bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 0 study to assess [111In]-DOTA-h11B6 to target human kallikrein-2 (hk2) in men with metastatic castration-resistant prostate cancer.
Authors: Morris Michael J. , O' Donoghue Joseph A. , Chetty Dushen , Russell Mike , Zulch Emma , Avadhani Anjali Narayan , Divgi Chaitanya R. , Pandit-Taskar Neeta 
Published: February 2020

TPS249 Background: Human kallikrein-2 (hk2) is a member of the kallikrein family, is produced by prostatic epithelium, has 80% DNA sequence homology with PSA, is both circulating and bound to prostatic tissue, and is highly expressed even in high grade tumors. hK2 holds the promise of serving as a new therapeutic target for radiopharmaceuticals in prostate cancer. h11B6 is a humanized antibody directed to an epitope found on the catalytically active form of hK2, which is permanently internalized after binding. This is a first-in-human trial of [111In]-DOTA-h11B6 to determine the radio-immunotherapeutic potential of targeting hK2 with nanomolar affinity. The trial will determine the most favorable antibody mass as well as assess tumor targeting. Methods: To determine the optimal antibody mass, two cohorts of patients will be studied. All patients will receive 2 mg of [111In]-labeled h11B6. The first cohort consists of escalating amounts of antibody mass in 2-6 patients: 2, 10 and 20 mg total antibody respectively. Patients will undergo serial whole-body images for up to a week, along with assessments of serum clearance kinetics and normal organ residence time. The lowest mass amount of antibody that demonstrates favorable biodistribution and evidence of radioactivity accumulation in tumor will be used for the second cohort. Up to 6 patients will be studied in the second cohort, which will focus on assessment of antibody tumor targeting. Following this optimization and targeting imaging trial, a phase 1 dose-escalation radioimmunotherapy trial may be performed. Clinical trial information: NCT04116164.
Targeting resistant prostate cancer with ATR and PARP inhibition (TRAP trial): A phase II study.
Authors: Reichert Zachery R. , Daignault Stephanie , Teply Benjamin A. , Devitt Michael Edward , Heath Elisabeth I. 
Published: February 2020

TPS254 Background: Inhibition of poly(ADP-ribose) polymerase (PARP) shows promise in prostate cancer, but is limited to the ~20% of men with defects in genes encoding for DNA repair proteins BRCA1, BRCA2 or ATM (homologous recombination defect positive, HRD+). The effect is modest for HRD+ patients with a progression free survival of ~7 months. Pharmacologically simulating genetic DNA repair defects may expand who benefits to homologous recombination defect negative (HRD-) patients and improve HRD+ response. The ataxia telangiectasia and Rad3-related protein (ATR) is ideal with its roles in cell cycle regulation, replication fork resolution and both single and double strand break repair. Preclinical studies on HRD-/HRD+ cell lines support this. We hypothesize co-inhibition of ATR and PARP will respond regardless of HRD status. Methods: TRAP is a prospective, multi-institutional, phase 2 clinical trial testing AZD6738 combined with olaparib in HRD+ and HRD- mCRPC patients. Primary endpoint is the response rate (RR) by RECIST radiographic response or PSA decline ≥50% in 35 HRD- patients, with a secondary objective of RR in 12 HRD+ patients. HRD+ is mono/biallelic loss of ATM or biallelic loss of BRCA1/2. Tissue based sequencing is done unless completed prior in mCRPC, known BRCA germline loss, treating provider deems biopsy unsafe or biopsy fails. Those unable or failing biopsy are designated as HRD-, but BRCA1/2 and ATM are tested via circulating tumor DNA in a commercial test. Eligible patients must progress after ≥1 line of mCRPC therapy. Progression on a second generation anti-androgen (e.g. apalutamide), abiraterone or within 6 months of docetaxel in hormone sensitive disease are eligible. Treatment entails 160 mg PO daily of AZD6738 on days 1-7 and 300 mg PO BID of olaparib on days 1-28 of a 28-day cycle. Statistical analysis will provide RR with 95% binomial confidence intervals. Analysis of tumor specimens, circulating tumor cells and DNA will be performed for predictors of response and acquired resistance. The study is at four sites in the US, participates in the Prostate Cancer Clinical Trials Consortium, LLC, is managed by the University of Michigan and funded by AstraZeneca. Clinical trial information: NCT03787680.
A phase Ib/IIa study of rucaparib (PARP inhibitor) combined with nivolumab in metastatic castrate-resistant prostate cancer.
Authors: Patnaik Akash , Duttagupta Priyanka , Chaudagar Kiranj , Alter Raanan , Hieromnimon Hanna , Szmulewitz Russell Zelig , Fleming Gini F. , Stadler Walter Michael 
Published: February 2020

TPS270 Background: Immune checkpoint blockade (ICB) therapies have had a major impact across a wide range of cancers. However, only subsets of patients across all malignancies benefit from ICB. In particular, metastatic castrate-resistant prostate cancers (mCRPC) have shown very limited responses to ICB. While there is ongoing work to identify predictive biomarkers to ICB responsiveness, early preclinical data from our group suggests that targeting fundamental DNA repair pathways could markedly increase the fraction of patients responsive to immunotherapeutic interventions. Based on these preclinical studies, we are conducting an investigator-initiated Phase Ib/IIa co-clinical trial of rucaparib and nivolumab singly and in combination, in mCRPC patients. Methods: Patients are randomized to one of three arms – rucaparib, nivolumab, or both drugs in combination for 4 weeks. Metastatic biopsy samples are collected at baseline and after 4 weeks on treatment, after which all arms switch to combination therapy. The primary objective is to assess feasibility of the combination, and to elucidate changes in T cell infiltration by RNA-seq analysis using established T-cell non-inflamed and inflamed gene signatures. Secondary objectives are to assess changes in immune cell infiltration via flow cytometry, multiplex IHC, transparent tissue tomography (3D mapping) and single-cell RNA-seq. We will correlate changes in the metastatic tumor microenvironment (TME) at baseline and following 4 weeks of treatment, with genomic alterations and clinical responses. We have currently enrolled 12 patients to the study, and collected pre- and 4 week on-treatment biopsies. This study utilizes novel emerging technologies for in-depth TME analysis that will unravel the impact of PARP inhibition, singly and in combination with PD-1 blockade, on specific immune subsets within the TME. The correlative analyses will also lead to the discovery of novel biomarkers of response/resistance, and suggest additional immuno-oncology combinations for specific genomic subsets of mCRPC. Clinical trial information: NCT03572478.
Intraoperative application of platelet-rich plasma to the neurovascular bundles during radical prostatectomy: A prospective clinical trial.
Authors: Joshi Vidhu B. , Juvet Tristan , Nichols Paige E. , Boorjian Stephen A. , Karnes Jeffrey , Tollefson Matthew K. , Gettman Matthew 
Published: February 2020

TPS380 Background: Radical prostatectomy (RP) is the most common surgical treatment for prostate cancer (PC). Yet even with nerve-sparing RP (NS-RP), a significant proportion of men experience transient or permanent erectile dysfunction (ED) partially due to intraoperative neurovascular bundle (NVB) damage from thermal or mechanical trauma. Studies have shown that platelet released growth factors counteract trauma and facilitate healing. We evaluate the use of platelet rich plasma (PRP) to facilitate early nerve healing and decrease ED after NS-RP. Methods: A prospective, open label, 20 subject human trial evaluating intraoperative topical NVB PRP application was approved by the IRB and FDA under an Investigational Device Exemption (IDE 16915) for the investigational use of an approved blood separation device. Men aged 50-60 with newly diagnosed, localized PC and normal preoperative sexual and urinary function, defined as a Sexual Health Inventory for Men (SHIM) score of >19 and an answer of “none” on question 5 of the Expanded Prostate Cancer Index Composite (EPIC) are eligible. Intraoperatively, a 10ml PRP product is created from a 180 mL sample of the patient’s whole blood using the Angel Concentrated Platelet Rich Plasma System (Cytomedix, Inc., Gaithersburg, MD USA). PRP is applied via mechanical transfer to the NVB after completion of the vesicourethral anastomosis. The primary endpoint is the safety and tolerability of PRP on the NVB after NS-RP. Secondary endpoints include feasibility of intraoperative PRP application and longitudinal assessment of erectile function and urinary continence by questionnaire administration at 3, 6, 9, 12 and 18 months after NS-RP. Clinical trial information: NCT02957149.
INTACT: Phase III randomized trial of concurrent chemoradiotherapy with or without atezolizumab in localized muscle invasive bladder cancer—SWOG/NRG1806.
Authors: Singh Parminder , Tangen Cathy , Efstathiou Jason A. , Lerner Seth P. , Jhavar Sameer G. , Hahn Noah M. , Costello Brian Addis , Sridhar Srikala S. , Du Weliang , Meeks Joshua J. , Faltas Bishoy Morris , Grivas Petros , Feng Felix Y , Chen Ronald C. , Morgans Alicia K. , Gupta Amit , Bangs Richard Carlton , Winter Kathryn A. , Vogelzang Nicholas J. , Thompson Ian Murchie 
Published: February 2020

TPS586 Background: Chemoradiotherapy(CRT) is a SOC for patients with muscle invasive bladder cancer (MIBC) who refuse or are not fit for radical cystectomy. Radiotherapy and chemotherapy are known to increases the PD-L1 expression in bladder cancer. Based on these observations, we hypothesized that addition of atezolizumab to CRT will increase its efficacy. Methods: This is a randomized phase III trial testing CRT with and without atezolizumab for 6 months in 475 patients with MIBC. Pts will be stratified on performance status (0-1 vs. 2); clinical stage (T2 vs T3/T4a, chemotherapy(cisplatin vs 5FU+mitomycin vs gemcitabine); and radiation field (bladder only vs small pelvis). Patients will undergo biopsy 18 week from registration. If they have residual disease they will be taken off protocol treatment and can proceed with alternative SOC option including radical cystectomy. Patients will be followed for 5 years. The primary end point of the study is bladder intact event –free survival (BIEFS). The event is comprised of: recurrence or residual muscle-invasive bladder cancer at 18 weeks or later, clinical evidence of nodal or metastatic disease, radical cystectomy, or death due to any cause. This composite endpoint is reflective of the intent of bladder preservation strategy with radical cystectomy included as one of the outcomes. Secondary end points include overall survival, modified event free survival, pathologic response at 18 weeks, metastasis free survival, cancer specific survival, rate of salvage cystectomy, rate of adverse event and QOL & PRO end points. The expected 3 year BIEFS for the control arm is 52%. The study leadership concluded that a 12% improvement in this endpoint is meaningful for this patient population. With a sample size of 475 patients the study has 85% power to detect the improvement from 52% to 64% in the BIEFS at 3 years (hazard ratio=0.68). The study team will perform translational studies evaluating tumor tissue, whole blood and urine for molecular and immunologic markers of immune response and response to RT. Successful completion of this trial could lead to a new treatment paradigm for patients with muscle invasive bladder cancer. Clinical trial information: NCT03775265.
PROOF 302: A randomized, double-blind, placebo-controlled, phase III trial of infigratinib as adjuvant therapy in patients with invasive urothelial carcinoma harboring FGFR3 alterations.
Authors: Pal Sumanta K. , Daneshmand Siamak , Matin Surena F. , Loriot Yohann , Sridhar Srikala S. , Grivas Petros , Gupta Shilpa , Sonpavde Guru , Fleming Mark T. , Lerner Seth P. , Berman Craig , Rearden Jessica , Ye Yining , Takkele Hiywot , Moran Susan , Bellmunt Joaquim 
Published: February 2020

TPS600 Background: Radical surgery ± cisplatin‐based (neo)adjuvant therapy (NAT) is the mainstay of treatment for invasive urothelial carcinoma of the upper urinary tract (UTUC) or bladder (UBC), but recurrence rates are high. Furthermore, many patients (pts) are unable to receive NAT because of cisplatin ineligibility. Fibroblast growth factor receptor 3 (FGFR3) genetic alterations occur in up to 70% of UTUC and up to 20% of UBC, and may constitute a potential candidate for targeted therapy. Infigratinib (BGJ398), a selective FGFR1–3 inhibitor, has shown promising clinical activity and tolerability in pts with advanced urothelial carcinoma having FGFR3 alterations [Pal et al. Cancer Discov 2018]. PROOF 302 has been designed to investigate the efficacy and safety of infigratinib versus placebo as adjuvant therapy in pts with high-risk invasive urothelial carcinoma and FGFR3 alterations. Methods: PROOF 302 is a randomized, double-blind, placebo-controlled, phase III study of approx. 218 pts. Adults with high-risk invasive UTUC or UBC with FGFR3 genetic alterations (i.e. mutations, gene fusions or translocations) who are ≤120 days following surgical resection and ineligible for cisplatin-based adjuvant chemotherapy or with residual disease after cisplatin- based NAT are eligible. Those who received non cisplatin-based NAT are eligible if they have residual disease and are ineligible for adjuvant cisplatin. Pts receive oral infigratinib 125 mg or placebo (1:1 ratio) once daily on days 1–21 every 28 days for up to 52 weeks or until disease recurrence, unacceptable toxicity or death. Primary endpoint: centrally reviewed disease-free survival (DFS). Secondary endpoints: DFS including intraluminal low-risk recurrence; metastasis-free survival; overall survival; DFS (per investigator); safety and tolerability. Exploratory endpoints include: quality of life; pharmacokinetics; cell-free DNA (cfDNA) and/or RNA for resistance mechanisms. The study will involve approximately 120 centers worldwide. Enrollment is expected to begin in January 2020. Trial registration: EudraCT 2019-003248-63. Clinical trial information: EudraCT 2019-003248-63.
Prediksi Akumulasi Sedimen Berdasarkan Survei Batimetri dan Hidrodinamika di Pesisir Teluk Mandeh, Kabupaten Pesisir Selatan, Sumatera Barat
Authors: Rahmawan Guntur Adhi , Wisha Ulung Jantama , Gemilang Wisnu Arya , Ilham Ilham , Husrin Semeidi 
Published: February 2020

Mandeh Bay is a semi-enclosed water area that there are two main estuaries, Mandeh and Nyalo River estuary. Sedimentation issue has been gotten worse due to the massive development in coastal area. This study aims to determine the sediment accumulation within Mandeh bay and its distribution patterns. The measurement of sedimentation rate applied in the Mandeh and Nyalo Estuaries. Oceanography parameters (tides and currents) recorded for 30 days measurement. The thickness of sediment accumulation was predicted by applying single beam echosounder dual frequency. The calculation of sediment volume was done using frustum formula grid 10 x10 meters. Flow model approach was also simulated to depict the distribution pattern of sediment. The thickness of sediment accumulation categorized into five spatial categories that are 0-0,3m, 0,4-0,6m, 0,7-0,9,1-1,2m, and 1,3-1,5m. The sedimentation rate in Mandeh estuary ranged from 60,85 up to 62,16 g.m-2.day-1, while in Nyalo estuary is approximately 48,86 g.m-2.day-1. The tidal current speed that is weak ranged from 0-0,05 m/s induces the sediment accumulation which mainly occurs during the neap tidal conditions. The thickness of sediment accumulation which is more than one meter identified around Mandeh River estuary and several areas near Carocok Tarusan Port where the sediment intake takes place and due to the weak current feature, it causes the increase of sedimentation in this region. Teluk mandeh merupakan kawasan teluk semi tertutup yang mempunyai 2 muara sungai besar yaitu sungai Mandeh dan sungai Nyalo. Masalah sedimentasi menjadi semakin parah karena pengembangan wilayah pesisir yang masif. Tujuan dari penelitian ini adalah untuk mengetahui ketebalan akumulasi sedimen di dalam Teluk Mandeh dan pola distribusinya. Pengukuran laju sedimentasi dilakukan pada dua fokus area yakni muara Sungai Mandeh dan Sungai Nyalo. Pengukuran parameter oseanografi (arus dan pasang surut) dilakukan selama 30 hari pengukuran. Ketebalan akumulasi sedimen diukur menggunakan alat Single Beam Echosounder Dual Frekuensi. Perhitungan volume sedimen dihitung dengan rumus frustum grid 10x10 meter. Simulasi flow model juga dilakukan untuk mengetahui pola distribusi sedimen. Sebaran ketebalan sedimen yang dibagi dalam 5 kategori spasial yakni 0-0,3m, 0,4-0,6m, 0,7-0,9,1-1,2m, dan 1,3-1,5m. Laju sedimentasi di muara Sungai Mandeh berkisar antara 60,85 sampai 62,16 g.m-2.hari-1 dan di muara Sungai Nyalo rata-rata 48,86 g.m-2.hari-1. Kecepatan arus pasang surut yang cukup lemah berkisar antara 0-0,05 m/s menyebabkan potensi akumulasi sedimen akan berlangsung terutama saat kondisi perbani. Sedimen dengan ketebalan lebih dari 1 meter teridentifikasi di sekitar Sungai Mandeh dan beberapa Kawasan Pelabuhan Carocok Tarusan dimana asupan sedimen mendominasi. Karena karakteristik arus yang lemah, sedimentasi meningkat diwilayah ini.
The Issue of Immunity of Private Actors Exercising Public Authority and the New Paradigm of International Law
Authors: Oddenino Alberto , Bonetto Diego 
Published: February 2020

Summary
1. The changing image and structure of international law – 2. The exercise of public authority through delegation – 3. The question of state immunity in the context of hybridisation between public and private – 4. The content of the activity as a paradigm to guide the extension of state immunity – 5. The issue of limiting the immunity of delegated non state actors – 6. Conclusions
High strength paper from high yield pulps by means of hot-pressing
Authors: Joelsson Tove , Pettersson Gunilla , Norgren Sven , Svedberg Anna , Höglund Hans , Engstrand Per 
Published: February 2020

AbstractThe hypothesis is that it should be possible to modify papermaking conditions in line with the softening properties of high yield pulp fibres and achieve similar strength properties to conventional chemical pulp based paper. We therefore investigated the rheological and physical properties of high yield pulp based papers during hot-pressing. Our results confirm that increased temperature combined with sufficient pressure enables permanent densification by softening of lignin, producing very high tensile strength. This treatment also significantly improved the wet tensile strength in comparison to bleached kraft pulp without using wet strength agents. The high yield pulps used here were spruce based thermomechanical pulp, chemi-thermomechanical pulp, and high temperature chemi-thermomechanical pulp, and birch-aspen based neutral sulphite semi chemical pulp, with spruce-pine based bleached kraft pulp as reference. Rapid Köhten sheets of150g/m2150\hspace{0.1667em}\text{g}/{\text{m}^{2}}and 50 % dryness were hot-pressed in a cylinder-press at 20–200 °C, 7 MPa, and 1 m/min. The mechanical properties showed great improvements in these high yield pulp papers, with tensile index increased to 75 kNm/kg and compression strength index to 45 kNm/kg; levels close to and better than bleached kraft. Wet strength increased to 16 Nm/g compared to 5 Nm/g for bleached kraft.
Análise do discurso do presidente do Brasil em 2019 no Fórum Econômico Mundial em Davos na Suíça e algumas ações do estadista sobre o meio ambiente, antes e depois do evento
Authors: Almeida Haroldo Oséias de , Almeida Ricardo Santos de 
Published: February 2020

RESUMO: Buscamos com esta análise problematizarmos os caminhos da política ambiental brasileira na contemporaneidade observando-se que a atual gestão do Governo Federal na figura do Presidente Jair Messias Bolsonaro, em 2019, adota posturas duvidosas no que se refere a operacionalização dos mecanismos de ordens sociais, ambientais e econômicas que confluiriam para o atendimento dos direitos de todos os cidadãos e ao desenvolvimento de forma justa, economicamente viável e ecologicamente correta. Para tal, explicitaremos trechos de suas falas antes, durante e depois da participação no Fórum Econômico Mundial em Davos na Suíça do Presidente. Destaca-se, portanto, os anseios por uma política ambiental que atenda a todos os anseios da nossa sociedade. Outro desafio refere-se a postura do estadista que demonstra um afastamento ideológico das discussões atuais da política ambiental que pode resultar um conflito abissal de interesses.
PALAVRAS-CHAVE: Planejamento, Meio ambiente, Gestão ambiental.
Ocorrência de Influenza A (H1N1) em Alagoas (2016-2019)
Authors: Lopes Ellen Karollyne Santos , Costa Allana Caroline Bonfim , Gomes Karoline Barbosa , Oliveira Samara dos Santos , Montiel Tariqat Sofia Machado , Santos Claudimary Bispo dos 
Published: February 2020

A Influenza A é uma doença viral do trato respiratório, que é transmitida em grande escala pelo vírus Myxovirus influenzae, através do contato de pessoa para pessoa por disseminação de gotículas contento partículas virais. Dentre os subtipos de influenza A, os subtipos H1N1 e H3N2 são os que se encontram em circulação ativa entre humanos. Os principais sintomas apresentados decorrentes da infecção são febre alta, dor muscular, dor de cabeça, tosse e cansaço. Neste contexto, o presente estudo objetivou quantificar os casos de Influenza A do subtipo H1N1, no Estado de Alagoas, durante o período de 2016 ao primeiro semestre do ano de 2019. A coleta dos dados ocorreu através da busca no site do Ministério da Saúde dos casos de SRAG por influenza A do subtipo H1N1 registrados em informes epidemiológicos. Em Alagoas, o ano de 2016 foi o que apresentou o maior número de casos de H1N1, 52 casos e 12 óbitos, enquanto em 2017 houve a menor expressividade, com 06 casos positivos e 03 óbitos. Em 2018, foram notificados 32 casos de H1N1 e 03 óbitos. No primeiro semestre de 2019 já foram confirmados 21 casos e 03 óbitos, porém, ainda, estão sendo investigados 37 casos e 05 óbitos. De acordo com os dados obtidos, conclui-se que, a doença viral H1N1, em Alagoas, no ano de 2016, houve uma positividade mais expressiva, enquanto, em 2017, ocorreu poucos casos, como também foi observado no país em geral.
PALAVRAS-CHAVE: Doença Viral; Informes Epidemiológicos; Trato Respiratório.
Lope de Estúñiga y la autoría de las Coplas de la panadera
Authors: Cáseda Teresa Jesús Fernando 
Published: February 2020

En este estudio, analizo la autoría de las Coplas de la panadera. Procedo a rebatir la autoría de Juan de Mena, de Rodrigo Cota, de los Manrique, de Pedro de Escavias y de Antón de Montoro. Concluyo que el autor es un miembro de la familia Estúñiga, Lope de Estúñiga, hijo del mariscal de Navarra y Castilla, Iñigo Ortiz de Estúñiga. Para ello, y tras seguir la pista que ofrece Juan de Mena, comparo una obra muy parecida a las Coplas de la panadera, el Decir de Lope de Estúñiga sobre la cerca de Atienza (1446), con la que coincide formalmente en la estructura métrica, rima, estribillo, formas léxicas, así como en la común crítica contra las guerras civiles entre los reinos peninsulares. Analizo las razones textuales que explican la autoría: el autor se esconde detrás de su familia y señalo la aparición de personas vinculadas a la vida de Lope de Estúñiga (los hijos de su primo Suero de Quiñones, con quien participó en el famoso paso honroso; el conde de Huelma – localidad que él ayudó a liberar, en su única acción bélica conocida-; el primo de su padre, marqués de Santillana…). Finalmente, intento explicar la causa de la escritura de la obra, en su doble condición de navarro y de castellano: como nieto del rey Carlos III el Noble y del justicia mayor de Castilla – Diego de Estúñiga- se burla por igual de unos y otros por su obstinación en una guerra fratricida.