bluuebunny/crossref_metadata_2025 huggingface dataset:
Classification of CT images in COVID-19 and Non-COVID-19 using CNN to extract features and multiple classifiers
Authors: Carvalho Edelson , Carvalho Edson
Published: September 2020

O COVID-19 é uma doença respiratória que já infectou mais de 12.3 milhões de pessoas em todo o mundo e é responsável por mais de 556.300 mortes. O diagnóstico precoce do COVID-19 é essencial para a cura e controle da doença. A tomografia computadorizada (TC) apresentou resultados eficientes na avaliação de pacientes com suspeita de infecção por COVID-19. A análise da TC requer o esforço de um especialista, o que pode levar a erros de diagnóstico. O uso de sistemas de diagnóstico auxiliado por computador pode minimizar os problemas gerados pela análise de TCs por especialistas. Este artigo apresenta uma metodologia para diagnosticar a COVID-19 usando CNN para extração de características e múltiplos classificadores em imagens de TC. A metodologia apresentou uma acurácia de 99,79%, recall de 99,79%, precisão de 99,80%, F-score de 0,997, AUC de 0,997 e índice kappa de 0,995. Os resultados obtidos mostram que a metodologia proposta pode ser utilizada como um sistema de auxílio ao diagnóstico.
Rätsel des Rechts
Authors: Gröschner Rolf , Mölkner Wolfgang
Published: September 2020

Im Untertitel des Buches kommen zwei Anliegen zum Ausdruck: „für juristische Laien“ verständlich zur Enträtselung des Rechts beizutragen und zugleich „für philosophierende Juristen“ einen Beitrag zum vertieften Verständnis ihrer traditionsreichen Disziplin, der stolzen „Jurisprudenz“, zu leisten. Im Gespräch zwischen einem Juristen und einem Philosophen können beide Anliegen verbunden und juristische Rätsel sozusagen über Kreuz mit zugrundeliegenden philosophischen Problemen kombiniert werden. Bereit, bei dieser Kombination an ein Kreuzworträtsel zu denken – waagrecht die juristischen, senkrecht die philosophischen Rätsel –, hätten die Autoren nichts dagegen, wenn ihrem ernsthaften wissenschaftlichen Dialog auch ein gewisser Unterhaltungswert attestiert würde.
Depression, social support, executive functioning, functionality, and quality of life in institutionalized elderly people
Authors: Ribeiro Anabela , Rosa Beatriz , Oliveira Jorge , Lopes Paulo
Published: September 2020

Aim

Our aim was to study the executive functioning, functionality, and quality of life of institutionalized old aged persons and to determine the potential roles of self-reported depression and satisfaction with social support on these domains.

Method

The sample comprised 36 volunteers (13 males and 23 females) aged between 71 and 94 years. The measures used consisted of well-established battery of neuropsychological tests. A comparative study was performed.

Results

Participants with depressive symptoms shown impaired executive functioning. Cognitive flexibility, functionality in instrumental activities of daily living, and quality of life are more affected in participants with higher levels of depression that also report higher levels of satisfaction with social support.

Conclusion

This result is intriguing and may highlight the relevance of considering not only depression, but also factors related to social isolation and loneliness in the explanation of cognitive performance, functionality, and quality of life.
Dinner and Data Management: Engaging undergraduates in research data management topics outside of the curriculum
Authors: Cook Cameron , Magle Tobin , Shimon Heather , Adamus Trisha
Published: September 2020

Researchers are faced with unprecedented challenges due to the size and complexity of data, and libraries are stepping in to help by providing guidance on research data management primarily to graduate students and faculty. Currently, many universities are encouraging an undergraduate research experience where students engage in research projects in the classroom and in research labs, yet research data management is often not included as part of these opportunities. At UW-Madison, we piloted researchERS (Emerging Research Scholars), a program for undergraduates from all disciplines to learn data management skills. Focusing on core concepts as well as data ethics, reproducibility, and research workflows, the format of the program included seven evening workshops, two networking events, and one field trip. Each workshop invited campus and community speakers relevant to the workshop’s theme as a way to introduce the students to the network of available resources and data expertise and provided food for attendees. The workshops also built in customized activities to show students how to incorporate best practices into their work. Local businesses provided a tour of their facilities as well as a talk on how they leverage data. This paper will describe this program as well as the benefits and drawbacks of tailoring a research data management program toward undergraduates.
Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement
Authors: Zhang Jie , Song Lihong , Pedersen Dennis V , Li Anna , Lambris John D , Andersen Gregers Rom , Mollnes Tom Eirik , Ma Ying Jie , Garred Peter
Published: September 2020

Properdin stabilizes the alternative C3 convertase (C3bBb), whereas its role as pattern-recognition molecule mediating complement activation is disputed for decades. Previously, we have found that soluble collectin-12 (sCL-12) synergizes complement alternative pathway (AP) activation. However, whether this observation is C3 dependent is unknown. By application of the C3-inhibitor Cp40, we found that properdin in normal human serum bound toAspergillus fumigatussolely in a C3b-dependent manner. Cp40 also prevented properdin binding when properdin-depleted serum reconstituted with purified properdin was applied, in analogy with the findings achieved by C3-depleted serum. However, when opsonized with sCL-12, properdin bound in a C3-independent manner exclusively via its tetrameric structure and directed in situ C3bBb assembly. In conclusion, a prerequisite for properdin binding and in situ C3bBb assembly was the initial docking of sCL-12. This implies a new important function of properdin in host defense bridging pattern recognition and specific AP activation.
A survey of RNA secondary structural propensity encoded within human herpesvirus genomes: global comparisons and local motifs
Authors: Andrews Ryan J. , O’Leary Collin A. , Moss Walter N.
Published: September 2020

There are nine herpesviruses known to infect humans, of which Epstein–Barr virus (EBV) is the most widely distributed (>90% of adults infected). This ubiquitous virus is implicated in a variety of cancers and autoimmune diseases. Previous analyses of the EBV genome revealed numerous regions with evidence of generating unusually stable and conserved RNA secondary structures and led to the discovery of a novel class of EBV non-coding (nc)RNAs: the stable intronic sequence (sis)RNAs. To gain a better understanding of the roles of RNA structure in EBV biology and pathogenicity, we revisit EBV using recently developed tools for genome-wide motif discovery and RNA structural characterization. This corroborated previous results and revealed novel motifs with potential functionality; one of which has been experimentally validated. Additionally, since many herpesviruses increasingly rival the seroprevalence of EBV (VZV, HHV-6 and HHV-7 being the most notable), analyses were expanded to include all sequenced human Herpesvirus RefSeq genomes, allowing for genomic comparisons. In total 10 genomes were analyzed, for EBV (types 1 and 2), HCMV, HHV-6A, HHV-6B, HHV-7, HSV-1, HSV-2, KSHV, and VZV. All resulting data were archived in the RNAStructuromeDB (https://structurome.bb.iastate.edu/herpesvirus) to make them available to a wide array of researchers.
A multi-class classification model for supporting the diagnosis of type II diabetes mellitus
Authors: Kuo Kuang-Ming , Talley Paul , Kao YuHsi , Huang Chi Hsien
Published: September 2020

Background

Numerous studies have utilized machine-learning techniques to predict the early onset of type 2 diabetes mellitus. However, fewer studies have been conducted to predict an appropriate diagnosis code for the type 2 diabetes mellitus condition. Further, ensemble techniques such as bagging and boosting have likewise been utilized to an even lesser extent. The present study aims to identify appropriate diagnosis codes for type 2 diabetes mellitus patients by means of building a multi-class prediction model which is both parsimonious and possessing minimum features. In addition, the importance of features for predicting diagnose code is provided.

Methods

This study included 149 patients who have contracted type 2 diabetes mellitus. The sample was collected from a large hospital in Taiwan from November, 2017 to May, 2018. Machine learning algorithms including instance-based, decision trees, deep neural network, and ensemble algorithms were all used to build the predictive models utilized in this study. Average accuracy, area under receiver operating characteristic curve, Matthew correlation coefficient, macro-precision, recall, weighted average of precision and recall, and model process time were subsequently used to assess the performance of the built models. Information gain and gain ratio were used in order to demonstrate feature importance.

Results

The results showed that most algorithms, except for deep neural network, performed well in terms of all performance indices regardless of either the training or testing dataset that were used. Ten features and their importance to determine the diagnosis code of type 2 diabetes mellitus were identified. Our proposed predictive model can be further developed into a clinical diagnosis support system or integrated into existing healthcare information systems. Both methods of application can effectively support physicians whenever they are diagnosing type 2 diabetes mellitus patients in order to foster better patient-care planning.
Recent Advances of Solid‐State NMR Spectroscopy for Microporous Materials
Authors: Li Shenhui , Lafon Olivier , Wang Weiyu , Wang Qiang , Wang Xingxing , Li Yi , Xu Jun , Deng Feng
Published: September 2020

Microporous materials have attracted a rapid growth of research interest in materials science and the multidisciplinary area because of their wide applications in catalysis, separation, ion exchange, gas storage, drug release, and sensing. A fundamental understanding of their diverse structures and properties is crucial for rational design of high‐performance materials and technological applications in industry. Solid‐state NMR (SSNMR), capable of providing atomic‐level information on both structure and dynamics, is a powerful tool in the scientific exploration of solid materials. Here, advanced SSNMR instruments and methods for characterization of microporous materials are briefly described. The recent progress of the application of SSNMR for the investigation of microporous materials including zeolites, metal–organic frameworks, covalent organic frameworks, porous aromatic frameworks, and layered materials is discussed with representative work. The versatile SSNMR techniques provide detailed information on the local structure, dynamics, and chemical processes in the confined space of porous materials. The challenges and prospects in SSNMR study of microporous and related materials are discussed.
Surface Submillimeter Papillae Enhanced Mechanical Property of Membrane
Authors: Wang Lei , Zhao Feng , Li Peiliu , Li Lei , Liu Jing
Published: September 2020

The surface topographies of natural surfaces play significant roles for improving the ability to adapt to the environment. The micropapilla of lotus leaf is always used to enhance its self‐cleaning performance. However, the function of the submillimeter papilla of lotus has not been well studied. In this study, it is found that the optimal distribution of submillimeter papilla can effectively prevent the rupture of lotus leaf. Under loading, the submillimeter papilla transfers the stress into its root region, which effectively keeps the leaf broadly intact and collaborates to realize relative functions with micropapilla. Further study by integrating the simulations and biofabricated membrane with artificial submillimeter papilla indicates the contribution of submillimeter papilla on the mechanical property. This study opens a novel avenue for designing strength membrane materials, which has potential applications in the fields of soft robot, electronic device, and packaging.
Incorporating Transition‐Metal Phosphides Into Metal‐Organic Frameworks for Enhanced Photocatalysis
Authors: Sun Kang , Liu Meng , Pei Junzhe , Li Dandan , Ding Chunmei , Wu Kaifeng , Jiang Hai‐Long
Published: September 2020

Metal‐organic frameworks (MOFs) have been shown to be an excellent platform in photocatalysis. However, to suppress electron–hole recombination, a Pt cocatalyst is usually inevitable, especially in photocatalytic H2 production, which greatly limits practical application. Herein, for the first time, monodisperse, small‐size, and noble‐metal‐free transitional‐metal phosphides (TMPs; for example, Ni2P, Ni12P5), are incorporated into a representative MOF, UiO‐66‐NH2, for photocatalytic H2 production. Compared with the parent MOF and their physical mixture, both TMPs@MOF composites display significantly improved H2 production rates. Thermodynamic and kinetic studies reveal that TMPs, behaving similar ability to Pt, greatly accelerate the linker‐to‐cluster charge transfer, promote charge separation, and reduce the activation energy of H2 production. Significantly, the results indicate that Pt is thermodynamically favorable, yet Ni2P is kinetically preferred for H2 production, accounting for the higher activity of Ni2P@UiO‐66‐NH2 than Pt@UiO‐66‐NH2.
A Carbocationic Triarylmethane‐Based Porous Covalent Organic Network
Authors: Freitas Sunny K. S. , Oliveira Felipe L. , dos Santos Thiago C. , Hisse Danilo , Merlini Claudia , Ronconi Célia M. , Esteves Pierre M.
Published: September 2020

A thermally stable carbocationic covalent organic network (CON), named RIO‐70 was prepared from pararosaniline hydrochloride, an inexpensive dye, and triformylphloroglucinol in solvothermal conditions. This nanoporous organic material has shown a specific surface area of 990 m2 g−1 and pore size of 10.3 Å. The material has CO2 uptake of 2.14 mmol g−1 (0.5 bar), 2.7 mmol g−1 (1 bar), and 6.8 mmol g−1 (20 bar), the latter corresponding to 3 CO2 molecules adsorbed per pore per sheet. It is shown to be a semiconductor, with electrical conductivity (σ) of 3.17×10−7 S cm−1, which increases to 5.26×10−4 S cm−1 upon exposure to I2 vapor. DFT calculations using periodic conditions support the findings.
Study of lipoprotein(a) and its impact on atherosclerotic cardiovascular disease: Design and rationale of the Mass General Brigham Lp(a) Registry
Authors: Berman Adam N. , Biery David W. , Ginder Curtis , Hulme Olivia L. , Marcusa Daniel , Leiva Orly , Wu Wanda Y. , Singh Avinainder , Divakaran Sanjay , Hainer Jon , Turchin Alexander , Januzzi James L. , Natarajan Pradeep , Cannon Christopher P. , Di Carli Marcelo F. , Bhatt Deepak L. , Blankstein Ron
Published: September 2020

Lipoprotein(a) [Lp(a)] is independently associated with atherosclerotic cardiovascular disease and calcific aortic valve stenosis. Elevated Lp(a) affects approximately one in five individuals and meaningfully contributes to the residual cardiovascular risk in individuals with otherwise well‐controlled risk factors. With targeted therapies in the therapeutic pipeline, there is a need to further characterize the clinical phenotypes and outcomes of individuals with elevated levels of this unique biomarker. The Mass General Brigham Lp(a) Registry will be built from the longitudinal electronic health record of two large academic medical centers in Boston, Massachusetts, to develop a detailed cohort of patients who have had their Lp(a) measured. In combination with structured data sources, clinical documentation will be analyzed using natural language processing techniques to accurately characterize baseline characteristics. Important outcome measures including all‐cause mortality, cardiovascular mortality, and cardiovascular events will be available for analysis. Approximately 30 000 patients who have had their Lp(a) tested within the Mass General Brigham system from January 2000 to July 2019 will be included in the registry. This large Lp(a) cohort will provide meaningful observational data regarding the differential risk associated with Lp(a) values and cardiovascular disease. With a new frontier of targeted Lp(a) therapies on the horizon, the Mass General Brigham Lp(a) Registry will help provide a deeper understanding of Lp(a)'s role in long term cardiovascular outcomes.
Current meta‐analysis does not support the possibility of COVID‐19 reinfections
Authors: Arafkas Mohamed , Khosrawipour Tanja , Kocbach Piotr , Zielinski Kacper , Schubert Justyna , Mikolajczyk Agata , Celinska Maria , Khosrawipour Veria
Published: September 2020

Coronavirus disease 2019 (COVID‐19) reinfections could be a major aggravating factor in this current pandemic, as this would further complicate potential vaccine development and help to maintain worldwide virus pockets. To investigate this critical question, we conducted a clinical meta‐analysis including all available currently reported cases of potential COVID‐19 reinfections. We searched for all peer‐reviewed articles in the search engine of the National Center for Biotechnology Information. While there are over 30,000 publications on COVID‐19, only about 15 specifically target the subject of COVID‐19 reinfections. Available patient data in these reports was analyzed for age, gender, time of reported relapse after initial infection and persistent COVID‐19 positive polymerase chain reaction (PCR) results. Following the first episode of infection, cases of clinical relapse are reported at 34 (mean) ± 10.5 days after full recovery. Patients with clinical relapse have persisting positive COVID‐19 PCR testing results until 39 ± 9 days following initial positive testing. For patients without clinical relapse, positive testing was reported up to 54 ± 24 days. There were no reports of any clinical reinfections after a 70‐day period following initial infection.
Suitable Camera and Rotation Navigation for People with Visual Impairment on Looking for Something Using Object Detection Technique
Authors: Iwamura Masakazu , Inoue Yoshihiko , Minatani Kazunori , Kise Koichi
Published: September 2020

For people with visual impairment, smartphone apps that use computer vision techniques to provide visual information have played important roles in supporting their daily lives. However, they can be used under a specific condition only. That is, only when the user knowswhere the object of interest is. In this paper, we first point out the fact mentioned above by categorizing the tasks that obtain visual information using computer vision techniques. Then, inlooking for somethingas a representative task in a category, we argue suitable camera systems and rotation navigation methods. In the latter, we propose novel voice navigation methods. As a result of a user study comprised of seven people with visual impairment, we found that (1) a camera with a wide field of view such as an omnidirectional camera was preferred, and (2) users have different preferences in navigation methods.
Adaptive User Interfaces for People with Cognitive Disabilities within the Easy Reading Framework
Authors: Heumader Peter , Miesenberger Klaus , Murillo-Morales Tomas
Published: September 2020

Adaptive user interfaces are user interfaces that dynamically adapt to the users’ preferences and abilities. These user interfaces have great potential to improve accessibility of user interfaces for people with cognitive disabilities. However automatic changes to user interfaces driven by adaptivity are also in contradiction to accessibility guidelines, as consistence of user interfaces is of utmost importance for people with cognitive disabilities. This paper describes how such user interfaces are implemented within the Easy Reading framework, a framework to improve the accessibility of web-pages for people with cognitive disabilities.
Poisson-Lie T-duality of WZW model via current algebra deformation
Authors: Bascone Francesco , Pezzella Franco , Vitale Patrizia
Published: September 2020

Abstract

Poisson-Lie T-duality of the Wess-Zumino-Witten (WZW) model having the group manifold of SU(2) as target space is investigated. The whole construction relies on the deformation of the affine current algebra of the model, the semi-direct sum $$ \mathfrak{su}(2)\left(\mathrm{\mathbb{R}}\right)\overset{\cdot }{\oplus}\mathfrak{a} $$
su

2

ℝ

⊕
⋅

a
, to the fully semisimple Kac-Moody algebra $$ \mathfrak{sl}\left(2,\mathrm{\mathbb{C}}\right)\left(\mathrm{\mathbb{R}}\right) $$
sl

2
ℂ

ℝ

. A two-parameter family of models with SL(2, ℂ) as target phase space is obtained so that Poisson-Lie T-duality is realised as an O(3, 3) rotation in the phase space. The dual family shares the same phase space but its configuration space is SB(2, ℂ), the Poisson-Lie dual of the group SU(2). A parent action with doubled degrees of freedom on SL(2, ℂ) is defined, together with its Hamiltonian description.
Lorentzian inversion and anomalous dimensions in Mellin space
Authors: Shyani Milind
Published: September 2020

Abstract

In this note, we derive a Mellin space version of the Lorentzian inversion formula for CFTs by explicitly integrating over the cross-ratios in d = 2 and d = 4 spacetime dimensions. We use the simplicity of the Mellin representation of Witten diagrams and the double discontinuity to find the OPE coefficients and anomalous dimensions of double- trace primaries in large N CFTs to order $$ \frac{1}{N^4} $$

1

N
4

. We find that our results match analytically at order $$ \frac{1}{N^2} $$

1

N
2

, and numerically at order $$ \frac{1}{N^4} $$

1

N
4

with existing literature.
Talar OsteoPeriostic grafting from the Iliac Crest (TOPIC) for large medial talar osteochondral defects
Authors: Kerkhoffs G. M. M. J. , Altink J. N. , Stufkens S. A. S. , Dahmen J.
Published: September 2020

Objective

Provision of a natural scaffold, good quality cells, and growth factors in order to facilitate the replacement of the complete osteochondral unit with matching talar curvature for large medial primary and secondary osteochondral defects of the talus.

Indications

Symptomatic primary and secondary medial osteochondral defects of the talus not responding to conservative treatment; anterior–posterior or medial–lateral diameter >10 mm on computed tomography (CT); closed distal tibial physis in young patients.

Contraindications

Tibiotalar osteoarthritis grade III; multiple osteochondral defects on the medial, central, and lateral talar dome; malignancy; active infectious ankle joint pathology.

Surgical technique

A medial distal tibial osteotomy is performed, after which the osteochondral defect is excised in toto from the talar dome. The recipient site is microdrilled in order to disrupt subchondral bone vessels. Then, the autograft is harvested from the ipsilateral iliac crest with an oscillating saw, after which the graft is adjusted to an exact fitting shape to match the extracted osteochondral defect and the talar morphology as well as curvature. The graft is implanted with a press-fit technique after which the osteotomy is reduced with two 3.5 mm lag screws and the incision layers are closed. In cases of a large osteotomy, an additional third tubular buttress plate is added, or a third screw at the apex of the osteotomy.

Postoperative management

Non-weight bearing cast for 6 weeks, followed by another 6 weeks with a walking boot. After 12 weeks, a CT scan is performed to assess consolidation of the osteotomy and the inserted autograft. The patient is referred to a physiotherapist.

Results

Ten cases underwent the TOPIC procedure, and at 1 year follow-up all clinical scores improved. Radiological outcomes showed consolidation of all osteotomies and all inserted grafts showed consolidation. Complications included one spina iliaca anterior avulsion and one hypaesthesia of the saphenous nerve; in two patients the fixation screws of the medial malleolar osteotomy were removed.
Das Data Monitoring Committee – State of the Art und Perspektiven für die Zukunft
Authors: Fischer Thomas
Published: September 2020

Hintergrund

Die klassische randomisierte und kontrollierte klinische Prüfung steht mit komplexen Studiendesigns und Disease-Interception-Konzepten vor neuen Herausforderungen. Dabei können Data Monitoring Committees (Datenüberwachungskomitees [DMCs]) eine zentrale Funktion übernehmen, wenn eine fachgerechte Integration in den methodischen Ablauf der klinischen Prüfungen erfolgt. Vor diesem Hintergrund haben die zuständige Bundesoberbehörde und die zuständige Ethikkommission im impliziten/expliziten Genehmigungsverfahren zu überprüfen, ob eine substanzielle Charta die Arbeitsweise des unabhängigen Gremiums abbildet.

Ziel

Es wurde der Frage nachgegangen, mit welchen Häufigkeiten und Gegebenheiten DMCs in klinischen Prüfungen eingesetzt werden.

Methode

Die Datenbank des Bundesinstituts für Arzneimittel und Medizinprodukte (BfArM) bildet die Grundlage für eine Datenanalyse hinsichtlich Häufigkeiten der Implementierung von Data Monitoring Committees unter verschiedenen Kriterien über einen Beobachtungszeitraum von mehr als 15 Jahren.

Ergebnisse

Bei insgesamt 14.135 klinischen Prüfungen mit Arzneimitteln wurde 4152 DMCs eingesetzt. Das unabhängige Expertengremium wurde überwiegend von kommerziellen Sponsoren in der Phase III der klinischen Entwicklung integriert. Die Ethikkommissionen waren mit unterschiedlichen absoluten Häufigkeiten eingebunden.

Diskussion

Die Sponsoren zeigen eine zunehmende Bereitschaft, DMCs in die methodische Durchführung von klinischen Prüfungen, insbesondere bei neuartigen Studiendesigns, zu integrieren. DMCs können eine wichtige wissenschaftliche Unterstützung sein, um die Implikationen des Coronavirus SARS-CoV‑2 auf klinische Prüfungen zu beurteilen.
Machine learning and optimization for production rescheduling in Industry 4.0
Authors: Li Yuanyuan , Carabelli Stefano , Fadda Edoardo , Manerba Daniele , Tadei Roberto , Terzo Olivier
Published: September 2020

Along with the fourth industrial revolution, different tools coming from optimization, Internet of Things, data science, and artificial intelligence fields are creating new opportunities in production management. While manufacturing processes are stochastic and rescheduling decisions need to be made under uncertainty, it is still a complicated task to decide whether a rescheduling is worthwhile, which is often addressed in practice on a greedy basis. To find a tradeoff between rescheduling frequency and the growing accumulation of delays, we propose a rescheduling framework, which integrates machine learning (ML) techniques and optimization algorithms. To prove the effectiveness, we first model a flexible job-shop scheduling problem with sequence-dependent setup and limited dual resources (FJSP) inspired by an industrial application. Then, we solve the scheduling problem through a hybrid metaheuristic approach. We train the ML classification model for identifying rescheduling patterns. Finally, we compare its rescheduling performance with periodical rescheduling approaches. Through observing the simulation results, we find the integration of these techniques can provide a good compromise between rescheduling frequency and scheduling delays. The main contributions of the work are the formalization of the FJSP problem, the development of ad hoc solution methods, and the proposal/validation of an innovative ML and optimization-based framework for supporting rescheduling decisions.
Structure-dependent genotoxic potencies of selected pyrrolizidine alkaloids in metabolically competent HepG2 cells
Authors: Rutz Lukas , Gao Lan , Küpper Jan-Heiner , Schrenk Dieter
Published: September 2020

1,2-unsaturated pyrrolizidine alkaloids (PAs) are natural plant constituents comprising more than 600 different structures. A major source of human exposure is thought to be cross-contamination of food, feed and phytomedicines with PA plants. In humans, laboratory and farm animals, certain PAs exert pronounced liver toxicity and can induce malignant liver tumors in rodents. Here, we investigated the cytotoxicity and genotoxicity of eleven PAs belonging to different structural classes. Although all PAs were negative in the fluctuation Ames test in Salmonella, they were cytotoxic and induced micronuclei in human HepG2 hepatoblastoma cells over-expressing human cytochrome P450 3A4. Lasiocarpine and cyclic diesters except monocrotaline were the most potent congeners both in cytotoxicity and micronucleus assays with concentrations below 3 μM inducing a doubling in micronuclei counts. Other open di-esters and all monoesters exhibited weaker or much weaker geno- and cytotoxicity. The findings were in agreement with recently suggested interim Relative Potency (iREP) factors with the exceptions of europine and monocrotaline. A more detailed micronuclei analysis at low concentrations of lasiocarpine, retrorsine or senecionine indicated that pronounced hypolinearity of the concentration–response curves was evident for retrorsine and senecionine but not for lasiocarpine. Our findings show that the genotoxic and cytotoxic potencies of PAs in a human hepatic cell line vary in a structure-dependent manner. Both the low potency of monoesters and the shape of prototype concentration–response relationships warrant a substance- and structure-specific approach in the risk assessment of PAs.
Virtual screening of potentially endocrine-disrupting chemicals against nuclear receptors and its application to identify PPARγ-bound fatty acids
Authors: Jaladanki Chaitanya K. , He Yang , Zhao Li Na , Maurer-Stroh Sebastian , Loo Lit-Hsin , Song Haiwei , Fan Hao
Published: September 2020

Nuclear receptors (NRs) are key regulators of energy homeostasis, body development, and sexual reproduction. Xenobiotics binding to NRs may disrupt natural hormonal systems and induce undesired adverse effects in the body. However, many chemicals of concerns have limited or no experimental data on their potential or lack-of-potential endocrine-disrupting effects. Here, we propose a virtual screening method based on molecular docking for predicting potential endocrine-disrupting chemicals (EDCs) that bind to NRs. For 12 NRs, we systematically analyzed how multiple crystal structures can be used to distinguish actives and inactives found in previous high-throughput experiments. Our method is based on (i) consensus docking scores from multiple structures at a single functional state (agonist-bound or antagonist-bound), (ii) multiple functional states (agonist-bound and antagonist-bound), and (iii) multiple pockets (orthosteric site and alternative sites) of these NRs. We found that the consensus enrichment from multiple structures is better than or comparable to the best enrichment from a single structure. The discriminating power of this consensus strategy was further enhanced by a chemical similarity-weighted scoring scheme, yielding better or comparable enrichment for all studied NRs. Applying this optimized method, we screened 252 fatty acids against peroxisome proliferator-activated receptor gamma (PPARγ) and successfully identified 3 previously unknown fatty acids with Kd = 100–250 μM including two furan fatty acids: furannonanoic acid (FNA) and furanundecanoic acid (FUA), and one cyclopropane fatty acid: phytomonic acid (PTA). These results suggested that the proposed method can be used to rapidly screen and prioritize potential EDCs for further experimental evaluations.
A robust equatorial Pacific westerly response to tropical volcanism in multiple models
Authors: Chai Jing , Liu Fei , Xing Chen , Wang Bin , Gao Chaochao , Liu Jian , Chen Deliang
Published: September 2020

After each of the 1963 Agung, 1982 El Chichón, and 1991 Pinatubo eruptions, an El Niño was observed. The increased likelihood of an El Niño after a tropical eruption has also been found in long-term reconstructed proxy data. Through examining simulations over the last millennium by 11 different models, we show that a tropical volcano eruption can robustly excite a western-to-central equatorial Pacific (WCEP) westerly anomaly at 850 hPa in eight out of the 11 models; such a westerly anomaly is favorable for El Niño development. Under the volcanic forcing, there are significant extratropical continent surface cooling and tropical drying with negative precipitation anomalies over the South–South East Asia (SSEA), West African monsoon, and Intertropical Convergence Zone (ITCZ) regions. This common precipitation suppression response occurs in most of the models. Sensitivity experiments show that a WCEP westerly anomaly can be excited by the tropical land cooling, especially the SSEA cooling induced precipitation suppression rather than by the extratropical land surface cooling. Theoretical results show that a WCEP westerly anomaly is excited due to a Gill response to reduced precipitation over the SSEA and West African monsoon regions; and the SSEA contributes more than the West African monsoon does. The ITCZ weakening, however, excites an easterly wind anomaly. The models with more sensitive convective feedback tend to simulate an El Niño more easily, while a failed simulation of an El Niño after a robust westerly anomaly in some models calls for further studies on these models’ delayed responses to radiative forcing induced by volcano eruptions.
A practical guide for investigating cardiac physiology using living myocardial slices
Authors: Watson S. A. , Dendorfer A. , Thum T. , Perbellini F.
Published: September 2020

Ex vivo multicellular preparations are essential tools to study tissue physiology. Among them, the recent methodological and technological developments in living myocardial slices (LMS) are attracting increasing interest by the cardiac research field. Despite this, this research model remains poorly perceived and utilized by most research laboratories. Here, we provide a practical guide on how to use LMS to interrogate multiple aspects of cardiac function, structure and biochemistry. We discuss issues that should be considered to conduct successful experiments, including experimental design, sample preparation, data collection and analysis. We describe how laboratory setups can be adapted to accommodate and interrogate this multicellular research model. These adaptations can often be achieved at a reasonable cost with off-the-shelf components and operated reliably using well-established protocols and freely available software, which is essential to broaden the utilization of this method. We will also highlight how current measurements can be improved to further enhance data quality and reliability to ensure inter-laboratory reproducibility. Finally, we summarize the most promising biomedical applications and envision how living myocardial slices can lead to further breakthroughs.
Prevalence and distribution of human papillomavirus genotypes in cervical intraepithelial neoplasia in China: a meta-analysis
Authors: Zhang Junya , Cheng Keyan , Wang Zhilian
Published: September 2020

Background and aim

Data on type-specific human papillomavirus (HPV) are needed to investigate HPV-based screening tests and HPV vaccines. However, Chinese relevant data are insufficient. Therefore, this meta-analysis aimed to summarize and demonstrate the prevalence and distribution of HPV genotypes in cervical intraepithelial neoplasia (CIN) and compensate for the shortage of HPV vaccines in China.

Methods

The Medline, Embase, and the Cochrane Library databases, as well as references cited in the selected studies, were systematically searched for studies investigating the prevalence and distribution of HPV genotypes between January 2000 and April 2019 in China.

Results

A total of 8 studies were identified, which comprised 2950 patients with CIN1 and 5393 with CIN2/3. The overall HPV infection rate was 84.37%. The HPV infection rate was significantly higher in the CIN2/3 group (87.00%) than in the CIN1 group (79.56%) (χ2 = 80.095, P < 0.001). The most common HPV types in CIN1 in order of decreasing prevalence were as follows: HPV52 (20.31%), HPV16 (16.81%), HPV58 (14.44%), HPV18 (6.44%), and HPV53 (5.76%). However, in the CIN2/3 group, HPV16 (45.69%) was the predominant type, followed by HPV58 (15.50%), HPV52 (11.74%), HPV33 (9.35%), and HPV31 (4.34%).

Conclusions

This study suggested that HPV16, HPV52, and HPV58 were the top three types of CIN in China. The findings might provide a reference for future HPV-based cervical cancer screening tests, treatment of HPV infection, and application of HPV vaccines in China.
Auditory dysfunction in type 2 Stickler Syndrome
Authors: Alexander Philip , Gomersall Philip , Stancel-Lewis Jack , Fincham Gregory Scott , Poulson Arabella , Richards Allan , McNinch Annie , Baguley David M. , Snead Martin
Published: September 2020

Purpose

To present the extent and site of lesion of auditory dysfunction in a large cohort of individuals with type 2 Stickler Syndrome. Type 2 Stickler Syndrome results from a mutation in the gene coding for α-1 type XI pro-collagen, which has been identified in the human vitreous, cartilage and the cochlea of the mouse. The condition is characterised by classic ocular abnormalities, auditory dysfunction, osteoarthropathy and oro-facial dysplasia.

Methods

This is a population study which used a combination of audiometric, tympanometric, and self-report measures on a series of 65 individuals (mean age 29.2 years, range 3–70, female 63.1%) with genetically confirmed type 2 Stickler Syndrome.

Results

Hearing impairment was identified in at least one ear for 69% of individuals. Analysis against age-matched normative data showed that reduced hearing sensitivity was present across all test frequencies. Sensorineural hearing loss was most common (77% of ears), with conductive (3%), mixed (7%) and no hearing loss (13%), respectively. The proportion of hypermobile tympanic membranes (24%) was less than previously documented in type 1 Stickler Syndrome. When present, this appears to arise as a direct result of collagen abnormalities in the middle ear. Self-report measures of speech and spatial hearing in sound were comparable to a non-syndromic cohort with similar audiometric thresholds.

Conclusions

Auditory impairment in type 2 Stickler Syndrome is predominantly associated with cochlear hearing loss of varying severities across affected individuals. The impact on hearing thresholds can be seen across the frequency range, suggesting a contribution of defective collagen throughout the cochlea. Self-report questionnaires showed that difficulties understanding speech, and spatial information in sound (such as that used for localisation), were worse than a young, normal-hearing population but comparable to a non-syndromic cohort with similar audiometric thresholds. Therefore, it is likely that hearing loss in type 2 Stickler Syndrome arises in the auditory periphery, without significant central processing deficits.
Surgical options in suprastomal collapse-induced severe airway obstruction
Authors: Onder Serap Sahin , Ishii A. , Sandu K.
Published: September 2020

Purpose

A single institutions experience with various surgical options in the treatment of severe suprastomal collapse (SSC).

Methods

The study included 18 tracheostomized children with SSC treated between January 2012 and December 2018. Data included: patient demography, initial airway lesions, comorbidities, indication and age at tracheostomy, prior airway surgery, stomal demography, type of surgery, postoperative management, complications and treatment outcomes.

Results

Four techniques were used to correct SSC. The surgical choice was dependent on stoma demography and associated airway lesions. Excision was done in eight patients and rib cartilage augmentation in five. Three patients had single stage tracheal resection and anastomosis. Two patients received stomal rigidification and temporary placement of Montgomery T tube. Three patients with anterior rib graft augmentation required additional lateral tracheal wall rigidification. Three patients (two with cartilage augmentation, and one with stomal rigidification) developed minimal granulation tissue in the postoperative period. Complete SSC resolution was seen in all except two patients who had a partial response to the treatment. All patients were successful decannulated and are currently asymptomatic.

Conclusion

Decannulation failures may be due to severe suprastomal collapse that could be either unique or associated with obstructing laryngotracheal lesions. Therefore, it is essential to select the most appropriate surgical treatment to obtain overall favorable outcomes.
Double bookkeeping and schizophrenia spectrum: divided unified phenomenal consciousness
Authors: Parnas Josef , Urfer-Parnas Annick , Stephensen Helene
Published: September 2020

Eugen Bleuler, the founder of the concept of schizophrenia, pointed out that psychotic patients were able to live in two disjoint worlds (namely, the social, intersubjective world and the delusional world). He termed this phenomenon “double bookkeeping,” but did not provide any conceptual elaboration of this phenomenon or its possible mechanisms. Double bookkeeping has been neglected in mainstream psychiatry, but it has been addressed in recent theoretical work, however mainly concerned with the issue of delusion. In this article, we present clinical material that supports the view that double bookkeeping manifests itself across various psychotic phenomena and its antecedent may be observed in premorbid (pre-onset) phases as well as in the schizotypal disorder. We try to conceptualize double bookkeeping to concretize an often atmospheric perception of paradoxicality in the encounter with the patient. A phenomenological analysis of double bookkeeping suggests an instability in the affective (“auto-affection”) articulation of selfhood. We point to four main implications of our presentation: (1) diagnostic, (2) epistemological, (3) therapeutic and (4) pathogenetic research.
Hearing loss and cognitive decline in the general population: a prospective cohort study
Authors: Croll Pauline H. , Vinke Elisabeth J. , Armstrong Nicole M. , Licher Silvan , Vernooij Meike W. , Baatenburg de Jong Robert J. , Goedegebure André , Ikram M. Arfan
Published: September 2020

Background

Previous studies identifying hearing loss as a promising modifiable risk factor for cognitive decline mostly adjusted for baseline age solely. As such a faster cognitive decline at a higher age, which is expected considering the non-linear relationship between cognition and age, may have been overlooked. Therefore it remains uncertain whether effects of hearing loss on cognitive decline extend beyond age-related declines of cognitive function.

Methods

3,590 non-demented participants were eligible for analysis at baseline, and a maximum of 837 participants were eligible for the longitudinal analysis. Hearing loss was defined at baseline. Cognitive function was measured at baseline and at follow-up (4.4 years [SD: 0.2]). Multivariable linear regression analysis was used for the cross-sectional analysis. Linear mixed models were used to assess the longitudinal association between hearing loss and cognitive decline over time while adjusting for confounders and the interaction of age and follow-up time.

Results

Hearing loss was associated with lower cognitive function at baseline. Moreover, hearing loss was associated with accelerated cognitive decline over time on a memory test. After additionally adjusting for the interaction between age and follow-up time, we found that hearing loss did not accelerate cognitive decline anymore.

Conclusions

Hearing loss was associated with lower cognitive function at baseline and accelerated cognitive decline on a memory test. The association between hearing loss and accelerated cognitive decline was non-significant after additional adjustment for non-linear age effects. More evidence is needed to ensure the role of hearing loss as a modifiable risk factor for cognitive decline.
Severe acute pancreatitis: surgical indications and treatment
Authors: Heckler Max , Hackert Thilo , Hu Kai , Halloran Cristopher M. , Büchler Markus W. , Neoptolemos John P.
Published: September 2020

Background

Acute pancreatitis (AP) is defined as an acute inflammatory attack of the pancreas of sudden onset. Around 25% of patients have either moderately severe or severe disease with a mortality rate of 15–20%.

Purpose

The aim of this article was to summarize the advances being made in the understanding of this disease and the important role of surgery.

Results and conclusions

An accurate diagnosis should be made a soon as possible, initiating resuscitation with large volume intravenous fluids and oxygen by mask. Predicted severe disease will require intensive monitoring. Most deaths within the first week are due to multi-organ failure; thus, these patients will require intensive therapy unit management. During the second phase of the disease, death is due to local complications arising from the pancreatic inflammation, requiring accurate identification to determine the correct form of treatment. Acute peripancreatic fluid collections arise < 4 weeks after onset of interstitial edematous pancreatitis, not requiring any treatment. Most pancreatic pseudocysts arise > 4 weeks and largely resolve on conservative management. Necrotizing pancreatitis causing acute necrotic collections and later walled-off necrosis will require treatment if symptomatic or infected. Initial endoscopic transgastric or percutaneous drainage will resolve less serious collections but necrosectomy using minimally invasive approaches will be needed for more serious collections. To prevent recurrent attacks of AP, causative factors need to be removed where possible such as cholecystectomy and cessation of alcohol. Future progress requires improved management of multi-organ failure and more effective minimally invasive techniques for the removal of necrosis.
Antineoplastic effects of targeting CCR5 and its therapeutic potential for colorectal cancer liver metastasis
Authors: Pervaiz Asim , Zepp Michael , Georges Rania , Bergmann Frank , Mahmood Saqib , Faiza Syeda , Berger Martin R. , Adwan Hassan
Published: September 2020

Purpose

Liver metastasis is observed in up to 50% of colorectal cancer (CRC) patients. Available treatment options are limited and disease recurrence is often. Chemokine receptor 5 (CCR5) has attracted attention as novel therapeutic target for treating cancers. In this study, we reinforced the importance of CCR5 as therapeutic target in CRC and its liver metastasis by applying in vitro, in vivo and clinical investigations.

Methods

By targeting CCR5 via siRNAs or an FDA approved antagonist (maraviroc), we investigated the ensuing antineoplastic effects in three CRC cell lines. An animal model for CRC liver metastasis was used to evaluate time-dependent expressional modulation of the CCR5 axis by cDNA microarray. The model was also used to evaluate the in vivo efficacy of targeting CCR5 by maraviroc. Circulatory and tumor associated levels of CCR5 and its cognate ligands (CCL3, CCL4, CCL5) were analyzed by ELISA, qRT-PCR and immunohistochemistry.

Results

Targeting the CCR5 inhibited proliferative, migratory and clonogenic properties and interfered with cell cycle-related signaling cascades. In vivo findings showed significant induction of the CCR5 axis during the early liver colonization phase. Treatment with maraviroc significantly inhibited CRC liver metastasis in the animal model. Differential expression profiles of circulatory and tumor associated CCR5/ligands were observed in CRC patients and healthy controls.

Conclusion

The findings indicate that targeting the CCR5 axis can be an effective strategy for treating CRC liver metastasis.