bluuebunny/crossref_metadata_2025_split huggingface dataset:
Catalyzed Michael addition, polycondensation, and the related performance of Diels–Alder self‐healing crosslinked polyamides
Authors: Chen Shuo , Feng Yu , Zhang Zhi‐Yuan , Li Xiang‐Yuan , Zhang Jun‐Ying , Zhao Jing‐Bo 
Published: February 2022

AbstractDiels–Alder (DA) addition is an efficient method to repair damages at mild conditions. It is often used in self‐healing polyurethanes and epoxy resins and seldom used in cross‐linked polyamides (cPAs). Michael addition becomes a useful method to synthesize cPAs. However, no efficient way has been established to conduct double‐addition of primary amines. In this work, organic catalyzed Michael addition and polycondensation were established to prepare polyamide oligomers with furan pendent groups (pFU‐PAs), and a DA addition was adopted to prepare self‐healing cross‐linked polyamides (SH‐cPAs). A bulk double Michael addition of furfurylamine and methyl acrylate was performed at 30–70°C in the presence of 1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene (TBD), 7‐methyl‐1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene (MTBD), or 4‐(N,N‐dimethylamino) pyridine (DMAP), and a high yield of furfurylamine‐N,N‐bis(methyl propionate) (FA‐BMP) was prepared. The catalytic activity order is MTBD>TBD >>DMAP in Michael addition. Melt polycondensation of FA‐BMP with bis(2‐aminopropyl) polypropyleneglycol and hexamethylene diamine was catalyzed by MTBD and N,N′‐diphenylthiourea. The DA addition of 1,5‐bismaleimido‐2‐methylpentane and pFU‐PAs was monitored by FT‐IR,1H NMR, DSC, polarizing optical microscopy, and gel content. In these catalyzed processes, the structures of FA‐BMP, pFU‐PAs, and SH‐cPAs were controlled easily, and the SH‐cPAs showed good mechanical property and excellent self‐healing performance of 88%–98%.
PP‐GF‐EPP sandwich structures as housing materials for rechargeable energy storage system of electric vehicles: Investigations into flame retardancy
Authors: Höhne Carl‐Christoph , Gettwert Volker , Kilian Sascha , Tillner Benjamin , Jahn Ivonne , Menrath Andreas 
Published: February 2022

AbstractThe growing importance of electric mobility has led to an increased demand for safety technologies in the automotive sector, such as the flame retardancy of materials used for electric vehicles. The fire protection of a fully equipped rechargeable energy storage system (REESS), including battery, housing, control electronics, etc., against a fuel fire must be tested according to UNECE Regulation No. 100 Annex 8E ‐ Fire Resistance (UNECE‐R100‐8E). To pass this fire retardancy requirement, the flame retardancy of the housing materials is of great importance. In this study, the flame retardancy of glass‐fiber‐reinforced polypropylene (PP‐GF) tape laminates containing the flame retardant magnesium hydroxide and different GF amounts, as well as sandwich structures of these PP‐GF tape laminates with a polypropylene bead foam (EPP) core, are investigated by a limiting oxygen index test, a UL94 test and a cone calorimeter test. Furthermore, a newly developed approach of a bench‐scale fuel fire test which simulates the fire treatment of the UNECE‐R100‐8E on component level is used.
“Communicating Lily’s Pain”: A reflective narrative commentary about co‐creating a resource to provoke thinking and change about assessing and managing the pain of children with profound cognitive impairment
Authors: Carter Bernie , Young Rob , Munro James 
Published: February 2022

AbstractThis paper draws together about 20 years of research work and discovery and the development of a resource about pain assessment and management in children with profound cognitive impairment. The animation tells the story of an imagined child called Lily and the skills her mother uses and the challenges that her mother faces in assessing and managing Lily's pain. The animation is built on stories drawn from qualitative research findings, conversations while in clinical practice and with members of the general public, parent advisers and other sources. Most of the “evidence” came from stories shared by parents and healthcare professionals. This paper draws on some elements of socio‐narratology and is predicated on the basis that stories are important and they can act on and with us. By using an animation to tell Lily's story, the intention was to communicate research findings to a wider and more diverse audience than the typical readership of an academic journal. The intention was to act in and on people's consciousness about children's pain and to strengthen relationships and create bonds between clinicians, parents, and children in pain to make their dialog more social, connected, and meaningful. All three of us—the researcher, the writer, and the animator—have been marked and “re‐shaped” by our work related to creating Lily; we have learned more about children like Lily and their mothers, and we have learned more about ourselves and our humanity. This animation is still a story in progress, a story ‘in the wild’, a story (and a resource) we would like you to re‐tell and share. The story of Lily's pain aimed to change the lives of parents and children and professionals. Our hope is that you can be part of that change.
Incorporating historical controls in clinical trials with longitudinal outcomes using the modified power prior
Authors: Qi Hongchao , Rizopoulos Dimitris , Lesaffre Emmanuel , van Rosmalen Joost 
Published: February 2022

AbstractSeveral dynamic borrowing methods, such as the modified power prior (MPP), the commensurate prior, have been proposed to increase statistical power and reduce the required sample size in clinical trials where comparable historical controls are available. Most methods have focused on cross‐sectional endpoints, and appropriate methodology for longitudinal outcomes is lacking. In this study, we extend the MPP to the linear mixed model (LMM). An important question is whether the MPP should use the conditional version of the LMM (given the random effects) or the marginal version (averaged over the distribution of the random effects), which we refer to as the conditional MPP and the marginal MPP, respectively. We evaluated the MPP for one historical control arm via a simulation study and an analysis of the data of Alzheimer's Disease Cooperative Study (ADCS) with the commensurate prior as the comparator. The conditional MPP led to inflated type I error rate when there existed moderate or high between‐study heterogeneity. The marginal MPP and the commensurate prior yielded a power gain (3.6%–10.4% vs. 0.6%–4.6%) with the type I error rates close to 5% (5.2%–6.2% vs. 3.8%–6.2%) when the between‐study heterogeneity is not excessively high. For the ADCS data, all the borrowing methods improved the precision of estimates and provided the same clinical conclusions. The marginal MPP and the commensurate prior are useful for borrowing historical controls in longitudinal data analysis, while the conditional MPP is not recommended due to inflated type I error rates.
Morus alba L. water extract changes gut microbiota and fecal metabolome in mice induced by high‐fat and high‐sucrose diet plus low‐dose streptozotocin
Authors: Du Yan , Li Ding‐xiang , Lu Dong‐yu , Zhang Ran , Zheng Xiao‐xiao , Xu Bing‐ju , Zhao Yan‐lin , Ji Shuai , Guo Meng‐zhe , Wang Liang , Tang Dao‐quan 
Published: February 2022

AbstractGut microbiota plays a key role in the pathophysiology of type 2 diabetes mellitus (T2D). Mulberry leaf has a hypoglycemic effect, but the potential mechanism is not fully understood. This study aimed to explore the influences and potential mechanisms of mulberry leaf water extract (MLWE) intervention on mice with T2D induced through a high‐fat and high‐sucrose diet combined with streptozotocin by the combination of fecal metabolomics and gut microbiota analysis. Results showed that MLWE could decrease fasting blood glucose and body weight while ameliorating lipid profiles, insulin resistance, liver inflammation, and the accumulation of lipid droplets in T2D mice. MLWE could reverse the abundances of the phyla Actinobacteria and Bacteroidetes and the ratio of Firmicutes/Bacteroidetes, and increase the abundances of the phyla Cyanobacteria and Epsilonbacteraeota in the feces of T2D mice. The abundances of genera Alloprevotella, Parabacteroides, Muribaculaceae, and Romboutsia in the feces of T2D mice could be reversed, while Oscillatoriales_cyanobacterium and Gastranaerophilales could be reinforced by MLWE supplementation. The levels of nine metabolites in the feces of T2D mice were improved, among which glycine, Phe‐Pro, urocanic acid, phylloquinone, and lactate were correlated with Romboutsia and Gastranaerophilales. Taken together, we conclude that MLWE can effectively alleviate T2D by mediating the host–microbial metabolic axis.
Anhydrous Nucleic Acid Nanoparticles for Storage and Handling at Broad Range of Temperatures
Authors: Tran Allison N. , Chandler Morgan , Halman Justin , Beasock Damian , Fessler Adam , McKeough Riley Q. , Lam Phuong Anh , Furr Daniel P. , Wang Jian , Cedrone Edward , Dobrovolskaia Marina A. , Dokholyan Nikolay V. , Trammell Susan R. , Afonin Kirill A. 
Published: February 2022

AbstractRecent advances in nanotechnology now allow for the methodical implementation of therapeutic nucleic acids (TNAs) into modular nucleic acid nanoparticles (NANPs) with tunable physicochemical properties which can match the desired biological effects, provide uniformity, and regulate the delivery of multiple TNAs for combinatorial therapy. Despite the potential of novel NANPs, the maintenance of their structural integrity during storage and shipping remains a vital issue that impedes their broader applications. Cold chain storage is required to maintain the potency of NANPs in the liquid phase, which greatly increases transportation costs. To promote long‐term storage and retention of biological activities at higher temperatures (e.g., +50 °C), a panel of representative NANPs is first exposed to three different drying mechanisms—vacuum concentration (SpeedVac), lyophilization (Lyo), and light‐assisted drying (LAD)—and then rehydrated and analyzed. While SpeedVac primarily operates using heat, Lyo avoids temperature increases by taking advantage of pressure reduction and LAD involves a near‐infrared laser for uniform drying in the presence of trehalose. This work compares and defines refinements crucial in formulating an optimal strategy for producing stable, fully functional NANPs and presents a forward advancement in their development for clinical applications.
Field‐assisted thermionic emission toward quantitative modeling of charge‐transfer mechanisms in contact electrification
Authors: Xia Xin , Wang Haoyu , Zi Yunlong 
Published: February 2022

AbstractCharge transfer mechanisms of contact electrification (CE) are essential for widening applications of the triboelectric nanogenerator, and thus are widely studied by scientists around the world. However, the quantitative modeling of CE, especially that between polymers, is still lacking. Herein, a model was proposed to describe the contributions from different mechanisms, including electron transfer and mass transfer in polymer/polymer CE through the field‐assisted thermionic emission, where three groups of charge transfer mechanisms were distinguished by the polarity of the charge transfer and the corresponding electric field. The results indicated that the total generated charge in CE is actually much larger than the measured net surface charge, confirming the bidirectional material‐dependent charge transfer mechanisms between two surfaces, which is meaningful for understanding the millennium puzzle in triboelectrification and provides a new perspective for promoting the applications to tailor surface charge generation.
Paediatric Acute Lymphoblastic Leukaemia (ALL)
Authors: Bader Peter , Locatelli Franco , Peters Christina 
Published: February 2022

AbstractAcute lymphoblastic leukaemia (ALL) is the most frequent malignant disease in childhood and adolescence, with an annual incidence of approximately 3–4 cases per 100,000 children under 15 years of age. Multimodal chemotherapy forms the base of current ALL treatment. Based on excellent national and international collaboration in consecutive prospective, randomized clinical trials, the prognosis of childhood ALL has significantly improved over time. Currently, up to 90% of all paediatric patients with ALL will survive.
Diffuse Large B Cell Lymphoma and Primary Mediastinal Lymphoma
Authors: Glass Bertram , Kersten Marie José 
Published: February 2022

AbstractThe outcome of patients with large B cell lymphoma (LBCL) who did not respond to a classical immunochemotherapy regimen at any time or relapsed within 1 year following chemoimmunotherapy is poor. The Scholar-One-Study showed long-term event-free survival for less than 20% of these patients (Crump et al. 2017). The introduction of chimeric antigen receptor T cell therapy (CAR-T) is a substantial advancement for these patients, offering long-term remission and a curative prospect for 30 to 40% of patients (summarized in Table 12.1), (Abramson et al. 2020; Neelapu et al. 2017; Schuster et al. 2019b). To date, in Europe, two products (axicabtagene ciloleucel and tisagenlecleucel) have been licenced by the European Medical Agency, and a third product (lisocabtagene maraleucel) will become available in 2021. All these products are licenced for patients who have failed at least two prior lines of systemic therapy. This initially defines, however broad, a range of possible situations in which the application of CART is indicated. The following considerations may help to further define the patient population that should be offered CAR-T cells as the next line of treatment. Studies addressing the potential benefit of CAR-T cells compared to high-dose chemotherapy and autologous stem cell transplantation for second-line treatment of LBCL have been fully recruited, but the results are still pending.
Developments in Solid Tumours
Authors: Pedrazzoli Paolo , Haanen John B. A. G. 
Published: February 2022

AbstractChimeric antigen receptor (CAR) T cells have emerged as breakthrough therapies in patients with refractory haematologic malignancies, and the highly encouraging clinical results have fuelled expectations of implementing these strategies in other cancer types. However, a similar success of CAR-T cell treatment has not yet been observed in solid tumours. Various factors, including the immunosuppressive nature of the tumour microenvironment, hinder CAR-T cell trafficking and infiltration into scarcely accessible tumour sites, and difficulties in identifying targetable antigens with optimal expression and a good toxicity profile, limiting CAR-T dose escalation, must be overcome to achieve success in the treatment of solid cancers (Comoli et al. 2019).
Bridging to CAR-T Cells in Children, Adolescents, and Young Adults with ALL
Authors: Baruchel André 
Published: February 2022

AbstractLeukapheresis can be performed in most patients, including infants, but not all patients will receive autologous CAR-T cells. The ELIANA trial can be taken as an example to help understand the issues: 97 patients were successfully screened and enrolled, but only 79 of them finally made it to the infusion. Of the remaining 18 patients, 10 died or experienced an AE during the manufacturing time, and 8 patients had issues with the manufacturing process (Grupp et al. 2018).
Bridging Chemotherapy: Multiple Myeloma
Authors: Manier Salomon , Jurczyszyn Artur , Vesole David H. 
Published: February 2022

AbstractIn the phase 2 KarMMa study, 88% of the patients received bridging therapy with only a 5% response (Munshi et al. 2021). In the CARTITUDE 1 trial, 75% of the patients received bridging therapy, with a reduction in tumour burden observed in 34% of the patients prior to cilta-cel infusion, but no patients achieved a CR or better while on bridging therapy (Madduri et al. 2019). Bridging therapy is recommended for virtually all patients. An exception can be discussed for patients with slowly progressive disease, who may not need to receive bridging therapy after leukapheresis; however, this strategy exposes them to a risk of rapid progression later during the manufacturing period. In the future, with allogeneic CAR-T cells, bridging therapy will likely not be necessary because the time between patient inclusion and CAR-T cell infusion is much reduced.
The Regulatory Framework for CAR-T Cells in Europe: Current Status and Foreseeable Changes AND Centre Qualification by Competent Authorities and Manufacturers
Authors: McGrath Eoin , Machalik Petr 
Published: February 2022

AbstractUnder current European Union regulations, CAR-T cell therapies fall under the advanced therapy medicinal products (ATMPs) framework. ATMPs represent a category of medicinal products defined in EU Regulation 1394/2007 and subdivided into four categories, of which autologous or allogeneic CAR-T cells, among other therapies, are considered gene therapy medicinal products (GTMPs). ATMPs are subject to a centralized evaluation framework whereby one authorization is valid for all countries in the EU led by the European Medicines Agency’s Committee for Advanced Therapies (CAT). The framework includes different regulatory pathways for bringing ATMPs from clinical trials to market authorization, and the regulatory pathway taken will depend on a product’s characteristics and the target patient population. In 2018, two chimeric antigen receptor (CAR) T cell therapies, Yescarta and Kymriah, completed their authorization process via the priority medicines PRIME scheme to Marketing Authorization (Detela and Lodge 2019).
Patient Referral
Authors: Snowden John , Duarte Rafael F. 
Published: February 2022

AbstractEarly and efficient patient referral is a critical step in the ability of potential candidates to access CAR-T therapy. Despite improvements in centre qualification and availability, regulatory and reimbursement frameworks, and addressing the educational needs of the various members of the health care team, referring haematologists and oncologists identify major barriers to prescribing CAR-T therapy, including cumbersome logistics, high cost and toxicity, and clinical challenges, such as deterioration of the patient prior to CAR-T administration and the need for bridging chemotherapy while awaiting manufacturing.
The relationship between bending and tension strength of Irish and UK spruce and pine
Authors: Gil-Moreno David , Ridley-Ellis Dan , O’Ceallaigh Conan , Harte Annette M. 
Published: February 2022

AbstractThe correct characterisation of wood properties is fundamental for the best utilisation of resources. In Europe, grading is defined by strength classes that are determined based on either bending or tension tests. The European standards give equations to estimate characteristic strength in tension from characteristic strength in bending, and vice versa depending on which was tested. These equations are applied to all softwoods. The aim of this paper is to empirically determine the relationship between bending and tension strength properties using two conifer species grown in Ireland and the UK. The results show that the relationships change with species. The standard conversion underestimates, importantly, the performance of spruce for tension loads calculated for the most common bending strength class for Ireland and the UK, C16. The opposite occurs on the reverse conversion. Additionally, the study includes published data from continental Europe, to establish a new conversion that uses timber from a broader range of grades, and that adjusts the tension performance of Irish and UK spruce obtained from bending strength classes, ensuring safe values for design.
Chancen und Risiken der Telemedizin in der Urologie
Authors: Wülfing Christian 
Published: February 2022

ZusammenfassungDie Telemedizin in Deutschland ist auf dem Vormarsch. Die gesetzlichen Rahmenbedingungen für die Telemedizin sind seit 2018 sehr vorangetrieben worden. Neben dem Terminservice- und Versorgungsgesetz (TSVG) traten das Digitale-Versorgung-Gesetz (DVG) und das Patientendaten-Schutz-Gesetz (PDSG) sowie das Krankenhauszukunftsgesetz (KHZG) in Kraft. Auf der Anbieterseite kommen nun besonders die digitalen Gesundheitsanwendungen (DiGA), die zukünftig als „App auf Rezept“ verfügbar und von den Kostenträgern erstattbar sein werden, in den Markt (inklusive urologischer Anwendungen). Ebenso ist die Videosprechstunde nicht zuletzt durch die Coronapandemie sehr vorangekommen und dabei, sich weiter zu etablieren. Auch die elektronische Patientenakte (ePA) wird hoffentlich in hoher Geschwindigkeit umfassend verfügbar sein und genutzt werden, weil hierdurch ein starker Effizienzschub in der täglichen Arbeit eintreten wird. Dieses wird ergänzt durch das E‑Rezept und weitere Innovationen im Bereich der Medikamentenversorgung und -zustellung, die diese Entwicklung unterstützen werden. Als Herausforderungen im Umsetzungsprozess der Telemedizin bleiben v. a. die sehr wichtigen Aspekte des Datenschutzes, der Datensicherheit und die Problematik der Interoperabilität erhalten, werden hoffentlich aber den Fortschritt, der dringend benötigt wird, nicht sonderlich abbremsen. Urologinnen und Urologen werden durch die Fortschritte in der Digitalisierung der Medizin und der Urologie einen erheblichen Effizienzgewinn in der täglichen Arbeit erreichen.
Improved high-throughput screening technique to rapidly isolate Chlamydomonas transformants expressing recombinant proteins
Authors: Sproles Ashley E. , Berndt Anthony , Fields Francis J. , Mayfield Stephen P. 
Published: February 2022

Abstract

The single-celled eukaryotic green alga Chlamydomonas reinhardtii has long been a model system for developing genetic tools for algae, and is also considered a potential platform for the production of high-value recombinant proteins. Identifying transformants with high levels of recombinant protein expression has been a challenge in this organism, as random integration of transgenes into the nuclear genome leads to low frequency of cell lines with high gene expression. Here, we describe the design of an optimized vector for the expression of recombinant proteins in Chlamydomonas, that when transformed and screened using a dual antibiotic selection, followed by screening using fluorescence activated cell sorting (FACS), permits rapid identification and isolation of microalgal transformants with high expression of a recombinant protein. This process greatly reduces the time required for the screening process, and can produce large populations of recombinant algae transformants with between 60 and 100% of cells producing the recombinant protein of interest, in as little as 3 weeks, that can then be used for whole population sequencing or individual clone analysis. Utilizing this new vector and high-throughput screening (HTS) process resulted in an order of magnitude improvement over existing methods, which normally produced under 1% of algae transformants expressing the protein of interest. This process can be applied to other algal strains and recombinant proteins to enhance screening efficiency, thereby speeding up the discovery and development of algal-derived recombinant protein products.

Key points
• A protein expression vector using double-antibiotic resistance genes was designed
• Double antibiotic selection causes fewer colonies with more positive for phenotype
• Coupling the new vector with FACS improves microalgal screening efficiency > 60%