bluuebunny/crossref_metadata_2025 huggingface dataset:
Extending accurate spectral induced polarization measurements into the kHz range: modelling and removal of errors from interactions between the parasitic capacitive coupling and the sample holder
Authors: Wang Chen , Slater Lee D
Published: April 2019

Spectral induced polarization (SIP), describing the measurement of the frequency domain electrical impedance magnitude and phase of porous materials, has been widely used to characterize subsurface hydrological/biogeochemical properties and processes. SIP data collected at frequencies higher than 100 Hz are expected to describe the polarization of small particles providing insights into the physicochemical properties of clays, nanoparticles and microorganisms. However, the phase measurements at these high frequencies are often contaminated by errors due to the parasitic capacitive coupling of the SIP instrument, especially for lower conductivity samples. We developed a model showing the measured phase is the sum of the true sample phase and an error term ωCinZx, where ω is the angular frequency; Cin is the instrument input capacitance and Zx is a measurable impedance function related to the sample holder properties and the reference resistor. Based on this model, a new phase correction method is proposed that results in highly accurate SIP data up to 20 kHz as well as the determination of Cin. We tested the correction method using electric circuits, NaCl fluids and three unconsolidated samples (sand, sand-clay and sand-pyrite mixtures). The corrected phase for the circuit and NaCl fluid experiments showed excellent agreement with the theoretical phase response across the studied frequency range (errors <1 mrad). For unconsolidated samples, removal of errors results in phase spectra more consistent with expected polarization mechanisms, as based on phase peaks recorded for small pyrite and clay particles at high frequencies. These phase peaks could not be identified in the uncorrected data. Our approach can substantially enhance the value of the SIP method for the characterization of fine-grained sediments and rocks.
Does liver cirrhosis have any impact on patients with lung cancer after surgical resection?
Authors: Deng Han-Yu , Hou Liang , Zha Panpan , Zhou Qinghua
Published: April 2019

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: does cirrhosis have any impact on patients with lung cancer after surgical resection? Altogether, 134 papers were found using the reported search, of which 6 cohort studies represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. Five of the cohort studies found that liver cirrhosis was correlated to higher postoperative mortality after lung cancer surgery, 4 also showed a correlation with higher postoperative morbidity and 2 of them found that patients with Child grade B or above experienced a higher risk of morbidity and mortality than those with Child grade A. Four of the cohort studies found that cirrhotic patients had poorer long-term survival, with 2 studies showing patients with Child grade B or above having a worse overall survival than those with Child grade A. Therefore, we conclude that liver cirrhosis (especially Child grade B or above) imposed a significant unfavourable impact on both short-term and long-term outcomes for patients intended for lung cancer surgery.
Annotating and detecting phenotypic information for chronic obstructive pulmonary disease
Authors: Ju Meizhi , Short Andrea D , Thompson Paul , Bakerly Nawar Diar , Gkoutos Georgios V , Tsaprouni Loukia , Ananiadou Sophia
Published: April 2019

Objectives

Chronic obstructive pulmonary disease (COPD) phenotypes cover a range of lung abnormalities. To allow text mining methods to identify pertinent and potentially complex information about these phenotypes from textual data, we have developed a novel annotated corpus, which we use to train a neural network-based named entity recognizer to detect fine-grained COPD phenotypic information.

Materials and methods

Since COPD phenotype descriptions often mention other concepts within them (proteins, treatments, etc.), our corpus annotations include both outermost phenotype descriptions and concepts nested within them. Our neural layered bidirectional long short-term memory conditional random field (BiLSTM-CRF) network firstly recognizes nested mentions, which are fed into subsequent BiLSTM-CRF layers, to help to recognize enclosing phenotype mentions.

Results

Our corpus of 30 full papers (available at: http://www.nactem.ac.uk/COPD) is annotated by experts with 27 030 phenotype-related concept mentions, most of which are automatically linked to UMLS Metathesaurus concepts. When trained using the corpus, our BiLSTM-CRF network outperforms other popular approaches in recognizing detailed phenotypic information.

Discussion

Information extracted by our method can facilitate efficient location and exploration of detailed information about phenotypes, for example, those specifically concerning reactions to treatments.

Conclusion

The importance of our corpus for developing methods to extract fine-grained information about COPD phenotypes is demonstrated through its successful use to train a layered BiLSTM-CRF network to extract phenotypic information at various levels of granularity. The minimal human intervention needed for training should permit ready adaption to extracting phenotypic information about other diseases.
Cases of low anterior resection and ileostomy for rectal cancer that required more than 18 months for stoma closure
Authors: Kojima Yutaka , Sakamoto Kazuhiro , Tomiki Yuichi , Takahashi Rina , Tsukamoto Ryoichi , Hagiwara Toshiaki , Nagakari Kunihiko
Published: April 2019

Laparoscopic surgery is performed worldwide, even for cases of rectal cancer close to the anus, and advances in surgical instruments and techniques have increased the number of cases for which anastomosis can be performed, even those cases for which abdominoperineal resection was performed previously. Consequently, as a measure to avoid complications in the event of suture failure after surgery, the number of cases of establishing diverting stoma has also increased. Diverting ostomy may require a closure operation earlier than planned due to colostomy complications, cases requiring a long period of time until closure due to postoperative complications, and cases in which closure operation cannot be performed. Herein, we report cases that took more than 36 months to allow closure of the diverting stoma.
Phylogenomics Reveals an Ancient Hybrid Origin of the Persian Walnut
Authors: Zhang Bo-Wen , Xu Lin-Lin , Li Nan , Yan Peng-Cheng , Jiang Xin-Hua , Woeste Keith E , Lin Kui , Renner Susanne S , Zhang Da-Yong , Bai Wei-Ning
Published: April 2019

Persian walnut (Juglans regia) is cultivated worldwide for its high-quality wood and nuts, but its origin has remained mysterious because in phylogenies it occupies an unresolved position between American black walnuts and Asian butternuts. Equally unclear is the origin of the only American butternut, J. cinerea. We resequenced the whole genome of 80 individuals from 19 of the 22 species of Juglans and assembled the genome of its relatives Pterocarya stenoptera and Platycarya strobilacea. Using phylogenetic-network analysis of single-copy nuclear genes, genome-wide site pattern probabilities, and Approximate Bayesian Computation, we discovered that J. regia (and its landrace J. sigillata) arose as a hybrid between the American and the Asian lineages and that J. cinerea resulted from massive introgression from an immigrating Asian butternut into the genome of an American black walnut. Approximate Bayesian Computation modeling placed the hybrid origin in the late Pliocene, ∼3.45 My, with both parental lineages since having gone extinct in Europe.
External validation of the US and UK kidney donor risk indices for deceased donor kidney transplant survival in the Australian and New Zealand population
Authors: Clayton Philip A , Dansie Kathryn , Sypek Matthew P , White Sarah , Chadban Steve , Kanellis John , Hughes Peter , Gulyani Aarti , McDonald Stephen
Published: April 2019

Background

The US Kidney Donor Risk Index (KDRI) and the UK KDRI were developed to estimate the risk of graft failure following kidney transplantation. Neither score has been validated in the Australian and New Zealand (ANZ) population.

Methods

Using data from the Australia and New Zealand Organ Donor (ANZOD) and Dialysis and Transplant (ANZDATA) Registries, we included all adult deceased donor kidney-only transplants performed in ANZ from 2005 to 2016 (n = 6405). The KDRI was calculated using both the US donor-only and UK formulae. Three Cox models were constructed (Model 1: KDRI only; Model 2: Model 1 + transplant characteristics; Model 3: Model 2 + recipient characteristics) and compared using Harrell’s C-statistics for the outcomes of death-censored graft survival and overall graft survival.

Results

Both scores were strongly associated with death-censored and overall graft survival (P < 0.0001 in all models). In the KDRI-only models, discrimination of death-censored graft survival was moderately good with C-statistics of 0.63 and 0.59 for the US and UK scores, respectively. Adjusting for transplant characteristics resulted in marginal improvements of the US KDRI to 0.65 and the UK KDRI to 0.63. The addition of recipient characteristics again resulted in marginal improvements of the US KDRI to 0.70 and the UK KDRI to 0.68. Similar trends were seen for the discrimination of overall graft survival.

Conclusions

The US and UK KDRI scores were moderately good at discriminating death-censored and overall graft survival in the ANZ population, with the US score performing slightly better in all models.
Ecological Integrity: Conceptual Foundations and Applications
Authors: Hughes Robert M.
Published: April 2019

As the term suggests, ecological integrity refers to the pristineness, undiminished wholeness, or completeness of an entire ecosystem, whether it be a planet, an ecoregion, a preserve, a pond, or an alpine meadow. The concept of protecting large natural areas from development is the basis for marine and terrestrial national parks, biological reserves, and wilderness areas distributed globally. Nonetheless, how one defines, determines, and assesses ecological integrity remains unclear, if not controversial, to many scientists, managers, politicians, and concerned citizens. Part of this ambiguity arises from the multiplicity of terms associated with ecological integrity, such as ecological health, ecological sustainability, ecosystem services, environmental health, biological integrity, biological diversity, and natural. Therefore, any comprehensive discussion of ecological integrity must incorporate discussion and clarification of those terms as well as a brief history of the use of the concept.
Legal Pluralism
Authors: Greenhouse Carol J.
Published: April 2019

Legal pluralism is a major theme for anthropologists concerned with law, and integral to anthropology’s fundamental concerns with the availability of law to sustaining cultural diversity as basic to the human condition. In its modern form, legal pluralism emerged as a scholarly field in the 1960s in exchanges among anthropologists and academic lawyers, first in Europe and later in North America, expanding worldwide with the development of sociolegal studies as a transnational interdisciplinary endeavor. The field has expanded along pathways traced by people’s demands for justice through law over time, as well as by institutional innovations in the state administration of justice, the organization of courts and legislatures, and other aspects of law confronting demands for cultural accommodation. At its inception as a scholarly field, legal pluralism dealt mainly with customary and indigenous rights in relation to the legal systems of colonial powers. Later, the field expanded as the classic research questions led back to the colonial powers themselves, and eventually to national states anywhere. In the early 21st century, the term refers to even wider horizons of inquiry, from the norms of private life to human rights law to the legal aspects of globalization, as these are diversely asserted and contested around the world. Whatever its referent, there is always an implication of law’s centrality to the experience of difference, and accordingly, to the inexhaustible possibility that law and society might be otherwise. While the field could at one time be associated with a discrete literature, this is no longer the case; legal pluralism is neither one conversation, nor one sole topic. It is a more or less borderless domain of inquiry for social scientists—especially sociocultural anthropologists—and academic lawyers, as they are separately or together engaged with the pragmatics of multicultural inclusion and the democratization of justice through law. The bibliography is selectively focused around zones indicated by those engagements, sometimes reaching beyond scholarship explicitly identified with literature on legal pluralism. The subtopics developed here merit separate treatment in themselves. The bibliographic discussion presents classic sources, subsequent debates, and applications as developed mainly by anthropologists. Beyond the opening section on classics, this article leans toward the future—focusing primarily on current work by anthropologists, and secondarily on that by legal scholars among others, aiming for a selection that conveys the substance and stakes of current debates, while sampling international scholarship. It inevitably includes but a small selection of the many country and regional studies of legal pluralism currently in print as monographs and articles. It does not include historical studies, notwithstanding their intrinsic interest for readers interested in legal pluralism. It is by no means a comprehensive account of people’s demands for rights and recognition.
Ideophones
Authors: Akita Kimi
Published: April 2019

Ideophones are words that vividly depict sensory experience with marked forms. They abound in many languages of the world, including Niger-Congo, Afro-Asiatic, Dravidian, Austroasiatic, and Quechuan languages as well as Japanese, Korean, Turkish, and Basque. The term “ideophone” originates in Bantu linguistics but is applied across languages. Ideophones are also known as “mimetics” in Japanese linguistics and “expressives” in South and Southeast Asian linguistics. Arguably all spoken languages have onomatopoeic (sound-imitative) ideophones (e.g., woof-woof, wham), and many languages also have ideophones for non-auditory information, such as motion (e.g., plisti-plasta ‘walking in water’ (Basque)), shine (e.g., ɡéɡéréré ‘shining brightly’ (Chewa)), shape (e.g., tíɡhí-tìɡhì-tíɡhí ‘twisted’ (Edo)), and texture (e.g., lip rip ‘smooth, flat’ (Hausa)). Ideophones in some languages further depict color (e.g., yibɔɔ ‘black’ (Ewe)), taste and smell (e.g., thuu ‘smelling horribly’ (Venda)), proprioceptive sensations (e.g., rupax ‘intensely warm or burning’ (Pastaza Quichua)), and emotion (e.g., zokuzoku ‘thrilled’ (Japanese)). These sensory meanings are often iconically represented by some marked morphophonological features, such as unusual phonotactics (e.g., /ɡb/ (Kisi)), vowel or tonal harmony (e.g., ɡbànɡbàlànɡ ‘long pole falling down’ (Dagaare)), and total or partial reduplication (e.g., tʃoɭtʃoɭ ‘in continuous flow’ (Korean), kananaa ‘silent’ (Siwu)). The formal markedness of ideophones may be further emphasized by lengthening (e.g., baaaang), prominent intonation, special phonation (e.g., falsetto, creaky voice), distinct speech rate, and syntactic isolation (e.g., holophrastic realization). Moreover, as a nonverbal manifestation of their performative nature, ideophones often synchronize with iconic gestures. Ideophones constitute a prototype category for which none of these features are either necessary or sufficient, and often, one cannot decide clearly whether a word is an ideophone or not. Furthermore, ideophones are integrated with the linguistic system to varying degrees both within and across languages. For example, holophrastic ideophones tend to have expressive prosody and be accompanied by iconic gestures, whereas predicative ideophones tend to be plain. Reflecting this behavioral diversity of ideophones, earlier studies focused on sound-symbolic generalizations and categorial definitions in individual languages, notably Asian and African languages. However, a growing body of research from the 1990s onward has sought the theoretical and typological significance of this word class.
Young People and Disadvantaged Environments in Affluent Countries
Authors: Visser Kirsten
Published: April 2019

Many social scientists over the last decades have focused on the question of the impacts of poverty on people. Studies in this field primarily examine the effects of social, cultural, and economic resources and structural factors on the development, social outcomes, and well-being of an individual. In the last decades, scholarly interest has increasingly focused on poverty among children and adolescents (hereafter “young people”). Young people are seen as a nation’s future, which forms a reason for societal concern with their well-being and developmental outcomes. In addition, scholars increasingly acknowledge that poverty is multidimensional and heterogenous: the effects of poverty differ according to personal characteristics such as age, gender, race/ethnicity, or disability, but they are also exemplified by the disadvantaged environments in which young people find themselves, such as dysfunctional families, deprived neighborhoods, and low-quality schools. This article gives an overview of the most important works in the field of the effects of poverty and disadvantaged environments on young people (0–18 years of age). As the nature of poverty differs significantly between affluent countries and low-income developing countries, this review is focused on studies in the United States, Europe, Australia, and New Zealand. Given the fact that disadvantage, and the different effects thereof on young people, can be approached from the perspectives offered by different social sciences, publications from geography, sociology, social work, anthropology, economics, and (environmental) psychology are included in this review. This article departs from the idea of ecological models, assuming that poverty impacts children within their various contexts such as the home, school, and neighborhood. After presenting general works on poverty among young people, attention is given to the impacts of disadvantages in home, neighborhood, and school environments. Most studies that are discussed in this review deal with disadvantage in urban areas, reflecting the focus of the overall literature in affluent countries. However, poverty and disadvantage also differ between urban and rural environments. Therefore, the article ends with an overview of literature on poverty among young people in rural areas.
Joanna Russ
Authors: March-Russell Paul
Published: April 2019

Joanna Russ was one of the most influential figures within postwar women’s science fiction. As a writer, she incorporated modernist techniques, such as collage, so as to defamiliarize generic science fiction scenarios, for example, the first contact narrative, time travel, and alternate history, and to question their ideological bases. As a critic, she was instrumental in propounding science fiction as a genre that estranges its readership but which, until the Women’s movement of the 1960s, had tended to assume that the reader was exclusively white, male, and heterosexual. Lastly, as a feminist, she united both her creative and critical practices in an attempt to deflect this male gaze, and to open up the possibilities of alternate forms of social and sexual identity. Russ was born in the Bronx, New York City, on February 22, 1937. Her parents were both schoolteachers, from whom she gained a love of reading. She studied English at Cornell University, where she was taught by Vladimir Nabokov. Russ then studied playwriting at Yale University, where she discovered the work of Bertolt Brecht. She published her first science fiction story, “Nor Custom Stale,” in 1959. After teaching at the University of Boulder, Russ returned to Cornell as a tutor in 1968. During the next twelve months, Russ would join the first-ever women’s group at Cornell, publish her first novella, Picnic on Paradise, leave her husband, come out as a lesbian, and begin work on her masterpiece, The Female Man (cited under Novels). During the early 1970s, Russ became, alongside her close friend and fellow author, Samuel R. Delany, one of the most important critical voices in science fiction. In 1977, she became an associate professor at the University of Washington, Seattle, where, six years later, she published her most influential work of literary criticism, How to Suppress Women’s Writing (cited under Nonfiction). Russ won several awards including the Nebula Award in 1972 for “When It Changed,” the Hugo Award in 1983 for “Souls,” and the Pilgrim Award for science fiction criticism in 1988. Her literary output diminished after the early 1980s; Russ’s final short story, “Invasion,” was published in 1996. Plagued by chronic back problems, Russ retired from academia to concentrate upon her critical writings. On April 29, 2011, following a series of strokes, Russ died in Tucson, Arizona.
Nairobi
Authors: Carrier Neil
Published: April 2019

Nairobi is one of the largest metropolises of Africa, with a current population of almost four million, and much larger with the wider metropolitan area taken into account. Its great contemporary size is hard to reconcile with its humble origins over a century ago as a campsite on a marshy plain, formed when building the Uganda Railway in the 1890s. This campsite grew quickly as a railway depot, taking its name from the Maasai enkare Nairobi, meaning “place of cold water,” and it was soon chosen as a provincial capital. It became a municipality in 1919, then designated a city in 1950. Despite initially being planned as a European town, Nairobi soon became highly cosmopolitan, with a large Indian population, many Africans from near and far, and others from as far afield as Somaliland and the Seychelles. Nairobi’s history is bound up with the wider story of colonial Kenya and East Africa, being a site of many of the tensions and contradictions of colonial rule, and this past still influences its current form. However, since Independence the city has grown into a vibrant political, commercial, touristic, artistic, and academic hub of East Africa. It hosts many international media and humanitarian organizations, as well as various branches of the United Nations. It is a city of great contrasts, with numerous slum settlements juxtaposed with estates of great wealth, and with its busy and often congested roads and streets contrasting with the nearby Nairobi National Park. Like many other cities in Africa, Nairobi faces great challenges in an era of rapid urbanization, and much of the academic literature reflects this, with work focusing on topics such as failing infrastructure, corruption, and violence. However, it is also a place where challenges are overcome, where much innovation takes place, and where many see brighter futures for themselves. In short, it is a compelling city that speaks to many of the ambiguities of contemporary urban life, and one deeply fascinating to scholars from a range of disciplines interested in urbanization in the 21st Century.
Stability of $\alpha$-chain states against disintegrations
Authors: Tohsaki Akihiro , Itagaki Naoyuki
Published: April 2019

We focus on the raison d’être of the $\alpha$-chain states on the basis of the fully microscopic framework, where the Pauli principle among all the nucleons is fully taken into account. Our purpose is to find the limiting number of $\alpha$ clusters on which the linear $\alpha$-cluster state can stably exist. How many $\alpha$ clusters can stably make an $\alpha$-chain state? We examine the properties of equally separated $\alpha$ clusters on a straight line and compare its stability with that on a circle. We also confirm its stability in terms of binary and ternary disintegrations including $\alpha$-decay and fission modes. For the effective nucleon–nucleon interaction we employ the F1 force, which has finite-range three-body terms and guarantees overall saturation properties of nuclei. This interaction also gives a reasonable binding energy and size of the $\alpha$ particle, and the $\alpha$–$\alpha$ scattering phase shift. The result astonishes us because we can point out the possible existence of $\alpha$-chain states with vast numbers of $\alpha$ clusters.
Rape Culture and Candidate Selection in the 2016 U.S. Presidential Election
Authors: Johnson Nicole L , Rocchino Gabrielle H , Wolf Jacob A , Gutekunst Malaïka H C , Paulvin Cléopatre , Farrell Jerome A
Published: April 2019

During the 2016 U.S. presidential election, violence against women was salient in the narratives surrounding both major party candidates: Hillary Clinton and Donald Trump. These discussions surrounding violence against women reflect a cultural ideology that excuses and/or supports such violence. This study aimed to understand the function of politics, particularly presidential campaigns, voting behavior, and candidate selection on perceptions of rape culture. Data were collected from two different samples: pre- and postelection from a medium-sized university. Results demonstrated differences between the samples on perceptions of rape culture as well as differences within the postelection sample based on candidate selection.
Assessment of campus community readiness for tailoring implementation of evidence-based online programs to prevent risky substance use among university students in Germany
Authors: Wichmann Frauke , Braun Michael , Ganz Thomas , Lubasch Johanna , Heidenreich Thomas , Laging Marion , Pischke Claudia R
Published: April 2019

Research suggests that online interventions preventing risky substance use can improve student health. There is an increasing interest in transferring evidence-based online programs into university health promotion practice. However, little is known about how to best tailor the implementation process to capacities and context of individual universities. The purpose of this study was to assess the level of readiness (capacity) of German universities concerning the implementation of evidence-based online programs for risky substance use prevention employing an adapted Community Readiness Assessment (CRA) and to develop tailored action plans for implementation. The CRA involved 43 semi-structured interviews with key persons at 10 German universities. The interviews addressed five dimensions (knowledge of efforts, leadership, community climate, knowledge of the issue, and resources) at nine possible readiness stages (no awareness—ownership) and additional contextual factors. Overall, readiness for implementing online interventions across universities was rather low. Universities readiness levels ranged between the denial stage with a score of 2.1 and the preplanning stage with a score of 4.4. University-specific readiness was very heterogeneous. On the basis of the results of the CRA, universities received feedback and options for training on how to take the necessary steps to increase readiness and to prepare program implementation. The adapted version of the CRA was well suited to inform future implementation of evidence-based online programs for the prevention of risky substance use at participating universities.
Expression and Localization Patterns of a Small Heat Shock Protein that Interacts with the Helicase Domain of Cucumber Green Mottle Mosaic Virus
Authors: Liu Shanshan , Liu Lifeng , Aranda Miguel A. , Peng Bin , Gu Qinsheng
Published: April 2019

Cucumber green mottle mosaic virus (CGMMV), a member of the genus Tobamovirus (family Virgaviridae), is an economically important virus that has detrimental effects on cucurbit crops worldwide. Understanding the interaction between host factors and CGMMV viral proteins will facilitate the design of new strategies for disease control. In this study, a yeast two-hybrid assay revealed that the CGMMV helicase (HEL) domain interacts with a Citrullus lanatus small heat shock protein (sHSP), and we verified this observation by performing in vitro GST pull-down and in vivo coimmunoprecipitation assays. Measurement of the levels of accumulated sHSP transcript revealed that sHSP is upregulated on initial CGMMV infection in both Nicotiana benthamiana and C. lanatus plants, although not in the systemically infected leaves. We also found that the subcellular localization of the sHSP was altered after CGMMV infection. To further validate the role of sHSP in CGMMV infection, we produced and assayed N. benthamiana transgenic plants with up- and down-regulated sHSP expression. Overexpression of sHSP inhibited viral RNA accumulation and retarded disease development, whereas sHSP silencing had no marked effect on CGMMV infection. Therefore, we postulate that the identified sHSP may be one of the factors modulating host defense mechanisms in response to CGMMV infection and that the HEL domain interaction may inhibit this sHSP function to promote viral infection.
The Moorfields AMD Database Report 2 - Fellow Eye Involvement with Neovascular Age-related Macular Degeneration
Authors: Fasler Katrin , Moraes Gabriella , Fu Dun Jack , Wagner Siegfried K. , Gokhale Eesha , Kortuem Karsten U. , Chopra Reena , Faes Livia , Preston Gabriella , Pontikos Nikolas , Patel Praveen J. , Tufail Adnan , Lee Aaron Y. , Balaskas Konstantinos , Keane Pearse A.
Published: April 2019

Background/Aims

Neovascular age-related macular degeneration (nAMD) is frequently bilateral, and previous reports on ‘fellow eyes’’ have assumed sequential treatment after a period of treatment of the first eye only. The aim of our study was to analyse baseline characteristics and visual acuity (VA) outcomes of fellow eye involvement with nAMD, specifically differentiating between sequential and non-sequential (due to macular scarring in the first eye) anti-vascular endothelial growth factor treatment and timelines for fellow eye involvement.

Methods

Retrospective, electronic medical record database study of the Moorfields AMD database of 8174 eyes/120,756 single entries with data extracted between October 21, 2008 and August 9, 2018. The dataset for analysis consisted of 1180 sequential, 413 nonsequential, and 1110 unilateral eyes.

Results

Mean VA of sequentially treated fellow eyes at baseline was significantly higher (62±13), VA gain over two years lower (0.65±14), and proportion of eyes with good VA (≥20/40 or 70 letters) higher (46%) than the respective first eyes (baseline VA 54±16, VA gain at two years 5.6±15, percentage of eyes with good VA 38%). Non-sequential fellow eyes showed baseline characteristics and VA outcomes similar to first eyes. Fellow eye involvement rate was 32% at two years, and median time interval to fellow eye involvement was 71 (IQR 27-147) weeks.

Conclusion

This reports shows sequentially treated nAMD fellow eyes have better baseline and final VA than non-sequentially treated eyes after 2 years of treatment. Sequentially treated eyes also had a greater proportion with good VA after 2 years of treatment.

PRECIS

Depending on age, fellow eye involvement occurs in 32% of patients with neovascular AMD by two years. Fellow eyes generally maintain better vision, except in cases where late-stage disease in the first eye was untreated.
Evaluation of DNA extraction methods on individual helminth egg and larval stages for whole genome sequencing
Authors: Doyle Stephen R. , Sankaranarayan Geetha , Allen Fiona , Berger Duncan , Jimenez Castro Pablo D. , Collins James Bryant , Crellen Thomas , Duque-Correa María A. , Ellis Peter , Jaleta Tegegn G. , Laing Roz , Maitland Kirsty , McCarthy Catherine , Moundai Tchonfienet , Softley Ben , Thiele Elizabeth , Ouakou Philippe Tchindebet , Tushabe John Vianney , Webster Joanne P. , Weiss Adam J. , Lok James , Devaney Eileen , Kaplan Ray M. , Cotton James A. , Berriman Matthew , Holroyd Nancy
Published: April 2019

Whole genome sequencing is being rapidly applied to the study of helminth genomes, including de novo genome assembly, population genetics, and diagnostic applications. Although late-stage juvenile and adult parasites typically produce sufficient DNA for molecular analyses, these parasitic stages are almost always inaccessible in the live host; immature life stages found in the environment for which samples can be collected non-invasively offer a potential alternative, however, these samples are typically yield very low quantities of DNA, can be environmentally resistant, and are susceptible to contamination, often from bacterial or host DNA. Here, we have tested five low-input DNA extraction protocols together with a low-input sequencing library protocol to assess the feasibility of whole genome sequencing of individual immature helminth samples. These approaches do not use whole genome amplification, a common but costly approach to increase the yield of low input samples. We first tested individual parasites from two species spotted onto FTA cards - egg and L1 stages of Haemonchus contortus and miracidia of Schistosoma mansoni - before further testing on an additional six species - Ancylostoma caninum, Ascaridia dissimilis, Dirofilaria immitis, Dracunculus medinensis, Strongyloides stercoralis, and Trichuris muris - with an optimal protocol. Whole genome sequencing followed by analyses to determine the proportion of on- and off-target mapping revealed successful sample preparations for six of the eight species tested with variation between species, and within species but between life stages, described. These results demonstrate the feasibility of whole genome sequencing of individual parasites, and highlight a new avenue towards generating sensitive, specific, and information-rich data for the diagnosis and surveillance of helminths.
MNC-RED A Chemically-Defined Method to Produce Enucleated Red Blood Cells from Adult Peripheral Blood Mononuclear Cells
Authors: Zhang Shouping , Olivier Emmanuel N , Yan Zi , Suzuka Sandra , Roberts Karl , Wang Kai , Bouhassira Eric E
Published: April 2019

Many methods have been developed to produce red blood cellsin vitrobut translational applications have been hampered by the high cost of production. We have developed R6, a chemically-defined, albumin-free, low-transferrin culture medium, and MNC-RED, a protocol to differentiate peripheral blood mononuclear cells into enucleated erythroid cells that does not require any albumin or any animal components. Erythropoiesis requires large amounts of iron for hemoglobin synthesis. In all existing protocols, these large iron needs are met by increasing the concentration of holo-transferrin. This is necessary because transferrin recycling does not take place in existing erythroid culture conditions. In the R6 medium, iron is provided to the differentiating erythroblasts by small amounts of recombinant transferrin supplemented with FeIII-EDTA, an iron chelator that allows transferrin recycling to take place in cell culture. As a result of the absence of albumin and the use of low amounts of transferrin, the production of cultured red blood cells using the MNC-RED protocol is much less expensive than with existing protocols. The MNC-RED protocol should therefore help make the many translational applications of cultured RBCs economically more feasible.

Highlights

We have developed R6, a chemically-defined, albumin-free low-transferrin culture medium, and MNC-RED, a protocol to differentiate peripheral blood mononuclear cells into enucleated erythroid E

R6 is suitable for red blood cell culture despite the low transferrin amounts because of the presence of FeIII-EDTA, an iron chelator that allows transferrin recycling to take place in cell culture.

The MNC-RED protocol should help make the many translational applications of cultured RBCs more economically feasible.
Syntenizer 3000: Synteny-based analysis of orthologous gene groups
Authors: Moslemi Camous , Skovbjerg Cathrine Kiel , Moeskjær Sara , Andersen Stig Uggerhøj
Published: April 2019

Motivation

The amorphous nature of genes combined with the prevalence of duplication events makes establishing correct genetic phylogenies challenging.

Since homologous gene groups are traditionally formed on basis of sequence similarity, both orthologs and paralogs are often placed in the same gene group by existing tools. Certain tools such as PoFF take syntenic relationship of genes into consideration when forming gene groups. However, a method to form gene groups consisting of only true syntelogs has not yet been developed.

In order to obtain orthologous gene groups consisting of the most likely syntelogs we need a method to filter out paralogs. If one strain has two or more copies of the same gene in a gene group we want to keep only the true syntelog in the group, and remove the paralogous copies by distinguishing between the two using synteny analysis.

Results

We present a novel algorithm for measuring the degree of synteny shared between two genes and successfully disambiguate gene groups. This synteny measure is the basis for a number of other useful functions such as gene neighbourhood visualisation to inspect suspect gene groups, strain visualisation for assessing assembly quality and finding genomic areas of interest, and chromosome/plasmid classification of contigs in partially classified datasets.

Availability

The latest version of Syntenizer 3000 can be downloaded from the GitHub repository at https://github.com/kamiboy/Syntenizer3000/

Consult the manual.pdf file in the repository for instructions on how to build and use the tool, as well as a in depth explanation of the algorithms utilised.
Control Theory Concepts for Modeling Uncertainty in Enzyme Kinetics of Biochemical Networks
Authors: Miskovic Ljubisa , Tokic Milenko , Savoglidis Georgios , Hatzimanikatis Vassily
Published: April 2019

Analysis of the dynamic and steady-state properties of biochemical networks hinge on information about the parameters of enzyme kinetics. The lack of experimental data characterizing enzyme activities and kinetics along with the associated uncertainties impede the development of kinetic models, and researchers commonly use Monte Carlo sampling to explore the parameter space. However, the sampling of parameter spaces is a computationally expensive task for larger biochemical networks. To address this issue, we exploit the fact that reaction rates of biochemical reactions and network responses can be expressed as a function of displacements from thermodynamic equilibrium of elementary reaction steps and concentrations of free enzymes and their intermediary complexes. For a set of kinetic mechanisms ubiquitously found in biochemistry, we express kinetic responses of enzymes to changes in network metabolite concentrations through these quantities both analytically and schematically. The tailor-made sampling of these quantities allows for characterizing the missing kinetic parameters and accelerating the efforts towards building genome-scale kinetic metabolic models.
Multi-Template Matching: a versatile tool for object-localization in microscopy images
Authors: Thomas Laurent S. V. , Gehrig Jochen
Published: April 2019

We implemented multiple template matching as both a Fiji plugin and a KNIME workflow, providing an easy-to-use method for the automatic localization of objects of interest in images. We demonstrate its application for the localization of entire or partial biological objects. The Fiji plugin can be installed by activating the Multi-Template-Matching and IJ-OpenCV update sites. The KNIME workflow can be downloaded from nodepit space or the associated GitHub repository. Python source codes and documentations are available on the following GitHub repositories: LauLauThom/MultiTemplateMatching and LauLauThom/MultipleTemplateMatching-KNIME.
EphB1 in Endothelial Cells Regulates Caveolae Formation and Endocytosis
Authors: Tiruppathi Chinnaswamy , Regmi Sushil C. , Wang Dong-Mei , Mo Gary C.H. , Toth Peter T. , Vogel Stephen M. , Stan Radu V. , Henkemeyer Mark , Minshall Richard D. , Malik Asrar B.
Published: April 2019

Caveolae, the cave-like structures abundant in endothelial cells (ECs), are important in regulating key functions such as caveolae-mediated endocytosis and generation of nitric oxide. Here we show that deletion of the receptor tyrosine kinase EphB1 (EphB1−/−) in mice markedly reduced the caveolae number in ECs of heart and lung vessels and prevented caveolae-mediated endocytosis. EphB1 expressed in adult ECs was shown to bind the caveolin-1 (Cav-1) scaffold domain (CSD) via the CSD binding motif (CSDBM) on EphB1. We demonstrated that activation of EphB1 by the native ligand Ephrin B1 uncoupled EphB1 from Cav-1, and licensedSrc-dependent Y-14 Cav-1 phosphorylation. Deletion of CSDBM on EphB1 prevented EphB1/Cav-1 interaction and the activation ofSrcandSrcmediated Y-14 Cav-1 phosphorylation. These studies identify the central role of endothelium expressed EphB1 in regulating caveolae biogenesis and caveolae-mediated endocytosis.
Validation of a CRISPR/cas9-based technology platform for examining specific immune gene functions in an experimental murine model of IBD
Authors: Wang Rui , Graham Sean , Sun Ning , McCarthy Donna , Peng Ruoqi , Erickson Jamie , Zhu Xiaochun , Wurbel Marc , Dunstan Robert , Chung Namjin , Fiebiger Edda , Ghayur Tariq , Gu Jijie
Published: April 2019

Inflammatory bowel diseases (IBD) are complex, multifactorial disorders characterized by chronic relapsing intestinal inflammation. Association studies have identified hundreds of genes that are linked to IBD and potentially regulate its pathology. The further dissection of the genetic network underlining IBD pathogenesis and pathophysiology is hindered by the limited capacity to investigate the role of each GWAS association through functional studies, including the generation of knockout animal models for each of the associated genes. The CRISPR/Cas9 system represents a cutting edge technology which has the potential to transform the field of IBD research by facilitating the introduction of genetic alterations in an efficient and effective manner. Using the CD40-mediated-colitis model, our results demonstrate the validity of a CRISPR/Cas9-based platform as a tool for the validation of target genes or interference strategies in experimental IBD. The utilization of this discovery strategy will allow for the timelyin vivovalidation of therapeutic targets as the rapidly emerge from current genetic and genomics efforts with human disease tissue. As such, the CRISPR/Cas9-based platform can significantly shorten the time span between target identification and generation of proof of principle experiments for drug discovery.
Deprivation of dietary fiber enhances susceptibility of mice to cryptosporidiosis
Authors: Oliveira Bruno César Miranda , Bresciani Katia Denise Saraiva , Widmer Giovanni
Published: April 2019

Based on our initial observations showing that mice consuming a probiotic product develop more severe cryptosporidiosis, we investigated the impact of other dietary interventions on the intracellular proliferation ofCryptosporidium parvumandC. tyzzeriin the mouse. Mice were orally infected with oocysts and parasite multiplication measured by quantifying fecal oocyst output. High-throughput sequencing of 16S ribosomal RNA amplicons was used to correlate oocyst output with diet and with the composition of the intestinal microbiota. On average, mice fed a diet without fiber (cellulose, pectin and inulin) developed more severe infections. As expected, a diet without fibers also significantly altered the fecal microbiota. Consistent with these observations, mice fed a prebiotic product sold for human consumption excreted significantly fewer oocysts. The fecal microbiota of mice consuming no plant polysaccharides was characterized by a lower relative abundance of Bacteroidetes bacteria. Since bacterial metabolites play an important role in the physiology of intestinal enterocytes, we hypothesize based on these observations that the impact of diet on parasite proliferation is mediated primarily by the metabolic activity of the anaerobic microbiota, specifically by the effect of certain metabolites on the host. This model is consistent with the metabolic dependence of intracellular stages of the parasite on the host cell. These observations underscore the potential of dietary interventions to alleviate the impact of cryptosporidiosis, particularly in infants at risk of recurrent enteric infections.

AUTHOR SUMMARY

The infection withCryptosporidiumparasite, a condition known as cryptosporidiosis, is a common cause of infant diarrhea in developing countries. We have previously shown that mice infected withC. parvum, one of the main cause of human cryptosporidiosis, develop a more severe infection if given probiotics. To investigate the mechanism of this effect, we fed mice prebiotics and diet lacking plant fiber. We found that fermentable fiber, whether administered as a prebiotic supplement or is part of the diet, has a protective effect against cryptosporidiosis in mice. We also observed a significant association between the severity of infection and the composition of the gut microbiota. A significant inverse correlation was found between severity of cryptosporidiosis and the ratio between the abundance of bacteria belonging to the phylum Bacteroidetes and the abundance of Firmicute bacteria. This ratio is frequently viewed as a marker of a healthy microbiota. These results raise the possibility that dietary interventions could be used to alleviate the impact of cryptosporidiosis.
Characterizing transmissive diamond gratings as beam splitters for the hard X-ray single-shot spectrometer of the European XFEL
Authors: Kujala Naresh , Makita Mikako , Liu Jia , Zozulya Alexey , Sprung Michael , David Christian , Grünert Jan
Published: April 2019

The European X-ray Free Electron Laser (EuXFEL) offers intense, coherent femtosecond pulses, resulting in characteristic peak brilliance values a billion times higher than that of conventional synchrotron facilities. Such pulses result in extreme peak radiation levels of the order of terawatts cm−2 for any optical component in the beam and can exceed the ablation threshold of many materials. Diamond is considered the optimal material for such applications due to its high thermal conductivity (2052 W mK−1 at 300 K) and low absorption for hard X-rays. Grating structures were fabricated on free-standing CVD diamond of 10 µm thickness with 500 µm silicon substrate support. The grating structures were produced by electron-beam lithography at the Laboratory for Micro- and Nanotechnology, Paul Scherrer Institut, Switzerland. The grating lines were etched to a depth of 1.2 µm, resulting in an aspect ratio of 16. The characterization measurements with X-rays were performed on transmissive diamond gratings of 150 nm pitch at the P10 beamline of PETRA III, DESY. In this paper, the gratings are briefly described, and a measured diffraction efficiency of 0.75% at 6 keV in the first-order diffraction is shown; the variation of the diffraction efficiency across the grating surface is presented.