bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genotype–phenotype correlation in IARS2‐related diseases: A case report and review of literature
Authors: Upadia Jariya , Li Yuwen , Walano Nicolette , Deputy Stephen , Gajewski Kelly , Andersson Hans C. 
Published: February 2022

AbstractIsoleucyl‐tRNA synthetase 2 (IARS2) encodes mitochondrial isoleucine‐tRNA synthetase. Pathogenic variants in the IARS2 gene are associated with mitochondrial disease. We report a female with IARS2 compound heterozygous variants, p.Val499Glyfs*14 and p.Arg784Trp who presented with infantile spasms, Leigh disease and Wolff‐Parkinson White (WPW) pattern. This report expands the phenotypic spectrum of IARS2‐related disease.
Expanded Mercaptocalixarenes: A New Kind of Macrocyclic Ligands for Stabilization of Polynuclear Thiolate Clusters
Authors: Schleife Frederik , Bonnot Clément , Chambron Jean‐Claude , Börner Martin , Kersting Berthold 
Published: February 2022

AbstractThe syntheses and properties of expanded 4‐tert‐butyl‐mercaptocalix[4]arenes, in which the methylene linkers are replaced by −CH2NRCH2− or −CH2NRCH2− and −CH2NRCH2CH2CH2NRCH2− units, are described. The new macrocycles were obtained in a step‐wise manner, utilizing fully protected, i. e. S‐alkylated, derivatives of the oxidation‐sensitive thiophenols in the cyclisation steps. Reductive cleavage of the macrobicyclic or macrotricyclic intermediates (6, 7, 11) afforded the free thiophenols (H48, H49, and H412) in preparative yields as their hydrochloride salts. The protected proligands can exist in two conformations, resembling the “cone” and “1,3‐alternate” conformations found for the parent calix[4]arenes. The free macrocycles do not show conformational isomerism, but are readily oxidized forming intramolecular disulfide linkages. Preliminary complexation experiments show that these expanded mercaptocalixarenes can serve as supporting ligands for tetranuclear thiolato clusters.
Exploring the Effects of Ionic Defects on the Stability of CsPbI3 with a Deep Learning Potential
Authors: Yang Weijie , Li Jiajia , Chen Xuelu , Feng Yajun , Wu Chongchong , Gates Ian D. , Gao Zhengyang , Ding Xunlei , Yao Jianxi , Li Hao 
Published: February 2022

AbstractInorganic metal halide perovskites, such as CsPbI3, have recently drawn extensive attention due to their excellent optical properties and high photoelectric efficiencies. However, the structural instability originating from inherent ionic defects leads to a sharp drop in the photoelectric efficiency, which significantly limits their applications in solar cells. The instability induced by ionic defects remains unresolved due to its complicated reaction process. Herein, to explore the effects of ionic defects on stability, we develop a deep learning potential for a CsPbI3 ternary system based upon density functional theory (DFT) calculated data for large‐scale molecular dynamics (MD) simulations. By exploring 2.4 million configurations, of which 7,730 structures are used for the training set, the deep learning potential shows an accuracy approaching DFT‐level. Furthermore, MD simulations with a 5,000‐atom system and a one nanosecond timeframe are performed to explore the effects of bulk and surface defects on the stability of CsPbI3. This deep learning potential based MD simulation provides solid evidence together with the derived radial distribution functions, simulated diffraction of X‐rays, instability temperature, molecular trajectory, and coordination number for revealing the instability mechanism of CsPbI3. Among bulk defects, Cs defects have the most significant influence on the stability of CsPbI3 with a defect tolerance concentration of 0.32 %, followed by Pb and I defects. With regards to surface defects, Cs defects have the largest impact on the stability of CsPbI3 when the defect concentration is less than 15 %, whereas Pb defects act play a dominant role for defect concentrations exceeding 20 %. Most importantly, this machine‐learning‐based MD simulation strategy provides a new avenue to explore the ionic defect effects on the stability of perovskite‐like materials, laying a theoretical foundation for the design of stable perovskite materials.
Wiskott–Aldrichsyndrome: Oral findings and microbiota in children and review of the literature
Authors: Lucchese Alessandra , Cenciarelli Sabina , Manuelli Maurizio , Marcolina Marta , Barzaghi Federica , Calbi Valeria , Migliavacca Maddalena , Bernardo Maria Ester , Tucci Francesca , Gallo Vera , Fraschetta Federico , Darin Silvia , Casiraghi Miriam , Aiuti Alessandro , Ferrua Francesca , Cicalese Maria Pia 
Published: February 2022

AbstractObjectiveWiskott–Aldrich syndrome (WAS) is a rare X‐linked primary immunodeficiency, characterized by micro‐thrombocytopenia, recurrent infections, and eczema. This study aims to describe common oral manifestations and evaluate oral microbioma of WAS patients.Material and methodsIn this cohort study, 11 male WAS patients and 16 male healthy controls were evaluated in our Center between 2010 and 2018. Data about clinical history, oral examination, Gingival Index (GI) and Plaque Index (PI) were collected from both groups. Periodontal microbiological flora was evaluated on samples of the gingival sulcus.ResultsWAS subjects presented with premature loss of deciduous and permanent teeth, inclusions, eruption disturbance, and significantly worse GI and PI. They also showed a trend toward a higher total bacterial load.Fusobacterium nucleatum, reported to contribute to periodontitis onset, was the most prevalent bacteria, together withPorphyromonas gingivalisandTannerella forsythia.ConclusionsOur data suggest that WAS patients are at greater risk of alterations in the oral cavity. The statistically higher incidence of periodontitis and the trend to higher prevalence of potentially pathological bacterial species in our small cohort, that should be confirmed in future in a larger population, underline the importance of dentistry monitoring as part of the multidisciplinary management of WAS patients.
Optimising the IgG‐degrading enzyme treatment regimen for enhanced adeno‐associated virus transduction in the presence of neutralising antibodies
Authors: Ros‐Gañán Irene , Hommel Mirja , Trigueros‐Motos Laia , Tamarit Blanche , Rodríguez‐García Estefanía , Salas David , Pérez Guiomar , Douar Anne , Combal Jean Philippe , Benichou Bernard , Ferrer Veronica , González‐Aseguinolaza Gloria 
Published: February 2022

AbstractObjectivePre‐existing neutralising antibodies (NAbs) to adeno‐associated viruses (AAVs) remain an impediment for systemically administered AAV‐mediated gene therapy treatment in many patients, and various strategies are under investigation to overcome this limitation. Here, IgG‐degrading enzymes (Ides) derived from bacteria of the genus Streptococcus were tested for their ability to cleave human IgG and allow AAV‐mediated transduction in individuals with pre‐existing NAbs.MethodsCleavage activity of three different Ides was evaluated in vitro in serum from different species. Passively immunised mice or non‐human primates (NHP) with naturally occurring anti‐AAV NAbs were used to define the optimal IdeS dose and administration window for AAVAnc80 and AAV8 vectors in mice and AAV3B in NHPs.ResultsThe selected candidate, IdeS, was found to be highly efficient at cleaving human IgG, less efficient against NHP IgG and inefficient against mouse IgG. In vivo, we observed differences in how IdeS affected liver transduction in the presence of NAbs depending on the AAV serotype. For AAVAnc80 and AAV3B, the best transduction levels were achieved when the vector was administered after IgG digestion products were cleared from circulation. However, for AAV8 we only observed a modest and transient inhibition of transduction by IdeS cleavage products.ConclusionPreconditioning with IdeS represents a unique treatment opportunity for patients primarily excluded from participation in gene therapy clinical trials because of elevated circulating anti‐AAV NAb levels. However, careful determination of the optimal IdeS dose and timing for the administration of each AAV serotype is essential for optimal transduction.
Pancreatic acinar cell carcinoma with predominant extension into the main pancreatic duct: A case report
Authors: Ishikawa Takuya , Ohno Eizaburo , Mizutani Yasuyuki , Iida Tadashi , Kawashima Hiroki 
Published: February 2022

AbstractA 34‐year‐old male was referred to our hospital for a possible pancreatic mass detected by computed tomography (CT) that was performed to find the cause of acute pancreatitis. Multiple imaging tests, including contrast‐enhanced CT scan, magnetic resonance imaging, contrast‐enhanced endoscopic ultrasonography, and endoscopic retrograde pancreatography, revealed a solid mass occupying the head of the main pancreatic duct (MDP), and pancreaticoduodenectomy was performed. In the resected specimen, the tumor showed expansive growth from the pancreatic parenchyma to the MDP and formed a tumor plug. Histopathological findings together with immunostaining findings led to the diagnosis of pancreatic acinar cell carcinoma (PACC). The patient was alive and recurrence‐free for 11 years after surgery. Extension into the MDP is more common in PACC than in conventional pancreatic ductal adenocarcinoma. PACC patients with MDP extension may have less aggressive clinicopathologic characteristics, and a relatively good prognosis can be expected.
Blood pressure categorization and subclinical left ventricular dysfunction in antihypertensive medication‐naive subjects
Authors: Nakanishi Koki , Daimon Masao , Yoshida Yuriko , Ishiwata Jumpei , Sawada Naoko , Hirokawa Megumi , Kaneko Hidehiro , Nakao Tomoko , Mizuno Yoshiko , Morita Hiroyuki , Di Tullio Marco R. , Homma Shunichi , Komuro Issei 
Published: February 2022

AbstractAimsThe impact of blood pressure (BP) levels on subclinical left ventricular (LV) dysfunction and possible sex‐specific difference remains unclarified. This study investigated the relationship between BP categories given in the new 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline and subclinical LV dysfunction in subjects free of cardiac disease.Methods and resultsWe examined antihypertensive medication‐naive 858 individuals who underwent extensive cardiovascular health check‐up. LV global longitudinal (LVGLS) and circumferential strain (LVGCS) were assessed by two‐dimensional speckle‐tracking echocardiography. Participants were categorized into four groups: normal BP, elevated BP, isolated diastolic hypertension (IDH), and systolic hypertension (SH). Among the 858 participants, 422 individuals had normal BP, 113 had elevated BP, 160 had IDH, and 163 had SH. Prevalence of abnormal LVGLS (>−18.6%) was greatest in SH (19.0%), followed by IDH (17.5%), elevated BP (14.2%), and normal BP (7.1%, P < 0.001); no significant differences were observed for LVGCS (P = 0.671). In the multivariable analyses, IDH and SH were associated with impaired LVGLS [adjusted odds ratio (OR) 2.69 and 2.66, P < 0.001], and borderline significance was observed for elevated BP (adjusted OR 1.90, P = 0.060); there was no significant association between any of the BP groups and LVGCS. In sex‐stratified analysis, IDH and SH carried the significant risk of abnormal LVGLS in both sexes, while elevated BP was associated with LVGLS only in women.ConclusionsIsolated diastolic hypertension and SH redefined by ACC/AHA guideline carried significant risk for LVGLS, but not LVGCS. Elevated BP was associated with LVGLS only in women. Our findings provide information on cardiac correlates of the newly established BP categories.
Characterizing the theory of energy transition in Luxembourg—Part three—In the residential sector
Authors: Arababadi Ali , Leyer Stephan , Hansen Joachim , Arababadi Reza 
Published: February 2022

AbstractIncreasing consciousness to address future concerns is a challenging subject, noticed considerably by policymakers and investors. Investigation of energy use in residential buildings in terms of quantity and sources of energy was the main focus of this study. Indeed, the paper was aimed to study the role of contextual factors on two points: the energy demand and the spreading of renewable technologies in the residential sector. It was theory‐driven research to highlight some future concerns. The first theory was to reveal how the growth of single‐family houses versus multi‐family houses could affect the growth of energy consumption and the application of renewable technologies. The second theory was built to highlight that spreading energy measures to increase efficiency or introducing a new energy carrier should be embedded in the context of new construction activities or in a template of renovation projects. The third theory was to emphasize the priority of thinking about managing the changes in residential buildings because of the lasting impact of the decision about the type of building. Finally, the purpose of the ongoing transition was argued to highlight that the growth of renewable technologies has not been necessarily aligned with getting away from fossil fuels.
Predicting monthly to multi‐annual foredune growth at a narrow beach
Authors: Ruessink Gerben , Sterk Geert , Smit Yvonne , De Winter Winnie , Hage Pam , Donker Jasper J. A. , Arens Sebastiaan M. 
Published: February 2022

AbstractAn open‐source quantitative model for predicting coastal foredune growth at monthly to multi‐annual (meso)temporal scales is developed. The model builds on the established fetch framework as a surrogate for the complex micro‐scale aeolian processes on the beach, to which rain and groundwater‐induced spatiotemporal surface moisture dynamics are added as factors limiting aeolian sand supply to foredunes. The model shows great skill in an application at Egmond aan Zee, The Netherlands, with a predicted growth of 16.5 m3/m/yr comparing favourably to the observed growth of 17.3 m3/m/yr. Rain, surface moisture dynamics as well as beach width reduction by storm‐induced elevated sea levels are shown to be important factors that jointly reduce meso‐scale sand supply below the potential (i.e., unlimited) maximum, in our case study by almost 5 m3/m/yr. These factors are most relevant for strong (here, above 15.5 m/s) onshore winds. Consistent with expectations from the literature, meso‐scale foredune growth results primarily from moderately strong (9.5–12.5 m/s) shore‐oblique winds, which are frequent and do not result in supply‐limited conditions. At the study site these winds are most common in winter and hence foredune growth is predicted to vary seasonally, consistent with the observations. Because of the promising results we believe that our model has potential for quantifying how quickly a foredune can recover after an episodic erosion event because of storm waves.
Development of a Robotic Shear Wave Elastography System for Noninvasive Staging of Liver Disease in Murine Models
Authors: Czernuszewicz Tomasz J. , Aji Adam M. , Moore Christopher J. , Montgomery Stephanie A. , Velasco Brian , Torres Gabriela , Anand Keerthi S. , Johnson Kennita A. , Deal Allison M. , Zukić Dženan , McCormick Matthew , Schnabl Bernd , Gallippi Caterina M. , Dayton Paul A. , Gessner Ryan C. 
Published: February 2022

Shear wave elastography (SWE) is an ultrasound‐based stiffness quantification technology that is used for noninvasive liver fibrosis assessment. However, despite widescale clinical adoption, SWE is largely unused by preclinical researchers and drug developers for studies of liver disease progression in small animal models due to significant experimental, technical, and reproducibility challenges. Therefore, the aim of this work was to develop a tool designed specifically for assessing liver stiffness and echogenicity in small animals to better enable longitudinal preclinical studies. A high‐frequency linear array transducer (12‐24 MHz) was integrated into a robotic small animal ultrasound system (Vega; SonoVol, Inc., Durham, NC) to perform liver stiffness and echogenicity measurements in three dimensions. The instrument was validated with tissue‐mimicking phantoms and a mouse model of nonalcoholic steatohepatitis. Female C57BL/6J mice (n = 40) were placed on choline‐deficient, L‐amino acid‐defined, high‐fat diet and imaged longitudinally for 15 weeks. A subset was sacrificed after each imaging timepoint (n = 5) for histological validation, and analyses of receiver operating characteristic (ROC) curves were performed. Results demonstrated that robotic measurements of echogenicity and stiffness were most strongly correlated with macrovesicular steatosis (R2 = 0.891) and fibrosis (R2 = 0.839), respectively. For diagnostic classification of fibrosis (Ishak score), areas under ROC (AUROCs) curves were 0.969 for ≥Ishak1, 0.984 for ≥Ishak2, 0.980 for ≥Ishak3, and 0.969 for ≥Ishak4. For classification of macrovesicular steatosis (S‐score), AUROCs were 1.00 for ≥S2 and 0.997 for ≥S3. Average scanning and analysis time was <5 minutes/liver. Conclusion: Robotic SWE in small animals is feasible and sensitive to small changes in liver disease state, facilitating in vivo staging of rodent liver disease with minimal sonographic expertise.
Employer image within and across industries: Moving beyond assessing points‐of‐relevance to identifying points‐of‐difference
Authors: Van Hoye Greet , Lievens Filip , Weijters Bert , Cromheecke Saartje 
Published: February 2022

AbstractThis study draws from brand positioning research to introduce the notions of points‐of‐relevance and points‐of‐difference to employer image research. Similar to prior research, this means that we start by investigating the relevant image attributes (points‐of‐relevance) that potential applicants use for judging organizations' attractiveness as an employer. However, we go beyond past research by examining whether the same points‐of‐relevance are used within and across industries. Next, we further extend current research by identifying which of the relevant image attributes also serve as points‐of‐difference for distinguishing between organizations and industries. The sample consisted of 24 organizations from 6 industries (total N = 7171). As a first key result, across industries and organizations, individuals attached similar importance to the same instrumental (job content, working conditions, and compensation) and symbolic (innovativeness, gentleness, and competence) image attributes in judging organizational attractiveness. Second, organizations and industries varied significantly on both instrumental and symbolic image attributes, with job content and innovativeness emerging as the strongest points‐of‐difference. Third, most image attributes showed greater variation between industries than between organizations, pointing at the importance of studying employer image at the industry level. Implications for recruitment research, employer branding, and best employer competitions are discussed.
Hall current effects on MHD flow of chemically reacting fluid through a porous medium with heat source
Authors: Swarnalathamma B. V. , Babu D. M. Praveen , Krishna M. Veera 
Published: February 2022

AbstractWe considered the magnetohydrodynamic (MHD) free convective flow of an incompressible electrically conducting viscous fluid past an infinite vertical permeable porous plate with a uniform transverse magnetic field, heat source and chemical reaction in a rotating frame taking Hall current effects into account. The momentum equations for the fluid flow during absorbent medium are controlled by the Brinkman model. Through the undisturbed state, both the plate and fluid are in a rigid body rotation by the uniform angular velocity perpendicular to an infinite vertical plate. The perpendicular surface is subject to the homogeneous invariable suction at a right angle to it and the heat on the surface varies about a non‐zero unvarying average whereas the warmth of complimentary flow is invariable. The systematic solutions of the velocity, temperature, and concentration distributions are acquired systematically by utilizing the perturbation method. The velocity expressions consist of steady‐state and fluctuating situations. It is revealed that the steady part of the velocity field has a three‐layer characteristic while the oscillatory part of the fluid field exhibits a multi‐layer characteristic. The influence of various governing flow parameters on the velocity, temperature, and concentration are analyzed graphically. We also discuss computational results for the skin friction, Nusselt number, and Sherwood number in the tabular forms.
Current status of sevoflurane anesthesia in association with microglia inflammation and neurodegenerative diseases
Authors: Huang Yan‐Li , Zhu Zhao‐Qiong 
Published: February 2022

AbstractSevoflurane is one of the most commonly used volatile anesthetics in clinical practice and is often used in pediatric anesthesia and intraoperative maintenance. Microglia exist in the central nervous system and are innate immune cells in the central nervous system. Under external stimulation, microglia are divided into two phenotypes: proinflammatory (M1 type) and anti‐inflammatory (M2 type), maintaining the stability of the central nervous system through induction, housekeeping, and defense functions. Sevoflurane can activate microglia, increase the expression of inflammatory factors through various inflammatory signaling pathways, release inflammatory mediators to cause oxidative stress, damage nerve tissues, and eventually develop into neurodegenerative diseases. In this article, the relationship between sevoflurane anesthesia and microglia inflammation expression and the occurrence of neurodegenerative diseases is reviewed as follows.
Metformin disrupts insulin secretion, causes proapoptotic and oxidative effects in rat pancreatic beta‐cells in vitro
Authors: Valle Maíra M.R. , Vilas‐Boas Eloisa Aparecida , Lucena Camila F. , Teixeira Simone A. , Muscara Marcelo N. , Carpinelli Angelo R. 
Published: February 2022

AbstractMetformin is the first‐line drug to treat type 2 diabetes mellitus. Its mechanism of action is still debatable, and recent studies report that metformin attenuates oxidative stress. This study evaluated the in vitro antioxidant effects of a broad range of metformin concentrations on insulin‐producing cells. The cell cycle, metabolism, glucose‐stimulated insulin secretion, and cell death were evaluated to determine the biguanide effects on beta‐cell function and survival. Antioxidant potential was based on reactive oxygen species (ROS), reduced glutathione (GSH), oxidative stress biomarker levels, and antioxidant enzyme and transcriptional factor Nrf2 activities. The results demonstrate that metformin disrupted GSIS in a concentration‐dependent manner, lowered insulin content, and attenuated beta‐cell metabolism. At high concentrations, metformin induced cell death and cell cycle arrest as well as increased ROS generation, consequently reducing GSH content. Although carbonylated protein content was elevated, indicating oxidative stress, the antioxidant enzyme and Nrf2 activities were not altered. In conclusion, our results show that metformin disrupts pancreatic beta‐cell functionality but does not exert a putative antioxidant effect. It is important to note that the drug could potentially affect beta‐cells, especially at high circulating levels.