bluuebunny/crossref_metadata_2025 huggingface dataset:
Ex situ breeding programs benefit from science‐based cooperative management
Authors: Putnam Andrea S. , Ferrie Gina M. , Ivy Jamie A.
Published: May 2022

Science‐based management confers a variety of benefits to wildlife populations that are cooperatively managed by zoos and aquariums, including those managed through the Association of Zoos and Aquariums. Briefly, when management strategies are successful, they result in reproductively robust populations that better retain genetic diversity and limit inbreeding than unmanaged populations. Although the benefits of demographic and genetic management have been well documented throughout both the scientific and popular literature, it has also been established that the majority of managed populations in zoos and aquariums are not meeting the minimum criteria believed to convey long‐term biological viability. For most of these populations, an inability to meet viability criteria is not an inherent failure of how cooperative management is implemented. Furthermore, in recent years, we have perceived that the need to meet specific viability goals sometimes has obscured the benefits that these populations receive from rigorous, science‐based management. To better clarify the conversation surrounding population viability in zoos and aquariums, we seek to decouple viability measures and how they predict population persistence from the benefits conferred to populations through science‐based management. A primary goal of population management is to facilitate the persistence of priority species for longer than would be expected if no such management were implemented. Although current viability measures and future projections of viability are important tools for assessing the likelihood of population persistence, they are not indicators of which populations may most benefit from science‐based management. Here, we review the history and purpose of applying science‐based management to zoo and aquarium populations, describe measures of population viability and caution against confusing those measures of viability with population management goals or long‐term population sustainability, and clearly articulate the benefits conferred to zoo and aquarium populations by science‐based management.
Bayesian Interpretation of Regularization
Authors: Pillonetto Gianluigi , Chen Tianshi , Chiuso Alessandro , De Nicolao Giuseppe , Ljung Lennart
Published: May 2022

In the previous chapter, it has been shown that the regularization approach is particularly useful when information contained in the data is not sufficient to obtain a precise estimate of the unknown parameter vector and standard methods, such as least squares, yield poor solutions. The fact itself that an estimate is regarded as poor suggests the existence of some form of prior knowledge on the degree of acceptability of candidate solutions. It is this knowledge that guides the choice of the regularization penalty that is added as a corrective term to the usual sum of squared residuals. In the previous chapters, this design process has been described in a deterministic setting where only the measurement noises are random. In this chapter, we will see that an alternative formalization of prior information is obtained if a subjective/Bayesian estimation paradigm is adopted. The major difference is that the parameters, rather than being regarded as deterministic, are now treated as a random vector. This stochastic setting permits the definition of new powerful tools for both priors selection, e.g., through the maximum entropy principle, and for regularization parameters tuning, e.g., through the empirical Bayes approach and its connection with the concept of equivalent degrees of freedom.
A Pipeline for Automated Coordinate Assignment in Anatomically Accurate Biventricular Models
Authors: Pankewitz Lisa , Abdala Laryssa , Bussooa Aadarsh , Arevalo Hermenegild
Published: May 2022

There is an increased interest, in the field of cardiac modeling, for an improved coordinate system that can consistently describe local position within a heart geometry across various distinct geometries. A newly designed coordinate system, Cobiveco, meets these requirements. However, it assumes the use of biventricular models with a flat base, ignoring important cardiac structures. Therefore, we extended the scope of this state-of-the-art biventricular coordinate system to work with various heart geometries which include basal cardiac structures that were previously unaccounted for in Cobiveco. First, we implemented a semi-automated input surface assignment for increased accessibility and reproducibility of assigned coordinates. Then, we extended the coordinate system to handle more anatomically accurate biventricular models including the valve planes, which are of great interest when modeling diseases that manifest themselves in the basal area. Furthermore, we added the functionality of mapping vector data, such as myocardial fiber orientations, which are crucial for replicating the anisotropic electrical propagation in cardiac tissue.
3D Simulations of Fetal and Maternal Ventricular Excitation for Investigating the Abdominal ECG
Authors: Uv Julie Johanne , Myklebust Lena , Rudsari Hamid Khoshfekr , Welle Hannes , Arevalo Hermenegild
Published: May 2022

Congenital heart disease (CHD) is a leading cause of infant death. To diagnose CHD, recordings from abdominal fetal electrocardiograms (fECG) can be used as a non-invasive tool. However, it is challenging to extract the fetal signal from fECG recordings partly due to the lack of data combining fECG recordings with a ground truth for the fetal signal, which can be obtained by using a scalp electrode during delivery. In this study, we present a computational model of a pregnant female torso, in which we simulate fetal and maternal ventricular excitation during sinus rhythm to derive fECGs, so as to enable isolated measurement of the fetal and maternal signal contributions. To extract the fetal contribution from a combined signal, we apply an adaptive filtering algorithm to wavelet transformed signals. Further development of the model may enable improvements in the recording and processing capabilities for fECGs, the reliable estimation of fetal heart rates, and possibly interpretation of fetal signal morphologies that could improve the overall diagnostic significance of abdominal fECGs.
Ordinary Differential Equation-based Modeling of Cells in Human Cartilage
Authors: Yamamoto Kei , Fischer-Holzhausen Sophie , Fjeldstad Maria P , Maleckar Mary M
Published: May 2022

Chondrocytes produce the extracellular cartilage matrix required for smooth joint mobility. As cartilage is not vascularised, and chondrocytes are not innervated by the nervous system, chondrocytes are therefore generally considered non-excitable. However, chondrocytes do express a range of ion channels, ion pumps, and receptors involved in cell homeostasis and cartilage maintenance. Dysfunction in these ion channels and pumps has been linked to degenerative disorders such as arthritis. Because the electrophysiological properties of chondrocytes are difficult to measure experimentally, mathematical modelling can instead be used to investigate the regulation of ionic currents. Such models can provide insight into the finely tuned parameters underlying fluctuations in membrane potential and cell behaviour in healthy and pathological conditions. Here, we introduce an open-source, intuitive, and extendable mathematical model of chondrocyte electrophysiology, implementing key proteins involved in regulating the membrane potential. Because of the inherent biological variability of cells and their physiological ranges of ionic concentrations, we describe a population of models that provides a robust computational representation of the biological data. This permits parameter variability in a manner mimicking biological variation, and we present a selection of parameter sets that suitably represent experimental data. Our mathematical model can be used to efficiently investigate the ionic currents underlying chondrocyte behaviour.
Computational Prediction of Cardiac Electropharmacology - How Much Does the Model Matter?
Authors: Dawson John , Gams Anna , Rajen Ivan , Soltisz Andrew M , Edwards Andrew G
Published: May 2022

Animal data describing drug interactions in cardiac tissue are abundant, however, nuanced inter-species differences hamper the use of these data to predict drug responses in humans. There are many computational models of cardiomyocyte electrophysiology that facilitate this translation, yet it is unclear whether fundamental differences in their mathematical formalisms significantly impact their predictive power. A common solution to this problem is to perform inter-species translations within a collection of models with internally consistent formalisms, termed a “lineage”, but there has been little effort to translate outputs across lineages. Here, we translate model outputs between lineages from Simula and Washington University for models of ventricular cardiomyocyte electrophysiology of humans, canines, and guinea pigs. For each lineage-species combination, we generated a population of 1000 models by varying common parameters, namely ion conductances, according to a Guassian log-normal distribution with a mean at the parameter’s species-specific default value and standard deviation of 30%.We used partial least squares regression to translate the influences of one model to another using perturbations to calculated descriptors of resulting electrophysiological behavior derived from these parameter variations. Finally, we evaluated translation fidelity by performing a sensitivity analysis between input parameters and output descriptors, as similar sensitivities between models of a common species indicates similar biological mechanisms underlying model behavior. Successful translation between models, especially those from different lineages, will increase confidence in their predictive power.
Investigating the Multiscale Impact of Deoxyadenosine Triphosphate (dATP) on Pulmonary Arterial Hypertension (PAH) Induced Heart Failure
Authors: Garcia Kristen , Hock Marcus , Jaltare Vikrant , Uysalel Can , McCabe Kimberly J , Teitgen Abigail , Valdez-Jasso Daniela
Published: May 2022

2-deoxy-ATP (dATP) is a myosin activator known to improve cardiac contractile force [1]. In vitro studies have shown that dATP alters the calcium transient profile in addition to the kinetics of the cross-bridge cycle [2]. Furthermore, in vivo studies of transgenic mice with increased production of dATP show elevated left ventricular systolic function [3]. Pulmonary arterial hypertension (PAH) is a rare disease of the pulmonary vasculature in which pressure overload in the right ventricle results in reduced contractile function and right heart failure [4]. We hypothesize that dATP may have a therapeutic effect on PAH-induced heart failure, by improving contractile function and restoring cardiac output and ejection fraction. However, because the effects of dATP cannot easily be assessed experimentally, we propose using a computational multiscale modeling approach to predict cardiac function. By altering parameters in an existing multiscale biventricular cardiac model [5], we were able to reproduce end-systolic and end-diastolic pressures and volumes that reflect the PAH condition, as well as healthy hearts. dATP was simulated by adjusting parameters in the model at the molecular and cellular levels based on experimental data [1], allowing us to predict the effects of dATP on PAH at the organ level. Our results show that the molecular effects of dATP can increase cardiac output and restore ejection fraction in PAH conditions, though at the cost of elevated mean arterial pressure, and may provide a new approach to treating this disease. Our multiscale modeling approach paves the way for further studies mapping out cardiovascular mechanics. As novel therapeutics continue to be discovered, their application and mechanism can be further explored through these computational models.
Identifying Ionic Channel Block in a Virtual Cardiomyocyte Population Using Machine Learning Classifiers
Authors: Singstad Bjørn Jostein , Dalen Bendik Steinsvåg , Sihra Sandhya , Forsch Nickolas , Wall Samuel
Published: May 2022

Immature cardiomyocytes, such as those obtained by stem cell differentiation, have been shown to be useful alternatives to mature cardiomyocytes, which are limited in availability and difficult to obtain, for evaluating the behaviour of drugs for treating arrhythmia. In silico models of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) can be used to simulate the behaviour of the transmembrane potential and cytosolic calcium under drug-treated conditions. Simulating the change in action potentials due to various ionic current blocks enables the approximation of drug behaviour. We used eight machine learning classification models to predict partial block of seven possible ion currents $$ (\textit{I}_{\textit{CaL}},\textit{I}_{\textit{Kr}},\textit{I}_{\textit{to}},\textit{I}_{\textit{K1}},\textit{I}_{\textit{Na}},\textit{I}_{\textit{NaL}} and \textit{I}_{\textit{Ks}}) $$ in a simulated dataset containing nearly 4600 action potentials represented as a paired measure of transmembrane potential and cytosolic calcium. Each action potential was generated under 1 $$ \textit{H}_{\textit{z}} $$ pacing. The Convolutional Neural Network outperformed the other models with an average accuracy of predicting partial ionic current block of 93% in noise-free data and 72% accuracy with 3% added random noise. Our results show that $$ \textit{I}_{\textit{CaL}} $$ and $$ \textit{I}_{\textit{Kr}} $$ current block were classified with high accuracy with and without noise. The classification of $$ \textit{I}_{\textit{to}} $$ , $$ \textit{I}_{\textit{K1}} $$ and $$ \textit{I}_{\textit{Na}} $$ current block showed high accuracy at 0% noise, but showed a significant decrease in accuracy when noise was added. Finally, the accuracy of $$ \textit{I}_{\textit{NaL}} $$ and $$ \textit{I}_{\textit{Ks}} $$ classification were relatively lower than the other current blocks at 0% noise and also showed a significant drop in accuracy when noise was added. In conclusion, these machine learning methods may present a pathway for estimating drug response in adult phenotype cardiac systems, but the data must be sufficiently filtered to remove noise before being used with classifier algorithms.
Finanzierungs- und Organisationsmodelle zur Sicherung gesellschaftlicher Dienste im Quartier
Authors: Dahlbeck Elke , Jochimsen Kerstin , Esch Dajana
Published: May 2022

Das Wegbrechen gesellschaftlicher Dienste in Quartieren, Neben- und Ortszentren bedingt Versorgungslücken und den Funktionsverlust als Ort sozialer Integration. Ihr Erhalt und Aufbau erfordern neue Dienstleistungsarrangements verschiedener gesellschaftlicher Akteure und neue Finanzierungsmodelle. Neben klassischen Förderinstrumenten können mit alternativen Finanzierungsmodellen weniger rentierliche Vorhaben gesellschaftlicher Dienste umgesetzt werden. Kommunen können diese Vorhaben initiieren, begleiten, aber müssen diese dort, wo notwendig, auch ggf. dauerhaft übernehmen.
Potenziale der Stadtaneignungskultur für eine gemeinsame Quartiersentwicklung
Authors: Esch Dajana , Brückner Felix
Published: May 2022

Heterogene Akteurslandschaften prägen ein dynamisches und diversifiziertes Geschehen in der Quartiersentwicklung: Neben kommunalen Akteur*innen und „klassischem“ Bürger*innenengagement ist zunehmend auch eine Form von zivilgesellschaftlichem Engagement zu erkennen, in Zuge dessen sich die aktiven Personen unmittelbar Stadt(räume) aneignen. Vor dem Hintergrund zahlreicher Herausforderungen gilt es, diese parallel verlaufenden Anstrengungen für und im Quartier – zum einen Maßnahmen, die von öffentlicher Seite auf den Weg gebracht werden, zum anderen Bürger*innen, die ihr Quartier eigenständig aktiv gestalten – zusammenzuführen, um Potenziale zu heben und Synergien zu nutzen.
Koproduktion Grüner Infrastruktur: Erfahrungen aus dem Grünzug Östliches Emschertal
Authors: Timpe Axel , Christenn Katharina
Published: May 2022

Lebensmittelproduktion, Ökosystemleistungen, Freizeitangebot – Grünzüge sind Lebensgrundlage, Erholungsraum und Grüne Infrastruktur. Sie stellen ein wertvolles Gemeinschaftsgut dar, stehen aber durch angespannte kommunale Haushalte sowie durch soziale und demografische Transformation vor Herausforderungen. Um Grünzüge zu sichern und zu gestalten, sind Kommunen auf die Zusammenarbeit mit der lokalen Wirtschaft, insbesondere der Landwirtschaft als wichtigstem Landnutzer, und der zivilgesellschaftlich organisierten Bürgerschaft angewiesen. Koproduktion überwindet die klassische Arbeitsteilung zwischen Produzierenden und Konsumierenden: Beide arbeiten gemeinsam an der Herstellung und der Nutzung Grüner Infrastruktur. Das Forschungsprojekt CoProGrün hat am Beispiel des Grünzugs Östliches Emschertal untersucht, wie Grüne Infrastruktur durch die Einbindung dieser Akteure nachhaltig ausgerichtet, langfristig gesichert und attraktiv gestaltet werden kann.
Bürger- und Akteursbeteiligung im ländlichen Raum
Authors: Knobloch Vanessa
Published: May 2022

Mobilitäts- und Nahversorgungsvorhaben im ländlichen Raum verfolgen das Ziel, die Teilhabe der Bevölkerung am täglichen Leben zu verbessern. An solchen Vorhaben können verschiedenste Akteure beteiligt sein. Dieser Beitrag reflektiert Formate der Bürger- und Akteursbeteiligung, die im Projekt iMONA erprobt wurden. Ziel des Projekts war es, Lösungsansätze für alternative Mobilitäts- und Nahversorgungslösungen mit den Anforderungen der Bürger*innen abzustimmen sowie politische und fachliche Akteure mitverantwortlich in das Vorhaben einzubinden.
Aktivierung endogener und exogener Potenziale – Erkenntnisse und Erfahrungen aus einem Beteiligungsprozess
Authors: Schäfer Ernst , Scheele Ulrich
Published: May 2022

Das im Rahmen des Kommunen-Innovativ-Programms geförderte Verbundvorhaben „Wat nu?“ befasst sich am Beispiel von ausgewählten niedersächsischen Kommunen mit der Frage, wie das bei den lokalen Akteuren und in den diversen Netzwerken vorhandene System- und Transformationswissen genutzt werden kann, um in einem kollaborativen Prozess adäquate Handlungsoptionen im Umgang mit den Folgen des demografischen Wandels zu entwickeln und zu erproben. Das Vorhaben greift dabei auf den Ansatz des Reallabors zurück, in dem unterschiedliche Akteure aus dem wirtschaftlichen, wissenschaftlichen und politisch-zivilgesellschaftlichen Bereich mit Bürger*innen zusammenarbeiten und nach Lösungen suchen. Im vorliegenden Beitrag werden die unterschiedlichen partizipativen Methoden beschrieben, mit denen das endogene und exogene Potenzial der Region aktiviert werden kann.
Offene Daten und offene Verwaltungsdaten – Öffnung von Datenbeständen
Authors: von Lucke Jörn , Gollasch Katja
Published: May 2022

Offene Daten und insbesondere offene Verwaltungsdaten bilden für gelebte Transparenz in Politik und Verwaltung eine wesentliche Grundlage. Im dritten Abschnitt werden daher Begriffsabgrenzungen vorgenommen und Anwendungsgebiete vorgestellt. Im Fokus stehen dabei große Datenbestände, Datenräume, Datenkataloge und Datenportale des öffentlichen Sektors. Ergänzend werden die Potenziale von datenwissenschaftlichen Erkenntnissen vorgestellt.
Bürgerbeteiligung 2.0
Authors: von Lucke Jörn , Gollasch Katja
Published: May 2022

Bürger stellen in einem offenem Regierungs- und Verwaltungshandeln wesentliche Akteure dar. In diesem Abschnitt wird thematisiert, wie die Einbindung der Zivilgesellschaft auch durch digitale Ansätze gelingen kann. Ausgehend von der theoretischen Annäherung an die Entscheidungsfindung von Politik und Verwaltung werden verschiedene Formen politischer Partizipation vorgestellt und auf Ansätze wie E-Partizipation, Bürgerbeteiligung in Echtzeit sowie durch die Unterstützung von künstlicher Intelligenz eingegangen.
Aktivitäten Deutschlands in der Open Government Partnership
Authors: von Lucke Jörn , Gollasch Katja
Published: May 2022

Wie wird Open Government eigentlich auf internationaler Ebene angegangen? Ein wesentlicher Akteur ist hier die Open Government Partnership (OGP). Diese Organisation hat es sich zum Ziel gesetzt, Vorhaben im Bereich des offenen Regierungs- und Verwaltungshandelns weltweit zu fördern und sichtbar zu machen. Die mittlerweile 78 Mitgliedsstaaten erstellen dafür in zweijährigen Zyklen nationale Aktionspläne (NAP) mit konkreten Selbstverpflichtungen. Deutschland ist seit 2016 Mitglied der Partnerschaft und hat bereits drei NAP erfolgreich auf den Weg gebracht. Das folgende Kapitel stellt die Open Government Partnership vor und gibt einen Einblick in das Engagement Deutschlands im Rahmen der OGP.
WNT and NOTCH signaling in human trophoblast development and differentiation
Authors: Dietrich Bianca , Haider Sandra , Meinhardt Gudrun , Pollheimer Jürgen , Knöfler Martin
Published: May 2022

Correct development of the human placenta and its differentiated epithelial cells, syncytial trophoblasts (STBs) and extravillous trophoblasts (EVTs), is crucial for a successful pregnancy outcome. STBs develop by cell fusion of mononuclear cytotrophoblasts (CTBs) in placental floating villi, whereas migratory EVTs originate from specialized villi anchoring to the maternal decidua. Defects in trophoblast differentiation have been associated with severe pregnancy disorders such as early-onset preeclampsia and fetal growth restriction. However, the evolutionary pathways underlying normal and adverse placentation are poorly understood. Herein, we discuss Wingless (WNT) and NOTCH signaling, two pathways that play pivotal roles in human placenta and trophoblast development. Whereas WNT is necessary for expansion of trophoblast progenitors and stem cells, NOTCH1 is required for proliferation and survival of EVT precursors. Differentiation of the latter is orchestrated by a switch in NOTCH receptor expression as well as by changes in WNT ligands and their downstream effectors.
Lieb–Thirring Estimates for Singular Measures
Authors: Rozenblum Grigori
Published: May 2022

We establish Lieb–Thirring type estimates for the Schrödinger operator with a singular measure serving as potential.
Oligometastasis in breast cancer—current status and treatment options from a radiation oncology perspective
Authors: Piroth Marc D. , Krug David , Feyer Petra , Baumann René , Combs Stephanie , Duma Marciana-Nona , Dunst Jürgen , Fastner Gerd , Fietkau Rainer , Guckenberger Matthias , Haase Wulf , Harms Wolfgang , Hehr Thomas , Sedlmayer Felix , Souchon Rainer , Strnad V. , Budach Wilfried
Published: May 2022

Evidence from a few small randomized trials and retrospective cohorts mostly including various tumor entities indicates a prolongation of disease free survival (DFS) and overall survival (OS) from local ablative therapies in oligometastatic disease (OMD). However, it is still unclear which patients benefit most from this approach. We give an overview of the several aspects of stereotactic body radiotherapy (SBRT) in extracranial OMD in breast cancer from a radiation oncology perspective. A PubMed search referring to this was conducted. An attempt was made to relate the therapeutic efficacy of SBRT to various prognostic factors. Data from approximately 500 breast cancer patients treated with SBRT for OMD in mostly in small cohort studies have been published, consistently indicating high local tumor control rates and favorable progression-free (PFS) and overall survival (OS). Predictors for a good prognosis after SBRT are favorable biological subtype (hormone receptor positive, HER2 negative), solitary metastasis, bone-only metastasis, and long metastasis-free interval. However, definitive proof that SBRT in OMD breast cancer prolongs DFS or OS is lacking, since, with the exception of one small randomized trial (n = 22 in the SBRT arm), none of the cohort studies had an adequate control group. Further studies are needed to prove the benefit of SBRT in OMD breast cancer and to define adequate selection criteria. Currently, the use of local ablative SBRT should always be discussed in a multidisciplinary tumor board.
A Note on Perfect Correctness by Derandomization
Authors: Bitansky Nir , Vaikuntanathan Vinod
Published: May 2022

We show a general compiler that transforms a large class of erroneous cryptographic schemes (such as public-key encryption, indistinguishability obfuscation, and secure multiparty computation schemes) into perfectly correct ones. The transformation works for schemes that arecorrect on all inputs with probability noticeably larger than half, and are secure under parallel repetition. We assume the existence of one-way functions and of functions with deterministic (uniform) time complexity$$2^{O(n)}$$2O(n)and non-deterministic circuit complexity$$2^{\Omega (n)}$$2Ω(n). Our transformation complements previous results that showed how public-key encryption and indistinguishability obfuscation that err on a noticeable fraction of inputs can be turned into ones thatfor all inputsare often correct, showing that they can be made perfectly correct. The technique relies on the idea of “reverse randomization” [Naor, Crypto 1989] and on Nisan–Wigderson style derandomization, previously used in cryptography to remove interaction from witness-indistinguishable proofs and commitment schemes [Barak, Ong and Vadhan, Crypto 2003].
Determination of trace elements in placenta by total reflection X-ray fluorescence spectrometry: effects of sampling and sample preparation
Authors: Hauser Sebastian , Andres Sophia , Leopold Kerstin
Published: May 2022

Placental elemental composition can serve as an indicator for neonatal health. Medical studies aiming at revealing such cause-and-effect relationships or studies monitoring potential environmental influences consist of large sample series to ensure statistically sufficient data. Several analytical techniques have been used to study trace metals in human placenta. However, most techniques require provision of clear liquid sample solutions and therefore time- and reagent-consuming total digestion of biological tissue is necessary. In total reflection X-ray fluorescence spectrometry (TXRF)—a straightforward multielement analytical technique—in contrast suspensions of minute sample amounts can be analyzed directly. Therefore, herein we report on a valid method to prepare homogenous sample suspensions for sustainable and fast TXRF analysis of large sample series. The optimized method requires only 10 mg of powdered placental tissue and 1 mL nitric acid. Suspensions are readily prepared within 30 min and the found mass fractions of major, minor, and trace elements are in good agreement in comparison to analysis of digests. In addition, possible effects on fixation time and the exact sampling location, i.e., maternal vs. fetal side of the placenta, were studied applying this method. Thereby, significant differences for fetal placenta tissue compared to maternal or intermediate tissue were observed revealing accumulation of trace elements in the fetal side of the placenta. Furthermore, considerable depletion of up to 60% mass fraction with longer fixation duration occurred in particular in fetal placenta tissue. These findings help to understand the large ranges of mass fraction of elements in placenta reported in the literature and at the same time indicate the necessity for more systematic investigation of non-homogenous elements distributed in placenta taking sampling and stabilization methods into account.

Graphical Abstract
The Thermodynamic Stability of Membrane Proteins in Micelles and Lipid Bilayers Investigated with the Ferrichrom Receptor FhuA
Authors: Pocanschi Cosmin L. , Kleinschmidt Jörg H.
Published: May 2022

Extraction of integral membrane proteins into detergents for structural and functional studies often leads to a strong loss in protein stability. The impact of the lipid bilayer on the thermodynamic stability of an integral membrane protein in comparison to its solubilized form in detergent was examined and compared for FhuA from Escherichia coli and for a mutant, FhuAΔ5-160, lacking the N-terminal cork domain. Urea-induced unfolding was monitored by fluorescence spectroscopy to determine the effective free energies $$ \Delta G{^\text{o}_{\rm u}} $$

Δ
G

u
o

of unfolding. To obtain enthalpic and entropic contributions of unfolding of FhuA, $$ \Delta G{^\text{o}_{\rm u}} $$

Δ
G

u
o

﻿were determined at various temperatures. When solubilized in LDAO detergent, wt-FhuA and FhuAΔ5-160 unfolded in a single step. The 155-residue cork domain stabilized wt-FhuA by $$ \Delta\Delta G{^\text{o}_{\rm u}} $$

Δ
Δ
G

u
o

﻿~ 40 kJ/mol. Reconstituted into lipid bilayers, wt-FhuA unfolded in two steps, while FhuAΔ5-160 unfolded in a single step, indicating an uncoupled unfolding of the cork domain. For FhuAΔ5-160 at 35 °C, $$ \Delta G{^\text{o}_{\rm u}} $$

Δ
G

u
o

increased from ~ 5 kJ/mol in LDAO micelles to about ~ 20 kJ/mol in lipid bilayers, while the temperature of unfolding increased from TM ~ 49 °C in LDAO micelles to TM ~ 75 °C in lipid bilayers. Enthalpies $$\Delta H{_{\rm M}^\text{o}}$$

Δ
H

M

o

﻿were much larger than free energies $$ \Delta G{^\text{o}_{\rm u}} $$

Δ
G

u
o

﻿, for FhuAΔ5-160 and for wt-FhuA, and compensated by a large gain of entropy upon unfolding. The gain in conformational entropy is expected to be similar for unfolding of FhuA from micelles or bilayers. The strongly increased TM and $$\Delta H{_{\rm M}^\text{o}}$$

Δ
H

M

o

observed for the lipid bilayer-reconstituted FhuA in comparison to the LDAO-solubilized forms, therefore, very likely arise from a much-increased solvation entropy of FhuA in bilayers.

Graphical abstract
Comparison of the Analgesic Efficacy of Opioid‐Sparing Multimodal Analgesia and Morphine‐Based Patient‐Controlled Analgesia in Minimally Invasive Surgery for Colorectal Cancer
Authors: Yeo Jinseok , Park Jun Seok , Choi Gyu‐Seog , Kim Hye Jin , Kim Jay Kyoung , Oh Jinyoung , Park Soo Yeun
Published: May 2022

Background

A multimodal analgesia (MMA) protocol has shown the effect of postoperative pain control and reduced the postoperative opioid consumption. However, it was questionable whether MMA could replace opioid‐based patient‐controlled analgesia (PCA) for postoperative pain control. Therefore, this study aimed to investigate whether an MMA protocol is non‐inferior to opioid‐based PCA for pain management after a minimally invasive colorectal cancer surgery.

Methods

A randomized, open‐label, non‐inferiority clinical trial was conducted on patients undergoing laparoscopic or robotic resection of colorectal cancer. The patients were randomly assigned to either the PCA or MMA group. The MMA protocol included pregabalin, tramadol, wound infiltration, and transversus abdominis plane block. The primary outcome was the numeric rating scale (NRS) score for pain at rest 24 h postoperatively.

Results

Ninety‐seven patients were included in the intention‐to‐treat analysis. The mean difference in NRS score at rest at 24 h was 0.25 (95% confidence interval, − 0.61 to 1.11). This result demonstrated the non‐inferiority of MMA to PCA in our non‐inferiority margin (− 1). Compared with the PCA group, the median remifentanil dose (996 vs. 654 μg; p < 0.001) and time in the post‐anesthesia care unit (35 vs. 25 min; p < 0.001) were significantly less in the MMA group.

Conclusions

Our MMA protocol successfully controlled postoperative pain and was non‐inferior to morphine‐based PCA based on patient‐reported pain intensity, with no significant increase in adverse events. These results will help construct a strategy to reduce conventional opioid prescriptions for pain management after a minimally invasive colorectal cancer surgery.

Trial Registration Number Trial Registration Clinical Research Information Service Identifier: KCT0002593
Efficacy of sirolimus in children with lymphatic malformations of the head and neck
Authors: Wiegand S. , Dietz A. , Wichmann G.
Published: May 2022

Purpose

Children with extensive lymphatic malformations of the head and neck often suffer from functional impairment and aesthetic deformity which significantly affect the quality of life and may be life-threatening. Treatment with sirolimus has the potential to improve symptoms and downsize lymphatic malformations. This systematic review summarizes the current information about sirolimus treatment of lymphatic malformations of the head and neck in children, its efficacy and side effects.

Methods

A systematic search of the literature regarding studies on sirolimus treatment of children with lymphatic malformations of the head and neck was performed in PubMed, Embase, and Google Scholar up to July 2021 with the search terms “lymphatic malformation”, “lymphangioma”, “cystic hygroma”, “low-flow malformation”, “sirolimus”, “rapamycin”, “mTOR inhibitor” and “children”.

Results

In all, 28 studies including 105 children from newborn to 17 years treated with sirolimus for lymphatic malformations of the head and neck were analyzed. The most frequent initial dose was 0.8 mg/m2 per dose, twice daily at 12-h interval. The target blood level differed between studies, 10–15 ng/mL and 5–15 ng/mL were most often used. More than 91% of the children responded to sirolimus treatment which lasts from 6 months to 4 years. Typical side effects were hyperlipidemia, neutropenia and infections.

Methods

Sirolimus could be an effective treatment for children with large complicated lymphatic malformations of the head and neck. As not all patients will benefit from treatment, the decision to treat sirolimus should be made by a multidisciplinary team.
nAMD: optimization of patient care and patient-oriented information with the help of an internet-based survey
Authors: Schmid Anke , Bucher Felicitas , Liczenczias Erika , Maslanka Figueroa Sara , Müller Bettina , Agostini Hansjürgen
Published: May 2022

Purpose

This survey was conducted to identify factors that influence how patients with neovascular age-related macular degeneration (nAMD) deal with their disease and information that are considered useful from a patient’s point of view.

Methods

A total of 5035 patients with nAMD living in Germany were interviewed via internet-based cross-sectional survey, where the following information was collected: personal data, disease awareness, and patients’ needs. In addition, a Quality of Life questionnaire (SF-12v2) could be completed.

Results

Out of the 5035 participants, more males than females participated (55% vs 45%), and most participants were in the age groups 76 to 85 years (37%) and 66 to 75 years (35%). Seventy-three percent of patients rated their understanding of the disease as at least sufficient, and more than two-thirds of the patients (68%) were aware that their disease needs to be controlled on a regular basis and treated on an “as needed” basis. Regarding potential risk factors for AMD, most participants were aware of age (89%), but only 39% of hereditary load and 33% of smoking as evidence-based risk factors, indicating a need for further information. The doctor remains the major source of information (93%), with internet (29%), brochures (14%), opticians (13%), or patient support groups (4%) with only limited contribution. Distance to the treatment center was identified as one of the factors, which had the greatest influence on patients’ compliance. A “treat as needed” regime turned out to be the preferred control and treatment schedule in contrast to a “fixed appointment” every 4 weeks.

Conclusion

This internet-based survey appears to be representative for nAMD patients. To increase patients’ compliance, proximity to the treatment center and a “treat as needed” regime turned out to be important factors as well as patients’ awareness of their disease. In this regard, the reported desire for more information indicates that patients’ knowledge still needs to be improved. Our results will help to further optimize patient care and patient-oriented information.
Two adjacent phosphorylation sites in the C-terminus of the channel’s α-subunit have opposing effects on epithelial sodium channel (ENaC) activity
Authors: Diakov Alexei , Nesterov Viatcheslav , Dahlmann Anke , Korbmacher Christoph
Published: May 2022

How phosphorylation of the epithelial sodium channel (ENaC) contributes to its regulation is incompletely understood. Previously, we demonstrated that in outside-out patches ENaC activation by serum- and glucocorticoid-inducible kinase isoform 1 (SGK1) was abolished by mutating a serine residue in a putative SGK1 consensus motif RXRXX(S/T) in the channel’s α-subunit (S621 in rat). Interestingly, this serine residue is followed by a highly conserved proline residue rather than by a hydrophobic amino acid thought to be required for a functional SGK1 consensus motif according to invitro data. This suggests that this serine residue is a potential phosphorylation site for the dual-specificity tyrosine phosphorylated and regulated kinase 2 (DYRK2), a prototypical proline-directed kinase. Its phosphorylation may prime a highly conserved preceding serine residue (S617 in rat) to be phosphorylated by glycogen synthase kinase 3 β (GSK3β). Therefore, we investigated the effect of DYRK2 on ENaC activity in outside-out patches of Xenopus laevis oocytes heterologously expressing rat ENaC. DYRK2 included in the pipette solution significantly increased ENaC activity. In contrast, GSK3β had an inhibitory effect. Replacing S621 in αENaC with alanine (S621A) abolished the effects of both kinases. A S617A mutation reduced the inhibitory effect of GKS3β but did not prevent ENaC activation by DYRK2. Our findings suggest that phosphorylation of S621 activates ENaC and primes S617 for subsequent phosphorylation by GSK3β resulting in channel inhibition. In proof-of-concept experiments, we demonstrated that DYRK2 can also stimulate ENaC currents in microdissected mouse distal nephron, whereas GSK3β inhibits the currents.
Application of Ultrasonography in Neurogenic Dysphagia: A Systematic Review
Authors: Potente Paola , Buoite Stella Alex , Vidotto Monica , Passerini Michelle , Furlanis Giovanni , Naccarato Marcello , Manganotti Paolo
Published: May 2022

Swallowing disorders are common in neurological diseases, with dysphagia representing one of the most prevalent complications that may cause poor quality of life, reduce independence, and increase mortality. Rapid identification of dysphagia is necessary to reduce the risk of penetration and aspiration, and to early start rehabilitation protocols. Among the methods that can be used to evaluate dysphagia and its components, ultrasound imaging has been suggested to support the evaluation of dysphagia by providing measures of both static and dynamic anatomical components. The aim of this systematic review is to evaluate the usefulness of ultrasonography in neurogenic dysphagia according to current literature. From 2000 to 2020, 633 studies with the appropriate search terms for ultrasound and dysphagia were identified. After screening them, 10 studies were included in the qualitative analysis. Patients with the following neurologic conditions were studied with ultrasonography for dysphagia: Parkinson’s disease, muscle dystrophy, amyotrophic lateral sclerosis, and stroke. The main outcomes of ultrasonography were swallowing muscles thickness (e.g., tongue), and dynamic measures such as hyoid displacement. The different protocols used in the studies, as well as their outcomes, did not allow to provide standard procedures and normative or cut-off values in the presented diseases. Because there are a variety of tools, methods, and techniques that have been used in the studies that were reviewed, it is difficult to evaluate them using established standards. However, ultrasonography correlates well with clinical evaluation of dysphagia and therefore has prognostic and rehabilitation potential. Future studies should aim to develop and utilize a common interdisciplinary protocol that includes standard procedures and outcomes to define normative values applicable in the different conditions.
Climacteric symptoms in postoperative patients among endometrial cancer, cervical cancer, and ovarian cancer: a cross-sectional study
Authors: Horiba Yuko , Yoshino Tetsuhiro , Yokota Megumi , Iwata Takashi , Watanabe Kenji , Mimura Masaru , Aoki Daisuke
Published: May 2022

Purpose

To date, no studies have assessed climacteric symptoms after hystero-adnexectomy for endometrial, cervical, or ovarian cancer. Thus, this study aimed to compare climacteric symptoms among patients who underwent surgery for these three cancer types.

Methods

In this cross-sectional study, we interviewed patients who were registered at a menopausal outpatient clinic between January 1999 and July 2016 after undergoing total hysterectomy, intrapelvic only or intrapelvic plus para-aortic lymph node dissection, and bilateral adnexectomy performed via laparotomy as a cancer treatment. Climacteric symptoms were assessed using a patient-reported questionnaire covering core domains with five symptoms only at the initial consultation. Each symptom was graded from 0 (no symptoms) to 3 (severe symptoms). We evaluated the frequency of symptom severity according to the time elapsed since surgery and the cancer type.

Results

The numbers of patients with endometrial, ovarian, and cervical cancer were 328, 90, and 107, respectively. Overall, climacteric symptoms were more severe in patients with cervical cancer than in those with endometrial or ovarian cancer; symptom severity decreased with increasing time since surgery. However, symptom severity did not decrease significantly over time in patients with cervical cancer even after > 5 years had elapsed since surgery.

Conclusion

The climacteric symptoms were less severe in patients with endometrial or ovarian cancer with longer time elapsed since surgery but not in those with cervical cancer. Patients with cervical cancer may require more prompt interventions, including symptomatic treatment and longer follow-up period, than those with endometrial or ovarian cancer.
GRaNN: feature selection with golden ratio-aided neural network for emotion, gender and speaker identification from voice signals
Authors: Garain Avishek , Ray Biswarup , Giampaolo Fabio , Velasquez Juan D. , Singh Pawan Kumar , Sarkar Ram
Published: May 2022

Compared to other features of the human body, voice is quite complex and dynamic, in a sense that a speech can be spoken in various languages with different accents and in different emotional states. Recognizing the gender, i.e. male or female from the voice of an individual, is by all accounts a minor errand for human beings. Similar goes for speaker identification if we are well accustomed with the speaker for a long time. Our ears function as the front end, accepting the sound signs which our cerebrum processes and settles on our disposition. Although being trivial for us, it becomes a challenging task to mimic for any computing device. Automatic gender, emotion and speaker identification systems have many applications in surveillance, multimedia technology, robotics and social media. In this paper, we propose a Golden Ratio-aided Neural Network (GRaNN) architecture for the said purposes. As deciding the number of units for each layer in deep NN is a challenging issue, we have done this using the concept of Golden Ratio. Prior to that, an optimal subset of features are selected from the feature vector extracted, common for all three tasks, from spectral images obtained from the input voice signals. We have used a wrapper-filter framework where minimum redundancy maximum relevance selected features are fed to Mayfly algorithm combined with adaptive beta hill climbing (A$$\beta$$
β
HC) algorithm. Our model achieves accuracies of 99.306% and 95.68% for gender identification in RAVDESS and Voice Gender datasets, 95.27% for emotion identification in RAVDESS dataset and 67.172% for speaker identification in RAVDESS dataset. Performance comparison of this model with existing models on the publicly available datasets confirms its superiority over those models. Results also ensure that we have chosen the common feature set meticulously, which works equally well on three different pattern classification tasks. The proposed wrapper-filter framework reduces the feature dimension significantly, thereby lessening the storage requirement and training time. Finally, strategically selecting the number units in each layer in NN help increases the overall performance of all three pattern classification tasks.
Prevalence of incidental intracranial findings on magnetic resonance imaging: a systematic review and meta-analysis
Authors: Sunny Divya Elizabeth , Amoo Michael , Al Breiki Maryam , Teng Elite Dong Wen , Henry Jack , Javadpour Mohsen
Published: May 2022

Background

As the volume and fidelity of magnetic resonance imaging (MRI) of the brain increase, observation of incidental findings may also increase. We performed a systematic review and meta-analysis to determine the prevalence of various incidental findings.

Methods

PubMed/MEDLINE, EMBASE and SCOPUS were searched from inception to May 24, 2021. We identified 6536 citations and included 35 reports of 34 studies, comprising 40,777 participants. A meta-analysis of proportions was performed, and age-stratified estimates for each finding were derived from age-adjusted non-linear models.

Results

Vascular abnormalities were observed in 423/35,706 participants (9.1/1000 scans, 95%CI 5.2–14.2), ranging from 2/1000 scans (95%CI 0–7) in 1-year-olds to 16/1000 scans (95%CI 1–43) in 80-year-olds. Of these, 204/34,306 were aneurysms (3.1/1000 scans, 95%CI 1–6.3), which ranged from 0/1000 scans (95%CI 0–5) at 1 year of age to 6/1000 scans (95%CI 3–9) at 60 years. Neoplastic abnormalities were observed in 456/39,040 participants (11.9/1000 scans, 95%CI 7.5–17.2), ranging from 0.2/1000 scans (95%CI 0–10) in 1-year-olds to 34/1000 scans (95%CI 12–66) in 80-year-olds. Meningiomas were the most common, in 246/38,076 participants (5.3/1000 scans, 95%CI 2.3–9.5), ranging from 0/1000 scans (95%CI 0–2) in 1-year-olds to 17/1000 scans (95%CI 4–37) in 80-year-olds. Chiari malformations were observed in 109/27,408 participants (3.7/1000 scans, 95%CI 1.8–6.3), pineal cysts in 1176/32,170 (9/1000 scans, 95%CI 1.8–21.4) and arachnoid cysts in 414/36,367 (8.5/1000 scans, 95%CI 5.8–11.8).

Conclusion

Incidental findings are common on brain MRI and may result in substantial resource expenditure and patient anxiety but are often of little clinical significance.
Numerical simulation of aquifer thermal energy storage using surface-based geologic modelling and dynamic mesh optimisation
Authors: Regnier G. , Salinas P. , Jacquemyn C. , Jackson M. D.
Published: May 2022

Aquifer thermal energy storage (ATES) has significant potential to provide largescale seasonal cooling and heating in the built environment, offering a low-carbon alternative to fossil fuels. To deliver safe and sustainable ATES deployments, accurate numerical modelling tools must be used to predict flow and heat transport in the targeted aquifers. This paper presents a simulation methodology for ATES based on surface-based geologic modelling (SBGM) and dynamic mesh optimisation (DMO). DMO has been previously applied in other fields of computational fluid dynamics to reduce the cost of numerical simulations. DMO allows the resolution of the mesh to vary during a simulation to satisfy a user-defined solution precision for selected fields, refining where the solution fields are complex and coarsening elsewhere. SBGM allows accurate representation of complex geological heterogeneity and efficient application of DMO. The paper reports the first systematic convergence study for ATES simulations, and demonstrates the application of these methods in two ATES scenarios: a homogeneous aquifer, and a realistic heterogeneous fluvial aquifer containing meandering, channelised sand bodies separated by mudstones. It is demonstrated that DMO reduces the required number of mesh elements by a factor of up to 22 and simulation time by a factor of up to 15, whilst maintaining the same accuracy as an equivalent fixed mesh. DMO offers significant potential to reduce the computational cost of ATES simulations in both homogeneous and heterogeneous aquifers.