bluuebunny/crossref_metadata_2025_split huggingface dataset:
Muscle weakness assessment tool for automated therapy selection in elbow rehabilitation
Authors: Gupta Sakshi , Agrawal Anupam , Singla Ekta 
Published: June 2022

AbstractClinical observations and subjective judgements have traditionally been used to evaluate patients with muscular and neurological disorders. As a result, identifying and analyzing functional improvements are difficult, especially in the absence of expertise. Quantitative assessment, which serves as the motivation for this study, is an essential prerequisite to forecast the task of the rehabilitation device in order to develop rehabilitation training. This work provides a quantitative assessment tool for muscle weakness in the human upper limbs for robotic-assisted rehabilitation. The goal is to map the assessment metrics to the recommended rehabilitation exercises. Measurable interaction forces and muscle correlation factors are the selected parameters to design a framework for muscular nerve cell condition detection and appropriate limb trajectory selection. In this work, a data collection setup is intended for extracting muscle intervention and assessment using MyoMeter, Goniometer and surface electromyography data for upper limbs. Force signals and human physiological response data are evaluated and categorized to infer the relevant progress. Based upon the most influencing muscles, curve fitting is performed. Trajectory-based data points are collected through a scaled geometric Open-Sim musculoskeletal model that fits the subject’s anthropometric data. These data are found to be most suitable to prescribe relevant exercise and to design customized robotic assistance. Case studies demonstrate the approach’s efficacy, including optimally synthesized automated configuration for the desired trajectory.
Statistical Analysis of Wave Propagation Properties of Equatorial Noise Observed at Low Altitudes
Authors: Hanzelka Miroslav , Němec František , Santolík Ondřej , Parrot Michel 
Published: June 2022

AbstractEquatorial noise is an electromagnetic emission with line spectral structure, predominantly located in the vicinity of the geomagnetic equatorial plane at radial distances ranging from 2 to 8 Earth's radii. Here we focus on the rare events of equatorial noise occurring at ionospheric altitudes during periods of strongly increased geomagnetic activity. We use multicomponent electromagnetic measurements from the entire 2004–2010 DEMETER spacecraft mission and present a statistical analysis of wave propagation properties. We show that, close to the Earth, these emissions experience a larger spread in latitudes than they would at large radial distances and that their wave normals can significantly deviate from the direction perpendicular to local magnetic field lines. These results are compared to ray tracing simulations, in which whistler mode rays with initially nearly perpendicular wave vectors propagate down to the low altitudes with wave properties corresponding to the observations. We perform nonlinear fitting of the simulated latitudinal distribution of incident rays to the observed occurrence and estimate the distribution of wave normal angles in the source. The assumed Gaussian distribution provides the best fit with a standard deviation of 2° from the perpendicular direction. Ray tracing analysis further shows that small initial deviations from the meridional plane can rapidly increase during the propagation and result in deflection of the emissions before they can reach the altitudes of DEMETER.
SARS-CoV-2 virus NSP14 Impairs NRF2/HMOX1 activation by targeting Sirtuin 1
Authors: Zhang Shilei , Wang Jingfeng , Wang Lulan , Aliyari Saba , Cheng Genhong 
Published: June 2022

AbstractMost deaths from the COVID-19 pandemic are due to acute respiratory distress syndrome (ARDS)-related respiratory failure. Cytokine storms and oxidative stress are the major players in ARDS development during respiratory virus infections. However, it is still unknown how oxidative stress is regulated by viral and host factors in response to SARS-CoV-2 infection. Here, we found that activation of NRF2/HMOX1 significantly suppressed SARS-CoV-2 replication in multiple cell types by producing the metabolite biliverdin, whereas SARS-CoV-2 impaired the NRF2/HMOX1 axis through the action of the nonstructural viral protein NSP14. Mechanistically, NSP14 interacts with the catalytic domain of the NAD-dependent deacetylase Sirtuin 1 (SIRT1) and inhibits its ability to activate the NRF2/HMOX1 pathway. Furthermore, both genetic and pharmaceutical evidence corroborated the novel antiviral activity of SIRT1 against SARS-CoV-2. Therefore, our findings reveal a novel mechanism by which SARS-CoV-2 dysregulates the host antioxidant defense system and emphasize the vital role played by the SIRT1/NRF2 axis in host defense against SARS-CoV-2.
Probing TDP-43 condensation using an in silico designed aptamer
Authors: Zacco Elsa , Kantelberg Owen , Milanetti Edoardo , Armaos Alexandros , Panei Francesco Paolo , Gregory Jenna , Jeacock Kiani , Clarke David J. , Chandran Siddharthan , Ruocco Giancarlo , Gustincich Stefano , Horrocks Mathew H. , Pastore Annalisa , Tartaglia Gian Gaetano 
Published: June 2022

AbstractAptamers are artificial oligonucleotides binding to specific molecular targets. They have a promising role in therapeutics and diagnostics but are often difficult to design. Here, we exploited thecatRAPID algorithm to generate aptamers targeting TAR DNA-binding protein 43 (TDP-43), whose aggregation is associated with Amyotrophic Lateral Sclerosis. On the pathway to forming insoluble inclusions, TDP-43 adopts a heterogeneous population of assemblies, many smaller than the diffraction-limit of light. We demonstrated that our aptamers bind TDP-43 and used the tightest interactor, Apt-1, as a probe to visualize TDP-43 condensates with super-resolution microscopy. At a resolution of 10 nanometers, we tracked TDP-43 oligomers undetectable by standard approaches. In cells, Apt-1 interacts with both diffuse and condensed forms of TDP-43, indicating that Apt-1 can be exploited to follow TDP-43 phase transition. The de novo generation of aptamers and their use for microscopy opens a new page to study protein condensation.
Identification of a quasi-liquid phase at solid–liquid interface
Authors: Peng Xinxing , Zhu Fu-Chun , Jiang You-Hong , Sun Juan-Juan , Xiao Liang-Ping , Zhou Shiyuan , Bustillo Karen C. , Lin Long-Hui , Cheng Jun , Li Jian-Feng , Liao Hong-Gang , Sun Shi-Gang , Zheng Haimei 
Published: June 2022

AbstractAn understanding of solid–liquid interfaces is of great importance for fundamental research as well as industrial applications. However, it has been very challenging to directly image solid–liquid interfaces with high resolution, thus their structure and properties are often unknown. Here, we report a quasi-liquid phase between metal (In, Sn) nanoparticle surfaces and an aqueous solution observed using liquid cell transmission electron microscopy. Our real-time high-resolution imaging reveals a thin layer of liquid-like materials at the interfaces with the frequent appearance of small In nanoclusters. Such a quasi-liquid phase serves as an intermediate for the mass transport from the metal nanoparticle to the liquid. Density functional theory-molecular dynamics simulations demonstrate that the positive charges of In ions greatly contribute to the stabilization of the quasi-liquid phase on the metal surface.
The obligate intracellular bacterium Orientia tsutsugamushi differentiates into a developmentally distinct extracellular state
Authors: Atwal Sharanjeet , Wongsantichon Jantana , Giengkam Suparat , Saharat Kittirat , Pittayasathornthun Yanin Jaiyen , Chuenklin Suthida , Wang Loo Chien , Chung Taerin , Huh Hyun , Lee Sang-Hyuk , Sobota Radoslaw M. , Salje Jeanne 
Published: June 2022

AbstractOrientia tsutsugamushi (Ot) is an obligate intracellular bacterium in the family Rickettsiaceae that causes scrub typhus, a severe mite-borne human disease. Its mechanism of cell exit is unusual amongst Rickettsiaceae, as Ot buds off the surface of infected cells enveloped in plasma membrane. Here, we show that Ot bacteria that have budded out of host cells are in a distinct developmental stage compared with intracellular bacteria. We refer to these two stages as intracellular and extracellular bacteria (IB and EB, respectively). These two forms differ in physical properties: IB is both round and elongated, and EB is round. Additionally, IB has higher levels of peptidoglycan and is physically robust compared with EB. The two bacterial forms differentially express proteins involved in bacterial physiology and host-pathogen interactions, specifically those involved in bacterial dormancy and stress response, and outer membrane autotransporter proteins ScaA and ScaC. Whilst both populations are infectious, entry of IB Ot is sensitive to inhibitors of both clathrin-mediated endocytosis and macropinocytosis, whereas entry of EB Ot is only sensitive to a macropinocytosis inhibitor. Our identification and detailed characterization of two developmental forms of Ot significantly advances our understanding of the intracellular lifecycle of an important human pathogen.
Macrocycle-stabilization of its interaction with 14-3-3 increases plasma membrane localization and activity of CFTR
Authors: Stevers Loes M. , Wolter Madita , Carlile Graeme W. , Macdonald Dwight , Richard Luc , Gielkens Frank , Hanrahan John W. , Thomas David Y. , Chakka Sai Kumar , Peterson Mark L. , Thomas Helmut , Brunsveld Luc , Ottmann Christian 
Published: June 2022

AbstractImpaired activity of the chloride channel CFTR is the cause of cystic fibrosis. 14-3-3 proteins have been shown to stabilize CFTR and increase its biogenesis and activity. Here, we report the identification and mechanism of action of a macrocycle stabilizing the 14-3-3/CFTR complex. This molecule rescues plasma membrane localization and chloride transport of F508del-CFTR and works additively with the CFTR pharmacological chaperone corrector lumacaftor (VX-809) and the triple combination Trikafta®. This macrocycle is a useful tool to study the CFTR/14-3-3 interaction and the potential of molecular glues in cystic fibrosis therapeutics.
High stress twinning in a compositionally complex steel of very high stacking fault energy
Authors: Wang Zhangwei , Lu Wenjun , An Fengchao , Song Min , Ponge Dirk , Raabe Dierk , Li Zhiming 
Published: June 2022

AbstractDeformation twinning is rarely found in bulk face-centered cubic (FCC) alloys with very high stacking fault energy (SFE) under standard loading conditions. Here, based on results from bulk quasi-static tensile experiments, we report deformation twinning in a micrometer grain-sized compositionally complex steel (CCS) with a very high SFE of ~79 mJ/m2, far above the SFE regime for twinning (<~50 mJ/m2) reported for FCC steels. The dual-nanoprecipitation, enabled by the compositional degrees of freedom, contributes to an ultrahigh true tensile stress up to 1.9 GPa in our CCS. The strengthening effect enhances the flow stress to reach the high critical value for the onset of mechanical twinning. The formation of nanotwins in turn enables further strain hardening and toughening mechanisms that enhance the mechanical performance. The high stress twinning effect introduces a so far untapped strengthening and toughening mechanism, for enabling the design of high SFEs alloys with improved mechanical properties.
Topological electronic structure of YbMg2Bi2 and CaMg2Bi2
Authors: Kundu Asish K. , Roy Tufan , Pakhira Santanu , Wu Ze-Bin , Tsujikawa Masahito , Shirai Masafumi , Johnston D. C. , Pasupathy Abhay N. , Valla Tonica 
Published: June 2022

AbstractZintl compounds have been extensively studied for their outstanding thermoelectric properties, but their electronic structure remains largely unexplored. Here, we present a detailed investigation of the electronic structure of the isostructural thermopower materials YbMg2Bi2 and CaMg2Bi2 using angle-resolved photoemission spectroscopy (ARPES) and density functional theory (DFT). The ARPES results show a significantly smaller Fermi surface and Fermi velocity in CaMg2Bi2 than in YbMg2Bi2. Our ARPES results also reveal that in the case of YbMg2Bi2, Yb-4f states reside well below the Fermi level and likely have a negligible impact on transport properties. To properly model the position of 4f-states, as well as the overall electronic structure, a Hubbard U at the Yb sites and spin-orbit coupling (SOC) have to be included in the DFT calculations. The theoretical results reveal that both materials belong to a Z2 topological class and host topological surface states around EF. Due to the intrinsic hole doping, the topological states reside above the Fermi level, inaccessible by ARPES. Our results also suggest that in addition to SOC, vacancies and the resulting hole doping play an important role in the transport properties of these materials.
Lipid A analog CRX-527 conjugated to synthetic peptides enhances vaccination efficacy and tumor control
Authors: Tondini Elena , Reintjens Niels R. M. , Castello Giulia , Arakelian Tsolere , Isendoorn Marjolein , Camps Marcel , Vree Jana , van der Marel Gijs A. , Filippov Dmitri V. , Codee Jeroen D. C. , Ossendorp Ferry 
Published: June 2022

AbstractAdjuvants play a determinant role in cancer vaccination by optimally activating APCs and shaping the T cell response. Bacterial-derived lipid A is one of the most potent immune-stimulators known, and is recognized via Toll-like receptor 4 (TLR4). In this study, we explore the use of the synthetic, non-toxic, lipid A analog CRX-527 as an adjuvant for peptide cancer vaccines. This well-defined adjuvant was covalently conjugated to antigenic peptides as a strategy to improve vaccine efficacy. We show that coupling of this TLR4 agonist to peptide antigens improves vaccine uptake by dendritic cells (DCs), maturation of DCs and T cell activation in vitro, and stimulates DC migration and functional T cell priming in vivo. This translates into enhanced tumor protection upon prophylactic and therapeutic vaccination via intradermal injection against B16-OVA melanoma and HPV-related TC1 tumors. These results highlight the potential of CRX-527 as an adjuvant for molecularly defined cancer vaccines, and support the design of adjuvant-peptide conjugates as a strategy to optimize vaccine formulation.
Skyrmion–antiskyrmion pair creation and annihilation in a cubic chiral magnet
Authors: Zheng Fengshan , Kiselev Nikolai S. , Yang Luyan , Kuchkin Vladyslav M. , Rybakov Filipp N. , Blügel Stefan , Dunin-Borkowski Rafal E. 
Published: June 2022

AbstractA fundamental property of particles and antiparticles (such as electrons and positrons, respectively) is their ability to annihilate one another. A similar behaviour is predicted for magnetic solitons1—localized spin textures that can be distinguished by their topological index Q. Theoretically, magnetic topological solitons with opposite values of Q, such as skyrmions2 and their antiparticles (namely, antiskyrmions), are expected to be able to continuously merge and annihilate3. However, experimental verification of such particle–antiparticle pair production and annihilation processes has been lacking. Here we report the creation and annihilation of skyrmion–antiskyrmion pairs in an exceptionally thin film of the cubic chiral magnet of B20-type FeGe observed using transmission electron microscopy. Our observations are highly reproducible and are fully consistent with micromagnetic simulations. Our findings provide a new platform for the fundamental studies of particles and antiparticles based on magnetic solids and open new perspectives for practical applications of thin films of isotropic chiral magnets.
Clinical outcomes of patients with multiple courses of radiosurgery for brain metastases from non-small cell lung cancer
Authors: Lee Won-Jae , Choi Jung-Won , Kong Doo-Sik , Seol Ho Jun , Nam Do-Hyun , Lee Jung-Il 
Published: June 2022

AbstractWe investigated the long-term clinical outcomes of patients who underwent multiple courses (≥ 5) of gamma knife radiosurgery (GKRS) due to recurrent brain metastases (BM) from non-small cell lung cancer (NSCLC). Between December 2001 and July 2019, consecutive 2571 patients underwent GKRS for BM from NSCLC. Clinical and radiological outcomes were investigated in 76 patients who underwent GKRS ≥ 5 times. The median follow-up period after the diagnosis of NSCLC was 54.6 months (range 14.5–159.1 months). The median number of GKRS procedures per patient was six (range 5–15). Actuarial post-GKRS survival rates at 1, 2, 3, 4, and 5 years following initial GKRS were 88.1%, 79.5%, 65.3%, 51.4%, and 37.3%, respectively. No significant difference in overall survival was observed between patients (n = 22) with whole-brain radiotherapy (WBRT) and patients (n = 54) without WBRT (p = 0.076). The incidence of radiation-induced leukoencephalopathy was 64% and 18% in patients with and without WBRT, respectively (p < 0.0001). Multiple courses of SRS are a tolerable and effective treatment option for recurrent BM from NSCLC. Repeat SRS may be an alternative treatment option to avoid or delay WBRT.
A mathematical model of GLUT1 modulation in rods and RPE and its differential impact in cell metabolism
Authors: Aparicio Andrea , Camacho Erika T. , Philp Nancy J. , Wirkus Stephen A. 
Published: June 2022

AbstractWe present a mathematical model of key glucose metabolic pathways in two cells of the human retina: the rods and the retinal pigmented epithelium (RPE). Computational simulations of glucose transporter 1 (GLUT1) inhibition in the model accurately reproduce experimental data from conditional knockout mice and reveal that modification of GLUT1 expression levels of both cells differentially impacts their metabolism. We hypothesize that, under glucose scarcity, the RPE’s energy producing pathways are altered in order to preserve its functionality, impacting the photoreceptors’ outer segment renewal. On the other hand, when glucose is limited in the rods, aerobic glycolysis is preserved, which maintains the lactate contribution to the RPE.
Complex trans-ridge normal faults controlling large earthquakes
Authors: Bello Simone , Lavecchia Giusy , Andrenacci Carlo , Ercoli Maurizio , Cirillo Daniele , Carboni Filippo , Barchi Massimiliano R. , Brozzetti Francesco 
Published: June 2022

AbstractStudying faults capable of releasing moderate-to-strong earthquakes is fundamental for seismic hazard studies, especially in a territory that was subject to the strongest peninsular Italy earthquake (1857, Mw7.1) and hosting the largest European oil field on-land. Fieldwork-based observations in the Campania-Lucania area highlight a SSW-dipping ~ 65 km-long normal-oblique-segmented fault, showing evidence of recent activity and possibly responsible for the 1857 earthquake. It crosses the Maddalena ridge, linking separate Quaternary basins. Two seismic reflection profiles cross the fault trace where it is buried beneath the Val d’Agri Quaternary deposits. Similarities between fault-controlled small basins in the highest portion of the massifs in the study area and the neighboring 1980 Irpinia area (1980 earthquake, Mw6.9) are interpreted as evidence of trans-ridge fault activity. Kinematic analyses and the stress field inversion provide a N032-trending near-horizontal s3-axis, the same computed in literature for the Irpinia area, highlighting a deviation from the ~N045-axis which characterizes most of the Apennines. This study demonstrates how detailed fieldwork, supported by geophysics and innovative data analysis techniques, can unravel unknown faults while giving a novel interpretation of the trans-ridge faults' style in controlling strong earthquakes, moving away from classical interpretations, and providing a helpful approach in similar contexts worldwide.
Functionalization of magnetic nanoparticles by creatine as a novel and efficient catalyst for the green synthesis of 2-amino-4H-chromene derivatives
Authors: Eivazzadeh-Keihan Reza , Bahrami Shahrzad , Ghafori Gorab Mostafa , Sadat Zahra , Maleki Ali 
Published: June 2022

AbstractBy employing the naturally-originated molecule of creatine, Fe3O4@SiO2-creatine as an environmentally benign magnetic organometallic nanobiocatalyst was successfully prepared via a convenient and green route. Then to acquire an inclusive comprehension of different properties of the catalyst, it was studied by various characterization techniques such as FT‐IR, FE-SEM, TEM, EDX, XRD, and VSM analyses. It was found that the size distribution of nanoparticles was an average diameter size of 70 nm. To examine the catalytic activity, it was applied in sequential knoevenagel condensation-Michael addition room temperature reaction of dimedone, malononitrile, and different substituted aromatic aldehydes to produce a variety of 2-amino-tetrahydro-4H-chromene-3-carbonitrile derivatives in a single step. Among the multiple outstanding advantages that can be mentioned for this work, some of the most noticeable ones include: affording the products in short reaction times with high yields, operating the reaction at ambient conditions and ease of catalyst separation.
Type 2 deiodinase p.Thr92Ala polymorphism does not affect the severity of obesity and weight loss after bariatric surgery
Authors: Benenati Nicoletta , Bufano Annalisa , Cantara Silvia , Ricci Claudia , Marzocchi Carlotta , Ciuoli Cristina , Sannino Ida , Tirone Andrea , Voglino Costantino , Vuolo Giuseppe , Castagna Maria Grazia 
Published: June 2022

AbstractA single nucleotide polymorphism in the Type 2 deiodinase (DIO2) gene (p.Thr92Ala) was found to be associated with hypertension, type 2 diabetes mellitus (T2DM), insulin resistance, and body mass index (BMI). We retrospectively evaluated 182 patients to assess whether the DIO2 p.Thr92Ala was associated with severe obesity and response to bariatric surgery. Genomic DNA was extracted from peripheral blood leukocytes before surgery. Glycemic control parameters, cardiometabolic risk biomarkers (waist circumference, lipid assessment and blood pressure) and hormonal parameters were assessed at baseline and after surgery. Based on genotype evaluation, 78/182 (42.9%) patients were homozygous wild-type (Thr/Thr), 83/182 (45.6%) heterozygous (Thr/Ala), and 21/182 (11.5%) rare homozygous (Ala/Ala). Age at the time of the first evaluation in our Unit was significantly lower in patients with DIO2 p.Thr92Ala. No significant association was observed between DIO2 p.Thr92Ala and BMI, excess weight, waist circumference, Homa Index. The prevalence of comorbidities was not associated with allele distribution except for hypertension that was more frequent in wild-type patients (p = 0.03). After bariatric surgery, excess weight loss (EWL) % and remission from comorbidities occurred without differences according to genotypes. DIO2 p.Thr92Ala does not affect the severity of obesity and its complications, but it seems to determine an earlier onset of morbid obesity. The presence of polymorphism seems not to impact on the response to bariatric surgery, both in terms of weight loss and remission of comorbidities.