bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coronavirus disease 2019 gastrointestinal and liver manifestations in adults: A review
Authors: Sirinawasatien Apichet , Chantarojanasiri Tanyaporn , Ekpanyapong Sirina , Tivatunsakul Naris , Luvira Viravarn 
Published: October 2021

AbstractCoronavirus disease 2019 (COVID‐19) is an important health problem that has a serious adverse impact on the global economy and healthcare systems. The virus is not only involved in the respiratory system, but also causes other systemic effects as well as several gastrointestinal and liver issues. Evidence has shown direct viral invasion into the gastrointestinal tissue and supporting vascular network, causing various manifestations such as diarrhea, nausea, gastrointestinal bleeding, and abnormal liver function tests. The degree of gastrointestinal injury, especially in terms of liver involvement, is correlated with disease severity. There is no specific treatment for gastrointestinal involvement, and the symptoms can be managed with supportive therapy. Moreover, increased liver decompensation and mortality can be found in COVID‐19‐infected patients with coexisting liver disease. As the virus can be identified in gastrointestinal contents, endoscopic procedures during the pandemic should be carefully selected and proper protection strategies should be encouraged to prevent viral transmission.
Adsorption isotherm, kinetics, and thermodynamic studies of O,O‐diethyl‐O‐(3,5,6‐trichloropyridin‐2‐yl) phosphorothioate (chlorpyrifos) on cinnamon verum–based activated carbon
Authors: Naser Ettish Mohamed , Abuzalat Osama , Wong Danny , El‐Sayyad Gharieb S. , Elsayed Mohamed A. 
Published: October 2021

AbstractCinnamon verum was used as a low‐cost precursor to produce microporous‐activated carbons with a high surface area (894 m2/g) and large total pore volume (0.49 cm3/g). Thermogravimetric analysis scanning electron microscopy, Fourier‐transform infrared spectroscopy, Brunauer–Emmett–Teller surface area, and pore size analyzer techniques were used to characterize the new sorbent. The new porous carbon's ability to remove chlorpyrifos (CPS), an organo‐phosphorus surrogate of ware gases and the active component in most insecticides and pesticides, has been assessed by a batch adsorption procedure. Different sorption factors such as initial CPS concentrations, contact time, pH, solution temperature, and sorbent dosage have been studied. The results show that the new sorbent could remove 100% of CPS at low concentrations of 20 ppm within 20 min of contact time under a favorable sorption process. CPS adsorption was found to be exothermic, and the adsorption capacity decreases with increasing temperature. Equilibrium results were modeled using three isotherm models: Langmuir, Freundlich, and Temkin. The Langmuir isotherm model was found to be the best model to represent the CPS adsorption data. The kinetic results were fitted to pseudo–first‐order, pseudo–second‐order, and intraparticle diffusion models and thoroughly followed the pseudo–second‐order kinetic model. Thermodynamic factors such as enthalpy (ΔHo), entropy (ΔSo), and free energy (ΔGo) were assessed. The negative values of ΔHo and ΔGo indicate the exothermic and spontaneous nature of the adsorption process. The sorbent from waste cinnamon bark was economically practical and eliminates organophosphorus compounds from aqueous solutions.
Eye‐of‐the‐Tiger Sign with an Unexpected Pathological Diagnosis
Authors: Natera‐Villalba Elena , Martínez‐Castrillo Juan Carlos , López‐Sendón Moreno José Luis , Gómez‐López Ana , Sánchez‐Sánchez Arantxa , López‐Martínez María José , Rábano Alberto , Alonso‐Cánovas Araceli 
Published: October 2021

ABSTRACTBackgroundClinical diagnosis of atypical parkinsonisms may be challenging. The eye‐of‐the‐tiger sign on brain MRI, typical of neurodegeneration with brain iron accumulation, has been anecdotally observed in cases clinically diagnosed as atypical parkinsonisms.ObjectivesTo show how clinical syndromes and even neuroimaging sometimes may lead the neurologist to a misunderstanding, just as to emphasize the important role of pathology to establish the final diagnosis in these cases.MethodsClinico‐pathological case.ResultsA 67‐year‐old‐woman presented with progressive painful stiffness and allodynia in her left arm. On examination, she presented parkinsonism without tremor with greater involvement of left limbs. She developed dystonia, with myoclonic tremor and hypoesthesia involving her left arm, as well as an impairment of balance with falls, a significant axial involvement with disabling rigidity, supranuclear gaze abnormalities, facial dystonia, dysphonia, severe dysphagia, and anarthria. There was no response to levodopa. Syndromic diagnosis and findings on neuroimaging are discussed. Afterwards, the underlying pathology is revealed.ConclusionsWe present the first case of neuropathologically confirmed multiple system atrophy with the eye‐of‐the‐tiger sign on brain MRI. The presence of supranuclear vertical gaze palsy further complicated a correct clinical diagnosis. A pathological postmortem study remains essential to establish a definite diagnosis in atypical parkinsonisms.
Radio‐magnetotelluric and controlled‐source magnetotelluric surveys on a frozen lake: Opportunities for urban applications in Nordic countries
Authors: Bastani Mehrdad , Wang Shunguo , Malehmir Alireza , Mehta Suman 
Published: October 2021

ABSTRACTIn a novel approach, we have carried out controlled‐source and radio‐magnetotelluric measurements in the frequency range of 2–250 kHz on a frozen lake located over a planned major multi‐lane underground road tunnel near the city of Stockholm. The aim was to gain a better understanding of the resistivity variations above and, potentially, within the crystalline bedrock. Previous studies on the lake water using the boat‐towed radio‐magnetotelluric technique at the higher end of the frequency band lacked resolution at depth and could not provide conclusive information about bedrock level and potential fracture systems within the bedrock. Taking advantage of Nordic winters, we measured four profiles on the frozen lake complementing the previously acquired boat‐towed radio‐magnetotelluric data utilizing a double horizontal magnetic dipole transmitter that generated signals down to 1 kHz. The new resistivity models, incorporating the lower frequency data, show improvements and deeper penetrations based on a combined analysis of penetration depth, data misfits and sensitivity studies. The resistivity models also show better correlation with the available high‐resolution shallow water seismic reflection data and the geological observations. A potential fracture system within the bedrock can also be inferred better in the new models. The idea of running similar surveys on frozen lakes can be further exploited in similar conditions in countries such as Sweden, where approximately 7% of the land is covered by freshwater bodies and poorly explored for infrastructure planning projects.
Re‐engineered imaging agent using biomimetic approaches
Authors: Nguyen Tuyen Duong Thanh , Marasini Ramesh , Aryal Santosh 
Published: October 2021

AbstractRecent progress in biomedical technology, the clinical bioimaging, has a greater impact on the diagnosis, treatment, and prevention of disease, especially by early intervention and precise therapy. Varieties of organic and inorganic materials either in the form of small molecules or nano‐sized materials have been engineered as a contrast agent (CA) to enhance image resolution among different tissues for the detection of abnormalities such as cancer and vascular occlusion. Among different innovative imaging agents, contrast agents coupled with biologically derived endogenous platform shows the promising application in the biomedical field, including drug delivery and bioimaging. Strategy using biocomponents such as cells or products of cells as a delivery system predominantly reduces the toxic behavior of its cargo, as these systems reduce non‐specific distribution by navigating its cargo toward the targeted location. The hypothesis is that depending on the original biological role of the naïve cell, the contrast agents carried by such a system can provide corresponding natural designated behavior. Therefore, by combining properties of conventional synthetic molecules and nanomaterials with endogenous cell body, new solutions in the field of bioimaging to overcome biological barriers have been offered as innovative bioengineering. In this review, we will discuss the engineering of cell and cell‐derived components as a delivery system for various contrast agents to achieve clinically relevant contrast for diagnosis and study underlining mechanism of disease progression.This article is categorized under:
Nanotechnology Approaches to Biology > Cells at the Nanoscale
Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Outlier Detection for Pandemic-Related Data Using Compositional Functional Data Analysis
Authors: Rieser Christopher , Filzmoser Peter 
Published: October 2021

AbstractWith accurate data, governments can make the most informed decisions to keep people safer through pandemics such as the COVID-19 coronavirus. In such events, data reliability is crucial and therefore outlier detection is an important and even unavoidable issue. Outliers are often considered as the most interesting observations, because the fact that they differ from the data majority may lead to relevant findings in the subject area. Outlier detection has also been addressed in the context of multivariate functional data, thus smooth functions of several characteristics, often derived from measurements at different time points (Hubert et al. in Stat Methods Appl 24(2):177–202, 2015b). Here the underlying data are regarded as compositions, with the compositional parts forming the multivariate information, and thus only relative information in terms of log-ratios between these parts is considered as relevant for the analysis. The multivariate functional data thus have to be derived as smooth functions by utilising this relative information. Subsequently, already established multivariate functional outlier detection procedures can be used, but for interpretation purposes, the functional data need to be presented in an appropriate space. The methodology is illustrated with publicly available data around the COVID-19 pandemic to find countries displaying outlying trends.
The Legal Challenges of Insuring Against a Pandemic
Authors: Hillier Rachel 
Published: October 2021

AbstractCOVID-19 has raised, and continues to raise, questions about the traditional approach to insurance cover. For instance, business interruption insurance covering “pandemics” under all risks insurance policies are likely to be a thing of the past. With tensions between businesses and the insurance industry on the rise, what can be done to offer businesses some protection at a premium they can afford, without emptying insurers’ reserves? In this chapter we talk about legal challenges related to traditional insurance against the risk of losses caused by a pandemic, and whether parametric insurance is the solution.
Stochastic Mortality Models and Pandemic Shocks
Authors: Regis Luca , Jevtić Petar 
Published: October 2021

AbstractAfter decades of worldwide steady improvements in life expectancy, the COVID-19 pandemic produced a shock that had an extraordinary immediate impact on mortality rates globally. This shock had largely heterogeneous effects across cohorts, socio-economic groups, and nations. It represents a remarkable departure from the secular trends that most of the mortality models have been constructed to capture. Thus, this chapter aims to review the existing literature on stochastic mortality, discussing the features that these models should have in order to be able to incorporate the behaviour of mortality rates following shocks such as the one produced by the COVID-19 pandemic. Multi-population models are needed to describe the heterogeneous impact of pandemic shocks across cohorts of individuals. However, very few of them so far have included jumps. We contribute to the literature by describing a general framework for multi-population models with jumps in continuous-time, using affine jump-diffusive processes.
Risk-Sharing and Contingent Premia in the Presence of Systematic Risk: The Case Study of the UK COVID-19 Economic Losses
Authors: Assa Hirbod , Boonen Tim J. 
Published: October 2021

AbstractMotivated by macroeconomic risks, such as the COVID-19 pandemic, we consider different risk management setups and study efficient insurance schemes in the presence of low probability shock events that trigger losses for all participants. More precisely, we consider three platforms: the risk-sharing, insurance and market platform. First, we show that under a non-discriminatory insurance assumption, it is optimal for everybody to equally share all risk in the market. This gives rise to a new concept of a contingent premium which collects the premia ex-post after the losses are realised. Insurance is then a mechanism to redistribute wealth, and we call this a risk-sharing solution. Second, we show that in an insurance platform, where the insurance is regulated, the tail events are not shared, but borne by the government. Third, in a competitive market we see how a classical solution can raise the risk of insolvency. Moreover, in a decentralised market, the equilibrium cannot be reached if there is adequate sensitivity to the common shock events. In addition, we have applied our theory to a case where the losses are calibrated based on the UK Coronavirus Job Retention Scheme.
All-Hands-On-Deck!—How International Organisations Respond to the COVID-19 Pandemic
Authors: Boado-Penas María del Carmen , Demarco Gustavo , Eisenberg Julia , Lundberg Kristoffer , Şahin Şule 
Published: October 2021

AbstractThe COVID-19 pandemic is affecting all countries. Since the World Health Organization declared the COVID-19 outbreak a Public Health Emergency of International Concern on 30 January 2021, governments across the world have mobilised on a tremendous scale and put in place different policies to contain the spread of the virus and its negative effects on society. International organisations have supported these efforts through evidence-based policy recommendations and emergency financing packages. This chapter presents a brief overview of the responses made by international organisations and European Union towards COVID-19. Special attention is given to the guidance of these organisations on the changes in social insurance and pension plans to protect the most vulnerable population groups.
COVID-19 and Optimal Lockdown Strategies: The Effect of New and More Virulent Strains
Authors: Caulkins Jonathan P. , Grass Dieter , Feichtinger Gustav , Hartl Richard F. , Kort Peter M. , Prskawetz Alexia , Seidl Andrea , Wrzaczek Stefan 
Published: October 2021

AbstractMost nations have responded to the COVID-19 pandemic by locking down parts of their economies starting in early 2020 to reduce the infectious spread. The optimal timing of the beginning and end of the lockdown, together with its intensity, is determined by the tradeoff between economic losses and improved health outcomes. These choices can be modelled within the framework of an optimal control model that recognises the nonlinear dynamics of epidemic spread and the increased risks when infection rates surge beyond the healthcare system’s capacity. Past work has shown that within such a framework very different strategies may be optimal ranging from short to long and even multiple lockdowns, and small changes in the valuation on preventing a premature death may lead to quite different strategies becoming optimal. There even exist parameter constellations for which two or more very different strategies can be optimal. Here we revisit those crucial questions with revised parameters reflecting the greater infectivity of variants such as the “UK variant” of the SARS-CoV-2 virus and describe how the new variant may affect levels of mortality and other outcomes.
Ansätze zur Begegnung der Hochpreisigkeit
Authors: Franzen Nora , van Harten Wim 
Published: October 2021

Zusammenfassung
Zusammenfassung
Dieses Kapitel bietet eine Darstellung und Einordnung innovativer Lösungsvorschläge jenseits inkrementeller Ansätze zur Bezahlbarkeit von hochpreisigen, patentgeschützten Spezialpräparaten. Die Autor:innen diskutieren mögliche Maßnahmen zur Preissenkung durch Veränderung geistiger Eigentumsrechte und arzneimittelrechtlicher Schutzrechte, Anpassungen in der Preisbildung sowie Veränderungen im Forschungs- und Entwicklungssektor einschließlich etwaiger Evidenzen in deren Wirksamkeit. Schließlich werden Lösungsvorschläge hinsichtlich ihrer Realisierbarkeit und nötiger struktureller Systemveränderungen aus deutscher Perspektive erörtert.
Der Arzneimittelmarkt 2020 im Überblick
Authors: Telschow Carsten , Schröder Melanie , Bauckmann Jana , Niepraschk-von Dollen Katja , Zawinell Anette 
Published: October 2021

Zusammenfassung
Zusammenfassung
Im Überblick zum Arzneimittelmarkt der gesetzlichen Krankenversicherung (GKV) im Jahr 2020 werden Ursachen und Hintergründe der Umsatzsteigerung um 4,9 % gegenüber 2019 analysiert. So wird mit Hilfe der Methode der Komponentenzerlegung die strukturelle Veränderung bei den Verordnungen als wichtigster Umsatztreiber für den durchschnittlichen Wert einer Arzneimittelverordnung identifiziert. Für diese Umsatzsteigerungen sind insbesondere neue und teure patentgeschützte Arzneimittel verantwortlich. Gleichzeitig sinkt der Anteil der Tagesdosen im Patentmarkt, sodass hier immer mehr Geld für immer weniger Versorgung aufzubringen ist. Dies trifft noch stärker für das stetig wachsende Marktsegment der Arzneimittel für seltene Erkrankungen (Orphan Drugs) zu, die mit extrem hohen Kosten jeweils nur bei wenigen Patient:innen angewendet werden und so einen Versorgungsanteil nach verordneten Tagesdosen von 0,06 %, aber einen Kostenanteil von 11,8 % am Gesamtmarkt ausmachen. Die Kosten im Zweitanbietermarkt bzw. Nicht-Patentmarkt stagnieren hingegen und auch die Erlöse aus Rabattverträgen haben 2020 das Niveau des Vorjahres erreicht. Viele der weltweit größten Pharmakonzerne konnten erneut Umsatzsteigerungen und höhere Gewinne verbuchen; alleine die 21 größten unter ihnen deckten über 50 % der Umsätze im deutschen Arzneimittelmarkt 2020 ab, wobei diese Konzerne ihren Umsatz in Deutschland zu 70 % mit Patentarzneimitteln erzielen. Ein Blick auf besondere Entwicklungen in der Arzneimittelversorgung während der COVID-19-Pandemie ergänzt die Sicht auf den GKV-Arzneimittelmarkt 2020.
Gesellschaftliche und volkswirtschaftliche Sicht auf die (zukünftige) Finanzierbarkeit von Arzneimitteln
Authors: Wasem Jürgen , Hüer Theresa , Abels Carina 
Published: October 2021

Zusammenfassung
Zusammenfassung
Angemessene Preise für patentgeschützte Arzneimittel zu finden ist kein neues Problem. Bei sich ändernden Rahmenbedingungen stellt sich die Frage jeweils wieder neu. Der Markt unterliegt derzeit insbesondere zwei strukturellen Veränderungen. Zum einen werden neue Arzneimittelimmer häufiger auf Basis besonderer Verfahren durch die Europäische Arzneimittel-Agentur (EMA, englisch European Medicines Agency) zugelassen, womit eine geringe Evidenzlage zum Zeitpunkt der Zulassung einhergeht. Zum anderen ergeben sich hauptsächlich durch Arzneimittel für neuartige Therapien transformierte Ausgabenverläufe, da es sich um Einmal-/Impulstherapien handelt, die eine jahre- bis lebenslange Wirkung versprechen. Aus der sich daraus ergebenden Unsicherheit hinsichtlich der (langfristigen) Wirksamkeit unmittelbar nach der Zulassung ergibt sich ein Spannungsfeld im Rahmen der Preisfindung. Um diesem Spannungsfeld in der derzeitigen Arzneimittelpreisbildung im deutschen System zu begegnen, werden in diesem Beitrag international diskutierte innovative Preis- und Erstattungsmechanismen betrachtet und in Bezug auf ihre Anwendbarkeit im deutschen Preisbildungssystem bewertet. Gleichzeitig wird darauf eingegangen, dass möglicherweise ein stärkerer Fokus auf Kosten-Nutzen-Bewertungen im Rahmen der Preisbildung gelegt wird, um die (zukünftige) Finanzierbarkeit von Arzneimitteln sicherzustellen.
Ethische Sichtweise auf hochpreisige Arzneimittel
Authors: Nagel Eckhard , Henzler Dennis , Lauerer Michael 
Published: October 2021

ZusammenfassungZusammenfassungDie Zulassung und Preisbildung neuer Arzneimittel ist in Deutschland, wie in vielen anderen Ländern, reglementiert. Damit fügen sie sich in die umfänglichen Vorgaben zur Strukturierung des Gesundheitswesens ein, die im Wesentlichen das Ziel haben, die Interessen des Leistungsanbieters, der Versichertengemeinschaft als Kostenträger sowie der behandlungsbedürftigen Personen adäquat zu berücksichtigen. Diese Ausgleichsfunktionen sind einer Reihe ethischer Normen unterworfen, die zum Teil explizit das Gesundheitswesen charakterisieren oder häufig auch implizit das genannte Ziel realisieren sollen. Der Artikel rekapituliert relevante ethische Grundlagen der Gesundheitsversorgung, welche einen engeren Bezug zur Preisfindung bei Medikamenten aufweisen. Dabei bedient er sich zweier Fallstudien anhand derer erkennbar wird, wie sich die Zusammenhänge zwischen Normensetzung und Verantwortung auf diesem Gebiet darstellen.
Hochpreisigkeit bei Onkologika
Authors: Ludwig Wolf-Dieter , Vokinger Kerstin Noëlle 
Published: October 2021

Zusammenfassung
Zusammenfassung
Onkologikasind seit mehreren Jahren die umsatzstärkste Arzneimittelgruppe in Deutschland. Während 2014 unter den 30 umsatzstärksten patentgeschützten Arzneimitteln nur drei Onkologika mit Nettokosten zwischen 184 Mio. € und 259 Mio. € je Arzneimittel waren, befinden sich unter den führenden 20 Arzneimitteln nach Nettokosten im Jahr 2020 bereits neun Onkologika. Sie sind deshalb inzwischen die mit weitem Abstand umsatzstärkste Arzneimittelgruppe mit 9,5 Mrd. € Nettokosten insgesamt. Verantwortlich hierfür sind die sehr hohen Preise, die heute von pharmazeutischen Unternehmern (pU) für neuartige Wirkstoffe zur Behandlung hämatologischer Neoplasien und solider Tumore (z. B. Proteinkinaseinhibitoren und monoklonale Antikörper) verlangt werden. Im Zusammenhang mit der Auswertung von Verordnungen ist zu berücksichtigen, dass für GKV-Patient:innen 2020 insgesamt nur 8,1 Mio. Verordnungen von Onkologika erfolgten, die nur 1,2 % aller verordneten Arzneimittel des GKV-Arzneimittelmarktes ausmachten. Anhand aktueller Untersuchungen konnte inzwischen gezeigt werden, dass die Kosten für Forschung & Entwicklung (F & E)neuer Wirkstoffe, die von pU häufig als Begründung für die sehr hohen Preise der Onkologika genannt wurden, deutlich niedriger liegen als früher behauptet (im Median circa 548 Mio. €), sodass Onkologika heute sehr hohe Erträge generieren, die die Kosten für F & E deutlich übersteigen. Darüber hinaus belegen sowohl aktuelle Studien aus den USA und Europa als auch die Ergebnisse der seit 2011 in Deutschland durchgeführten frühen Nutzenbewertung von Onkologika, dass ein Zusammenhang zwischen deren klinischem Nutzen und den Behandlungskosten meist nicht besteht.