bluuebunny/crossref_metadata_2025 huggingface dataset:
A Supramolecular Porous Organic Cage Platform Promotes Electrochemical Hydrogen Evolution from Water Catalyzed by Cobalt Porphyrins
Authors: Smith Peter T. , Benke Bahiru Punja , An Lun , Kim Younghoon , Kim Kimoon , Chang Christopher J.
Published: May 2021

We report a supramolecular porous organic cage platform composed of cobalt porphyrins for catalyzing the electrochemical hydrogen evolution reaction (HER) from water at neutral pH. Owing to its permanent porosity, the supramolecular structure yields a catalyst film with a fivefold increase in the number of electrochemically active cobalt atoms and an improvement in Tafel slope from 170 mV/decade to 119 mV/decade compared to a planar cobalt porphyrin analog, reaching activities over 19,000 turnovers for HER over a 24‐hour period with 100 % Faradaic efficiency.
O/N/S trifunctional doping on graphite felts: A novel strategy toward performance boosting of cerium‐based redox flow batteries
Authors: Na Zhaolin , Wang Xinran , Liu Xiaoting , Li Wenjing , Sun Xudong
Published: May 2021

The cerium‐based redox flow battery (RFB) is regarded as a compelling grid‐scale energy storage technology to revolutionize the utilization of renewable energy by storing the energy in liquid electrolytes. However, its widespread implementation is impeded by the cerium redox reactions that exhibit slow kinetics on commercial graphite felt (GF) electrodes. Surface functionalization may be an available activation strategy to achieve a significant boost in the electrochemical performance of GFs. However, conventional chemical and/or electrochemical routes for the surface functionalization of GFs suffer from the issues of complication, and the deterioration of the resulting modified electrode surface over long‐term cycle processes leads to catalytic activity decline. Here, we develop a facile and general strategy for introducing the functional groups to the electrode through the addition of l‐cysteine into electrolytes. The –COOH, –NH2, and –SH groups in l‐cysteine can induce oxygen/nitrogen/sulfur trifunctional doping on GF surfaces with lower deterioration rates, which enables the activated GFs to demonstrate a promising electrocatalytic activity toward cerium redox reactions and excellent durability when used as a cerium‐based RFB electrode. This study proposes a rational strategy to overcome the intrinsic limitations of existing modification techniques for GFs and provides a potential pathway toward high‐performance RFBs.
Photoinduced Force Microscopy as an Efficient Method Towards the Detection of Nanoplastics
Authors: C. ten Have Iris , Duijndam Adriaan J. A. , Oord Ramon , van Berlo‐van den Broek Hannie J. M. , Vollmer Ina , Weckhuysen Bert M. , Meirer Florian
Published: May 2021

Invited for this month's cover is the group of Bert M. Weckhuysen and Florian Meirer at Utrecht University (The Netherlands). The cover picture shows polystyrene nanoplastics and how they are detected with photo‐induced force microscopy. This method overcomes the diffraction limit of infrared light by employing a nano‐sized tip as detector. Oxidative degradation and chain scission occurred on the surface of the polystyrene nanoplastics in salt water, as depicted by the carbonyl and aliphatic functionalities. Detecting nano‐sized plastic particles is essential for understanding how plastic waste breaks down into smaller particles in the environment.

Read the full text of their Communication at 10.1002/cmtd.202100017.
Promotional Effect of Ni−Sn Interaction over Ni Supported on Sn‐incorporated MCM‐41 Catalysts for CO2 Reforming of CH4
Authors: Zhao Yutong , Wang Zichun , Yang Wenjie , Gu Shengshen , Yang Xiaoxia , Kheradmand Amanj , Zhang Xingmo , Luo Yongming , Huang Jun , Jiang Yijiao
Published: May 2021

Sintering of active Ni sites and deposition of coke remain challenging issues for catalytic dry reforming of methane. Herein, Ni supported on the Sn‐incorporated MCM‐41 catalysts were synthesized and tested for DRM process. The structural and physicochemical properties of fresh and spent samples were studied by N2 adsorption‐desorption, XRD, H2‐TPR, XPS, TEM, STEM‐EDS, Raman, and TGA techniques. It was revealed that Sn addition improved the dispersion and decreased the size of active Ni nanoparticles by tuning the charger transfer between Ni and Sn. The formation of Ni−SnOx interface provides more possibilities to activate CO2. The best results were obtained by 2Ni/Sn−MCM‐41 sample with the Ni/Sn mole ratio of 2 : 1, contributing CH4 conversion of 95% and CO2 conversion of 94% at 800 °C. Moreover, the presence of Sn increased the resistance to sintering of Ni‐based catalysts during the severe conditions, thereby the Ni nanoparticle size only appeared a slight growth after 32 h TOS. Combined with the characterization of the spent 2Ni/Sn−MCM‐41 sample, it was revealed that the coke deposition of the deactivated catalyst was dominated by amorphous carbon, which could be responsible for the desirable regeneration ability of the catalyst.
A Single Supratherapeutic Dose of Atogepant Does Not Affect Cardiac Repolarization in Healthy Adults: Results From a Randomized, Single‐Dose, Phase 1 Crossover Trial
Authors: Boinpally Ramesh , McNamee Brian , Yao Li , Butler Matthew , McGeeney Danielle , Borbridge Lisa , Periclou Antonia
Published: May 2021

Atogepant is a selective, oral calcitonin gene–related peptide receptor antagonist in development for preventive treatment of migraine. This randomized, double‐blind, phase 1 crossover study evaluated the cardiac repolarization effect of a single supratherapeutic (300 mg) atogepant dose vs placebo in healthy adults. Moxifloxacin 400 mg was the open‐label active control. The primary end point was a change from baseline in Fridericia‐corrected QT intervals (ΔQTcF). Sixty participants were randomized to atogepant 300 mg, placebo, and moxifloxacin; 59 (98.3%) completed all interventions. Assay sensitivity was confirmed: lower 90% confidence interval limit for QTcF interval change from baseline (ΔΔQTcF) for moxifloxacin was >5 millisecond vs placebo at prespecified 2‐, 3‐, and 4‐hour time points. Following single‐dose atogepant 300 mg, mean atogepant ΔΔQTcF and upper 90% confidence interval limits were lower than the 10‐millisecond threshold at all time points. Atogepant mean peak plasma concentration was 3197 ng/mL, area under the concentration‐time curve from time 0 to time t was 16 640 ng • h/mL, area under the concentration‐time curve from time 0 to 24 hours was 16 607 ng • h/mL, and median time to peak plasma concentration was 2.1 hours. The incidence of adverse events was low; no serious adverse events or elevations of liver enzymes were reported. Overall, a single supratherapeutic dose of atogepant was safe and did not impact cardiac repolarization in healthy participants.
Effects of Light Intensity and Reaction Temperature on Photoreactions in Commercial Photoreactors
Authors: Svejstrup Thomas D. , Chatterjee Anamitra , Schekin Denis , Wagner Thomas , Zach Julia , Johansson Magnus J. , Bergonzini Giulia , König Burkhard
Published: May 2021

In the last decade, visible‐light photoredox catalysis has evolved into a versatile tool in organic synthesis. However, most reports have used homemade photoreactors in their design and optimisation of new methods, complicating the reproducibility of some transformations. To improve reproducibility and efficiency, laboratory photoreactors have been developed and commercialized. Herein we report a comparison of four commercially available photoreactors in six mechanistically distinct photoredox reactions focusing on the difference in product yields and kinetics as well as the factors which lead to these differences, including reaction temperature and light intensity.
An Improved PEG‐Linked Solid Support for Minimizing Process‐Related Impurities During Solid‐Phase Synthesis of DNA and RNA Sequences
Authors: Grajkowski Andrzej , Takahashi Mayumi , Cawrse Brian M. , Beaucage Serge L.
Published: May 2021

The preparation of controlled pore glass (CPG) supports, functionalized with several hexaethylene glycol spacers, to alleviate the problems associated with the porosity of commercial CPG supports is described in this article. The pore size of CPG restricts the diffusion of reagents to the leader nucleoside embedded in porous supports; this inhibits efficient solid‐phase syntheses of DNA and RNA sequences and, by default, the purity of those sequences through formation of a shorter than full‐length oligonucleotide. Functionalization of a CPG support with five hexaethylene glycol spacers led to a 42% reduction in process‐related impurities contaminating oligonucleotide sequences, compared to that obtained using the commercial long‐chain alkylamine (LCAA) CPG support. © 2021 Wiley Periodicals LLC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Basic Protocol 1: Preparation of the hydroxylated CPG support 3

Basic Protocol 2: Automated preparation of the CPG support 6

Basic Protocol 3: Automated preparation of the poly(hexaethylene glycol)‐derived CPG 7

Basic Protocol 4: Automated functionalization of the poly(hexaethylene glycol)‐derived CPG support 7 with leader deoxyribo‐ and ribonucleosides to provide the CPG support 9

Basic Protocol 5: Automated syntheses of DNA and RNA sequences on poly(hexaethylene glycol)‐derived CPG support 9 and on a commercial long‐chain alkylamine (LCAA) CPG support

Support Protocol: Release and deprotection of the DNA and RNA sequences linked to the poly(hexaethylene glycol)‐derived CPG support 10 and commercial LCAA‐CPG support

Basic Protocol 6: Comparative RP‐HPLC analyses of crude, fully deprotected DNA or RNA sequences released from the poly(hexaethylene glycol)‐derived CPG support 10 and from a commercial LCAA‐CPG support
IPM Toolkit Preservation
Authors: Ulmer Bryan
Published: May 2021

Integrated pest management (IPM) is a holistic approach that considers all farming practices and control tactics to discourage the development of economically damaging pest populations with a focus on preventing and managing pest populations as opposed to single interventions to eliminate pests once a problem has occurred. The idea of the IPM toolkit analogy is to keep as many tools in the toolbox as possible to manage agricultural pests; the more tools available, the better chance of providing a solution to a given pest threat. Preserving these tools is critically important to IPM. This article is the second in the three‐part series in Crops & Soils magazine. It is part of an American Society of Agronomy training series sponsored by the Kellogg Company. Earn 1 CEU in Integrated Pest Management by reading this article and taking the quiz at www.certifiedcropadviser.org/education/classroom/classes/983.
Threshold‐based key management scheme for space network
Authors: Tong Xiaojun , Liu Jie , Wang Zhu , Zhang Miao , Ma Jing
Published: May 2021

The data link protocols proposed by the Consultative Committee for Space Data Systems (CCSDS) is widely used in space missions. However, the current space key management schemes are inefficient in scalability, security, and key update. In this work, a threshold‐based spatial key management scheme is proposed and applied to the CCSDS telecommunication control (TC) protocol to ensure the security of spatial networks. The threshold‐based key management algorithm using LDPC code is designed to generate, distribute, update, and deactivate the master key. The bilinear pairing cryptosystem is used to protect the group key and provide authentication. The security and performance of the proposed scheme are analyzed. Furthermore, the network model, node model, and process model of CCSDS‐TC protocol based on the proposed scheme are constructed and simulated on OPNET platform. The result shows that the storage overhead of the proposed scheme is lower than the improved Shamir and ECC‐based key management schemes. Its computational overhead is approximately changeless, whereas the network scale is increasing. Furthermore, the proposed scheme only uses binary multiplication, which takes lower computation overhead. Therefore, the proposed scheme has higher security, scalability, and low resource consumption.
Food cravings and loss‐of‐control eating in youth: Associations with gonadal hormone concentrations
Authors: Parker Megan N. , Tanofsky‐Kraff Marian , Crosby Ross D. , Byrne Meghan E. , LeMay‐Russell Sarah , Swanson Taylor N. , Ramirez Eliana , Shank Lisa M. , Djan Kweku G. , Kwarteng Esther A. , Faulkner Loie M. , Yang Shanna B. , Zenno Anna , Chivukula K. Karthik , Engel Scott G. , Brady Sheila M. , Yanovski Susan Z. , Yanovski Jack A.
Published: May 2021

Objective

Among youth with overweight, food cravings (FC) are associated with loss‐of‐control (LOC)‐eating, but the impact of sex‐associated biological characteristics on this relationship is unknown. We examined whether sex and gonadal hormone concentrations moderated the relationships between FC and LOC‐eating severity among healthy boys and girls across the weight strata in natural and laboratory environments.

Method

Using ecological momentary assessment (EMA), FC, and LOC‐eating severity were reported 3–5 times a day for 2 weeks. In the laboratory, participants reported FC, consumed lunch from a buffet test meal designed to simulate LOC‐eating, and rated LOC‐eating severity during the meal.

Results

Eighty‐seven youth (13.0 ± 2.7 years, 58.6% female, 32.2% with overweight/obesity) participated. EMA measured general and momentary FC were positively associated with LOC‐eating severity (ps < .01), with no differences by sex (ps = .21–.93). Estradiol and progesterone significantly moderated the relationships between FC and LOC‐eating such that general FC and LOC‐eating severity were only positively associated among girls with greater (vs. lower) estradiol (p = .01), and momentary FC and LOC‐eating severity were only positively associated among girls with greater (vs. lower) progesterone (p = .01). Boys' testosterone did not significantly moderate the associations between FC and LOC‐eating severity (ps = .36–.97). At the test meal, pre‐meal FC were positively related to LOC‐eating severity (p < .01), without sex or hormonal moderation (ps = .20–.64).

Discussion

FC were related to LOC‐eating severity in boys and girls. In the natural environment, gonadal hormones moderated this relationship in girls, but not boys. The mechanisms through which gonadal hormones might affect the relationship between FC and LOC‐eating warrant investigation.
Deep learning‐based pose estimation for African ungulates in zoos
Authors: Hahn‐Klimroth Max , Kapetanopoulos Tobias , Gübert Jennifer , Dierkes Paul Wilhelm
Published: May 2021

The description and analysis of animal behavior over long periods of time is one of the most important challenges in ecology. However, most of these studies are limited due to the time and cost required by human observers. The collection of data via video recordings allows observation periods to be extended. However, their evaluation by human observers is very time‐consuming. Progress in automated evaluation, using suitable deep learning methods, seems to be a forward‐looking approach to analyze even large amounts of video data in an adequate time frame.

In this study, we present a multistep convolutional neural network system for detecting three typical stances of African ungulates in zoo enclosures which works with high accuracy. An important aspect of our approach is the introduction of model averaging and postprocessing rules to make the system robust to outliers.

Our trained system achieves an in‐domain classification accuracy of >0.92, which is improved to >0.96 by a postprocessing step. In addition, the whole system performs even well in an out‐of‐domain classification task with two unknown types, achieving an average accuracy of 0.93. We provide our system at https://github.com/Klimroth/Video‐Action‐Classifier‐for‐African‐Ungulates‐in‐Zoos/tree/main/mrcnn_based so that interested users can train their own models to classify images and conduct behavioral studies of wildlife.

The use of a multistep convolutional neural network for fast and accurate classification of wildlife behavior facilitates the evaluation of large amounts of image data in ecological studies and reduces the effort of manual analysis of images to a high degree. Our system also shows that postprocessing rules are a suitable way to make species‐specific adjustments and substantially increase the accuracy of the description of single behavioral phases (number, duration). The results in the out‐of‐domain classification strongly suggest that our system is robust and achieves a high degree of accuracy even for new species, so that other settings (e.g., field studies) can be considered.
Immunological analysis of the murine anti‐CD3‐induced cytokine release syndrome model and therapeutic efficacy of anti‐cytokine antibodies
Authors: Nouveau Lise , Buatois Vanessa , Cons Laura , Chatel Laurence , Pontini Guillemette , Pleche Nicolas , Ferlin Walter G.
Published: May 2021

The aberrant release of inflammatory mediators often referred to as a cytokine storm or cytokine release syndrome (CRS), is a common and sometimes fatal complication in acute infectious diseases including Ebola, dengue, COVID‐19, and influenza. Fatal CRS occurrences have also plagued the development of highly promising cancer therapies based on T‐cell engagers and chimeric antigen receptor (CAR) T cells. CRS is intimately linked with dysregulated and excessive cytokine release, including IFN‐γ, TNF‐α, IL 1, IL‐6, and IL‐10, resulting in a systemic inflammatory response leading to multiple organ failure. Here, we show that mice intravenously administered the agonistic hamster anti‐mouse CD3ε monoclonal antibody 145‐2C11 develop clinical and laboratory manifestations seen in patients afflicted with CRS, including body weight loss, hepatosplenomegaly, thrombocytopenia, increased vascular permeability, lung inflammation, and hypercytokinemia. Blood cytokine levels and gene expression analysis from lung, liver, and spleen demonstrated a hierarchy of inflammatory cytokine production and infiltrating immune cells with differentiating organ‐dependent kinetics. IL‐2, IFN‐γ, TNF‐α, and IL‐6 up‐regulation preceded clinical signs of CRS. The co‐treatment of mice with a neutralizing anti‐cytokine antibody cocktail transiently improved early clinical and laboratory features of CRS. We discuss the predictive use of this model in the context of new anti‐cytokine strategies to treat human CRS.
The limits of gender and regional diversity in the European Association of Social Psychology
Authors: Nyúl Boglárka , Lantos Nóra Anna , Reicher Stephen D. , Kende Anna
Published: May 2021

Academic associations define the scientific standards and affect individual academic careers within a discipline. The European Association of Social Psychology (EASP) was founded in 1966 to become an association for all social psychologists in Europe. However, this was unattainable during the Cold War, and more subtle obstacles, such as women's underrepresentation in academia, prevented EASP from due representation of all social psychologists. Social psychological theory offers insights into why social hierarchies are maintained and how they can be dismantled. We used the case of EASP to analyse challenges to creating a diverse and inclusive association by analysing membership data, participation, distinction and influence throughout the organisation's history (1966–2020) and conducting a more in‐depth analysis for the 2011–2017 period. We found a glass‐ceiling effect for women and a persistent underrepresentation of non‐Western European scholars on all levels. We conclude that increasing diversity requires more fundamental changes to overcome structural inequalities.
Mapping the electronic structure of polypyrrole with image‐based electrochemical scanning tunneling spectroscopy
Authors: Gonçalves Roger , Paiva Robert S. , Ramírez Andrés M. R. , Mwanda Jonathan A. , Pereira Ernesto C. , Cuesta Angel
Published: May 2021

Conducting polymers are semiconductors whose applications cover a wide range of devices. Their versatility is due, in addition to other factors, to properties that can be easily modulated according to the intended application. It is therefore important to study and map the electronic structure of these materials for a better correlation between structure and properties. Electrochemical scanning tunneling spectroscopy (EC‐STS) can be a powerful tool to characterize the electronic structure of the semiconductor interface. In this work, we have used image‐based EC‐STS (IB‐EC‐STS) to describe quantitatively the band structure of an electrochemically deposited polypyrrole film. IB‐EC‐STS located the band edge of the polymer's valence band (VB) at 0.95 V vs. RHE (‐5.33 eV in the absolute potential scale) and the intragap polaron states formed when the polymer is doped, at 0.46 V vs. RHE (‐4.84 eV). The IB‐EC‐STS data were cross‐checked with electrochemical impedance spectroscopy (EIS) and Mott‐Schottky analysis of the interfacial capacitance. The DOS spectrum obtained from EIS data is consistent with the STS‐deduced location of the VB and the polarons.
Antiepileptogenesis and disease modification: Progress, challenges, and the path forward—Report of the Preclinical Working Group of the 2018 NINDS‐sponsored antiepileptogenesis and disease modification workshop
Authors: Galanopoulou Aristea S. , Löscher Wolfgang , Lubbers Laura , O’Brien Terence J. , Staley Kevin , Vezzani Annamaria , D’Ambrosio Raimondo , White H. Steve , Sontheimer Harald , Wolf John A. , Twyman Roy , Whittemore Vicky , Wilcox Karen S. , Klein Brian
Published: May 2021

Epilepsy is one of the most common chronic brain diseases and is often associated with cognitive, behavioral, or other medical conditions. The need for therapies that would prevent, ameliorate, or cure epilepsy and the attendant comorbidities is a priority for both epilepsy research and public health. In 2018, the National Institute of Neurological Disease and Stroke (NINDS) convened a workshop titled “Accelerating the Development of Therapies for Antiepileptogenesis and Disease Modification” that brought together preclinical and clinical investigators and industry and regulatory bodies’ representatives to discuss and propose a roadmap to accelerate the development of antiepileptogenic (AEG) and disease‐modifying (DM) new therapies. This report provides a summary of the discussions and proposals of the Preclinical Science working group. Highlights of the progress of collaborative preclinical research projects on AEG/DM of ongoing research initiatives aiming to improve infrastructure and translation to clinical trials are presented. Opportunities and challenges of preclinical epilepsy research, vis‐à‐vis clinical research, were extensively discussed, as they pertain to modeling of specific epilepsy types across etiologies and ages, the utilization of preclinical models in AG/DM studies, and the strategies and study designs, as well as on matters pertaining to transparency, data sharing, and reporting research findings. A set of suggestions on research initiatives, infrastructure, workshops, advocacy, and opportunities for expanding the borders of epilepsy research were discussed and proposed as useful initiatives that could help create a roadmap to accelerate and optimize preclinical translational AEG/DM epilepsy research.
The role of rubber farming in household dietary diversity in the upper Mekong region, Southwest China
Authors: Luo Yajie , Min Shi , Bai Junfei
Published: May 2021

The expansion of cash tree crops, such as natural rubber, in the tropical region of South Asia has resulted in an agricultural transformation from subsistence production to market‐oriented production, implicating the local ecological environment, economy, and household welfare. Based on representative household survey data collected from 611 smallholder rubber farmers in the upper Mekong region, Southwest China, this study examines the impacts of rubber farming on the household dietary diversity of smallholders and explores its potential impact channels through farm production diversity and household income. The results show that rubber expansion has significantly improved household income but negatively affected farm production diversity. While rubber cultivation always has significant and positive effects on dietary diversity, it also indirectly impacts on dietary diversity by the two channels, namely farm production diversity and household income. A set of heterogeneous analyses reveals that rubber cultivation contributes more to household dietary diversity for smallholders having relatively low household wealth or living in a village without a market. While the findings confirm the contribution of rubber cultivation to improving household incomes, food security, and nutrition, the potential risks under the background of falling rubber prices cannot be ignored. The findings of this study not only have important policy implications for improving the food security and nutrition of smallholder rubber farmers but also provide a better understanding of the welfare effects of cash tree crop expansion in tropical regions.
Evaluation of the bioaccessibility of a carotenoid beadlet blend using an in vitro system mimicking the upper gastrointestinal tract
Authors: Hu Chun , Salter Venzon Dawna , Lange Katja , Maathuis Annet , Bellmann Susann , Gellenbeck Kevin
Published: May 2021

The release characteristics of a unique blend of carotenoid beadlets designed to increase bioavailability were tested using the dynamic gastrointestinal model TIM‐1. Individual carotenoid bioaccessibility peaks were observed over approximately 3–4 hr in the order of lutein and zeaxanthin first, followed by lycopene, and then finally α‐ and β‐carotene; when tested as a beadlet blend or when the beadlets were compressed into tablets. Bioaccessibility measurements of 7%–20% were similar to those previously reported in literature and comparable between the two formulations, beadlet blend and tablet formulations. Total recovery of carotenoids from all compartments ranged from 70% to 90% for all carotenoids, except lycopene where almost 50% was unrecoverable after digestion in the TIM system.
An updated global atmospheric paleo‐reanalysis covering the last 400 years
Authors: Valler Veronika , Franke Jörg , Brugnara Yuri , Brönnimann Stefan
Published: May 2021

Data assimilation techniques are becoming increasingly popular for climate reconstruction. They benefit from estimating past climate states from both observation information and from model simulations. The first monthly global paleo‐reanalysis (EKF400) was generated over the 1600 and 2005 time period, and it provides estimates of several atmospheric fields. Here we present a new, considerably improved version of EKF400 (EKF400v2). EKF400v2 uses atmospheric‐only general circulation model simulations with a greatly extended observational network of early instrumental temperature and pressure data, documentary evidences and tree‐ring width and density proxy records. Furthermore, new observation types such as monthly precipitation amounts, number of wet days and coral proxy records were also included in the assimilation. In the version 2 system, the assimilation process has undergone methodological improvements such as the background‐error covariance matrix is estimated with a blending technique of a time‐dependent and a climatological covariance matrices. In general, the applied modifications resulted in enhanced reconstruction skill compared to version 1, especially in precipitation, sea‐level pressure and other variables beside the mostly assimilated temperature data, which already had high quality in the previous version. Additionally, two case studies are presented to demonstrate the applicability of EKF400v2 to analyse past climate variations and extreme events, as well as to investigate large‐scale climate dynamics.
Oligodendrocytes are susceptible to Zika virus infection in a mouse model of perinatal exposure: Implications for CNS complications
Authors: Schultz Verena , Barrie Jennifer A. , Donald Claire L. , Crawford Colin L. , Mullin Margaret , Anderson Thomas J. , Solomon Tom , Barnett Susan C. , Linington Christopher , Kohl Alain , Willison Hugh J. , Edgar Julia M.
Published: May 2021

Some children with proven intrauterine Zika virus (ZIKV) infection who were born asymptomatic subsequently manifested neurodevelopmental delays, pointing to impairment of development perinatally and postnatally. To model this, we infected postnatal day (P) 5–6 (equivalent to the perinatal period in humans) susceptible mice with a mammalian cell‐propagated ZIKV clinical isolate from the Brazilian outbreak in 2015. All infected mice appeared normal up to 4 days post‐intraperitoneal inoculation (dpi), but rapidly developed severe clinical signs at 5–6 dpi. All nervous tissue examined at 5/6 dpi appeared grossly normal. However, anti‐ZIKV positive cells were observed in the optic nerve, brain, and spinal cord; predominantly in white matter. Co‐labeling with cell type specific markers demonstrated oligodendrocytes and astrocytes support productive infection. Rarely, ZIKV positive neurons were observed. In spinal cord white matter, which we examined in detail, apoptotic cells were evident; the density of oligodendrocytes was significantly reduced; and there was localized microglial reactivity including expression of the NLRP3 inflammasome. Together, our observations demonstrate that a clinically relevant ZIKV isolate can directly impact oligodendrocytes. As primary oligodendrocyte cell death can lead later to secondary autoimmune demyelination, our observations may help explain neurodevelopmental delays in infants appearing asymptomatic at birth and commend lifetime surveillance.
Submandibular gland degloving: A minimally invasive function‐preserving surgical approach for benign diseases
Authors: Piras Antonio , Rizzo Davide , Gallus Roberto , Artuso Alberto , Bussu Francesco
Published: May 2021

In the Video S1, a modified technique for submandibular gland resection in benign disease is shown. The main plane of dissection is below the fascia and immediately superficial to the fibrous capsule of the gland. The video shows the surgical steps and the structures that become evident along the procedure and illustrates some tips and tricks. Facial vessels are dissected, easily spared, and not ligated as it occurs in the classical technique. This technical variant is minimally invasive, respectful of anatomy, and through preservation of the fascial layer investing the gland aims at reducing the risk of injury to the marginalis mandibulae branch of the facial nerve, which lies within the fascia itself.
Hepatocellular Carcinoma Screening Process Failures in Patients with Cirrhosis
Authors: Marquardt Patrick , Liu Po‐Hong , Immergluck Joshua , Olivares Jocelyn , Arroyo Ana , Rich Nicole E. , Parikh Neehar D. , Yopp Adam C. , Singal Amit G.
Published: May 2021

Professional society guidelines recommend semiannual screening for hepatocellular carcinoma (HCC) in patients with cirrhosis; however, studies suggest underuse of screening in clinical practice. Our study’s aim was to characterize reasons for HCC screening underuse among patients with cirrhosis. We conducted a retrospective cohort study of patients with cirrhosis diagnosed with HCC in two large health systems from 2011 to 2019. We classified screening receipt as consistent, inconsistent, or no screening in the year before HCC diagnosis. We categorized reasons for screening underuse as a potential failure at each of the following steps required for HCC screening: receipt of regular outpatient care, recognition of liver disease, recognition of cirrhosis, screening orders in patients with cirrhosis, and adherence to screening ultrasound appointments. Among 1,014 patients with cirrhosis with HCC, only 377 (37.2%) had regular outpatient care in the year before HCC presentation. Consistent screening was observed in 93 (24.7%) patients under regular outpatient care, whereas 161 (42.7%) had inconsistent screening and 123 (32.6%) no screening. We found screening underuse related to failures at each step in the screening process, although nearly half (49.6%) were due to lack of screening orders in patients with known cirrhosis. Conclusion: The most common reasons for HCC screening underuse in patients with cirrhosis are lack of regular outpatient care and lack of screening orders in those with known cirrhosis, highlighting the need for interventions targeted at these steps to increase HCC screening use.
Sleep as a window on the sensorimotor foundations of the developing hippocampus
Authors: Del Rio‐Bermudez Carlos , Blumberg Mark S.
Published: May 2021

The hippocampal formation plays established roles in learning, memory, and related cognitive functions. Recent findings also suggest that the hippocampus integrates sensory feedback from self‐generated movements to modulate ongoing motor responses in a changing environment. Such findings support the view of Bland and Oddie (Behavioural Brain Research, 2001, 127, 119–136) that the hippocampus is a site of sensorimotor integration. In further support of this view, we review neurophysiological evidence in developing rats that hippocampal function is built on a sensorimotor foundation and that this foundation is especially evident early in development. Moreover, at those ages when the hippocampus is first establishing functional connectivity with distant sensory and motor structures, that connectivity is preferentially expressed during periods of active (or REM) sleep. These findings reinforce the notion that sleep, as the predominant state of early infancy, provides a critical context for sensorimotor development, including development of the hippocampus and its associated network.
Risk factors of ocular morbidity among under‐five years old children in Khartoum State‐ Sudan‐ 2020
Authors: Ibrahim Mohanad Kamaleldin Mahmoud , Wolvaardt Jacqueline Elizabeth , Elnimeiri Mustafa Khidir Mustafa
Published: May 2021

Background and Aims

Visual impairment in early childhood can significantly affect the development of visual, motor, and cognitive function and potentially lead to long‐term adverse psychosocial consequences. This study aimed to identify the risk factors of ocular morbidity among under 5‐year old children in Khartoum State, Sudan.

Methods

A cross‐sectional study was conducted in three tertiary eye care hospitals in Khartoum State, Sudan. The study included 391 children under the age of 5 years. The parent(s) were interviewed using a precoded, pretested, closed‐ended questionnaire that included questions regarding socio‐demographic profile and possible risk factors. Data were analyzed using Statistical Package for the Social Sciences (version 21.0). A P‐value of less than .05 was regarded as significant.

Results

There was a significant association between participants with diabetes mellitus and poor vision (P‐value <.001). Two‐thirds of participants (57%) with visual impairment had mothers, who reportedly attended antenatal care services regularly (P‐value .001), revealing a significant statistical association. Maternal diseases, specifically diabetes, was identified as a risk factor for poor visual acuity in their offspring (P‐value <.001). A significant relation was revealed between family history of eye disease and the degree of relationship to the affected participant (P‐value <.001). There was an association between watching TV and current visual acuity (P‐value <.001); as well as using mobile phones and current visual acuity (P‐value <.001). Multilinear analysis revealed the stronger influence of TV watching rather than the use of mobile phones (P‐value <.001).

Conclusions

Diabetes, diabetic mothers, a family history of ocular morbidity, watching television, and using mobile phones emerged as significant risk factors of ocular morbidity among children under the age of 5 years in this study. Many of these risk factors are either modifiable or controllable ocular morbidities among under‐five children can be reduced with suitable interventions.
The PI3K pathway as a therapeutic intervention point in inflammatory bowel disease
Authors: Winkelmann Paula , Unterweger Anna‐Lena , Khullar Diya , Beigel Florian , Koletzko Leandra , Siebeck Matthias , Gropp Roswitha
Published: May 2021

With glucose being the preferred source of energy in activated T cells, targeting glycolysis has become an attractive therapeutic intervention point for chronic inflammatory bowel diseases (IBD). The switch to glycolysis is mediated by phosphoinositide‐3‐kinases (PI3K) which relay signals from surface receptors to the AKT pathway. We first confirmed by analysis of the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) that metabolism is shifted towards glycolysis in IBD patients as compared to non‐IBD donors. In contrast to non‐IBD donors, OCR correlated with ECAR (IBD: cor = 0.79, p = 2E‐10; non‐IBD: cor = 0.37, p = n.s.), in IBD patients. Second, we tested the PI3K inhibitor copanlisib as a potential therapeutic. Ex vivo, copanlisib suppressed the ECAR significantly in T cells activated by anti‐CD3 antibodies and significantly decreased ECAR rates in the presence of copanlisib (anti‐CD3: 58.24 ± 29.06; copanlisib: 43.16 ± 20.23, p < .000. In addition, copanlisib impaired the activation of CD4+ CD25+ T cells (anti‐CD3: 42.15 ± 21.46; anti‐CD3 + copanlisib: 26.06 ± 21.82 p = .013) and the secretion of cytokines (IFNγ: anti‐CD3: 6332.0 ± 5707.61 pmol/ml; anti‐CD3 + copanlisib: 6332.0 ± 5707.61, p = .018). In vivo, copanlisib significantly improved the histological scores (ethanol: 8.5 ± 3.81; copanlisib: 4.57 ± 2.82, p = .006) in the NSG‐UC mouse model. Orthogonal partial least square analysis confirmed the efficacy of copanlisib. These data suggest that the PI3K pathway provides an attractive therapeutic intervention point in IBD for patients in relapse. Targeting metabolic pathways have the potential to develop phase dependent therapies.
CCL17‐expressing dendritic cells in the intestine are preferentially infected by Salmonella but CCL17 plays a redundant role in systemic dissemination
Authors: Erazo Anna B. , Wang Nancy , Standke Lena , Semeniuk Adrian D. , Fülle Lorenz , Cengiz Sevgi C. , Thiem Manja , Weighardt Heike , Strugnell Richard A. , Förster Irmgard
Published: May 2021

Introduction

Salmonella spp. are a recognized and global cause of serious health issues from gastroenteritis to invasive disease. The mouse model of human typhoid fever, which uses Salmonella enterica serovar Typhimurium (STM) in susceptible mouse strains, has revealed that the bacteria gain access to extraintestinal tissues from the gastrointestinal tract to cause severe systemic disease. Previous analysis of the immune responses against Salmonella spp. revealed the crucial role played by dendritic cells (DCs) in carrying STM from the intestinal mucosa to the mesenteric lymph nodes (mLNs), a key site for antigen presentation and T cell activation. In this study, we investigated the influence of chemokine CCL17 on the dissemination of STM.

Methods

WT, CCL17/EGFP reporter, or CCL17‐deficient mice were infected orally with STM (SL1344) or mCherry‐expressing STM for 1–3 days. Colocalization of STM with CCL17‐expressing DCs in Peyer's patches (PP) and mLN was analyzed by fluorescence microscopy. In addition, DCs and myeloid cell populations from naïve and Salmonella‐infected mice were analyzed by flow cytometry. Bacterial load was determined in PP, mLN, spleen, and liver 1 and 3 days after infection.

Results

Histological analysis revealed that CCL17‐expressing cells are located in close proximity to STM in the dome area of PP. We show that, in mLN, STM were preferentially located within CCL17+ rather than CCL17− DCs, besides other mononuclear phagocytes, and identified the CD103+ CD11b− DC subset as the main STM‐carrying DC population in the intestine. STM infection triggered upregulation of CCL17 expression in specific intestinal DC subsets in a tissue‐specific manner. The dissemination of STM from the gut to the mLN, however, was only moderately influenced by the presence of CCL17.

Conclusion

CCL17‐expressing DCs were preferentially infected by Salmonella in the intestine in comparison to other DC. Nevertheless, the production of CCL17 was not essential for the early dissemination of Salmonella from the gut to systemic organs.
A Distinct Variant of Pseudohypoparathyroidism (PHP) First Characterized Some 41 Years Ago Is Caused by the 3‐kbSTX16 Deletion
Authors: Kiuchi Zentaro , Reyes Monica , Brickman Arnold S , Jüppner Harald
Published: May 2021

In 1980, Farfel and colleagues (NEJM, 1980;303:237–42) provided first evidence for two distinct variants of pseudohypoparathyroidism (PHP) that present with hypocalcemia and impaired parathyroid hormone (PTH)‐stimulated urinary cAMP and phosphate excretion, either in the presence or absence of Albright's hereditary osteodystrophy (AHO). An “abnormal allele” and an “unexpressed allele” were considered as underlying defects, predictions that turned out to be correct for both forms of PHP. Patients affected by the first variant (now referred to as PHP1A) were later shown to be carriers of inactivating mutations involving the maternal GNAS exons encoding Gsα. Patients affected by the second variant (now referred to as PHP1B) were shown in the current study to carry a maternal 3‐kb STX16 deletion, the most frequent cause of autosomal dominant PHP1B, which is associated with loss of methylation at GNAS exon A/B that reduces or abolishes maternal Gsα expression. However, the distinct maternal mutations leading to either PHP1A or PHP1B are disease‐causing only because paternal Gsα expression in the proximal renal tubules is silenced, ie, “unexpressed.” Our findings resolve at the molecular level carefully conducted investigations reported some 41 years ago that had provided first clues for the existence of two distinct PHP variants. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Impact of Tenofovir Disoproxil‐Induced Fanconi Syndrome on Bone Material Quality: A Case Report
Authors: Hadzimuratovic Benjamin , Haschka Judith , Hartmann Markus A , Blouin Stéphane , Fratzl‐Zelman Nadja , Zwerina Jochen , Kocijan Roland
Published: May 2021

Tenofovir is a nucleotide analog reverse‐transcriptase inhibitor (NtARTI) used for treatment of chronic hepatitis B and human immunodeficiency virus (HIV). Fanconi syndrome (FS) is a condition affecting the proximal tubules of the kidney, leading to increased passage and impaired reabsorption of various small molecules such as glucose, phosphate, bicarbonate, and amino acids. Tenofovir disoproxil fumarate (TDF) is one of two pro‐drugs of tenofovir associated with a greater nephrotoxicity and renal complications such as FS with subsequent osteomalacia, acute kidney injury, and reduction of glomerular filtration rate (GFR) compared with tenofovir alafenamide (TAF). We present the case of a 33‐year‐old white woman treated with TDF because of chronic hepatitis B infection suffering four atraumatic fractures over the period of 2 years. The patient was taken off the TDF regimen 3 months before presentation. Initial blood and urine samples suggested the presence of TDF‐induced osteomalacia, which was confirmed by transiliac bone biopsy and histomorphometry. Moreover, bone mineral density distribution (BMDD) by quantitative backscattered electron imaging (qBEI) analysis showed that approximately 56% of the bone surface was normally mineralized and 44% showed a reduced mineralization consistent with the presence of osteomalacia. The patient made a significant recovery upon cessation of the causative agent. This case report emphasizes the use of bone biopsy, histomorphometry and qBEI in confirming the diagnosis of drug‐induced Fanconi syndrome and associated osteomalacia. © 2021 The Authors.JBMR Pluspublished by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Design, synthesis, and in vitro/vivo anticancer activity of 4‐substituted 7‐(3‐fluoro‐4‐methoxybenzyl)‐7H‐pyrrolo[2,3‐d]pyrimidines
Authors: Tsai Pei‐Yi , Hu Gong‐Siang , Huang Po‐Hsun , Jheng Huei‐Lin , Lan Chi‐Hsuan , Chen You‐Sin , Chang Jia‐Ming , Chuang Shih‐Hsien , Huang Jiann‐Jyh
Published: May 2021

In this paper, we report the design and synthesis of 4‐substituted 7‐(3‐fluoro‐4‐methoxybenzyl)‐7H‐pyrrolo[2,3‐d]pyrimidines of scaffold 6 as anticancer agents. A total of 19 derivatives of scaffold 6 bearing a C‐4 alkoxy, dialkylamino, alkyl, vinyl, or phenyl substituent were synthesized and evaluated. Among them, compound 6q having a C‐4 ethyl group and a benzylic methyl group showed the most potent in vitro anticancer activity, inhibiting the proliferation of Hela, MDA‐MB‐231, and MDA‐MB‐426 cancer cells at submicromolar concentrations (GI50: 0.11–0.58 μM). Compound 6q arrested the cell cycle of MDA‐MB‐231 at G2/M phase, and showed in vivo activity on nude mice bearing MDA‐MB‐231 xenografts. Compound 6q has served as an anticancer lead for further optimization.
The extended binary quadratic residue code of length 42 holds a 3‐design
Authors: Bonnecaze A. , Solé P.
Published: May 2021

The codewords of weight 10 of the [42, 21, 10] extended binary quadratic residue code are shown to hold a design of parameters . Its automorphism group is isomorphic to . Its existence can be explained neither by a transitivity argument, nor by the Assmus–Mattson theorem.
Elevated levels of interleukin‐35 and interleukin‐37 in adult patients with obstructive sleep apnea
Authors: Chen Bi , Liu Ya‐nan , Ji Lei , Liu Ping‐li , He Jun , Gan Yu‐ying , Ji Gui‐juan , Zhu Shu‐yang , Zhang Wen‐hui
Published: May 2021

Background

Systemic inflammation has a critical role in the pathogenesis of obstructive sleep apnea (OSA). Interleukin (IL)‐35 and IL‐37 have been identified as novel immune‐modulating cytokines with anti‐inflammatory activities in numerous types of inflammatory disease. The present study aimed to examine the serum levels of IL‐35 and IL‐37 in patients with OSA, and to investigate their associations with the severity of OSA.

Methods

A total of 97 patients, including 67 cases of OSA and 30 age‐ and gender‐matched healthy control subjects, were enrolled in the present study. All subjects were evaluated by overnight polysomnography. Serum IL‐35, IL‐37, and pro‐inflammatory cytokine IL‐1β levels were examined by ELISA.

Results

Compared with those in the control subjects, serum IL‐35, IL‐37, and IL‐1β levels were significantly elevated in patients with mild, moderate, or severe OSA. Furthermore, a severity‐dependent increase in serum IL‐35 and IL‐37 levels was observed in patients with OSA. IL‐35 and IL‐37 levels were positively correlated with the apnea‐hypopnea index (r = 0.742 and 0.578, respectively; both p < 0.001), while they were negatively correlated with the mean oxygen saturation (r = −0.461 and −0.339, respectively; both p < 0.001) and lowest oxyhaemoglobin saturation (r = −0.616 and −0.463, respectively; both p < 0.001) in patients with OSA. In addition, a positive correlation was observed between IL‐35 or IL‐37 and IL‐1β levels (all p < 0.001).

Conclusion

The serum levels of IL‐35 and IL‐37 were significantly increased in patients with OSA and associated with the severity of OSA, implying that IL‐35 and IL‐37 may have a protective role in OSA by counteracting inflammatory responses.