bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cdk5 and GSK3β inhibit fast endophilin-mediated endocytosis
Authors: Ferreira Antonio P. A. , Casamento Alessandra , Carrillo Roas Sara , Halff Els F. , Panambalana James , Subramaniam Shaan , Schützenhofer Kira , Chan Wah Hak Laura , McGourty Kieran , Thalassinos Konstantinos , Kittler Josef T. , Martinvalet Denis , Boucrot Emmanuel 
Published: April 2021

AbstractEndocytosis mediates the cellular uptake of micronutrients and cell surface proteins. Fast Endophilin-mediated endocytosis, FEME, is not constitutively active but triggered upon receptor activation. High levels of growth factors induce spontaneous FEME, which can be suppressed upon serum starvation. This suggested a role for protein kinases in this growth factor receptor-mediated regulation. Using chemical and genetic inhibition, we find that Cdk5 and GSK3β are negative regulators of FEME. They antagonize the binding of Endophilin to Dynamin-1 and to CRMP4, a Plexin A1 adaptor. This control is required for proper axon elongation, branching and growth cone formation in hippocampal neurons. The kinases also block the recruitment of Dynein onto FEME carriers by Bin1. As GSK3β binds to Endophilin, it imposes a local regulation of FEME. Thus, Cdk5 and GSK3β are key regulators of FEME, licensing cells for rapid uptake by the pathway only when their activity is low.
How cyanophage S-2L rejects adenine and incorporates 2-aminoadenine to saturate hydrogen bonding in its DNA
Authors: Czernecki Dariusz , Legrand Pierre , Tekpinar Mustafa , Rosario Sandrine , Kaminski Pierre-Alexandre , Delarue Marc 
Published: April 2021

AbstractBacteriophages have long been known to use modified bases in their DNA to prevent cleavage by the host’s restriction endonucleases. Among them, cyanophage S-2L is unique because its genome has all its adenines (A) systematically replaced by 2-aminoadenines (Z). Here, we identify a member of the PrimPol family as the sole possible polymerase of S-2L and we find it can incorporate both A and Z in front of a T. Its crystal structure at 1.5 Å resolution confirms that there is no structural element in the active site that could lead to the rejection of A in front of T. To resolve this contradiction, we show that a nearby gene is a triphosphohydolase specific of dATP (DatZ), that leaves intact all other dNTPs, including dZTP. This explains the absence of A in S-2L genome. Crystal structures of DatZ with various ligands, including one at sub-angstrom resolution, allow to describe its mechanism as a typical two-metal-ion mechanism and to set the stage for its engineering.
Convergent synthesis of diversified reversible network leads to liquid metal-containing conductive hydrogel adhesives
Authors: Xu Yong , Rothe Rebecca , Voigt Dagmar , Hauser Sandra , Cui Meiying , Miyagawa Takuya , Patino Gaillez Michelle , Kurth Thomas , Bornhäuser Martin , Pietzsch Jens , Zhang Yixin 
Published: April 2021

AbstractMany features of extracellular matrices, e.g., self-healing, adhesiveness, viscoelasticity, and conductivity, are associated with the intricate networks composed of many different covalent and non-covalent chemical bonds. Whereas a reductionism approach would have the limitation to fully recapitulate various biological properties with simple chemical structures, mimicking such sophisticated networks by incorporating many different functional groups in a macromolecular system is synthetically challenging. Herein, we propose a strategy of convergent synthesis of complex polymer networks to produce biomimetic electroconductive liquid metal hydrogels. Four precursors could be individually synthesized in one to two reaction steps and characterized, then assembled to form hydrogel adhesives. The convergent synthesis allows us to combine materials of different natures to generate matrices with high adhesive strength, enhanced electroconductivity, good cytocompatibility in vitro and high biocompatibility in vivo. The reversible networks exhibit self-healing and shear-thinning properties, thus allowing for 3D printing and minimally invasive injection for in vivo experiments.
Cryopreservation method for Drosophila melanogaster embryos
Authors: Zhan Li , Li Min-gang , Hays Thomas , Bischof John 
Published: April 2021

AbstractThe development of a widely adopted cryopreservation method remains a major challenge in Drosophila research. Here we report a robust and easily implemented cryopreservation protocol of Drosophila melanogaster embryos. We present innovations for embryo permeabilization, cryoprotectant agent loading, and rewarming. We show that the protocol is broadly applicable, successfully implemented in 25 distinct strains from different sources. We demonstrate that for most strains, >50% embryos hatch and >25% of the resulting larvae develop into adults after cryopreservation. We determine that survival can be significantly improved by outcrossing to mitigate the effect of genetic background for strains with low survival after cryopreservation. We show that flies retain normal sex ratio, fertility, and original mutation after successive cryopreservation of 5 generations and 6-month storage in liquid nitrogen. Lastly, we find that non-specialists are able to use this protocol to obtain consistent results, demonstrating potential for wide adoption.
Characterisation of PALB2 tumours through whole-exome and whole-transcriptomic analyses
Authors: Ng Pei Sze , Pan Jia Wern , Ahmad Zabidi Muhammad Mamduh , Rajadurai Pathmanathan , Yip Cheng Har , Reuda Oscar M. , Dunning Alison M. , Antoniou Antonis C. , Easton Douglas F. , Caldas Carlos , Chin Suet-Feung , Teo Soo Hwang 
Published: April 2021

AbstractRare protein-truncating variants (PTVs) in PALB2 confer increased risk to breast cancer, but relatively few studies have reported the characteristics of tumours with PALB2 PTVs. In this study, we describe molecular characteristics of tumours with either germline or somatic alterations in PALB2. DNA from fresh frozen tumour tissues and matched peripheral blood lymphocytes for 560 breast cancer patients was subjected for whole-exome sequencing (WES), and RNA from tumour tissues was subjected to RNA sequencing (RNA-seq). We found six cases with germline and three with somatic protein-truncating variants in PALB2. The characteristics of tumours in patients with PALB2 PTVs were similar to those with BRCA1 and BRCA2 PTVs, having significantly more somatic alterations, and a high proportion of the mutational signature and genomic scar scores characteristic of deficiencies in homologous recombination (HR), compared to tumours arising in non-carriers. Unlike tumours arising in patients with BRCA1 and BRCA2 PTVs, PALB2 tumours did not have high prevalence of TP53 somatic alterations or an enriched immune microenvironment. In summary, PALB2 tumours show the homologous recombination deficiencies characteristic of BRCA1 and BRCA2 tumours, and highlight the potential clinical relevance of PALB2 mutational status in guiding therapeutic choices.
Study on abnormal hot corrosion behavior of nickel-based single-crystal superalloy at 900 °C after drilling
Authors: Chen Zehao , Wu Mengmeng , Pei Yanling , Li Shusuo , Gong Shengkai 
Published: April 2021

AbstractThe hot corrosion behavior of nickel-based single-crystal superalloy after drilling is investigated at 900 °C. The characteristics of hot corrosion after drilling which are different from normal hot corrosion are reflected in the formation of a more stable oxide layer and less severe spallation. The change of microstructure around the hole is the main reason for the formation of a stable oxide layer during hot corrosion by changing the diffusion process of alloying elements. Subsequently, the formation of a stable oxide layer can reduce the effect of spalling by optimizing surface stress.
Glucose and fatty acid metabolism involved in the protective effect of metformin against ulipristal-induced endometrial changes in rats
Authors: Hamza Marwa S. , Ramadan Eman , Salama Salama A. 
Published: April 2021

AbstractUlipristal acetate (UPA) is effective in the treatment of uterine fibroids. However, its clinical use is hampered by the development of pathologic progesterone receptor modulator-associated endometrial changes (PAECs). The current study was designed to test the hypothesis that UPA-induced PAECs are associated with deranged expression of some metabolic genes. In addition, metformin can mitigate UPA-induced PAECs through modulating the expression of these genes. In the present study, twenty-eight female non-pregnant, nulligravid Wistar rats were treated with UPA (0.1 mg/kg/day, intragastric) and/or metformin (50 mg/kg/day, intragastric) for 8 weeks. Our results demonstrated that co-treatment with metformin significantly reduced UPA-induced PAECs. In addition, co-treatment with metformin and UPA was associated with significant increase in the Bax and significant reduction in Bcl-2, PCNA, Cyclin-D1and ER-α as compared to treatment with UPA alone. Furthermore, treatment with UPA alone was associated with deranged expression of 3-phosphoglycerate dehydrogenase (3-PHGDH), glucose-6-phosphate dehydrogenase (G6PD), transketolase (TKT), fatty acid synthase (FAS) and CD36. Most importantly, co-treatment with metformin markedly reduced UPA-induced altered expression of these metabolic genes in endometrial tissues. In conclusion, UPA-induced PAECs are associated with altered expression of genes involved in cell proliferation, apoptosis, estrogen receptor, glucose metabolism and lipid metabolism. Co-treatment with metformin abrogated UPA-induced PAECs most likely through the modulation of the expression of these genes.
Boom-bust population dynamics increase diversity in evolving competitive communities
Authors: Doebeli Michael , Jaque Eduardo Cancino , Ispolatov Yaroslav 
Published: April 2021

AbstractThe processes and mechanisms underlying the origin and maintenance of biological diversity have long been of central importance in ecology and evolution. The competitive exclusion principle states that the number of coexisting species is limited by the number of resources, or by the species’ similarity in resource use. Natural systems such as the extreme diversity of unicellular life in the oceans provide counter examples. It is known that mathematical models incorporating population fluctuations can lead to violations of the exclusion principle. Here we use simple eco-evolutionary models to show that a certain type of population dynamics, boom-bust dynamics, can allow for the evolution of much larger amounts of diversity than would be expected with stable equilibrium dynamics. Boom-bust dynamics are characterized by long periods of almost exponential growth (boom) and a subsequent population crash due to competition (bust). When such ecological dynamics are incorporated into an evolutionary model that allows for adaptive diversification in continuous phenotype spaces, desynchronization of the boom-bust cycles of coexisting species can lead to the maintenance of high levels of diversity.
Integrated bioinformatics analysis reveals novel key biomarkers and potential candidate small molecule drugs in gestational diabetes mellitus
Authors: Alur Varun , Raju Varshita , Vastrad Basavaraj , Tengli Anandkumar , Vastrad Chanabasayya , Kotturshetti Shivakumar 
Published: April 2021

Abstract
Gestational diabetes mellitus (GDM) is the metabolic disorder that appears during pregnancy. The current investigation aimed to identify central differentially expressed genes (DEGs) in GDM. The transcription profiling by array data (E-MTAB-6418) was obtained from the ArrayExpress database. The DEGs between GDM samples and non-GDM samples were analyzed. Functional enrichment analysis were performed using ToppGene. Then we constructed the protein–protein interaction (PPI) network of DEGs by the Search Tool for the Retrieval of Interacting Genes database (STRING) and module analysis was performed. Subsequently, we constructed the miRNA–hub gene network and TF–hub gene regulatory network. The validation of hub genes was performed through receiver operating characteristic curve (ROC). Finally, the candidate small molecules as potential drugs to treat GDM were predicted by using molecular docking. Through transcription profiling by array data, a total of 869 DEGs were detected including 439 up-regulated and 430 down-regulated genes. Functional enrichment analysis showed these DEGs were mainly enriched in reproduction, cell adhesion, cell surface interactions at the vascular wall and extracellular matrix organization. Ten genes, HSP90AA1, EGFR, RPS13, RBX1, PAK1, FYN, ABL1, SMAD3, STAT3 and PRKCA were associated with GDM, according to ROC analysis. Finally, the most significant small molecules were predicted based on molecular docking. This investigation identified hub genes, signal pathways and therapeutic agents, which might help us, enhance our understanding of the mechanisms of GDM and find some novel therapeutic agents for GDM.
Formation of formaldehyde through methanol-ice-mantle (CH3OH)10 bombardment by OH+ cation
Authors: Inostroza-Pino Natalia , MacLeod-Carey Desmond , Heyser Cristopher , Mardones Diego , Espinoza Carlos , Ge Jixing 
Published: April 2021

Context. Formaldehyde H2CO was the first organic polyatomic molecule discovered in the interstellar medium to have been detected in a variety of sources. However, pathways to synthesize this molecule under interstellar conditions have yet to be discussed.
Aims. We carried out a systematic study to analyze the chemical processes that can explain the H2CO formation mechanism toward a decamer of methanol (CH3OH)10 as target material to mimic an ice mantle bombarded by an OH+ cation.
Methods. We performed Born-Oppenheimer (ab initio) molecular dynamics simulations to obtain the formation mechanisms of complex organic molecules (COMs) such as formaldehyde H2CO and its HCOH isomer.
Results. We found that CH2OH+ and CH2(OH)2 are the main precursors to form H2CO and HCOH. We discuss its formation mechanisms and the astrophysical implications in star-forming regions. These processes are likely relevant to the production of COMs.
Cannabis als Medizin: Sonderregelungen sicher anwenden
Authors: Cremer-Schaeffer Peter 
Published: April 2021

ZusammenfassungSeit März 2017 können Cannabisblüten und -extrakte verschrieben werden, die nicht als Arzneimittel zugelassen sind. Sie werden vor allem zur Behandlung von Schmerzen eingesetzt. Bei Patienten mit chronischen Schmerzen, die auf etablierte Therapieverfahren nicht mehr ansprechen, können cannabisbasierte Arzneimittel eine Option für einen Behandlungsversuch sein. Dieser Beitrag zeigt, wie die rechtlichen Regelungen zur Verschreibung solcher Arzneimittel sicher angewendet werden können.
Severe upper gastrointestinal bleeding is halted by endoscopically delivered self-propelling thrombin powder: A porcine pilot study
Authors: Ali-Mohamad Nabil , Cau Massimo , Baylis James , Zenova Veronika , Semple Hugh , Beckett Andrew , McFadden Andrew , Donnellan Fergal , Kastrup Christian 
Published: April 2021

Abstract
Background and study aims Hemostatic powders have emerged recently to treat upper gastrointestinal bleeding (UGIB). Previously, we developed a novel self-propelling thrombin powder (SPTP) that effectively manages external pulsatile arterial bleed without compression, by effervescing and carrying thrombin into the wound. Here, we tested if SPTP, sprayed endoscopically, can manage severe UGIB in a live porcine model.
Materials and methods Anesthetized pigs underwent laparotomy to insert the gastroepiploic vascular bundles into the stomach lumen via a gastrotomy. Bleeding was initiated endoscopically in the stomach by needle knife. SPTP was delivered to the site of bleeding from a CO2-powered spray device using a 7 FR catheter. Successful primary hemostasis, time to hemostasis, and the mass of SPTP delivered were measured.
Results Hemostasis was achieved at all bleeding sites using SPTP. Mean time to hemostasis was 4.2 ± 0.9 minutes (mean ± standard error of the mean, n = 12). The average mass of SPTP delivered was 2.4 ± 0.6 g.
Conclusions In this pilot study, SPTP successfully stopped 12 cases of severe UGIB, demonstrating early promise asa novel hemostatic powder.
Training methods in optical diagnosis and characterization of colorectal polyps: a systematic review and meta-analysis
Authors: Siau Keith , Cannatelli Rosanna , Antonelli Giulio , Smith Samuel C.L. , Shivaji Uday N. , Ghosh Subrata , Saltzman John R. , Hassan Cesare , Iacucci Marietta 
Published: April 2021

Abstract
Background and study aims Correct optical diagnosis of colorectal polyps is crucial to implement a resect and discard strategy. Training methods have been proposed to reach recommended optical diagnosis thresholds. The aim of our study was to present a systematic review and meta-analysis on optical diagnosis training.
Methods PubMed/Medline and Cochrane databases were searched between 1980 and October 2019 for studies reporting outcomes on optical diagnosis training of colorectal polyps. The primary outcome was optical diagnosis accuracy compared to histological analysis pre-training and post-training intervention. Subgroup analyses of experienced/trainee endoscopists, training methods, and small/diminutive polyps were included.
Results Overall, 16 studies met inclusion criteria, analyzing the impact of training on 179 endoscopists. Pre-training accuracy was 70.3 % (6416/9131 correct diagnoses) whereas post-training accuracy was 81.6 % (7416/9213 correct diagnoses) (risk ratio [RR] 1.17; 95 % confidence interval [CI]: 1.09–1.24, P < 0.001). In experienced endoscopists, accuracy improved from 69.8 % (3771/5403 correct diagnoses) to 82.4 % (4521/5485 correct diagnoses) (RR 1.20; 95 % CI: 1.11–1.29, P < 0.001). Among trainees, accuracy improved from 69.6 % (2645/3803 correct diagnoses) to 78.8 % (2995/3803 correct diagnoses) (RR 1.14; 95 % CI 1.06–1.24, P < 0.001). In the small/diminutive polyp subgroup, accuracy improved from 68.1 % (3549/5214 correct diagnoses) to 77.1 % (4022/5214 correct diagnoses) in (RR 1.16 95 % CI 1.08–1.24 P < 0.001). On meta-regression analysis, the improvement in accuracy did not differ between computerized vs. didactic training approaches for experienced (P = 0.792) and trainee endoscopists (P = 0.312).
Conclusions Optical diagnosis training is effective in improving accuracy of histology prediction in colorectal polyps. Didactic and computer-based training show comparable effectiveness in improving diagnostic accuracy.
Real-time deep learning-based colorectal polyp localization on clinical video footage achievable with a wide array of hardware configurations
Authors: Podlasek Jeremi , Heesch Mateusz , Podlasek Robert , Kilisiński Wojciech , Filip Rafał 
Published: April 2021

Abstract
Background and study aims Several computer-assisted polyp detection systems have been proposed, but they have various limitations, from utilizing outdated neural network architectures to a requirement for multi-graphics processing unit (GPU) processing, to validating on small or non-robust datasets. To address these problems, we developed a system based on a state-of-the-art convolutional neural network architecture able to detect polyps in real time on a single GPU and tested on both public datasets and full clinical examination recordings.
Methods The study comprised 165 colonoscopy procedure recordings and 2678 still photos gathered retrospectively. The system was trained on 81,962 polyp frames in total and then tested on footage from 42 colonoscopies and CVC-ClinicDB, CVC-ColonDB, Hyper-Kvasir, and ETIS-Larib public datasets. Clinical videos were evaluated for polyp detection and false-positive rates whereas the public datasets were assessed for F1 score. The system was tested for runtime performance on a wide array of hardware.
Results The performance on public datasets varied from an F1 score of 0.727 to 0.942. On full examination videos, it detected 94 % of the polyps found by the endoscopist with a 3 % false-positive rate and identified additional polyps that were missed during initial video assessment. The system’s runtime fits within the real-time constraints on all but one of the hardware configurations.
Conclusions We have created a polyp detection system with a post-processing pipeline that works in real time on a wide array of hardware. The system does not require extensive computational power, which could help broaden the adaptation of new commercially available systems.
Heilkreidetherapie: Nachhaltigkeit und Verträglichkeit bei chronischem Rückenschmerz
Authors: Wiebelitz Karl Rüdiger , Schneider Jörg , Beer André-Michael 
Published: April 2021

Zusammenfassung
Hintergrund Rückenschmerzen stellen ein wesentliches Problem der Volksgesundheit dar. Obwohl Rügener Heilkreide seit Jahrzehnten zur Behandlung eingesetzt wird, gibt es bisher kaum klinische Untersuchungen zur Wirksamkeit und insbesondere keine zu ihrer Dauer, also zur Nachhaltigkeit.
Material und Methoden Eine nicht-interventionelle prospektive Anwendungsbeobachtung mit 3-monatigem Follow-up untersucht mithilfe etablierter (HFAQ, VAS, Oswestry Score) und freier Fragebögen die Wirksamkeit der Heilkreidebehandlung bei Patienten mit chronischen Rückenschmerzen.
Ergebnisse Die Ergebnisse der sekundären Zielkriterien aus dem freien Fragebogen bei Abschluss der Behandlung, nämlich den VAS, der Patienteneinschätzung, dass sich die Heilkreidebehandlung gelohnt habe und der Zufriedenheit der Patienten mit der Behandlung, bestätigen die aus vorangehenden Studien bekannten akuten Verbesserungen der Symptomatik. Darüber hinaus kann erstmals gezeigt werden, dass die Behandlungserfolge (gemessen mit den VAS zum Rückenschmerz, sonstigen Schmerzen und Muskelverspannungen, dem Oswestry Score und der semiquantitativen Einschätzung der Rückenschmerzen sowie der fortbestehenden Patienteneinschätzung, dass sich die Heilkreidebehandlung gelohnt habe und der fortbestehenden Zufriedenheit der Patienten mit der Behandlung) auch nach 3 Monaten noch praktisch unvermindert anhalten, also die Heilkreidebehandlung nachhaltig ist. Relevante Nebenwirkungen wurden nicht beobachtet. Schlussfolgerungen: Die Heilkreidebehandlung stellt eine wirksame und günstige Ergänzung der Behandlung chronischer Rückenschmerzen ohne erkennbare Nebenwirkungsrisiken dar.
Großzellig-anaplastisches T-Zell-Lymphom und Mycosis fungoides unter der Therapie mit Dupilumab
Authors: Troyanova-Slavkova S. 
Published: April 2021

ZusammenfassungDupilumab ist das erste zielgerichtete Biologikum, das bei mittelschwerer bis schwerer atopischer Dermatitis angewendet werden kann. Der monoklonale Antikörper hemmt die Interleukin-4- und Interleukin-13-Signalübertragung 1. Dupilumab belegt für die Behandlung von atopischen und allergischen Erkrankungen ein gutes Verträglichkeitsprofil. Gleichwohl sollten Ärzte seine Neuheit und das Potenzial für unerwartete und unerwünschte Arzneimittelwirkungen berücksichtigen. Wir stellen einen Patienten vor, der nach Einleitung von Dupilumab ein großzellig-anaplastisches T-Zell-Lymphom mit Befall des supraklavikulären Lymphknotens und eine Mycosis fungoides entwickelte.