bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell of Origin Influences Pancreatic Cancer Subtype
Authors: Flowers Brittany M. , Xu Hang , Mulligan Abigail S. , Hanson Kathryn J. , Seoane Jose A. , Vogel Hannes , Curtis Christina , Wood Laura D. , Attardi Laura D. 
Published: March 2021

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with a 5-year survival rate of approximately 9%. An improved understanding of PDAC initiation and progression is paramount for discovering strategies to better detect and combat this disease. Although transcriptomic analyses have uncovered distinct molecular subtypes of human PDAC, the factors that influence subtype development remain unclear. Here, we interrogate the impact of cell of origin and different Trp53 alleles on tumor evolution, using a panel of tractable genetically engineered mouse models. Oncogenic KRAS expression, coupled with Trp53 deletion or point mutation, drives PDAC from both acinar and ductal cells. Gene-expression analysis reveals further that ductal cell–derived and acinar cell–derived tumor signatures are enriched in basal-like and classical subtypes of human PDAC, respectively. These findings highlight cell of origin as one factor that influences PDAC molecular subtypes and provide insight into the fundamental impact that the very earliest events in carcinogenesis can have on cancer evolution.

Significance:
Although human PDAC has been classified into different molecular subtypes, the etiology of these distinct subtypes remains unclear. Using mouse genetics, we reveal that cell of origin is an important determinant of PDAC molecular subtype. Deciphering the biology underlying pancreatic cancer subtypes may reveal meaningful distinctions that could improve clinical intervention.
This article is highlighted in the In This Issue feature, p. 521
Poorer Clinical Outcomes for Black Patients with AML: A Wake-Up Call for Better Data and Greater Understanding of Cancer Outcomes in All Ethnic Groups
Authors: Vyas Paresh 
Published: March 2021

Abstract

Summary:
In this issue of Cancer Discovery, Bhatnagar and colleagues show that Black patients in the United States with acute myeloid leukemia have a shorter survival compared with white patients. This is an important paper as it addresses an under researched issue: the complex interaction of race, tumor genetics, socioeconomic factors, and access to treatment in defining treatment outcomes for a devastating cancer.
See related article by Bhatnagar et al., p. 626.
Genetic Ancestry Correlations with Driver Mutations Suggest Complex Interactions between Somatic and Germline Variation in Cancer
Authors: Gomez Felicia , Griffith Malachi , Griffith Obi L. 
Published: March 2021

Abstract

Summary:
Carrot-Zhang and colleagues describe associations between Native American ancestry and the somatic mutational landscape in lung cancer, including tumor mutation burden and specific driver mutations in EGFR, KRAS, and STK11. Local ancestry analysis suggests that specific germline loci, and not environment, underlie these associations.
See related article by Carrot-Zhang et al., p. 591.
Forced and Child Marriage at the Intersection of Health, Gender and Human Rights: Understanding the Determinants in Morocco and the Impact of the Migratory Context in Belgium
Authors: Sabbe Alexia 
Published: March 2021

With over 650 million women alive today already suffering the consequences of child marriage, the practice of forced and child marriage disproportionally affects girls and women. Given its impact on physical and psychological wellbeing, it is a serious form of violence against women.
In view of the global magnitude of forced and child marriage, and the increasing numbers of international migrants, the general objective of this research is to ascertain the determinants of forced and child marriage in Morocco and the impact of the migratory context on the issue among Moroccan migrants in Belgium.
Our research analysed forced and child marriage in both settings from two angles. First, we studied policies and the socio-cultural context in a top-down perspective through the analysis of legislation, public debates and through expert/stakeholder interviews. Secondly, we investigated the determinants of forced and child marriage in both research settings from a bottom-up perspective through Focus Group Discussions and household interviews, as well as investigating the impact of legislative conditions and restrictions on migrants and their families.
Genomic analysis of circulating tumor DNA in 3,334 patients with advanced prostate cancer to identify targetable BRCA alterations and AR resistance mechanisms.
Authors: Tukachinsky Hanna , Madison Russell , Chung Jon , Dennis Lucas , Fendler Bernard , Morley Samantha , Zhong Lei , Graf Ryon , Ross Jeffrey S. , Alexander Brian M , Abida Wassim , Chowdhury Simon , Ryan Charles J. , Fizazi Karim , Golsorkhi Anthony A. , Watkins Simon Paul , Simmons Andrew , Loehr Andrea , Venstrom Jeffrey , Oxnard Geoffrey R. 
Published: March 2021

25 Background: Comprehensive genomic profiling (CGP) by next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) from plasma provides a minimally invasive method to identify targetable genomic alterations (GAs) and resistance mechanisms in patients with metastatic castration-resistant prostate cancer (mCRPC). The circulating tumor fraction in patients with mCRPC and the clinical validity of GAs detected in plasma remain unknown. We evaluated the landscape of GAs using ctDNA-based CGP and assessed concordance with tissue-based CGP. Methods: Plasma from 3,334 patients with advanced prostate cancer (including 1,674 mCRPC screening samples from the TRITON2/3 trials and 1,660 samples from routine clinical CGP) was analyzed using hybrid-capture-based gene panel NGS assays. Results were compared with CGP of 2,006 metastatic prostate cancer tissue biopsies. Concordance was evaluated in 837 patients with both tissue (archival or contemporaneous) and plasma NGS results. Results: 3,127 patients [94%] had detectable ctDNA. BRCA1/2 were mutated in 295 patients [8.8%]. In concordance analysis, 72/837 [8.6%] patients had BRCA1/2 mutations detected in tissue, 67 [93%] of whom were also identified by ctDNA, and 20 patients were identified using ctDNA but not tissue [23% of all patients identified using ctDNA]. ctDNA detected subclonal BRCA1/2 reversions in 10 of 1,660 [0.6%] routine clinical CGP samples. AR alterations, including amplifications and hotspot mutations, which were detected in 940/2,213 patients [42%]. Rare AR compound mutations, rearrangements, and novel in-frame deletions were identified. Altered pathways included PI3K/AKT/mTOR [14%], WNT/β-catenin [17%], and RAS/RAF/MEK [5%]. Microsatellite instability was detected in 31/2,213 patients [1.4%]. Conclusions: In the largest study of mCRPC plasma samples conducted to date, CGP of ctDNA recapitulated the genomic landscape detected in tissue biopsies, with a high level of agreement in detection of BRCA1/2 alterations. It also identified patients who may have gained somatic BRCA1/2 alterations since archival tissue was collected. ctDNA detected more acquired resistance GAs than tissue, including novel AR-activating variants. The large percentage of patients with rich genomic signal from ctDNA, and the sensitive, specific detection of BRCA1/2 alterations position liquid biopsy as a compelling clinical complement to tissue CGP for patients with mCRPC.
A phase II study of onvansertib in combination with abiraterone and prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Einstein David Johnson , Choudhury Atish Dipankar , Saylor Philip James , Patterson Jesse Christopher , Croucher Peter , Ridinger Maya , Erlander Mark G. , Yaffe Michael B. , Bubley Glenn 
Published: March 2021

TPS186 Background: Metastatic CRPC remains a leading cause of cancer-related deaths worldwide. Although abiraterone + prednisone (abi) in either the castration-sensitive or castration-resistant setting increases survival, resistance is universal and generally occurs within 9-16 months of initiating treatment. Polo-like kinase 1 (PLK1) is a serine/threonine protein kinase that regulates mitotic functions and progression, and it is highly upregulated in prostate cancer following castration. Onvansertib is an oral and highly-selective PLK1 inhibitor that demonstrated safety and tolerability in a Phase 1 trial. Preclinical studies showed that PLK1 inhibition enhanced abi efficacy in cell line models and in patient-derived tumor xenografts via an AR-independent mechanism. Transcriptomic analyses revealed that abi induced mitosis-related gene sets in cells synergistic for abi + onvansertib, and identified an abi-onvansertib synergy gene signature. Methods: The goal of this phase 2 study (NCT03414034) is to observe the effects of onvansertib in combination with abi on disease control, as assessed by prostate-specific antigen (PSA) decline or stabilization after 12 weeks of study treatment, in subjects with mCRPC and early resistance to abi. Patients are enrolled at time of PSA progression while on standard abi. Patients with prior treatment with enzalutamide or apalutamide are excluded. Three onvansertib dosing schedules are tested in noncomparative arms: arm A (24 mg/m2 on days 1-5 of a 21-day cycle), arm B (18 mg/m2 on days 1-5 of a 14-day cycle), and arm C (12 mg/m2 on days 1-14 of a 21-day cycle). The 3 arms have completed their safety-lead phases and expansion phases are ongoing. With 32 patients in each arm, there will be 90% power to detect a change in disease-control rate from 10% (null) to 30% (alternative). Based on a Simon’s two-stage optimal design, the study will terminate early if < 2 of the first 13 patients in each arm achieve disease control. Exploratory analyses include evaluation of the presence of the androgen receptor variant 7 (AR-V7) in circulating tumor cells and targeted genomic profiling of circulating tumor DNA to assess associations between genomic alterations and response to treatment. Additionally, transcriptomic analysis of archived tumor tissue will be performed to determine whether enrichment for gene expression signatures, such as the abi-onv synergy signature identified in preclinical models, could be used to predict clinical response. Clinical trial information: NCT03414034.
A single-blinded, multicenter, randomized controlled trial to evaluate NeuroSAFE robotic-assisted radical prostatectomy (RARP) versus standard robotic-assisted radical prostatectomy (RARP) in men with localized prostate cancer: NeuroSAFE PROOF—Trial in progress.
Authors: Dinneen Eoin , Grierson Jack , Haider Aiman , Freeman Alex , Aning Jonathan , Persad Rajendra , Oakley Neil , Ahmad Imran , Dutto Lorenzo , Shaw Greg ,   NeruoSAFE PROOF Research Group
Published: March 2021

TPS262 Background: Robot-assisted radical prostatectomy (RARP) offers cure for localised prostate cancer but is associated with considerable toxicity. Potency and urinary continence are improved when the neurovascular bundles (NVBs) are preserved during a nerve-sparing (NS) RARP. The NeuroSAFE (intra-operative frozen section examination of the neurovascular structure adjacent prostate margin) seeks to promote optimal NS to maximise the opportunity for functional recovery without jeopardising oncological safety. The NeuroSAFE technique in RP has never been evaluated against a standard of care in an randomised controlled trial. Methods: This is a pragmatic, multicentre, single-blinded randomised controlled trial (RCT) in which men are allocated in a 1:1 ratio to NeuroSAFE RARP or standard RARP. Men in the NeuroSAFE RARP arm will undergo RARP with NS guided by the NeuroSAFE technique. Men in the standard RARP arm will undergo RARP with NS guided by standard current practice (prostate cancer clinical characteristics, multi-parametric magnetic resonance imaging (mpMRI) recommendations and digital rectal examination (DRE)). Eligible men will have operable localised prostate cancer, will be opting for RARP as primary treatment and will have good baseline erectile function (EF) (as defined by an Internatinoal Index of Erectile Function (IIEF)-5 score >21). The primary outcome is the proportion of men who achieve EF recovery at 12-months according to the IIEF. Oncological safety will be ensured by the independent DMC who will routinely review proportions of men with treatment failure (adjuvant therapy or biochemical recurrence (BCR)) in each arm. A sample size of 404 is estimated required. NeuroSAFE PROOF will continue to follow participant recovery for 5 years following treatment. Key secondary outcomes include patient-reported urinary continence recovery, sexual satisfaction, quality of life, and economic analyses. NeuroSAFE PROOF will be the first RCT of frozen section in radical prostatectomy (RP) in the world. Ethics and dissemination: Ethical approval was obtained from the National Research Ethics Committee North London (17/LO/1978). Results of this study will be disseminated through national and international papers, and to study participants. Clinical trial information: NCT03317990.
Insider Trading, Competition, and Real Activities Manipulation
Authors: Chen Hui , Jorgensen Bjorn N. 
Published: March 2021

We consider a setting where managers manipulate the firms’ real activities in anticipation of insider trading opportunities. Managers choose strictly higher production quantities than the quantities chosen absent insider trading, implying lower firm profit but higher consumer surplus. Through comparative statics, we show the overproduction is mitigated by the degree of competition in the industry, the manager’s current equity stake in the firm, and the precision of cost information. We also analyze the effects of insider trading in several extensions including asymmetric ownership structure, potential horizontal merger, and common market maker. This paper was accepted by Shiva Rajgopal, accounting.
KONSTRUKSI TAHLIL KELILING SELAMA BULAN RUWAH
Authors: Idris Muhammad Anwar 
Published: March 2021

AbstractJavanese society is known for its people who hold tightly to traditions from their ancestors, one of which is tahlilan. Tahlilan is an inseparable part in the midst of the majority of Javanese people. As with the tradition of tahlilan carried out by the people of Belor Village, Ngaringan District, Grobogan Regency, Central Java, it is a unique activity, because the implementation of tahlil is carried out alternately in each house during the intricate month. This study uses a living hadith study approach. The results of this study show that the traveling tahlil tradition is a tradition inherited from their ancestors, the implementation time is for 30 days in the month of ruwah, usually more until the middle of the month of Ramadan due to the enthusiasm of the people who want their homes to hold this tradition. The motives and goals of the perpetrators of this tradition are to send spirits or pray for families who have died through tahlil. The majority of people are not satisfied if they do not carry out this tradition and there is something missing in their life. In terms of the benefits of this activity, there are many, including strengthening the relationship between Muslims, competing to give alms and others.Keyword: Tradition, Tahlilan, Ruwah, Living HadisAbstrakMasyarakat Jawa dikenal dengan masyarakat yang memegang erat tradisi-tradisi peninggalan nenek moyang, salah satunya adalah tahlilan. Tahlilan merupakan bagian yang tidak dapat dipisahkan di tengah-tangah mayoritas masyarakat Jawa. Seperti halnya tradisi tahlilan yang dilakukan oleh masyarakat Desa Belor Kecamatan Ngaringan Kabupaten Grobogan Jawa Tengah menjadi kegiatan yang unik, karena pelaksanaan tahlil dilakukan keliling bergantian setiap rumah selama bulan ruwah. Penelitian ini menggunakan pendekatan kajian living hadis. Hasil dari penelitian ini bahwasannya tradisi tahlil keliling ini merupakan tradisi tinggalan nenek moyang mereka, waktu pelaksanaanya ialah selama 30 hari di bulan ruwah, bahkan biasanya lebih sampai pertengahan bulan ramadhan dikarenakan antusianya masyarakat yang ingin rumahnya mengadakan tradisi ini. Adapun motif dan tujuan para pelaku tradisi ini adalah ingin mengirim arwah atau mendoakan keluarga yang telah meninggal dunia melalui tahlil. Mayoritas masyarakat merasa belum puas jika tidak mengadakan tradisi ini serta ada yang kurang dalam hidupnya. Dari sisi manfaat kegiatan ini sangatlah banyak diantaranya mempererat tali silaturahmi sesama umat Islam, berlomba-lomba ingin mengulurkan sedekah dan lain-lain.Kata kunci : Tradisi, Tahlilan, Ruwah, Living Hadis
Glossary and tutorial of xenobiotic metabolism terms used during small molecule drug discovery and development (IUPAC Technical Report)
Authors: Erhardt Paul , Bachmann Kenneth , Birkett Donald , Boberg Michael , Bodor Nicholas , Gibson Gordon , Hawkins David , Hawksworth Gabrielle , Hinson Jack , Koehler Daniel , Kress Brian , Luniwal Amarjit , Masumoto Hiroshi , Novak Raymond , Portoghese Phillip , Sarver Jeffrey , Serafini M. Teresa , Trabbic Christopher , Vermeulen Nico , Wrighton Steven 
Published: March 2021

Abstract
This project originated more than 15 years ago with the intent to produce a glossary of drug metabolism terms having definitions especially applicable for use by practicing medicinal chemists. A first-draft version underwent extensive beta-testing that, fortuitously, engaged international audiences in a wide range of disciplines involved in drug discovery and development. It became clear that the inclusion of information to enhance discussions among this mix of participants would be even more valuable. The present version retains a chemical structure theme while expanding tutorial comments that aim to bridge the various perspectives that may arise during interdisciplinary communications about a given term. This glossary is intended to be educational for early stage researchers, as well as useful for investigators at various levels who participate on today’s highly multidisciplinary, collaborative small molecule drug discovery teams.
A Lisístrata e a Megera: panoramas da figura feminina na dramaturgia de Aristófanes e Shakespeare
Authors: Ruzene Felipe Daniel 
Published: March 2021

O seguinte texto trata sobre a visão do feminino dentro da dramaturgia de dois períodos históricos diversos, de modo a ilustrar quais os papéis sociais e perfis idealizados para a figura da mulher, dentro do recorte temporal estabelecido e por meio de duas comédias que tem sua trama desenvolvida por uma personagem feminina. Tais apontamentos serão analisados na antiguidade grega, bem como no período Elisabetano da Inglaterra por meio das obras “Lisístrata”, de Aristófanes, e “A megera domada”, de Shakespeare.Palavras-chave: A megera domada; Lisístrata; Feminino; Teatro. AbstractThe following text deals with the view of the feminine within the dramaturgy of two different historical periods, in order to illustrate the social roles and profiles idealized for the figure of the woman, within the established temporal cut and through two comedies that have their plot developed by a female character. Such notes will be analyzed in Greek antiquity, as well as in the Elizabethan period of England through the works of “Lysistrata” by Aristophanes and Shakespeare's “The Taming of the Shrew”.Keywords: The Taming of the Shrew; Lysistrata; Feminin; Theater.
POPULARIZAÇÃO CIENTÍFICA E TECNOLÓGICA: EXPERIMENTOS DE FÍSICA ITINERANTES NO AMBIENTE ESCOLAR
Authors: Just Márcio Carlos , Neckel Leandro 
Published: March 2021

O projeto Popularização Científica e Tecnológica é um projeto de extensão da Universidade do Extremo Sul Catarinense que busca levar até as escolas experimentos demonstrativos de física por meio de apresentações interativas. O projeto existe desde 2011 e surgiu da necessidade de tornar o ensino de física mais atrativo e próximo da realidade vivencial, no que se refere à compreensão da natureza por meio dos estudantes. Para isto, experimentos são desenvolvidos com o objetivo de apresentar, explorar e compreender fenômenos físicos naturais dentro das diferentes áreas da física (mecânica, térmica, óptica, elétrica, ondulatória e moderna). Os experimentos são apresentados em um formato de espetáculo, de forma a inspirar os estudantes que participam da apresentação. O projeto já atendeu 59 escolas até o momento e, durante a pandemia, realizou 4 apresentações por meio de transmissão via internet feita do laboratório de física experimental da Unesc (LaFiEx). Como resultado, percebe-se um aumento no interesse dos alunos das escolas atendidas por ciência e tecnologia e, ainda, uma conscientização de professores das próprias escolas em relação à importância da utilização de recursos experimentais para aprimoramento do processo de ensino-aprendizagem.
HUBUNGAN KECERDASAN EMOSIONAL DENGAN PRESTASI BELAJAR MAHASISWA PENDIDIKAN TEKNIK ELEKTRO FAKULTAS TEKNIK UNIVERSITAS NEGERI JAKARTA
Authors: Rachmadini Nur Aulia , Suyitno  , Zakir Irzan 
Published: March 2021

As purposes of this research are to know the level of emotional intelligence, learning achievement, and the closeness of the relationship of emotional intelligence and learning achievement of students.This research is an ex-post facto study and use a quantitative approach. The population of this research is students of Electrical Engineering Education, Faculty of Engineering, State Univerisity of Jakarta, years generation of 2015, 2016, and 2017, with a sample of 141. The analysis data techniques use descriptive statistical techniques and product moment correlation.The result of this research, showed that level of emotional intelligence and learning achievement of students had a good result with the result of tcount variabel X = -0,00634 and the result of tcount variabel Y = 0.940 with ttable = ±1,65581. Then, the result of the analysis with product moment correlation obtained a value rcount = 0,331, then that result are compared with rtable = 0,165 with a significance level of 5% and N = 141. Because rcount>rtable then shows a positive and significant relationship between emotional intelligence and learning achievement of students.
ABSTRAK
Penelitian ini bertujuan untuk mengetahui tingkat kecerdasan emosional dan prestasi belajar, dan keeratan hubungan antara kecerdasan emosional dengan prestasi belajar mahasiswa.
Penelitian ini merupakan penelitian ex-post facto dan menggunakan pendekatan kuantitatif. Populasi dalam penelitian ini adalah mahasiswa Pendidikan Teknik Elektro Fakultas Teknik Univeristas Negeri Jakarta angkatan tahun 2015, 2016, dan 2017 dengan sampel sebanyak 141. Teknik analisis data menggunakan teknik statistik deskriptif dan korelasi product moment.
Hasil penelitian ini, menunjukkan bahwa tingkat kecerdasan emosional dan prestasi belajar mahasiswa memiliki hasil yang baik dengan hasil thitung variabel X = -0,00634 dan hasil thitung variabel Y = 0,940 dengan ttabel = ±1,65581. Selanjutnya, hasil analisis dengan korelasi product moment diperoleh nilai rhitung = 0,331 kemudian hasil tersebut dibandingkan dengan rtabel = 0,165 dengan taraf signifikansi 5% dan N=141. Karena rhitung>rtabel maka menunjukan hubungan yang positif dan signifikan antara kecerdasan emosional dengan prestasi belajar mahasiswa.