bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cabazitaxel multiple rechallenge in metastatic castration-resistant prostate cancer: A therapeutic option to increase overall survival?
Authors: Pobel Cedric , Auclin Edouard , Teyssonneau Diego , Laguerre Brigitte , Cancel Mathilde , Boughalem Elouen , Noel Johanna , Brachet Pierre Emmanuel , Maillet Denis , Barthelemy Philippe , Helissey Carole , Thibault Constance , Oudard Stephane 
Published: March 2021

97 Background: Cabazitaxel rechallenge could be a more efficient therapy with an acceptable toxicity than docetaxel in the treatment of patients with a metastatic castration resistant prostate cancer (mCRPC). The aim of this study was to assess the feasibility and efficacy of cabazitaxel multiple rechallenge. Methods: This is a multicenter, retrospective cohort study including patients from 9 centers in France who received 3 lines or more of cabazitaxel from February 2012 to July 2020. Cabazitaxel schedule differed between patients: 25 mg/m2 q3w, 20 mg/m2 q3w, 16 mg/m2 q2w or 10 mg/m2 weekly. Efficacy was assessed by overall survival (OS) and progression-free survival (PFS) from each cabazitaxel line start. Only toxicities grade ≥ 3 were reported. Results: Twenty-two patients were included. The median follow-up from mCRPC was 94.7 months, median age at initial diagnosis was 59.5 years old, median ISUP score at diagnosis was 4 and median PSA at diagnosis was 55 ng/ml. Median number of cabazitaxel cycles was 7 at first-line, 6 at first rechallenge, and 5 for subsequent rechallenges. Median OS from mCRPC diagnosis was 105 months. Median PFS from cabazitaxel line start was 11.8 months at first use, 9.6 for first rechallenge and 5.6 in second rechallenge (table). Only one case of febrile neutropenia and 6 events of grade ≥ 3 toxicity were reported. Conclusions: Cabazitaxel multiple rechallenge could efficiently extend OS with manageable toxicities for patients. Even if anti-PARP therapy and immunotherapy are promising treatments, cabazitaxel rechallenge could be also a relevant therapeutic option for long responder patients. Specific biomarkers should be explored to predict the efficacy of cabazitaxel rechallenge. [Table: see text]
A phase I/II study of REGN5678 (Anti-PSMAxCD28, a costimulatory bispecific antibody) with cemiplimab (anti–PD-1) in patients with metastatic castration-resistant prostate cancer.
Authors: Zhang Jingsong , Stein Mark N. , Kelly William Kevin , Tsao Che-Kai , Falchook Gerald Steven , Xu Yuanfang , Seebach Frank A. , Lowy Israel , Mohan Kosalai Kal , Kroog Glenn , Miller Elizabeth 
Published: March 2021

TPS174 Background: Bispecific antibodies (bsAbs) are emerging as a protein-based therapeutic strategy for directing T-cell-mediated cytotoxicity in a tumor antigen-specific manner, typically by binding to both tumor antigen and the CD3 receptor on T-cells. REGN5678 is a human IgG4-based, first-in-class costimulatory bsAb designed to target prostate tumors by bridging prostate specific membrane antigen expressing tumor cells with the costimulatory receptor, CD28, on T-cells, and providing amplified T-cell receptor-CD3 complex-mediated T-cell activation within the tumor through the activation of CD28 signaling. At the tumor site, REGN5678 may synergize with PD-1 inhibitors. In mouse models, REGN5678 in combination with a PD-1 antibody has improved anti-tumor activity compared with either therapy alone (Waite JC et al. Sci Transl Med. 2020:12;549). Methods: This is an open label, Phase I/II, first-in-human study evaluating safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of REGN5678 alone and in combination with cemiplimab in patients with metastatic castration resistant prostate cancer (mCRPC) who progressed after prior therapy (NCT03972657). For inclusion, patients must have received at least two prior lines of systemic therapy (in addition to androgen deprivation therapy) approved for metastatic and/or castration-resistant disease including a second-generation anti-androgen therapy. REGN5678 is administered weekly; cemiplimab (350 mg) is administered once every 3 weeks. During dose escalation, a 3-week safety lead-in of REGN5678 monotherapy will be administered prior to addition of cemiplimab. Study therapies are administered until disease progression, intolerable adverse events, withdrawal of consent, or study withdrawal criterion is met. The primary objectives in dose escalation are to evaluate safety, tolerability, and PK of REGN5678 alone and in combination with cemiplimab. Expansion cohort(s) will be enrolled once a maximum-tolerated REGN5678/cemiplimab dose is reached, or if a recommended Phase 2 dose or doses have been determined. During the expansion phase, the primary objective is to assess clinical activity, as measured by objective response rate of REGN5678 in combination with cemiplimab per modified Prostate Cancer Working Group 3 criteria. At selected sites, prostate-specific membrane antigen PET/CT scans are performed at baseline and select time points on study. This study is currently open to enrollment. Clinical trial information: NCT03972657.
AMPLITUDE: A study of niraparib in combination with abiraterone acetate plus prednisone (AAP) versus AAP for the treatment of patients with deleterious germline or somatic homologous recombination repair (HRR) gene-altered metastatic castration-sensitive prostate cancer (mCSPC).
Authors: Rathkopf Dana E. , Chi Kim N. , Olmos David , Cheng Heather H. , Agarwal Neeraj , Graff Julie N , Sandhu Shahneen Kaur , Hayreh Vinny , Lopez-Gitlitz Angela , Francis Peter St. John , Attard Gerhardt 
Published: March 2021

TPS176 Background: Clinical benefit has been observed with poly(ADP-ribose) polymerase (PARP) inhibition in patients with metastatic castration-resistant prostate cancer tumors that carry HRR gene defects. Niraparib is a highly selective and potent PARP inhibitor, with activity against PARP-1 and PARP-2 deoxyribonucleic acid (DNA)-repair polymerases. The objective of AMPLITUDE is to assess the efficacy and safety of niraparib/placebo added to AAP with androgen deprivation therapy (ADT) in a biomarker-selected population with mCSPC. Methods: AMPLITUDE (NCT04497844) is a phase 3, randomized, double-blind, placebo-controlled study with an expected enrollment of 788 patients at ~350 sites in ~30 countries. Clinical trial information: NCT04497844. [Table: see text]
Uncertainty and complementarity relations based on generalized skew information
Authors: Huang Huaijing , Wu Zhaoqi , Fei Shao-Ming 
Published: March 2021

Abstract
Uncertainty relations and complementarity relations are core issues in quantum mechanics and quantum information theory. By use of the generalized Wigner-Yanase-Dyson (GWYD) skew information, we derive several uncertainty and complementarity relations with respect to mutually unbiased measurements (MUMs), and general symmetric informationally complete positive operator valued measurements (SIC-POVMs), respectively. Our results include some existing ones as particular cases. We also exemplify our results by providing a detailed example.
Transient absorption with a femtosecond tunable excitation pump reveals the emission kinetics of color centers in amorphous silica
Authors: De Michele Vincenzo , Sciortino Alice , Messina Fabrizio , Cannas Marco , Boukenter Aziz , Marin Emmanuel , Girard Sylvain , Ouerdane Youcef 
Published: March 2021

We report a set of femtosecond (fs) transient absorption (TA) measurements following the dynamics of the so-called nonbridging oxygen hole center in silica, a model color center in wide bandgap amorphous solids, characterized by a very large Stokes shift between the UV excitation and its associated red emission at 1.9 eV. The changes in the TA spectrum were probed in the UV-visible range at various delays after photoexcitation and analyzed as a function of the UV excitation energy, in single-photon absorption conditions. The combination of the experiments helps to clarify the defect photocycle, highlighting how TA measurements with tunable UV excitation could represent a powerful tool to investigate the dynamics of color centers embedded in transparent materials.
Optimising passive surveillance of a neglected tropical disease in the era of elimination: A modelling study
Authors: Longbottom Joshua , Wamboga Charles , Bessell Paul R. , Torr Steve J. , Stanton Michelle C. 
Published: March 2021

BackgroundSurveillance is an essential component of global programs to eliminate infectious diseases and avert epidemics of (re-)emerging diseases. As the numbers of cases decline, costs of treatment and control diminish but those for surveillance remain high even after the ‘last’ case. Reducing surveillance may risk missing persistent or (re-)emerging foci of disease. Here, we use a simulation-based approach to determine the minimal number of passive surveillance sites required to ensure maximum coverage of a population at-risk (PAR) of an infectious disease.Methodology and principal findingsFor this study, we use Gambian human African trypanosomiasis (g-HAT) in north-western Uganda, a neglected tropical disease (NTD) which has been reduced to historically low levels (<1000 cases/year globally), as an example. To quantify travel time to diagnostic facilities, a proxy for surveillance coverage, we produced a high spatial-resolution resistance surface and performed cost-distance analyses. We simulated travel time for the PAR with different numbers (1–170) and locations (170,000 total placement combinations) of diagnostic facilities, quantifying the percentage of the PAR within 1h and 5h travel of the facilities, as per in-country targets. Our simulations indicate that a 70% reduction (51/170) in diagnostic centres still exceeded minimal targets of coverage even for remote populations, with >95% of a total PAR of ~3million individuals living ≤1h from a diagnostic centre, and we demonstrate an approach to best place these facilities, informing a minimal impact scale back.ConclusionsOur results highlight that surveillance of g-HAT in north-western Uganda can be scaled back without substantially reducing coverage of the PAR. The methodology described can contribute to cost-effective and equable strategies for the surveillance of NTDs and other infectious diseases approaching elimination or (re-)emergence.
Pharmacokinetic / pharmacodynamic relationships of liposomal amphotericin B and miltefosine in experimental visceral leishmaniasis
Authors: Voak Andrew A. , Harris Andy , Coteron-Lopez Jose Miguel , Angulo-Barturen Iñigo , Ferrer-Bazaga Santiago , Croft Simon L. , Seifert Karin 
Published: March 2021

Background
There is a continued need to develop effective and safe treatments for visceral leishmaniasis (VL). Preclinical studies on pharmacokinetics and pharmacodynamics of anti-infective agents, such as anti-bacterials and anti-fungals, have provided valuable information in the development and dosing of these agents. The aim of this study was to characterise the pharmacokinetic and pharmacodynamic properties of the anti-leishmanial drugs AmBisome and miltefosine in a preclinical disease model of VL.

Methodology / Principal findings
BALB/c mice were infected with L. donovani (MHOM/ET/67/HU3) amastigotes. Groups of mice were treated with miltefosine (orally, multi-dose regimen) or AmBisome (intravenously, single dose regimen) or left untreated as control groups. At set time points groups of mice were killed and plasma, livers and spleens harvested. For pharmacodynamics the hepatic parasite burden was determined microscopically from tissue impression smears. For pharmacokinetics drug concentrations were measured in plasma and whole tissue homogenates by LC-MS. Unbound drug concentrations were determined by rapid equilibrium dialysis. Doses exerting maximum anti-leishmanial effects were 40 mg/kg for AmBisome and 150 mg/kg (cumulatively) for miltefosine. AmBisome displayed a wider therapeutic range than miltefosine. Dose fractionation at a total dose of 2.5 mg/kg pointed towards concentration-dependent anti-leishmanial activity of AmBisome, favouring the administration of large doses infrequently. Protein binding was >99% for miltefosine and amphotericin B in plasma and tissue homogenates.

Conclusion / Significance
Using a PK/PD approach we propose optimal dosing strategies for AmBisome. Additionally, we describe pharmacokinetic and pharmacodynamic properties of miltefosine and compare our findings in a preclinical disease model to available knowledge from studies in humans. This approach also presents a strategy for improved use of animal models in the drug development process for VL.
Potential mechanisms of action of convalescent plasma in COVID-19
Authors: Franchini Massimo , Glingani Claudia , Liumbruno Giancarlo Maria 
Published: March 2021

Abstract
The COVID-19 pandemic will be remembered as one of the worst catastrophic events in human history. Unfortunately, no universally recognized effective therapeutic agents are currently available for the treatment of severe SARS-CoV-2 infection. In this context, the use of convalescent plasma from recovered COVID-19 patients has gained increasing interest thanks to the initially positive clinical reports. A number of mechanisms of action have been proposed for convalescent plasma, including direct neutralization and suppression of viremia, anti-inflammatory and immunomodulation effects and mitigation of the COVID-19-associated hypercoagulable state. These immune and non-immune mechanisms will be critically discussed in this narrative review.
Univerbation
Authors: Lehmann Christian 
Published: March 2021

AbstractUniverbation is the syntagmatic condensation of a sequence of words recurrent in discourse into one word, as when the Spanish combinationa tras(to back) becomesatrás‘behind’. It affects both lexemes and grammatical formatives. Unlike processes of word formation, including conversion of a syntactic construction into a word, as inforget-me-not, and compounding, as in Spanishlavaplatos‘dishwasher’, univerbation is a spontaneous process. There are two main types of univerbation: phrasal univerbation downgrades a phrase to a word, as when Latinterrae motus‘earth’s movement’ becomes Spanishterremoto‘earthquake’. Transgressive univerbation coalesces a string of words which do not form a syntagma into a word, as when Frenchpar ce quebecomesparce que. A set of univerbations may share structural features and may therefore evolve into a pattern of compounding. Thus,blackbirdoriginated by univerbation, but may now provide a pattern of compounding. As a consequence, univerbation and compounding are not always easily distinguishable. The discussion uses empirical evidence adduced in earlier work, mostly from Romance and Germanic languages. Its aim is not to present novel phenomena but to provide a theoretical background for the phenomenology and improve on available analyses.
Ageing mechanisms of the papers with zeolite and PCC fillers
Authors: Engin Merve , Yılgör Nural , Atik Celil 
Published: March 2021

AbstractThis work has been conducted to investigate the effect of accelerated ageing on the filler-free (control) handsheets and the ones having Precipitated Calcium Carbonate (PCC) and Zeolite (Clinoptilolite) fillers. The diagnosis approach of this work has been based on the use of the techniques of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray diffraction (XRD). The FT-IR technique has allowed identifying the changes in cellulose components of handsheets. Likewise, the XRD technique has provided to diagnose the changes in crystallinity of the handsheets and fillers. The results found out that PCC and Zeolite fillers could be easily added to the structure of the paper network by changing various experimental variables. The loss of C−O functional groups and the formation of carbonyl groups in handsheets has been analysed by accelerated ageing. The spectroscopy results confirmed that usage of zeolite filler has a retarding and structurally improving effect on the glycosidic linkages. Recent findings have been provided new insights into the role of the synergistic effect of the combination of PCC and zeolite fillers in the decelerating of certain ageing mechanism.
Distributive Consequences of Risk Privatization: The Case of the Swedish Unemployment Insurance System
Authors: Lindellee Jayeon 
Published: March 2021

Abstract
The public unemployment insurance program in Sweden has retrenched in terms of its benefit generosity in the last three decades. As a response to this trend, in which an ever-smaller proportion of the previous income of unemployed persons is compensated by public unemployment insurance benefit, complementary income insurance schemes provided by unions have expanded rapidly in the last 15 years, currently covering one half of the working population. What does this change mean for people who need income protection upon unemployment and are more likely to find themselves unemployed or underemployed? By analyzing survey-based benefit recipiency data among retail workers who were unemployed in 2014, this article explores the outcomes of the multi-pillarized unemployment benefit provision system in Sweden. While public unemployment insurance benefit does not fully compensate for the income loss for the majority of retail workers, the promise of a complementary income insurance scheme seems to be illusory for many individuals as they repeatedly oscillate between precarious work and benefits, accompanied by the burden of navigating a complex system.
Biomechanical Effects of a 6-Week Change of Direction Speed and Technique Modification Intervention: Implications for Change of Direction Side step Performance
Authors: Dos'Santos Thomas , Thomas Christopher , Comfort Paul , Jones Paul A. 
Published: March 2021

Abstract
Dos'Santos, T, Thomas, C, Comfort, P, and Jones, PA. Biomechanical effects of a 6-week change of direction speed and technique modification intervention: implications for change of direction side step performance. J Strength Cond Res 36(10): 2780–2791, 2022—The aim of this study was to evaluate the biomechanical effects of change of direction (COD) speed and technique modification training on COD performance (completion time, ground contact time [GCT], and exit velocity) during 45° (CUT45) and 90° (CUT90) side step cutting. A nonrandomized, controlled 6-week intervention study was administrated. Fifteen male, multidirectional, sport athletes (age, 23.5 ± 5.2 years; height, 1.80 ± 0.05 m; mass, 81.6 ± 11.4 kg) formed the intervention group (IG) who participated in two 30-minute COD speed and technique modification sessions per week, whereas 12 male, multidirectional, sport athletes (age, 22.2 ± 5.0 years; height, 1.76 ± 0.08 m; mass, 72.7 ± 12.4 kg) formed the control group (CG) and continued their normal training. All subjects performed 6 trials of the CUT45 and CUT90 task whereby pre-to-post intervention changes in lower-limb and trunk kinetics and kinematics were evaluated using 3-dimensional motion and ground reaction force analyses. Two-way mixed analysis of variances revealed significant main effects for time (pre-to-post changes) for CUT45 completion time, exit velocity, and CUT90 completion time (p ≤ 0.045; η2 = 0.152–0.539), and significant interaction effects of time and group were observed for CUT45 completion time, GCT, exit velocity, and CUT90 completion time (p ≤ 0.010; η2 = 0.239–0.483), with the IG displaying superior performance postintervention compared with the CG (p ≤ 0.109; g = 0.83–1.35). Improvements in cutting performance were moderately to very largely associated (p ≤ 0.078; r or ρ = 0.469–0.846) with increased velocity profiles, increased propulsive forces over shorter GCTs, and decreased knee flexion. Change of direction speed and technique modification is a simple, effective training method requiring minimal equipment that can enhance COD performance, which practitioners should consider incorporating into their pitch- or court-based training programs.
“Colorindo o passado com um valor que nos é caro”: memórias que educam, histórias que se entrelaçam
Authors: Vieira Maria Letícia 
Published: March 2021

Este estudo versa sobre a cultura escolar no Colégio Alfredo Dantas, tomando como objetivo trabalhar com a Cultura Escolar desenvolvida na instituição já mencionada no período de 1968- 1987, o qual se situa no campo da História Cultural em diálogo com a História da Educação a partir das práticas de memória, dialogando com as perspectivas de Dominique Julia (2001), Verena Alberti (2004) e Foucault (2014). Adotamos como metodologia a coleta de narrativas de memória de ex-alunos e ex-professor, em que estes sujeitos educativos representam a escola em suas lembranças a partir das festividades, dos desfiles cívicos, do fardamento e apontam para sensibilidades educativas, cujos atos de memória permite alcançar. Esta pesquisa, acaba nos fazendo perceber que o Colégio Alfredo Dantas, é também espaço de sensibilidade, em que as emoções se afloram e as subjetividades podem ser lidas por meio das memórias.Palavras-chaves: Cultura Escolar; Memória; Práticas Educativas; Ditadura Militar. AbstractThis study deals with school culture at Alfredo Dantas School, taking as objective to work with the School Culture developed in the institution already mentioned in the period 1968-1987. These characteristics locate this study in the field of Cultural History, in dialogue with the History of Education from the practices of memory, dialoguing with the perspectives of Domenique Julia (2001), Verena Alberti (2004) and Foucault (2014). We adopted as method the collection of memory narratives of former students and teachers, since these educational subjects represent the school in their memories as of the festivities, civic parades and uniforms. Data collected point to educational sensitivities, whose acts of memory allow to achieve. This research ends up making us realize that the Alfredo Dantas School is also a space of sensitivity, in which emotions surface and subjectivities can be read through memories.Keywords: School Culture; Memory; Educational Practices; Military Dictatorship.
Representações das histórias das mulheres na coleção indumentária do Museu Julio de Castilhos (1995-2010)
Authors: Da Silveira Andréa Reis 
Published: March 2021

O artigo apresenta a investigação sobre as representações das histórias das mulheres no acervo de indumentária do Museu Julio de Castilhos (MJC), PoA, RS, no recorte temporal de 1995-2010. Analisa os objetos de três exposições que abordaram perfil das mulheres rio-grandenses. Avalia as doações e a musealização feitas por mulheres, nas quais denominei intelectuais mediadoras. Os dados assinalaram que as construções narrativas da historicidade das peças passaram pela interpretação desse grupo de classe média, branco e de idade cronológica média, que compôs as informações que constam na documentação museológica do banco de dados Donato, e, no Livro Diário do acervo. Os resultados apontaram permanências de estereótipos sobre as histórias das mulheres, problematizando as ações educativas realizadas pelo MJC.Palavras-chave: Museu; Coleção indumentária; História das mulheres.AbstractThe paper presents the investigation about the representations of the women's stories in the collection of clothing of the Julio de Castilhos Museum (MJC), PoA, RS, in the 1995-2010 period. The objects of three exhibitions that addressed the profile of women from Rio Grande do Sul are analyzed. It evaluates donations and musealization made by women, which I have called mediating intellectuals. Data indicated that the narrative constructions of the historicity of the pieces went through the interpretation of this group of middle class, white and middle chronological age, which composed the information contained in the museum documentation of the Donato database, and in the Daily Book of the collection. The results pointed to the permanence of stereotypes about the women's stories, problematizing the educational actions carried out by the MJC.Keywords: Museum; Collections; women's history.