bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of the combination chemotherapy of bevacizumab and gemcitabine in women with platinum-resistant recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer
Authors: Nagao Shoji , Kogiku Ai , Suzuki Kazuhiro , Shibutani Takashi , Yamamoto Kasumi , Jimi Tomoatsu , Kitai Miho , Shiozaki Takaya , Matsuoka Kazuko , Yamaguchi Satoshi 
Published: February 2020

Abstract
Introduction
Bevacizumab and gemcitabine are key drugs for treating recurrent epithelial ovarian cancer. However, information about the combination of bevacizumab and gemcitabine is insufficient. We conducted a phase II study to assess the feasibility, clinical activity, and toxicity of this combination chemotherapy.

Methods
This study included women with platinum-resistant recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer who received one to three regimens of platinum-based chemotherapy between April 1, 2015 and December 31, 2018. The patients received bevacizumab 15 mg/kg intravenously on day 1 and gemcitabine 1000 mg/m2 intravenously on days 1 and 8 every 21 days until disease progression or unacceptable toxicity. The primary endpoint was the completion rate of three cycles of chemotherapy. This study was registered in the University Medical Information Network (UMIN) Clinical Trials Registry (UMIN000016619).

Results
Among the 19 patients, 18 (95%) received ≥3 and 9 (47%) received ≥6 cycles of the study therapy. The objective response rate was 42% (complete response of 16% and partial response of 26%), and the clinical control rate was 84%. Hematological toxicity included neutropenia grade 3/4 in 9 patients (47%), anemia grade 3/4 in 2 (11%), and thrombocytopenia grade 3/4 in 1 (5%). One patient (5%) had grade 3 hypertension, and 1 (5%) had grade 3 protein urea. Possibly related grade 3 pulmonary toxicity was observed in 1 patient. Three patients needed dose reduction of gemcitabine to 800 mg/m2 due to treatment delay by 15 to 21 days on day1. There was no treatment delay more than 14 days on day 8. The median progression-free survival duration was 5.1 months and median overall survival duration was 21.3 months.

Conclusion
The combination chemotherapy with gemcitabine and bevacizumab was feasible, effective and safe. This combination chemotherapy may be explored in a further randomized trial.
Systematic functional identification of cancer multi-drug resistance genes
Authors: Lau Man-Tat , Ghazanfar Shila , Parkin Ashleigh , Chou Angela , Rouaen Jourdin R. , Littleboy Jamie B. , Nessem Danielle , Khuong Thang M. , Nevoltris Damien , Schofield Peter , Langley David , Christ Daniel , Yang Jean , Pajic Marina , Neely G. Gregory 
Published: February 2020

Abstract
Background
Drug resistance is a major obstacle in cancer therapy. To elucidate the genetic factors that regulate sensitivity to anti-cancer drugs, we performed CRISPR-Cas9 knockout screens for resistance to a spectrum of drugs.

Results
In addition to known drug targets and resistance mechanisms, this study revealed novel insights into drug mechanisms of action, including cellular transporters, drug target effectors, and genes involved in target-relevant pathways. Importantly, we identified ten multi-drug resistance genes, including an uncharacterized gene C1orf115, which we named Required for Drug-induced Death 1 (RDD1). Loss of RDD1 resulted in resistance to five anti-cancer drugs. Finally, targeting RDD1 leads to chemotherapy resistance in mice and low RDD1 expression is associated with poor prognosis in multiple cancers.

Conclusions
Together, we provide a functional landscape of resistance mechanisms to a broad range of chemotherapeutic drugs and highlight RDD1 as a new factor controlling multi-drug resistance. This information can guide personalized therapies or instruct rational drug combinations to minimize acquisition of resistance.
Admixture-enabled selection for rapid adaptive evolution in the Americas
Authors: Norris Emily T. , Rishishwar Lavanya , Chande Aroon T. , Conley Andrew B. , Ye Kaixiong , Valderrama-Aguirre Augusto , Jordan I. King 
Published: February 2020

AbstractBackgroundAdmixture occurs when previously isolated populations come together and exchange genetic material. We hypothesize that admixture can enable rapid adaptive evolution in human populations by introducing novel genetic variants (haplotypes) at intermediate frequencies, and we test this hypothesis through the analysis of whole genome sequences sampled from admixed Latin American populations in Colombia, Mexico, Peru, and Puerto Rico.ResultsOur screen for admixture-enabled selection relies on the identification of loci that contain more or less ancestry from a given source population than would be expected given the genome-wide ancestry frequencies. We employ a combined evidence approach to evaluate levels of ancestry enrichment at single loci across multiple populations and multiple loci that function together to encode polygenic traits. We find cross-population signals of African ancestry enrichment at the major histocompatibility locus on chromosome 6, consistent with admixture-enabled selection for enhanced adaptive immune response. Several of the human leukocyte antigen genes at this locus, such asHLA-A,HLA-DRB51, andHLA-DRB5, show independent evidence of positive selection prior to admixture, based on extended haplotype homozygosity in African populations. A number of traits related to inflammation, blood metabolites, and both the innate and adaptive immune system show evidence of admixture-enabled polygenic selection in Latin American populations.ConclusionsThe results reported here, considered together with the ubiquity of admixture in human evolution, suggest that admixture serves as a fundamental mechanism that drives rapid adaptive evolution in human populations.
Protocol for a randomised controlled trial of a co-produced, complex, health promotion intervention for women with prior gestational diabetes and their families: the Face-it study
Authors:   On behalf of the Face-it Study Group, Nielsen Karoline Kragelund , Dahl-Petersen Inger Katrine , Jensen Dorte Møller , Ovesen Per , Damm Peter , Jensen Nanna Husted , Thøgersen Maja , Timm Anne , Hillersdal Line , Kampmann Ulla , Vinter Christina Anne , Mathiesen Elisabeth Reinhardt , Maindal Helle Terkildsen 
Published: February 2020

Abstract
Background
Gestational diabetes mellitus (GDM) is associated with an increased risk of future diabetes in both mother, father and offspring. More knowledge is needed about how to effectively reduce the risk of diabetes through sustained behavioural interventions in these families. The Face-it intervention is a complex health promotion intervention embedded in multi-level supportive environments. The aim of the intervention is to reduce type 2 diabetes risk and increase quality of life among families in the first year following a GDM-affected pregnancy by promoting physical activity, healthy dietary behaviours and breastfeeding through a focus on social support, motivation, self-efficacy, risk perception and health literacy.

Methods
This national multicentre study is a two-arm randomised controlled trial including 460 women with GDM in a ratio of 2 (intervention):1 (usual care). The Face-it intervention consists of three main components: 1) additional visits from municipal health visitors, 2) digital health coaching tailored to family needs and 3) a structured cross-sectoral communication system in the health care system. The intervention runs from 3 to 12 months after delivery. The primary outcome is maternal body mass index at 12 months after delivery as a proxy for diabetes risk.
The women will be examined at baseline and at follow-up, and this examination will include blood tests, oral glucose tolerance test (OGTT), anthropometrics, blood pressure, self-reported diet and physical activity, breastfeeding, quality of life, health literacy, physical and mental health status, risk perception and social support. Aside from those data collected for OGTT and breastfeeding and offspring parameters, the same data will be collected for partners. Data on offspring anthropometry will also be collected. Information on pregnancy- and birth-related outcomes will be derived from the medical records of the woman and child.

Discussion
This randomised controlled trial seeks to demonstrate whether the Face-it intervention, addressing the individual, family and health care system levels, is superior to usual care in reducing diabetes risk for mothers and their families. Coupled with a process evaluation and an economic analysis, the study will provide evidence for policymakers and health services about health promotion among families affected by GDM and the potential for reducing risk of type 2 diabetes and associated conditions.

Trial registration
ClinicalTrials.gov NCT03997773. Registered June 25, 2019 – Retrospectively registered.
Evaluation of anti-infective potencies of formulated aloin A ointment and aloin A isolated from Aloe barbadensis Miller
Authors: Donkor Addai-Mensah , Donkor Martin Ntiamoah , Kuubabongnaa Ngmenpone 
Published: February 2020

Abstract
Introduction
Isolated bioactive components of plants or their raw extract are utilized as complementary or alternate remedy in copious illnesses. The current research was aimed at assessing the activity of aloin A isolated from Aloe barbadensis Miller and its formulated ointment against six (6) selected clinical isolates.

Methods
The column chromatography was utilized in isolating aloin A from chloroform/methanol solvent polarity. The characterization of the isolated compound was performed by spectroscopy techniques corresponding to UV, IR, 1H- and 13C-NMR spectroscopy. It was formulated as ointment using polyethylene glycol (PEG) and both the ointment and the isolated compound were probed for in vitro antimicrobial activity.

Results
Aloin A has been isolated from chloroform/methanol solvent mixture. The structure has been explicated as (10S)-10-β-d-glucopyranosyl-1,8-dihydroxy-3-(hydroxymethyl)-9(10H)-anthracenone(1S)-1,5-anhydro-1-[(9S)-4,5-dihydroxy-2-(hydroxymethyl)-10-oxo-9,10-dihydro-9-anthracenyl]-d-glucitol. The minimum inhibitory concentration (MIC) of the isolated aloin A on the pathogens ranged from 2.5 to 5.0 mg/ml and 0.32 to 5.0 mg/ml for both aloin A and the formulated ointment respectively. It was further revealed that the activity of aloin A showed dose dependence against all the test microorganisms. There was no significant difference in the activity of the drug against K. pneumoniae, S. aureus, E. coli, C. albicans and T. flavus (P > 0.05) when the concentration was raised from 2.5 to 5 mg/ml, however, there was significant difference (P ˂ 0.05) in activity against P. aeruginosa. The formulated ointment exhibited dose dependent activity against all test microorganisms. At low concentrations, the ointment showed no significant difference in diameter zone of inhibition against all test microorganisms (P > 0.05) except P. aeruginosa which exhibited a highly significant difference (P < 0.05).

Conclusion
Both the isolated aloin A and its formulated ointment demonstrated substantial inhibition of growth of the pathogenic strains. These findings sturdily suggest that aloin A is a nascent drug that could be explored as skin and wound transmittable agent.
Aryl hydrocarbon receptor signals attenuate lung fibrosis in the bleomycin-induced mouse model for pulmonary fibrosis through increase of regulatory T cells
Authors: Takei Hiroshi , Yasuoka Hidekata , Yoshimoto Keiko , Takeuchi Tsutomu 
Published: February 2020

Abstract
Background
Interstitial lung disease (ILD) is a serious complication of connective tissue diseases (CTDs). Although immune dysregulation triggered by genetic and environmental factors is thought to provoke inflammation and subsequent fibrosis, precise mechanisms of these processes remain unclear. Recent reports suggest that activation of aryl hydrocarbon receptor (AhR) signals by various ligands such as tryptophan derivatives can induce hyper-immune responses and are involved in autoimmunity. We investigated the effects of AhR signals on the process of lung fibrosis and changes in immunological features using a bleomycin (BLM)-induced lung fibrosis mouse model.

Methods
BLM was administered intratracheally to C57BL/6JJcl mice and either 5,11-dihydroindolo[3,2-b]carbazole-6-carboxaldehyde (FICZ), a natural AhR ligand, or vehicle was subsequently injected intraperitoneally on day 0, 1, and 2 from BLM administration. Mice were sacrificed at week 3, and lung fibrosis was quantified by the histological changes using the Ashcroft score and deposition of soluble collagen levels in the lung using Sircol assay. The population of immune cells infiltrated into the lungs was analyzed using flow cytometry.

Results
Both the Ashcroft score and soluble collagen level in FICZ-treated mice were significantly lower than those in the vehicle group. Moreover, the survival rate of FICZ-treated mice was significantly higher than that of control mice during the 3 weeks after treatment. Interestingly, flow cytometric analysis revealed that the number of CD4+Foxp3+ regulatory T cells (Tregs) was significantly increased and CD4+IFNγ+ and γδ+IL-17A+ T cells were decreased in the lungs of FICZ-treated mice, while the total number of T, B, and NK cells were unaffected by FICZ treatment.

Conclusions
Our findings suggest that stimulation of AhR signals attenuated lung fibrosis by increasing Tregs and suppressing inflammatory T cell subsets in a BLM-induced fibrosis model. AhR signaling pathways may therefore be useful therapeutic targets for connective tissue disease-associated ILD.
Vascular lesions of the head and neck: an update on classification and imaging review
Authors: Brahmbhatt Akshaar N. , Skalski Kamila A. , Bhatt Alok A. 
Published: February 2020

AbstractVascular lesions have a varied appearance and can commonly occur in the head and neck. A majority of these lesions are cutaneous and congenital; however, some may be acquired and malignant. The presentation and clinical history of patients presenting with head and neck lesions can be used to guide further imaging, which can provide important diagnostic and therapeutic considerations. This review discusses the revised International Society for the Study of Vascular Anomalies (ISSVA) classification system for vascular tumors and malformations, as well as explores the most common vascular anomalies including their clinical presentations and imaging findings.
Colorimetric determination of amaranth followed enrichment and separation using buoyant adsorbents
Authors: Wu Shu , Yu Yuanyuan , Zhang Cengceng , Chen Fang 
Published: February 2020

AbstractA buoyant solid-phase extraction adsorbent was prepared by sodium alginate-coated hollow glass microspheres (HGMs) modified with 3-aminopropyltrimethoxysilane (3-APTS) for the separation and enrichment of anionic dye amaranth. After adsorbing amaranth, these low-density adsorbents can float on the surface of the solution, so the separation between adsorbents and substrates can be carried out by flotation. Quantitative determination of amaranth after separation and enrichment can be achieved by combining spectrophotometry. Under the optimum conditions, the linear range and detection limit for amaranth detection were 0.02 mg L−1–2.0 mg L−1 and 0.0021 mg L−1, respectively. The proposed method was applied to the determination of amaranth in different beverages, and the results were in good agreement with those by high-performance liquid chromatography (HPLC). The recoveries of amaranth in different beverages were between 97.93 and 105.91%. The floating adsorbent can be used as a conventional sample preparation method for the detection of low concentration analytes in complex samples.
Does the application of diffusion weighted imaging improve the prediction of survival in patients with resected brain metastases? A retrospective multicenter study
Authors: Zakaria Rasheed , Chen Yin Jie , Hughes David M. , Wang Sumei , Chawla Sanjeev , Poptani Harish , Berghoff Anna S. , Preusser Matthias , Jenkinson Michael D. , Mohan Suyash 
Published: February 2020

AbstractBackgroundBrain metastases are common in clinical practice. Many clinical scales exist for predicting survival and hence deciding on best treatment but none are individualised and none use quantitative imaging parameters. A multicenter study was carried out to evaluate the prognostic utility of a simple diffusion weighted MRI parameter, tumor apparent diffusion coefficient (ADC).MethodsA retrospective analysis of imaging and clinical data was performed on a cohort of 223 adult patients over a ten-year period 2002–2012 pooled from three institutions. All patients underwent surgical resection with histologically confirmed brain metastases and received adjuvant whole brain radiotherapy and/or chemotherapy. Survival was modelled using standard clinical variables and statistically compared with and without the addition of tumor ADC.ResultsThe median overall survival was 9.6 months (95% CI 7.5–11.7) for this cohort. Greater age (p = 0.002), worse performance status (p < 0.0001) and uncontrolled extracranial disease (p < 0.0001) were all significantly associated with shorter survival in univariate analysis. Adjuvant whole brain radiotherapy (p = 0.007) and higher tumor ADC (p < 0.001) were associated with prolonged survival. Combining values of tumor ADC with conventional clinical scoring systems such as the Graded Prognostic Assessment (GPA) score significantly improved the modelling of survival (e.g. concordance increased from 0.5956 to 0.6277 with Akaike’s Information Criterion reduced from 1335 to 1324).ConclusionsCombining advanced MRI readings such as tumor ADC with clinical scoring systems is a potentially simple method for improving and individualising the estimation of survival in patients having surgery for brain metastases.
Implementation of vector control on electric vehicle traction system
Authors: Ibrahim Nady , Abdelaziz Mohamed , Ghoneima Maged , Hammad Sherif 
Published: February 2020

Abstract
Background
Nowadays, electric vehicle development takes a great attention in vehicle industry and researches, due to demising supplies of fuel, less pollution, and developing many resources of generating electricity as renewable energy and clean resources.

Results
This research is a part of the Autotronics Research Lab (ARL), applying researches on autonomous and electric vehicles. The main aim of the research is to apply vector control method on traction control system of electric vehicle (mini golf cart) by using two hub motors on the rear wheels while the two front wheels are used for steering; it is assumed that the controlled vehicle is fitted with some equipment which can used in autonomous driving.
Simulation results show the output response of speed and torque of the vehicle motors and vehicle speed while the vehicle is moving in a straight line or during steering and also show the fusion between vector control and power steering algorithm.

Conclusions
The system preforms the efficiency, safety, accuracy, and more controllability of electric vehicle traction system, leading to more stability in vehicle speed, lower troubleshoots, and less error in unstable surfaces and bad roads.
Alexander Kluge’s Installations
Authors: Hottman Tara 
Published: February 2020

Abstract
Analysis of recent exhibitions featuring Alexander Kluge’s earlier films and televisual work in dialogue with work by other artists demonstrates how the aesthetics of installation art and modes of exhibiting moving images in art museums and galleries have allowed Kluge to continue developing but also revise practices he first engaged in other media. The so-called white-cube exhibition space presents Kluge’s earlier works in terms of remediation and provides him with an opportunity to employ and reconceptualize his approach to montage techniques and reception aesthetics. With their deployment in the white cube, his earlier works become emphatically transmedial, their content and forms no longer bound to one primary medium. This article proposes that the white cube might be better suited for actively and collectively engaging with Kluge’s work in the twenty-first century than the black box of the cinema, the late-night television screen, or the internet.
Bringing immersive science to undergraduate laboratory courses using CRISPR gene knockouts in frogs and butterflies
Authors: Martin Arnaud , Wolcott Nora S. , O'Connell Lauren A. 
Published: February 2020

ABSTRACT
The use of CRISPR/Cas9 for gene editing offers new opportunities for biology students to perform genuine research exploring the gene-to-phenotype relationship. It is important to introduce the next generation of scientists, health practitioners and other members of society to the technical and ethical aspects of gene editing. Here, we share our experience leading hands-on undergraduate laboratory classes, where students formulate hypotheses regarding the roles of candidate genes involved in development, perform loss-of-function experiments using programmable nucleases and analyze the phenotypic effects of mosaic mutant animals. This is enabled by the use of the amphibian Xenopus laevis and the butterfly Vanessa cardui, two organisms that reliably yield hundreds of large and freshly fertilized eggs in a scalable manner. Frogs and butterflies also present opportunities to teach key biological concepts about gene regulation and development. To complement these practical aspects, we describe learning activities aimed at equipping students with a broad understanding of genome editing techniques, their application in fundamental and translational research, and the bioethical challenges they raise. Overall, our work supports the introduction of CRISPR technology into undergraduate classrooms and, when coupled with classroom undergraduate research experiences, enables hypothesis-driven research by undergraduates.
The turquoise killifish: a genetically tractable model for the study of aging
Authors: Poeschla Michael , Valenzano Dario R. 
Published: February 2020

ABSTRACTLifespan is a remarkably diverse trait in nature, ranging from just hours in adult mayflies to hundreds of years in the Greenland shark and quahog clam. Great disparities in lifespan are often observed even among somewhat closely related species; for example, in the laboratory, wild-derived strains of the common house mouse have a maximum observed lifespan of approximately 6 years, while a similarly sized rodent, the naked mole rat, can live for over 30 years. Comparative biology of aging across the tree of life provides a tremendous opportunity for understanding the molecular and genetic basis underlying lifespan and aging. However, a lack of molecular and laboratory tools has limited the ability of researchers to take full advantage of the incredible diversity of aging phenotypes in nature. Recent developments in genomic technology have made it increasingly possible to study non-canonical model organisms for aging. One promising new genetic model organism amenable to a range of experimental interventions is the turquoise killifish (Nothobranchius furzeri). This fish species has a naturally short lifespan and undergoes a wide range of aging-related transformations. These fish have a fully sequenced genome and transcriptome, and killifish embryos are accessible to transgenesis and genome editing. Furthermore, different killifish species and populations show striking differences in lifespan, providing the opportunity for comparative analysis of aging. This Review introduces the natural life history of the turquoise killifish, its emerging applicability as an aging model system, the genetic tools that have been developed to study aging for this species and a summary of recent studies facilitated by these new tools.