bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized, double-blind, phase 3 trial of first-line pembrolizumab + platinum doublet chemotherapy (chemo) ± lenvatinib in patients (pts) with metastatic nonsquamous non–small-cell lung cancer (NSCLC): LEAP-006.
Authors: Hui Rina , Nishio Makoto , Reck Martin , Rodriguez-Abreu Delvys , Fouad Tamer M. , Flaim Doreen , Yin Lina , Dang Thao , Herbst Roy S. 
Published: May 2019

TPS9118 Background: Lenvatinib (multiple-receptor tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1–3, fibroblast growth factor receptors 1–4, platelet-derived growth factor receptors α, c-kit, and RET) has antitumor activity in combination with pembrolizumab (anti–PD-1 inhibitor) or with chemo in advanced NSCLC. LEAP-006 (NCT03829319) evaluates first-line lenvatinib with pembrolizumab + chemo for metastatic nonsquamous NSCLC. Methods: This randomized, double-blind, 2-part, phase 3 study enrolls pts ≥18 years with histologically/cytologically confirmed metastatic, nonsquamous, treatment-naive NSCLC without sensitizing genetic aberrations. Pts receive lenvatinib 8 mg daily or matching placebo + pembrolizumab 200 mg + pemetrexed 500 mg/m2 + carboplatin AUC 5 mg/mL/min or cisplatin 75 mg/m2 Q3W (4 cycles) followed by maintenance pembrolizumab (35 cycles) + lenvatinib/placebo + pemetrexed (no limit). In part 1 (open-label safety run-in), ~12 pts receive lenvatinib + pembrolizumab + chemo (n ≥6 in each chemo arm). If < 3 dose-limiting toxicities (DLTs; select prespecified AEs) occur in 6 pts in each arm in cycle 1, part 2 will begin enrolling. If ≥3 DLTs occur in 6 pts in each arm, enrollment in part 1 may continue with advisement by the study oversight committee. In part 2, pts are randomized 1:1 to lenvatinib or placebo + pembrolizumab + chemo, stratified by PD-L1 tumor proportion score ( < 50%/≥50%), geographic site (East Asian/other), and ECOG PS (0/1). Tumor imaging occurs at baseline and Q6W until wk 18; then Q9W until wk 54; then Q12W until verified PD, initiation of new cancer therapy, study withdrawal, or death. AEs are graded by NCI CTCAE v4.0. The primary endpoint in part 1 is safety. The primary endpoints in part 2 are PFS (RECIST v1.1 by BICR) and OS, analyzed by Kaplan-Meier method and stratified log-rank test. Secondary endpoints in part 2 are ORR and DOR (RECIST v1.1 by BICR), safety, and quality of life. Enrollment into part 1 will begin in March 2019. For part 2, approximately 714 pts will enroll in 160 sites in 17 countries. Clinical trial information: NCT03829319.
SAVANNAH: A Phase II trial of osimertinib plus savolitinib for patients (pts) with EGFR-mutant, MET-driven (MET+), locally advanced or metastatic non-small cell lung cancer (NSCLC), following disease progression on osimertinib.
Authors: Oxnard Geoffrey R. , Cantarini Mireille , Frewer Paul , Hawkins George , Peters Jane , Howarth Paul , Ahmed Ghada F. , Sahota Tarjinder , Hartmaier Ryan , Li-Sucholeiki Xiaocheng , Ahn Myung-Ju 
Published: May 2019

TPS9119 Background: The toxicity profile of the third-generation EGFR-tyrosine kinase inhibitor (TKI) osimertinib makes it an attractive backbone for combination with other targeted agents, possibly overcoming acquired resistance mechanisms. Combination with a MET-inhibitor is an intuitive approach as MET-amplification was identified as the most common mechanism of resistance to osimertinib in preliminary ctDNA data from the Phase III FLAURA (15% of pts) and AURA3 (19% of pts) studies. Savolitinib (AZD6094, HMPL-504, volitinib) is an oral, potent and highly selective MET-TKI that had an acceptable safety profile when combined with osimertinib in the Phase Ib TATTON study, providing the basis for this Phase II SAVANNAH study (NCT03778229). Other mechanisms of acquired resistance to osimertinib, including secondary EGFR mutations (e.g. C797S), RAS/RAF activation, and oncogenic gene fusions, provide additional opportunities for developing osimertinib-based combinations. Methods: Eligible pts will have histologically/cytologically confirmed EGFR-mutant NSCLC, and MET+ disease by central FISH, central IHC, or local NGS (retrospectively confirmed by central FISH/IHC). Pts must have documented radiological progression following 1–3 lines of prior therapy (must include osimertinib). Pts will receive osimertinib 80 mg plus weight-based dosing with savolitinib 300 or 600 mg PO QD, in 28-day cycles. The primary objective is efficacy (RECIST 1.1) by overall response rate (ORR) in pts who are MET+ by central FISH. Secondary endpoints include: ORR ( MET+ by central IHC and all pts); progression-free survival, overall survival, duration of response, percent change in tumor size, HRQoL, and EGFR mutation ctDNA clearance ( MET+ by central FISH, central IHC, and all pts); safety, and pharmacokinetics (all pts). Based on the TATTON study, we anticipate enrolling ~172 MET+ pts to include ≥117 pts with MET+ disease by central FISH. Enrolment began in Q1 2019. Ongoing development of complementary trials targeting other osimertinib resistance mechanisms will also be discussed. Clinical trial information: NCT03778229.
ORION: A Phase 2, randomized, multicenter, double-blind study to assess efficacy and safety of durvalumab+olaparib vs durvalumab alone as maintenance therapy in Stage IV non-small cell lung cancer (NSCLC).
Authors: Ahn Myung-Ju , Liu Yufan , Improta Teresa , Marcovitz Michelle , DiPiazza Kate , Lanasa Mark C. 
Published: May 2019

TPS9126 Background: Systemic chemotherapy for first-line (1L) metastatic NSCLC shows mixed outcomes. Results from studies using immunotherapy alone or combined with chemotherapy as 1L treatment in patients (pts) with metastatic NSCLC represent a substantial advance, but further improvement is needed. Increased DNA damage triggered by polyadenosine 5’diphosphoribose polymerase inhibition may confer antitumor activity, modify tumor immunogenicity, and further sensitize tumors to immune checkpoint inhibition, thus promoting a more durable antitumor response. This Phase 2, randomized, multicenter, double-blind study (NCT03775486) is designed to assess the efficacy and safety of durvalumab + olaparib vs durvalumab alone as maintenance therapy in pts whose Stage IV NSCLC has not progressed following 1L platinum-based chemotherapy + durvalumab. Methods: Adult pts with Stage IV NSCLC with tumors lacking activating EGFR mutations and ALK fusions are eligible. In the initial therapy phase, all pts will receive durvalumab (1500 mg IV) concurrent with platinum-based doublet therapy. Durvalumab + chemotherapy will be administered for 4 cycles for both squamous NSCLC (nanoparticle albumin-bound [nab]-paclitaxel + carboplatin or gemcitabine + carboplatin/cisplatin) and nonsquamous NSCLC (nab-paclitaxel + carboplatin or pemetrexed + carboplatin/cisplatin). Pts whose disease does not progress (complete or partial response [CR/PR] or stable disease [SD]; investigator-assessed RECIST 1.1) will be randomized (1:1) to durvalumab (1500 mg IV, every 4 weeks) + either olaparib (300 mg, oral, BID) or its matching placebo until disease progression. Randomization will be stratified based on objective response to durvalumab + chemotherapy (CR/PR or SD) during the initial therapy phase and histology (squamous or nonsquamous). The primary endpoint is PFS (investigator-assessed, RECIST 1.1). Secondary endpoints are OS, PFS in pts with homologous recombination repair related gene mutation, ORR, duration of response, HRQoL, pharmacokinetics and immunogenicity of durvalumab, and safety. Pt enrollment is ongoing. Clinical trial information: NCT03775486.
Spindle checkpoint silencing at kinetochores with submaximal microtubule occupancy
Authors: Etemad Banafsheh , Vertesy Abel , Kuijt Timo E. F. , Sacristan Carlos , van Oudenaarden Alexander , Kops Geert J. P. L. 
Published: May 2019

ABSTRACT
The spindle assembly checkpoint (SAC) ensures proper chromosome segregation by monitoring kinetochore–microtubule interactions. SAC proteins are shed from kinetochores once stable attachments are achieved. Human kinetochores consist of hundreds of SAC protein recruitment modules and bind up to 20 microtubules, raising the question of how the SAC responds to intermediate attachment states. We show that one protein module (‘RZZS-MAD1-MAD2’) of the SAC is removed from kinetochores at low microtubule occupancy and remains absent at higher occupancies, while another module (‘BUB1-BUBR1’) is retained at substantial levels irrespective of attachment states. These behaviours reflect different silencing mechanisms: while BUB1 displacement is almost fully dependent on MPS1 inactivation, MAD1 (also known as MAD1L1) displacement is not. Artificially tuning the affinity of kinetochores for microtubules further shows that ∼50% occupancy is sufficient to shed MAD2 and silence the SAC. Kinetochores thus respond as a single unit to shut down SAC signalling at submaximal occupancy states, but retain one SAC module. This may ensure continued SAC silencing on kinetochores with fluctuating occupancy states while maintaining the ability for fast SAC re-activation.
Perbandingan Dosis Induksi dan Pemeliharaan Propofol Pada Operasi Onkologi Mayor yang Mendapatkan Pemedikasi Gabapentin dan Tanpa Gabapentin
Authors: Okta Ida Bagus , Subagiartha I Made , Wiryana Made 
Published: May 2019

Latar Belakang : Anestesi umum merupakan teknik anestesi yang paling sering dikerjakan dibandingkan dengan teknik anestesi lain. Total Intravena Anestesi menggunakan propofol telah dikembangkan secara luas, karena menurunnya angka insiden PONV, biaya anestesi yang lebih murah, dan waktu pulih yang cepat. Berbagai teknik, alat dan obat-obatan diteliti untuk mengurangi dosis propofol yang diperlukan durasi operasi karena efek samping propofol yang berbahaya, yang dikenal PRIS (Propofol Related Infusion Syndrome), yang dapat menyebabkan morbiditas dan mortalitas yang tinggi. Tujuan : Untuk membandingkan dosis induksi dan pemeliharaan propofol yang diperlukan intraoperatif antara kelompok gabapentin dan kelompok kontrol. Selanjutnya hasil penelitian dapat digunakan secara umum dalam penggunaan gabapentin sebagai obat akut pada periode perioperatif.Metode : Penelitian ini adalah double blind clinical trial. Teknik penelitian ini dapat mengkontrol ekspektasi dan manipulasi subjek penelitian terhadap prosedur penelitian sehingga dapat menghasilkan hasil yang valid dan terpercaya. Penelitian dibagi menjadi dua kelompok, kelompok gabapentin dan kelompok kontrol. 32 sampel tiap kelompok telah menjalani operasi onkologi mayor dengan teknik anestesi yang sama total intravena propofol dengan TCI. Hasil : Dosis induksi kelompok gabapentin memiliki 1,15 mg/kgbb dibandingkan dengan kelompok kontrol yang memiliki median 1,48 mg/kgbb (p < 0,001). Dosis pemeliharaan kelompok gabapentin memiliki median 93,27 mcg/kgbb/menit dibandingkan kelompok kontrol yang memiliki median 123,80 mcg/kgbb/menit (p < 0,001).Simpulan : Premedikasi oral gabapentin 600 mg efektif menurunkan dosis induksi dan pemeliharaan propofol yang digunakan pada teknik TIVA untuk menjaga operasi mayor onkologi. Selanjutnya premedikasi gabapentin dapat digeneralisir penggunaannya pada operasi lain untuk menurunkan kebutuhan propofol intraoperatif.
Implementation of a novel self-induced promoter for the expression of pharmaceutical peptides in Escherichia coli: YY(3-36) peptide
Authors: Momen Amir Hossein , Harzandi Naser , Haddadi Azam , Bambai Bijan 
Published: May 2019

Abstract

Background
Increasing the expression rate of recombinant mammalian hormones in Escherichia coli by combining efficient promoters and signal sequences is a never ending process. A self-induced promoter will have some beneficial gains compared to the classical T7 promoter or its variants with isopropyl β-D-1-thiogalactopyranoside (IPTG) as the inducer. Obesity is the prime suspect in widespread frequency of diabetes type II and cardiovascular diseases worldwide. YY (tyrosine-tyrosine) peptide is a local acting hormone, controlling appetite. Excitingly, it was has been shown that a truncated version of the YY peptide, YY(3-36) peptide, has potential as a worthy biopharmaceutical agent in the fight against obesity.

Materials and methods
To develop an economical expression system for the large scale production of the peptide in Gram-negative bacteria, we introduced a promoter sequence upstream of a chimeric gene for the extracellular expression of this peptide with the assistance of a signal sequence of asparaginase II from E. coli. This system has the advantage of producing a complete sequence of a truncated YY peptide, YY(3-36), without any extra tags that would require further removal with the assistance of expensive specific proteases and reduced the downstream steps, significantly.

Results
Recombinant production of YY(3-36) peptide under a self-induced promoter proves the efficacy of the asparaginase II signal sequence as a communicator of foreign peptides and proteins into the extracellular space of E. coli.

Conclusions
The application of fusion protein expression of biopharmaceuticals, especially mammalian hormones, in prokaryotic systems with the help of native signal sequences makes some common tags with expensive proteases for the removal of the attached protein Tag redundant.
Educational interventions to improve menstrual health: approaches and challenges
Authors: Rastogi Shreya , Khanna Aparna , Mathur Pulkit 
Published: May 2019

Abstract

Background
Inappropriate menstrual care practices result in adverse health consequences among girls. Developing and implementing interventions that minimize these adverse consequences and facilitate development of healthy menstrual behavior are a priority for any nation.

Objectives
This study aimed at collating, summarizing and reviewing evidence to assess the effectiveness of interventions to improve menstrual health and the challenges faced in doing the same.

Methods
A systematic review of studies published in peer-reviewed journals and project reports was conducted. Intervention studies related to menstrual health management conducted from 2007 to 2018 were analyzed. A total of 27 interventions conducted among young girls in different countries were identified and study characteristics and outcomes were reviewed.

Results
Different intervention studies used a variety of methods like lectures, discussions, demonstrations using multiple audio-visual aids and provision of resources like menstrual cups, sanitary pads and washing soap to spread awareness about menstrual hygiene. Most of the interventions reported a positive impact on the awareness and menstrual practices of girls. However, in a few studies no significant change was observed in the attitude regarding regular bathing, practices related to self-medication for dysmenorrhea and socio-cultural taboos.

Conclusion
This review of literature has offered insights into the scope and development of future interventions so that apart from increasing awareness and knowledge on menstrual health issues, sustained behavior change can be brought about among girls to improve their health.
Tort Policy in a Plural Context: Pathways Towards Objective Liability in UAE Tort Law
Authors: Jadalhaq Iyad Mohammad 
Published: May 2019

Abstract
This article approaches tort policy contextually, as an argument around actually available alternatives within a historically-specific legal tradition, like that of the United Arab Emirates (UAE), which combines French civil law influence with roots in Islamic law. The article examines alternative tunings of the requirements of tort liability, in view of cases where a technically sophisticated investigation is required to ascertain what precautions the tortfeasor might have taken to prevent injury. For this purpose, it takes as its point of departure a careful assessment of the availability of the “extraneous cause” exception in UAE law, which allows defendants to avoid liability by demonstrating the occurrence of a causal factor outside their sphere of control. To understand when this exception ought to be available, the paper engages in critical dialogue with French doctrines on tort liability, distinguishing a fault-based “subjective approach” from an “objective approach” (strict liability). These doctrines also speak to Arab jurisdictions that have adopted a civil code (like the UAE), modelled after the French one. The article therefore proceeds to situate the tort regime in the UAE Civil Code with respect to those French doctrines. With respect to these, the UAE Civil Code takes an intermediate position drawn from Islamic law. However, additional provisions, e.g. on liability for nuclear installations or for machinery of which a person is in charge, demonstrate a timid reception of the objective approach. The article proposes a reform of UAE tort liability on the basis of the objective approach, which is robust even in complex cases, where an investigation around causation would risk being inconclusive. Finally, the paper considers the additional possibility of arguing for a voluntary assumption of liability on the part of the tortfeasor, as yet another way of orienting tort liability in the UAE towards an objective approach.
Social and psychological causes of gender inequality in present-day female career development
Authors: Чуйко Оксана 
Published: May 2019

The article actualize the issue of gender equality as a precondition for successful female career pursuit. We study issues of gender equality in the light of gender inequality manifestation and its influence on female career opportunities. We have analyzed primary indicators of gender inequality with regard to employment, such as gender segregation, glass ceiling effect, gap in wages, dual employment of women (family and work), gender stereotypes, gender-based harass­ment and violence.

We have outlined primary ways to reduce gender inequality with regard to employment, namely:

challenging gender stereotypes (public awareness campaign aimed at iden­tifying and studying gender stereotypes of a certain community; analyzing one’s own gender stereotypes, examining their sources, etc.);
developing wider concepts and beliefs with regard to gender-sensitive issues in the workplace;
understanding signs and limits of gender-based harassment and violence, their prevention and avoidance;
developing effective coping strategies for pressure;
balancing work, family and private life by women;
developing psychological characteristics and personality features essential for one’s occupation, which can contribute to professional development of a person, acknowledgment of their expertise irrespective of gender identity;
developing harmonious personality (personal growth trainings), self-education and lifelong learning;
practical trainings for successful career, coaching;
public legal education (awareness of laws on gender-sensitive issues in the labor market);
implementing and abiding by gender equality policies in various sectors, fostering organizational culture based on gender equality.
Конструювання картини світу особистості за умов інформаційного суспільства
Authors: Шевченко Вікторія , Байєр Оксана 
Published: May 2019

За умов інформаційного суспільства трансформується світ, а разом з ним і людина. Змінюється характер становлення особистості та соціальної взаємодії. Сучасна людина нерозривно пов’язана з технологіями, які розширюють її світогляд та впливають на світо­сприйняття. В ході цього відбуваються зміни когнітивних процесів. У статті ана­лізується трансформація свідомості особистості та її когнітивних процесів в умовах інформаційного суспільства, розглядається поняття «кліпової культури» покоління Z. Кліпова свідомість формується на основі засвоєння невеликих фрагментів інформації, які позбавлені основної ідеї та доповнені витягами вражень, постійно перезавантажуються та оновлюються. Основними характеристиками такого сприйняття є динамізм, лабіль­ність та ак­туальність.
Sintesis dan Karakterisasi Nanopartikel Perak-Tricalcium Phosphate (TCP) dengan Bantuan Ekstrak Daun Alpukat (Percea americana)
Authors: Rahmayani Yessi , Zulhadjri Zulhadjri , Arief Syukri 
Published: May 2019

Sintesis nanopartikel perak-TCP telah dilakukan pada penelitian ini. Nanopartikel perak dibuat dengan mereduksi larutan perak nitrat dengan menggunakan ekstrak daun alpukat sebagai bioreduktor. Tricalsium Phosphate (TCP) dicelupkan kedalam nanopartikel perak membentuk komposit perak-tricalcium phosphate. Hasil analisis UV-Vis menunjukkan pembentukan puncak serapan nanopartikel perak pada panjang 445-446 nm, yakni puncak yang khas dari nanopartikel perak yang disebabkan oleh adanya fenomena Surface Plasmon Resonance (SPR). Penelitian ini menghasilkan perak-TCP dengan ukuran nanopartikel. Sesuai hasil X-Ray Diffraction (XRD) yang menunjukkan bahwa ukuran kristal TCP adalah 64 nm dan ukuran Kristal perak dalam komposit adalah 46 nm. Hasil Scanning Electron Microscopy (SEM) menunjukan partikel perak terdistribusi dipermukaan partikel TCP. Kata Kunci: Komposit perak-TCP, nanopartikel perak, Percea americana, tricalcium phosphate. The silver-TCP nanoparticle synthesis was carried out in this study. Silver nanoparticles are made by reducing silver nitrate solution using avocado leaf extract as a bioreactor. Tricalcium Phosphate (TCP) is dipped into silver nanoparticles to form a silver-tricalcium phosphate composite. The UV-Vis analysis shows the formation of silver nanoparticle absorption peaks at a length of 445-446 nm, which is a typical peak of silver nanoparticles caused by the Surface Plasmon Resonance (SPR) phenomenon. X-Ray Diffraction (XRD) shows that the TCP crystal size is 64 nm and the size of the Silver Crystal in the composite is 46 nm. The results of Scanning Electron Microscopy (SEM) show silver particles distributed on the surface of TCP particles Keywords: Percea americana, silver-TCP composite, silver nanoparticle, tricalcium phosphate.
Accurate detection of Helicobacter pylori antigen in human stool specimens by two novel immunoassays
Authors: Ignatius Ralf , Berg Christiane , Weiland Chris , Darmer Angela , Wenzel Thilo , Lorenz Marion , Fuhrmann Jörg , Müller Michael 
Published: May 2019

Stool antigen tests are recommended for the diagnosis of Helicobacter pylori infection. Here, we compared two novel assays, i.e., one enzyme immunoassay (EIA) and one immunochromatography assay (ICA), with a chemiluminescence immunoassay (CLIA) that had previously been compared with rapid urease test, histology, and urea breath test. Two hundred sixty-six frozen stool samples with defined CLIA results (42 positives, 219 negatives, and 5 samples with borderline results) collected between January and May 2018 were thawed and immediately tested by EIA, ICA, and CLIA.
In 248 samples with repeatedly positive/negative CLIA results, EIA and ICA were positive for 40 and 37 of 41 CLIA-positive samples and yielded negative results for 206 and 201 of 207 CLIA-negative samples, respectively. There was a high positive percent agreement (EIA, 97.6%; 95% confidence interval (95% CI), 86.3–100%; ICA, 90.2%; 95% CI, 76.9–96.7%), as well as a negative percent agreement between the assays (EIA, 99.5%; 95% CI, 97.0–100%; ICA, 97.1%; 95% CI, 93.7–98.8%). This was further supported by kappa values indicating very good agreement (CLIA vs. EIA, 0.971; CLIA vs. ICA, 0.857). In conclusion, both EIA and ICA comprise valuable assays for the detection of H. pylori antigen in stool samples.
Solid state synthesis and characterization of n–p (SnO2)1.3/(α ∼ Bi2O3)x/(β ∼ Bi2O3)1−x photocatalyst modulated by PVA and its photocatalytic performance
Authors: Qiu Taoyu , Zhu Weiwei , Liu Shaoyou , Chen Kao , Liang Siliang , Feng Qingge 
Published: May 2019

Abstract
Hillery-type Amplitude Squeezing in Linear and Nonlinear Fan-states
Authors: Duc Truong Minh 
Published: May 2019

Squeezing properties of the Hillery-type $N$-powered amplitude are investigated in the linear and nonlinear fan-state. For a given $k$, squeezing may appear to the even power $N=2k$ and
the number of directions along which the Nth-powered amplitude is squeezed is exactly equal to $N,$ in both linear (the light field) and nonlinear (the vibrational motion of the trapped ion) fan-states.