bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validating Comprehensive Next-Generation Sequencing Results for Precision Oncology: The NCT/DKTK Molecularly Aided Stratification for Tumor Eradication Research Experience
Authors: Lier Amelie , Penzel Roland , Heining Christoph , Horak Peter , Fröhlich Martina , Uhrig Sebastian , Budczies Jan , Kirchner Martina , Volckmar Anna-Lena , Hutter Barbara , Kreutzfeldt Simon , Endris Volker , Richter Daniela , Wolf Stephan , Pfütze Katrin , Neumann Olaf , Buchhalter Ivo , Morais de Oliveira Cristiano M. , Singer Stephan , Leichsenring Jonas , Herpel Esther , Klauschen Frederick , Jost Philipp J. , Metzeler Klaus H. , Schulze-Osthoff Klaus , Kopp Hans-Georg , Kindler Thomas , Rieke Damian T. , Lamping Mario , Brandts Christian , Falkenhorst Johanna , Bauer Sebastian , Schröck Evelin , Folprecht Gunnar , Boerries Melanie , von Bubnoff Nikolas , Weichert Wilko , Brors Benedikt , Lichter Peter , von Kalle Christof , Schirmacher Peter , Glimm Hanno , Fröhling Stefan , Stenzinger Albrecht 
Published: November 2018

Purpose Rapidly evolving genomics technologies, in particular comprehensive next-generation sequencing (NGS), have led to exponential growth in the understanding of cancer biology, shifting oncology toward personalized treatment strategies. However, comprehensive NGS approaches, such as whole-exome sequencing, have limitations that are related to the technology itself as well as to the input source. Hence, clinical implementation of comprehensive NGS in a quality-controlled diagnostic workflow requires both the standardization of sequencing procedures and continuous validation of sequencing results by orthogonal methods in an ongoing program to enable the determination of key test parameters and continuous improvement of NGS and bioinformatics pipelines. Patients and Methods We present validation data on 220 patients who were enrolled between 2013 and 2016 in a multi-institutional, genomics-guided precision oncology program (Molecularly Aided Stratification for Tumor Eradication Research) of the National Center for Tumor Diseases Heidelberg and the German Cancer Consortium. Results More than 90% of clinically actionable genomic alterations identified by combined whole-exome sequencing and transcriptome sequencing were successfully validated, with varying frequencies of discordant results across different types of alterations (fusions, 3.7%; single-nucleotide variants, 2.6%; amplifications, 1.1%; overexpression, 0.9%; deletions, 0.6%). The implementation of new computational methods for NGS data analysis led to a substantial improvement of gene fusion calling over time. Conclusion Collectively, these data demonstrate the value of a rigorous validation program that partners with comprehensive NGS to successfully implement and continuously improve cancer precision medicine in a clinical setting.
Mouse Idh3a mutations cause retinal degeneration and reduced mitochondrial function
Authors: Findlay Amy S. , Carter Roderick N. , Starbuck Becky , McKie Lisa , Nováková Klára , Budd Peter S. , Keighren Margaret A. , Marsh Joseph A. , Cross Sally H. , Simon Michelle M. , Potter Paul K. , Morton Nicholas M. , Jackson Ian J. 
Published: November 2018

Isocitrate dehydrogenase (IDH) is an enzyme required for the production of α-ketoglutarate from isocitrate. IDH3 generates the NADH used in the mitochondria for ATP production, and is a tetramer made up of two α, a β and a γ subunit. Loss of function and missense mutations in both IDH3A andIDH3B have previously been implicated in families exhibiting retinal degeneration. Using mouse models we have investigated the role of IDH3 in retinal disease and mitochondrial function.
We identified mice with late-onset retinal degeneration in a screen of ageing mice carrying an ENU-induced mutation, E229K, in Idh3a. Mice homozygous for this mutation exhibit signs of retinal stress, indicated by GFAP staining, as early as 3 months, but no other tissues appear to be affected. We produced a knockout of Idh3a and found that homozygous mice do not survive past early embryogenesis. Idh3a−/E229K compound heterozygous mutants exhibit a more severe retinal degeneration when compared to Idh3aE229K/E229K. Analysis of mitochondrial function in mutant cell lines highlighted a reduction in mitochondrial maximal respiration and reserve capacity levels in both Idh3aE229K/E229K and Idh3a−/E229K cells. Loss-of function Idh3b mutants do not exhibit the same retinal degeneration phenotype, with no signs of retinal stress or reduction in mitochondrial respiration.
It has been previously reported that the retina operates with a limited mitochondrial reserve capacity and we suggest that this, in combination with the reduced reserve capacity in mutants, explains the degenerative phenotype observed in Idh3a mutant mice.
SHP-2 is activated in response to force on E-cadherin and dephosphorylates vinculin Y822
Authors: Campbell Hannah , Heidema Christy , Pilarczyk Daisy G. , DeMali Kris A. 
Published: November 2018

ABSTRACT
The response of cells to mechanical inputs is a key determinant of cell behavior. In response to external forces, E-cadherin initiates signal transduction cascades that allow the cell to modulate its contractility to withstand the force. Much attention has focused on identifying the E-cadherin signaling pathways that promote contractility, but the negative regulators remain undefined. In this study, we identify SHP-2 as a force-activated phosphatase that negatively regulates E-cadherin force transmission by dephosphorylating vinculin Y822. To specifically probe a role for SHP-2 in E-cadherin mechanotransduction, we mutated vinculin so that it retains its phosphorylation but cannot be dephosphorylated. Cells expressing the mutant vinculin have increased contractility. This work provides a mechanism for inactivating E-cadherin mechanotransduction and provides a new method for specifically targeting the action of phosphatases in cells.
Novel Wolbachia strains in Anopheles malaria vectors from Sub-Saharan Africa
Authors: Jeffries Claire L. , Lawrence Gena G. , Golovko George , Kristan Mojca , Orsborne James , Spence Kirstin , Hurn Eliot , Bandibabone Janvier , Tantely Luciano M. , Raharimalala Fara N. , Keita Kalil , Camara Denka , Barry Yaya , Wat’senga Francis , Manzambi Emile Z. , Afrane Yaw A. , Mohammed Abdul R. , Abeku Tarekegn A. , Hedge Shivanand , Khanipov Kamil , Pimenova Maria , Fofanov Yuriy , Boyer Sebastien , Irish Seth R. , Hughes Grant L. , Walker Thomas 
Published: November 2018

Background: Wolbachia, a common insect endosymbiotic bacterium that can influence pathogen transmission and manipulate host reproduction, has historically been considered absent from the Anopheles (An.) genera, but has recently been found in An. gambiae s.l. populations in West Africa. As there are numerous Anopheles species that have the capacity to transmit malaria, we analysed a range of species across five malaria endemic countries to determine Wolbachia prevalence rates, characterise novel Wolbachia strains and determine any correlation between the presence of Plasmodium, Wolbachia and the competing bacterium Asaia. Methods: Anopheles adult mosquitoes were collected from five malaria-endemic countries: Guinea, Democratic Republic of the Congo (DRC), Ghana, Uganda and Madagascar, between 2013 and 2017. Molecular analysis was undertaken using quantitative PCR, Sanger sequencing, Wolbachia multilocus sequence typing (MLST) and high-throughput amplicon sequencing of the bacterial 16S rRNA gene. Results: Novel Wolbachia strains were discovered in five species: An. coluzzii, An. gambiae s.s., An. arabiensis, An. moucheti and An. species A, increasing the number of Anopheles species known to be naturally infected. Variable prevalence rates in different locations were observed and novel strains were phylogenetically diverse, clustering with Wolbachia supergroup B strains. We also provide evidence for resident strain variants within An. species A. Wolbachia is the dominant member of the microbiome in An. moucheti and An. species A but present at lower densities in An. coluzzii. Interestingly, no evidence of Wolbachia/Asaia co-infections was seen and Asaia infection densities were shown to be variable and location dependent. Conclusions: The important discovery of novel Wolbachia strains in Anopheles provides greater insight into the prevalence of resident Wolbachia strains in diverse malaria vectors. Novel Wolbachia strains (particularly high-density strains) are ideal candidate strains for transinfection to create stable infections in other Anopheles mosquito species, which could be used for population replacement or suppression control strategies.
Sex and Rosaceae apomicts
Authors: Dickinson Timothy A. 
Published: November 2018

AbstractThis paper updates earlier reviews of polyploidy and reproductive biology in the Rosaceae, and does so with a focus on hybridization in relation to polyploidy and (facultative) gametophytic apomixis. Taking data mainly from tribe Maleae, it also seeks to point out evidence for a potential role for fertilization of infrequent unreduced gametes in diploid‐diploid crosses in producing autopolyploids. Apomixis may originate in these autopolyploids, and spread as they cross with diploids and other polyploids.
Does Change in the Information Environment Affect Financing Choices?
Authors: Li Xu , Lin Chen , Zhan Xintong 
Published: November 2018

Using brokerage mergers and closures as natural experiments, we examine how exogenous changes in the information environment affect a firm’s financing choice. Our difference-in-differences approach shows that exogenous increases in information asymmetry lead firms to substitute away from equity and public debt toward bank debt. Firms with higher risk tend to substitute equity for bank debt, and firms with lower risk tend to substitute bonds for bank debt. The effect of the change in the information environment on a firm’s financing choice is more pronounced for firms with worse information environments, such as those with few initial analysts and younger firms. We demonstrate that the mechanism of the change is through a reduction of the issuance of equity and bonds but with an increase of the issuance of bank loans. Further analysis reveals that such firms tend to reduce long-term borrowing, reduce their issuance of subordinated debt, and increase their revolving credit lines. This paper was accepted by Tomasz Piskorski, finance.
Throughput Scalability Analysis of Fork-Join Queueing Networks
Authors: Zeng Yun , Chaintreau Augustin , Towsley Don , Xia Cathy H. 
Published: November 2018

Parallel and distributed processing systems have expanded in size as technology advances in cloud computing and big data analytics. A critical issue concerns throughput scalability: whether throughput decreases to zero as the systems scale in size and capabilities. We model parallel and distributed processing systems as fork and join queueing networks with blocking (FJQN/Bs). Such networks can have arbitrary topology, arbitrary initial state, and generally distributed service times. We propose a key topological concept, called the “minimum level,” that determines the throughput scalability of FJQN/Bs. We construct throughput bounds as functions of minimum level, network degree, buffer sizes, and processing speed, and we present necessary and/or sufficient conditions to guarantee throughput scalability of arbitrary size and topology FJQN/Bs. The e-companion is available at https://doi.org/10.1287/opre.2018.1748 .
Securing The Future: Clay-Based Solutions For a Comprehensive and Sustainable Potable-Water Supply System
Authors: Rytwo Giora 
Published: November 2018

AbstractToday’s water-treatment plants combine practices designed to cope individually with various types of purification challenges. In some cases, the solution to one has detrimental effects on others, e.g. disinfection by chlorination forming hazardous organic contaminants. Water-treatment plants have large ecological footprints and operational costs, making the availability of high-quality water in developing areas almost impossible, due to lack of resources and infrastructure. Indeed, >2 billion people are exposed to diseases caused by contaminated water. Clearly, bringing safe, clean drinking water to people’s homes is essential to a good quality of life. Clay minerals may offer technologies and innovative practices which would help to develop a reliable, low-maintenance device with a small environmental footprint that processes stream, lake, or pond water into high-quality potable water. The basis for such technologies has already been established and improved approaches are being introduced on an ongoing basis by clay scientists: nanocomposite pre-treatment and disinfection, photodegradation of organic pollutants using clay-based catalysts, polishing of inorganic contaminants, and removal of biological pathogens by adsorption or deactivation onto specifically designed clay-based filters, etc. This short review presents a vision for combining those technologies in a tandem system for the delivery of high-quality water that is low-maintenance, affordable, and environmentally sustainable for the benefit of mankind.
A caution about causation
Authors: Henderson Michael , Redmond Petrea , Heinrich Eva 
Published: November 2018

Educational technology research, like all education research, is dominated by explicit or implicit claims of causation. The dominance of cause-effect models in research is not surprising, and for many it is unnoticed and unquestioned. However, regardless of the cause-effect model being applied or the methodology in measuring it, we are unable to detect cause-effect directly. It is in this context that we need to be cautious in our interpretations of educational technology interventions and their implications for the future. Claims of causation are unlikely to decrease in the face of the increasing calls for “evidence-based” policy and practice. With this in mind it is even more important to consider how we can resist deterministic or mechanical claims of cause and effect. This dilemma should not stop our drive for evidence based approaches, but it is a reminder that we need to take care in the rigour of our research, and equally, in the way we describe it.
Significance of bacteriophages in fermented soybeans: A review
Authors: Chukeatirote Ekachai , Phongtang Wallapat , Kim Jeongjin , Jo Ara , Jung Lae-Seung , Ahn Juhee 
Published: November 2018

AbstractBacteriophages are ubiquitous and have been reported to have been found in many food products. Their presence is important as they have the ability to interact with their bacterial host in food matrices. Fermented soybean products, one of the most widely consumed ethnic foods among Asian people, are prepared naturally and include Japanese Natto, Indian Kinema, Korean Chongkukjang and Thai Thua Nao. This review highlights bacteriophages which have been isolated from fermented soybean products and also includes an overview of their diversity, occurrence as well as their significance.
Profiling L2 writing development: The case of CFL learners in intermediate classes
Authors: Yang Li , Zhao Zenan 
Published: November 2018

AbstractThis exploratory study examined the writings of a small group of learners enrolled in intermediate CFL classes at two U.S. universities and attempted to profile these learners’ writing development over five months. It collected data through both in-class timed essays and out-of-class writing assignments and analyzed them in terms of overall rating and a variety of writing measures (i.e., fluency, accuracy, complexity, content, and organization). The results showed negligible improvement in these learners’ overall writing proficiency at the end of the observation period and revealed a non-linear trend of development of their writing competence over time. In addition, the analysis of the learners’ writing profile as well as the errors committed in their writings provided new insights into the promotion of L2 writing skills in CFL classrooms.
会话分析路向的课堂研究
Authors: 刘 运同 
Published: November 2018

提要：会话分析（Conversation Analysis）的研究对象是人们的交际活动，包括日常的会话和机构性交谈。课堂教学是机构性交谈的一种，因此从会话分析创立之初，就有研究者按照会话分析的理论和方法来对课堂交流进行研究。本文从课堂交互研究和课堂学习研究两个方面概述了会话分析路向的课堂教学研究，包括主要的课题及其成果。在课堂交互活动研究方面，研究者从话轮转换、序列结构、会话补救三个方面深入挖掘课堂交互活动的特点。早期的一些研究较多关注于教师主导的课堂活动，描述教师在话轮分配上的主导地位；新近的研究开始关注其他类型的课堂活动或教师主导的课堂中其他类型的活动中的话轮替换形式。在课堂教学活动序列结构方面，会话分析路向的课堂研究显示了它微观分析的优势，细致而深入地描述 IRE 在课堂教学中的具体实现过程，准确地描写了后续话轮的作用。纠正学生的错误是课堂教学中的重要一环，会话分析路向的课堂研究表明，把课堂教学中的补救或纠错与日常会话的补救做简单的对比是不恰当的。课堂的补救行为跟 IRE 序列有密切的关联，并且研究还发现课堂上的补救行为与课堂教学环境有很大关联，跟课堂教学中不同阶段的特定教学目标密切相关。此外，会话分析路向的习得研究在很多方面丰富和补充了已有的第二语言习得研究。它最大的优势在于利用真实的语料来揭示学习者的理解和学习是否、何时、怎样、为什么产生。同时由于会话分析导向的习得研究把学习看作是一种社会交流活动，突破了大多数 SLA 研究把学习当作是个体认知活动的局限。我们认为，会话分析注重真实语料以及交互者视角的特点给汉语作为第二语言的课堂研究提供了有益的借鉴。
Risk model in women with ovarian cancer without mutations
Authors: Cymbaluk-Płoska Aneta , Chudecka-Głaz Anita , Sompolska-Rzechuła Agnieszka , Rasinska Kamila , Dubiel Paulina , Menkiszak Janusz 
Published: November 2018

Abstract
Ovarian cancer is characterised by the greatest mortality among all tumors of the reproductive tract.
This study included 246 patients which consisted of 136 women with ovarian cancer without genetic mutation and 110 women with benign ovarian cysts.
We created two mathematical logic models containing positive and negative risk factors of ovarian cancer such as: age at last menstruation cycle, patient age, OC, HRT, smoking, education status, and alcohol consumption. The calculated cut-off point for the first model was 0.5117. Classification determined on the basis of that cut-off point yielded 87.19% of correctly classified cases, of which 91.38% are “case” and 81.61% - „noncase”. For the second model the designated cut-off point was set at 0.5149 and the percentage of correctly classified patients was 88.12%, with 92.24% correctly rated as cancer patients and 82.56% of the cases rightly recognised as having no ovarian cancer.
Logit is a simple mathematical model that can be a useful tool for identification of patients with increased risk of ovarian cancer.
Financing for Development in the MENA Region
Authors: Awdeh Ali 
Published: November 2018

AbstractFinancing for Development was addressed by the international community since more than 25 years, when the Monterrey Consensus of the International Conference on Financing for Development (Monterrey, Mexico, March 2002) urged mobilising and increasing the effective use of financial resources to fulfil the internationally agreed Millennium Development Goals. In 2015, a new Development Agenda was designed and was based on the Development Finance. Consequently, the efficient exploitation of traditional and innovative finance resources in economic, social and human development has become a global top priority. This study analyses the impact of 7 resources of financial flows on 6 socio-economic variables in a sample of 19 MENA countries over the period 1991–2015 to test the efficient exploitation of these resources in development. The results show that government spending and official development assistance are the most important factor in boosting development in the MENA region. International trade plays a limited role in financing development, whereas foreign direct investment has the least effect on MENA development.
Utilisation of gonadotrophin-releasing hormone (GnRH) analogue to differentiate ovarian from adrenal hyperandrogenism in postmenopausal women
Authors: Bahaeldein E , Brassill M J 
Published: November 2018

Summary
Postmenopausal hyperandrogenism is a relatively rare diagnosis resulting from excess androgen production from the adrenals or ovaries. The exclusion of malignant causes is a priority. Laboratory tests and imaging are utilised to help differentiate the source of excess androgens. We report two cases of postmenopausal hyperandrogenism in women aged 75 and 67 years. Both cases presented with clinical features suggestive of hyperandrogenism which had developed gradually over the previous 2 years. Laboratory investigations confirmed a significant elevation in their serum testosterone levels. In both cases, imaging did not reveal any abnormality of the adrenals or ovaries. To help differentiate an adrenal vs ovarian source a single-dose GnRH analogue was given with measurement of testosterone and gonadotrophin levels pre and post. The reduction in gonadotrophins achieved by the GnRH analogue resulted in suppression of testosterone levels which suggested an ovarian source. Both patients proceeded to bilateral oophorectomy. Histology revealed a benign hilus cell tumour in one case and a benign Leydig cell tumour in the other.

Learning points:

A key part of the work-up of postmenopausal hyperandrogenism is to differentiate between an adrenal or an ovarian source of excess androgens;

Imaging may not identify small ovarian tumours or hyperthecosis and may also identify incidental adrenal masses which are non-functioning;

Current guidelines suggest ovarian and adrenal venous sampling when imaging is inconclusive but this requires technical expertise and has a high failure rate;

GnRH analogue use can successfully confirm ovarian source and should be considered as a diagnostic tool in this setting.
Bone microarchitecture and volumetric bone density impairment in young male adults with childhood-onset growth hormone deficiency
Authors: Yang Hongbo , Yan Kemin , Yuping Xu , Zhang Qi , Wang Linjie , Gong Fengying , Zhu Huijuan , Xia Weibo , Pan Hui 
Published: November 2018

Context
Adult growth hormone deficiency (AGHD) is characterized by low bone density and increased risk of fracture. Bone microarchitecture is insufficiently evaluated in patients with childhood-onset AGHD (CO AGHD).

Objective
To assess volumetric bone density (vBMD) and bone microarchitecture in CO AGHD in early adulthood after cessation of recombinant growth hormone (rhGH) treatment.

Design and subjects
Case–control study in a major academic medical center in Beijing, including 20 young male adults with CO AGHD and 30 age- and weight-matched non-athletic healthy men. High-resolution peripheral quantitative computerized tomography (HR-pQCT) of distal radius and tibia was performed.

Outcomes
The main outcomes were vBMD and morphometry parameters from HR-pQCT.

Results
Compared with healthy controls, CO AGHD group had significantly decreased insulin-like growth factor 1 (IGF-1) level and IGF-1 SDS (P < 0.001). β-CTX and alkaline phosphatase levels in CO AGHD group were significantly increased (P < 0.001). CO AGHD group had significantly decreased total vBMD, cortical vBMD, trabecular vBMD, cortical area, cortical thickness as well as trabecular thickness and trabecular bone volume fraction of both tibia and radius (P < 0.001). CO AGHD patients had an 8.4 kg decrease in grip strength and a significant decrease in creatinine levels (P = 0.001). At both tibia and radius, by finite element analysis, bone stiffness and failure load of the CO AGHD patients were significantly decreased (P < 0.001). After adjusting for age, BMI and serum levels of testosterone and free thyroxin, serum IGF-1 level was a positive predictor for total vBMD, cortical vBMD, cortical area, trabecular vBMD, bone stiffness and failure load of both tibia and distal radius in all subjects.

Conclusions
Young adult male patients with childhood-onset adult growth hormone deficiency who are no longer receiving growth hormone replacement have prominently impaired volumetric bone density and bone microarchitecture and lower estimated bone strength.