bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gruppe-ekspertise i pædagogik med henblik på omsorgsarbejde
Authors: Engelsen Søren 
Published: April 2021

ResumeArtiklen argumenterer for, at pædagogisk ekspertise kan tilskrives grupper og ikke kun individer. Hvordan skal vi helt fundamentalt forstå pædagogisk gruppe-ekspertise? Artiklen anlægger et pædagogisk-filosofisk perspektiv på dette spørgsmål. Med et fokus på pædagogisk omsorgsarbejde afklarer den, hvad de fundamentale forudsætninger er for gruppeekspertise. Første del undersøger minimumsbetingelserne for, hvad man kan kalde pædagogisk ekspertise. Idealet om pædagogisk ekspertise må forstås bredt, hvis vi skal fastholde det som et meningsfuldt forbillede for pædagogisk teori og praksis. Artiklen analyserer og kategoriserer væsentlige aspekter af ekspertise i en pædagogisk sammenhæng. Pædagogisk ekspertise må rumme en pluralisme af former for viden og kompetencer, både praktiske, teoretiske, før-refleksive og refleksive, samt adfærdsdispositioner, emotionel opmærksomhed og intellektuelle kapaciteter. Artiklens anden del undersøger de filosofiske betingelser for gruppe-ekspertise og drager nogle vigtige distinktioner. Det argumenteres således, at grupper kan have overlegen viden qua gruppe, som de enkelte medlemmer hver især ikke besidder, og denne viden kan under de rette betingelser udgøre ekspertise. For at anskueliggøre denne forståelse af gruppeekspertise illustrerer artiklen til slut idéen i en sammenhæng af pædagogisk omsorgsarbejde. Her eksemplificeres det, hvordan gruppe-ekspertise i pædagogisk omsorgsarbejde kan bestå af samspillet mellem konstitutive delelementer.
Abstract Group expertise in pedagogy for care workThe article argues that pedagogical expertise can be attributed to groups and not just individuals. How should we fundamentally understand pedagogical group expertise? The article takes a pedagogical-philosophical perspective on this issue. With a focus on pedagogical care work, it clarifies the fundamental prerequisites for group expertise. The first part examines the minimum conditions for what can be called pedagogical expertise. If we are to maintain it as a meaningful ideal of pedagogical theory and practice, pedagogical expertise must be understood broadly. The article analyzes and categorizes significant aspects of expertise in a pedagogical context. Pedagogical expertise must accommodate a pluralism of knowledge forms and competencies. These include practical, theoretical, pre-reflexive and reflexive competencies, behavioral dispositions, emotional awareness, and intellectual capacities. The second part of the article examines the philosophical conditions of group expertise and draws some important distinctions. Groups can have superior knowledge, which the individual members do not possess individually, and this knowledge can, under the right conditions, constitute expertise. Finally, an example of how constitutive elements of group expertise in pedagogical care work can unfold illustrates the main idea of group expertise in a specific pedagogical care work context.
The Role of Permeability in Drug ADME/PK, Interactions and Toxicity, and the Permeability‐Based Classification System (PCS)
Authors: Fagerholm Urban 
Published: April 2021

Abstract

Permeability (
P
e
) is one of the key determinants in the absorption, distribution, metabolism, excretion/pharmacokinetics (ADME/PK) of drugs and their metabolites. Predictions of ADME/PK, interactions, elimination routes, exposures, and toxicity require, therefore, that the role of permeability in different organs is considered, investigated and understood. That includes studies of and knowledge about the relation between
P
e
and fraction absorbed (
f
a
) (or fraction reabsorbed;
f
ra
) in various organs, and the interplay between passive permeability and active permeability, metabolism and solubility/dissolution. Relationships between passive
P
e
and
f
a
in the human intestine, liver, renal tubuli (
f
ra
), and brain have been established, and these are the basis of the Permeability‐Based Classification System (PCS). This system demonstrates sigmoidal
P
e
versus
f
a
and
f
ra
relationships of different shapes and shifts, and is divided into four permeability categories (very high/high/intermediate/low). Results show or indicate that the liver and brain have comparably high intrinsic passive uptake capacities, metabolism (rather than uptake, diffusion, and dissociation) is the general rate‐limiting step in hepatic metabolic clearance (CL
H
), and few high permeability compounds have dissolution‐limited gastrointestinal
f
a
. Active transport processes contribute to the intestinal and hepatic uptake, and renal, biliary, and intestinal drug excretion, of many drugs with limited passive
P
e
. Active transport could be clinically relevant for brain uptake of both low and high passive permeability compounds. Related drug–drug interactions and polymorphism appear most pronounced for drugs actively absorbed and excreted by the liver. Combined with intrinsic metabolic CL data, the PCS is useful for predictions of CL
H
, renal and biliary excretion potential, gut‐wall extraction ratio, oral bioavailability and effects of polymorphism, and for assessment of potential drug–drug or drug–metabolite interactions, and drug and metabolite organ/cell trapping.
Current and Emerging Therapies in Chronic Obstructive Pulmonary Disease
Authors: Montana John G. , Dyke Hazel J. , Fox J. Craig , Ray Nicholas C. 
Published: April 2021

AbstractChronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease that is a leading cause of morbidity and mortality worldwide with an overall prevalence in adults >40 years estimated at 9–10%. The World Health Organization (WHO) estimates that, by 2020, COPD will be the third leading cause of mortality and the fifth leading cause of morbidity in the world. This smoking‐related disease is characterized by progressive airway obstruction that, unlike asthma, is relatively insensitive to bronchodilators and to the classic anti‐inflammatory therapy, corticosteroids. Current therapy focuses mainly on reducing symptoms using inhaled short‐acting and long‐acting bronchodilators either as monotherapies or in combination with inhaled corticosteroids. During the last decade, the pharmaceutical industry has focused on treating COPD distinctly from asthma but no novel agents that target the disease itself have been launched as therapies for this disease. As our understanding of the pathology of COPD has increased it has been established that the progressive pulmonary inflammation that is associated with COPD relates to disease severity. Thus, it is anticipated that drugs that reduce pulmonary inflammation will provide effective, disease‐modifying therapies. Here, we consider the potential of anti‐inflammatory drugs that are currently in clinical development for COPD and discuss how these might reduce pulmonary inflammation in this disease.
Drug Discovery and Development for Kinetoplastid Diseases
Authors: Caffrey Conor R. , Steverding Dietmar , Ferreira Rafaela S. , de Oliveira Renata B. , O'Donoghue Anthony J. , Monti Ludovica , Ballatore Carlo , Bachovchin Kelly A. , Ferrins Lori , Pollastri Michael P. , Zorn Kimberley M. , Foil Daniel H. , Clark Alex M. , Mottin Melina , Andrade Carolina H. , de Siqueira‐Neto Jair L. , Ekins Sean 
Published: April 2021

AbstractIn this article, we review the disease, biology, and biochemistry of kinetoplastids, as well as the new drugs and drug candidates that have entered the clinic in the last decade. We also describe examples of the preclinical exploration of small molecules against various protein targets (e.g. cysteine proteases, the proteasome, and tubulin), as well as cutting‐edge molecular and computational strategies and technologies being brought to bear to discover and develop new antitrypanosomal drugs. For comprehensive descriptions of the disease, biology, and drug therapies prior to 2011, the reader is encouraged to review the article by P.M. Woster that appeared in 2010 in the seventh edition of Burger's Medicinal Chemistry, Drug Discovery, and Development, entitled Antiprotozoal/Antiparasitic Agents.
Health Outcomes Research
Authors: McCollam Pat , Birt Julie , Hunter Theresa 
Published: April 2021

Abstract
What is health outcomes research? For the purpose of this article, we use a broad definition of health outcomes research and discuss three major domains of research – patient‐reported outcomes (PROs), real‐world evidence (RWE), and health economic evaluations.
An important question is – who uses this information? The audience is very diverse. The pharmaceutical industry might use RWE data to inform clinical trial design, to suggest substudies in populations of interest, to examine secondary endpoints, or perhaps use PROs to apply for promotional claims with regulators. Through collaboration with manufacturers, academics publish from clinical trials, use registries and other large databases to publish RWE, and sometimes use these data to develop treatment algorithms or policy statements. Managed care organizations in the United States and other payers around the globe may use health outcomes data in an attempt to position the most cost‐effective use of a new technology. Healthcare practitioners and patients may use PRO data to target important specific symptoms.
The Design and Application of Bioisosteres in Drug Design
Authors: Meanwell Nicholas A. 
Published: April 2021

Abstract
Bioisosterism, the design of structural motifs that emulate established functionality to effect a biological response, has evolved into a powerful design principle in medicinal chemistry and drug discovery that can be implemented to address issues associated with intrinsic potency and/or a range of developability challenges. While bioisosterism has its origins in the concept of isosterism, which was invoked to explain the similarity of physicochemical properties between molecules with analogous size and shape, the contemporary interpretation of bioisosterism extends well beyond this simple definition to encompass relationships that reflect a recapitulation of biological properties by molecules that can be structurally quite disparate. This article provides a synopsis of established and emerging bioisosteric relationships that are discussed in the context of applications to solving problems in drug discovery and development. Bioisosteres that are described range from the replacement of hydrogen atoms by deuterium or fluorine to more esoteric higher order bioisosteres that convene intricate arrays of functionality. These are considered nonclassical in nature and offer functional mimesis of a range of simple and complex functionalities encompassing exchangeable groups, cyclic/noncyclic substructures capable of mimicking rings, and extends to include drug–water and drug–metal complexes.
Automated Synthesis
Authors: Masquelin Thierry , Kaerner Andreas , Bernhardt Ryan J. , Wang Jibo , Nicolaou Christos A. 
Published: April 2021

Abstract
In a world where budgets and head counts are increasingly constrained and environmental impact scrutinized, new automated laboratory capabilities spanning from organic synthesis, analytical chemistry, through mechanical, chemical, and electrical engineering to robotics, computer science, and information technologies, are finding use as transformative methods for facilitating faster and better drug discovery operations as well as accelerated development of patient‐centric treatments and personalized medical applications.
A significant challenge for life sciences researchers is gaining rapid access to probe molecules to query biological targets or pathways identified through various screening activities. Additional challenges include the ability to quickly and interactively optimize molecules identified as hits from screening activities. In the past two decades, the race has been on to build an automated laboratory to address gaps in organic synthesis and thereby supporting biological and drug discovery research by providing rapid access to a synthetic chemistry resource that is both cost‐effective and robust. This review focuses on concepts and approaches that have already been introduced in the automated synthesis world and also innovative technologies that could radically change small and large molecules research and, thus, have far‐reaching implications in the intelligent automation drug discovery world in the near future.
Glucagon‐Like Peptide‐1 Receptor Activators
Authors: Wagner Michael , Evers Andreas , Bossart Martin , Konkar Anish 
Published: April 2021

AbstractType 2 diabetes (T2D) and obesity have reached pandemic levels and represent a major health burden to modern society. Peptidic GLP‐1 receptor agonists (GLP‐1RAs) have been established as an effective therapy with respect to glycemic control and provide moderate body weight reduction. Marketed first‐generation GLP‐1RAs are suitable for once‐ or twice‐daily subcutaneous dosing. Their substantial benefit on glucose control led to the discovery and development of longer lasting therapeutic options to improve patient convenience and compliance. Recently reported positive cardiovascular outcome studies for some GLP‐1RAs further underscore their therapeutic value. Besides long‐lasting action, alternative delivery formats for injectable GLP‐1RAs have been explored, for example oral formulations. One such oral formulation of a GLP‐1 analog has completed Phase 3 studies and is now approved for the treatment of T2D. In contrast, the discovery of orally available small molecule agonists of the GLP‐1R has been historically challenging, and only recently a few compounds have reached early clinical development. To further improve the efficacy of GLP‐1RAs, so‐called GLP‐1R dual or triple agonists have been developed. These peptides show promising results in early clinical trials but are awaiting confirmation of their therapeutic benefit in late‐stage development.
Structure‐Based Drug Design for G Protein‐Coupled Receptors
Authors: Congreve Miles , Christopher John A. , de Graaf Chris 
Published: April 2021

Abstract
A transformation in the structural biology of membrane‐associated receptors, particularly of G Protein‐Coupled Receptors (GPCRs), has occurred over the last 10 years and continues to build momentum today. Remarkable new protein–ligand X‐ray crystal and latterly cryo‐EM structures have been published giving a detailed appreciation of how molecules bind to a plethora of fascinating binding sites. The profound impact of these new data on design of ligands for drug discovery, a detailed consideration of the consequences to the computational chemistry community, and a description of some representative applications of Structure‐Based Drug Design (SBDD) are described in this article, with a focus on GPCRs.
The Design and Development of Antibody–Drug Conjugates (ADCs) for the Treatment of Cancer
Authors: Tumey L. Nathan 
Published: April 2021

AbstractOver the past 10 years, antibody–drug conjugates (ADCs) have rapidly become an important player in the oncology therapeutic space. ADCs consist of three components: (i) A potently cytotoxic drug; (ii) An antibody that is designed to deliver the drug to specific antigen‐expressing cells; and (iii) A linker that holds these two components together but is rapidly cleaved by cancer cells. Tremendous technical advances have been made in the ADC field over the past 15 years that have culminated in the FDA approval of six ADCs and the clinical evaluation (currently) of nearly 100 ADCs. This article provides an overview of the history of ADCs and highlighted important developments in the selection of antigens, design of the linker, selection of conjugation chemistry, and the design of the payload itself. We will focus on promising preclinical strategies that are working their way toward clinical evaluation.
Eicosanoid Pathway Modulators: Prostaglandins, Prostacyclin, and Thromboxane
Authors: Mazaleuskaya Liudmila L. , Ricciotti Emanuela 
Published: April 2021

AbstractProstanoids (prostaglandins, prostacyclin, and thromboxane) are bioactive lipids, members of the eicosanoid class of compounds, derived from arachidonic acid (AA). They are involved in controlling homeostatic and pathophysiological processes. Their biosynthesis is the result of the coordinated actions of several enzymes. Cyclooxygenases (COXs) catalyze the committed step in the conversion of AA into prostanoids. There are two COX isozymes: the constitutive COX‐1 and the inducible COX‐2, both of which have different patterns of expression and biological functions. COX‐1 and COX‐2 are the targets of traditional nonsteroidal anti‐inflammatory drugs (tNSAIDs), which are used to relieve pain, fever and inflammation. Despite their clinical efficacy, tNSAIDs cause side effects, particularly in the gastrointestinal (GI) tract. NSAIDs selective for COX‐2 inhibition (coxibs) were purposefully designed to spare GI side effects, but predisposed patients to increased cardiovascular (CV) risks. The GI and CV complications from existing NSAIDs prompted interest in the downstream effectors of the COX enzymes as novel drug targets. This article describes various safety issues with tNSAIDs and coxibs, and discusses the current development of novel classes of drugs targeting the AA pathway, including nitric oxide‐releasing and hydrogen sulfide‐releasing NSAIDs, inhibitors of prostanoid synthases, dual inhibitors, and prostanoid receptor agonists and antagonists.
Small‐molecule Effectors of
DNA
Repair Proteins: Applications for Development of Cancer Therapeutics and Research
Authors: Chheda Pratik , Spies Maria , Spies M. Ashley 
Published: April 2021

Abstract
A ubiquitous aspect of cellular life is the need to repair the many deleterious DNA lesions that arise due to environmental damage and as byproducts of normal cellular metabolism. The same DNA repair processes, which are critical for life, are also employed by cancer cells in their resistance to radiation and DNA‐damaging therapies. Inhibition of DNA repair or entrapment of the toxic DNA repair intermediates with the help of small molecules has both potential therapeutic and research utility. Although many proteins that maintain genome integrity and repair DNA damage appear to be attractive targets, they lack well‐defined small‐molecule binding determinants and clear structure–activity relationships. This article summarizes a number of studies that have led to the identification of small‐molecule drug lead compounds, which may also be useful in dissecting complex DNA repair networks. Systems that are particularly noteworthy are inhibition of PARP1, as it is a paradigm case for achieving successful clinical applications, and the emerging targets RAD51 recombinase, RAD52 DNA repair protein, MRE11 nuclease, and WRN DNA helicase.
Paramecium
Authors: Aufderheide Karl J 
Published: April 2021

Abstract

Members of the genus
Paramecium
(from the classical Greek, παραμηκης, meaning oblong or oval shaped) are ciliated protozoa with an elongated shape (length approximately three to four times the width), a uniform distribution of cilia over the cell surface and a ciliated oral groove leading from the anterior of the cell to a midventral deep oral cavity. The oral apparatus is shaped like a funnel, with 12 rows of oral cilia in a helical array inside. Each cell has two distinct types of nuclei: one large, transcriptionally active, polycopy macronucleus and one or more small, transcriptionally inactive micronuclei.

Many features make paramecia favourable organisms for the study of diverse cellular/developmental/genetic aspects of cells. Their large size allows microscopic observations as well as microinjections and cell surgery. They show Mendelian and non‐Mendelian inheritance and several different epigenetic inheritance patterns. The genomes of
Paramecium tetraurelia
and others have been sequenced and are available for analysis.

Key Concepts

Species of Paramecium are distributed worldwide in freshwater habitats and are easy to cultivate in the laboratory.

Morphological differences are not enough to distinguish some species of Paramecium.

The genomes of the macronucleus and micronucleus are not identical, even though both are derived from the same zygote nucleus.

The genomes of
Paramecium tetraurelia
have been sequenced; 30 000 genes have been identified.

Paramecia do not use two of the three ‘stop codons’ for translation termination.

The trichocysts of paramecia are examples of a regulated exocytotic process.

The cortex of the cell contains the cilia, basal bodies and associated accessory structures.

Paramecia can carry a number of different types of endosymbiotic organisms.
In Vivo Plain X‐Ray Imaging of Cancer Using Perovskite Quantum Dot Scintillators
Authors: Ryu Ilhwan , Ryu Jee‐Yeon , Choe Geunpyo , Kwon Hyemin , Park Hyeji , Cho Young‐Seok , Du Rose , Yim Sanggyu 
Published: April 2021

AbstractReal‐time in vivo detection of cancer via attenuation‐based plain X‐ray imaging is proposed to fundamentally overcome the penetration depth limits of current fluorescence‐based imaging techniques. Using cesium lead bromide (CsPbBr3, CPB) quantum dot (QD) scintillators, real‐time X‐ray detection of 5 mm‐sized Panc‐1 cell tumors grown in a mouse is successfully performed. The QDs are rapidly co‐synthesized and double‐encapsulated with silicon dioxide (SiO2) to completely prevent them from being aggregated, decomposed, or released; they are then conjugated with antibodies to target pancreatic cancer. Due to the dramatic X‐ray attenuation, the X‐ray signal from the CPB QDs placed under the 2 cm‐thick tissue is clearly observed, while their fluorescence signal is not detected at all. In in vivo mouse experiments, the injection of a tiny amount (2.8 μg on a QD basis) of the CPB–SiO2@SiO2–Ab nanoparticles gives rise to a bright spot at the location of the tumor. Cell viability assay and histological analysis confirm the biocompatibility and nontoxicity of the nanoparticles.
Quantum Topological Photonics
Authors: Yan Qiuchen , Hu Xiaoyong , Fu Yulan , Lu Cuicui , Fan Chongxiao , Liu Qihang , Feng Xilin , Sun Quan , Gong Qihuang 
Published: April 2021

AbstractQuantum topological photonics is a new research field with great potential that is based on developments in both quantum optics and topological photonics. Topological photonics offers unique properties, including topological robustness and an anti‐backscattering property, and these advantages are strongly required in quantum optics. Quantum technology, which includes quantum optics, represents an important direction for future technological development. However, existing quantum light sources are unstable and quantum information may easily be lost during transmission. These disadvantages have troubled researchers for a long time and no perfect solution is available thus far. Fortunately, application of topological photonics to quantum optics can help to generate robust quantum light sources and protect photons from decoherence during photon propagation. This allows the correlation and entanglement to be maintained even when photons travel over long distances. To date, quantum topological photonics has provided major breakthroughs in certain quantum devices. This Review presents the basic concepts of quantum topological photonics and summarizes how the topological protection property works in quantum light sources, quantum information transmission, and other quantum devices. Finally, an outlook is provided on the remaining challenges and potential future directions of quantum topological photonics, which can aid in exploration of additional new phenomena.