bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abiraterone decanoate (AD): Potent and long-acting activity of a novel intramuscular (IM) abiraterone prodrug depot in a castrate monkey model.
Authors: Moore William R. , Sharp Matthew , Bell Caroline , Freeman Stuart , Parr Alan , Eisner Joel Robert , Schotzinger Robert 
Published: March 2021

78 Background: Oral abiraterone acetate (AA) is a standard of care for castration-resistant (CRPC) and castration-sensitive prostate cancer (CSPC). Due to poor oral bioavailability, the recommended AA dose is 1,000 mg (4 x 250mg) once-daily on an empty stomach. The daily oral regimen produces high peak plasma concentrations that may be associated with safety issues (e.g., hepatotoxicity) and low trough concentrations that may be associated with inadequate CYP17 inhibition. AD is one of a series of novel abiraterone prodrugs that were designed to provide a controlled release of abiraterone and long-acting CYP17 inhibition with IM delivery. Following successful preclinical pilot studies, AD was further developed into a clinically acceptable formulation (PRL-02) and its PK/PD characteristics were evaluated and compared to oral AA in a castrate monkey pharmacology model in support of future clinical development. Methods: Sexually mature male cynomolgus monkeys underwent chemical castration using Lupron depot. Plasma samples were analyzed for prodrug, abiraterone and steroid concentrations following a single oral AA dose (5, 15 or 45 mg/kg) and a single IM AD injection (10, 30 or 100 mg/kg) (n=3/dose group). The combined activity of IM AD plus glucocorticoid replacement (single 0.5 mg/kg IM dexamethasone (DEX) dose or weekly doses of 1.29 mg/kg IM methylprednisolone acetate (MPA)) was also evaluated. AD, abiraterone and adrenal steroid levels were evaluated by LC-MS/MS. Results: Chemical castration resulted in a plasma testosterone (T) decrease of 72% from intact. T was further reduced to sub-castrate levels by both AA and AD (98.6% and 99.7% maximum decrease from castrate baseline, respectively). All dose levels of AD were highly effective in reducing plasma T yet led to abiraterone plasma concentrations (Cmax, AUC, Cmin) that were much less than those associated with steady-state clinical levels from oral AA. Sustained T suppression was observed following all single AD IM doses for 14 weeks, the last timepoint tested.The addition of a glucocorticoid replacement (DEX or MPA) starting at week 9 further reduced T in all AD groups. Conclusions: Single-dose IM AD suppressed T to the same or greater extent than single-dose oral AA in castrate monkeys, while providing much lower abiraterone exposures than the oral acetate prodrug. As such, IM AD may offer an improved risk-benefit profile due to the consistently lower abiraterone levels. The durable, profound T reductions provided by all AD doses are consistent with a 3-month clinical regimen that can be given in conjunction with Lupron. IM AD may thus offer patients with CSPC and CRPC a more convenient, safe and effective alternative than daily oral AA.
ICEPAC: A phase II multicenter study of avelumab combined with stereotactic ablative body radiotherapy (SABR) in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Azad Arun , Spain Lavinia Anne , Anton Angelyn , Gan Chun Loo , Garrett Linda , Chang Deborah , Bennett Caitlin , Kothari Gargi , Shaw Mark , Parente Phillip , Pezaro Carmel Jo , Tran Ben , Siva Shankar , Kwan Edmond Michael 
Published: March 2021

86 Background: Studies investigating immune checkpoint inhibitors (ICI) in mCRPC have produced modest results. Radiation therapy may be synergistic with ICIs. We hypothesised that SABR would enhance anti-tumour activity of PD-L1 inhibitor avelumab in patients (pts) with progressive mCRPC. Methods: This phase II, single arm, multicentre study enrolled mCRPC pts following progression on ≥1 novel androgen receptor-directed therapy. Up to two lines of prior taxane chemotherapy were permitted. Pts received avelumab 10mg/kg IV q2weeks for a total of 24 weeks (12 cycles). A single fraction of 20Gy SABR was administered to 1-2 disease sites within five days prior to first and second doses of avelumab. Primary endpoint was disease control rate (DCR); secondary endpoints were PSA response (PSA50), overall response rate (ORR), radiographic progression-free survival (rPFS), overall survival (OS) and safety. Radiographic disease assessment (CT and bone scintigraphy) was performed after cycles 6 and 12 of avelumab treatment. Following enrolment of 14 pts, a protocol amendment allowed avelumab beyond 12 cycles in pts with disease control at 24 weeks. Results: Thirty-one pts were enrolled, with 30 evaluable for the primary endpoint. Median follow-up was 18 months (mo). Pt characteristics: median age 71 years (IQR 64-75), bone-only disease 42%, visceral disease 16%, prior taxane chemotherapy 84%, treatment with both abiraterone and enzalutamide 13%. Seventy metastatic sites received SABR, most frequently to bone (90%) and soft tissue (29%) disease. Avelumab was given as second-line, third-line and fourth- or greater line systemic therapy in 29%, 42% and 29% of pts, respectively. Median cycles of avelumab administered was 9 (IQR 5-13). DCR (95% CI) was 50% (31-69) and 60% (32-84) in all-comers and soft tissue disease subgroup, respectively. Following protocol amendment, 7/17 pts (41%) received avelumab beyond 12 cycles. Incidence of grade 3-4 treatment-related AEs was 16% (no grade 5 events), with three pts requiring oral/IV corticosteroid therapy. Conclusions: Avelumab with SABR demonstrated durable disease control in treatment-refractory mCRPC with an acceptable toxicity profile. This combination warrants further investigation. Clinical trial information: ACTRN12618000954224. [Table: see text]
DASL-HiCaP: Darolutamide augments standard therapy for localized very high-risk cancer of the prostate (ANZUP1801)—A randomized phase III double-blind, placebo-controlled trial of adding darolutamide to androgen deprivation therapy and definitive or salvage radiation.
Authors: Niazi Tamim , Williams Scott , Davis Ian D. , Stockler Martin R. , Martin Andrew James , Bracken Karen , Roncolato Felicia , Horvath Lisa , Martin Jarad , Lim Tee Sin , Hughes Simon , McDermott Raymond S. , Catto James WF , Kelly Paul J. , McBride Sean Matthew , Parulekar Wendy R. , Morgan Scott Carlyle , Rendon Ricardo A. , Sweeney Christopher ,   Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
Published: March 2021

TPS266 Background: Radiation therapy (RT), plus androgen deprivation therapy (ADT) with a luteinizing hormone releasing hormone analogue (LHRHA), is standard of care for men with very high-risk localized prostate cancer (PC), or with very high- risk features and persistent PSA after radical prostatectomy (RP). Despite this, incurable distant metastases develop within 5 years in 15% of men with very high-risk features. Darolutamide is a structurally distinct oral androgen receptor antagonist with low blood-brain-barrier penetration, a demonstrated favorable safety profile and low potential for drug-drug interactions. Our aim is to determine the efficacy of adding darolutamide to ADT and RT in the setting of either primary definitive therapy, or adjuvant therapy for very high-risk PC. Methods: This study is a randomized (1:1) phase III placebo-controlled, double-blind trial for men planned for RT who have very high-risk localized PC; or very high-risk features with PSA persistence or rise within one year following RP. The trial will be stratified by: RP; use of adjuvant docetaxel; pelvic nodal involvement. 1100 participants will be randomized to darolutamide 600 mg or placebo twice daily for 96 weeks. Participants will receive LHRHA for 96 weeks, plus RT starting week 8-24 from randomisation. Participants are allowed nonsteroidal antiandrogen (up to 90 days) in addition to LHRHA up until randomisation. Early treatment with up to 6 cycles of docetaxel completed at least 4 weeks prior to RT is permitted. The primary endpoint is metastasis-free survival (ICECaP-validated), with secondary endpoints overall survival, PC-specific survival, PSA-progression free survival, time to subsequent hormonal therapy, time to castration-resistance, frequency and severity of adverse events, health related quality of life, fear of recurrence. Tertiary endpoints include incremental cost-effectiveness, and identification of prognostic and/or predictive biomarkers of treatment response, safety and resistance to study treatment. Clinical trial information: NCT04136353.
Phase III study evaluating efficacy and safety of MK-6482 + lenvatinib versus cabozantinib for second- or third-line therapy in patients with advanced renal cell carcinoma (RCC) who progressed after prior anti-PD-1/L1 therapy.
Authors: Motzer Robert J. , Liu Yanfang , Perini Rodolfo F. , Zhang Yayan , Heng Daniel Yick Chin 
Published: March 2021

TPS372 Background: There is an unmet need for treatment options in the second-line or later setting following anti–PD-1/L1 or VEGF tyrosine kinase inhibitor (TKI) therapy in patients with advanced RCC. Hypoxia-inducible factor (HIF)-2α is a transcription factor that has been established as an oncogenic driver in clear cell RCC (ccRCC). Promising antitumor activity has been reported for the first-in-class small molecular HIF-2α inhibitor, MK-6482, in heavily pretreated patients with ccRCC and patients with VHL disease–associated RCC. HIF-2α also regulates VEGF gene expression and plays a role in resistance to anti-VEGF therapy. Therefore, combining MK-6842 with a VEGF receptor TKI, such as lenvatinib, is an attractive treatment option in the advanced RCC setting. Methods: This is a randomized, open-label, active-controlled, multicenter phase III trial evaluating the efficacy and safety of MK-6482 + lenvatinib compared with cabozantinib in patients with advanced ccRCC who have progressed on prior anti–PD-1/L1 therapy (NCT04586231). Eligibility criteria include age ≥18 years; histologically confirmed, unresectable, locally advanced or metastatic ccRCC; disease progression on or after first- or second-line systemic treatment with an anti–PD-1/L1 therapy (monotherapy or in combination with other agent[s]) for locally advanced or metastatic disease, the immediately preceding line of treatment must be an anti–PD-1/L1 therapy; no more than 2 prior systemic regimens, with only 1 prior anti–PD-1/L1 therapy; measurable disease per RECIST v1.1; and Karnofsky performance status ≥70%. Patients must provide tissue for biomarker analysis. Approximately 708 patients will be randomly assigned in a 1:1 ratio to receive MK-6482 120 mg orally once daily (QD) + lenvatinib 20 mg orally QD or cabozantinib 60 mg orally QD. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent. The stratification factors are International mRCC Database Consortium prognostic scores (0, 1-2, or 3-6), number of prior lines of therapy (1 or 2), and geographic region (North America, Western Europe, or rest of the world). Imaging will be assessed by CT or MRI every 8 weeks through week 80, then every 12 weeks thereafter. The dual primary end points are progression-free survival per RECIST v1.1 as assessed by blinded independent central review (BICR) and overall survival. Secondary end points are objective response rate and duration of response per RECIST v1.1 as assessed by BICR, and safety. Safety and tolerability will be evaluated using a tiered approach. Clinical trial information: NCT04586231 .
A shortcut tour of quantum control methods for modern quantum technologies
Authors: Stefanatos D. , Paspalakis E. 
Published: March 2021

Abstract
Quantum control methods, like rapid adiabatic passage, stimulated Raman adiabatic passage, shortcuts to adiabaticity and optimal control, have become an integral part of modern quantum technologies, for example quantum computation and sensing, where they are exploited in order to find the optimal pulse sequences which drive quantum systems to the desired target state in minimum time or with maximum fidelity, overcoming decoherence and dissipation. In this perspective, we use the basic example of adiabatic population inversion in a two-level system in order to present these methods and review the latest developments in the field, while we touch upon the emerging method of reinforcement learning.
The Conditional Effects of Health on Voter Turnout
Authors: Lyon Gregory 
Published: March 2021

AbstractContext: Voting is the central instrument of democracy, yet there are a number of impediments that affect citizens' ability to turn out to vote. Health is one such impediment.Methods: This study draws on 2012 and 2016 election data from the Cooperative Congressional Election Study and the American National Election Studies and uses objective validated measures of voter turnout as well as postelection data on respondents' reasons for nonvoting to examine the relationship between self-reported health and voter turnout.Findings: The results indicate poor health depresses turnout among low-income voters but not high-income voters. A low-income citizen in poor health is 7 points less likely to turn out to vote than a low-income citizen in excellent health is. In contrast, a high-income citizen in poor health is just as likely to vote as a high-income citizen in excellent health is. Moreover, low-income citizens in poor health are 10 points more likely to cite sickness as an impediment to voting than are otherwise similar high-income citizens who are also in poor health.Conclusions: The findings have implications for health policy and unequal electoral engagement and suggest that health may narrow the scope of US democracy as poor health pushes low-income citizens out of the electoral sphere while high-income citizens continue to turn out to vote regardless of their underlying health conditions.
The Influence of Corporate Income Taxes on Investment Location: Evidence from Corporate Headquarters Relocations
Authors: Chow Travis , Huang Sterling , Klassen Kenneth J. , Ng Jeffrey 
Published: March 2021

This study examines the effects of jurisdictions’ corporate taxes and other policies on firms’ headquarters (HQ) location decisions. Using changes in state corporate income tax rates across time and states as the setting, we find that a one-percentage-point increase in the HQ state corporate income tax rate increases the likelihood of firms relocating their HQ out of the state by 16.8%, and an equivalent decrease in the HQ state rate decreases the likelihood of HQ relocations by 9.1%. Exploiting the unique tax policy features within the state apportionment system lends strong support to the interpretation that taxation drives this effect. Our analyses also demonstrate that state income tax features affect the destination of the HQ move. We contribute to the literature on corporate decision making by showing how state income taxation affects a real corporate decision that has significant economic consequences for the company and the state.This paper was accepted by Brian Bushee, accounting.
The nursing management required to provide effective end-of-life care in a care home setting: a case study
Authors: Hickey Simona , Williams Mary 
Published: March 2021

Background: This case study is a practical experience example from a nursing home setting. It will describe how a holistic approach to care, provided to a resident living with dementia at end of life, ensured a peaceful death. Aims: The importance of advance care planning and effective pain and symptom management in end-of-life care will be explored. The psychosocial issues experienced by the resident and their family and any ethical issues associated with the delivery of care will be addressed. The factors and challenges that need to be overcome in order to ensure effective pain and symptom management for the dying patient, particularly in a nursing home setting, are discussed. Finally, this article will make recommendations for future practice. Methods: This is a case study based on an author's experience while working in a nursing home setting. Findings: Challenges associated with end-of-life care have been identified and recommendations have been made.
Two-dimensional extreme skin depth engineering for CMOS photonics
Authors: van Niekerk Matthew , Jahani Saman , Bickford Justin , Cho Pak , Anderson Stephen , Leake Gerald , Coleman Daniel , Fanto Michael L. , Tison Christopher C. , Howland Gregory A. , Jacob Zubin , Preble Stefan F. 
Published: March 2021

Extreme skin depth engineering (e-skid) can be applied to integrated photonics to manipulate the evanescent field of a waveguide. Here we demonstrate thate-skidcan be implemented in two directions in order to deterministically engineer the evanescent wave allowing for dense integration with enhanced functionalities. In particular, by increasing the skin depth, we enable the creation of two-dimensional (2D)e-skiddirectional couplers with large gaps and operational bandwidth. Here we experimentally validate 2De-skidfor integrated photonics in a complementary metal–oxide semiconductor (CMOS) photonics foundry and demonstrate strong coupling with a gap of 1.44 µm.
Petahertz-scale nonlinear photoconductive sampling in air
Authors: Zimin Dmitry , Weidman Matthew , Schötz Johannes , Kling Matthias F. , Yakovlev Vladislav S. , Krausz Ferenc , Karpowicz Nicholas 
Published: March 2021

The electric field waveform of a light field can be used to unlock a detailed recording of its interaction with matter, but accessing it requires a measurement with subfemtosecond temporal resolution. We demonstrate nonlinear photoconductive sampling of light fields at optical frequencies in ambient air. The resulting detection method provides broadband electric field measurement in an inexpensive setup using a self-healing medium. A direct comparison is made between detection in air and in quartz, validating the technique up to 0.7 PHz. This provides both a simple route toward field metrology and a new platform for future studies in attosecond physics without the need for complex vacuum setups or sophisticated sample preparation.
Intention to voluntary blood donation among private higher education students, Jimma town, Oromia, Ethiopia: Application of the theory of planned behaviour
Authors: Aschale Abiot , Fufa Diriba , Kekeba Tilahun , Birhanu Zewdie 
Published: March 2021

Background
Blood is an important and crucial component in the management of patients presenting with severe accident injuries, surgical conditions, malignancies, pregnancy-related complications, and other medical conditions.

Objectives
To assess intention to voluntary blood donation among private higher education students in Jimma Town, South West Ethiopia, 2019.

Methods
Institution-based cross-sectional study with quantitative methods was conducted in private higher education students in Jimma town. A multistage sampling technique was used to recruit study participants. First, a simple random sampling technique was used to select departments in each private higher education institution. Seven departments were included in the study and after proportionally allocated in each department, a total of 595 were participated in the study, producing a response rate of 98%. The data was collected using self-administered structured questioners with 3 trained data collectors. Multivariable linear regression analysis was done to assess association between the independent variables and dependent variable.

Results
The mean score for intention of the respondents to donate blood voluntarily was 15.41 out of 25 with standard deviation of 4.42.The TPB variables explained 61.3% of the variance of intention to donate blood. Direct perceived behavioral control (β = 0.745, P < 0.001), direct attitude (B = 0.295, P<0.001) and direct subjective norm (β = 0.131, P< 0.001) were significant predictors of the intention.

Conclusion
Respondents’ intentions are mainly determined by perceived barriers and, subjective norms, the attitude of respondents towards voluntary blood donation.
Resistin is a risk factor for all-cause mortality in elderly Finnish population: A prospective study in the OPERA cohort
Authors: Parkkila Karri , Kiviniemi Antti , Tulppo Mikko , Perkiömäki Juha , Kesäniemi Y. Antero , Ukkola Olavi 
Published: March 2021

Objective
Resistin is a small, cysteine-rich proinflammatory molecule that is primarily secreted by peripheral blood mononuclear cells and macrophages in humans. Previous studies have shown resistin to participate in various pathological processes including atherosclerosis and cancer progression but not many studies have assessed the role of resistin as a risk factor for all-cause mortality. The objective of this prospective study was to evaluate whether resistin predicts mortality among elderly Finnish people.

Methods
The study population consisted of 599 elderly (71.7 ± 5.4 years) patients and the follow-up was approximately six years. A thorough clinical examination including anthropometric and other clinical measurements such as blood pressure as well as various laboratory parameters (including resistin) was conducted at baseline.

Results
After the follow-up, 65 (11%) of the patients died. Resistin was a significant risk factor for all-cause mortality (HR 3.02, 95% CI: 1.64–5.56, p<0.001) when the highest tertile was compared to the lowest. Resistin remained as a significant risk factor even after adjusting for various covariates such as age, sex, systolic blood pressure, smoking habits, alcohol consumption, medications (antihypertensive, lipid-lowering, glucose-lowering), hsCRP and leisure time physical activity. Receiver operating characteristic (ROC) curve analysis for resistin demonstrated area under the curve (AUC) of 0.656 (95% CI: 0.577–0.734), p<0.001 and an optimal cutoff value of 12.88 ng/ml.

Conclusions
Our results indicate that resistin is a significant risk factor for all-cause mortality among elderly Finnish subjects, independent from traditional cardiovascular risk factors.
From PhD Thesis to Monograph
Authors: Deblasio Lisamarie 
Published: March 2021

This essay provides a personal and reflective account of the process of adapting a PhD thesis, which was written for a panel of examiners to demonstrate academic competence, to a monograph, which in simple terms is written for a wide audience including students and academics with the aim of communicating ideas. It is hoped that this article provides insight to postdoctoral researchers who may be thinking about submitting a proposal to a publisher for adaptation of their PhD thesis to a monograph.
Keywords: thesis adaptation; monograph; academic publishers.