bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary analysis of a U.S. phase II study of the safety and tolerability of proxalutamide (GT0918) in subjects with mCRPC who had progressed on either abiraterone (Abi) or enzalutamide (Enza).
Authors: Vogelzang Nicholas J. , Levin Richard , Rezazadeh Arash , Park Chandler H. , Bolemon Britt Haley , Gabrail Nashat Y. , Malik Zulfiqar A. , Nordquist Luke T. , Ross Ashley , Zhang Phoebe , Zhou Karl 
Published: March 2021

99 Background: GT0918, an androgen receptor (AR) antagonist, is a new chemical entity with reduced drug accumulation in the CNS. In a phase I dose escalation trial (NCT02826772), GT0918 was well tolerated with some durable responses in mCRPC patients (pts) who had progressed on ≥2 lines of standard and experimental therapies. This Phase 2 was designed to study the safety and efficacy of GT0918 400 mg vs. 500 mg oral daily in mCRPC pts who had progressed on either Abi or Enza with or without prior docetaxel. Methods: Pts with histologically confirmed mCRPC who had progressed on either Abi or Enza with or without prior docetaxel were eligible and randomized to 400 mg or 500 mg of GT0918 administered once daily orally. Pts continued treatment with GT0918 at their assigned dose until disease progression, intolerable toxicities or withdrawal of consent. PSA and labs were checked monthly. Imaging scans (CT/MRI and bone scan), circulating tumor cells and cf-DNA/RNA were performed every 3 months. Results: 61 pts were enrolled at 9 US sites and randomized 1:1 to 400 mg (n = 31) or 500 mg (n = 30) daily dose. All pts had progressed on either Abi (n = 34) or Enza (n = 27). Most of the reported AEs related to GT0918 were grade 1 or 2 as per CTCAE v4.03, but 22 AEs (5.3%) were reported as grade ≥ 3, such as fatigue, increase ALT/AST, rhabdomyolysis, or muscle weakness. Some AEs were due to drug-drug interaction with lipid-lowering medications leading to early discontinuation (26.2%). As of 5 October 2020, twelve pts finished 6 cycles. Among them, three finished 12 cycles and remained on the treatment. Treatment duration showed more pts in the 400 mg cohort with stable disease (SD) on imaging (9/31 finished 6 cycles) compared to the 500 mg cohort (3/30 finished 6 cycles). Further, all three pts who finished 12 cycles had progressed on Abi indicating that GT0918 might be a good treatment option for pts who had progressed on Abi. Conclusions: Proxalutamide (GT0918) administrated orally once a day is well tolerated and resulted in SD in pts who had progressed on either Abi or Enza. The 400 mg/day will be considered as the recommended phase II dose for further clinical trials. GT0918 is warranted for pts failed either Abi or Enza. Clinical trial information: NCT03899467.
Phase III randomized trial of PSMA PET prior to definitive radiation therapy for unfavorable intermediate-risk or high-risk prostate cancer [PSMA dRT]: Study protocol NCT04457245.
Authors: Calais Jeremie , Zhu Shaojun , Hirmas Nader , Eiber Matthias , Hadaschik Boris A. , Stuschke Martin , Herrmann Ken , Czernin Johannes , Kishan Amar Upadhyaya , Nickols Nicholas George , Elashoff David , Fendler Wolfgang Peter 
Published: March 2021

TPS172 Background: Definitive radiation therapy (dRT) is an effective initial treatment of intermediate-risk (IR) and high-risk (HR) prostate cancer (PCa). Positron emission tomography (PET) using small molecule probes targeting prostate-specific membrane antigen (PSMA PET) is superior to standard of care imaging (CT, MRI, bone scan) for detecting regional and distant metastatic PCa. PSMA PET thus has the potential to guide primary radiotherapy planning in patients and improve outcomes. The purpose of the present randomized trial is to evaluate the success rate of dRT for IR or HR PCa with and without planning based on PSMA PET. Methods: We will randomize 312 patients to proceed with standard dRT (control Arm 1, n=150), or undergo a PSMA PET scan prior to dRT planning (intervention arm 2, n = 162). In the control arm, dRT will be performed as routinely planned in accordance with initial stratification. In the intervention arm, the treating radiation oncologist can incorporate PSMA PET findings into the RT planning. We assume that approximately 8% of subjects randomized to arm 2 will be found to have M1 disease and thus will be more appropriate candidates for long-term systemic or multimodal therapy, rather than curative intent dRT. PET M1 patients will thus not be included in the analysis of the primary endpoint. The primary endpoint is the success rate of dRT measured as PFS after initiation of dRT. Progression is defined as (whichever occurs first): biochemical recurrence defined as a rise by 2 ng/mL or more above the nadir PSA (defined as the lowest PSA achieved) after radiotherapy with or without short-term hormonal therapy; appearance of metastasis or loco-regional recurrence (diagnosed by any imaging or biopsy); initiation of any new salvage therapy, or death from any cause. Discussion: This is the first randomized phase 3 prospective trial designed to determine whether PSMA PET molecular imaging can improve outcomes in patients with PCa who receive dRT. In this trial the incorporation of PSMA PET may improve the success rate of curative intent radiotherapy in two ways: to optimize patient selection and to personalizes the radiotherapy plan. Clinical trial registration: IND#147591, UCLA IRB #20-000378, ClinicalTrials.gov Identifier NCT04457245. Clinical trial information: NCT04457245.
INNOVATE (NRG-GU008): A randomized phase III trial of salvage radiotherapy and androgen deprivation therapy (ADT) with/without abiraterone and apalutamide for patients with node-positive prostate cancer after radical prostatectomy.
Authors: Chen Ronald C. , Karrison Theodore , Lawton Colleen Anne , Hall William Adrian , Borno Hala , Rosu Mihaela , Jani Ashesh B. , Schuster David M. , Seider Michael J. , Efstathiou Jason A. , Posadas Edwin Melencio , Nguyen Paul L. , Feng Felix Y 
Published: March 2021

TPS179 Background: Node-positive prostate cancer comprises for approximately 13% of newly-diagnosed patients and represents an aggressive form of the disease, but has been historically understudied in therapeutic clinical trials. Cure rates remain suboptimal for these patients with early stage IV disease, so clinical trials to intensify systemic treatment are warranted. Abiraterone and apalutamide have each demonstrated efficacy in improving metastasis-free survival and/or overall survival in the advanced stage setting, including both castrate-resistant and metastatic castration-sensitive prostate cancer. The mechanisms of action of abiraterone and apalutamide are complementary, and combination therapy has been shown in a prior Phase Ib trial to be safe and well-tolerated. Methods: Patients with pathologic node-positive disease by radical prostatectomy and who subsequently have a detectable PSA are eligible for this randomized controlled trial. All patients are required to receive molecular imaging (FACBC, PSMA, or choline PET scan) at trial entry and must have no radiographic evidence of distant metastasis in order to remain eligible. Eligible patients are randomized 1:1 to (control arm) salvage radiation therapy with 2 years of ADT vs (experimental arm) addition of 2 years of abiraterone/prednisone and apalutamide. The primary endpoint is metastasis-free survival. With a sample size of 586 and with a potential for 10% loss to follow-up, the trial has 90% power with one-sided alpha=0.025 to detect a HR of 0.53 for the experimental arm vs control arm for the primary endpoint. Secondary endpoints include quality of life (EPIC-26, EQ5D-5L, Brief Pain Inventory, PROMIS-Fatigue), overall survival, time to castrate resistance, and other disease-related outcomes. In addition, data will be collected to validate the Decipher score and PAM50-based classification as predictive biomarkers in this node-positive patient population. Trial was activated on March 5, 2020, and is currently enrolling patients. This project was supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), U24CA196067 (NRG Oncology Specimen Bank) from the National Cancer Institute (NCI) and Janssen and GenomeDX. Clinical trial information: NCT04134260.
A phase I/II dose-escalation study of fractionated and multiple dose 225Ac-J591 for progressive metastatic castration-resistant prostate cancer (mCRPC).
Authors: Sun Michael , Nauseef Jones T. , Lebenthal Justin M , Niaz Muhammad Junaid , Singh Sharon , Chamberlain Tessa A , Bissassar Mahelia , Patel Amie , Tan Angela , Vallabhajosula Shankar , Babich John , Christos Paul J. , Osborne Joseph , Molina Ana M. , Sternberg Cora N. , Nanus David M. , Bander Neil Harrison , Tagawa Scott T. 
Published: March 2021

TPS188 Background: Prostate-specific membrane antigen (PSMA)-based targeted radionuclide therapy (TRT) is a promising treatment. PSMA-targeting via large antibodies vs small molecules has different kinetics, biodistribution, and resulting clinical toxicities. Using beta-TRT, 177Lu-J591 has more heme toxicity and 177Lu-PSMA-617 more non-heme toxicity (xerostomia and nausea) [Niaz AUA 2020]. Alpha-emitters are more potent than beta radionuclides, and alpha-PSMA-TRT has efficacy even after beta-PSMA-TRT. In a first-in-human phase I dose-escalation study of 225Ac-J591, patients with mCRPC were treated with a single dose of 225Ac-J591 on seven dose levels, up to 93.3 KBq/kg [Tagawa ASCO 2020]. No maximal tolerated dose (MTD) was achieved. One patient treated at 80 KBq/kg developed dose-limiting toxicity (DLT) of grade 4 anemia and thrombocytopenia, but 0 of 6 at 93.3 KBq/Kg had grade > 3 heme toxicity or grade > 2 non-heme toxicity. Preliminary results indicate 64% had any PSA decline and 41% had > 50% PSA decline (PSA50) across all doses, despite lack of selection for PSMA expression and the majority having been previously treated with 177Lu-PSMA. Methods: Entry criteria include progressive mCRPC by PCWG3 criteria, ECOG PS 0-2, intact organ function (including normal neutrophil and platelet counts), and prior receipt of AR pathway inhibitor and chemotherapy (or refuse/ineligible for chemotherapy). There is no limit to prior lines of therapy except alpha-PSMA-TRT. Phase I includes 2 separate parallel dose-escalation cohorts. In the fractionated-dose cohort, men will receive a single cycle of 225Ac-J591 administered on D1 and D15. In the multiple-dose cohort, 225Ac-J591 will be given every 6 weeks for up to 4 cycles. The phase I component is a 3+3 dose-escalation study design, with the goal of identifying MTD. Each phase II component will treat up to 27 men with PSMA+ PET scans in a Simon 2-stage design with 90% power to exclude the null hypothesis (35% or fewer patients with PSA50). Eligible men with negative PSMA PET scans will be offered treatment with informed consent in an exploratory subgroup, but will not be counted towards phase II efficacy. Secondary outcomes include radiographic response by PCWG modified RECIST 1.1 criteria and PSMA PET, biochemical and radiographic progression-free survival, circulating tumor cell counts, and overall survival. Patient reported outcomes, genomic, and immune analyses are exploratory. Enrollment began in August 2020 (NCT04506567). Clinical trial information: NCT04506567.
The SPARC-1 trial: A phase I study of neoadjuvant combination interleukin-1 beta and PD-1 blockade in localized clear cell renal cell carcinoma.
Authors: Dallos Matthew , Aggen David Henry , Ager Casey , Obradovic Aleksandar , Easterlin Clara A , Hawley Jessica , Lim Emerson A. , Stein Mark N. , Drake Charles G. 
Published: March 2021

TPS373 Background: Immune checkpoint blockade has significantly improved outcomes for patients with renal cell carcinoma (RCC) in the metastatic setting. However, there is currently no neoadjuvant systemic therapy that improves outcomes for patients with localized RCC. Emerging data suggests that immunosuppressive myeloid cell populations within the tumor microenvironment (TME) represent a key mechanism of adaptive immune resistance. In pre-clinical models, targeting interleukin 1 beta (IL-1beta) can successfully re-establish anti-tumor immunity by shifting the myeloid cells towards M1-like tumor associated macrophages (TAM) and decreasing infiltration of immunosuppressive myeloid-derived suppressor cells (MDSCs). The SPARC-1 study is testing the hypothesis that neoadjuvant therapy with combined IL-1beta blockade (canakinumab) plus PD-1 blockade (spartalizumab) is safe and can successfully remodel the myeloid compartment towards a pro-inflammatory state in patients with localized RCC. Methods: This is a single-center, single-arm, phase I trial of patients with localized clear cell RCC (ccRCC) planned for nephrectomy (stage T1b-T4NanyM0). 14 patients will receive immunotherapy with combination canakinumab (300mg IV) plus spartalizumab (400mg IV) every 4 weeks x 2 doses given 6 weeks prior to nephrectomy. The primary endpoints are safety and feasibility. Secondary endpoints include tumor CD8 T cell infiltration, tumor MDSC infiltration and objective response rate. SPARC-1 offers a unique opportunity to utilize fresh tumor tissue to identify changes in the immune TME with single-cell discrimination following therapy. Therefore, correlative studies will include single-cell RNA-sequencing, multi-color flow cytometry and multiplexed immunofluorescence to quantify changes in the density and spatial proximity of distinct immune cell populations within the TME. The study is open with 4 patient currently enrolled at the time of submission. Clinical trial information: NCT04028245 .
Attention and distraction in the modular visual system of a jumping spider
Authors: Bruce Margaret , Daye Daniel , Long Skye M. , Winsor Alex M. , Menda Gil , Hoy Ronald R. , Jakob Elizabeth M. 
Published: March 2021

ABSTRACT
Animals must selectively attend to relevant stimuli and avoid being distracted by unimportant stimuli. Jumping spiders (Salticidae) do this by coordinating eyes with different capabilities. Objects are examined by a pair of high-acuity principal eyes, whose narrow field of view is compensated for by retinal movements. The principal eyes overlap in field of view with motion-sensitive anterior-lateral eyes (ALEs), which direct their gaze to new stimuli. Using a salticid-specific eyetracker, we monitored the gaze direction of the principal eyes as they examined a primary stimulus. We then presented a distractor stimulus visible only to the ALEs and observed whether the principal eyes reflexively shifted their gaze to it or whether this response was flexible. Whether spiders redirected their gaze to the distractor depended on properties of both the primary and distractor stimuli. This flexibility suggests that higher-order processing occurs in the management of the attention of the principal eyes.
Responses ofManduca sextalarvae to heat waves
Authors: Kingsolver Joel G. , Moore M. Elizabeth , Augustine Kate E. , Hill Christina A. 
Published: March 2021

ABSTRACTClimate change is increasing the frequency of heat waves and other extreme weather events experienced by organisms. How does the number and developmental timing of heat waves affect survival, growth and development of insects? Do heat waves early in development alter performance later in development? We addressed these questions using experimental heat waves with larvae of the tobacco hornworm, Manduca sexta. The experiments used diurnally fluctuating temperature treatments differing in the number (0–3) and developmental timing (early, middle and/or late in larval development) of heat waves, in which a single heat wave involved three consecutive days with a daily maximum temperature of 42°C. Survival to pupation declined with increasing number of heat waves. Multiple (but not single) heat waves significantly reduced development time and pupal mass; the best models for the data indicated that both the number and developmental timing of heat waves affected performance. In addition, heat waves earlier in development significantly reduced growth and development rates later in larval development. Our results illustrate how the frequency and developmental timing of sublethal heat waves can have important consequences for life history traits in insects.
Effectiveness of turmeric-enriched pellets to improve the immunity of Clarias batrachus toward motile Aeromonas septicemia disease
Authors: Riauwaty Morina , Siregar Yusni I. , Mulyani Isma 
Published: March 2021

Background: Turmeric is known as a natural remedy to improve the immunity of organisms. This study aims to understand the effectiveness of turmeric-enriched pellets to improve the immunity of Clarias batrachus to Aeromonas hydrophila. Methods: The study was conducted from May to August 2020. C. batrachus fingerlings, 7-8 cm total length (TL) and 4-5 g (BW) at baseline, were kept in 30 L aquaria (10 fishes/aquarium; three replicated/treatment). Commercial pellets were mixed with turmeric powder. There were five treatment groups: P0 (control, no turmeric); P1 (0.5 g turmeric per Kg of pellets); P2 (0.7 g/Kg); P3 (0.9 g/Kg); Pp (positive control). Thirty days after being feed with turmeric-enriched pellets, all groups of fish were infected with 0.1 ml (108) of A. hydrophila suspension, intramuscularly. The P0 group did not receive injection, while Pp group were not fed with turmeric-enriched pellets but were infected with the bacteria. Fourteen days after infection, clinical signs and hematology of the fish were studied. Results: Pp fish showed heavy clinical signs of A. hydrophila, such as loss of balance, pigmentation, hemorrhages and ulcers. P0 fish did not show any symptoms, while the treated fish reveled some clinical signs of A. hydrophila to a lesser extent than Pp, indicating that the fish is able to face the A. hydrophila attack. Hematology for Pp fish revealed high white blood cells, indicating that the fish were infected. The blood condition of the P0 fish, as well as those of the turmeric-treated fish were normal. In general, the P3 fish showed the least clinical signs of A. hydrophila and normal blood condition, indicating that P3 treatment is best. Conclusion: The best turmeric dosage to improve the immunity of C. batrachus toward A. hydrophila infection is 0.9 g/Kg pellets.
Hair Cortisol and Self-Injurious Behavior Among Children With Autism Spectrum Disorder
Authors: Courtemanche Andrea B. , Black William R. , Meyer Jerrold S. 
Published: March 2021

Abstract
Elevated salivary cortisol levels have been documented in individuals who engage in self-injurious behavior (SIB), indicating acute physiological stress. Less is known about the chronicity of stress and SIB. We analyzed the relationship between parent ratings of problem behavior and hair cortisol concentrations (an index of chronic adrenocortical activity) in 23 children with autism spectrum disorder (ASD). Parent ratings of problem behavior were not significantly correlated with hair cortisol concentrations. When children were categorized into groups based on the frequency and severity of SIB, participants with the greatest frequency and severity of SIB had higher hair cortisol concentrations compared to children without SIB. Frequent and severe SIB may be associated with altered hypothalamic-pituitary-adrenal (HPA) axis activity in children with ASD.
Production of 23Na Bose–Einstein condensates in the F = 2 state using D2 gray molasses
Authors: Shi Zhenlian , Li Ziliang , Wang Pengjun , Sadiq Nawaz Khan , Chen Liangchao , Meng Zengming , Huang Lianghui , Zhang Jing 
Published: March 2021

We report on the production of Bose–Einstein condensates of sodium atoms in the hyperfine state

|

F
=
2
,

m
F

=
2
⟩

in a crossed optical dipole trap using

D
2

gray molasses. We use the gray molasses sub-Doppler cooling technique to obtain an atomic sample of

3
×

10
8

at 56 µK. After the radio frequency (RF) evaporation cooling in an optically plugged magnetic trap, we transfer the atoms sample of

2.5
×

10
6

at 5.7 µK to a crossed optical dipole trap where a pure condensate with an atom number of

2
×

10
5

and lifetime of 6.3 s is obtained by further evaporation. We compare the cooling process of sodium atoms in the

|

2
,
2
⟩

and the

|

1
,
1
⟩

states by evaporation in the optical trap, and also observe the different three-body loss rates by the lifetime measurement.
Dual-channel illumination surface plasmon resonance holographic microscopy for resolution improvement
Authors: Dou Jiazhen , Dai Siqing , Dong Chen , Zhang Jiwei , Di Jianglei , Zhao Jianlin 
Published: March 2021

Surface plasmon resonance holographic microscopy (SPRHM), combining digital holographic microscopy with surface plasmon resonance (SPR), can simultaneously obtain the amplitude and phase distributions of the reflected beam carrying specimen information in SPR. Due to the decaying length of the surface plasmon wave as large as tens of micrometers, the spatial resolution of SPRHM is lower than that of ordinary optical microscopes. In this work, we propose a scheme to improve the spatial resolution of SPRHM by applying dual-channel SPR excitations. Through the polarization multiplexing technique, two holograms carrying the information of SPR excited in orthogonal directions are simultaneously acquired. Via a numerical reconstruction and filtering algorithm for holograms, the lateral spatial resolution of SPRHM can be effectively enhanced to reach nearly 1 µm at a wavelength of 632.8 nm. This is comparable to the resolution of traditional optical microscopes, while possessing the advantages of wide-field imaging and high measurement sensitivity of SPR.
Integrated multi-beam optical phased array based on a 4  ×  4 Butler matrix
Authors: Lu Ping , Xu Weihan , Zhu Chen , Liu Chuxin , Lu Liangjun , Zhou Linjie , Chen Jianping 
Published: March 2021

We design and demonstrate the first, to the best of our knowledge, silicon-based multi-beam optical phased array (MOPA), incorporating a

4

×
4

Butler matrix beamforming network. The one-dimensional end-fire array consists of 16 emitters at a uniform pitch together with their corresponding phase shifters and is shared among the beams to realize large-scale aliasing-free beam-steering at reduced complexity. Experimental results show that the device is capable of individual beam aliasing-free operation with a field of view up to 46°. The steering envelope shows a plateau where the peak intensities fluctuate within 0.5 dB. The beamforming and beam-steering performance are also evaluated for simultaneous multi-beam operation. Our work validates the feasibility of beamforming-network-based MOPAs, which are promising for applications including light detection and ranging and free-space optical communication.