bluuebunny/crossref_metadata_2025 huggingface dataset:
Corona theorem for strictly pseudoconvex domains
Authors: Gwizdek Sebastian
Published: November 2021

Nearly 60 years have passed since Lennart Carleson gave his proof of Corona Theorem for unit disc in the complex plane. It was only recently that M. Kosiek and K. Rudol obtained the first positive result for Corona Theorem in multidimensional case. Using duality methods for uniform algebras the authors proved "abstract" Corona Theorem which allowed to solve Corona Problem for a wide class of regular domains. In this paper we expand Corona Theorem to strictly pseudoconvex domains with smooth boundaries.
Large‐Scale Micropillar 3D Patterning with High‐Aspect Ratio Using a Theta‐Pipette
Authors: Liao Xiaobo , Zhuang Jian , Yang Jiulin , Cheng Lei , Zheng Qiangqiang , Li Junzhong , Yuan Weifeng
Published: November 2021

Meniscus‐confined electrodeposition (MCED) has received widespread attention because of its simple physical construction and low economic cost. The matching of probe lifting rate and growth current in the MCED is the key to continuous and stable deposition. However, changes in the meniscus droplet morphology and surface evaporation will affect the stability deposition. Therefore, it is difficult to continuously fabricate high‐aspect ratio array microstructures. This article proposes a novel electrodeposition physical model based on theta‐pipette, and then proposes a closed‐loop control method based on this model. The numerical analysis and experiment results demonstrate that 1) the deposition current decreases continuously with time using a constant voltage between electrodes for fabrication, which is easy to cause the fabrication to be interrupted; 2) adjusting the voltage between the electrodes in theta‐pipette can approximately linearly adjust the deposition current, which can ensure stable fabrication. Finally, MCED process is controlled using a closed‐loop control algorithm; a large‐scale array (4 × 4) of micropillars with high‐aspect ratio of 12:1 (the diameter 1.65 μm and the height 21.4 μm) has been stably fabricated. This approach can offer versatility and robustness for high‐resolution 3D patterning at the microscale.
Microstructure and Formation Mechanism of β Eutectoid Decomposition in a γ‐TiAl Alloy with Ru Addition
Authors: Xie Lishuai , Wang Anzhe
Published: November 2021

A eutectoid decomposition of β→α + τ1 occurs during water quenching (WQ) and the corresponding formation mechanism in a γ‐TiAl alloy with Ru addition is studied. A novel morphology consisting of outer lamellar and inner net‐like eutectoid microstructure is observed. The α and τ1 products are determined to nucleate and grow with the same crystalline orientation in a eutectoid aggregation, respectively. No specific crystalline orientation is confirmed between α and τ1. The eutectoid reaction is found to be controlled by diffusion. Moreover, α and τ1 grow in a synchronous manner. The outer lamellar region absorbs Ti, but excludes both Ru and Al atoms to the center of the β matrix during the eutectoid reaction. Correspondingly, the high Ru and Al contents promote the sidewise growth of τ1 lamellae and result in the distinctions in microstructure with the outer lamellae.
Electric‐Driven Meta‐Optic Dynamics for Simultaneous Near‐/Far‐Field Multiplexing Display
Authors: Wan Chengwei , Li Zhe , Wan Shuai , Dai Chenjie , Tang Jiao , Shi Yangyang , Li Zhongyang
Published: November 2021

Heading towards to intelligent photonic technology, meta‐optics is in the revolutionary process of changing from passive to active controllable devices. Despite various emerging tuning mechanisms exploration and demonstration, they mainly focus on spectral amplitude alternation or near‐field imaging switch. Most tuning schemes inevitably demand quite complicated nanofabrication to incorporate nanotextured active materials, thus limiting its applicable scenarios outside the laboratory. Hence, a practically accessible solution in real life to simultaneously realize multi‐field (both near‐ and far‐field) dynamic displays remains a critical challenge. Here, a practical electric‐driven liquid‐crystal‐integrated metasurface (ELIM) is proposed and demonstrated toward advanced intelligent dynamic display. Through elaborately screening building block (α‐Si nanopillar) geometry to build up a systematic architectural dictionary, conventional spatial‐multiplexing is successfully achieved and the degeneracy for amplitude/phase selections is created and thus any arbitrary multi‐field encryptions are allowed. By leveraging ELIM anisotropic characteristics for orthogonal polarizations, an electric‐driven dynamic tuning is practically realized for the first time to enable quad‐fold dynamic exhibitions, including switchable dual‐nanoprinting (near‐field) and simultaneous dual‐holography (far‐field) images with independent‐encryption freedom. Overall, it is envisioned that meta‐optics integrated with the liquid‐crystal platform can easily find practical applications in real life for intelligent dynamic display, imaging multiplexing, information encryption/security, etc.
Resolving Atomic‐Scale Interactions in Nonfullerene Acceptor Organic Solar Cells with Solid‐State NMR Spectroscopy, Crystallographic Modelling, and Molecular Dynamics Simulations
Authors: R. Luginbuhl Benjamin , Raval Parth , Pawlak Tomasz , Du Zhifang , Wang Tonghui , Kupgan Grit , Schopp Nora , Chae Sangmin , Yoon Sangcheol , Yi Ahra , Jung Kim Hyo , Coropceanu Veaceslav , Brédas Jean‐Luc , Nguyen Thuc‐Quyen , Reddy G. N. Manjunatha
Published: November 2021

Fused‐ring core nonfullerene acceptors (NFAs), designated “Y‐series,” have enabled high‐performance organic solar cells (OSCs) achieving over 18% power conversion efficiency (PCE). Since the introduction of these NFAs, much effort has been expended to understand the reasons for their exceptional performance. While several studies have identified key optoelectronic properties that govern high PCEs, little is known about the molecular level origins of large variations in performance, spanning from 5% to 18% PCE, for example, in the case of PM6:Y6 OSCs. Here, a combined solid‐state NMR, crystallography, and molecular modeling approach to elucidate the atomic‐scale interactions in Y6 crystals, thin films, and PM6:Y6 bulk heterojunction (BHJ) blends is introduced. It is shown that the Y6 morphologies in BHJ blends are not governed by the morphology in neat films or single crystals. Notably, PM6:Y6 blends processed from different solvents self‐assemble into different structures and morphologies, whereby the relative orientations of the sidechains and end groups of the Y6 molecules to their fused‐ring cores play a crucial role in determining the resulting morphology and overall performance of the solar cells. The molecular‐level understanding of BHJs enabled by this approach will guide the engineering of next‐generation NFAs for stable and efficient OSCs.
Covariation of proximal finger and toe phalanges inHomo sapiens: A novel approach to assess covariation of serially corresponding structures
Authors: van Heteren Anneke H. , Friess Martin , Détroit Florent , Balzeau Antoine
Published: November 2021

Objectives

As hands and feet are serially repeated corresponding structures in tetrapods, the morphology of fingers and toes is expected to covary due to a shared developmental origin. The present study focuses on the covariation of the shape of proximal finger and toe phalanges of adultHomo sapiensto determine whether covariation is different in the first ray relative to the others, as its morphology is also different.

Material and methods

Proximal phalanges of 76 individuals of unknown sex (Muséum national d'Histoire naturelle, Paris, and the Natural History Museum, London) were digitized using a surface scanner. Landmarks were positioned on 3D surface models of the phalanges. Generalized Procrustes analysis and two‐block partial least squares (PLS) analyses were conducted. A novel landmark‐based geometric morphometric approach focusing on covariation is based on a PCoA of the angles between PLS axes in morphospace. The results can be statistically evaluated.

Results

The difference in PCo scores between the first and the other rays indicates that the integration between the thumb and the big toe is different from that between the lateral rays of the hand and foot.

Discussion

We speculate that the results are possibly the evolutionary consequence of differential selection pressure on the big toe relative to the other toes related to the rise of bipedalism, which is proposed to have emerged very early in the hominin clade. In contrast, thumb morphology and its precision grip never ceased undergoing changes, suggesting less acute selection pressures related to the evolution of the precision grip.
Dynamische kinetische Sensibilisierung von β‐Dicarbonyl‐verbindungen – Zugang zu mittelgroßen Ringen durch eine De‐Mayo‐artige Ringerweiterung
Authors: Paulisch Tiffany O. , Mai Lukas A. , Strieth‐Kalthoff Felix , James Michael J. , Henkel Christian , Guldi Dirk M. , Glorius Frank
Published: November 2021

In diesem Forschungsartikel stellen wir eine photokatalysierte C2‐Ringerweiterung von β‐Dicarbonylverbindungen mit nicht aktivierten Olefinen vor, die einen einfachen Zugang zu mittelgroßen Ringen ermöglicht. Durch selektive Sensibilisierung des substöchiometrischen Enol‐Tautomers können Substrate umgesetzt werden, welche mit den klassischen De Mayo‐Reaktionsbedingungen nicht kompatibel sind. Der Schlüssel zum Erfolg ist die Identifizierung des metallbasierten Sensibilisators fac‐[Ir(CF3‐pmb)3], der mit herkömmlichen LEDs im nahen des sichtbaren Bereichs angeregt werden kann und eine hohe Triplettenergie von 73.3 kcal mol−1aufweist. Diese liegt genau im Bereich zwischen den Triplett‐Energien des Enol‐ und des Keto‐Tautomers und ermöglicht somit eine dynamische kinetische Sensibilisierung. Um die Anwendbarkeit von fac‐[Ir(CF3‐pmb)3] als Photokatalysator in der organischen Synthese zu demonstrieren, beschreiben wir erstmals eine zweischrittige Photocycloaddition‐Ringöffnungs‐Kaskade mit β‐Ketoestern, ‐Diketonen und ‐Ketoamiden. Der Mechanismus wurde durch zeitaufgelöste Spektroskopie sowie weitere experimentelle und computergestützte Studien analysiert.
Optimizing Hydrogen Binding on Ru Sites with RuCo Alloy Nanosheets for Efficient Alkaline Hydrogen Evolution
Authors: Cai Chao , Liu Kang , Zhu Yuanmin , Li Pengcheng , Wang Qiyou , Liu Bao , Chen Shanyong , Li Huangjingwei , Zhu Li , Li Hongmei , Fu Junwei , Chen Yu , Pensa Evangelina , Hu Junhua , Lu Ying‐Rui , Chan Ting‐Shan , Cortés Emiliano , Liu Min
Published: November 2021

Ruthenium (Ru)‐based catalysts, with considerable performance and desirable cost, are becoming highly interesting candidates to replace platinum (Pt) in the alkaline hydrogen evolution reaction (HER). The hydrogen binding at Ru sites (Ru−H) is an important factor limiting the HER activity. Herein, density functional theory (DFT) simulations show that the essence of Ru−H binding energy is the strong interaction between the
orbital of Ru and the 1s orbital of H. The charge transfer between Ru sites and substrates (Co and Ni) causes the appropriate downward shift of the
‐band center of Ru, which results in a Gibbs free energy of 0.022 eV for H* in the RuCo system, much lower than the 0.133 eV in the pure Ru system. This theoretical prediction has been experimentally confirmed using RuCo alloy‐nanosheets (RuCo ANSs). They were prepared via a fast co‐precipitation method followed with a mild electrochemical reduction. Structure characterizations reveal that the Ru atoms are embedded into the Co substrate as isolated active sites with a planar symmetric and Z‐direction asymmetric coordination structure, obtaining an optimal
modulated electronic structure. Hydrogen sensor and temperature program desorption (TPD) tests demonstrate the enhanced Ru−H interactions in RuCo ANSs compared to those in pure Ru nanoparticles. As a result, the RuCo ANSs reach an ultra‐low overpotential of 10 mV at 10 mA cm−2 and a Tafel slope of 20.6 mV dec−1 in 1 M KOH, outperforming that of the commercial Pt/C. This holistic work provides a new insight to promote alkaline HER by optimizing the metal‐H binding energy of active sites.
Dükerung des Hafenkanals in Duisburg
Authors: Engelke Nils , Hente Jonas , Ebers‐Ernst Jeannette
Published: November 2021

Als Teilmaßnahme des Infrastrukturprojekts „Erneuerung des OB‐Karl‐Lehr‐Brückenzugs, 2. Bauabschnitt“ in Duisburg wird seit 2019 die Dükerung und Leitungsumverlegung unter dem Hafenkanal als vorgezogene Maßnahme durchgeführt. Der im gesteuerten Rohrvortrieb über eine Strecke von 220 m hergestellte Düker wird zukünftig alle derzeit mit den Brückenbauwerken überführten Versorgungsleitungen aufnehmen und damit einen beschleunigten Bauablauf für den Ersatzneubau des Brückenzugs ermöglichen. Neben dem eigentlichen Rohrvortrieb stellten die sehr tiefen Baugruben von ca. 30 m eine Herausforderung für die Planung und die Ausführung dar. Der vorliegende Beitrag erläutert den Werdegang und die technischen Aspekte der Planung und gibt Einblicke in die bauliche Umsetzung der Spezialtiefbaumaßnahme. Darüber hinaus wird kompakt über das Gesamtprojekt und den aktuell laufenden Ersatzneubau der Ruhr‐ und Hafenkanalbrücke informiert.
New Insights into Tolytoxin Effect in Human Cancer Cells: Apoptosis Induction and the Relevance of Hydroxyl Substitution of Its Macrolide Cycle on Compound Potency
Authors: Delawská Kateřina , Divoká Petra , Sedlák David , Kuzma Marek , Saurav Kumar , Macho Markéta , Steinbach Gabor , Hrouzek Pavel
Published: November 2021

Scytophycins, including tolytoxin, represent a class of actin disrupting macrolides with strong antiproliferative effects on human cells. Despite intense research, little attention has been paid to scytophycin‐induced cell death or the structural features affecting its potency. We show that tolytoxin and its natural analogue, 7‐O‐methylscytophycin B, lacking the hydroxyl substitution in its macrolactone ring, differ substantially in their cytotoxic effect. Both compounds increase the level of caspases 3/7, which are the main executioner proteases during apoptosis, in HeLa wild‐type (WT) cells. However, no caspase activity was detected in HeLa cells lacking Bax/Bak proteins crucial for caspase activation via the mitochondrial pathway. Obtained data strongly suggests that scytophycins are capable of inducing mitochondria‐dependent apoptosis. These findings encourage further research in structure‐activity relationships in scytophycins and highlight the potential of these compounds in targeted drug delivery.
Deep Sequencing of a Systematic Peptide Library Reveals Conformationally‐Constrained Protein Interface Peptides that Disrupt a Protein‐Protein Interaction
Authors: Boragine David M. , Huang Wanzhi , Su Lynn H. , Palzkill Timothy
Published: November 2021

Disrupting protein‐protein interactions is difficult due to the large and flat interaction surfaces of the binding partners. The BLIP and BLIP‐II proteins are unrelated in sequence and structure and yet each potently inhibit β‐lactamases. High‐throughput oligonucleotide synthesis was used to construct a 12,470‐member library containing overlapping linear and cyclic peptides ranging in size from 6 to 21 amino acids that scan through the sequences of BLIP and BLIP‐II. Phage display affinity selections and deep sequencing revealed that, despite the differences in interaction surfaces with β‐lactamases, rapid enrichment of consensus peptide regions originating from both BLIP and BLIP‐II contact residues in the binding interface occurred. BLIP and BLIP‐II peptides that were enriched by affinity selection were shown to bind β‐lactamases and disrupt the BLIP/β‐lactamase interaction. The results suggest that peptides that bind at and disrupt PPI interfaces can be identified through systematic peptide library construction, affinity selection, and deep sequencing.
Naphthalene Exchange in [Re(η6‐napht)2]+ with Pharmaceuticals Leads to Highly Functionalized Sandwich Complexes [M(η6‐pharm)2]+ (M=Re/99mTc)
Authors: Nadeem Qaisar , Battistin Federica , Blacque Olivier , Alberto Roger
Published: November 2021

Bis‐arene sandwich complexes are generally prepared by the Fischer‐Hafner reaction, which conditions are incompatible with most O‐ and N‐ functional groups. We report a new way for the synthesis of sandwich type complexes [Re(η6‐arene)2]+ and [Re(η6‐arene)(η6‐benzene)]+ from [Re(η6‐napht)2]+ and [Re(η6‐napht)(η6‐benzene)]+, with functionalized arenes and pharmaceuticals. N‐methylpyrrolidine (NMP) facilitates the substitution of naphthalene with the incoming arene. A series of fully characterized rhenium sandwich complexes with simple arenes, such as aniline, as well as with active compounds like lidocaine and melatonin are presented. With these rhenium compounds in hand, the radioactive sandwich complexes [99mTc(η6‐pharm)2]+ (pharm=pharmaceutical) can be unambiguously confirmed. The direct labelling of pharmaceuticals with 99mTc through η6‐coordination to phenyl rings and the confirmation of the structures with the rhenium homologues opens a path into molecular theranostics.
Development of microglia in fetal and postnatal neocortex of the pig, the European wild boar (Sus scrofa)
Authors: Sobierajski Eric , Lauer German , Aktas Meriyem , Beemelmans Christa , Beemelmans Christoph , Meyer Gundela , Wahle Petra
Published: November 2021

Knowledge on cortical development is based mainly on rodents besides primates and carnivores, all being altricial. Here, we analyzed a precocial animal, the pig, looking at dorsoparietal cortex from E45 to P90. At E45, most ionized calcium‐binding adapter molecule 1‐positive (Iba1+) cells had a macrophage‐like morphology and resided in meninges and choroid plexus. Only a few cells were scattered in the ventricular and subventricular zone (VZ and SVZ). At E60/E70, all laminar compartments displayed microglia cells at a low‐to‐moderate density, being highest in VZ and SVZ followed by intermediate zone/white matter (IZ/WM). The cortical plate and marginal zone displayed only a few Iba1+ cells. Cells were intensely labeled, but still had poorly arborized somata and many resembled ameboid, macrophage‐like microglia. Concurrent with a massive increase in cortical volume, microglia cell density increased until E85, and further until E100/E110 (birth at E114) to densities that resemble those seen postnatally. A fraction of microglia colabeled with Ki67 suggesting proliferation in all laminar compartments. Cell‐to‐cell distance decreased substantially during this time, and the fraction of microglia to all nuclei and to neurons increases in the laminar compartments. Eventually, of all cortical DAPI+ nuclei 7–12% were Iba1+ microglia. From E70 onwards, more and more cells with ramified processes were present in MZ down to IZ/WM, showing, for instance, a close association with NeuN+, NPY+, and GAD65/67+ somata and axon initial segments. These results suggested that the development of microglia cell density and morphology proceeds rapidly from mid‐gestation onwards reaching near‐adult status already before birth.
Theoretical Screening of Transition Metal Doped Defective MoS2 as Efficient Electrocatalyst for CO Conversion to CH4
Authors: Zheng Guokui , Gong Shun , Tian Ziqi , Wang Hui , Zhang Qiuju
Published: November 2021

CO is a key intermediate during electrochemical CO2 conversion. The deep reduction of CO to value‐added chemical products is a crucial strategy for effective carbon utilization. Single transition metal atoms supported by two‐dimensional material present a novel paragon for various catalytic reactions. Herein, we employ first principle theory to study a series of single 3d‐transition metal atoms supported by monolayered MoS2 with S vacancy as efficient electrocatalyst for CO electroreduction to CH4. The screening result indicates that Cr doped defective MoS2 (labeled as Cr/Sv‐MoS2) is beneficial to electroreduction of CO to CH4, with even less negative limiting potential (−0.32 V) than Cu that has been widely studied as the most promising electrocatalyst in experiment. The outstanding activity is derived from the regulation of the d‐band‐center of doped Cr and Mo atoms exposed on the surface. This discovery provides a theoretical basis for the preparation of future electrocatalysts for CORR.
Disorder of three‐dimensional chromosome structure plays a role in carcinogenesis
Authors: Zhang Linlin , Liu Fangming , Wu Lihong , Fu Suolan , Xing Leilei , Zhang Lianghui , Wang Xiangdong , Wang Yong‐Xiao
Published: November 2021

The three‐dimensional structure of chromatin is an essential part of gene expression and regulation. Modules far apart in the one‐dimensional DNA sequence can be close to each other in 3D and activated by spatially folding. Normal gene activation requires such long‐distance interactions. However, the formation of faulty structures of chromosomes can lead to disorders of genetic function, such as cancer. With the development of three‐dimensional (3D) capture techniques, chromatin disorders associated with cancer are gaining attention. In this review, we combined several studies on the 3D genome, regulation and progress of gene expression and involvement of 3D chromatin variation in the development of cancer. We will discuss the possibility and potential value of using the 3D genome as a new target in the clinical diagnosis and treatment of cancer. In a word, high‐order chromatin architecture can provide a new perspective for the study of oncogenic alterations.
Multiple esophageal hematomas with oozing observed and successfully treated after transcatheter mitral valve edge‐to‐edge repair procedure
Authors: Shirai Yasuyuki , Kinoshita Yoshihiro , Koumoto Tatsuya , Kawano Michitaka , Ogoshi Ayako , Harada Katsunori , Isotani Akihiro , Shirai Shinichi , Ando Kenji , Yoshida Tomoharu
Published: November 2021

Although previously reported as relatively rare, esophageal hematoma can likely develop in patients on anticoagulants or those with underlying hemorrhagic disorders. From April 2018 to December 2018, among 36 patients who received transcatheter mitral valve edge‐to‐edge repair (TMVr) at our hospital, seven (19.4%), who were suspected of having digestive tract hemorrhage evidenced by blood stains on a probe extracted after transesophageal echocardiography, underwent esophagogastroduodenoscopy. Esophageal hematomas were noted in all patients, and endoscopic hemostasis was performed in two cases. Depending on their form, hematomas were noted on the submucosa and the epithelium of the shallow esophageal layer. Esophageal hematomas caused by transesophageal echocardiography for TMVr are not rare, and clinicians should be aware of it.
Effect of lncRNA H19 on nerve degeneration and regeneration after sciatic nerve injury in rats
Authors: Li Yuting , Cai Min , Feng Yumei , Yung Bryant , Wang Yi , Gao Nannan , Xu Xi , Zhang Huanhuan , Huang Huiwei , Yao Dengbing
Published: November 2021

Hundreds of millions of people worldwide suffer from peripheral nerve damage resulting from car accidents, falls, industrial accidents, residential accidents, and wars. The purpose of our study was to further investigate the effects of Wallerian degeneration (WD) after rat sciatic nerve injury and to screen for critical long noncoding RNAs (lncRNAs) in WD. We found H19 to be essential for nerve degeneration and regeneration and to be highly expressed in the sciatic nerves of rats with WD. lncRNA H19 potentially impaired the recovery of sciatic nerve function in rats. H19 was mainly localized in the cytoplasm of Schwann cells (SCs) and promoted their migration. H19 promoted the apoptosis of dorsal root ganglion (DRG) neurons and slowed the growth of DRG axons. The lncRNA H19 may play a role in WD through the Wnt/β‐catenin signaling pathway and is coexpressed with a variety of crucial mRNAs during WD. These data provide further insight into the molecular mechanisms of WD.
P2‐Na2/3Ni2/3Te1/3O2 Cathode for Na‐ion Batteries with High Voltage and Excellent Stability
Authors: Wang Wenhui , Zhang Jiaolong , Li Chaolin , Kou Xiaohang , Li Baohua , Yu Denis Y. W.
Published: November 2021

Air‐stable layered structured cathodes with high voltage and good cycling stability are highly desired for the practical application of Na‐ion batteries. Herein, we report a P2‐Na2/3Ni2/3Te1/3O2 cathode that is stable in ambient air with an average operating voltage of ~3.8 V, demonstrating excellent cycling stability with a capacity retention of more than 92.7% after 500 cycles at 20 mA g−1 and good rate capability with 91.9% capacity utilization at 500 mA g−1 with respect to capacity at 5 mA g−1 between 2.0 and 4.0 V. When the upper cutoff voltage is increased to 4.4 V, P2‐Na2/3Ni2/3Te1/3O2 delivers a reversible capacity of 71.9 mAh g−1 and retains 91.8% of the capacity after 100 cycles at 20 mA g−1. The charge compensation during charge/discharge is mainly due to the redox couple of Ni2+/Ni3+ in the host with a small amount of contribution from oxygen. The stable structure of the material without phase transformation and with small volume change during charge‐discharge allows it to give excellent cycle performance especially when the upper cutoff voltage is not higher than 4.2 V.
Focal impaired awareness seizures in a rodent model: A functional anatomy
Authors: Adotevi Nadia , Kapur Jaideep
Published: November 2021

Objective

Patients with temporal lobe epilepsy (TLE) frequently report debilitating comorbidities such as memory impairments, anxiety, and depression. An extensive neuronal network generates epileptic seizures and associated comorbidities, but a detailed description of this network is unavailable, which requires the generation of neuronal activation maps in experimental animals.

Methods

We recorded electrographic seizures from the hippocampi during a kindling‐evoked focal impaired awareness seizure with observed freezing, facial twitching, and involuntary head bobbing. We mapped seizure circuits activated during these seizures by permanently tagging neurons through activity‐induced immediate early genes, combined with immunohistochemical approaches.

Results

There was bilateral activation of circuits necessary for memory consolidation, including the hippocampal complex, entorhinal cortex, cingulate gyrus, retrosplenial cortex, piriform cortex, and septohippocampal complex in kindled animals compared with unstimulated awake behaving mice. Neuronal circuits in the ventral hippocampus, amygdala, and anterior cingulate cortex, which regulate the stress response of hypothalamic‐pituitary‐adrenal axis, were also markedly activated during a focal impaired awareness seizure.

Significance

This study highlights neuronal circuits preferentially activated during a focal awareness impaired seizure in a rodent model. Many of the seizure‐activated neuronal circuits are critical modulators of memory consolidation and long‐term stress/depression response. The hijack of these memory and depression regulatory systems by a focal seizure could account for the frequent reports of comorbidities such as memory impairment and depression in many TLE patients.
Organ‐Specific Comorbidities Are Associated With Distinct Complications After Liver Transplantation for Biliary Atresia
Authors: Taylor Sarah A. , Venkat Veena , Arnon Ronen , Gopalareddy Vani V. , Rosenthal Philip , Anderson Sarah G. , Anand Ravinder , Daniel James F. ,   Society of Pediatric Liver Transplantation
Published: November 2021

Although transplant outcomes for biliary atresia (BA) have improved, there are few data to predict the risk of specific posttransplant complications. We therefore defined the impact of comorbidities in BA on posttransplant outcomes. Patients enrolled in the Society of Pediatric Liver Transplantation registry from 2011 to 2019 (n = 1034) were grouped by comorbidities of >1.0% incidence: any supplemental feeding, dialysis, other abdominal surgery (not Kasai portoenterostomy [KPE]), hepatopulmonary syndrome, and cardiac disease requiring intervention. Demographic and outcome data were compared using the Kruskal‐Wallis, chi‐square, and log‐rank tests. Cox proportional hazards models and binary logistic regression were performed for modeling. Patients with BA with comorbidities comprised 77% (n = 799) of our cohort and had evidence of greater medical acuity, including higher calculated Pediatric End‐Stage Liver Disease scores and hospitalizations in the intensive care unit before transplant (P < 0.001 for both) versus those without comorbidities. After transplant, patients with BA with comorbidities had more graft loss (P = 0.02), longer initial hospitalization and intubation (P < 0.001 for both), and increased rates of reoperation (P = 0.001) and culture‐proven infection (P < 0.001) within 30 days after transplant. Only patients with BA with comorbidities on supplemental feed had increased rates of patient death (P = 0.02). Multivariate analysis identified lower z weight and higher creatinine as risk factors for graft and patient loss in patients with BA with comorbidities. Prior KPE was protective against culture‐proven infection and vascular complications within 30 and 90 days, respectively. Patients with BA with comorbidities have evidence of higher medical acuity at transplant and reduced graft survival; however, they overall did not experience greater incidence of patient death. Our data provide organ‐system–specific data to risk‐stratify patients with BA and posttransplant outcomes.
Possible EIF2AK2‐Associated Stress‐Related Neurological Decompensation with Combined Dystonia and Striatal Lesions
Authors: Waller Sophie E. , Morales‐Briceño Hugo , Williams Laura , Mohammad Shekeeb S. , Fellner Avi , Kumar Kishore R. , Tchan Michel , Fung Victor S.C.
Published: November 2021

Background

Variants in EIF2AK2 have been recently associated with a spectrum of neurological disease encompassing isolated dystonia to fever‐related neurological decompensation, movement disorders and leukodystrophy.

Case

A 32‐year old patient presented with childhood‐onset episodes of neurological decompensation after febrile illness, progressive anarthria, dystonia and spasticity. The T2/FLAIR MRI showed bilateral posterolateral putamen hyperintensities and white matter changes suggestive of leukodystrophy. Initial extensive metabolic workup and whole genome sequencing (WGS) was unremarkable. Re‐analysis of the WGS data revealed a variant in exon 3 of the EIF2AK2 gene [(NM_001135651.3): c.92C > G (p.Pro31Arg)].

EIF2AK2‐associated disorders should be incorporated into the differential diagnosis of the syndrome of fever‐related neurological decompensation with movement disorders, especially in the presence of abnormal neuroimaging.

Literature review

Disease‐causing variants in EIF2AK2 have been reported in 24 individuals from 16 families in the literature to date. Two broad phenotypes have been described, including: (1) childhood‐onset generalized dystonia and a normal brain MRI; and (2) early childhood‐onset developmental delay combined with movement disorders, spasticity, and seizures in some. Notably, 92% of these patients have neurological deterioration after febrile illness or other physiological stress. Hypomyelination or delayed myelination and thin corpus callosum are seen in most patients and lower medullary lessions are common. Basal ganglia lesions have been reported previously in one case.

Conclusions

EIF2AK2‐associated disorders should be incorporated into the differential diagnosis of the syndrome of fever‐related neurological decompensation with movement disorders, especially in the presence of abnormal neuroimaging.
Ex Vivo Fecal Fermentation of Human Ileal Fluid Collected After Wild Strawberry Consumption Modulates Human Microbiome Community Structure and Metabolic Output and Protects Against DNA Damage in Colonic Epithelial Cells
Authors: Diotallevi Camilla , Fontana Massimiliano , Latimer Cheryl , Ternan Nigel G. , Pourshahidi L. Kirsty , Lawther Roger , O'Connor Gloria , Conterno Lorenza , Gasperotti Mattia , Angeli Andrea , Lotti Cesare , Bianchi Martina , Vrhovsek Urska , Fava Francesca , Gobbetti Marco , Gill Chris I. R. , Tuohy Kieran M.
Published: November 2021

Scope

Wild strawberries (Fragaria vesca) are richer in (poly)phenols than common commercial strawberry varieties, e.g., Fragaria × ananassa. (Poly)phenols and their microbiota‐derived metabolites are hypothesized to exert bioactivity within the human gut mucosa. To address this, the effects of wild strawberries are investigated with respect to their bioactivity and microbiota‐modulating capacity using both in vitro and ex vivo approaches.

Methods and Results

Ileal fluids collected pre‐ (0h) and post‐consumption (8h) of 225 g wild strawberries by ileostomates (n = 5) and also in vitro digested strawberry varieties (Fragaria vesca and Fragaria × ananassa Duchesne) supernatants are collected. Subsequent fermentation of these supernatants using an in vitro batch culture proximal colon model reveals significant treatment‐specific changes in microbiome community structure in terms of alpha but not beta diversity at 24 h. Nutri‐kinetic analysis reveals a significant increase in the concentration of gut microbiota catabolites, including 3‐(4hydroxyphenyl)propionic acid, 3‐(3‐hydroxyphenyl)propanoic acid, and benzoic acid. Furthermore, post‐berry ileal fermentates (24 h) significantly (p < 0.01) decrease DNA damage (% Tail DNA, COMET assay) in both HT29 cells (∼45%) and CCD 841 CoN cells (∼25%) compared to untreated controls.

Conclusions

Post berry consumption fermentates exhibit increased overall levels of (poly)phenolic metabolites, which retains their bioactivity, reducing DNA damage in colonocytes.
VF‐4 and DR‐8 Derived from Salted Egg White Inhibit Inflammatory Activity via NF‐κB/PI3K‐Akt/MAPK Signal Transduction Pathways in HT‐29 Cells Induced by TNF‐α
Authors: Zhou Na , Yao Yao , Wu Na , Du Huaying , Xu Mingsheng , Zhao Yan , Tu Yonggang
Published: November 2021

Scope

Inflammation is the pathological basis of many chronic diseases, and persistent intestinal inflammation is a key factor in the further development of colon cancer. Egg‐derived peptides have been proven to have anti‐intestinal inflammation activity. Egg white treated with salt contains a lot of rich protein, whether its peptides have anti‐inflammatory activity and how their mechanism of action is still unclear.

Methods and Results

In this study, ELISA is used to determine the anti‐inflammatory activity of the peptides (VF‐4 and DR‐8 from salted egg white), and then RNA‐seq is used to explore the mechanism of their anti‐inflammatory activity, and then verified by western blotting and inhibitors. The results show that VF‐4 and DR‐8 significantly inhibit TNF‐α‐induced IL‐8 secretion in HT‐29 cells in a concentration‐dependent manner, and VF‐4 show a more significant anti‐inflammatory effect than DR‐8. The anti‐inflammatory mechanism of VF‐4 and DR‐8 is through inhibiting the activation of Nuclear factor kappa B (NF‐κB), mitogen‐activated protein kinase (MAPK), and phosphatidylinositol 3' ‐kinase(PI3K)‐Akt pathways, reducing the production of inflammatory mediators.

Conclusion

VF‐4 and DR‐8 have obvious anti‐inflammatory activity, which can reduce intestinal inflammation and inhibit its further development into colon cancer.
The long exercise test as a functional marker of periodic paralysis
Authors: Ribeiro Ana , Suetterlin Karen J. , Skorupinska Iwona , Tan S. Veronica , Morrow Jasper M. , Matthews Emma , Hanna Michael G. , Fialho Doreen
Published: November 2021

Aims

The aim of this study was to evaluate the sensitivity of the long exercise test (LET) in the diagnosis of periodic paralysis (PP) and assess correlations with clinical phenotypes and genotypes.

Methods

From an unselected cohort of 335 patients who had an LET we analyzed 67 patients with genetic confirmation of PP and/or a positive LET.

Results

32/45 patients with genetically confirmed PP had a significant decrement after exercise (sensitivity of 71%). Performing the short exercise test before the LET in the same hand confounded results in four patients. Sensitivity was highest in patients with frequent (daily or weekly) attacks (8/8, 100%), intermediate with up to monthly attacks (15/21, 71%) and lowest in those with rare attacks (9/16, 56%) (p = .035, Mann–Whitney U‐test). Patients with a positive LET without confirmed PP mutation comprised those with typical PP phenotype and a group with atypical features.

Discussion

In our cohort, the LET is strongly correlated with the frequency of paralytic attacks suggesting a role as a functional marker. A negative test in the context of frequent attacks makes a diagnosis of PP unlikely but it does not rule out the condition in less severely affected patients.
Association between antidepressant use in pregnancy and gestational diabetes mellitus: Results from the Norwegian Mother, Father and Child Cohort Study
Authors: Lupattelli Angela , Barone‐Adesi Francesco , Nordeng Hedvig
Published: November 2021

Purpose

This study sought to determine the association between gestational diabetes mellitus (GDM) and antidepressant exposure during early‐mid pregnancy, overall and according to antidepressant affinity to the histamine‐1 (H1) receptor.

Methods

Data originate from the nation‐wide, Norwegian Mother, Father and Child Cohort Study conducted in 1999–2008, linked to the national Medical Birth Registry. The study included 6647 pregnancies within women with depressive/anxiety disorders during and/or 6 months prior to pregnancy. Pregnancies exposed in early‐mid gestation to antidepressants having low (group 1, n = 814) or high (group 2, n = 77) affinity to the H1 receptor were compared to non‐medicated (n = 5756). We fit crude and weighted modified Poisson regression models using inverse probability of treatment weighting (IPTW).

Results

Overall, 84 (1.3%) of the pregnancies developed GDM. Relative to non‐medicated pregnancies, the risk of GDM was slightly lower in antidepressant group 1 exposed (1.3% vs 1.1%), but more elevated in those exposed to group 2 antidepressants (3.9%). In the weighted analysis, there was no evidence for an association between antidepressant group 1 exposure in early‐mid pregnancy and risk of GDM [relative risk (RR): 0.69, 95% confidence interval: 0.31–1.51].

Conclusions

Gestational use of antidepressants with low H1 receptor affinity, mainly SSRIs and SNRIs, does not pose a substantial risk of GDM in women with depressive/anxiety disorders in pregnancy, compared to no use.
Apixaban and rivaroxaban use for atrial fibrillation in patients with obesity and BMI ≥50 kg/m2
Authors: O’Kane Cavan P. , Avalon Juan Carlo O. , Lacoste Jordan L. , Fang Wei , Bianco Christopher M. , Davisson Laura , Piechowski Kara L.
Published: November 2021

Background

Apixaban and rivaroxaban are increasingly used for thromboembolism prophylaxis in patients with non‐valvular atrial fibrillation (NVAF) and commonly in patients with obesity and body mass index (BMI) ≥50 kg/m2 despite the limited data.

Objectives

This study aimed to establish the effectiveness and safety of apixaban and rivaroxaban in patients with NVAF and BMI ≥50 kg/m2.

Methods

A single health‐system, retrospective cohort study evaluated the effectiveness and safety of apixaban and rivaroxaban initiated in adult patients (≥18 years of age) with BMI ≥50 kg/m2 and NVAF. Outcomes of ischemic stroke, systemic embolic events, and bleeding were compared to a cohort of patients with BMI 18 to 30 kg/m2.

Results

After 1619 patient‐years worth of follow‐up in 595 patients, the primary endpoint of incidence of ischemic stroke was numerically similar in both groups, 1.3 per 100 patient‐years in the BMI ≥50 kg/m2 group, compared to 2.0 per 100 patient‐years in the BMI <30 kg/m2 group (RR 0.65, 95% CI 0.38–1.82, p = 0.544). Incidence of major bleeding and clinically relevant non‐major bleeding was also numerically similar between the two groups.

Conclusions

This study demonstrated that apixaban and rivaroxaban in patients with a BMI ≥50 kg/m2 for treatment of NVAF may be safe and effective at preventing thromboembolic events and had no increased risk of bleeding. Although, findings should be interpreted with caution and confirmed with additional studies. This study contributes to the growing body of evidence that direct oral anticoagulants (DOACs) may be effective and safe to use for the treatment of NVAF in patients with BMI ≥50 kg/m2.
Overall and progression‐free survival of Afro‐Caribbean men with metastatic castration‐resistant prostate cancer (mCRPC)
Authors: Vestris Pierre‐Gilles , Gourtaud Gilles , Senechal Cédric , Sadreux Yvanne , Roux Virginie , Blanchet Pascal , Brureau Laurent
Published: November 2021

Introduction

Several studies in the Caucasian population have shown the benefit of using docetaxel, abiraterone, or enzalutamide for patients with metastatic prostate cancer at the castration‐resistant stage (mCRPC). However, there are no strong data for men of African ancestry. The objective of this study was to estimate the overall and progression‐free survival of patients according to these treatments at the mCRPC stage.

Patients and Methods

This was a monocentric retrospective study that consecutively included 211 men with mCRPC between June 1, 2009 and August 31, 2020. The primary end point was overall survival (OS). The secondary end point was progression‐free survival. Kaplan–Meier survival and Cox proportional hazard analyses were performed.

Results

The present study included 180 patients for analyses. There was no difference in OS (log‐rank test = 0.73), with a median follow‐up of 20.7 months, regardless of the treatment administered in the first line. Men with mCRPC who received hormonotherapy (abiraterone or enzalutamide) showed better progression‐free survival than those who received docetaxel (log‐rank test = 0.004), with a particular interest for abiraterone hazard ratio (HR) = 0.51 (95% confidence interval: 0.39–0.67). The patient characteristics were similar, except for bone lesions, irrespective of the treatment administered in the first line. After univariate then multivariate analysis, only World Health Organization status and metastases at diagnosis were significantly associated with progression.

Conclusion

Our results suggest the use of hormonotherapy (abiraterone or enzalutamide) with a tendency for abiraterone in first line for men with African ancestry at the mCRPC stage.
The N‐glycosylation‐related genes as potential targets for RNAi‐mediated pest control of the Colorado potato beetle (Leptinotarsa decemlineata)
Authors: Liu Dongdong , De Schutter Kristof , Chen Pengyu , Smagghe Guy
Published: November 2021

BACKGROUND

N‐glycosylation is one of the most common and important post‐translational modifications in the eukaryotic cell. The study of protein N‐glycosylation in several model insects confirmed the importance of this process in insect development, immunity, survival and fertility. The Colorado potato beetle (Leptinotarsa decemlineata) (CPB) is a common pest of Solanaceae crops. With the infamous title of champion of insecticide resistance, novel pest control strategies for this insect are needed. Luckily this pest insect is reported as very sensitive for the post‐genomic technology of RNA interference (RNAi).

RESULTS

In this project, we investigated the importance of N‐glycosylation in the survival and development of CPB using RNAi‐mediated gene silencing of N‐glycosylation‐related genes (NGRGs) during the different transition steps from the larva, through the pupa to the adult stage. High mortality was observed in the larval stage with the silencing of early NGRGs, as STT3a, DAD1 and GCS1. With dsRNA against middle NGRGs, abnormal phenotypes at the ecdysis process and adult formation were observed, while the silencing of late NGRGs did not cause mortality.

CONCLUSION

The lethal phenotypes observed on silencing of the genes involved in the early processing steps of the N‐glycosylation pathway suggest these genes are good candidates for RNAi‐mediated control of CPB. Next to the gene‐specific mechanism of RNAi for biosafety and possible implementation in integrated pest management, we believe these early NGRGs provide a possible alternative to the well‐known target genes Snf7 and vacuolar ATPases that are now used in the first commercial RNAi‐based products and thus they may be useful in the context of proactive resistance management. © 2021 Society of Chemical Industry.
Phytosanitary irradiation using X‐rays prevents reproduction in the semi‐slug Parmarion martensi (Stylommatophora: Ariophantidae), a host of the human pathogenic nematode Angiostrongylus cantonensis (Rhabditida: Angiostrongylidae)
Authors: Follett Peter , Hamilton Lindsey , Tagami Yaeko , Kaluna Lisa , Jarvi Susan
Published: November 2021

BACKGROUND

Phytosanitary irradiation is used to control insect pests of quarantine concern on exported fresh horticultural products. Generic irradiation doses of 150 and 400 Gy are approved for tephritid fruit flies and all other insects, respectively. Other invertebrates such as gastropods (snails and slugs) may be classified as quarantine pests and require a disinfestation treatment. Parmarion martensi Simroth (Stylommatophora: Ariophantidae) is a semi‐slug quarantine pest sometimes found on fresh sweet potatoes and other fruits and vegetables exported from Hawai'i to the continental USA. Also, P. martensi is a host of the parasitic nematode Angiostrongylus cantonensis (Rhabditida: Angiostrongylidae), the causative agent of neuroangiostrongyliasis or rat lungworm disease in humans. We conducted a study to determine if phytosanitary irradiation could control P. martensi and thereby reduce the risk of transmitting A. cantonensis in the USA.

RESULTS

Two‐, 12‐, and 21‐week‐old P. martensi were treated with X‐ray radiation at a dose of 150 or 400 Gy or left untreated as controls then held in the laboratory for up to 250 days. Survivorship and reproduction were recorded every 2–3 days and individual weights were measured biweekly. Irradiation at 150 and 400 Gy reduced growth and increased the mortality rate compared to untreated controls and prevented reproduction.

CONCLUSION

Phytosanitary irradiation treatment at doses ≥150 Gy will prevent the establishment of viable populations of P. martensi. The literature on radiation tolerance in gastropods suggests that the internationally approved generic dose for tephritid fruit flies of 150 Gy may be effective against many slug and snail pest species.
Flat deformations of type IIB S-folds
Authors: Guarino Adolfo , Sterckx Colin
Published: November 2021

Abstract

Type IIB S-folds of the form AdS4× S1× S5 have been shown to contain axion-like deformations parameterising flat directions in the 4D scalar potential and corresponding to marginal deformations of the dual S-fold CFT’s. In this note we present a group-theoretical characterisation of such flat deformations and provide a 5D interpretation thereof in terms of $$ \mathfrak{s}(6) $$
s

6

-valued duality twists inducing a class of Cremmer-Scherk-Schwarz flat gaugings in a reduction from 5D to 4D. In this manner we establish the existence of two flat deformations for the $$ \mathcal{N} $$
N
= 4 and SO(4) symmetric S-fold causing a symmetry breaking down to its U(1)2 Cartan subgroup. The result is a new two-parameter family of non-supersymmetric S-folds which are perturbatively stable at the lower-dimensional supergravity level, thus providing the first examples of such type IIB backgrounds.
Tumortherapieassoziierte neurologische Symptome
Authors: Renovanz Mirjam , Rieger Johannes , Tabatabai Ghazaleh
Published: November 2021

Die onkologische Behandlung ist biomarkerbasierter, molekular maßgeschneiderter und effektiver geworden. Aufbauend auf der zunehmenden Entschlüsselung zellbiologischer und molekularer Mechanismen steigt auch die Zahl zielgerichteter medikamentöser Therapien. Es steigt zudem die Zahl der Langzeitüberlebenden. Eine neuro(onko)logische Betreuung wird immer wichtiger, nicht nur wegen vermehrter direkter tumorbedingter Symptome – wie etwa der höheren Inzidenz einer Metastasierung in das Zentralnervensystem –, sondern weil im Zuge dieser modernen onkologischen systemischen Therapieformen ein breites Spektrum therapieassoziierter neurologischer Symptome auftritt, die einer sorgfältigen und raschen neurologischen/neuroonkologischen Evaluation und Therapiekonzeption bedürfen. Das Ziel dieses Artikels ist es, das Bewusstsein für die häufigsten therapieassoziierten neurologischen Symptome zu schärfen.