bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Genomic Characterization in Upper Tract Urothelial Carcinoma and Urothelial Carcinoma of the Bladder
Authors: Yang Kaiwei , Yu Wei , Liu Huanhuan , Ding Feng , Zhang Yanrui , Zhang Yun , Wang Wang , Lou Feng , Cao Shanbo , Wang Huina , He Zhisong
Published: May 2021

Background

Different genomic characterization in urothelial carcinoma (UC) by site of origin may imply contrasting therapeutic opportunities and pathogenetic mechanisms. The aim of this study was to investigate whether differences between upper tract UC (UTUC) and UC of the bladder (UCB) result from intrinsic biological diversity.

Materials and Methods

We prospectively sequenced 118 tumors and matched blood DNA from Chinese patients with UC using next-generation sequencing techniques, including 45 UTUC and 73 UCB. Two hundred twenty-six patients with UTUC and 350 patients with UCB for The Cancer Genome Atlas were acquired from the cbioportal.

Results

There were marked disparities in the mutational landscape for UC according to race and site of origin. Signature 22 for exposure to aristolochic acid was only observed in the UTUC cohort. Conversely, signature 6 for defective DNA mismatch repair only existed in the UCB cohort. Compared with UCB, UTUC had higher clonal and subclonal mutation numbers. TP53, PIK3CA, and FGFR3 mutations may be the driver genes for UTUC, whereas for UCB, the driver gene may be BRCA1. Patients with UTUC had lower PD-L1 than those with UCB. There was no significant difference in the number of DDR mutations, copy number variation counts, and tumor mutational burden between UTUC and UCB.

Conclusion

UTUC and UCB exhibit significant differences in the prevalence of genomic landscape and carcinogenesis. Consequently, molecular subtypes differ according to location, and these results may imply the site-specific management of patients with urothelial carcinoma. Mutational signature may be used as a screening tool to assist clinical differential diagnosis between UTUC and UCB.

Implications for Practice

This study's findings lay the foundation for a deeper understanding of distinct molecular mechanisms and similar treatment opportunities between upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) and had important implications for the site-specific management of patients with urothelial carcinoma. A comprehensive understanding of the biology of UTUC and UCB is needed to identify new drug targets in order to improve clinical outcomes.
A case of lichenoid oral mucositis associated with nivolumab therapy
Authors: Ito Nanako , Tani Ryouji , Obayashi Fumitaka , Okamoto Kosei , Toratani Shigeaki , Okamoto Tetsuji
Published: May 2021

An 80‐year‐old man diagnosed with recurrent lung squamous cell carcinoma had complaints of an erosion formation in the lower lip 4 weeks upon nivolumab administration which resulted in the discontinuation of nivolumab. At the first visit, oral candidiasis due to inappropriate handling of the patient's denture was observed. We administered antifungal medicine and treated the patient with a new dental prosthesis. As a result of a biopsy, a pathological diagnosis of oral mucositis similar to lichen planus was obtained. We successfully treated the patient with a beclomethasone spray. The mucosal erosion re‐epithelialized, and pain in the oral cavity completely disappeared.
A Retrospective Analysis Comparing Post‐Operative Bleeding with Various Doses of Aspirin after Lower Extremity Joint Arthroplasty or Revision
Authors: Watts Paula J. , Kopstein Michael , Harkness Weston , Cornett Brendon , Dziadkowiec Oliwier , Jenkins Patrick , Hicks Mary E. , Hassan Shakib , Scherbak Dmitriy
Published: May 2021

Study Objective

Previous studies have shown that aspirin is noninferior to other anticoagulation therapies in preventing postoperative venous thromboembolism following lower extremity arthroplasty or revision; however, its optimal dosing for this indication is less clear. This study aims to compare the odds of bleeding between different aspirin dosages following lower extremity joint arthroplasty or revision.

Design

This is a 3‐year retrospective multi‐center cohort study across the United States and its territories.

Setting

This study included patients admitted for total hip or knee arthroplasty or revision and were treated with prophylactic aspirin.

Patients, Intervention, Measurements

Patients were assigned to groups based on a total daily aspirin dose of 81, 162, 325, or 650 mg. Data were analyzed for postsurgical bleeding and thromboembolism events occurring during the initial admission and up to 40 days following surgery. Other exploratory variables included type of surgery, hip or knee arthroplasty, length of stay, and patient demographic data.

Main Results

Among 53,848 patients receiving aspirin, 3922 received a total daily dose of 81 mg, 19,341 received a total daily dose of 162 mg, 5256 received a total daily dose of 325 mg, and 25,329 received a total daily dose of 650 mg. Bleeding occurred in 466 (0.87%) patients and venous thromboembolism (VTE) in 209 patients (0.39%). The odds of bleeding were compared using logistic regression, with the 650‐mg dose as the reference group. None were statistically significant for bleeding between all studied aspirin doses: 81 mg (OR 1.12, 95% CI 0.83–1.51, p = 0.451), 162 mg (OR 0.83, 95% CI 0.67–1.03, p = 0.097), and 325 mg (OR 0.83, 95% CI 0.59–1.13, p = 0.245). The odds of VTE were also not statistically significant: 81 mg (OR 0.71, 95% CI 0.40–1.17, p = 0.181), 162 mg (OR 0.75 95% CI 0.54–1.03, p = 0.072), and 325 mg (OR 1.00, 95% CI 0.64–1.53, p = 0.989).

Conclusions

There were no significant differences in the odds of bleeding or venous thromboembolism among all studied aspirin dosages in patients receiving aspirin for thromboprophylaxis following lower extremity joint arthroplasty or revision.
A retrospective analysis of bleeding risk with rivaroxaban, enoxaparin, and aspirin following total joint arthroplasty or revision
Authors: Watts Paula J. , Kopstein Michael , Harkness Weston , Cornett Brendon , Dziadkowiec Oliwier , Hicks M. Elizabeth , Hassan Shakib , Scherbak Dmitriy
Published: May 2021

Study Objective

Rivaroxaban, enoxaparin, and aspirin are commonly used medications for thromboprophylaxis following lower extremity joint arthroplasty or revision. Previous research has demonstrated efficacy in preventing venous thromboembolism with each medication, however, the comparative risk of bleeding between them remains poorly understood. The aim of this study was to compare the odds of bleeding between rivaroxaban, enoxaparin, and aspirin following lower extremity joint arthroplasty or revision.

Design

This is a 3‐year retrospective cohort study.

Setting

Data were obtained from 148 facilities across 55 states and territories of the United States.

Patients

This study included 85,938 patients who underwent hip or knee arthroplasty or revision.

Intervention

Patients received enoxaparin, rivaroxaban, or aspirin as monotherapy for thromboprophylaxis.

Measurements

The primary outcome was all bleeding, classified as major or minor bleeding, occurring in the 40 days following surgery. The secondary outcome was venous thromboembolism.

Main Results

Among 85,938 patients, 10,465 received rivaroxaban, 14,047 received enoxaparin, and 61,426 received aspirin. Bleeding occurred in 126 (1.20%) patients with rivaroxaban, 253 (1.80%) with enoxaparin, and 611 (0.99%) with aspirin. There was a significant increase in odds of bleeding in the enoxaparin compared to aspirin group odds ratio (OR) 1.18, 95% confidence interval (CI) 1.01–1.38, p = 0.042), and a trend toward increased odds of bleeding in rivaroxaban compared to aspirin group (OR 1.21, 95% CI 0.99–1.47, p = 0.058) and rivaroxaban compared to enoxaparin (OR 1.03, 95% CI 0.82–1.28, p = 0.827). Odds of venous thromboembolism were not statistically significant between all three study medications.

Conclusions

Among rivaroxaban, enoxaparin, and aspirin used for thromboprophylaxis in knee and hip arthroplasty or revision, aspirin had significantly decreased odds of bleeding complications compared to enoxaparin. Although not statistically significant, aspirin also had a trend toward decreased odds of bleeding complications compared to rivaroxaban.

Our study results suggest that aspirin is a safer alternative for use in postoperative thromboprophylaxis following lower extremity joint arthroplasty or revision.
Optimization of temporal UAS‐based imagery analysis to estimate plant maturity date for soybean breeding
Authors: Volpato Leonardo , Dobbels Austin , Borem Aluízio , Lorenz Aaron Joel
Published: May 2021

Estimating the date of maturity of soybean breeding field plots is necessary for breeding line characterization and for informing yield comparisons among varieties. The main drawback of visually dating soybean maturity is the sheer scale of note recording entailed and the frequency at which these notes need to be taken. The overall aim of this study was to build upon prior work in using low‐cost UAS‐based RGB cameras to estimate soybean maturity date by examining the effect of vegetation index, summary statistic of the pixel values from each region of interest (plot), statistical model, and flight frequency. Maturity dates collected from five environments with 53 experimental trials (4,415 plots) were both visually dated and imaged using a RGB camera carried by a UAS. Using the mean greenness leaf index on each plot combined with LOESS regression, we achieved high correlations between ground and UAS‐based estimates (r = 0.84–0.97). Precision, quantified by broad‐sense heritability estimates, was greater for UAS‐based dates in 29 of 53 field trials, and nearly equivalent in 11 more field trials. We found that 54% of the significant deviations between ground and UAS‐based estimates were caused by inaccurate UAS‐based estimates, while errors in the ground‐based estimates accounted for 46% of the deviations. Reasons for these inaccurate estimates were attributed to lodging, presence of weeds, low germination, and within‐line genetic heterogeneity in the plots. A detailed description of the analysis pipeline, a user‐friendly R script, and all of the images and ground data have been made publicly available to help other researchers and breeders test and adopt these methods.
Influence of Plasma‐Enhanced Chemical Vapor Deposition Poly‐Si Layer Thickness on the Wrap‐Around and the Quantum Efficiency of Bifacial n‐TOPCon (Tunnel Oxide Passivated Contact) Solar Cells
Authors: Grübel Benjamin , Nagel Henning , Steinhauser Bernd , Feldmann Frank , Kluska Sven , Hermle Martin
Published: May 2021

In typical industrial processing of tunnel oxide passivated contact (TOPCon) solar cells, poly‐Si is deposited on the entire back of the cells. During the deposition process, a wrap‐around of poly‐Si onto the edges and the front side of the cells is virtually unavoidable if chemical vapor deposition processes are used. Plasma‐enhanced chemical vapor deposition (PECVD) is used to investigate very thin poly‐Si films and their effect on wrap‐around on bifacial TOPCon solar cells fabricated without wrap‐around etching. As a result, reduction of the poly‐Si thickness down to 30 nm significantly increases the shunt resistance, reduces the reverse bias current, and thus reduces the risk of hot spots as measured by IR imaging and microcharacterization by secondary electron microscopy. Electroplated metallization proves to be a suitable candidate for contacting such thin TOPCon layers, being less sensitive than screen‐printed metallization.
Bayesian phase II clinical trial design with noncompliance
Authors: Ren Tingyang , Shen Weining , Zhang Liwen , Zhao Haibing
Published: May 2021

Noncompliance issue is common in early phase clinical trials; and may lead to biased estimation of the intent‐to‐treat effect and incorrect conclusions for the clinical trial. In this work, we propose a Bayesian approach for sequentially monitoring the phase II randomized clinical trials that takes account for the noncompliance information. We adopt the principal stratification framework and propose to use Bayesian additive regression trees for selecting useful baseline covariates and estimating the complier average causal effect (CACE) for both efficacy and toxicity outcomes. The decision of early termination or not is then made adaptively based on the estimated CACE from the accumulated data. Simulation studies have confirmed the excellent performance of the proposed design in the presence of noncompliance.
The initial impact of COVID‐19 on Australasian Sonographers Part 1: Changes in scan numbers and sonographer work hours
Authors: Childs Jessie , Lamb Kathryn , Osborne Brooke , Maranna Sandhya , Esterman Adrian
Published: May 2021

Introduction

COVID‐19 has seen a series of lockdowns and suspension on non‐urgent elective surgeries. Subsequently, there was a drop in the number of diagnostic imaging services billed in April, May, 2020. A survey was undertaken from March to June 2020 to determine the initial impact of COVID‐19 on Australasian Sonographers. This article, the first in a 3‐part series presents and discusses the results of this survey pertaining to changes in the number of scans performed, and changes in the working hours of sonographers. The remaining two articles in this series address other initial COVID‐19 impacts on Australasian Sonographers.

Methods

An online survey was conducted containing questions regarding changes to work hours and examination numbers.

Results

444 participants answered the survey. Seventy eight percent of sonographers reported a decrease in the number of examinations being performed in their department A decrease in work hours was reported by 68% of sonographers with almost a quarter of these reporting that they had lost all their hours. A higher percentage of work hours changes were seenin private practices. Many reductions in work hours were reported to be voluntary.

Conclusion

Scan numbers in ultrasound departments were affected by COVID‐19, as were sonographers' work hours.
Enhanced Magnetic Microwave Absorption at Low‐Frequency Band by Ferrite Assembled Microspheres with Controlled Components and Morphologies
Authors: Huang Mengqiu , Yu Xuefeng , Wang Lei , Liu Jiwei , You Wenbin , Wang Min , Che Renchao
Published: May 2021

Because of the frequency‐dispersion characteristic, electromagnetic wave energy dissipation depends mainly on the magnetic loss at low frequency (S‐band, 2–4 GHz). Herein, a strong magnetic microsphere is constructed via a simple spray drying and subsequent calcination process. With the reaction temperature increasing, the microparticles are forcibly assembled by different contents of ferrite crystallites and Fe metal (mainly containing Fe2O3, Fe5O12, FeO, and Fe), accompanying morphology evolution. Attributed to the component and microstructure controlling, the permeability parameters of the heterogeneous ferrite composite microspheres (HFCOMP) can be considerably promoted, contributing to the optimized impedance matching in S‐band. As expected, the maximum reflection loss (RLmax) of HFCOMP is enhanced to −41 dB in S‐band, and the effective absorption bandwidth (EAB) is widened to 1.52 GHz (equivalent to 75% of the S‐band). The HFCOMP can achieve an RLmax of −53.5 dB at only 2 mm in X‐band. Observed by electron holography, the series of HFCOMP composites show the visual magnetic coupling effect, which boost the magnetic responding ability. Therefore, this study provides a guideline value for microstructure design in low‐frequency absorption.
Morphological, Structural, and Physicochemical Properties of Starch in Hybrids and Inbred Lines from Sweet–Waxy Maize
Authors: Hu Yifan , Wang Jun , Chi Ming , Yang Siling , Lu Dalei
Published: May 2021

Sweet–waxy maize is a special type of maize with recessive mutations of waxy gene and a gene disturbed sugar‐starch transition, and its starch is composed of nearly pure amylopectin. The starch physicochemical properties of four inbred lines and six hybrids of sweet–waxy maize are studied. The starch granules are irregular and large in hybrids and oval and small in inbred lines. The chain length, molecular weight, and crystallinity are significantly different among the samples. However, no distinct difference is observed between hybrids and inbred lines. The branching degree of hybrids (except THN2000) is significantly higher than that of inbred lines. The pasting, gelatinization, retrogradation temperatures, peak and breakdown viscosities, retrogradation enthalpy, and percentage are lower in inbred lines than in hybrids. By contrast, trough, final, and setback viscosities and gelatinization enthalpy are indistinctly different between the hybrids and inbred lines. Among the six hybrids, HTN2 is suitable to make glutinous food due to its high viscosity, whereas MTN2 may enable the production of food with minimal retrogradation. The high viscosity of JH1501 and the low retrogradation percentage of JSW15525 among the four inbred lines endow different advantages on quality breeding.
Optimization of α‐amylase and Glucoamylase Production Using Cull Potatoes as Substrate
Authors: Bansal Riya , Katyal Priya
Published: May 2021

Amylases are required for the conversion of starchy substrate into sugars. Commercially available enzymes are quite costly which makes the process uneconomical. This study is conducted to standardize physico‐chemical parameters such as substrate concentration (1.0–5.0%), temperature (25–40 °C), pH (4.0–7.0), incubation time (18–24) h for α‐amylase and 3–6 days for glucoamylase production) for optimum production of α‐amylase from bacterial isolate (AM1) and glucoamylase from Aspergillus niger by using cull potatoes as a substrate. Various organic and inorganic nitrogen sources (urea, yeast extract and soybean meal, and ammonium sulphate) are tried for maximum enzyme production. Among the four nitrogen sources, yeast extract supported maximum α‐amylase and glucoamylase production. Among the different amylolytic isolates from fermented jalebi dough and AM1culture, maximum α‐amylase activity is shown by AM1 (90.46 U mL−1) as compared to J1 (71.02 U mL−1). After optimization, α‐amylase activity of AM1 increases by 41.73% from 198.20 to 280.92 U mL−1 at 5.0% substrate concentration, 30 °C temperature, 24 h of incubation and pH 5.0. Glucoamylase activity of A. niger increases by 38.78% from 228.72 to 317.44 U mL−1 after optimization at 5% substrate concentration, pH 5, incubation period of 4 days and temperature 30 °C.
Correction to: Lewis Fry Richardson: His Intellectual Legacy and Influence in the Social Sciences
Authors: Gleditsch Nils Petter
Published: May 2021

In the original version of the book, the following correction were incorporated: The name “Gregory D. Hess” has now been corrected to “George D. Hess” in the pages 70, 83, 98, 111 and 145. The book and the chapters have been updated with the changes.
Reluctantly Solo? Representations of Single Mothers via Donor Procedure, Insemination and IVF in Swedish Newspapers
Authors: Wahlström Henriksson Helena , Bergnehr Disa
Published: May 2021

This chapter explores representations of single mothers via ARTs (assisted reproductive technologies) in Swedish newspapers. These women are gender-politically interesting to study because they stand as examples of ‘families we choose’ that subvert the hegemony of the nuclear family ideal, and they activate pertinent questions concerning reproductive choices and practices. The mothers in the news articles are typically white, heterosexual and urban, and they, their parenthood and ‘choice’, are framed in particular ways to project maternal and feminine respectability as well as ‘intensive mothering’. This suggests that, although in an international comparison there is generally little stigma attached to single motherhood in Sweden, these mothers need to become ‘understandable’ as good mothers in specific ways to deflect (risk of) stigma.
Cosmological Cutting Rules
Authors: Melville Scott , Pajer Enrico
Published: May 2021

Abstract

Primordial perturbations in our universe are believed to have a quantum origin, and can be described by the wavefunction of the universe (or equivalently, cosmological correlators). It follows that these observables must carry the imprint of the founding principle of quantum mechanics: unitary time evolution. Indeed, it was recently discovered that unitarity implies an infinite set of relations among tree-level wavefunction coefficients, dubbed the Cosmological Optical Theorem. Here, we show that unitarity leads to a systematic set of “Cosmological Cutting Rules” which constrain wavefunction coefficients for any number of fields and to any loop order. These rules fix the discontinuity of an n-loop diagram in terms of lower-loop diagrams and the discontinuity of tree-level diagrams in terms of tree-level diagrams with fewer external fields. Our results apply with remarkable generality, namely for arbitrary interactions of fields of any mass and any spin with a Bunch-Davies vacuum around a very general class of FLRW spacetimes. As an application, we show how one-loop corrections in the Effective Field Theory of inflation are fixed by tree-level calculations and discuss related perturbative unitarity bounds. These findings greatly extend the potential of using unitarity to bootstrap cosmological observables and to restrict the space of consistent effective field theories on curved spacetimes.
Classical solutions and their double copy in split signature
Authors: Monteiro Ricardo , O’Connell Donal , Veiga David Peinador , Sergola Matteo
Published: May 2021

Abstract

The three-point amplitude is the key building block in the on-shell approach to scattering amplitudes. We show that the classical objects computed by massive three-point amplitudes in gauge theory and gravity are Newman-Penrose scalars in a split-signature spacetime, where three-point amplitudes can be defined for real kinematics. In fact, the quantum state set up by the particle is a coherent state fully determined by the three-point amplitude due to an eikonal-type exponentiation. Having identified this simplest classical solution from the perspective of scattering amplitudes, we explore the double copy of the Newman-Penrose scalars induced by the traditional double copy of amplitudes, and find that it coincides with the Weyl version of the classical double copy. We also exploit the Kerr-Schild version of the classical double copy to determine the exact spacetime metric in the gravitational case. Finally, we discuss the direct implication of these results for Lorentzian signature via analytic continuation.
Gopakumar-Vafa hierarchies in winding inflation and uplifts
Authors: Carta Federico , Mininno Alessandro , Righi Nicole , Westphal Alexander
Published: May 2021

Abstract

We propose a combined mechanism to realize both winding inflation and de Sitter uplifts. We realize the necessary structure of competing terms in the scalar potential not via tuning the vacuum expectation values of the complex structure moduli, but by a hierarchy of the Gopakumar-Vafa invariants of the underlying Calabi-Yau threefold. To show that Calabi-Yau threefolds with the prescribed hierarchy actually exist, we explicitly create a database of all the genus 0 Gopakumar-Vafa invariants up to total degree 10 for all the complete intersection Calabi-Yau’s up to Picard number 9. As a side product, we also identify all the redundancies present in the CICY list, up to Picard number 13. Both databases can be accessed at this link (https://www.desy.de/∼westphal/GV_CICY_webpage/GVInvariants.html).
On small black holes, KK monopoles and solitonic 5-branes
Authors: Cano Pablo A. , Murcia Ángel , Ramírez Pedro F. , Ruipérez Alejandro
Published: May 2021

Abstract

We review and extend results on higher-curvature corrections to different configurations describing a superposition of heterotic strings, KK monopoles, solitonic 5-branes and momentum waves. Depending on which sources are present, the low-energy fields describe a black hole, a soliton or a naked singularity. We show that this property is unaltered when perturbative higher-curvature corrections are included, provided the sources are fixed. On the other hand, this character may be changed by appropriate introduction (or removal) of sources regardless of the presence of curvature corrections, which constitutes a non-perturbative modification of the departing system. The general system of multicenter KK monopoles and their 5-brane charge induced by higher-curvature corrections is discussed in some detail, with special attention paid to the possibility of merging monopoles. Our results are particularly relevant for small black holes (Dabholkar-Harvey states, DH), which remain singular after quadratic curvature corrections are taken into account. When there are four non-compact dimensions, we notice the existence of a black hole with regular horizon whose entropy coincides with that of the DH states, but the charges and supersymmetry preserved by both configurations are different. A similar construction with five non-compact dimensions is possible, in this case with the same charges as DH, although it fails to reproduce the DH entropy and supersymmetry. No such configuration exists if d > 5, which we interpret as reflecting the necessity of having a 5-brane wrapping the compact space.
On Gauss-Bonnet gravity and boundary conditions in Lorentzian path-integral quantization
Authors: Narain Gaurav
Published: May 2021

Abstract

Recently there has been a surge of interest in studying Lorentzian quant urn cosmology using Picard-Lefschetz methods. The present paper aims to explore the Lorentzian path-integral of Gauss-Bonnet gravity in four spacetime dimensions with metric as the field variable. We employ mini-superspace approximation and study the variational problem exploring different boundary conditions. It is seen that for mixed boundary conditions non-trivial effects arise from Gauss-Bonnet sector of gravity leading to additional saddle points for lapse in some case. As an application of this we consider the No-boundary proposal of the Universe with two different settings of boundary conditions) and compute the transition amplitude using Picard-Lefschetz formalism. In first case the transition amplitude is a superposition of a Lorentzian and a Euclidean geometrical configuration leading to interference incorporating non-perturbative effects coming from Gauss-Bonnet sector of gravity. In the second case involving complex initial momentum we note that the transition amplitude is an analogue of Hartle-Hawking wave-function with non-perturbative correction coming from Gauss-Bonnet sector of gravity.
Correction to: Infrared Problem vs Gauge Choice: Scattering of Classical Dirac Field
Authors: Herdegen Andrzej
Published: May 2021

A Correction to this paper has been published: https://doi.org/10.1007/s00023-020-01015-y
The Cosmological Semiclassical Einstein Equation as an Infinite-Dimensional Dynamical System
Authors: Gottschalk Hanno , Siemssen Daniel
Published: May 2021

We develop a comprehensive framework in which the existence of solutions to the semiclassical Einstein equation (SCE) in cosmological spacetimes is shown. Different from previous work on this subject, we do not restrict to the conformally coupled scalar field and we admit the full renormalization freedom. Based on a regularization procedure, which utilizes homogeneous distributions and is equivalent to Hadamard point splitting, we obtain a reformulation of the evolution of the quantum state as an infinite-dimensional dynamical system with mathematical features that are distinct from the standard theory of infinite-dimensional dynamical systems (e.g., unbounded evolution operators). Nevertheless, applying methods closely related to Ovsyannikov’s method, we show existence of maximal/global solutions to the SCE for vacuum-like states and of local solutions for thermal-like states. Our equations do not show the instability of the Minkowski solution described by other authors.
Extracellular matrix remodeling in animal models of anthracycline-induced cardiomyopathy: a meta-analysis
Authors: Leerink Jan M. , van de Ruit Mabel , Feijen Elizabeth A.M. , Kremer Leontien C.M. , Mavinkurve-Groothuis Annelies M.C. , Pinto Yigal M. , Creemers Esther E. , Kok Wouter E.M.
Published: May 2021

As in other cardiomyopathies, extracellular matrix (ECM) remodeling plays an important role in anthracycline-induced cardiomyopathy. To understand the pattern and timing of ECM remodeling pathways, we conducted a systematic review in which we describe protein and mRNA markers for ECM remodeling that are differentially expressed in the hearts of animals with anthracycline-induced cardiomyopathy. We included 68 studies in mice, rats, rabbits, and pigs with follow-up of 0.1–8.2 human equivalent years after anthracycline administration. Using meta-analysis, we found 29 proteins and 11 mRNAs that were differentially expressed in anthracycline-induced cardiomyopathy compared to controls. Collagens, matrix metalloproteinases (MMPs), inflammation markers, transforming growth factor ß signaling markers, and markers for cardiac hypertrophy were upregulated, whereas the protein kinase B (AKT) pro-survival pathway was downregulated. Their expression patterns over time from single time point studies were studied with meta-regression using human equivalent years as the time scale. Connective tissue growth factor showed an early peak in expression but remained upregulated at all studied time points. Brain natriuretic peptide (BNP) and MMP9 protein levels increased in studies with longer follow-up. Significant associations were found for higher atrial natriuretic peptide with interstitial fibrosis and for higher BNP and MMP2 protein levels with left ventricular systolic function.
Proteomic profiling of murine biliary-derived hepatic organoids and their capacity for drug disposition, bioactivation and detoxification
Authors: Howell Lawrence , Jenkins Rosalind E. , Lynch Stephen , Duckworth Carrie , Kevin Park B. , Goldring Christopher
Published: May 2021

Hepatic organoids are a recent innovation in in vitro modeling. Initial studies suggest that organoids better recapitulate the liver phenotype in vitro compared to pre-existing proliferative cell models. However, their potential for drug metabolism and detoxification remains poorly characterized, and their global proteome has yet to be compared to their tissue of origin. This analysis is urgently needed to determine what gain-of-function this new model may represent for modeling the physiological and toxicological response of the liver to xenobiotics. Global proteomic profiling of undifferentiated and differentiated hepatic murine organoids and donor-matched livers was, therefore, performed to assess both their similarity to liver tissue, and the expression of drug-metabolizing enzymes and transporters. This analysis quantified 4405 proteins across all sample types. Data are available via ProteomeXchange (PXD017986). Differentiation of organoids significantly increased the expression of multiple cytochrome P450, phase II enzymes, liver biomarkers and hepatic transporters. While the final phenotype of differentiated organoids is distinct from liver tissue, the organoids contain multiple drug metabolizing and transporter proteins necessary for liver function and drug metabolism, such as cytochrome P450 3A, glutathione-S-transferase alpha and multidrug resistance protein 1A. Indeed, the differentiated organoids were shown to exhibit increased sensitivity to midazolam (10–1000 µM) and irinotecan (1–100 µM), when compared to the undifferentiated organoids. The predicted reduced activity of HNF4A and a resulting dysregulation of RNA polymerase II may explain the partial differentiation of the organoids. Although further experimentation, optimization and characterization is needed relative to pre-existing models to fully contextualize their use as an in vitro model of drug-induced liver injury, hepatic organoids represent an attractive novel model of the response of the liver to xenobiotics. The current study also highlights the utility of global proteomic analyses for rapid and accurate evaluation of organoid-based test systems.
Preoperative breast magnetic resonance imaging in patients with ductal carcinoma in situ: a systematic review for the European Commission Initiative on Breast Cancer (ECIBC)
Authors: Canelo-Aybar Carlos , Taype-Rondan Alvaro , Zafra-Tanaka Jessica Hanae , Rigau David , Graewingholt Axel , Lebeau Annette , Pérez Gómez Elsa , Rossi Paolo Giorgi , Langendam Miranda , Posso Margarita , Parmelli Elena , Saz-Parkinson Zuleika , Alonso-Coello Pablo
Published: May 2021

Objective

To evaluate the impact of preoperative MRI in the management of Ductal carcinoma in situ (DCIS).

Methods

We searched the PubMed, EMBASE and Cochrane Library databases to identify randomised clinical trials (RCTs) or cohort studies assessing the impact of preoperative breast MRI in surgical outcomes, treatment change or loco-regional recurrence. We provided pooled estimates for odds ratios (OR), relative risks (RR) and proportions and assessed the certainty of the evidence using the GRADE approach.

Results

We included 3 RCTs and 23 observational cohorts, corresponding to 20,415 patients. For initial breast-conserving surgery (BCS), the RCTs showed that MRI may result in little to no difference (RR 0.95, 95% CI 0.90 to 1.00) (low certainty); observational studies showed that MRI may have no difference in the odds of re-operation after BCS (OR 0.96; 95% CI 0.36 to 2.61) (low certainty); and uncertain evidence from RCTs suggests little to no difference with respect to total mastectomy rate (RR 0.91; 95% CI 0.65 to 1.27) (very low certainty). We also found that MRI may change the initial treatment plans in 17% (95% CI 12 to 24%) of cases, but with little to no effect on locoregional recurrence (aHR = 1.18; 95% CI 0.79 to 1.76) (very low certainty).

Conclusion

We found evidence of low to very low certainty which may suggest there is no improvement of surgical outcomes with pre-operative MRI assessment of women with DCIS lesions. There is a need for large rigorously conducted RCTs to evaluate the role of preoperative MRI in this population.

Key Points

• Evidence of low to very low certainty may suggest there is no improvement in surgical outcomes with pre-operative MRI.

• There is a need for large rigorously conducted RCTs evaluating the role of preoperative MRI to improve treatment planning for DCIS.
Thermally tolerant symbionts may explain Caribbean octocoral resilience to heat stress
Authors: Pelosi Jessie , Eaton Katherine M. , Mychajliw Samantha , terHorst Casey P. , Coffroth Mary Alice
Published: May 2021

Coral reef ecosystems are under threat from the frequent and severe impacts of anthropogenic climate change, particularly rising sea surface temperatures. The effects of thermal stress may be ameliorated by adaptation and/or acclimation of the host, symbiont, or holobiont (host + symbiont) to increased temperatures. We examined the role of the symbiont in promoting thermal tolerance of the holobiont, using Antillogorgia bipinnata (octocoral host) and Breviolum antillogorgium (symbiont) as a model system. We identified five distinct genotypes of B. antillogorgium from symbiont populations isolated from Antillogorgia colonies in the Florida Keys. Three symbiont genotypes were cultured and maintained at 26 °C (ambient historical temperature), and two were cultured and maintained at 30 °C (elevated historical temperature) for 2 yrs. We analyzed the growth rate and carrying capacity of each symbiont genotype at both ambient and elevated temperatures in culture (in vitro). All genotypes grew well at both temperatures, indicating that thermal tolerance exists among these B. antillogorgium cultures. However, a history of long-term growth at 30 °C did not yield better performance for B. antillogorgium at 30 °C (as compared to 26 °C), suggesting that prior culturing at the elevated temperature did not result in increased thermal tolerance. We then inoculated juvenile A. bipinnata polyps with each of the five symbiont genotypes and reared these polyps at both ambient and elevated temperatures (in hospite experiment). All genotypes established symbioses with polyps in both temperature treatments. Survivorship of polyps at 30 °C was significantly lower than survivorship at 26 °C, but all treatments had surviving polyps at 56 d post-infection. Our results suggest broad thermal tolerance in B. antillogorgium, which may play a part in the increased resilience of Caribbean octocorals during heat stress events.
Exploiting large ensembles for a better yet simpler climate model evaluation
Authors: Suarez-Gutierrez Laura , Milinski Sebastian , Maher Nicola
Published: May 2021

We use a methodological framework exploiting the power of large ensembles to evaluate how well ten coupled climate models represent the internal variability and response to external forcings in observed historical surface temperatures. This evaluation framework allows us to directly attribute discrepancies between models and observations to biases in the simulated internal variability or forced response, without relying on assumptions to separate these signals in observations. The largest discrepancies result from the overestimated forced warming in some models during recent decades. In contrast, models do not systematically over- or underestimate internal variability in global mean temperature. On regional scales, all models misrepresent surface temperature variability over the Southern Ocean, while overestimating variability over land-surface areas, such as the Amazon and South Asia, and high-latitude oceans. Our evaluation shows that MPI-GE, followed by GFDL-ESM2M and CESM-LE offer the best global and regional representation of both the internal variability and forced response in observed historical temperatures.
Intraocular epidermal growth factor concentration, axial length, and high axial myopia
Authors: Jonas Jost B. , Dong Li , Da Chen Shi , Neumaier Michael , Findeisen Peter , Panda-Jonas Songhomitra , Jonas Rahul A.
Published: May 2021

Purpose

Various molecules such as dopamine have been found to be associated with axial elongation in experimental studies. Here, we examined whether intraocular EGF is associated with axial length in myopic patients.

Methods

The hospital-based investigation included patients of European descent without optic nerve, retinal, or macular diseases except for myopic maculopathy. Using aqueous humor samples collected during surgery, the EGF concentration was examined applying a cytometric bead array. High myopia was defined by an axial length of ≥ 27.0 mm.

Results

The study included a non-highly myopic group of 11 patients (mean age, 72.9 ± 10.8 years; mean axial length, 24.3 ± 1.1 mm) and a highly myopic group of three patients (age, 81.11 ± 12.3 years; axial length, 29.5 ± 1.3 mm), with one of them having pathologic myopic maculopathy. In multivariable linear regression analysis, higher EGF concentration was correlated with the highly myopic versus non-highly myopic group (beta, 1.24; non-standardized correlation coefficient B, 6.24; 95% confidence interval (CI), 0.10,12.4;P = 0.047) after adjusting for axial length. The amount of intraocular EGF was significantly higher in the highly myopic group than in the non-highly myopic group (89.1 ± 40.8 pg versus 34.1 ± 13.2 pg;P = 0.005), and it was highest in the eye with myopic maculopathy (135 pg).

Conclusions

The intraocular amount of EGF is higher in highly myopic versus non-highly myopic eyes.
In Colore Veritas? Color effects on the speed and accuracy of true/false responses
Authors: Nadarevic Lena , Symeonidou Nikoletta , Kias Alina
Published: May 2021

In addition to their perceptual or aesthetic function, colors often carry conceptual meaning. In quizzes, for instance, true and false answers are typically marked in green and red. In three experiments, we used a Stroop task to investigate automatic green-true associations and red-false associations, respectively. In Experiments 1 and 2, stimuli were true statements (e.g., “tables are furniture”) and false statements (e.g., “bananas are buildings”) that were displayed in different combination of green, red, and gray depending on the experimental condition. In Experiment 3, we used true-related and false-related words shown in green, red, or gray. Participants had to indicate the validity (or semantic meaning) of each statement (or word) as fast and as accurately as possible. We expected that participants would perform best when they had to categorize green stimuli as “true” and red stimuli as “false”. The prediction was only confirmed when green and red stimuli were presented within the same context (i.e., same experimental condition). This finding supports the dimension-specificity hypothesis which states that cross-modal associations (here: associations between color and validity) depend on the context (here: the color-context). Moreover, the observed color-validity effects were stronger when participants had to categorize single words instead of sentences and when they had to provide speeded responses. Taken together, these results suggest that controlled processing counteracts the influence of automatic color associations on true/false responses.
Why so few Nobel Prizes for cancer researchers? An analysis of Nobel Prize nominations for German physicians with a focus on Ernst von Leyden and Karl Heinrich Bauer
Authors: Hansson Nils , Padrini Giacomo , Moll Friedrich H. , Halling Thorsten , Timmermann Carsten
Published: May 2021

Purpose

To date, 11 scientists have received the Nobel Prize for discoveries directly related to cancer research. This article provides an overview of cancer researchers nominated for the Nobel Prize from 1901 to 1960 with a focus on Ernst von Leyden (1832–1910), the founder of this journal, and Karl Heinrich Bauer (1890–1978).

Methods

We collected nominations and evaluations in the archive of the Nobel committee of physiology or medicine in Sweden to identify research trends and to analyse oncology in a Nobel Prize context.

Results

We found a total of 54 nominations citing work on cancer as motivation for 11 candidates based in Germany from 1901 to 1953. In the 1930s, the US became the leading nation of cancer research in a Nobel context with nominees like Harvey Cushing (1869–1939) and George N. Papanicolaou (1883–1962).

Discussion

The will of Alfred Nobel stipulates that Nobel laureates should have “conferred the greatest benefit to mankind”. Why were then so few cancer researchers recognized with the Nobel medal from 1901 to 1960? Our analysis of the Nobel dossiers points at multiple reasons: (1) Many of the proposed cancer researchers were surgeons, and surgery has a weak track record in a Nobel context; (2) several scholars were put forward for clinical work and not for basic research (historically, the Nobel committee has favoured basic researchers); (3) the scientists were usually not nominated for a single discovery, but rather for a wide range of different achievements.
Native trees provide more benefits than exotic trees when ecosystem services are weighted in Santiago, Chile
Authors: Arcos-LeBert Gabriela , Aravena-Hidalgo Tamara , Figueroa Javier A. , Jaksic Fabián M. , Castro Sergio A.
Published: May 2021

Urban forests are conformed by a variable representation of native and exotic species. Because these species differ in the morpho-functional traits that possess, they may have a differential participation in the provision of ecosystem services in cities. Here, we compare ecosystem services inferred from morpho-functional traits of native and exotic tree species present in Santiago, Chile. Five traits associated with ecosystem services valuation (Vi) were scored (1 versus 0), and compared between native and exotic tree species, weighting those ecosystem services according to multi-criteria decision analysis procedure (MCDA). We found that native and exotic species did not have significant differences in the ecosystem services provided to urban dwellers (F = 1.2; P > 0.05); but these results were obtained when ecosystem services were not weighted according to their demand in Santiago. When weights were pondered, native species provided more ecosystem services than did exotic trees (F = 7.1; P < 0.008). Complementarily, we also found that the ecosystem services ranked for native and exotic species did not correlate with their spatial distribution (occupancy, Oi). These results highlight the need to use criteria based on ecosystem services to tree planting in Santiago, prioritizing native species because, in comparison to exotic ones, they provide more ecosystem services demanded city dwellers.
Assessment of sleep problems with the Insomnia Severity Index (ISI) and the sleep item of the Patient Health Questionnaire (PHQ-9) in cancer patients
Authors: Schulte Thomas , Hofmeister Dirk , Mehnert-Theuerkauf Anja , Hartung Tim , Hinz Andreas
Published: May 2021

Objective

The objectives of this study were to examine sleep problems in cancer patients, to test the psychometric properties of the Insomnia Sleep Index (ISI) in comparison with the sleep item of the Patient Health Questionnaire-9 (PHQ-9), and to analyze disrupting factors which might cause the sleep problems.

Methods

A sample of 1026 mixed-site cancer patients in treatment at a German oncological rehabilitation clinic was examined.

Results

The reliability of the ISI was very good (Cronbach’s alpha = 0.92), and the results of the confirmatory factor analysis were acceptable. Females reported worse sleep quality (ISI mean: 13.7 ± 6.6) than males (10.7 ± 6.4). Sleep problems as measured with the PHQ-9 sleep item were markedly higher than those in the general population (effect size d = 1.15).

Patients reported that, of the factors that disrupted their sleep, psychological factors (brooding, worries) were more relevant than symptom factors (pain, nocturnal urination, or restless legs).

Conclusions

The ISI is effective in detecting sleep problems in cancer patients. Normative studies with the ISI would be helpful for assessing ISI mean scores. Sex differences should be taken into account when groups of patients are compared. The sleep item of the PHQ-9 can be used in epidemiological studies.
Transcultural differences in suicide attempts among children and adolescents with and without migration background, a multicentre study: in Vienna, Berlin, Istanbul
Authors: Özlü-Erkilic Zeliha , Diehm Robert , Wenzel Thomas , Bingöl Ҫağlayan R. Hülya , Güneş Hatice , Üneri Özden Şükran , Winter Sibylle , Akkaya-Kalayci Türkan
Published: May 2021

While suicide can occur throughout the lifespan, worldwide suicide is the second leading cause of death among young people aged between 15 and 29 years. The aim of this multicentre study, conducted in Austria, Germany and Turkey, is to investigate the transcultural differences of suicide attempts among children and adolescents with and without migration background. The present study is a retrospective analyses of the records of 247 young people, who were admitted after a suicide attempt to Emergency Outpatient Clinics of Departments of Child and Adolescent Psychiatry of the collaborating Universities including Medical University of Vienna, Charité University Medicine Berlin and Cerrahpaşa School of Medicine and Bakirkoy Training and Research Hospital for Mental Health in Istanbul over a 3-year period. The results of the present study show significant transcultural differences between minors with and without migration background in regard to triggering reasons, method of suicide attempts and psychiatric diagnosis. The trigger event “intra-familial conflicts” and the use of “low-risk methods” for their suicide attempt were more frequent among patients with migration background. Moreover among native parents living in Vienna and Berlin divorce of parents were more frequent compared to parents living in Istanbul and migrants in Vienna. These results can be partly explained by cultural differences between migrants and host society. Also disadvantages in socio-economic situations of migrants and their poorer access to the healthcare system can mostly lead to acute and delayed treatments. Larger longitudinal studies are needed to understand better the impact of migration on the suicidal behaviour of young people.