bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Molecular Assay for the Proliferation Signature in Mantle Cell Lymphoma Applicable to Formalin-Fixed Paraffin-Embedded Biopsies
Authors: Scott David W. , Abrisqueta Pau , Wright George W. , Slack Graham W. , Mottok Anja , Villa Diego , Jares Pedro , Rauert-Wunderlich Hilka , Royo Cristina , Clot Guillem , Pinyol Magda , Boyle Merrill , Chan Fong Chun , Braziel Rita M. , Chan Wing C. , Weisenburger Dennis D. , Cook James R. , Greiner Timothy C. , Fu Kai , Ott German , Delabie Jan , Smeland Erlend B. , Holte Harald , Jaffe Elaine S. , Steidl Christian , Connors Joseph M. , Gascoyne Randy D. , Rosenwald Andreas , Staudt Louis M. , Campo Elias , Rimsza Lisa M. ,   for the Lymphoma/Leukemia Molecular Profiling Project
Published: March 2017

Purpose Mantle cell lymphoma is an aggressive B-cell neoplasm that displays heterogeneous outcomes after treatment. In 2003, the Lymphoma/Leukemia Molecular Profiling Project described a powerful biomarker—the proliferation signature—using gene expression in fresh frozen material. Herein, we describe the training and validation of a new assay that measures the proliferation signature in RNA derived from routinely available formalin-fixed paraffin-embedded (FFPE) biopsies. Methods Forty-seven FFPE biopsies were used to train an assay on the NanoString platform, using microarray gene expression data of matched fresh frozen biopsies as a gold standard. The locked assay was applied to pretreatment FFPE lymph node biopsies from an independent cohort of 110 patients uniformly treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. Seventeen biopsies were tested across three laboratories to assess assay reproducibility. Results The MCL35 assay, which contained a 17-gene proliferation signature, yielded gene expression of sufficient quality to assign an assay score and risk group in 108 (98%) of 110 archival FFPE biopsies. The MCL35 assay assigned patients to high-risk (26%), standard-risk (29%), and low-risk (45%) groups, with different lengths of overall survival (OS): a median of 1.1, 2.6, and 8.6 years, respectively (log-rank for trend, P < .001). In multivariable analysis, these risk groups and the Mantle Cell Lymphoma International Prognostic Index were independently associated with OS ( P < .001 for both variables). Concordance of risk assignment across the three independent laboratories was 100%. Conclusion The newly developed and validated MCL35 assay for FFPE biopsies uses the proliferation signature to define groups of patients with significantly different OS independent of the Mantle Cell Lymphoma International Prognostic Index. Importantly, the analytic and clinical validity of this assay defines it as a reliable biomarker to support risk-adapted clinical trials.
Lung organoids: current uses and future promise
Authors: Barkauskas Christina E. , Chung Mei-I , Fioret Bryan , Gao Xia , Katsura Hiroaki , Hogan Brigid L. M. 
Published: March 2017

ABSTRACT
Lungs are composed of a system of highly branched tubes that bring air into the alveoli, where gas exchange takes place. The proximal and distal regions of the lung contain epithelial cells specialized for different functions: basal, secretory and ciliated cells in the conducting airways and type II and type I cells lining the alveoli. Basal, secretory and type II cells can be grown in three-dimensional culture, with or without supporting stromal cells, and under these conditions they give rise to self-organizing structures known as organoids. This Review summarizes the different methods for generating organoids from cells isolated from human and mouse lungs, and compares their final structure and cellular composition with that of the airways or alveoli of the adult lung. We also discuss the potential and limitations of organoids for addressing outstanding questions in lung biology and for developing new drugs for disorders such as cystic fibrosis and asthma.
Ethical issues in human organoid and gastruloid research
Authors: Munsie Megan , Hyun Insoo , Sugarman Jeremy 
Published: March 2017

ABSTRACT
Research involving human organoids and gastruloids involves ethical issues associated with their derivation as well as their current and future uses. These include unique issues related to the extent of maturation that can be achieved in vitro or through chimeric research, as well as fundamental ethical considerations such as those concerning the provenance of human biomaterials and the use of gene-editing technologies. Many of these issues are not specifically addressed by existing ethics oversight mechanisms, but these mechanisms might be easily extended to help ensure that human organoid and related research moves forward in an ethically appropriate manner.
Using brain organoids to understand Zika virus-induced microcephaly
Authors: Qian Xuyu , Nguyen Ha Nam , Jacob Fadi , Song Hongjun , Ming Guo-li 
Published: March 2017

ABSTRACT
Technologies to differentiate human pluripotent stem cells into three-dimensional organized structures that resemble in vivo organs are pushing the frontiers of human disease modeling and drug development. In response to the global health emergency posed by the Zika virus (ZIKV) outbreak, brain organoids engineered to mimic the developing human fetal brain have been employed to model ZIKV-induced microcephaly. Here, we discuss the advantages of brain organoids over other model systems to study development and highlight recent advances in understanding ZIKV pathophysiology and its underlying pathogenesis mechanisms. We further discuss perspectives on overcoming limitations of current organoid systems for their future use in ZIKV research.
Pluripotent stem cell-derived organoids: using principles of developmental biology to grow human tissues in a dish
Authors: McCauley Heather A. , Wells James M. 
Published: March 2017

ABSTRACT
Pluripotent stem cell (PSC)-derived organoids are miniature, three-dimensional human tissues generated by the application of developmental biological principles to PSCs in vitro. The approach to generate organoids uses a combination of directed differentiation, morphogenetic processes, and the intrinsically driven self-assembly of cells that mimics organogenesis in the developing embryo. The resulting organoids have remarkable cell type complexity, architecture and function similar to their in vivo counterparts. In the past five years, human PSC-derived organoids with components of all three germ layers have been generated, resulting in the establishment of a new human model system. Here, and in the accompanying poster, we provide an overview of how principles of developmental biology have been essential for generating human organoids in vitro, and how organoids are now being used as a primary research tool to investigate human developmental biology.
Dissecting the stem cell niche with organoid models: an engineering-based approach
Authors: Murrow Lyndsay M. , Weber Robert J. , Gartner Zev J. 
Published: March 2017

ABSTRACT
For many tissues, single resident stem cells grown in vitro under appropriate three-dimensional conditions can produce outgrowths known as organoids. These tissues recapitulate much of the cell composition and architecture of the in vivo organ from which they derive, including the formation of a stem cell niche. This has facilitated the systematic experimental manipulation and single-cell, high-throughput imaging of stem cells within their respective niches. Furthermore, emerging technologies now make it possible to engineer organoids from purified cellular and extracellular components to directly model and test stem cell-niche interactions. In this Review, we discuss how organoids have been used to identify and characterize stem cell-niche interactions and uncover new niche components, focusing on three adult-derived organoid systems. We also describe new approaches to reconstitute organoids from purified cellular components, and discuss how this technology can help to address fundamental questions about the adult stem cell niche.
The physics of organoids: a biophysical approach to understanding organogenesis
Authors: Dahl-Jensen Svend , Grapin-Botton Anne 
Published: March 2017

ABSTRACT
Organoids representing a diversity of tissues have recently been created, bridging the gap between cell culture and experiments performed in vivo. Being small and amenable to continuous monitoring, they offer the opportunity to scrutinize the dynamics of organ development, including the exciting prospect of observing aspects of human embryo development live. From a physicist's perspective, their ability to self-organize – to differentiate and organize cells in space – calls for the identification of the simple rules that underlie this capacity. Organoids provide tractable conditions to investigate the effects of the growth environment, including its molecular composition and mechanical properties, along with the initial conditions such as cell number and type(s). From a theoretical standpoint, different types of in silico modeling can complement the measurements performed in organoids to understand the role of chemical diffusion, contact signaling, differential cell adhesion and mechanical controls. Here, we discuss what it means to take a biophysical approach to understanding organogenesis in vitro and how we might expect such approaches to develop in the future.
Intestinal epithelial organoids fuse to form self-organizing tubes in floating collagen gels
Authors: Sachs Norman , Tsukamoto Yoshiyuki , Kujala Pekka , Peters Peter J. , Clevers Hans 
Published: March 2017

ABSTRACT
Multiple recent examples highlight how stem cells can self-organize in vitro to establish organoids that closely resemble their in vivo counterparts. Single Lgr5+ mouse intestinal stem cells can be cultured under defined conditions forming ever-expanding epithelial organoids that retain cell polarization, cell type diversity and anatomical organization of the in vivo epithelium. Although exhibiting a remarkable level of self-organization, the so called ‘mini-guts’ have a closed cystic structure of microscopic size. Here, we describe a simple protocol to generate macroscopic intestinal tubes from small cystic organoids. Embedding proliferating organoids within a contracting floating collagen gel allows them to align and fuse to generate macroscopic hollow structures (‘tubes’) that are lined with a simple epithelium containing all major cell types (including functional stem cells) of the small intestine. Cells lining the central contiguous lumen closely resemble the epithelial cells on luminal villi in vivo, whereas buds that protrude from the main tube into the surrounding matrix closely resemble crypts. Thus, the remarkable self-organizing properties of Lgr5+ stem cells extend beyond the level of the microscopic cystic organoid to the next, macroscopic, level of tube formation.
Bringing together the organoid field: from early beginnings to the road ahead
Authors: Muthuswamy Senthil K. 
Published: March 2017

ABSTRACT
From October 12-15th, 2016, EMBO∣EMBL held a symposium to bring together those in the scientific community with a shared interest in using three-dimensional (3D) culture methods to study biology, model disease and personalize treatments. The symposium, entitled ‘Organoids: modelling organ development and disease in 3D culture', which was organized by Juergen Knoblich, Mina Bissell and Esther Schnapp, was particularly timely as there were otherwise few opportunities for those interested in using 3D culture platforms to interact outside of their organ-specific scientific community. The meeting was a fantastic success, creating a lot of discussion and cross-fertilization of ideas from developmental biologists to bioengineers and biophysicists. This Meeting Review provides a summary of the talks presented and the major themes that emerged from the symposium.
Dual role of pericyte α6β1-integrin in tumour blood vessels
Authors: Reynolds Louise E. , D'Amico Gabriela , Lechertier Tanguy , Papachristodoulou Alexandros , Muñoz-Félix José M. , De Arcangelis Adèle , Baker Marianne , Serrels Bryan , Hodivala-Dilke Kairbaan M. 
Published: March 2017

ABSTRACT
The α6β1-integrin is a major laminin receptor, and formation of a laminin-rich basement membrane is a key feature in tumour blood vessel stabilisation and pericyte recruitment, processes that are important in the growth and maturation of tumour blood vessels. However, the role of pericyte α6β1-integrin in angiogenesis is largely unknown. We developed mice where the α6-integrin subunit is deleted in pericytes and examined tumour angiogenesis and growth. These mice had: (1) reduced pericyte coverage of tumour blood vessels; (2) reduced tumour blood vessel stability; (3) increased blood vessel diameter; (4) enhanced blood vessel leakiness, and (5) abnormal blood vessel basement membrane architecture. Surprisingly, tumour growth, blood vessel density and metastasis were not altered. Analysis of retinas revealed that deletion of pericyte α6-integrin did not affect physiological angiogenesis. At the molecular level, we provide evidence that pericyte α6-integrin controls PDGFRβ expression and AKT–mTOR signalling. Taken together, we show that pericyte α6β1-integrin regulates tumour blood vessels by both controlling PDGFRβ and basement membrane architecture. These data establish a novel dual role for pericyte α6-integrin as modulating the blood vessel phenotype during pathological angiogenesis.
Gestão do Conhecimento: Desvendando a Tecnologia
Authors: Petrini Maira 
Published: March 2017

Microempresa de consultoria sediada em Belo Horizonte (MG), a Rizoma se vê diante de um dilema. Um de seus dois diretores e sócios, por razões pessoais, precisa mudar-se para São Paulo. Nesse quadro, como manter a produção e compartilhamento de conhecimento entre os dois sócios, atividade vital para o funcionamento da empresa?
Rapid inducible protein displacement in Plasmodium in vivo and in vitro using knocksideways technology
Authors: Hughes Katie R. , Waters Andy P. 
Published: March 2017

A deeper understanding of the biology of the Plasmodium parasite is essential in order to identify targets for interventions, with the ultimate aim of eliminating malaria. Determining the function(s) of essential proteins in Plasmodium has, until recently, been hampered by the lack of efficient conditional systems to abrogate proteins. We report the adaptation of a conditional technology, knocksideways (KS), for use in Plasmodium berghei, which can potentially rapidly inactivate proteins of interest through relocalisation. The system is induced using rapamycin, which allows for KS both in vitro and in vivo and is effective more rapidly than any other reported system. KS utilises pairs of fluorescent tags that facilitate live imaging and allows for rapid confirmation of efficient protein redistribution on live parasites, allowing for streamlined workflows. We demonstrate the characteristics of the system using transgenically expressed cytoplasmic GFP and provide proof of principle by inducibly redistributing a number of proteins with different native, subcellular locations. We also demonstrate that KS can be applied to both mammalian and insect stages of Plasmodium. KS expands the range of (conditional) technologies for genetic manipulation of malaria parasites and offers the potential to be further developed for medium throughput phenotype screens.
Nuclear Medicine in Diagnosis of Angiopathy in Patients with Diabetes Mellitus Type 2
Authors: Никитин  , Nikitin A. , Мосин  , Mosin D. , Кондаков  , Kondakov A. , Полетаева  , Poletaeva T. , Харина  , Kharina D. , Знаменский  , Znamenskiy I. 
Published: March 2017

Purpose: To determine the role of nuclear medicine techniques in the early detection of angiopathy in patients with diabetes and to estimate their accuracy in comparison with routine diagnostic methods for evaluation of target organ damage.
Material and methods: A literature review, selected from the Russian and international bibliographic databases (RSCI, Medline, Google Scholar), dedicated to diagnostic technologies for identification of angiopathy in patients with diabetes mellitus.
Results: 193 sources dedicated to the diagnosis of micro- and macrovascular damage were analyzed, 66 of which were included in this study, 54 of them international and 12 domestic ones responding to the purpose of the study. The analysis revealed that the radionuclide methods of investigation reflecting the functional state of the tissues were evaluated in a small number of publications on early diagnosis angiopathy caused by diabetes mellitus type 2. Most often, high blood glucose concentration damages kidney tissue and myocardium. It is shown that the methods of dynamic nephroscintigraphy and ECG-
gated myocardial perfusion SPECT allow to evaluate the progression of micro- and macrovascular disease before the manifestation of paraclinical signs according to other diagnostic methods. Key determined parameter in dynamic nephroscintigraphy is glomerular filtration rate, which declines on the early stages of the disease. Myocardial perfusion SPECT imaging provides a possibility to assess frequency and severity of ischemic myocardial injury.
Conclusions: The use of nuclear medicine techniques in the diagnosis of angiopathy in diabetes allows verification of early damage to target organs. The most effective diagnostic methods for this purpose are dynamic nephroscintigraphy and myocardial perfusion SPECT which sensitivity is substantially higher than conventional diagnostic methods.
The expansion of nurse prescribing in Scotland: an evaluation
Authors: Coull Alison , Murray Ian , Turner-Halliday Fiona , Watterson Andrew 
Published: March 2017

Medicine prescribing by community nurses commenced in the UK in 1996. By 2001, nurse prescribing was extended to include more nurses and to cover a wider formulary. This research project provides an evaluation of the extension of prescribing powers to nurses in Scotland, following the introduction of legislation in 2001. It aimed to evaluate the impact of nurse prescribing powers on patients, nurses, prescribers, and other stakeholders. A range of methods were used, including two public surveys, stakeholder interviews, postal questionnaires and case studies. The benefits of extended nurse prescribing include: improved patient access to treatment; enhanced patient care; enabled more effective use of medical staff time and greater professional satisfaction for nurses who used nursing skills; and built inter-professional working. Some obstacles existed, including organisational, institutional and resource factors that restricted the overall success of the extension of nurse prescribing. There are high levels of agreement between patients, the public, nurse prescribers, physicians and other health professionals about the benefits of nurse prescribing to patients. The extension of nurse prescribing has been largely successful, with some organisational and procedural areas that could be addressed.
A 50+ year search for effective, efficient and engaging instruction
Authors: Merrill M. David 
Published: March 2017

In this paper I will chronicle my 50+ year career, from my interest in making education more effective, to an epiphany about theories, and some of my published work that, for a time, gained the attention of others in the field of instructional technology. My extensive experience with computer-assisted learning covers early efforts to teach concepts to attempts to design automated authoring systems. My most recent work attempts to identify underlying principles common to most theories of instruction.The professional press publishes reports of theory, research, data, prescriptions, and opinions, but seldom do we get the back story. Where did these ideas originate? What events led to a particular theoretical or research approach? What were the challenges—personal and interpersonal—that affected a given approach, theory or research study? In this paper, in addition to identifying a few of the most notable contributions to this literature, I will provide some of the back story that contributed to my career and inspired or significantly influenced my work. I will also highlight some of the lessons learned along the way.Download the PDF and read more...
Social problem solving as a mediator and a moderator of the link between stress and psychological well-being<p>Stres ve psikolojik iyi olma arasındaki ilişkide sosyal problem çözmenin aracı ve düzenleyici rolü
Authors: Cenkseven Önder Fulya , Eşigül Engin 
Published: March 2017

The main purpose of this was to investigate the role of social problem solving as a mediator or a moderator of percieved stress and psychological well-being in university students. The participants of this study consisted of 350 females and 164 males, a total of 514 university students. Their ages ranged from 18 to 25 years. Data were collected by using the Percieved Stres Inventory (Cohen, Kamarck, & Mermelstein, 1983), Social Problem Solving Inventory Revised Short Form (D’Zurilla, Nezu, & Maydeu-Olivares, 2002) and Scales of Psychological Well-Being (Ryff, 1989). The results indicated that the percieved stress was negatively correlated with the social problem and the psychological well-being. The social problem solving was positively correlated with the psychological well-being. Hierarchial regression analysis showed that social problem solving partially mediated the relationship between perceived stress and psychological well-being. However, social problem solving did not moderate the relationship between perceived stress and psychological well-being. These findings were discussed in the light of related literature and implications were suggested for future research. ÖzetBu çalışmanın temel amacı üniversite öğrencilerinin algıladıkları stres düzeyleri ile psikolojik iyi olma düzeyleri arasındaki ilişkide sosyal problem çözme becerilerinin aracı ve düzenleyici rolünün incelenmesidir. Araştırma 350’si kadın 164’ü erkek toplam 514 üniversite öğrencisi üzerinde gerçekleştirilmiştir. Araştırmaya katılan öğrenciler 18-25 yaş arasında olup, yaş ortalamaları 20.09’dur (Ss=2.02). Araştırmada veri toplamak amacıyla Algılanan Stres Ölçeği (Cohen, Kamarck ve Mermelstein, 1983), Sosyal Problem Çözme Envanteri Kısa Formu (D’Zurilla, Nezu ve Maydeu-Olivares, 2002) ve Psikolojik İyi Olma Ölçekleri (Ryff, 1989) kullanılmıştır. Araştırma sonucunda algılanan stres ile sosyal problem çözme ve psikolojik iyi olma arasında negatif yönde anlamlı, sosyal problem çözme ve psikolojik iyi olma arasında pozitif yönde anlamlı ilişkiler olduğu tespit edilmiştir. Hiyerarşik regresyon analizleri sonucunda sosyal problem çözmenin, algılanan stres ve psikolojik iyi olma arasındaki ilişkide kısmi aracı role sahip iken, düzenleyici bir rolü olmadığı belirlenmiştir. Elde edilen bulgular ilgili alanyazın ve sınırlılıklar ışığında tartışılmış, daha sonra yapılacak çalışmalara ve uygulayıcılara yönelik öneriler sunulmuştur.