoscopy intervals, with 3–6 months as the reference. Models were adjusted for age, sex, race/ethnicity, smoking, diabetes, body mass index, and Charlson Comorbidity Index. Results: We included 222,004 patients with abnormal SBTs; the average age was 63 with a standard deviation of 7.2 years, 97% were male, 72% were Non-Hispanic White and 20% were Black. Of the 222,004 patients, 69% completed diagnostic colonoscopy within 12 months of abnormal SBT, 4% were diagnosed with CRC, and 1% died of CRC specific death. Compared to patients with a colonoscopy at 3–6 months (standard of care), CRC-related mortality risk was significantly higher for patients with colonoscopies at 0–3 months (HR = 1.29; 95% CI, 1.14–1.47), 18–21 months (HR = 1.57; 95% CI, 1.19–2.06), and 21–24 months (HR = 1.46; 95% CI, 1.07–1.97). No significant increase in mortality risk was shown for 6–9 month, 9–12 month, 12–15 month, 15–18 months, and 24+ month intervals. Conclusion: Time to colonoscopy plays a significant role in CRC death after abnormal SBT. Compared to a colonoscopy performed during a 3–6-month window, a colonoscopy performed outside of the 15-month window had a higher risk for mortality. Given the impact of timely diagnostic colonoscopy on CRC mortality, development of interventions to increase timely diagnostic follow-up after abnormal SBT are essential to CRC outcome improvement.
Composition of the Vaginal Microbiome Associated with High Risk HPV Infection and Increased Risk for Cervical Cancer
Authors: Madhivanan P , Bokulich NA , Coudray M , Colbert B , Ruiz-Perez D , Krupp K , Mathee K , Narasimhan G , Caporaso JG 
Published: March 2020

Abstract
Persistent high-risk Human papillomavirus (HPV) is a necessary but not sufficient cause for development of cervical cancer. Changes in the vaginal microbiota including reduction of Lactobacillus and increased microbial diversity may facilitate HPV infection and persistence as well as the pathogenesis of cervical cancer. Our objective was to characterize the vaginal microbiota among women with and without persistent HPV infection with HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 in a cohort of young U.S. women. Methods: This analysis used data from a longitudinal study of 1365 women followed for 12 months every two months apart from six locations across the US. HPV genotyping was performed using quantitative PCR using TaqMan probes in a customized plate (ThermoFisher Scientific). Bacterial communities were profiled by 16S rRNA gene sequences from the V3-V4 region using high-throughput pyrosequencing. Persistence was defined by examining for HPV presence in two consecutive visits. Results: Participants included 80 African-American women tested at 3 consecutive time-points. The mean age of participants was 21.4 years. About 43.7% (95% CI: 32.7%–55.3%) had persistent HPV infection, 20% (11.9%–30.4%) were able to clear the infection, and 36.2% (25.8%–47.8%) were consistently negative for HPV infection at all three time points. Atopobium and Peptoniphilus were significantly more abundant in women who were HPV negative suggesting possible protective effects. Prevotella bivia was enriched among women with persistent HPV. Conclusion: Based on these data, we can hypothesize that Prevotella richness is significantly associated with HPV persistence, suggesting a possible role in chronic HPV infection and development of cervical cancer.
Financial Distress and its Associated Burden in Couples Coping with an Incurable Cancer
Authors: Milbury K , Lopez G , Contreras J , Weather S-P , Bruera E 
Published: March 2020

Abstract
Although financial toxicity has been linked to poor disease outcomes in cancer patients, the associations between subjective financial distress (FD) and symptom burden and quality of life (QOL) are rarely examined from a patient-partner dyadic perspective. Thus, this cross-sectional study seeks to examine dyadic associations in couples coping with an incurable cancer. Method: Patients undergoing systemic and/or radiotherapy for advanced lung cancer (n = 50) or high grade glioma (n = 50) and their spouses/romantic partners completed measures of psychological distress (BSI-18), symptom severity including FD (ESAS, 0–10 scale), QOL (PROMIS-10), relationship wellbeing (SRI), and avoidance (AAQ-2). Results: Patients were mainly female (60%), and patients and partners were all in a heterosexual relationship (mean length: 30.12 ± 15.1 yrs), mainly non-Hispanic White (80%), married to each other (93%) and well educated with a mean age of 57.9 years (range: 28.5–79.0 years). FD was interrelated in couples (ICC = 0.53, P&lt;0.0001), and mean score did not significantly differ by role (patient = 2.32 vs partner = 2.81). Controlling for medical and demographic factors, based on dyadic level analyses, FD was significantly associated with physical QOL (P = 0.01) so that those with higher FD reported lower QOL. Interestingly, FD was significantly associated with psychological distress (P = 0.001), mental QOL (P&lt;0.001), avoidance (P = 0.01), and relationship wellbeing (P = 0.03) for partners but not for patients so that partners reporting higher FD had worse health and wellbeing. Moreover, in terms of relative burden, FD was the 7th (out of 12) most severe symptom for patients, and the 2nd most severe symptom for partners (after sleep disturbances). Based on concordance analyses, patients significantly underestimated their partners' FD (P = 0.007), which was further associated with increased partner psychological distress (P = 0.04). Conclusion: Although FD is interdependent in couples coping with an incurable cancer, FD appears to be a greater relative burden for partners than patients. In the palliative care setting, reducing FD may be an important target for caregiver interventions seeking to improve their health and wellbeing and reduce the overall cancer burden.
First-in-Human Study of Utomilumab, a 4-1BB/CD137 Agonist, in Combination with Rituximab in Patients with Follicular and Other CD20+ Non-Hodgkin Lymphomas
Authors: Gopal Ajay K. , Levy Ronald , Houot Roch , Patel Sandip P. , Popplewell Leslie , Jacobson Caron , Mu Xinmeng J. , Deng Shibing , Ching Keith A. , Chen Ying , Davis Craig B. , Huang Bo , Fly Kolette D. , Thall Aron , Woolfson Adrian , Bartlett Nancy L. 
Published: March 2020

Abstract

Purpose:
In this phase I study (NCT01307267), we evaluated safety, pharmacokinetics, clinical activity, and pharmacodynamics of treatment with utomilumab plus rituximab in patients with relapsed/refractory follicular lymphoma (FL) and other CD20+ non-Hodgkin lymphomas (NHL).

Patients and Methods:
Primary objectives were to assess treatment safety and tolerability for estimating the MTD, using a modified time-to-event continual reassessment method, and selecting the recommended phase II dose (RP2D).

Results:
Sixty-seven patients received utomilumab (0.03–10.0 mg/kg every 4 weeks) and rituximab (375 mg/m2 weekly) in the dose-escalation groups or utomilumab (1.2 mg/kg every 4 weeks) plus rituximab in the dose-expansion cohort. No patient experienced dose-limiting toxicity. The MTD for utomilumab in combination with rituximab was not reached and estimated to be ≥10 mg/kg every 4 weeks. The majority of the utomilumab treatment-related adverse events (AE) were grade 1 to 2; the most common AE was fatigue (16.4%). The pharmacokinetics of utomilumab in combination with rituximab was linear in the 0.03 to 10 mg/kg dose range. A low incidence (1.5%) of treatment-induced antidrug antibodies against utomilumab was observed. The objective response rate was 21.2% (95% CI, 12.1%–33.0%) in all patients with NHL, including four complete and 10 partial responses. Analysis of paired biopsies from a relapsed/refractory FL patient with complete response showed increased T-cell infiltration and cytotoxic activity in tumors. Biomarker correlations with outcomes suggested that clinical benefit may be contingent on patient immune function.

Conclusions:
Utomilumab in combination with rituximab demonstrated clinical activity and a favorable safety profile in patients with CD20+ NHLs.
A Multi-level Model to Understand Cervical Cancer Disparities in Appalachia
Authors: Paskett Electra D. , Pennell Michael L. , Ruffin Mack T. , Weghorst Christopher M. , Lu Bo , Hade Erinn M. , Peng Juan , Bernardo Brittany M. , Wewers Mary Ellen 
Published: March 2020

Abstract
The Appalachian region experiences higher incidence and mortality due to cervical cancer compared with other regions of the United States. The goal of the Ohio State University Center for Population Health and Health Disparities (CPHHD), called the Community Awareness Resources and Education (CARE) project, was to understand reasons for this disparity. The first wave (2003–2008) of funding included three projects focusing on the known risk factors for cervical cancer, lack of screening, smoking, and infection with human papillomavirus (HPV). On the basis of the results of these projects, the second wave (2011–2017) included four projects, designed to address a multi-level model of factors contributing to cervical disparities in Appalachia. The results of these projects were then used to refine a multi-level model that explains cervical cancer disparities in Appalachia. Future funded projects will take these multi-level explanations for cervical disparities and focus on implementation science strategies to reduce the burden of cervical cancer morbidity and mortality in Appalachia.
See all articles in this Special Collection Honoring Paul F. Engstrom, MD, Champion of Cancer Prevention
Dysplastic Aberrant Crypt Foci: Biomarkers of Early Colorectal Neoplasia and Response to Preventive Intervention
Authors: Clapper Margie L. , Chang Wen-Chi L. , Cooper Harry S. 
Published: March 2020

Abstract
The discovery of aberrant crypt foci (ACF) more than three decades ago not only enhanced our understanding of how colorectal tumors form, but provided new opportunities to detect lesions prior to adenoma development and intervene in the colorectal carcinogenesis process even earlier. Because not all ACF progress to neoplasia, it is important to stratify these lesions based on the presence of dysplasia and establish early detection methods and interventions that specifically target dysplastic ACF (microadenomas). Significant progress has been made in characterizing the morphology and genetics of dysplastic ACF in both preclinical models and humans. Image-based methods have been established and new techniques that utilize bioactivatable probes and capture histologic abnormalities in vivo are emerging for lesion detection. Successful identification of agents that target dysplastic ACF holds great promise for intervening even earlier in the carcinogenesis process to maximize tumor inhibition. Future preclinical and clinical prevention studies should give significant attention to assessing the utility of dysplastic ACF as the earliest identifiable biomarker of colorectal neoplasia and response to therapy.
See all articles in this Special Collection Honoring Paul F. Engstrom, MD, Champion of Cancer Prevention