bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimeric ACE2-IgM fusions as broadly active antivirals that potently neutralize SARS-CoV-2 variants
Authors: Svilenov Hristo L. , Bester Romina , Sacherl Julia , Absmeier Ramona , Peters Carsten , Protzer Ulrike , Brockmeyer Carsten , Buchner Johannes 
Published: November 2022

AbstractCoronavirus infections are a world-wide threat to human health. A promising strategy to develop a broadly active antiviral is the use of fusion proteins consisting of an antibody IgG Fc region and a human ACE2 domain to which the viral spike proteins bind. Here we create antiviral fusion proteins based on IgM scaffolds. The hexameric ACE2-IgM-Fc fusions can be efficiently produced in mammalian cells and they neutralize the infectious virus with picomolar affinity thus surpassing monomeric ACE2-IgM-Fc by up to 96-fold in potency. In addition, the ACE2-IgM fusion shows increased neutralization efficiency for the highly infectious SARS-CoV-2 omicron variant in comparison to prototypic SARS-CoV-2. Taken together, these multimeric IgM fusions proteins are a powerful weapon to fight coronavirus infections.
Molecular divergence with major morphological consequences: development and evolution of organ size and shape
Authors: Masly John P. , Azom Md Golam 
Published: November 2022

Abstract
Understanding the causes of the morphological diversity among organisms is a topic of great interest to evolutionary developmental biologists. Although developmental biologists have had great success in identifying the developmental mechanisms and molecular processes that specify organ size and shape within species, only relatively recently have the molecular tools become available to study how variation in these mechanisms gives rise to the phenotypic differences that are observed among closely related species. In addition to these technological advances, researchers interested in understanding how molecular variation gives rise to phenotypic variation have used three primary strategies to identify the molecular differences underlying species-specific traits: the candidate gene approach, differential gene expression screens, and between-species genetic mapping experiments. In this review, we discuss how these approaches have been successful in identifying the genes and the cellular mechanisms by which they specify variation in one of the most recognizable examples of the evolution of organ size, the adaptive variation in beak morphology among Darwin’s finches. We also discuss insect reproductive structures as a model with great potential to advance our understanding of the specification and evolution of organ size and shape differences among species. The results from these two examples, and those from other species, show that species-specific variation in organ size and shape typically evolves via changes in the timing, location, and amount of gene/protein expression that act on tissue growth processes.
Shapeshifting tau: from intrinsically disordered to paired-helical filaments
Authors: Mengham Kurtis , Al-Hilaly Youssra , Oakley Sebastian , Kasbi Kamillia , Maina Mahmoud B. , Serpell Louise C. 
Published: November 2022

Abstract
Tau is an intrinsically disordered protein that has the ability to self-assemble to form paired helical and straight filaments in Alzheimer’s disease, as well as the ability to form additional distinct tau filaments in other tauopathies. In the presence of microtubules, tau forms an elongated form associated with tubulin dimers via a series of imperfect repeats known as the microtubule binding repeats. Tau has recently been identified to have the ability to phase separate in vitro and in cells. The ability of tau to adopt a wide variety of conformations appears fundamental both to its biological function and also its association with neurodegenerative diseases. The recently highlighted involvement of low-complexity domains in liquid–liquid phase separation provides a critical link between the soluble function and the insoluble dysfunctional properties of tau.
Stator current identification in generator among single and composite faults composed by static air‐gap eccentricity and rotor inter‐turn short circuit
Authors: He Yu‐Ling , Qiu Ming‐Hao , Jiang Meng‐Ya , Zhou Fu‐Cheng , Gerada David , Zhang Xiao‐Chen , Du Xiao‐Dong 
Published: November 2022

AbstractIn this study, a fault diagnosis model based on magnetic density is proposed to analyse the current characteristics of synchronous generator rotor inter‐turn short circuit and air gap eccentric single fault and composite fault. The model considers the influence of rotor inter‐turn short circuit and air gap eccentricity on air gap magnetic density. According to two main factors, the short circuit turns and eccentric distance, are used to reflect the short circuit and eccentricity of the generator. The detailed parameter input model of the generator can easily and quickly predict the development trend of these current parameters based on the air gap magnetic density. And the phase current is selected as the current parameter. The validity of the proposed model is verified by two‐dimensional finite element analysis and experimental research.
Solution of constrained mixed‐integer multi‐objective optimal power flow problem considering the hybrid multi‐objective evolutionary algorithm
Authors: Ali Aamir , Abbas Ghulam , Keerio Muhammad Usman , Koondhar Mohsin Ali , Chandni Kiran , Mirsaeidi Sohrab 
Published: November 2022

AbstractAn Optimal power flow (OPF) is non‐linear and constrained multi‐objective problem. OPF problems are expensive and evolutionary algorithms (EAs) are computationally complex to obtain uniformly distributed and global Pareto front (PF). Therefore, here, hybrid two‐phase algorithm integrated with parameter less constraint technique is applied to solve OPF problem. Proposed technique combines single and multi‐objective EAs to find better convergence and evenly distributed PF. For the validation and effectiveness of proposed algorithm, various conflicting objective functions are formulated and implemented on IEEE 30 and 300‐bus network. Each case is independently run twenty times. Hyper volume indicator technique is employed to find the best PF, and the best‐compromised solution is obtained by using fuzzy decision‐making technique. Recently, maximum integration of wind and solar power is highly encouraged. Complexity of OPF is increased with the integration of uncertain renewable energy resources. Hence, 30‐bus test system is modified by replacing some conventional generators with the wind and solar generation. Uncertainties in wind, solar and load demand are modelled by appropriate probability distribution functions. Simulation results show that the proposed method can find the near global PF of highly complex problems subject to satisfying all the operational constraints.
Service restoration for resilient distribution system with coordination of battery swapping stations and distributed generations
Authors: Guo Yina , Liao Kai , Yang Jianwei , He Zhengyou 
Published: November 2022

AbstractDue to sufficient energy storage resources and central dispatch, the battery swapping station (BSS) offers a promising solution for the service restoration and resilience enhancement of the distribution system (DS). This paper proposes a joint service restoration strategy for the DS by coordinating BSSs and distributed generations (DGs) with distribution network reconfiguration. Firstly, the spatio‐temporal distribution of battery swapping demand for electric vehicles (EVs) is analyzed. On this basis, the participation of the BSS in the DS service restoration is investigated, and the model of restoration capacity for the BSS is established, which can describe the power supply ability of the BSS to support the DS restoration. Secondly, a mathematical model for the resilient DS restoration with coordination between BSSs and DGs is established, aiming to minimize the total system cost by optimally allocating BSSs and DGs during the restoration stage. The second‐order cone programming (SOCP) relaxation is also adopted to transform the proposed restoration model into a mixed‐integer convex formulation, which can be tractably solved. Finally, numerical simulations are conducted based on the modified IEEE 33‐bus distribution test system. The results demonstrate the effectiveness of the proposed strategy for the service restoration and resilience enhancement of the DS.
Behandlungsspektrum von Lymphomen und Plasmozytomen der Wirbelsäule
Authors: Aftahy Amir Kaywan , Meyer Bernhard , Gempt Jens 
Published: November 2022

ZusammenfassungDiese Übersichtsarbeit beschäftigt sich mit dem Behandlungsspektrum von Lymphomen und Plasmozytomen der Wirbelsäule, insbesondere hinsichtlich der operativen Versorgung bei akuter neurologischer Beeinträchtigung sowie instabilitätsgefährdenden Frakturen mit dem Risiko der weiteren funktionellen Verschlechterung. Die Manifestation eines malignen Lymphoms an der Wirbelsäule ist vergleichsweise selten; in der Literatur sind nur wenige Fälle und Fallserien beschrieben. Daher gibt es keinen Goldstandard für die Behandlung von Patienten mit Lymphom-Manifestationen an der Wirbelsäule. Ebenso verhält es sich bei Plasmazellneoplasien; diese lassen sich in Subtypen unterteilen, darunter das multiple Myelom (MM) und das solitäre Plasmozytom des Knochens (SBP). Die ersten klinischen Anzeichen sind Skelettschmerzen, die meist Rippen und Wirbel betreffen. Bei osteolytischen Knochenläsionen ist die Wirbelsäule bei 60–80 % der MM-Patienten betroffen, hier mit fortschreitender Osteolyse, so dass eine Stabilität der Wirbelsäule nicht gewährleistet ist.
Vestibuläre Migräne
Authors: Rambold Holger A. 
Published: November 2022

ZUSAMMENFASSUNGEine Sonderform der Migräne ist die vestibuläre Migräne (VM), die die häufigste Drehschwindelerkrankung und die zweithäufigste Form des Schwindels ist. Diese Erkrankung ist für Patienten sehr belastend und schränkt die Lebensqualität stark ein. Die Diagnosestellung gestaltet sich oft schwierig, sodass die VM leider vielfach unter- oder fehldiagnostiziert wird. Ursache ist das variable klinische Bild und das Fehlen von objektiven, die VM definierenden Untersuchungen. Diese Übersichtsarbeit fasst die Diagnosekriterien, die klinischen und epidemiologischen Befunde, die Zusatzuntersuchungen und die wichtigsten Differenzialdiagnosen zusammen und soll somit helfen, die VM besser zu diagnostizieren.
Über die Entdeckung des 6. Sinnes vor 152 Jahren
Authors: Scherer Hans , Engel-Murke Frank 
Published: November 2022

ZUSAMMENFASSUNGJahrhundertelang kannten die Menschen 5 Sinne. Sie waren lokalisierbar und z. T. abschaltbar. Den 6. Sinn, den statischen oder Gleichgewichtssinn fand man erst im 19. Jahrhundert mit dem Einsatz neurophysiologischer Methoden. Damit konnten die Bogengänge im Innenohr, die schon seit Galen und vor allem durch die Schule von Vesalius in Padua bekannt waren, richtig zugeordnet werden. Nach der Entdeckung des 6. Sinnes wurden Stimulations- und Registriermethoden entwickelt.
Geschmacksknospen – gebündelt in Pilz-, Blatt- und Wallpapillen
Authors: Corts Magga 
Published: November 2022

SummaryGeschmacksknospen sind Gewebestrukturen in einem Epithelverband der Mundschleimhaut, die sich hauptsächlich auf der Zunge befinden. Sie kommen zudem in der Mundschleimhaut von Gaumensegel, Nasenrachen, Kehlkopf und Speiseröhre vor. Die Gesamtheit der Geschmacksknospen bezeichnet man auch als das Geschmacksorgan, denn sie enthält die sekundären Sinneszellen der Geschmackswahrnehmung.
Digitale Gesundheitsanwendungen in der Diabetologie
Authors: Bretschneider Maxi Pia , Schwarz Peter E.H. 
Published: November 2022

ZUSAMMENFASSUNGStand Oktober 2022 sind bereits 2 Diabetes-DiGAs zugelassen – HelloBetter (Zulassung Dezember 2021) und Vitadio (Zulassung April 2022). Des Weiteren gibt es mit zanadio (Zulassung November 2020) und Oviva Direkt (Zulassung Oktober 2021) 2 Adipositas-DiGAs, welche ebenfalls Patientinnen und Patienten mit Diabetes mellitus unterstützen. Viele weitere DiGAs sind in den Startlöchern und werden im Laufe des nächsten halben Jahres das DiGA-Verzeichnis füllen. Die Entwicklung erfolgt einerseits von ärztlichen Kolleginnen und Kollegen, andererseits von Start-Ups oder Konsortien gemeinsam mit Universitäten. Neben der ambulanten und stationären Therapie haben DiGAs das Potenzial, die dritte Säule in der Gesundheitsversorgung darzustellen. Die rasante Entwicklung wird von einigen Kolleginnen und Kollegen kritisch oder mit Skepsis gesehen, andere hingegen integrieren DiGAs bereits in die Praxis und sammeln erste Erfahrungen mit dem Einsatz dieser. Das Zulassungsverfahren von DiGAs ist vergleichbar mit dem neuer Medikamente und zusätzlich zum Therapieindikator muss auch ein positiver Versorgungseffekt nachgewiesen werden. Informationen darüber, wie die erstattungsfähigen DiGAs verordnet werden, finden sich im DiGA-Verzeichnis unter Informationen für Fachkreise. DiGAs ermöglichen ein besseres Empowerment der Patientinnen und Patienten für ein optimiertes Selbstmanagement und weisen den Weg zu einem patientenzentrierten Behandlungsansatz.
Affenpocken – eine neue Geschlechtskrankheit
Authors: Erkens Gudrun , Pappa Georgia , Thölken Karisa Farias Miksza 
Published: November 2022

ZusammenfassungAktuell steht zur Diskussion, wie und über welchen Verbreitungsweg es zu der deutlichen Zunahme von Affenpocken-Infektionen in Europa gekommen ist. Anhand unserer zweier Fallbeispiele möchten wir die histopathologischen Charakteristika und Unterschiede zu anderen viralen Infektionen wie etwa Schafpocken- oder Herpes simplex-Infektionen zeigen. Zudem möchten wir aufgrund der klinisch ähnlichen Präsentation von Affenpocken zu anderen STDs (sexual transmitted diseases) bezüglich genitaler Ulzerationen und Lymphadenopathien sowie der häufigen Koinfektionen mit weiteren STDs die differenzialdiagnostische Inkludierung in die gängige STD-Routinediagnostik vorschlagen.
Aloe Vera-Containing Matrix in Transdermal Fentanyl Therapy
Improves Adhesion, Skin Tolerance and Quality of Life: Results of a German
Multicenter Study with a New Fentanyl Patch
Authors: Dietrich Christoph G. , Kottmann Tanja , Voß Hans Werner , Lorenz Roxane 
Published: November 2022

Abstract
Background Chronic pain represents a significant and costly healthcare
problem especially in the older patient. Transdermal opioid therapy is easy to
apply and ensures constant supply of active ingredients. However, skin
irritation, poor adhesion and systemic side effects complicate transdermal pain
therapy.
Methods In the Relief study, comprising 54 centers, all in Germany, 252
patients were recruited and data about the general care situation as well as the
characteristics, effects and side effects of the Aloe vera fentanyl patch
were collected. 92 patients had a prior treatment with fentanyl patch without
Aloe vera, allowing a comparative analysis.
Results Compared to patches without Aloe vera, the new fentanyl
patch showed better adhesion. Systemic and local tolerance and pain reduction
were also significantly better. Patients also reported improvements in side
effects and central parameters of quality of life. The data regarding the care
situation in Germany showed remarkably low use of coanalgetics and laxatives in
pain patients.
Discussion
Aloe vera in transdermal pain treatment improves adhesion
and local tolerance of the patch. Pain control and quality of life were also
improved. Regional care data concerning cotreatment in pain therapy from this
study indicate a lack of penetration of existing guidelines in general
practitioners’ pain therapy.
Using Simulation to Support Evidence-Based Design of Safer Health Care Environments
Authors: Halamek Louis P. 
Published: November 2022

The design of health care environments and the technologies used within them have tremendous influence on the performance of the professionals who care for patients in those spaces. In turn, the performance of those professionals greatly impacts the safety of the care that is delivered to patients. Active and latent safety errors can be greatly reduced by rigorous testing of the patient care environment.While there are numerous types of testing that can be conducted, this manuscript will focus on the use of simulated clinical scenarios in realistic/real physical environments to detect and remediate weaknesses in the design of those environments with a focus on their use in perinatal centers.
Key Points
The Limitations and Unmet Needs of the Five Cornerstones to Guarantee Lifelong Optimization of Prophylaxis in Hemophilia Patients
Authors: Núñez Ramiro , Álvarez-Román María Teresa , Bonanad Santiago , González-Porras José Ramón , De La Corte-Rodriguez Hortensia , Berrueco Rubén , Jiménez-Yuste Víctor 
Published: November 2022

AbstractProphylaxis to prevent bleeding is highly recommended for hemophilia patients. The development of new drugs and tools for modeling personalized prophylaxis provides the means for people with hemophilia to lead active lives with a quality of life comparable to that of nonhemophilic individuals. The choice of regimens must be made on a highly individual basis. Unfortunately, reference guides neither always concur in their recommendations nor provide directions to cover all possible scenarios. In this review, a group of experts identify the significant limitations and unmet needs of prophylaxis, taking advantage of their clinical experience in the disease, and supported by a rigorous literature update. To perform a more systematic and comprehensive search for gaps, the main cornerstones that influence decisions regarding prophylactic patterns were first identified.Bleeding phenotype, joint status, physical activity, pharmacokinetics/medication properties, and adherence to treatment were considered as the primary mainstays that should allow physicians guiding prophylaxis to secure the best outcomes. Several challenges identified within each of these topics require urgent attention and agreement. The scores to assess severity of bleeding are not reliable, and lead to no consensus definition of severe bleeding phenotype. The joint status is to be redefined in light of new, more efficient treatments with an agreement to establish one scale as the unique reference for joint health. Further discussion is needed to establish the appropriateness of high-intensity physical activities according to patient profiles, especially because sustaining trough factor levels within the safe range is not always warranted for long periods. Importantly, many physicians do not benefit from the advantages provided by the programs based on population pharmacokinetic models to guide individualized prophylaxis through more efficient and cost-saving strategies. Finally, ensuring correct adherence to long-term treatments may be time-consuming for practitioners, who often have to encourage patients and review complex questionnaires.In summary, we identify five cornerstones that influence prophylaxis and discuss the main conflicting concerns that challenge the proper long-term management of hemophilia. A consensus exercise is warranted to provide reliable guidelines and maximize benefit from recently developed tools that should notably improve patients' quality of life.
From the Discovery of ADAMTS13 to Current Understanding of Its Role in Health and Disease
Authors: Woods Adriana Inés , Paiva Juvenal , Dos Santos Celia , Alberto María Fabiana , Sánchez-Luceros Analía 
Published: November 2022

AbstractADAMTS13 (a disintegrin-like metalloprotease domain with thrombospondin type 1 motif, member 13) is a protease of crucial importance in the regulation of the size of von Willebrand factor multimers. Very low ADAMTS13 activity levels result in thrombotic thrombocytopenic purpura, a rare and life-threatening disease. The mechanisms involved can either be acquired (immune-mediated thrombotic thrombocytopenic purpura [iTTP]) or congenital (cTTP, Upshaw–Schulman syndrome) caused by the autosomal recessive inheritance of disease-causing variants (DCVs) located along the ADAMTS13 gene, which is located in chromosome 9q34. Apart from its role in TTP, and as a regulator of microthrombosis, ADAMTS13 has begun to be identified as a prognostic and/or diagnostic marker of other diseases, such as those related to inflammatory processes, liver damage, metastasis of malignancies, sepsis, and different disorders related to angiogenesis. Since its first description almost 100 years ago, the improvement of laboratory tests and the description of novel DCVs along the ADAMTS13 gene have contributed to a better and faster diagnosis of patients under critical conditions. The ability of ADAMTS13 to dissolve platelet aggregates in vitro and its antithrombotic properties makes recombinant human ADAMTS13 treatment a potential therapeutic approach targeting not only patients with cTTP but also other medical conditions.
Crucial Stepping Stones in Platelet History
Authors: Hvas Anne-Mette 
Published: November 2022

AbstractThis review summarizes the time that has passed from the initial registration of the cells that turned out to be platelets up to today's advanced methodologies in platelet investigation. The first reports of “granular masses” appeared in the 1840s, but these “granular masses” remained an unsolved mystery until the 1870s. The breakthrough came in the 1873–1882 period. The cells that later turned out to be platelets were further identified by the German Professor Max Schultze, and later by Osler, who described their disk-like structure. These initial descriptions of platelets were expanded by impressive studies performed by the Italian Pathologist Bizzozero who uncovered the anatomy of platelets and described their role, first in experimental thrombosis and later in the clotting process. Nearly 20 years later, in 1906, Wright published the discovery of megakaryocytes as platelet precursors. Shortly thereafter, the clinical proof of concept illustrating the pivotal role of platelets in arresting bleeding was revealed by Duke who introduced the bleeding time test, also in this period. To investigate platelet function more specifically, light transmission aggregometry was introduced in 1962 and remains the gold standard today. This method inspired the development of several devices employing whole blood using different principles for evaluating platelet function. As of today, flow cytometry is the most advanced method and holds promise to provide new insights into platelet activation. Additionally, advances in genetic testing by the use of next-generation sequencing will allow further improvement of our ability to diagnose inherited platelet disorders.
Microsurgical Gender Affirmation Surgery
Authors: Watt Andrew J. , Safa Bauback , Chen Mang L. 
Published: November 2022

AbstractPhalloplasty in the female to male transgender patient is a complex operation aimed at creating a functional and aesthetic phallus, external genitalia, and perineum. Functional goals include standing micturition and sexual function with erogenous and tactile sensation as well as the ability to participate in penetrative intercourse. Functional genital reconstruction relies on creating of a fully lengthened urethra from local tissues as well as the provision for additional length via tissue transplantation. This manuscript will review techniques for the creation of perineal urethral segment as well as primary flaps available for the creation of neophallus. Particular emphasis is given to our preferred method of reconstruction: single-stage urethral lengthening with radial forearm flap phalloplasty including a review of surgical techniques and complications.