bluuebunny/crossref_metadata_2025 huggingface dataset:
Ketamine activates adult-born immature granule neurons to rapidly alleviate depression-like behaviors in mice
Authors: Rawat Radhika , Tunc-Ozcan Elif , McGuire Tammy L. , Peng Chian-Yu , Kessler John A.
Published: May 2022

Ketamine treatment decreases depressive symptoms within hours, but the mechanisms mediating these rapid antidepressant effects are unclear. Here, we demonstrate that activity of adult-born immature granule neurons (ABINs) in the mouse hippocampal dentate gyrus is both necessary and sufficient for the rapid antidepressant effects of ketamine. Ketamine treatment activates ABINs in parallel with its behavioral effects in both stressed and unstressed mice. Chemogenetic inhibition of ABIN activity blocks the antidepressant effects of ketamine, indicating that this activity is necessary for the behavioral effects. Conversely, chemogenetic activation of ABINs without any change in neuron numbers mimics both the cellular and the behavioral effects of ketamine, indicating that increased activity of ABINs is sufficient for rapid antidepressant effects. These findings thus identify a specific cell population that mediates the antidepressant actions of ketamine, indicating that ABINs can potentially be targeted to limit ketamine’s side effects while preserving its therapeutic efficacy.
Structure and mechanism of NALCN-FAM155A-UNC79-UNC80 channel complex
Authors: Kang Yunlu , Chen Lei
Published: May 2022

NALCN channel mediates sodium leak currents and is important for maintaining proper resting membrane potential. NALCN and FAM155A form the core complex of the channel, the activity of which essentially depends on the presence of both UNC79 and UNC80, two auxiliary proteins. NALCN, FAM155A, UNC79, and UNC80 co-assemble into a large hetero-tetrameric channel complex. Genetic mutations of NALCN channel components lead to neurodevelopmental diseases. However, the structure and mechanism of the intact channel complex remain elusive. Here, we present the cryo-EM structure of the mammalian NALCN-FAM155A-UNC79-UNC80 quaternary complex. The structure shows that UNC79-UNC80 form a large piler-shaped heterodimer which was tethered to the intracellular side of the NALCN channel through tripartite interactions with the cytoplasmic loops of NALCN. Two interactions are essential for proper cell surface localization of NALCN. The other interaction relieves the self-inhibition of NALCN by pulling the auto-inhibitory CTD Interacting Helix (CIH) out of its binding site. Our work defines the structural mechanism of NALCN modulation by UNC79 and UNC80.
Structural basis of ion – substrate coupling in the Na+-dependent dicarboxylate transporter VcINDY
Authors: Sauer David B. , Marden Jennifer J. , Sudar Joseph C. , Song Jinmei , Mulligan Christopher , Wang Da-Neng
Published: May 2022

The Na+-dependent dicarboxylate transporter from Vibrio cholerae (VcINDY) is a prototype for the divalent anion sodium symporter (DASS) family. While the utilization of an electrochemical Na+ gradient to power substrate transport is well established for VcINDY, the structural basis of this coupling between sodium and substrate binding is not currently understood. Here, using a combination of cryo-EM structure determination, succinate binding and site-directed cysteine alkylation assays, we demonstrate that the VcINDY protein couples sodium- and substrate-binding via a previously unseen cooperative mechanism by conformational selection. In the absence of sodium, substrate binding is abolished, with the succinate binding regions exhibiting increased flexibility, including HPinb, TM10b and the substrate clamshell motifs. Upon sodium binding, these regions become structurally ordered and create a proper binding site for the substrate. Taken together, these results provide strong evidence that VcINDY’s conformational selection mechanism is a result of the sodium-dependent formation of the substrate binding site.
Rapid meniscus-guided printing of stable semi-solid-state liquid metal microgranular-particle for soft electronics
Authors: Lee Gun-Hee , Lee Ye Rim , Kim Hanul , Kwon Do A , Kim Hyeonji , Yang Congqi , Choi Siyoung Q. , Park Seongjun , Jeong Jae-Woong , Park Steve
Published: May 2022

Liquid metal is being regarded as a promising material for soft electronics owing to its distinct combination of high electrical conductivity comparable to that of metals and exceptional deformability derived from its liquid state. However, the applicability of liquid metal is still limited due to the difficulty in simultaneously achieving its mechanical stability and initial conductivity. Furthermore, reliable and rapid patterning of stable liquid metal directly on various soft substrates at high-resolution remains a formidable challenge. In this work, meniscus-guided printing of ink containing polyelectrolyte-attached liquid metal microgranular-particle in an aqueous solvent to generate semi-solid-state liquid metal is presented. Liquid metal microgranular-particle printed in the evaporative regime is mechanically stable, initially conductive, and patternable down to 50 μm on various substrates. Demonstrations of the ultrastretchable (~500% strain) electrical circuit, customized e-skin, and zero-waste ECG sensor validate the simplicity, versatility, and reliability of this manufacturing strategy, enabling broad utility in the development of advanced soft electronics.
Sox2 levels regulate the chromatin occupancy of WNT mediators in epiblast progenitors responsible for vertebrate body formation
Authors: Blassberg Robert , Patel Harshil , Watson Thomas , Gouti Mina , Metzis Vicki , Delás M. Joaquina , Briscoe James
Published: May 2022

WNT signalling has multiple roles. It maintains pluripotency of embryonic stem cells, assigns posterior identity in the epiblast and induces mesodermal tissue. Here we provide evidence that these distinct functions are conducted by the transcription factor SOX2, which adopts different modes of chromatin interaction and regulatory element selection depending on its level of expression. At high levels, SOX2 displaces nucleosomes from regulatory elements with high-affinity SOX2 binding sites, recruiting the WNT effector TCF/β-catenin and maintaining pluripotent gene expression. Reducing SOX2 levels destabilizes pluripotency and reconfigures SOX2/TCF/β-catenin occupancy to caudal epiblast expressed genes. These contain low-affinity SOX2 sites and are co-occupied by T/Bra and CDX. The loss of SOX2 allows WNT-induced mesodermal differentiation. These findings define a role for Sox2 levels in dictating the chromatin occupancy of TCF/β-catenin and reveal how context-specific responses to a signal are configured by the level of a transcription factor.
Depression symptoms 6 years after stroke are associated with higher perceived impact of stroke, limitations in ADL and restricted participation
Authors: Ytterberg Charlotte , Cegrell Linda , von Koch Lena , Wiklander Maria
Published: May 2022

Late post-stroke depression symptoms are understudied. This study aimed to investigate depression symptoms 6 years after stroke, and associations with perceived impact of stroke, activities of daily living (ADL), and participation in social and everyday activities. Data was collected in a 6-year follow-up in a longitudinal study of stroke. Assessments included Hospital Anxiety and Depression Scale (HADS) for depression symptoms, Stroke Impact Scale 3.0. for perceived impact of stroke,
Barthel Index for ADL, Frenchay Activities Index for participation in social and everyday activities. The research questions were addressed by bivariate analyses (with HADS-D ≥ 4 as cut-off), and hierarchical multiple regression
analyses using continuous HADS-D scores. Forty percent of the 105 participants (57% men, age 30–91) showed depression symptoms (HADS-D ≥ 4). Depression symptoms were associated with higher perceived impact of
stroke, more dependence in ADL, and more restrictions in participation in social and everyday activities. Most of those with depression symptoms had low scores on HADS, indicating that even mild depression symptoms might
be relevant to identify and target in treatment and rehabilitation of long-term consequences of stroke.
First biphotochromic fluorescent protein moxSAASoti stabilized for oxidizing environment
Authors: Marynich N. K. , Khrenova M. G. , Gavshina A. V. , Solovyev I. D. , Savitsky A. P.
Published: May 2022

Biphotochromic proteins simultaneously possess reversible photoswitching (on-to-off) and irreversible photoconversion (green-to-red). High photochemical reactivity of cysteine residues is one of the reasons for the development of “mox”-monomeric and oxidation resistant proteins. Based on site-saturated simultaneous two-point C105 and C117 mutagenesis, we chose C21N/C71G/C105G/C117T/C175A as the moxSAASoti variant. Since its on-to-off photoswitching rate is higher, off-to-on recovery is more complete and photoconversion rates are higher than those of mSAASoti. We analyzed the conformational behavior of the F177 side chain by classical MD simulations. The conformational flexibility of the F177 side chain is mainly responsible for the off-to-on conversion rate changes and can be further utilized as a measure of the conversion rate. Point mutations in mSAASoti mainly affect the pKavalues of the red form and off-to-on switching. We demonstrate that the microscopic measure of the observed pKavalue is the C–O bond length in the phenyl fragment of the neutral chromophore. According to molecular dynamics simulations with QM/MM potentials, larger C–O bond lengths are found for proteins with larger pKa. This feature can be utilized for prediction of the pKavalues of red fluorescent proteins.
High-speed X-ray ptychographic tomography
Authors: Batey Darren , Rau Christoph , Cipiccia Silvia
Published: May 2022

X-ray ptychography is a coherent scanning imaging technique widely used at synchrotron facilities for producing quantitative phase images beyond the resolution limit of conventional x-ray optics. The scanning nature of the technique introduces an inherent overhead to the collection at every scan position and limits the acquisition time of each 2D projection. The overhead associated with motion can be minimised with a continuous-scanning approach. Here we present an acquisition architecture based on continuous-scanning and up-triggering which allows to record ptychographic datasets at up to 9 kHz. We demonstrate the method by applying it to record 2D scans at up to 273 µm2/s and 3D scans of a (20 µm)3 volume in less than three hours. We discuss the current limitations and the outlook toward the development of sub-second 2D acquisition and minutes-long 3D ptychographic tomograms.
Preyssler-type phosphotungstate is a new family of negative-staining reagents for the TEM observation of viruses
Authors: Sahiro Koichi , Kawato Yasuhiko , Koike Kanae , Sano Tsuneji , Nakai Toshihiro , Sadakane Masahiro
Published: May 2022

Transmission electron microscopy (TEM) is an essential method in virology because it allows for direct visualization of virus morphology at a nanometer scale. Negative staining to coat virions with heavy metal ions must be performed before TEM observations to achieve sufficient contrast. Herein, we report that potassium salts of Preyssler-type phosphotungstates (K(15-n)[P5W30O110Mn+], M = Na+, Ca2+, Ce3+, Eu3+, Bi3+, or Y3+) are high-performance negative staining reagents. Additionally, we compare the staining abilities of these salts to those of uranyl acetate and Keggin-type phosphotungstate. The potassium salt of Preyssler-type phosphotungstates has the advantage of not requiring prior neutralization because it is a neutral compound. Moreover, the potassium counter-cation can be protonated by a reaction with H+-resin, allowing easy exchange of protons with other cations by acid–base reaction. Therefore, the counter-cations can be changed. Encapsulated cations can also be exchanged, and clear TEM images were obtained using Preyssler-type compounds with different encapsulated cations. Preyssler-type phosphotungstates may be superior negative staining reagents for observing virus. Polyoxotungstates (tungsten-oxide molecules with diverse molecular structures and properties) are thus promising tools to develop negative staining reagents for TEM observations.
Sotatercept analog suppresses inflammation to reverse experimental pulmonary arterial hypertension
Authors: Joshi Sachindra R. , Liu Jun , Bloom Troy , Karaca Atabay Elif , Kuo Tzu-Hsing , Lee Michael , Belcheva Elitza , Spaits Matthew , Grenha Rosa , Maguire Michelle C. , Frost Jeffrey L. , Wang Kathryn , Briscoe Steven D. , Alexander Mark J. , Herrin Brantley R. , Castonguay Roselyne , Pearsall R. Scott , Andre Patrick , Yu Paul B. , Kumar Ravindra , Li Gang
Published: May 2022

Sotatercept is an activin receptor type IIA-Fc (ActRIIA-Fc) fusion protein that improves cardiopulmonary function in patients with pulmonary arterial hypertension (PAH) by selectively trapping activins and growth differentiation factors. However, the cellular and molecular mechanisms of ActRIIA-Fc action are incompletely understood. Here, we determined through genome-wide expression profiling that inflammatory and immune responses are prominently upregulated in the lungs of a Sugen-hypoxia rat model of severe angio-obliterative PAH, concordant with profiles observed in PAH patients. Therapeutic treatment with ActRIIA-Fc—but not with a vasodilator—strikingly reversed proinflammatory and proliferative gene expression profiles and normalized macrophage infiltration in diseased rodent lungs. Furthermore, ActRIIA-Fc normalized pulmonary macrophage infiltration and corrected cardiopulmonary structure and function in Bmpr2 haploinsufficient mice subjected to hypoxia, a model of heritable PAH. Three high-affinity ligands of ActRIIA-Fc each induced macrophage activation in vitro, and their combined immunoneutralization in PAH rats produced cardiopulmonary benefits comparable to those elicited by ActRIIA-Fc. Our results in complementary experimental and genetic models of PAH reveal therapeutic anti-inflammatory activities of ActRIIA-Fc that, together with its known anti-proliferative effects on vascular cell types, could underlie clinical activity of sotatercept as either monotherapy or add-on to current PAH therapies.
Hydrochemical characteristics of surface waters and their relationships to the Kashin–Beck Disease in Longzi County, Tibet
Authors: Zha Xinjie , Tian Yuan , Xiao Jianyu , Yu Chengqun
Published: May 2022

Although previous studies have been reported between the Kashin–Beck Disease (KBD) epidemic and the hydrochemical characteristics of surface waters, the etiology of the disease remains unclear. In the present study, we comprehensively investigated the relationship between the KBD and the hydrochemical characteristics of surface waters in Longzi County. Results show that, the pH (mean = 7.27 ± 0.30), total hardness (TH, mean = 57.08 ± 45.74 mg L−1), total dissolved solids (TDS, mean = 67.56 ± 44.00 mg L−1) and oxidation–reduction potential (ORP, mean = 84.11 ± 23.55 mV) of surface waters in KBD endemic areas are lower than those in the non-KBD endemic areas (means of pH = 7.49 ± 0.30; TH = 262.06 ± 123.29 mg L−1; TDS = 253.25 ± 100.39 mg L−1; ORP = 215.90 ± 55.99 mV). These results suggest that long-term consumption of low TDS, essential trace elements (e.g., nickel, cobalt, iron, selenium, zinc, molybdenum, and iodine) deficient, and potential toxic elements (e.g., arsenic) enriched waters by humans likely causes the KBD. Environmental factors such as the geology and geomorphology may produce biogeochemical imbalance, geomorphic, vegetation types and local climatic conditions may have significant impact on food fungi toxin poisoning and water organic compound poisoning, and these also impact the KBD occurrence.
Early prediction of acute necrotizing pancreatitis by artificial intelligence: a prospective cohort-analysis of 2387 cases
Authors: Kiss Szabolcs , Pintér József , Molontay Roland , Nagy Marcell , Farkas Nelli , Sipos Zoltán , Fehérvári Péter , Pecze László , Földi Mária , Vincze Áron , Takács Tamás , Czakó László , Izbéki Ferenc , Halász Adrienn , Boros Eszter , Hamvas József , Varga Márta , Mickevicius Artautas , Faluhelyi Nándor , Farkas Orsolya , Váncsa Szilárd , Nagy Rita , Bunduc Stefania , Hegyi Péter Jenő , Márta Katalin , Borka Katalin , Doros Attila , Hosszúfalusi Nóra , Zubek László , Erőss Bálint , Molnár Zsolt , Párniczky Andrea , Hegyi Péter , Szentesi Andrea ,   Hungarian Pancreatic Study Group, Kiss Szabolcs , Farkas Nelli , Sipos Zoltán , Fehérvári Péter , Pecze László , Földi Mária , Vincze Áron , Takács Tamás , Czakó László , Izbéki Ferenc , Halász Adrienn , Boros Eszter , Hamvas József , Varga Márta , Mickevicius Artautas , Faluhelyi Nándor , Farkas Orsolya , Váncsa Szilárd , Nagy Rita , Bunduc Stefania , Hegyi Péter Jenő , Márta Katalin , Borka Katalin , Doros Attila , Hosszúfalusi Nóra , Zubek László , Erőss Bálint , Molnár Zsolt , Párniczky Andrea , Hegyi Péter , Szentesi Andrea , Bajor Judit , Gódi Szilárd , Sarlós Patrícia , Czimmer József , Szabó Imre , Pár Gabriella , Illés Anita , Hágendorn Roland , Németh Balázs Csaba , Kui Balázs , Illés Dóra , Gajdán László , Dunás-Varga Veronika , Fejes Roland , Papp Mária , Vitális Zsuzsanna , Novák János , Török Imola , Macarie Melania , Ramírez-Maldonado Elena , Sallinen Ville , Galeev Shamil , Bod Barnabás , Ince Ali Tüzün , Pécsi Dániel , Varjú Péter , Juhász Márk Félix , Ocskay Klementina , Mikó Alexandra , Szakács Zsolt
Published: May 2022

Pancreatic necrosis is a consistent prognostic factor in acute pancreatitis (AP). However, the clinical scores currently in use are either too complicated or require data that are unavailable on admission or lack sufficient predictive value. We therefore aimed to develop a tool to aid in necrosis prediction. The XGBoost machine learning algorithm processed data from 2387 patients with AP. The confidence of the model was estimated by a bootstrapping method and interpreted via the 10th and the 90th percentiles of the prediction scores. Shapley Additive exPlanations (SHAP) values were calculated to quantify the contribution of each variable provided. Finally, the model was implemented as an online application using the Streamlit Python-based framework. The XGBoost classifier provided an AUC value of 0.757. Glucose, C-reactive protein, alkaline phosphatase, gender and total white blood cell count have the most impact on prediction based on the SHAP values. The relationship between the size of the training dataset and model performance shows that prediction performance can be improved. This study combines necrosis prediction and artificial intelligence. The predictive potential of this model is comparable to the current clinical scoring systems and has several advantages over them.
Psychometric properties of the oral feeding assessment in premature infants scale
Authors: Alonso-Fernández Sergio , de Liria Carlos Rodrigo Gonzalo , Lluch-Canut Teresa , Poch-Pla Laura , Perapoch-López Josep , Juvé-Udina Maria-Eulàlia , Martínez-Momblan Maria-Antonia , Hurtado-Pardos Bárbara , Roldán-Merino Juan-Francisco
Published: May 2022

Professionals that work in neonatal units need to identify the strengths and weaknesses of the premature infant who is in the transition process from feeding through a gastric tube to oral feeding. The main aim of this study was to validate the Oral FEeding Assessment in premaTure INfants (OFEATINg) instrument. A psychometric validity and reliability study was conducted in Neonatal Intensive Care Units of two public, metropolitan, university hospitals. The study population were premature infants at a postconceptional age of 31–35 weeks. The study included evaluation of the reliability, convergent, discriminant and construct validity, sensitivity and specificity of the OFEATINg instrument. A total of 621 feedings of 56 preterm infants were evaluated. Confirmatory factor analysis identified 3 factors and 13 indicators with a good fit to the model. Cronbach's alpha coefficient was 0.78. The instrument showed high indices of inter-rater reliability (Pearson 0.9 and intraclass correlation coefficient 0.95). The OFEATINg scale is a valid and reliable instrument for evaluating the readiness for oral feeding of preterm infants. It may enable clinicians to evaluate the physiological and behavioral abilities involved in the oral feeding process and help them make decisions related to the transition to full oral feeding.

Clinical trial registration: This study was prospectively registered at the two Institutional review boards.
Nanoengineering of conductively coupled metallic nanoparticles towards selective resonance modes within the near-infrared regime
Authors: Hadilou Naby , Souri Somayeh , Navid H. A. , Sadighi Bonabi Rasoul , Anvari Abbas
Published: May 2022

In this work, the mode transition effect of different plasmonic resonances in linked dimers by a conductive junction is numerically investigated.Without the junction, the dimer supports a single dipolar bonding plasmon mode, while two new resonance modes, a screened bonding dipolar mode and a low energy charge transfer plasmon mode, emerge when two nanoparticles are linked via a bridge. Such effect is proved to be unrelated to the shape of the nanoparticles, whether sphere, core-shell or nanoegg. However, it was found that the status of each specific resonance mode is profoundly influenced by the shape of nanoparticles. Furthermore, a detailed discussion of mechanisms of controlling plasmon modes, specially charge transfer mode, and tuning their corresponding spectra in bridged nanoparticles as functions of nanoparticle parameters and junction conductance is presented. These results show that the optical response of the dimer is highly sensitive to changes in the inter-particle gap. While the capacitive dimer provides a strong hotstop, the conductive dimer leads to highly controllable low energy plasmon mode at the mid-infrared region appropriate for novel applications. These findings may serve as an important guide for optical properties of linked nanoparticles as well as understanding the transition between the capacitive and conductive coupling.
Different time patterns of the presence of red-eared slider influence the ontogeny dynamics of common frog tadpoles
Authors: Vodrážková M. , Šetlíková I. , Navrátil J. , Berec M.
Published: May 2022

The coexistence of species in a given community depends on the set of species involved and the timing of their interactions. Many native communities are increasingly forced to face both direct and indirect pressures from new alien predators, which, in extreme cases, can lead to the extinction of prey populations. In this study, we examine the dynamics of the ontogeny of common frog (Rana temporaria) tadpoles under different time patterns of an alien predator—the red-eared slider (Trachemys scripta elegans) presence. We found that the tadpoles had a longer larval period and were smaller in size at metamorphosis and lower in body mass when the predator was present in early development than when the tadpoles developed without a predator. The early presence of a predator conspicuously reduced the growth increments of the tadpoles at early development. After the removal of the predator, growth accelerated above the level measured under the conditions of both the late predator and no predator. However, these growth rates did not exceed the growth rates of equally sized tadpoles in the other treatments and therefore were not sufficient to compensate for the growth slowdown in the first part of development. The presence of a predator in late tadpole development influenced neither the time to metamorphosis nor size/body mass at metamorphosis. In conclusion, the predator had the effect on metamorphosis traits only if it was present in the early development of tadpoles.
Association of antibiotic-consumption patterns with the prevalence of hematological malignancies in European countries
Authors: Ternák Gábor , Berényi Károly , Németh Balázs , Szenczi Ágnes , Márovics Gergely , Kiss István
Published: May 2022

Hematological malignancies are considered the fifth most common cancer in the world. Several risk factors and probable etiological agents have been suspected in the pathomechanism of those malignancies as infections, chemicals, irradiation, etc., and recently, the contribution of the altered gut flora, dysbiosis, was identified also as a possible additional factor to the existing ones. Host, and external factors, like antibiotics, which were identified as a major disruptor of the "normal" gut flora, influence the composition of the microbiome. Considering the several-fold differences in antibiotic consumption patterns and the incidence of hematological malignancies in European countries, the hypothesis was raised that the dominant consumption of certain antibiotic classes might influence the incidence of different hematological malignancies through the modification of gut flora. Comparisons were performed between the average antibiotic consumption databases reported yearly by ECDC (2009–2019) and the incidence rate of Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), multiple myeloma (MM), and leukemia (LEU) estimated for 2020 in 30 European countries. Applying Spearman calculations, significant positive correlation has been found between the incidence of HL and tetracycline (J01A) consumption (r = 0.399, p = 0.029), NHL and narrow spectrum, beta-lactamase resistant penicillin (J01CF) (r = 0.580, p = 0.001), MM and tetracycline (r = 0.492, p = 0.006), penicillin (J01C) (r = 0.366, p = 0.047), narrow spectrum, beta-lactamase resistant penicillin (J01CF) (r = 0.574, p = 0.001), while strong, significant negative correlation has been recorded between NHL and cephalosporin (r = − 0.460, p = 0.011), and quinolone (r = − 0.380, p = 0.038). The incidence of LEU did not show any positive or negative association with any antibiotic classes using Spearman calculation. Multivariate ordinal logistic regression (OR) indicated increased risk between HL and the total consumption of systemic antibiotics (J01 p: 0.038), and tetracyclin (J01A p: 0.002). Similarly, increased risk has been detected between the MM and tetracyclin (J01A p: 0.02), and narrow spectrum, beta-lactamase resistant penicillin (J01CF p: 0.042) and decreased risk between cephalosporin and MM (J01D p:0.022). LEU showed increased risk with the consumption of macrolides (p: 0.047).
A mechanical and simplified model for RC elements subjected to combined shear and axial tension
Authors: Deifalla A. , Mukhtar F. M.
Published: May 2022

Very little is known about the shear behavior of elements, in particular those subjected to axial tension. The shear accompanied by tensile forces could cause premature failure of reinforced concrete, which is sudden with minimal warning. Therefore, understanding the shear behavior of reinforced concrete (RC) elements, including those subjected to axial tension, is an ultimate goal of the worldwide research community. In the current study, a new shear mechanical model for RC elements subjected to axial tension is developed, which makes physical sense and explains the behavior. The model is strain-based, inspired by the critical crack theory model (CSCT). In addition, the proposed model extended CSCT (ECSCT) quantifies the effect of axial tension forces on the shear strength in terms of reduction in the compression zone depth and increase in the longitudinal strain. Moreover, the nonlinear trend observed in the literature was implemented using nonlinear multi-variable regression. The ECSCT is validated and compared with available design methods with respect to an extensive database, including 180 elements tested under shear and tension from 18 different research investigations. The ECSCT provided an accurate and physically sound model yet safe to an acceptable extent. Last but not least, a simplified model for the purpose of design is proposed. The simplified model was chosen based on the mechanical model and calibrated using the extensive experimental database. The simplified model provided an accurate and simple model, yet safe to an acceptable extent.
Incidence of fracture of ProDesign Logic system instruments: A cross-sectional retrospective study
Authors: Machado Ricardo , de Souza Júnior Claudemir , Mendes Bruna Larissa , Vieira Viviane , Glaci Reinke Stella Maria , Gonçalves Kovalik Ana Cristina , Donato Eing Elgelke Back Eduardo , Comparin Daniel
Published: May 2022

The aim of the present study was to analyze the incidence of fracture of ProDesign Logic system instruments in endodontic treatments performed by a specialist, in addition to identifying the dental group, arch, and the root canal thirds in which the fractures occurred more frequently. Digital radiographs and medical records were initially analyzed and resulted in the selection of 561 teeth (1302 canals) treated between 2018 and 2020, using the ProDesign Logic system instruments. These data were reassessed to determine the occurrence of fractures and identify the dental group and root canal thirds in which they occurred. Then, the data were statistically analyzed using the Fisher’s Exact Test (p < 0.05). The general fracture rates were 8.5 and 3.69%, considering the number of teeth and canals treated, respectively. Mandibular first molars were the teeth most associated with the occurrence of fractures (19.1%). When the arches were compared, there was no statistical difference regarding the number of fractures in the different root canal thirds (p = 0.307). However, they were more frequent in the apical third in both arches (p = 0.000). The incidence of fracture of ProDesign Logic system instruments was relatively high and occurred more frequently in the apical third of molars.
Composite 3D printing of biomimetic human teeth
Authors: Cresswell-Boyes A. J. , Davis G. R. , Krishnamoorthy M. , Mills D. , Barber A. H.
Published: May 2022

Human teeth are mechanically robust through a complex structural composite organisation of materials and morphology. Efforts to replicate mechanical function in artificial teeth (typodont teeth), such as in dental training applications, attempt to replicate the structure and morphology of real teeth but lack tactile similarities during mechanical cutting of the teeth. In this study, biomimetic typodont teeth, with morphology derived from X-ray microtomography scans of extracted teeth, were 3D printed using an approach to develop novel composites. These composites with a range of glass, hydroxyapatite and porcelain reinforcements within a methacrylate-based photopolymer resin were compared to six commercial artificial typodont teeth. Mechanical performance of the extracted human teeth and 3D printed typodont teeth were evaluated using a haptic approach of measuring applied cutting forces. Results indicate 3D printed typodont teeth replicating enamel and dentine can be mechanically comparable to extracted human teeth despite the material compositions differing from the materials found in human teeth. A multiple parameter variable of material elastic modulus and hardness is shown to describe the haptic response when cutting through both human and biomimetic, highlighting a critical dependence between the ratio of material mechanical properties and not absolute material properties in determining tooth mechanical performance under the action of cutting forces.
Impact of host phonons on interstitial diffusion
Authors: Tang Chunguang , Sun Gang , Liu Yun
Published: May 2022

The net effect of host phonons on interstitial diffusion has remained as a fundamental knowledge gap in our current theories since the motions of the host atoms and interstitials were coupled in these theories. Here we study this effect through molecular dynamics simulations of hydrogen diffusion in palladium, in which the motions can be decoupled through pinning the host atoms. Mathematically this decoupling corresponds to expanding the total diffusion coefficient into a Taylor series, which separates the phonon contribution from the intrinsic interstitial jumping. Our results clearly show that palladium phonons significantly promote hydrogen diffusion. The phonon contribution, being linear with temperature at high temperatures and exponential at low temperatures, is fitted with Brownian motion model. The total diffusion of interstitials can be understood as the intrinsic interstitial jumping in a pinned host plus phonon-induced Brownian diffusion. The generality of our findings is validated by examining the motion of lithium in manganese oxide and carbon in iron.
Gadoxetic acid-enhanced magnetic resonance imaging predicts hyperbilirubinemia induced by glecaprevir during hepatitis C virus treatment
Authors: Okubo Hironao , Atsukawa Masanori , Okubo Tomomi , Ando Hitoshi , Nakadera Eisuke , Ikejima Kenichi , Nagahara Akihito
Published: May 2022

Glecaprevir is a substrate for organic anion-transporting polypeptide (OATP) 1B1/1B3, which transports bilirubin. Hyperbilirubinemia is an adverse event during anti-hepatitis C virus treatment with glecaprevir and pibrentasvir. Gadoxetic acid is also transported by OATP1B1/1B3, and we aimed to evaluate whether gadoxetic acid-enhanced magnetic resonance (MR) imaging was associated with glecaprevir trough concentrations (Ctrough). We further determined whether this was predictive of hyperbilirubinemia development in a cohort of 33 patients. The contrast enhancement index (CEI), a measure of hepatic enhancement effect on the hepatobiliary image, was assessed. Glecaprevir Ctrough was determined 7 days after administration. Five of the 33 patients (15%) developed Common Terminology Criteria for Adverse Events grade ≥ 2 hyperbilirubinemia. We found a negative relationship between CEI and Ctrough (r = − 0.726, p < 0.001). The partial correlation coefficient between CEI and Ctrough was − 0.654 (p < 0.001), while excluding the effects of albumin, FIB-4 index, and indirect bilirubin at baseline. The Ctrough was significantly higher in patients with hyperbilirubinemia than in those without (p = 0.008). In multivariate analysis, CEI ≤ 1.71 was an independent factor influencing the development of hyperbilirubinemia (p = 0.046). Our findings indicate that gadoxetic acid MR imaging can help predict glecaprevir concentration and development of hyperbilirubinemia.
Decision tree based ensemble machine learning model for the prediction of Zika virus T-cell epitopes as potential vaccine candidates
Authors: Bukhari Syed Nisar Hussain , Webber Julian , Mehbodniya Abolfazl
Published: May 2022

Zika fever is an infectious disease caused by the Zika virus (ZIKV). The disease is claiming millions of lives worldwide, primarily in developing countries. In addition to vector control strategies, the most effective way to prevent the spread of ZIKV infection is vaccination. There is no clinically approved vaccine to combat ZIKV infection and curb its pandemic. An epitope-based peptide vaccine (EBPV) is seen as a powerful alternative to conventional vaccinations because of its low production cost and short production time. Nonetheless, EBPVs have gotten less attention, despite the fact that they have a significant untapped potential for enhancing vaccine safety, immunogenicity, and cross-reactivity. Such a vaccine technology is based on target pathogen’s selected antigenic peptides called T-cell epitopes (TCE), which are synthesized chemically based on their amino acid sequences. The identification of TCEs using wet-lab experimental approach is challenging, expensive, and time-consuming. Therefore in this study, we present computational model for the prediction of ZIKV TCEs. The model proposed is an ensemble of decision trees that utilizes the physicochemical properties of amino acids. In this way a large amount of time and efforts would be saved for quick vaccine development. The peptide sequences dataset for model training was retrieved from Virus Pathogen Database and Analysis Resource (ViPR) database. The sequences dataset consist of experimentally verified T-cell epitopes (TCEs) and non-TCEs. The model demonstrated promising results when evaluated on test dataset. The evaluation metrics namely, accuracy, AUC, sensitivity, specificity, Gini and Mathew’s correlation coefficient (MCC) recorded values of 0.9789, 0.984, 0.981, 0.987, 0.974 and 0.948 respectively. The consistency and reliability of the model was assessed by carrying out the five (05)-fold cross-validation technique, and the mean accuracy of 0.97864 was reported. Finally, model was compared with standard machine learning (ML) algorithms and the proposed model outperformed all of them. The proposed model will aid in predicting novel and immunodominant TCEs of ZIKV. The predicted TCEs may have a high possibility of acting as prospective vaccine targets subjected to in-vivo and in-vitro scientific assessments, thereby saving lives worldwide, preventing future epidemic-scale outbreaks, and lowering the possibility of mutation escape.
Improvement in sensitivity for lateral flow immunoassay of ferritin using novel device design based on gold-enhanced gold nanoparticles
Authors: Preechakasedkit Pattarachaya , Teekayupak Kanyapat , Citterio Daniel , Ruecha Nipapan
Published: May 2022

This work introduces a low-cost adhesive tape combined with a hydroxylamine/polyvinyl alcohol/polyethylene oxide (HA/PVA/PEO) blend film to fabricate novel devices for improving sensitivity of gold nanoparticle (AuNP)-based lateral flow immunoassays (LFIAs) via two platforms: (1) LFIA device with integrated gold enhancement and (2) LFIA device with two independent sample inlets. The detection of ferritin has been used for proof-of-concept. The adhesive tape inserted in the devices assists to separate two solutions independently flowing from two different inlets toward a nitrocellulose membrane. On-device gold enhancement was achieved by the enlargement of AuNPs via the catalytic reaction of KAuCl4 and HA using the HA/PVA/PEO blend film easily prepared via a solution-casting technique, which could delay the flow of HA released from the film for 180s and improve storage stability of the device. Under optimal conditions evaluated by naked eyes, the gold enhancement (LOD = 0.5 ng/mL) and double-sample inlet (LOD = 2 ng/mL) devices exhibited 20-fold and fivefold higher sensitivity respectively than a conventional device, verifying the sensitivity improvement. Furthermore, the proposed device was successfully detected ferritin in human serum samples within 10 min via naked-eye observation, exhibiting rapidity and simplicity of use, and the capability to perform on-site assays.
Analysis of voltage rise phenomena in electrical power network with high concentration of renewable distributed generations
Authors: Akinyemi Ayodeji Stephen , Musasa Kabeya , Davidson Innocent E.
Published: May 2022

The increasing penetration levels of renewable distributed generation (RDG) into a power system have proven to bring both positive and negative impacts. The occurrence of under voltage at the far end of a conventional electrical distribution network (DN) may not raise concern anymore with RDGs integration into a power system. However, a penetration of RDGs into power system may cause problems such as voltage rise or over-voltage and reverse power flows at the Point of Common Coupling (PCC) between RDG and DN. This research paper presents the impact of voltage rise effect and reverse power flow constraint in power system with high concentration of RDG. The analysis is conducted on a sample DN, i.e., IEEE 13-bus test system, with RDG penetration by considering the most critical scenario such as low power demand in DN and a peak power injection by RDG. For studying the impact of voltage rise and reverse power flow, a mathematical model of a DN integrating RDG is developed. Furthermore, a controller incorporating an advance control-algorithm is proposed to be installed at PCC between DN and RDG to regulate the voltage rise effects and to mitigate the reverse power flow when operating at a worst critical scenario of minimum load and maximum generation from RDG. The proposed control strategy also mitigates the voltage–current harmonic distortions, improves the power factor, and maintain the voltage stability at PCC. The simulations are carried out using MATLAB/Simulink software. Finally, recommendations are provided for the power producers to counteract the effects of voltage rise at PCC. The study has demonstrated that, voltage at PCC can be sustained with a high concentration of RDG during a worst-case scenario without a reverse power flow and voltage rise beyond grid code limits.
In silico mutational analysis of ACE2 to check the susceptibility of lung cancer patients towards COVID-19
Authors: Khalid Zumama , Khan Abeedha Tu-Allah , Alnajjar Radwan , Santali Eman , Shakoori Abdul Rauf
Published: May 2022

Being the second major cause of death worldwide, lung cancer poses a significant threat to the health of patients. This worsened during the era of pandemic since lung cancer is found to be more prone to SARS-CoV-2 infection. Many recent studies imply a high frequency of COVID-19 infection associated severe outcome. However, molecular studies are still lacking in this respect. Hence the current study is designed to investigate the binding affinities of ACE2 lung cancer mutants with the viral spike protein to find the susceptibility of respective mutants carrying patients in catching the virus. Quite interestingly, our study found lesser binding affinities of all the selected mutants thus implying that these cancer patients might be less affected by the virus than others. These results are opposed to the recent studies’ propositions and open new avenues for more in-depth studies.
Preparation, mechanics and self-sensing performance of sprayed reactive powder concrete
Authors: Zhang Yunlong , Wang Jianxin , Wang Jing , Qian Xuesong
Published: May 2022

The emergence of shotcrete provides a new idea for construction methods, but with the development of society, the traditional shotcrete has been unable to meet the needs of structure. Therefore, concrete with better material properties is needed to replace traditional shotcrete. Reactive powder concrete (RPC) is a well-known ultrahigh strength concrete and widely used. Its material properties are better than shotcrete. However, the sprayable performance of RPC and the properties of this sprayed materials have not been reported. Therefore, to make up for the deficiency of ordinary shotcrete, the material properties of sprayed RPC were studied in depth. Response surface method was used to study the effects of different silica fume content, fly ash content and steel fiber volume content on workability, mechanical properties and crack sensitivity. The sprayed reactive powder concrete (sprayed RPC) was proposed for the first time. All models were reliable through variance analysis. The performance of sprayed RPC was better when the workability was between 140 and 160 mm. When the silica fume/binder ratio was 15%, the fly ash/binder ratio was 13.203%, and the volume content of steel fibers was 2%, the mechanical properties and crack sensitivity of sprayed RPC can reach a satisfactory degree. By studying the workability, mechanical properties and crack sensitivity of sprayed RPC, the optimum mix ratio of sprayed RPC was obtained. Steel fiber sprayed RPC can detect structural damage. Results lay the foundation for popularization and application to practical engineering.
Human-to-dog transmission of SARS-CoV-2, Colombia
Authors: Rivero Ricardo , Garay Evelin , Botero Yesica , Serrano-Coll Héctor , Gastelbondo Bertha , Muñoz Marina , Ballesteros Nathalia , Castañeda Sergio , Patiño Luz Helena , Ramirez Juan David , Calderon Alfonso , Guzmán Camilo , Martinez-Bravo Caty , Aleman Ader , Arrieta Germán , Mattar Salim
Published: May 2022

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of the current COVID-19 pandemic, has evolved to have a wide range of hosts, including non-human primates, wild and domestic animals. The ACE2 protein has a high level of conservation and is the common receptor invertebrate species for a viral infection to occur; this receptor could give rise to anthroponotic events. This article describes the first event of symptomatic transmission in Latin America from a human to a dog by the B.1.625 lineage of SARS-CoV-2. We found 21 shared mutations in the complete genomes of viral sequences from owners and dogs. Further phylogenetic and molecular analysis showed that 100% co-localization of the clade helps to understand human-animal transmission. Prediction of the Spike protein structure of the sequenced virus and docking analyzes showed that the E484K mutation in the receptor-binding domain (RBD) could contribute to the viral affinity of dACE2. Therefore, close contact between SARS-CoV-2-infected humans and pets should be avoided to prevent the emergence of novel mutations of public health importance from anthroponotic events.
MEA-Net: multilayer edge attention network for medical image segmentation
Authors: Liu Huilin , Feng Yue , Xu Hong , Liang Shufen , Liang Huizhu , Li Shengke , Zhu Jiajian , Yang Shuai , Li Fufeng
Published: May 2022

Medical image segmentation is a fundamental step in medical analysis and diagnosis. In recent years, deep learning networks have been used for precise segmentation. Numerous improved encoder–decoder structures have been proposed for various segmentation tasks. However, high-level features have gained more research attention than the abundant low-level features in the early stages of segmentation. Consequently, the learning of edge feature maps has been limited, which can lead to ambiguous boundaries of the predicted results. Inspired by the encoder–decoder network and attention mechanism, this study investigates a novel multilayer edge attention network (MEA-Net) to fully utilize the edge information in the encoding stages. MEA-Net comprises three major components: a feature encoder module, a feature decoder module, and an edge module. An edge feature extraction module in the edge module is designed to produce edge feature maps by a sequence of convolution operations so as to integrate the inconsistent edge information from different encoding stages. A multilayer attention guidance module is designed to use each attention feature map to filter edge information and select important and useful features. Through experiments, MEA-Net is evaluated on four medical image datasets, including tongue images, retinal vessel images, lung images, and clinical images. The evaluation values of the Accuracy of four medical image datasets are 0.9957, 0.9736, 0.9942, and 0.9993, respectively. The values of the Dice coefficient are 0.9902, 0.8377, 0.9885, and 0.9704, respectively. Experimental results demonstrate that the network being studied outperforms current state-of-the-art methods in terms of the five commonly used evaluation metrics. The proposed MEA-Net can be used for the early diagnosis of relevant diseases. In addition, clinicians can obtain more accurate clinical information from segmented medical images.