bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractPast 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

AbstractThe 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

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

AbstractDrug 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

AbstractBackgroundThe 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.MethodsThe 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.ResultsMolecular 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.ConclusionsThis 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

AbstractIn 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

AbstractMany 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

AbstractObjectiveTo stimulate obstetric centers to start training in breech counseling and selection and performing vaginal breech deliveries.MethodsThe 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.ResultsIn 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.ConclusionWe 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.
Influence of divalent ions on composition and viscoelasticity of polyelectrolyte complexes
Authors: Iyer Divya , Syed Vaqar M. S. , Srivastava Samanvaya 
Published: November 2021

AbstractThe 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

AbstractBACKGROUNDAlmond 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.RESULTSOur 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.CONCLUSIONHoney 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

AbstractRozanolixizumab 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.
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

Abstract
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

ZusammenfassungDie 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.