bluuebunny/crossref_metadata_2025 huggingface dataset:
Unfinished Business: A Systematic Review of Stump Appendicitis
Authors: Manatakis Dimitrios K. , Aheimastos Vasileios , Antonopoulou Maria‐Ioanna , Agalianos Christos , Tsiaoussis John , Xynos Evanghelos
Published: August 2019

Background

Stump appendicitis is defined as interval inflammation of any residual appendicular tissue, after an appendicectomy. We present a systematic review of case series and case reports on stump appendicitis, emphasising on risk factors, diagnosis and surgical management.

Methods

The English literature (1945–2018) was reviewed, using PubMed, Embase and GoogleScholar, combining the terms “appendix”, “appendicitis”, “stump”, “residual”, “recurrent” and “retained”. In total, 127 studies were included, describing 164 patients (males 59%, mean age 36 ± 17 years).

Results

Index surgery was open in 59% and laparoscopic in 38%. It was described as “difficult” or “complicated” in 31%. 20% of patients reported episodes of recurrent abdominal pain during the time interval between index and stump appendicitis (range 2 weeks to 60 years, median 2 years). Right lower quadrant pain was the most frequent complain (88%), leukocytosis was found in 56%, whereas 92% of patients underwent imaging testing, which was diagnostic or highly suspicious in 67.5%. Mean delay between beginning of symptoms and surgery was 2.4 ± 2.3 days. The operative approach was open in 61% and laparoscopic in 35% of cases. The operation was characterised as “difficult” or “complicated” in 45%. In the majority (88%), a completion stump appendicectomy was performed, with 11% requiring more extensive procedures. Mean length of resected stump was 3.1 ± 1.6 cm (range 0.5–10 cm).

Conclusions

Stump appendicitis may occur following both open and laparoscopic approach, when the residual stump is > 0.5 cm. Its clinical significance lies in the delayed diagnosis, leading to higher incidence of complications and the need for more extensive surgery.
Understanding traditional Chinese medicine via statistical learning of expert‐specific Electronic Medical Records
Authors: Yang Yang , Li Qi , Liu Zhaoyang , Ye Fang , Deng Ke
Published: August 2019

Background

Traditional Chinese medicine (TCM) has been attracting lots of attentions from various disciplines recently. However, TCM is still mysterious because of its unique philosophy and theoretical thinking. Due to the lack of high quality data, understanding TCM thoroughly faces critical challenges. In this study, we introduce the Zhou Archive, a large‐scale database of expert‐specific Electronic Medical Records containing information about 73,000+ visits to one TCM doctor for over 35 years. Covering the full spectrum of diagnosis‐treatment model behind TCM practice, the archive provides an opportunity to understand TCM from the data‐driven perspective.

Methods

Processing the text data in the archive via a series of data processing steps, we transformed the semi‐structured EMRs in the archive to a well‐structured feature table. Based on the structured feature table obtained, a series of statistical analyses are implemented to learn principles of TCM clinical practice from the archive, including correlation analysis, enrichment analysis, embedding analysis and association pattern discovery.

Results

A structured feature table of 14,000+ features is generated at the end of the proposed data processing procedure, with a feature codebook, a term dictionary and a term‐feature map as byproducts. Statistical analysis of the feature table reveals underlying principles about the diagnosis‐treatment model of TCM, helping us better understand the TDM practice from a data‐driven perspective.

Conclusion

Expert‐specific EMRs provide opportunities to understand TCM from the data‐driven perspective. Taking advantage of recent progresses on NLP for Chinese, we can process a large number of TCM EMRs efficiently to gain insights via statistical analysis.
A Practitioner’s Guide to Performing a Holistic Evaluation of Technology-Enhanced Learning in Medical Education
Authors: Pickering James D. , Lazarus Michelle D. , Hallam Jennifer L.
Published: August 2019

Technology-enhanced learning (TEL) is now a common mode of educational delivery within medical education. Despite this upsurge, there remains a paucity in comprehensive evaluation of TEL efficacy. In order to make meaningful and evidence-informed decisions on ‘how’ and ‘when’ to utilise technology within a course, ‘useful knowledge’ is required to support faculty in these decision-making processes. In this monograph, a series of pragmatic and achievable approaches for conducting a holistic evaluation of a TEL resource intervention are detailed. These suggestions are based on an established TEL evaluation framework, as well as the author’s own experience and that of the broader literature. The approaches cover development of an appropriate research question that is based on the availability of existing TEL resources alongside the peer-reviewed literature; the development of an appropriate team as well as recommendations for navigating ethical approval; conducting small-scale quantitative and qualitative measure; and performing a large-scale mixed methods assessment to understand the holistic impact of the TEL resource.
The discovery and prediction of vortex flow aerodynamics
Authors: Luckring J.M.
Published: August 2019

High-speed aircraft often develop separation-induced leading-edge vortices and vortex flow aerodynamics. In this paper, the discovery of separation-induced vortex flows and the development of methods to predict these flows for wing aerodynamics are reviewed. Much of the content for this article was presented at the 2017 Lanchester Lecture and the content was selected with a view towards Lanchester’s approach to research and development.
Black Power in the Boardroom: Corporate America, the Sullivan Principles, and the Anti-Apartheid Struggle
Authors: LEVY JESSICA ANN
Published: August 2019

This article traces the history of General Motors’ first black director, Leon Sullivan, and his involvement with the Sullivan Principles, a corporate code of conduct for U.S. companies doing business in Apartheid South Africa. Building on and furthering the postwar civil rights and anti-colonial struggles, the international anti-apartheid movement brought together students, union workers, and religious leaders in an effort to draw attention to the horrors of Apartheid in South Africa. Whereas many left-leaning activists advocated sanctions and divestment, others, Sullivan among them, helped lead the way in drafting an alternative strategy for American business, one focused on corporate-sponsored black empowerment. Moving beyond both narrow criticisms of Sullivan as a “sellout” and corporate propaganda touting the benefits of the Sullivan Principles, this work draws on corporate and “movement” records to reveal the complex negotiations between white and black executives as they worked to situate themselves in relation to anti-racist movements in the Unites States and South Africa. In doing so, it furthermore reveals the links between modern corporate social responsibility and the fight for Black Power within the corporation.
Comparative Causal Mediation and Relaxing the Assumption of No Mediator–Outcome Confounding: An Application to International Law and Audience Costs
Authors: Bansak Kirk
Published: August 2019

Experiments often include multiple treatments, with the primary goal to compare the causal effects of those treatments. This study focuses on comparing the causal anatomies of multiple treatments through the use of causal mediation analysis. It proposes a novel set of comparative causal mediation (CCM) estimands that compare the mediation effects of different treatments via a common mediator. Further, it derives the properties of a set of estimators for the CCM estimands and shows these estimators to be consistent (or conservative) under assumptions that do not require the absence of unobserved confounding of the mediator–outcome relationship, which is a strong and nonrefutable assumption that must typically be made for consistent estimation of individual causal mediation effects. To illustrate the method, the study presents an original application investigating whether and how the international legal status of a foreign policy commitment can increase the domestic political “audience costs” that democratic governments suffer for violating such a commitment. The results provide novel evidence that international legalization can enhance audience costs via multiple causal channels, including by amplifying the perceived immorality of violating the commitment.
The Rise of the European Migration Regime and Its Paradoxes (1945–2020)
Authors: Lucassen Leo
Published: August 2019

How can we explain the demise of the new postwar moral framework of anti-racism and equality and the subsequent rise of integration pessimism in Western Europe in the 1980s, a pessimism that led to the widely accepted idea, from left to right, that “multiculturalism” has failed? And how does this square with the simultaneous establishment of an extraordinary free migration regime within Europe that enables EU citizens to move and pick up work in any other member state? Answers to these questions can be found in three very different, yet complimentary studies that help us to understand more deeply the current alarmist public view of migration and integration, as well as its historical roots:The Crisis of Multiculturalismby Rita Chin, based in Ann Arbor;The European Migration Regimeby Emmanuel Comte, from Berkeley; and Steven Jensen's (Danish Institute for Human Rights)The Making of International Human Rights. The studies by Chin and Comte offer a representative gauge of the blossoming field of migration studies and, in particular, show how this specialist niche can enrich insights into much broader (political, cultural, economic, and social) postwar developments in Europe and beyond. Jensen's innovative and critical book on the postwar “humanitarian turn” is highly relevant for migration studies, as it places the establishment of the United Nations (UN) and a number of its institutions, such as UNHCR and UNESCO, in a new light. Although many more books have been published on these topics in recent years, these three complement each other and provide a useful building block for a new understanding of the emergence of the postwar European migration regime, its paradoxes and consequences. In this review, I will first sketch the wider context and then detail the three books and how they relate to each other.
LANGUAGE REFLECTION FOSTERED BY INDIVIDUAL L2 WRITING TASKS
Authors: López-Serrano Sonia , Roca de Larios Julio , Manchón Rosa M.
Published: August 2019

There has been a growing interest in the study of writing from the perspective of its potential contribution to language development. However, scant attention has been paid to key methodological considerations regarding the analysis of the connection between L2 writing processes, reflection on language while writing, and language learning. In an attempt to advance in this domain, and informed by models of L2 writing, and cognitive L2 writing research framed in the problem-solving paradigm, this study provides a comprehensive description of the language reflection individual writers engage in when solving the linguistic problems they face while completing writing tasks in their L2. The think-aloud protocols generated by 21 EFL learners while writing an individual argumentative essay were analyzed on the basis of a reconceptualization of language-related episodes as problem-solving strategy clusters. The result is a comprehensive, theoretically motivated, and empirically based coding system that is offered as a basis for future research in the domain. We discuss the methodological implications of our analytic approach and advance some theoretical implications for future debates on the language learning potential of individual writing tasks.
Phantom Borders in Eastern Europe: A New Concept for Regional Research
Authors: von Hirschhausen Béatrice , Grandits Hannes , Kraft Claudia , Müller Dietmar , Serrier Thomas
Published: August 2019

This paper is programmatic: it defines the concept of “phantom borders” and describes its heuristic potential. The proposed approach positions itself between structuralist methodologies that postulate stable social and cultural regional structures and deconstructive viewpoints that reject the former, while focusing on the discursive dimension of regions. The paper takes this tension as its point of departure. Viewed from a situational perspective, phantom borders are neither to be understood as immutable structures nor as purely discursive constructions, but rather as an outcome of the interaction between three interwoven levels, which are simultaneously: 1) imagined in mental maps and discourses, 2) experienced and perceived by the respective actors, and 3) shaped by everyday practices and continuously updated and implemented. Phantom borders are context sensitive. We argue that the topic of phantom borders is not only relevant for research on eastern Europe, but also for research in “new area studies” in general.
The Synchronous War Novel: Ordeal of the Unarmed Person in Serhiy Zhadan'sInternat
Authors: Zaharchenko Tanya
Published: August 2019

In Serhiy Zhadan's recent novelInternat(2017), the protagonist epitomizes the quintessential east Ukrainian under scrutiny today, while his journey depicts working through trauma. His transformation portrays the ultimate shedding of melancholy when, in response to violence, the past is replaced by the present. I elicit some of the key symbols and features of this process, which I call triggered mourning, and attend to the role of real-time menace in initiating it. This article draws connections not only between the story's plot arc and the ongoing war, but also between Ukraine's past and present from the perspective of trauma theory. The four sections of the article (on the transformation, the void, the defect, and the antidote) propose and expand upon the notion thatInternatis a synchronous war novel—a narrative that emerges parallel to, and closely entwined with, unfolding warfare—and examine its significance for scholarship on Ukraine, for Slavic studies, and beyond. Trauma studies in the context of literature are central to this analysis, with postcolonial studies providing some helpful illustrative parallels.
Painting Light Scientifically: Arkhip Kuindzhi's Intermedial Environment
Authors: Paranyuk Viktoria
Published: August 2019

In art historical scholarship, inasmuch as he is considered at all, the painter Arkhip Kuindzhi has long been viewed as a peculiar outlier. His landscapes, with their coloristic drama, light effects, and simplified forms, hardly fit the accounts of Russian nineteenth-century painting that focus on the development of the realist school. Questioning the artist's anomalous status, this essay discusses his canvases from the 1870s and 1880s within the broader framework of nineteenth-century popular visual amusements, discourses on realism, and the physiology of vision. Considered through this wider lens—beyond the institution of easel painting and beyond Russia—Kuindzhi is revealed to be an innovator whose approach to painting was profoundly modern and aligned with the aesthetic preoccupations of many west European artists. His painterly pursuits and exhibition practices, furthermore, force a reconsideration of the biases associated with the established narrative of modern art in the west.
On the Curious History of the Big Six
Authors: Saucier Gerard
Published: August 2019

Abstract. The Big Five became the foremost model of personality-trait structure in the last three decades, but was formed out of item/variable selections that partially or totally omitted dispositional content related to morality, ethics, integrity, and honesty. Such morality-relevant content has, for several reasons reviewed, extreme importance within the dimension of dispositional tendencies. Previous histories of the Big Five ignore details that account for this pattern of moral-content exclusion, exclusion that tended to impede identification of a key factor in a Big Six or HEXACO model. Here, a set of frequently referenced and highly morality-relevant adjective concepts are identified, based on ratings by 10 judges. The treatment of these concepts enables a tracing of the specific routes and rationales by which exclusion (and partial inclusion) operated in key lexical studies of the archaic period of lexical studies (up through 1993; in English and German), that reveals how variable-selection decisions by early investigators tended to impede identification of an important dimension of personality. Recommendations are offered for future personality-structure research.
Temporal and Spatial Variability of Near‐Inertial Waves in the East/Japan Sea From a High‐Resolution Wind‐Forced Ocean Model
Authors: Jeon Chanhyung , Park Jae‐Hun , Park Young‐Gyu
Published: August 2019

Near‐inertial waves (NIWs), a fundamental oceanic response to wind forcing, play an important role in dynamical processes related to ocean mixing and hence have attracted sustained interest. Herein, we investigate temporally and spatially varying NIW distributions in the mixed and deep layers of the East/Japan Sea (EJS) using high‐resolution hourly‐wind‐forced data‐assimilated ocean model outputs. Temporally, the kinetic energy of NIWs in the mixed and deep layers is higher in fall and winter than in spring and summer, showing maxima in December, corresponding to wind forcings of both wind stress and wind‐current resonance. Spatially, the NIW energy in the mixed layer is higher on the northern side of the subpolar front (SPF), although there are no significant spatial differences in the wind forcings. Because of intensive background currents and their vorticities in the upper layer on the southern side of the SPF, vertical transfer of NIW energy is facilitated, shown by a shorter e‐folding decay time scale of NIWs in the mixed layer on the southern side of the SPF. The NIW kinetic energy in the deep layer of 400–1,000 m is higher on the southern side than on the northern side, an opposite spatial pattern to that in the mixed layer, but consistent with a previous observational study. Our results confirm that energetic anticyclonic circulations with negative relative vorticity in the upper layer on the southern side enable vertical penetration of NIW energy from the mixed layer to the deep layer more effectively.
Assimilation of Satellite Altimetry Data for Effective River Bathymetry
Authors: Brêda J. P. L. F. , Paiva R. C. D. , Bravo J. M. , Passaia O. A. , Moreira D. M.
Published: August 2019

One of the main problems of hydrologic/hydrodynamic routing models is defining the right set of parameters, especially on inaccessible and/or large basins. Remote sensing techniques provide measurements of the basin topography, drainage system, and channel width; however current methods for estimating riverbed elevation are not as accurate. This paper presents methods of altimetry data assimilation (DA) for estimating effective bathymetry of a hydrodynamic model. We tested past altimetry observations from satellites ENVISAT, ICESAT, and JASON 2 and synthetic altimetry data from satellites ICESAT 2, JASON 3, SARAL, and Surface Water and Ocean Topography to assess future/present mission's potential. The DA methods used were direct insertion, linear interpolation, the Shuffled Complex Evolution‐University of Arizona optimization algorithm, and an adapted Kalman filter developed with hydraulically based variance and covariance introduced in this paper. The past satellite altimetry DA was evaluated comparing simulated and observed water surface elevation while the synthetic altimetry DA were assessed through a direct comparison with a true bathymetry. The Shuffled Complex Evolution‐University of Arizona and hydraulically based Kalman filter methods presented the best performances, reducing water surface elevation error in 65% in past altimetry data experiment and reducing biased bathymetry error in 75% in the synthetic experiment; however, the latter method is much less computationally expensive. Regarding satellites, it was observed that the performance is related to the satellite intertrack distance, as higher number of observation sites allows more accurate bed elevation estimation.
Abrupt Arctic Climate Shifts Trigger Rapid Ecosystem Responses
Authors: Katz Cheryl
Published: August 2019

New research finds that the Greenland environment is highly sensitive to recent warming trends.
Enhanced Tropical Cyclone Intensity in the Western North Pacific During Warm Periods Over the Last Two Millennia
Authors: Zhou Xin , Liu Zhonghui , Yan Qing , Zhang Xiaolin , Yi Liang , Yang Wenqing , Xiang Rong , He Yuxin , Hu Bangqi , Liu Yi , Shen Yanan
Published: August 2019

It is assumed that the potential intensity of tropical cyclones (TC) will increase with rising global temperature. The western North Pacific is one of the three principal TC centers, but TC records from the region are scarce and sometimes controversial. Here we present grain‐size distributions and element contents of sediment cores from the East China Sea, in the western North Pacific. We interpret changes in the mean grain size of the coarse fraction as a proxy for TC intensity, and we infer a linkage of TC intensity to temperature changes over the last two millennia. Supported by model simulations, our results show that TC intensity increased (decreased) during relatively warm (cool) periods, confirming the control of temperature on TC intensity on a multicentennial scale. Our results suggest that long‐term TC intensity in the western North Pacific may increase with continued global warming.
Age and Provenance of the Nindam Formation, Ladakh, NW Himalaya: Evolution of the Intraoceanic Dras Arc Before Collision With India
Authors: Walsh Jessica M. J. , Buckman Solomon , Nutman Allen P. , Zhou Renjie
Published: August 2019

The Dras Arc in NW India Himalaya is a belt of basaltic‐andesites intercalated with arkose‐dominated volcaniclastic rocks of the Nindam Formation situated along the Indus Suture between India and Eurasia. Debates exist as to whether these rocks developed in a forearc basin to the Eurasian margin or as part of an intraoceanic island arc system that collided with either India or Eurasia before final continental collision. Detrital zircons from the Nindam Formation yield U‐Pb age spectra with dominant youngest age populations of ~84–125 Ma, corresponding with arc magmatism. Sandstone provenance analysis from the Nindam Formation indicates that the Dras Arc evolved from an undissected arc to dissected arc over a period of ~41 Myr. Slightly older, smaller populations occur at ~135–185 Ma, corresponding with reported ages of Neotethyan ophiolites (e.g., Spongtang). The basal section of the Nindam Formation reveals the presence of arc‐derived basaltic‐andesite and tonalite clasts, plus ophiolitic components sourced from an adjacent accretionary complex. There is a distinct absence of quartz or felsic granitic clasts, suggesting that the Nindam Formation did not develop as a forearc basin to the Ladakh Batholith of southern Eurasia but rather as separate intraoceanic island arc. A distinct “Gondwanan” signature occurs in all samples, with zircon age peaks at ~514–988, ~1000–1588, ~1627–2444, and ~2500 Ma. We suggest that the Dras and Spong arcs are the same intraoceanic island arc system that developed as a result of subduction initiation along NNE‐SSW transform faults perpendicular to the Indian and Eurasia continents.
A genome-wide positioning systems network algorithm for in silico drug repurposing
Authors: Cheng Feixiong , Lu Weiqiang , Liu Chuang , Fang Jiansong , Hou Yuan , Handy Diane E. , Wang Ruisheng , Zhao Yuzheng , Yang Yi , Huang Jin , Hill David E. , Vidal Marc , Eng Charis , Loscalzo Joseph
Published: August 2019

Recent advances in DNA/RNA sequencing have made it possible to identify new targets rapidly and to repurpose approved drugs for treating heterogeneous diseases by the ‘precise’ targeting of individualized disease modules. In this study, we develop a Genome-wide Positioning Systems network (GPSnet) algorithm for drug repurposing by specifically targeting disease modules derived from individual patient’s DNA and RNA sequencing profiles mapped to the human protein-protein interactome network. We investigate whole-exome sequencing and transcriptome profiles from ~5,000 patients across 15 cancer types from The Cancer Genome Atlas. We show that GPSnet-predicted disease modules can predict drug responses and prioritize new indications for 140 approved drugs. Importantly, we experimentally validate that an approved cardiac arrhythmia and heart failure drug, ouabain, shows potential antitumor activities in lung adenocarcinoma by uniquely targeting a HIF1α/LEO1-mediated cell metabolism pathway. In summary, GPSnet offers a network-based, in silico drug repurposing framework for more efficacious therapeutic selections.
MYC paralog-dependent apoptotic priming orchestrates a spectrum of vulnerabilities in small cell lung cancer
Authors: Dammert Marcel A. , Brägelmann Johannes , Olsen Rachelle R. , Böhm Stefanie , Monhasery Niloufar , Whitney Christopher P. , Chalishazar Milind D. , Tumbrink Hannah L. , Guthrie Matthew R. , Klein Sebastian , Ireland Abbie S. , Ryan Jeremy , Schmitt Anna , Marx Annika , Ozretić Luka , Castiglione Roberta , Lorenz Carina , Jachimowicz Ron D. , Wolf Elmar , Thomas Roman K. , Poirier John T. , Büttner Reinhard , Sen Triparna , Byers Lauren A. , Reinhardt H. Christian , Letai Anthony , Oliver Trudy G. , Sos Martin L.
Published: August 2019

MYC paralogs are frequently activated in small cell lung cancer (SCLC) but represent poor drug targets. Thus, a detailed mapping of MYC-paralog-specific vulnerabilities may help to develop effective therapies for SCLC patients. Using a unique cellular CRISPR activation model, we uncover that, in contrast to MYCN and MYCL, MYC represses BCL2 transcription via interaction with MIZ1 and DNMT3a. The resulting lack of BCL2 expression promotes sensitivity to cell cycle control inhibition and dependency on MCL1. Furthermore, MYC activation leads to heightened apoptotic priming, intrinsic genotoxic stress and susceptibility to DNA damage checkpoint inhibitors. Finally, combined AURK and CHK1 inhibition substantially prolongs the survival of mice bearing MYC-driven SCLC beyond that of combination chemotherapy. These analyses uncover MYC-paralog-specific regulation of the apoptotic machinery with implications for genotype-based selection of targeted therapeutics in SCLC patients.
Construction of stabilized bulk-nano interfaces for highly promoted inverse CeO2/Cu catalyst
Authors: Yan Han , Yang Chun , Shao Wei-Peng , Cai Li-Hua , Wang Wei-Wei , Jin Zhao , Jia Chun-Jiang
Published: August 2019

As the water-gas shift (WGS) reaction serves as a crucial industrial process, strategies for developing robust WGS catalysts are highly desiderated. Here we report the construction of stabilized bulk-nano interfaces to fabricate highly efficient copper-ceria catalyst for the WGS reaction. With an in-situ structural transformation, small CeO2 nanoparticles (2–3 nm) are stabilized on bulk Cu to form abundant CeO2-Cu interfaces, which maintain well-dispersed under reaction conditions. This inverse CeO2/Cu catalyst shows excellent WGS performances, of which the activity is 5 times higher than other reported Cu catalysts. Long-term stability is also very solid under harsh conditions. Mechanistic study illustrates that for the inverse CeO2/Cu catalyst, superb capability of H2O dissociation and CO oxidation facilitates WGS process via the combination of associative and redox mechanisms. This work paves a way to fabricate robust catalysts by combining the advantages of bulk and nano-sized catalysts. Catalysts with such inverse configurations show great potential in practical WGS applications.
A flexible readout mechanism of human sensory representations
Authors: Birman Daniel , Gardner Justin L.
Published: August 2019

Attention can both enhance and suppress cortical sensory representations. However, changing sensory representations can also be detrimental to behavior. Behavioral consequences can be avoided by flexibly changing sensory readout, while leaving the representations unchanged. Here, we asked human observers to attend to and report about either one of two features which control the visibility of motion while making concurrent measurements of cortical activity with BOLD imaging (fMRI). We extend a well-established linking model to account for the relationship between these measurements and find that changes in sensory representation during directed attention are insufficient to explain perceptual reports. Adding a flexible downstream readout is necessary to best explain our data. Such a model implies that observers should be able to recover information about ignored features, a prediction which we confirm behaviorally. Thus, flexible readout is a critical component of the cortical implementation of human adaptive behavior.
Maternal control of suspensor programmed cell death via gibberellin signaling
Authors: Shi Ce , Luo Pan , Du Yu-Ting , Chen Hong , Huang Xiaorong , Cheng Tian-He , Luo An , Li Hong-Ju , Yang Wei-Cai , Zhao Peng , Sun Meng-Xiang
Published: August 2019

Plant embryos are generated and develop in a stable and well-protected microenvironment surrounded by maternal tissue, which is vital for embryogenesis. However, the signaling mechanisms responsible for maternal tissue-to-proembryo communication are not well understood. Here, we report a pathway for maternal tissue-to-proembryo communication. We identify a DELLA protein, NtCRF1 (NtCYS regulative factor 1), which regulates suspensor programmed cell death (PCD). NtCRF1 can bind to the promoter of NtCYS and regulate the suspensor PCD-switch module NtCYS-NtCP14 in response to gibberellin (GA). We confirm that GA4, as a primary signal triggering suspensor PCD, is generated in the micropylar endothelium by the transient activation of NtGA3oxs in the maternal tissue. Thus, we propose that GA is a maternal-to-proembryo communication signal that is decoded in the proembryo by a GID1-CRF1-CYS-CP14 signaling cascade. Using this mode of communication, maternal tissue precisely controls the embryonic suspensor PCD and is able to nurse the proembryo in a stage-dependent manner.
Publisher Correction: npj Quantum Information, volume 5
Authors:   npj Quantum Information
Published: August 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Constructing Smaller Pauli Twirling Sets for Arbitrary Error Channels
Authors: Cai Zhenyu , Benjamin Simon C.
Published: August 2019

Twirling is a technique widely used for converting arbitrary noise channels into Pauli channels in error threshold estimations of quantum error correction codes. It is vitally useful both in real experiments and in classical quantum simulations. Minimising the size of the twirling gate set increases the efficiency of simulations and in experiments it might reduce both the number of runs required and the circuit depth (and hence the error burden). Conventional twirling uses the full set of Pauli gates as the set of twirling gates. This article provides a theoretical background for Pauli twirling and a way to construct a twirling gate set with a number of members comparable to the size of the Pauli basis of the given error channel, which is usually much smaller than the full set of Pauli gates. We also show that twirling is equivalent to stabiliser measurements with discarded measurement results, which enables us to further reduce the size of the twirling gate set.
Examining the identification of age-related atrophy between T1 and T1 + T2-FLAIR cortical thickness measurements
Authors: Lindroth Heidi , Nair Veena A. , Stanfield Casandra , Casey Cameron , Mohanty Rosaleena , Wayer Daniel , Rowley Paul , Brown Roger , Prabhakaran Vivek , Sanders Robert D.
Published: August 2019

Cortical thickness is traditionally derived from T1-weighted MRI images. Recent studies have shown an improvement in segmentation with the combination of T1 + T2-FLAIR images. MRI data from 54 adults (mean: 71 years, 65–81 years, 48% females) that are part of an ongoing cohort study were analyzed to investigate whether T1 + T2-FLAIR cortical thickness measurements were superior to those derived from T1-weighted images in identifying age-related atrophy. T1-weighted and T2-FLAIR MRI images were processed through FreeSurfer v6.0. Data was extracted using the Desikan-Killiany (DKT) atlas. FreeSurfer’s GUI QDEC examined age-related atrophy. Nonparametric tests, effect sizes, and Pearson correlations examined differences between T1-only and T1 + T2-FLAIR cortical thickness data. These analyses demonstrated that T1 + T2-FLAIR processed images significantly improved the segmentation of gray matter (chi-square x2, p < 0.05) and demonstrated significantly thicker cortical thickness means (p < 0.05) with medium to large effect sizes. Significant regions of age-related cortical atrophy were identified within the T1 + T2-FLAIR data (FDR corrected, p < 0.05). This is in contrast to the T1-only data where no regions survived FDR correction. In summary, T1 + T2-FLAIR data were associated with significant improvement in cortical segmentation and the identification of age-related cortical atrophy. Future studies should consider employing this imaging strategy to obtain cortical thickness measurements sensitive to age-related changes.
Sharing of heteroplasmies between human liver lobes varies across the mtDNA genome
Authors: Hübner Alexander , Wachsmuth Manja , Schröder Roland , Li Mingkun , Eis-Hübinger Anna Maria , Madea Burkhard , Stoneking Mark
Published: August 2019

Mitochondrial DNA (mtDNA) heteroplasmy (intra-individual variation) varies among different human tissues and increases with age, suggesting that the majority of mtDNA heteroplasmies are acquired, rather than inherited. However, the extent to which heteroplasmic sites are shared across a tissue remains an open question. We therefore investigated heteroplasmy in two liver samples (one from each primary lobe) from 83 Europeans, sampled at autopsy. Minor allele frequencies (MAF) at heteroplasmic sites were significantly correlated between the two liver samples from an individual, with significantly more sharing of heteroplasmic sites in the control region than in the non-control region. We show that this increased sharing for the control region cannot be explained by recent mutations at just a few specific heteroplasmic sites or by the possible presence of 7S DNA. Moreover, we carried out simulations to show that there is significantly more sharing than would be predicted from random genetic drift from a common progenitor cell. We also observe a significant excess of non-synonymous vs. synonymous heteroplasmies in the protein-coding region, but significantly more sharing of synonymous heteroplasmies. These contrasting patterns for the control vs. the non-control region, and for non-synonymous vs. synonymous heteroplasmies, suggest that selection plays a role in heteroplasmy sharing.
A trade-off between speckle size and intensity enhancement of a focal point behind a scattering layer
Authors: Edrei Eitan , Scarcelli Giuliano
Published: August 2019

Focusing light through highly scattering materials by modifying the phase profile of the illuminating beam has attracted a great deal of attention in the past decade paving the way towards novel applications. Here we report on a tradeoff between two seemingly independent quantities of critical importance in the focusing process: the size of the focal point obtained behind a scattering medium and the maximum achievable intensity of such focal point. We theoretically derive and experimentally demonstrate the practical limits of intensity enhancement of the focal point and relate them to the intrinsic properties of the scattering phenomenon. We demonstrate that the intensity enhancement limitation becomes dominant when the focusing plane gets closer to the scattering layer thus limiting the ability to obtain tight focusing at high contrast, which has direct relevance for the many applications exploring scattering materials as a platform for high resolution focusing and imaging.
Increased glucocorticoid receptor activity and proliferation in metastatic colon cancer
Authors: Tian Dan , Tian Miao , Han Gang , Li Jin-Long
Published: August 2019

Metastasis is regarded as the fatal hallmark for colon cancer, but molecular mechanisms responsible for it have remained poorly defined. Glucocorticoid receptor (GR) within the tumor microenvironment mediates the effects of stress hormones which are used in clinics for their inflammation-modulatory and immunosuppressive properties. Further, epigenetic activation of GR promotes tumor heterogeneity and metastasis. Here, we sought to investigate the correlation between GR activation and proliferation and invasion in metastatic colon cancer microenvironment. We used proliferation/invasion assays, western blot, RT-qPCR, immunofluorescence staining and quantitative methylation to study glucocorticoid-GR signaling, including the involvement of CDK1, in human colon adenocarcinoma cell lines HT29 and T84 (a representative metastatic cell line). Nuclear expression levels of GR were significantly upregulated in metastatic T84 cells, and glucocorticoid derivative, dexamethasone (DEX) treatment caused increased proliferation and invasion in T84 cell, compared to HT29 cell. DEX treatment induced CDK1 expression which was accompanied by reduced CDK1 methylation, indicating epigenetic regulation. Depletion of GR suppressed proliferation of metastatic colon carcinoma cells and depletion of CDK1 had similar suppressing effects on proliferation as well as invasion of metastatic cells. Our study suggests that glucocorticoid-GR-CDK1 signaling induces proliferation and invasion of colon cancer cells and therapies involving the use of glucocorticoids need to exercise caution and re-evaluation.
Do population-level risk prediction models that use routinely collected health data reliably predict individual risks?
Authors: Li Yan , Sperrin Matthew , Belmonte Miguel , Pate Alexander , Ashcroft Darren M. , van Staa Tjeerd Pieter
Published: August 2019

The objective of this study was to assess the reliability of individual risk predictions based on routinely collected data considering the heterogeneity between clinical sites in data and populations. Cardiovascular disease (CVD) risk prediction with QRISK3 was used as exemplar. The study included 3.6 million patients in 392 sites from the Clinical Practice Research Datalink. Cox models with QRISK3 predictors and a frailty (random effect) term for each site were used to incorporate unmeasured site variability. There was considerable variation in data recording between general practices (missingness of body mass index ranged from 18.7% to 60.1%). Incidence rates varied considerably between practices (from 0.4 to 1.3 CVD events per 100 patient-years). Individual CVD risk predictions with the random effect model were inconsistent with the QRISK3 predictions. For patients with QRISK3 predicted risk of 10%, the 95% range of predicted risks were between 7.2% and 13.7% with the random effects model. Random variability only explained a small part of this. The random effects model was equivalent to QRISK3 for discrimination and calibration. Risk prediction models based on routinely collected health data perform well for populations but with great uncertainty for individuals. Clinicians and patients need to understand this uncertainty.
Compartmental-modelling-based measurement of murine glomerular filtration rate using 18F-fluoride PET/CT
Authors: Lee Hyo Sang , Kang Yeon-koo , Lee Hyunjong , Han Jeong Hee , Moon Byung Seok , Byun Seok-Soo , Chae Dong-Wan , Kang Keon Wook , Lee Won Woo
Published: August 2019

Accurate measurement of glomerular filtration rate (GFR) is essential for optimal decision making in many clinical settings of renal failure. We aimed to show that GFR can be accurately measured using compartmental tracer kinetic analysis of 18F-fluoride dynamic PET/CT. Twenty-three male Sprague-Dawley rats of three experimental groups (cyclosporine-administered [n = 8], unilaterally nephrectomized [n = 8], and control [n = 7]) underwent simultaneous 18F-fluoride dynamic PET/CT and reference 51Cr-EDTA GFR (GFRCrEDTA) test at day 0 and post-intervention day 3. 18F-fluoride PET GFR (GFRF-PET) was calculated by multiplying the influx rate and functional kidney volume in a single-tissue-compartmental kinetic model. Within-test repeatability and between-test agreement were evaluated by intraclass correlation coefficient (ICC) and Bland-Altman analysis. In the control group, repeatability of GFRF-PET was excellent (ICC = 0.9901, repeatability coefficient = 12.5%). GFRF-PET significantly decreased in the renally impaired rats in accordance with respective GFRCrEDTA changes. In the pooled population, GFRF-PET agreed well with GFRCrEDTA with minimal bias (−2.4%) and narrow 95% limits of agreement (−25.0% to 20.1%). These data suggest that the single-compartmental kinetic analysis of 18F-fluoride dynamic PET/CT is an accurate method for GFR measurement. Further studies in humans are warranted.
Electrodeposition of α-MnO2/γ-MnO2 on Carbon Nanotube for Yarn Supercapacitor
Authors: Jeong Jae-Hun , Park Jong Woo , Lee Duck Weon , Baughman Ray H. , Kim Seon Jeong
Published: August 2019

Yarn supercapacitors have attracted renewed interest as promising energy storage for wearable devices due to their lightweight, long cycling lifetime and excellent weavability. There has been much effort to fabricate high performance yarn supercapacitor by depositing pseudo-capacitive materials on the outer surface of the carbon fibers. However, a key challenge still remains to achieve high capacitance and high mass loading without sacrificing the cycling stability. Herein, we perform a phase-controlled of MnO2 at various deposition temperatures with ultrahigh mass loading of 11 mg/cm2 on a MWNT sheets and fabricate it to yarn structure to achieve high capacitance without decreasing in the electrochemical performance. The structure of optimized sample (MnO2/CNTs-60, deposition at 60 °C) consists of the composite of primary α-MnO2 nanosheets and secondary γ-MnO2 nanoparticles. The heteronanostructures of MnO2 provide facile ionic and electric transport in the yarn electrode, resulting in improvement of electrochemical performance and cycling stability. The MnO2/CNTs-60 yarn electrode with ultrahigh mass loading delivers a high areal capacitance of 3.54 F/cm2 at 1 mA/cm2 and an excellent rate capability. Finally, the MnO2/CNTs-60 device exhibits an outstanding high areal energy density of 93.8 μWh/cm2 at the power density of 193 μW/cm2, which is superior to previously reported symmetric yarn supercapacitors.
Rapid affinity chromatographic isolation method for LDL in human plasma by immobilized chondroitin-6-sulfate and anti-apoB-100 antibody monolithic disks in tandem
Authors: Liangsupree Thanaporn , Multia Evgen , Metso Jari , Jauhiainen Matti , Forssén Patrik , Fornstedt Torgny , Öörni Katariina , Podgornik Aleš , Riekkola Marja-Liisa
Published: August 2019

Low-density lipoprotein (LDL) is considered the major risk factor for the development of atherosclerotic cardiovascular diseases (ASCVDs). A novel and rapid method for the isolation of LDL from human plasma was developed utilising affinity chromatography with monolithic stationary supports. The isolation method consisted of two polymeric monolithic disk columns, one immobilized with chondroitin-6-sulfate (C6S) and the other with apolipoprotein B-100 monoclonal antibody (anti-apoB-100 mAb). The first disk with C6S was targeted to remove chylomicrons, very-low-density lipoprotein (VLDL) particles, and their remnants including intermediate-density lipoprotein (IDL) particles, thus allowing the remaining major lipoprotein species, i.e. LDL, lipoprotein(a) (Lp(a)), and high-density lipoprotein (HDL) to flow to the anti-apoB-100 disk. The second disk captured LDL particles via the anti-apoB-100 mAb attached on the disk surface in a highly specific manner, permitting the selective LDL isolation. The success of LDL isolation was confirmed by different techniques including quartz crystal microbalance. In addition, the method developed gave comparable results with ultracentrifugation, conventionally used as a standard method. The reliable results achieved together with a short isolation time (less than 30 min) suggest the method to be suitable for clinically relevant LDL functional assays.
The Genomic Landscape of Centromeres in Cancers
Authors: Saha Anjan K. , Mourad Mohamad , Kaplan Mark H. , Chefetz Ilana , Malek Sami N. , Buckanovich Ronald , Markovitz David M. , Contreras-Galindo Rafael
Published: August 2019

Centromere genomics remain poorly characterized in cancer, due to technologic limitations in sequencing and bioinformatics methodologies that make high-resolution delineation of centromeric loci difficult to achieve. We here leverage a highly specific and targeted rapid PCR methodology to quantitatively assess the genomic landscape of centromeres in cancer cell lines and primary tissue. PCR-based profiling of centromeres revealed widespread heterogeneity of centromeric and pericentromeric sequences in cancer cells and tissues as compared to healthy counterparts. Quantitative reductions in centromeric core and pericentromeric markers (α-satellite units and HERV-K copies) were observed in neoplastic samples as compared to healthy counterparts. Subsequent phylogenetic analysis of a pericentromeric endogenous retrovirus amplified by PCR revealed possible gene conversion events occurring at numerous pericentromeric loci in the setting of malignancy. Our findings collectively represent a more comprehensive evaluation of centromere genetics in the setting of malignancy, providing valuable insight into the evolution and reshuffling of centromeric sequences in cancer development and progression.
A Randomised Controlled Trial on the Effectiveness and Adherence of Modified Alternate-day Calorie Restriction in Improving Activity of Non-Alcoholic Fatty Liver Disease
Authors: Johari Muhammad Izzad , Yusoff Khairiah , Haron Juhara , Nadarajan Chandran , Ibrahim Khairun Nisah , Wong Mung Seong , Hafidz Muhammad Ilham Abdul , Chua Bee Eng , Hamid Nurhazwani , Arifin Wan Nor , Ma Zheng Feei , Lee Yeong Yeh
Published: August 2019

Currently, there is no effective therapy for non-alcoholic fatty liver disease (NAFLD), and although calorie restriction is recommended in guidelines, but adherence is an issue. The current study aimed to determine the effectiveness of eight weeks intermittent fasting (IF) strategy in the control of NAFLD activity and the adherence rate of such strategy. This was a randomized controlled trial with modified alternate-day calorie restriction (MACR), a form of IF, as the active intervention and usual habitual diet as control. The outcome measures included changes in body mass index (BMI), blood lipids (cholesterol, LDL, HDL and triglyceride), fasting blood sugar (FBS), liver enzymes (ALT and AST), and ultrasound measurements of liver steatosis and 2-dimensional shear wave elastography (SWE). Per-protocol (PP) analysis was performed with comparison within (post vs. pre-intervention) and between (MACR vs. control) groups and P < 0.05 as significant. Of 115 individuals with NAFLD, 43 satisfied the study entry criteria, and 33 were randomised to MACR and 10 to control group, and after 8 weeks, 30 from MACR and 9 from control group completed PP. Significant reduction in weight and BMI (P = 0.001 and 0.02 respectively) was observed in MACR vs. control. Likewise, ALT was reduced with MACR but not control (P = 0.02). No reductions in lipid parameters and FBS were found in between-group analyses (all P > 0.22). Both liver steatosis and fibrosis (SWE) scores were significantly reduced in MACR vs. controls (both P < 0.01). Adherence level for MACR remained between 75-83% throughout the study. As a conclusion, eight weeks of IF (MACR) strategy appears more effective than usual habitual diet in the control of NAFLD activity and with good adherence rate.