bluuebunny/crossref_metadata_2025 huggingface dataset:
‘What did it achieve?’ – Students’ conceptions about the significance of the French Revolution
Authors: Mathis Christian
Published: November 2021

Este estudio presenta las percepciones de los estudiantes sobre las consecuencias y la relevancia histórica de la Revolución Francesa. Se recogieron datos de alumnos suizos-alemanes de noveno grado (de 15 a 16 años; N=22) mediante discusiones de grupo y entrevistas centradas en problemas. Los datos se analizaron mediante un método cualitativo reconstructivo. El pensamiento histórico de los alumnos está dominado por la creencia en el progreso y el presentismo. Los jóvenes se ven envueltos en la historia de la Revolución Francesa, que tiene una relevancia y significado simbólico y presente-futuro (Cercadillo). Así, construyen la relevancia histórica de forma ejemplar (Rüsen). Estos patrones explicativos están anclados en las ideas cotidianas y no en una comprensión científica. Una consecuencia de esto es que los profesores deben modelar cognitivamente el pensamiento mostrando cómo los historiadores narran la relevancia histórica de la Revolución Francesa, haciendo explícito este concepto de segundo orden y ofreciéndoles la oportunidad de conocer y analizar diferentes tipos de narrativa (Rüsen).

This study presents students’ conceptions about the consequences and significance of the French Revolution. The data were collected from Swiss ninth graders (15 to 16 years old; N=22) by means of group discussions and problem-centred interviews. The data were evaluated using a reconstructive qualitative method. The students’ historical thinking is dominated by a belief in progress and paramount presentism. The adolescents feel entangled in the history of the French Revolution, it has a symbolic and present-future significance (Cercadillo). Thus, they construct historical significance in an exemplary way (Rüsen). These explanatory patterns are anchored in the everyday conceptions of the students and not in an academic understanding of history. Therefore, teachers should cognitively model learners’ thinking by showing how historians narrate and construct the historical significance of the French Revolution, by making this second-order concept explicit and by giving them the opportunity to explore different types of narrative (Rüsen).
Narrativa y significación histórica en la comunicación de los museos nacionales canadienses en Facebook
Authors: Navarro Neri Iñaki , Rivero Pilar , Aso Borja , Mendióroz-Lacambra Ana María
Published: November 2021

El patrimonio juega un papel determinante en la construcción de la ciudadanía y las identidades, de ahí la responsabilidad que las instituciones culturales, como los museos, tienen a la hora de articular sus propuestas y discursos. En este artículo se presentan los resultados obtenidos tras analizar el discurso emitido a través de sus posts de los cinco museos nacionales canadienses más activos en Facebook durante 2020, en cuanto a narrativa histórica y al enfoque elegido a la hora de tratar la significación histórica de una pintura, una pieza de la colección, etc. Los resultados muestran una actividad planificada con discursos donde predomina la narrativa histórica tradicional y un enfoque, en cuanto al tipo de significación histórica otorgada a una pieza, centrado principalmente en la relevancia e importancia de los elementos patrimoniales en el imaginario colectivo canadiense.Los datos contribuyen a conocer mejor el desarrollo de pensamiento histórico en el ámbito de la educación no formal en el contexto digital. Teniendo en cuenta la escasez de investigaciones en esta línea, se abre una vía de trabajo novedosa en la didáctica de la historia y del patrimonio.

and the approach chosen when dealing with the historical significance of a painting, work of art, etc. The results show a constant and planned activity with discourses dominated by traditional historical narrative, and an approach, in terms of the type of historical significance given to a piece, mainly focused on the relevance and importance of heritage elements in the Canadian collective imagination.The results contribute to a better understanding of the development of historical thinking in the field of non-formal education in the digital context. As there is hardly any research in this area, this research constitutes a new line of investigation in the context of history and heritage education.
Libelos, camarillas y banquetes: una propuesta para reconstruir las proclamaciones militares en la Antigüedad Tardía a través de los casos de Probo, Magnencio y Juliano
Authors: Sancho Gómez Miguel Pablo
Published: November 2021

Pese a la gran cantidad de sublevaciones militares acontecidas en el Imperio Romano, y muy especialmente en el siglo III, sabemos muy poco de cómo se preparaban y ejecutaban sobre el papel estos complots. Quitando el atípico caso de Procopio, relatado con detalle por Amiano Marcelino, las fuentes literarias, ya en muchos casos problemáticas y/o escasas, dejan bastantes lagunas en los relatos de tales procesos, que la historiografía reciente intenta suplir con hipótesis. Sin entrar a valorar las motivaciones del fenómeno o el grado de responsabilidad de los diferentes involucrados en las denominadas usurpaciones, nos planteamos ofrecer una propuesta explicativa desde el punto de vista meramente técnico, esto es, cómo un determinado grupo de conjurados logra idear, planear y ejecutar un plan o una serie de planes con el objetivo de alcanzar el poder mediante el apoyo de ciertas fuerzas militares para derrocar, casi siempre asesinando, al emperador reinante.

Despite the large number of military uprisings that occurred in the Roman Empire, and especially in the Third Century, we know very little about how these conspiracies were prepared and executed on paper. Not counting the atypical case of Procopius, related in detail by Ammianus Marcellinus, the literary sources, already problematic and /or scarce in many cases, leave many gaps in the accounts of such processes, which recent historiography tries to fill with hypotheses. Without assessing the motivations of the phenomenon or the degree of responsibility of the different parties involved in the so-called usurpations, we offer an explanatory proposal from the merely technical point of view, that is, how a certain group of conspirators manages to devise, scheme and execute a plan or series of plans with the aim of attaining power through the support of certain military forces and overthrow, almost always assassinating, the reigning emperor.
L’insertion professionnelle des enseignants au travers des multiples aspects de la socialisation au travail : l’ISaTE, un instrument de mesure pour les appréhender
Authors: Coppe Thibault , Raemdonck Isabel , März Virginie , Parmentier Michaël , Brouhier Quentin , Colognesi Stéphane
Published: November 2021

Cette étude présente la conception et le processus de validation d’un instrument de mesure de la socialisation au travail des enseignants débutants. Un total de 1487 enseignants de différents niveaux d’enseignement obligatoire ont été interrogés. Les fondations théoriques ainsi que les analyses factorielles exploratoires et confirmatoires mettent en évidence quatre dimensions de socialisation au travail : la socialisation au groupe de travail, au climat micropolitique, aux tâches d’enseignement ainsi qu’à l’organisation. L’instrument proposé présente, en respect de différents critères consensuels quant aux processus de validation d’échelles, des arguments de validité élevés. Cette contribution nourrit l’enjeu majeur d’une approche globalisante de l’insertion des enseignants qui va au-delà des approches centrées sur le travail de l’enseignant en classe.
Spatial and temporal dynamics of SAR11 marine bacteria across a nearshore to offshore transect in the tropical Pacific Ocean
Authors: Tucker Sarah J. , Freel Kelle C. , Monaghan Elizabeth A. , Sullivan Clarisse E. S. , Ramfelt Oscar , Rii Yoshimi M. , Rappé Michael S.
Published: November 2021

Surveys of microbial communities across transitions coupled with contextual measures of the environment provide a useful approach to dissect the factors determining distributions of microorganisms across ecological niches. Here, monthly time-series samples of surface seawater along a transect spanning the nearshore coastal environment within Kāneʻohe Bay on the island of Oʻahu, Hawaiʻi, and the adjacent offshore environment were collected to investigate the diversity and abundance of SAR11 marine bacteria (order Pelagibacterales) over a 2-year time period. Using 16S ribosomal RNA gene amplicon sequencing, the spatiotemporal distributions of major SAR11 subclades and exact amplicon sequence variants (ASVs) were evaluated. Seven of eight SAR11 subclades detected in this study showed distinct subclade distributions across the coastal to offshore environments. The SAR11 community was dominated by seven (of 106 total) SAR11 ASVs that made up an average of 77% of total SAR11. These seven ASVs spanned five different SAR11 subclades (Ia, Ib, IIa, IV, and Va), and were recovered from all samples collected from either the coastal environment, the offshore, or both. SAR11 ASVs were more often restricted spatially to coastal or offshore environments (64 of 106 ASVs) than they were shared among coastal, transition, and offshore environments (39 of 106 ASVs). Overall, offshore SAR11 communities contained a higher diversity of SAR11 ASVs than their nearshore counterparts, with the highest diversity within the little-studied subclade IIa. This study reveals ecological differentiation of SAR11 marine bacteria across a short physiochemical gradient, further increasing our understanding of how SAR11 genetic diversity partitions into distinct ecological units.
Modeling Metastatic Colonization in a Decellularized Organ Scaffold‐Based Perfusion Bioreactor
Authors: Rafaeva Maria , Horton Edward R. , Jensen Adina R.D. , Madsen Chris D. , Reuten Raphael , Willacy Oliver , Brøchner Christian B. , Jensen Thomas H. , Zornhagen Kamilla Westarp , Crespo Marina , Grønseth Dina S. , Nielsen Sebastian R. , Idorn Manja , Straten Per thor , Rohrberg Kristoffer , Spanggaard Iben , Højgaard Martin , Lassen Ulrik , Erler Janine T. , Mayorca‐Guiliani Alejandro E.
Published: November 2021

Metastatic cancer spread is responsible for most cancer‐related deaths. To colonize a new organ, invading cells adapt to, and remodel, the local extracellular matrix (ECM), a network of proteins and proteoglycans underpinning all tissues, and a critical regulator of homeostasis and disease. However, there is a major lack in tools to study cancer cell behavior within native 3D ECM. Here, an in‐house designed bioreactor, where mouse organ ECM scaffolds are perfused and populated with cells that are challenged to colonize it, is presented. Using a specialized bioreactor chamber, it is possible to monitor cell behavior microscopically (e.g., proliferation, migration) within the organ scaffold. Cancer cells in this system recapitulate cell signaling observed in vivo and remodel complex native ECM. Moreover, the bioreactors are compatible with co‐culturing cell types of different genetic origin comprising the normal and tumor microenvironment. This degree of experimental flexibility in an organ‐specific and 3D context, opens new possibilities to study cell–cell and cell–ECM interplay and to model diseases in a controllable organ‐specific system ex vivo.
Rapid construction of hierarchically porous metal–organic frameworks by a spray‐drying strategy for enhanced tannic acid adsorption
Authors: Liu Jingran , Wei Yan , Chang Miao , Wang Ni , Wang Dan , Wang Jie‐Xin
Published: November 2021

Metal–organic frameworks (MOFs) have attracted much attention owing to their tailored pore environment and surface functionality. However, most of the currently reported MOFs are confined to small pore sizes (<5 nm), limiting their practical applications. Here, a facile and versatile strategy for rapid construction of hierarchically porous MOFs (HP‐MOFs) by spray‐drying is reported, in which presynthesized nanosized MOFs (N‐MOFs) can be assembled to form MOF microspheres with meso/macropores resulting from the interspace among closely arranged N‐MOFs. This strategy enables the construction of multicomponent HP‐MOFs with various functions. As a proof of concept, we show that the adsorption for tannic acid (TA) can be significantly enhanced using HP‐MIL‐101(Cr). Particularly, HP‐MIL‐101‐30 (30 represents the primary nanoparticle size) exhibits a record‐high adsorption capacity (1175 mg g−1), and the adsorption rate of HP‐MIL‐101‐30 is increased by 50% compared to that of N‐MIL‐101‐30. These findings have important implications for the rapid construction of HP‐MOFs, which is beneficial for the adsorption of large molecules.
Innovativer Einsatz von Ringfedern in der Erdbebenauslegung
Authors: Helm Lukas , Sadegh‐Azar Hamid , Jahnel Lars , Jandrey Hauke
Published: November 2021

Ringfedern finden im Erdbebeningenieurwesen kaum Anwendung und sind nur wenig erforscht. Dabei bieten sie eine Reihe von Vorteilen: sie sind äußerst robust, hitzebeständig, langlebig und wartungsarm. Ihr Verhalten ist superelastisch, wobei die Feder trotz großer plastischer Verformungen und hoher Energiedissipation immer wieder in den Ausgangszustand zurückkehrt. Ein mit Ringfedern ausgestattetes System kann ein Erdbeben ohne große plastische Verformungen und Schäden überstehen und liefert somit einen maßgeblichen Beitrag zum Investitionsschutz (Wirtschaftlichkeit) und zum nachhaltigen Einsatz von knappen Materialien und Ressourcen. Die Dämpfer selbst bleiben dabei ebenfalls schadensfrei und müssen nicht ausgetauscht werden. In diesem Aufsatz wird ein neuartiger Einsatz von Ringfedern zur Erhöhung der Erdbebensicherheit und zur Schwingungsreduktion von Strukturen untersucht. Hierbei werden die klassischen Aussteifungselemente durch Ringfedern ersetzt. Um die praktische Anwendung im Erdbebeningenieurwesen zu ermöglichen und die Effizienz im Vergleich zu anderen Systemen zu bewerten, werden nichtlineare dynamische Simulationen durchgeführt, wobei die klassischen schwingungstechnischen Eigenschaften der Feder analytisch und numerisch quantifiziert werden. Abschließend wird die praktische Anwendung von Ringfedern zur Schwingungsreduktion und zur Optimierung der Erdbebenauslegung eines Hochhauses anhand eines Praxisbeispiels demonstriert.
Examining the influence of brain stimulation to the medial prefrontal cortex on the self‐reference effect in memory
Authors: Burden Camill , Leach Ryan C. , Sklenar Allison M. , Urban Levy Pauline , Frankenstein Andrea N. , Leshikar Eric D.
Published: November 2021

Past work shows that processing information in relation to the self improves memory which is known as the self‐reference effect in memory. Other work suggests that transcranial direct current stimulation (tDCS) can also improve memory. Given recent research on self‐reference context memory effects (improved memory for contextual episodic details associated with self‐referential processing), we were interested in examining the extent stimulation might increase the magnitude of the self‐reference context memory effect. In this investigation, participants studied objects superimposed on different background scenes in either a self‐reference or other‐reference condition while receiving either active or sham stimulation to the dorsal medial prefrontal cortex (dmPFC), a cortical region known to support self‐reference context memory effects. Participants then completed a memory test that assessed item memory (have you seen this object before?) and context memory (with which background scene was this object paired?). Results showed a self‐reference context memory effect driven by enhanced memory for stimuli processed in the self‐reference compared to the other‐reference condition across all participants (regardless of stimulation condition). tDCS, however, had no effect on memory. Specifically, stimulation did not increase the magnitude of the self‐reference context memory effect under active compared to sham stimulation. These results suggest that stimulation of the dmPFC at encoding may not add to the memory benefits induced by self‐referential processing suggesting a boundary condition to tDCS effects on memory.
Direct Near Infrared Light–Activatable Phthalocyanine Catalysts
Authors: Katsurayama Yoshino , Ikabata Yasuhiro , Maeda Hajime , Segi Masahito , Nakai Hiromi , Furuyama Taniyuki
Published: November 2021

The high penetration of near‐infrared (NIR) light makes it effective for use in selective reactions under light‐shielded conditions, such as in sealed reactors and deep tissues. Herein, we report the development of phthalocyanine catalysts directly activated by NIR light to transform small organic molecules. The desired photocatalytic properties were achieved in the phthalocyanines by introducing the appropriate peripheral substituents and central metal. These phthalocyanine photocatalysts promote cross‐dehydrogenative‐coupling (CDC) under irradiation with 810 nm NIR light. The choice of solvent is important, and a mixture of a reaction‐accelerating (pyridine) and ‐decelerating (methanol) solvents was particularly effective. Moreover, we demonstrate photoreactions under visible‐light‐shielded conditions through the transmission of NIR light. A combined experimental and computational mechanistic analysis revealed that this NIR reaction does not involve a photoredox‐type mechanism with electron transfer, but instead a singlet‐oxygen‐mediated mechanism with energy transfer.
Epicardial and endothelial cell activation concurs with extracellular matrix remodeling in atrial fibrillation
Authors: van den Berg Nicoline W. E. , Kawasaki Makiri , Fabrizi Benedetta , Nariswari Fransisca A. , Verduijn Arianne C. , Neefs Jolien , Wesselink Robin , Al‐Shama Rushd F. M. , van der Wal Allard C. , de Boer Onno J. , Aten Jan , Driessen Antoine H. G. , Jongejan Aldo , de Groot Joris R.
Published: November 2021

Background

Improved understanding of the interconnectedness of structural remodeling processes in atrial fibrillation (AF) in patients could identify targets for future therapies.

Methods

We present transcriptome sequencing of atrial tissues of patients without AF, with paroxysmal AF, and persistent AF (total n = 64). RNA expression levels were validated in the same and an independent cohort with qPCR. Biological processes were assessed with histological and immunohistochemical analyses.

Results

In AF patients, epicardial cell gene expression decreased, contrasting with an upregulation of epithelial‐to‐mesenchymal transition (EMT) and mesenchymal cell gene expression. Immunohistochemistry demonstrated thickening of the epicardium and an increased proportion of (myo)fibroblast‐like cells in the myocardium, supporting enhanced EMT in AF. We furthermore report an upregulation of endothelial cell proliferation, angiogenesis, and endothelial signaling. EMT and endothelial cell proliferation concurred with increased interstitial (myo)fibroblast‐like cells and extracellular matrix gene expression including enhanced tenascin‐C, thrombospondins, biglycan, and versican. Morphological analyses discovered increased and redistributed glycosaminoglycans and collagens in the atria of AF patients. Signaling pathways, including cell–matrix interactions, PI3K‐AKT, and Notch signaling that could regulate mesenchymal cell activation, were upregulated.

Conclusion

Our results suggest that EMT and endothelial cell proliferation work in concert and characterize the (myo)fibroblast recruitment and ECM remodeling of AF. These processes could guide future research toward the discovery of targets for AF therapy.
Baicalein resensitizes tamoxifen‐resistant breast cancer cells by reducing aerobic glycolysis and reversing mitochondrial dysfunction via inhibition of hypoxia‐inducible factor‐1α
Authors: Chen Yan , Zhang Jingyu , Zhang Minqin , Song Yuxuan , Zhang Yue , Fan Shuangqin , Ren Shuang , Fu Lingyun , Zhang Nenling , Hui Hui , Shen Xiangchun
Published: November 2021

Drug resistance is a major hurdle for the effectiveness of tamoxifen (TAM) to provide clinical benefit. Therefore, it is essential to identify a sensitizer that could be used to improve TAM efficacy in treating TAM‐resistant breast cancer. Here, we investigated the ability of baicalein to reverse TAM resistance. We found that baicalein increased the efficacy of TAM in inhibiting proliferation and inducing apoptosis of TAM‐resistant cells. It also enhanced the TAM‐induced growth reduction of resistant cells from NOD/SCID mouse mammary fat pads, without causing obvious systemic toxicity. Analyses using the CellMiner tool and the Kaplan–Meier plotter database showed that HIF‐1α expression was inversely correlated with TAM therapeutic response in NCI‐60 cancer cells and breast cancer patients. HIF‐1α expression was increased in TAM‐resistant cells due to an increase in mRNA levels and reduced ubiquitin‐mediated degradation. Baicalein reduced HIF‐1α expression by promoting its interaction with PHD2 and pVHL, thus facilitating ubiquitin ligase‐mediated proteasomal degradation and thereby suppressing the nuclear translocation, binding to the hypoxia‐response element, and transcriptional activity of HIF‐1α. As a result, baicalein downregulated aerobic glycolysis by restricting glucose uptake, lactate production, ATP generation, lactate/pyruvate ratio and expression of HIF‐1α‐targeted glycolytic genes, thereby enhancing the antiproliferative efficacy of TAM. Furthermore, baicalein interfered with HIF‐1α inhibition of mitochondrial biosynthesis, which increased mitochondrial DNA content and mitochondrial numbers, restored the generation of reactive oxygen species in mitochondria, and thus enhanced the TAM‐induced mitochondrial apoptotic pathway. The HIF‐1α stabilizer dimethyloxallyl glycine prevented the baicalein‐induced downregulation of glycolysis and mitochondrial biosynthesis and reduced the effects of baicalein on reversing TAM resistance. Our results indicate that baicalein is a promising candidate to help overcome TAM resistance by sensitizing resistant cells to TAM‐induced growth inhibition and apoptosis. The mechanism underlying the effects of baicalein consists of inhibition of HIF‐1α–mediated aerobic glycolysis and mitochondrial dysfunction.
HIF2α promotes tumour growth in clear cell renal cell carcinoma by increasing the expression of NUDT1 to reduce oxidative stress
Authors: Shi Jian , Xiong Zhiyong , Wang Keshan , Yuan Changfei , Huang Yu , Xiao Wen , Meng Xiangui , Chen Zhixian , Lv Qingyang , Miao Daojia , Liang Huageng , Xu Tianbo , Xie Kairu , Yang Hongmei , Zhang Xiaoping
Published: November 2021

Background

The key role of hypoxia‐inducible factor 2alpha (HIF2α) in the process of renal cancer has been confirmed. In the field of tumour research, oxidative stress is also considered to be an important influencing factor. However, the relationship and biological benefits of oxidative stress and HIF2α in ccRCC remain unclear. This research attempts to explore the effect of oxidative stress on the cancer‐promoting effect of HIF2α in ccRCC and reveal its mechanism of action.

Methods

The bioinformatics analysis for ccRCC is based on whole transcriptome sequencing and TCGA database. The detection of the expression level of related molecules is realised by western blot and PCR. The expression of Nucleoside diphosphate‐linked moiety X‐type motif 1 (NUDT1) was knocked down by lentiviral infection technology. The functional role of NUDT1 were further investigated by CCK8 assays, transwell assays and cell oxidative stress indicator detection. The exploration of related molecular mechanisms is realised by Luciferase assays and Chromatin immunoprecipitation (ChIP) assays.

Results

Molecular screening based on knockdown HIF2α sequencing data and oxidative stress related data sets showed that NUDT1 is considered to be an important molecule for the interaction of HIF2α with oxidative stress. Subsequent experimental results showed that NUDT1 can cooperate with HIF2α to promote the progression of ccRCC. And this biological effect was found to be caused by the oxidative stress regulated by NUDT1. Mechanistically, HIF2α transcription activates the expression of NUDT1, thereby inhibiting oxidative stress and promoting the progression of ccRCC.

Conclusions

This research clarified a novel mechanism by which HIF2α stabilises sirtuin 3 (SIRT3) through direct transcriptional activation of NUDT1, thereby inhibiting oxidative stress to promote the development of ccRCC. It provided the possibility for the selection of new therapeutic targets for ccRCC and the study of combination medication regimens.
Drilling study of bit in gravel environment based on DEM–MBD
Authors: Gao Kuidong , Liu Jihai , Wu Tianjiao , Zeng Qingliang , Sun Liqing , Zhang Xiaodi
Published: November 2021

In the process of rock bolt support for the roadway with floor heave, the rock bolt cannot reach the bottom of the borehole smoothly due to the influence of the collapse gravels around the borehole. In order to solve the problem of difficult rock bolt installation, the auxiliary installation device of rock bolt drilling was innovatively designed. At the same time, a new method of auxiliary bolt installation was put forward, in which a bit was installed at the bottom of the bolt to assist the bolt drilling. The drilling process of the bit was simulated by the co‐simulation of discrete element method (DEM) and multibody dynamics method (MBD). The axial resistance of the bit and the change law of the particles movement were studied under different motion parameters and structural parameters. It was found that the drilling performance of bit was directly related to the motion parameters and structure of bit. And the selection of gravel parameters in DEM was verified by experiments. The research results can provide technical guidance for bit structure design and the selection of motion parameters of bolt drilling auxiliary installation device, and can effectively improve the rock bolt installation efficiency.
Decentering whiteness: Rethinking the instruction of undergraduate research methods within developmental science
Authors: Camacho Tissyana C. , Echelbarger Margaret
Published: November 2021

Many social scientists are working to course correct the historical mistakes, abuses, and exclusionary practices of the field. To diversify who participates in developmental science, both as participants and as researchers, we argue that more attention must be paid to how we teach the science of developmental science (i.e., research methods). We propose that undergraduate research methods courses offer an opportunity to intervene on the academic pipeline and invite students of color into research through course curriculum. In this essay, we discuss guiding principles instructors should consider to transform their curriculum in the research training of undergraduate developmental scientists.
Implementation of a breech program in a Belgian obstetric team
Authors: Casteels Martine , Podevyn Kathleen , Vanoverschelde Henk , Louwen Frank
Published: November 2021

Objective

To stimulate obstetric centers to start training in breech counseling and selection and performing vaginal breech deliveries.

Methods

The different steps that were needed to roll out a breech program, are described: the “walking” epidural (PIEB protocol), the breech consultation with a structured counseling tool, and training of the whole team (gynecologists, midwives, anesthesiologists, and pediatricians). We describe below the results of 111 women who were counseled at the breech consultation, in the period May 2019 to August 2021.

Results

In all, 86.5% of patients (n= 96) with a singleton term breech met the criteria for a vaginal breech delivery; 77% of this group (n= 74) accepted a planned vaginal breech delivery. Of this group, 54% (n=40) had a successful vaginal breech delivery, 27% (n=20) ended up in a secondary cesarean section, and 19% (n=14) had a planned cesarean section.

Conclusion

We were able to roll out a successful breech program, including vaginal breech delivery, in a safe way. The breech consultation is the most essential part of the process. Training of the whole team is mandatory. The results of the first 2 years are encouraging to continue this program.
Modeling choice across time: Effects of response–reinforcer discriminability
Authors: Davison Michael , Cowie Sarah
Published: November 2021

This experiment asks whether timing is affected by animals’ discrimination of response‐reinforcer contingencies, and if so, how this effect can be understood. Six pigeons were trained on a procedure in which concurrent‐schedule reinforcer ratios between left and right keys changed at 30 s after the last reinforcer. One stimulus signaled a reinforcer‐ratio reversal from 9:1 to 1:9 on that key, and the other stimulus signaled the inverse reversal, with the key on which these stimuli occurred randomized. Across conditions, the physical difference between the stimuli signaling the two responses was varied and the directional changes in the reinforcer ratio signaled by each stimulus were reversed. Choice changed appropriately across time when the two stimuli were discriminable, and points of subjective equality fell with decreasing stimulus difference. A model which assumed that reinforcers obtained in time bins were redistributed across other time bins according to ogivally changing standard deviations, and between response locations according to an ogivally changing redistribution measure, accounted well for the data. This model was shown to be preferable to one in which across‐time redistributions were scalar, and across‐location redistribution was constant. These results show the critical importance of stimulus‐response‐reinforcer discriminability to measures of timing.
Increase Disinfectant Residual While Reducing Disinfection Byproducts
Authors: Sweeney Sharon
Published: November 2021

The relationship between the amount of disinfectant residual and disinfection byproducts measured in finished water poses a challenge for water treatment and distribution operators. Central Arkansas Water investigated how to effectively reduce microbial and chemical contaminants.
Influence of divalent ions on composition and viscoelasticity of polyelectrolyte complexes
Authors: Iyer Divya , Syed Vaqar M. S. , Srivastava Samanvaya
Published: November 2021

The addition of monovalent salts to polyelectrolyte complexes (PECs) comprising oppositely charged polyelectrolytes results in diminishing propensity for complexation, leading to complexes with higher water contents and lower moduli. However, the corresponding influence of multivalent ions on polyelectrolyte complexation has not yet been explored beyond enhanced screening effects. Here, we elucidate the significant impact of the valency of the salt cation on the composition, ion partitioning, and viscoelasticity of charge‐matched PECs comprising sodium salt of poly(acrylic acid) and poly(allylamine hydrochloride). Notably, preferential partitioning of divalent cations (Ca2+ and Sr2+) into the complexes is observed, in stark contrast to the depletion of monovalent ions (Na+) from the complexes. Concomitantly, electrostatic bridging of polyanion chains by divalent ions is found to hinder their relaxation, manifesting as a non‐monotonic evolution of the shear moduli of the complexes with increasing divalent salt concentrations. Relatedly, a failure of time‐salt and time‐ionic strength superposition approaches in presence of divalent ions is demonstrated, highlighting the nontrivial influence of these ions on chain relaxation behavior.
A mechanism‐based approach unveils metabolic routes potentially mediating chlorantraniliprole synergism in honey bees, Apis melliferaL., by azole fungicides
Authors: Haas Julian , Glaubitz Johannes , Koenig Udo , Nauen Ralf
Published: November 2021

BACKGROUND

Almond production in California is an intensively managed agroecosystem dependent on managed pollination by honey bees, Apis mellifera L. A recent laboratory study reported synergism in honey bees between chlorantraniliprole, a common diamide insecticide used in almond orchards, and the fungicide propiconazole. Indeed, there is an emerging body of evidence that honey bee cytochrome P450 monooxygenases of the CYP9Q subfamily are involved in the detoxification of insecticides across a diverse range of chemical classes. The objective of the present study was to unveil the molecular background of the described synergism and to explore the potential role of CYP9Q enzymes in diamide detoxification.

RESULTS

Our study confirmed the previously reported synergistic potential of propiconazole on chlorantraniliprole in acute contact toxicity bioassays, whereas no synergism was observed for flubendiamide. Fluorescence‐based biochemical assays revealed an interaction of chlorantraniliprole, but not flubendiamide, with functionally expressed CYP9Q2 and CYP9Q3. These findings were validated by an increased chlorantraniliprole tolerance of transgenic Drosophila lines expressing CYP9Q2/3, and an analytically confirmed oxidative metabolism of chlorantraniliprole by recombinantly expressed enzymes. Furthermore, we showed that several triazole fungicides used in almond orchards, including propiconazole, were strong nanomolar inhibitors of functionally expressed honey bee CYP9Q2 and CYP9Q3, whereas other fungicides such as iprodione and cyprodinil did not inhibit these enzymes.

CONCLUSION

Honey bee CYP9Q enzymes are involved in chlorantraniliprole metabolism and inhibited by triazole fungicides possibly leading to synergism in acute contact toxicity bioassays. Our mechanistic approach has the potential to inform tier I honey bee pesticide risk assessment.
Pharmacokinetic‐pharmacodynamic modelling of the anti‐FcRn monoclonal antibody rozanolixizumab: Translation from preclinical stages to the clinic
Authors: Lledo‐Garcia Rocio , Dixon Kate , Shock Anthony , Oliver Ruth
Published: November 2021

Rozanolixizumab is a fully humanized high‐affinity anti‐human neonatal Fc receptor (FcRn) monoclonal antibody (mAb) that accelerates the removal of circulating immunoglobulin G (IgG), including pathogenic IgG autoantibodies, via the natural lysosomal degradation pathway. The aim of this study was to develop a pharmacokinetic/pharmacodynamic (PK/PD) model characterizing the effect of rozanolixizumab on IgG levels in cynomolgus monkeys, translate it into humans to support the first‐in‐human (FIH) rozanolixizumab clinical trial study design, and, ultimately, develop a PK/PD model in humans. Simulations from the preclinical model were performed to predict IgG responses in humans and select clinically relevant doses in the FIH study. Good alignment was observed between predicted and observed reductions in IgG, which increased with increasing dose in the FIH study. The model successfully described the PK of the 4 and 7 mg/kg intravenous (i.v.) dose groups, although the PKs were underpredicted for the 1 mg/kg i.v. dose group. Updating the model with subsequent human data identified parameters that deviated from preclinical assumptions. The updated PK/PD model was able to effectively characterize the PK FcRn‐IgG nonlinear system in response to rozanolixizumab in the FIH data.
Explicit microstates at the Schwarzschild horizon
Authors: Giveon Amit
Published: November 2021

Abstract

The claim that the microstates of Schwarzschild black holes in perturbative string theory amount to the modes of long folded strings in the vicinity of its horizon is supported by more evidence.
Hydrodynamic magneto-transport in holographic charge density wave states
Authors: Amoretti Andrea , Areán Daniel , Brattan Daniel K. , Martinoia Luca
Published: November 2021

Abstract

We employ hydrodynamics and gauge/gravity to study magneto-transport in phases of matter where translations are broken (pseudo-)spontaneously. First we provide a hydrodynamic description of systems where translations are broken homogeneously at nonzero lattice pressure and magnetic field. This allows us to determine analytic expressions for all the relevant transport coefficients. Next we construct holographic models of those phases and determine all the DC conductivities in terms of the dual black hole geometry. Combining the hydrodynamic and holographic descriptions we obtain analytic expression for the AC thermo-electric correlators. These are fixed in terms of the black hole geometry and a pinning frequency we determine numerically. We find an excellent agreement between our hydrodynamic and holographic descriptions and show that the holographic models are good avatars for the study of magneto-phonons.
Role of chaperone-assisted selective autophagy (CASA) in mechanical stress protection of periodontal ligament cells
Authors: Salim Corinna , Muders Hannah , Jäger Andreas , Konermann Anna
Published: November 2021

Objective

The periodontal ligament (PDL) is exposed to constant mechanical forces potentiated by orthodontic tooth movement (OTM). The aim of our study was to investigate the involvement of chaperone-assisted selective autophagy (CASA) in mechanosensing and cellular adaption to forces in the PDL.

Materials and methods

Human PDL cells were loaded with 2.5, 5, and 10% of static mechanical strain for 24 h in vitro. Untreated cells served as controls. Gene expression of HSPA8, HSPB8, BAG3, STUB1, SYNPO2 was investigated via RT-qPCR (Quantitative reverse transcription PCR). Western blot evidenced protein expression of these molecules and of Filamin A. In vivo analyses of CASA were performed via immunohistochemistry on teeth with and without OTM.

Results

CASA machinery genes were inherently expressed in PDL cells and exhibited transcriptional induction upon mechanical strain. Protein analyses underlined these findings, even though modulation upon force exertion also demonstrated a decrease for some molecules and loading strengths. In vivo results evidenced again the uniform upregulation of HSPA8, HSPB8, BAG3, STUB1, SYNPO2 and Filamin A in teeth with OTM compared to controls. Experiments generally evidenced a pronounced variability in the expression between donors both on the gene and protein level.

Conclusions

Our study is the first to identify both the expression and functional relevance of CASA in the PDL. The data reflect its probable central role in adequate adaption to forces exerted by OTM and in mechanical stress protection of cells. Deeper knowledge of the CASA pathway will allow better assessment of predisposing factors regarding side effects during mechanical force application that can be used in orthodontic practice.
Krankheitsmodifizierende Therapieansätze bei Alzheimer-Krankheit
Authors: Frölich Lutz , Hausner Lucrezia
Published: November 2021

Die Alzheimer-Krankheit ist eine der großen Volkskrankheiten mit bisher allein symptomatischen Therapieoptionen. Neue Erkenntnisse zu einem Krankheitskontinuum mit einer sehr langen präklinischen und frühsymptomatischen Krankheitsphase sowie molekulare Therapiestrategien, die auf den Erkenntnissen zur molekularen Neurobiologie der Erkrankung fußen, eröffnen eine Vielzahl neuer therapeutischer Strategien. Im Jahr 2021 ist erstmals ein Antiamyloidantikörper in den USA als krankheitsmodifizierende Therapie bei Alzheimer-Krankheit zugelassen worden, was einen ersten, sehr kontrovers diskutierten Schritt hin zu einer molekularen, ursachenorientierten Therapie darstellt. Die Übersicht stellt die am weitesten entwickelten molekularen Therapiestrategien sowie die Auswirkungen der zugelassenen Antikörpertherapie für die Praxis vor. Die Besonderheiten einer Langzeittherapie mit i.v. Infusionen in einer besonders vulnerablen Patientenpopulation und einem speziellen Nebenwirkungsprofil wird für die Implementierung in die Praxis große Herausforderungen mit sich bringen und ein hohes Maß an Kooperation erfordern. Die Zukunft der Alzheimer-Therapie mit einem multimodalen Therapieansatz mit verschiedenen Substanzen wird diesen Trend wahrscheinlich noch verstärken.
Psychedelic experience dose-dependently modulated by cannabis: results of a prospective online survey
Authors: Kuc Joanna , Kettner Hannes , Rosas Fernando , Erritzoe David , Haijen Eline , Kaelen Mendel , Nutt David , Carhart-Harris Robin L.
Published: November 2021

Rationale.

Classic psychedelics are currently being studied as novel treatments for a range of psychiatric disorders. However, research on how psychedelics interact with other psychoactive substances remains scarce.

Objectives

The current study aimed to explore the subjective effects of psychedelics when used alongside cannabis.

Methods

Participants (n = 321) completed a set of online surveys at 2 time points: 7 days before, and 1 day after a planned experience with a serotonergic psychedelic. The collected data included demographics, environmental factors (so-called setting) and five validated questionnaires: Mystical Experience Questionnaire (MEQ), visual subscales of Altered States of Consciousness Questionnaire (ASC-Vis), Challenging Experience Questionnaire (CEQ), Ego Dissolution Inventory (EDI) and Emotional Breakthrough Inventory (EBI). Participants were grouped according to whether they had reported using no cannabis (n = 195) or low (n = 53), medium (n = 45) or high (n = 28) dose, directly concomitant with the psychedelic. Multivariate analysis of covariance (MANCOVA) and contrasts was used to analyse differences in subjective effects between groups while controlling for potential confounding contextual ‘setting’ variables.

Results

The simultaneous use of cannabis together with classic serotonergic psychedelics was associated with more intense psychedelic experience across a range of measures: a linear relationship was found between dose and MEQ, ASC-Vis and EDI scores, while a quadratic relationship was found for CEQ scores. No relationship was found between the dose of cannabis and the EBI.

Conclusions

Results imply a possible interaction between the cannabis and psychedelic on acute subjective experiences; however, design limitations hamper our ability to draw firm inferences on directions of causality and the clinical implications of any such interactions.
Metrological framework to support accurate, reliable, and reproducible nucleic acid measurements
Authors: Milavec Mojca , Cleveland Megan H. , Bae Young-Kyung , Wielgosz Robert I. , Vonsky Maxim , Huggett Jim F.
Published: November 2021

Nucleic acid analysis is used in many areas of life sciences such as medicine, food safety, and environmental monitoring. Accurate, reliable measurements of nucleic acids are crucial for maximum impact, yet users are often unaware of the global metrological infrastructure that exists to support these measurements. In this work, we describe international efforts to improve nucleic acid analysis, with a focus on the Nucleic Acid Analysis Working Group (NAWG) of the Consultative Committee for Amount of Substance: Metrology in Chemistry and Biology (CCQM). The NAWG is an international group dedicated to improving the global comparability of nucleic acid measurements; its primary focus is to support the development and maintenance of measurement capabilities and the dissemination of measurement services from its members: the National Metrology Institutes (NMIs) and Designated Institutes (DIs). These NMIs and DIs provide DNA and RNA measurement services developed in response to the needs of their stakeholders. The NAWG members have conducted cutting edge work over the last 20 years, demonstrating the ability to support the reliability, comparability, and traceability of nucleic acid measurement results in a variety of sectors.
Investigations into the elimination profiles and metabolite ratios of micro-dosed selective androgen receptor modulator LGD-4033 for doping control purposes
Authors: Wagener Felicitas , Guddat Sven , Görgens Christian , Angelis Yiannis S. , Petrou Michael , Lagojda Andreas , Kühne Dirk , Thevis Mario
Published: November 2021

LGD-4033 (ligandrol) is a selective androgen receptor modulator (SARM), which is prohibited in sports by the World Anti-Doping Agency (WADA) and led to 62 adverse analytical findings (AAFs) in 2019. But not only deliberate doping with LGD-4033 constitutes a problem. In the past years, some AAFs that concerned SARMs can be attributed to contaminated dietary supplements (DS). Thus, the urgency to develop methods to differentiate between inadvertent doping and abuse of SARMs to benefit from the performance-enhancing effect of the compound in sports is growing. To gain a better understanding of the metabolism and excretion patterns of LGD-4033, human micro-dose excretion studies at 1, 10, and 50 µg LGD-4033 were conducted. Collected urine samples were prepared for analysis using enzymatic hydrolysis followed by solid-phase extraction and analyzed via LC-HRMS/MS. Including isomers, a total of 15 phase I metabolites were detected in the urine samples. The LC-HRMS/MS method was validated for qualitative detection of LGD-4033, allowing for a limit of detection (LOD) of 8 pg/mL. The metabolite M1, representing the epimer of LGD-4033, was synthesized and the structure elucidated by NMR spectroscopy. As the M1/LGD-4033 ratio changes over time, the ratio and the approximate LGD-4033 concentration can contribute to estimating the time point of drug intake and dose of LGD-4033 in doping control urine samples, which is particularly relevant in anti-doping result management.

Graphical abstract
Biochemistry strategies for label-free optical sensor biofunctionalization: advances towards real applicability
Authors: Soler Maria , Lechuga Laura M.
Published: November 2021

Label-free biosensors, and especially those based on optical transducers like plasmonic or silicon photonic systems, have positioned themselves as potential alternatives for rapid and highly sensitive clinical diagnostics, on-site environmental monitoring, and for quality control in foods or other industrial applications, among others. However, most of the biosensor technology has not yet been transferred and implemented in commercial products. Among the several causes behind that, a major challenge is the lack of standardized protocols for sensor biofunctionalization. In this review, we summarize the most common methodologies for sensor surface chemical modification and bioreceptor immobilization, discussing their advantages and limitations in terms of analytical sensitivity and selectivity, reproducibility, and versatility. Special focus is placed on the suggestions of innovative strategies towards antifouling and biomimetic functional coatings to boost the applicability and reliability of optical biosensors in clinics and biomedicine. Finally, a brief overview of research directions in the area of device integration, automation, and multiplexing will give a glimpse of the future perspectives for label-free optical biosensors.
State-of-the-art surgical treatment of IPMNs
Authors: Salvia Roberto , Burelli Anna , Perri Giampaolo , Marchegiani Giovanni
Published: November 2021

Background

A “pandemic” of incidentally discovered pancreatic cyst neoplasms (PCNs) is ongoing. Among PCNs, intraductal papillary mucinous cystic neoplasms (IPMNs) are the most common and with their complex biology could represent a precursor lesion of pancreatic cancer. Although multiple guidelines exist to guide their treatment, there are still many “gray areas” on indications for surgery for IPMNs.

Methods

The current indications for surgery of IPMNs were reappraised, considering potential discrepancies between available evidence and guidelines policies. The practice at a high-volume center for the diagnosis and treatment of PCN was presented and discussed.

Results

Most IPMNs do not and will never require surgery, as they won’t progress to malignancy. The current literature is solid in identifying high-grade dysplasia (HGD) as the right and timely target for IPMN resection, but how to precisely assess its presence remains controversial and guidelines lack of accuracy in this regard. Multiple tumorigenic pathways of progression of IPMNs exist, and their knowledge will likely lead to more accurate tests for malignancy prediction in the future.

Conclusions

The surgical management of IPMNs still is a matter of debate. Indication for resection should be considered only in highly selected cases with the ideal target of HGD. Clinicians should critically interpret the guidelines’ indications, refer to a multidisciplinary team discussion, and always consider the outcome of an adequate counselling with the patient.