bluuebunny/crossref_metadata_2025 huggingface dataset:
Driver Behavior Profiling and Recognition Using Deep-Learning Methods: In Accordance with Traffic Regulations and Experts Guidelines
Authors: Al-Hussein Ward Ahmed , Por Lip Yee , Kiah Miss Laiha Mat , Zaidan Bilal Bahaa
Published: January 2022

The process of collecting driving data and using a computational model to generate a safety score for the driver is known as driver behavior profiling. Existing driver profiles attempt to categorize drivers as either safe or aggressive, which some experts say is not practical. This is due to the “safe/aggressive” categorization being a state that describes a driver’s conduct at a specific point in time rather than a continuous state or a human trait. Furthermore, due to the disparity in traffic laws and regulations between countries, what is considered aggressive behavior in one place may differ from what is considered aggressive behavior in another. As a result, adopting existing profiles is not ideal. The authors provide a unique approach to driver behavior profiling based on timeframe data segmentation. The profiling procedure consists of two main parts: row labeling and segment labeling. Row labeling assigns a safety score to each second of driving data based on criteria developed with the help of Malaysian traffic safety experts. Then, rows are accumulated to form timeframe segments. In segment labeling, generated timeframe segments are assigned a safety score using a set of criteria. The score assigned to the generated timeframe segment reflects the driver’s behavior during that time period. Following that, the study adopts three deep-learning-based algorithms, namely, Deep Neural Network (DNN), Recurrent Neural Network (RNN), and Convolutional Neural Network (CNN), to classify recorded driving data according to the established profiling procedure, and selects the most suitable one for a proposed recognition system. Various techniques were used to prevent the classification algorithms from overfitting. Using gathered naturalistic data, the validity of the modulated algorithms was assessed on various timeframe segments ranging from 1 to 10 s. Results showed that the CNN, which achieved an accuracy of 96.1%, outperformed the other two classification algorithms and was therefore recommended for the recognition system. In addition, recommendations were outlined on how the recognition system would assist in improving traffic safety.
Impact of Land Use/Land Cover Change on Landslide Susceptibility in Rangamati Municipality of Rangamati District, Bangladesh
Authors: Rabby Yasin Wahid , Li Yingkui , Abedin Joynal , Sabrina Sabiha
Published: January 2022

Landslide susceptibility depends on various causal factors such as geology, land use/land cover (LULC), slope, and elevation. Unlike other factors that are relatively stable over time, LULC is a dynamic factor associated with human activities. This study evaluates the impact of LULC change on landslide susceptibility in the Rangamati municipality of Rangamati district, Bangladesh, based on three LULC scenarios—the existing (2018) LULC, the proposed LULC (proposed in 2010, but not yet implemented), and the simulated LULC of 2028—using artificial neural network (ANN)-based cellular automata. The random forest model was used for landslide susceptibility mapping. The model showed good accuracy for all three LULC scenarios (existing: 82.7%; proposed: 81.4%; and 2028: 78.3%) and strong positive correlations (>0.8) between different landslide susceptibility maps. LULC is either the third or fourth most important factor in these scenarios, suggesting that is has a moderate impact on landslide susceptibility. Future LULC changes will likely increase landslide susceptibility, with up to 14.5% increases in the high susceptibility zone for both the proposed and simulated LULC scenarios. These findings may help policymakers carry out proper urban planning and highlight the importance of considering landslide susceptibility in LULC planning.
Oral Pathology in COVID-19 and SARS-CoV-2 Infection—Molecular Aspects
Authors: Drozdzik Agnieszka , Drozdzik Marek
Published: January 2022

This review article was designed to evaluate the existing evidence related to the molecular processes of SARS-CoV-2 infection in the oral cavity. The World Health Organization stated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and transmission is produced by respiratory droplets and aerosols from the oral cavity of infected patients. The oral cavity structures, keratinized and non-keratinized mucosa, and salivary glands’ epithelia express SARS-CoV-2 entry and transmission factors, especially angiotensin converting enzyme Type 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Replication of the virus in cells leads to local and systemic infection spread, and cellular damage is associated with clinical signs and symptoms of the disease in the oral cavity. Saliva, both the cellular and acellular fractions, holds the virus particles and contributes to COVID-19 transmission. The review also presents information about the factors modifying SARS-CoV-2 infection potential and possible local pharmacotherapeutic interventions, which may confine SARS-CoV-2 virus entry and transmission in the oral cavity. The PubMed and Scopus databases were used to search for suitable keywords such as: SARS-CoV-2, COVID-19, oral virus infection, saliva, crevicular fluid, salivary gland, tongue, oral mucosa, periodontium, gingiva, dental pulp, ACE2, TMPRSS2, Furin, diagnosis, topical treatment, vaccine and related words in relevant publications up to 28 December 2021. Data extraction and quality evaluation of the articles were performed by two reviewers, and 63 articles were included in the final review.
Temperature Dependence of Interfacial Bonding and Configuration Transition in Graphene/Hexagonal Boron Nitride Containing Grain Boundaries and Functional Groups
Authors: Fan Lei , Yao Wenjuan
Published: January 2022

The quasi-three-dimensional effect induced by functional groups (FGo) and the in-plane stress and structural deformation induced by grain boundaries (GBs) may produce more novel physical effects. These physical effects are particularly significant in high-temperature environments and are different from the behavior in bulk materials, so its physical mechanism is worth exploring. Considering the external field (strain and temperature field), the internal field (FGo and GBs) and the effect of distance between FGs and GBs on the bonding energy, configuration transition, and stress distribution of graphene/h-BN with FGo and GBs (GrO-BN-GBs) in the interface region were studied by molecular dynamics (MD). The results show that the regions linked by hydroxyl + epoxy groups gradually change from honeycomb to diamond-like structures as a result of a hybridization transition from sp2 to sp3. The built-in distortion stress field generated by the coupling effect of temperature and tension loading induces the local geometric buckling of two-dimensional materials, according the von Mises stresses and deflection theory. In addition, the internal (FGo and GBs) and external field (strain and temperature field) have a negative chain reaction on the mechanical properties of GrO-BN-GBs, and the negative chain reaction increases gradually with the increase in the distance between FGo and GBs. These physical effects are particularly obvious in high-temperature environments, and the behavior of physical effects in two-dimensional materials is different from that in bulk materials, so its physical mechanism is worth exploring.
Reductions in Hydrogen Sulfide and Changes in Mitochondrial Quality Control Proteins Are Evident in the Early Phases of the Corneally Kindled Mouse Model of Epilepsy
Authors: Cho Christi , Zeigler Maxwell , Mizuno Stephanie , Morrison Richard S. , Totah Rheem A. , Barker-Haliski Melissa
Published: January 2022

Epilepsy is a heterogenous neurological disorder characterized by recurrent unprovoked seizures, mitochondrial stress, and neurodegeneration. Hydrogen sulfide (H2S) is a gasotransmitter that promotes mitochondrial function and biogenesis, elicits neuromodulation and neuroprotection, and may acutely suppress seizures. A major gap in knowledge remains in understanding the role of mitochondrial dysfunction and progressive changes in H2S levels following acute seizures or during epileptogenesis. We thus sought to quantify changes in H2S and its methylated metabolite (MeSH) via LC-MS/MS following acute maximal electroshock and 6 Hz 44 mA seizures in mice, as well as in the early phases of the corneally kindled mouse model of chronic seizures. Plasma H2S was acutely reduced after a maximal electroshock seizure. H2S or MeSH levels and expressions of related genes in whole brain homogenates from corneally kindled mice were not altered. However, plasma H2S levels were significantly lower during kindling, but not after established kindling. Moreover, we demonstrated a time-dependent increase in expression of mitochondrial membrane integrity-related proteins, OPA1, MFN2, Drp1, and Mff during kindling, which did not correlate with changes in gene expression. Taken together, short-term reductions in plasma H2S could be a novel biomarker for seizures. Future studies should further define the role of H2S and mitochondrial stress in epilepsy.
Integrin Signaling in the Central Nervous System in Animals and Human Brain Diseases
Authors: Ikeshima-Kataoka Hiroko , Sugimoto Chikatoshi , Tsubokawa Tatsuya
Published: January 2022

The integrin family is involved in various biological functions, including cell proliferation, differentiation and migration, and also in the pathogenesis of disease. Integrins are multifunctional receptors that exist as heterodimers composed of α and β subunits and bind to various ligands, including extracellular matrix (ECM) proteins; they are found in many animals, not only vertebrates (e.g., mouse, rat, and teleost fish), but also invertebrates (e.g., planarian flatworm, fruit fly, nematodes, and cephalopods), which are used for research on genetics and social behaviors or as models for human diseases. In the present paper, we describe the results of a phylogenetic tree analysis of the integrin family among these species. We summarize integrin signaling in teleost fish, which serves as an excellent model for the study of regenerative systems and possesses the ability for replacing missing tissues, especially in the central nervous system, which has not been demonstrated in mammals. In addition, functions of astrocytes and reactive astrocytes, which contain neuroprotective subpopulations that act in concert with the ECM proteins tenascin C and osteopontin via integrin are also reviewed. Drug development research using integrin as a therapeutic target could result in breakthroughs for the treatment of neurodegenerative diseases and brain injury in mammals.
Therapeutic Potential of Human Fetal Mesenchymal Stem Cells in Musculoskeletal Disorders: A Narrative Review
Authors: Song Insun , Rim Jongseop , Lee Jaemin , Jang Inseok , Jung Bosung , Kim Kisoo , Lee Soonchul
Published: January 2022

Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for diverse diseases and injuries. The biological and clinical advantages of human fetal MSCs (hfMSCs) have recently been reported. In terms of promising therapeutic approaches for diverse diseases and injuries, hfMSCs have gained prominence as healing tools for clinical therapies. Therefore, this review assesses not the only biological advantages of hfMSCs for healing human diseases and regeneration, but also the research evidence for the engraftment and immunomodulation of hfMSCs based on their sources and biological components. Of particular clinical relevance, the present review also suggests the potential therapeutic feasibilities of hfMSCs for musculoskeletal disorders, including osteoporosis, osteoarthritis, and osteogenesis imperfecta.
Pleiotropic, Unique and Shared Responses Elicited by IL-6 Family Cytokines in Human Vascular Endothelial Cells
Authors: Lindkvist Madelene , Zegeye Mulugeta M. , Grenegård Magnus , Ljungberg Liza U.
Published: January 2022

Vascular endothelial cells express glycoprotein 130 (gp130), which is utilized as a signaling receptor by cytokines in the interleukin-6 (IL-6) family. Several IL-6 family cytokines can be found in the circulatory system during physiological or pathological conditions, and may influence endothelial function and response. This study evaluated and compared the cellular and molecular responses induced by IL-6 family cytokines in human endothelial cells. A proteomic analysis showed that IL-6 family cytokines induce the release of a range of proteins from endothelial cells, such as C-C motif chemokine ligand 23, hepatocyte growth factor, and IL-6. Pathway analysis indicated that gp130-signaling in endothelial cells regulates several functions related to angiogenesis and immune cell recruitment. The present investigation also disclosed differences and similarities between different IL-6 family cytokines in their ability to induce protein release and regulate gene expression and intracellular signaling, in regards to which oncostatin M showed the most pronounced effect. Further, this study showed that soluble gp130 preferentially blocks trans-signaling-induced responses, but does not affect responses induced by classic signaling. In conclusion, IL-6 family cytokines induce both specific and overlapping molecular responses in endothelial cells, and regulate genes and proteins involved in angiogenesis and immune cell recruitment.
Functional Characterization of FH Mutation c.557G>A Underlies Uterine Leiomyomas
Authors: Li Ping , Wu Yanru , Wu Huizhi , Xiong Qiuhong , Zhao Na , Chen Guangxin , Wu Changxin , Xiao Han
Published: January 2022

The FH gene encodes the fumarate hydratase of the Krebs cycle and functions as a homotetramer to catalyze the hydration of fumarate to malate. Mutations in FH result in uterine leiomyomas, a rare autosomal dominant inherited metabolic disease. However, how FH mutations result in this disease is poorly understood. Here, the FH mutation c.557G>A (p.S186N) was identified in a family with uterine leiomyomas phenotype. A series of studies were performed to confirm the pathogenicity of this mutation. Results showed that the FH mutant exhibited significantly lower fumarase enzyme activity and increased the fumarates level compared with the wildtype, which might be due to the impaired homotetramer formation in the native gel electrophoresis. Interestingly, the immunofluorescence study revealed that the overexpressed FH mutant exhibited puncta structures compared with the evenly expressed FH wildtype in cytoplasm suggesting that the altered amino acid might result in dysfunctional proteins which were accumulated to reduce its cytotoxicity. Importantly, the cells overexpressing the FH mutant exhibited higher proliferation and extracellular acidification rate value (ECAR) which might be caused by the upregulated HIF-1α indicating the tumor phenotype. Notably, phospho-mTOR was significantly increased and autophagy was inhibited in the FH mutant overexpression cells compared with the wildtype. Our work provides new insight into the FH mutation c.557G>A (p.S186N) underlies uterine leiomyomas and important information for accurate genetic counseling and clinical diagnosis of the disease.
The Discovery and Function of Filaggrin
Authors: Hoober J. Kenneth , Eggink Laura L.
Published: January 2022

Keratohyalin granules were discovered in the mid-19th century in cells that terminally differentiate to form the outer, cornified layer of the epidermis. The first indications of the composition of these structures emerged in the 1960s from a histochemical stain for histidine, followed by radioautographic evidence of a high incidence of histidine incorporation into newly synthesized proteins in cells containing the granules. Research during the next three decades revealed the structure and function of a major protein in these granules, which was initially called the ‘histidine-rich protein’. Steinert and Dale named the protein ‘filaggrin’ in 1981 because of its ability to aggregate keratin intermediate filaments. The human gene for the precursor, ‘profilaggrin,’ was reported in 1991 to encode 10, 11 or 12 nearly identical repeats. Remarkably, the mouse and rat genes encode up to 20 repeats. The lifetime of filaggrin is the time required for keratinocytes in the granular layer to move into the inner cornified layer. During this transition, filaggrin facilitates the collapse of corneocytes into ‘building blocks’ that become an impermeable surface barrier. The subsequent degradation of filaggrin is as remarkable as its synthesis, and the end-products aid in maintaining moisture in the cornified layer. It was apparent that ichthyosis vulgaris and atopic dermatitis were associated with the absence of this protein. McLean’s team in 2006 identified the cause of these diseases by discovering loss-of-function mutations in the profilaggrin gene, which led to dysfunction of the surface barrier. This story illustrates the complexity in maintaining a healthy, functional epidermis.
Development of a Gene-Activated Scaffold Incorporating Multifunctional Cell-Penetrating Peptides for pSDF-1α Delivery for Enhanced Angiogenesis in Tissue Engineering Applications
Authors: Power Rachael N. , Cavanagh Brenton L. , Dixon James E. , Curtin Caroline M. , O’Brien Fergal J.
Published: January 2022

Non-viral gene delivery has become a popular approach in tissue engineering, as it permits the transient delivery of a therapeutic gene, in order to stimulate tissue repair. However, the efficacy of non-viral delivery vectors remains an issue. Our lab has created gene-activated scaffolds by incorporating various non-viral delivery vectors, including the glycosaminoglycan-binding enhanced transduction (GET) peptide into collagen-based scaffolds with proven osteogenic potential. A modification to the GET peptide (FLR) by substitution of arginine residues with histidine (FLH) has been designed to enhance plasmid DNA (pDNA) delivery. In this study, we complexed pDNA with combinations of FLR and FLH peptides, termed GET* nanoparticles. We sought to enhance our gene-activated scaffold platform by incorporating GET* nanoparticles into collagen–nanohydroxyapatite scaffolds with proven osteogenic capacity. GET* N/P 8 was shown to be the most effective formulation for delivery to MSCs in 2D. Furthermore, GET* N/P 8 nanoparticles incorporated into collagen–nanohydroxyapatite (coll–nHA) scaffolds at a 1:1 ratio of collagen:nanohydroxyapatite was shown to be the optimal gene-activated scaffold. pDNA encoding stromal-derived factor 1α (pSDF-1α), an angiogenic chemokine which plays a role in BMP mediated differentiation of MSCs, was then delivered to MSCs using our optimised gene-activated scaffold platform, with the aim of significantly increasing angiogenesis as an important precursor to bone repair. The GET* N/P 8 coll–nHA scaffolds successfully delivered pSDF-1α to MSCs, resulting in a significant, sustained increase in SDF-1α protein production and an enhanced angiogenic effect, a key precursor in the early stages of bone repair.
A Central Role for TRPM4 in Ca2+-Signal Amplification and Vasoconstriction
Authors: Csípő Tamás , Czikora Ágnes , Fülöp Gábor Á. , Gulyás Hajnalka , Rutkai Ibolya , Tóth Enikő Pásztorné , Pórszász Róbert , Szalai Andrea , Bölcskei Kata , Helyes Zsuzsanna , Pintér Erika , Papp Zoltán , Ungvári Zoltán , Tóth Attila
Published: January 2022

Transient receptor potential melastatin-4 (TRPM4) is activated by an increase in intracellular Ca2+ concentration and is expressed on smooth muscle cells (SMCs). It is implicated in the myogenic constriction of cerebral arteries. We hypothesized that TRPM4 has a general role in intracellular Ca2+ signal amplification in a wide range of blood vessels. TRPM4 function was tested with the TRPM4 antagonist 9-phenanthrol and the TRPM4 activator A23187 on the cardiovascular responses of the rat, in vivo and in isolated basilar, mesenteric, and skeletal muscle arteries. TRPM4 inhibition by 9-phenanthrol resulted in hypotension and a decreased heart rate in the rat. TRPM4 inhibition completely antagonized myogenic tone development and norepinephrine-evoked vasoconstriction, and depolarization (high extracellular KCl concentration) evoked vasoconstriction in a wide range of peripheral arteries. Vasorelaxation caused by TRPM4 inhibition was accompanied by a significant decrease in intracellular Ca2+ concentration, suggesting an inhibition of Ca2+ signal amplification. Immunohistochemistry confirmed TRPM4 expression in the smooth muscle cells of the peripheral arteries. Finally, TRPM4 activation by the Ca2+ ionophore A23187 was competitively inhibited by 9-phenanthrol. In summary, TRPM4 was identified as an essential Ca2+-amplifying channel in peripheral arteries, contributing to both myogenic tone and agonist responses. These results suggest an important role for TRPM4 in the circulation. The modulation of TRPM4 activity may be a therapeutic target for hypertension. Furthermore, the Ca2+ ionophore A23187 was identified as the first high-affinity (nanomolar) direct activator of TRPM4, acting on the 9-phenanthrol binding site.
Cyclophilin A Is Not Acetylated at Lysine-82 and Lysine-125 in Resting and Stimulated Platelets
Authors: Rosa Annabelle , Butt Elke , Hopper Christopher P. , Loroch Stefan , Bender Markus , Schulze Harald , Sickmann Albert , Vorlova Sandra , Seizer Peter , Heinzmann David , Zernecke Alma
Published: January 2022

Cyclophilin A (CyPA) is widely expressed by all prokaryotic and eukaryotic cells. Upon activation, CyPA can be released into the extracellular space to engage in a variety of functions, such as interaction with the CD147 receptor, that contribute to the pathogenesis of cardiovascular diseases. CyPA was recently found to undergo acetylation at K82 and K125, two lysine residues conserved in most species, and these modifications are required for secretion of CyPA in response to cell activation in vascular smooth muscle cells. Herein we addressed whether acetylation at these sites is also required for the release of CyPA from platelets based on the potential for local delivery of CyPA that may exacerbate cardiovascular disease events. Western blot analyses confirmed the presence of CyPA in human and mouse platelets. Thrombin stimulation resulted in CyPA release from platelets; however, no acetylation was observed—neither in cell lysates nor in supernatants of both untreated and activated platelets, nor after immunoprecipitation of CyPA from platelets. Shotgun proteomics detected two CyPA peptide precursors in the recombinant protein, acetylated at K28, but again, no acetylation was found in CyPA derived from resting or stimulated platelets. Our findings suggest that acetylation of CyPA is not a major protein modification in platelets and that CyPA acetylation is not required for its secretion from platelets.
DFT Quantum-Chemical Calculation of Thermodynamic Parameters and DSC Measurement of Thermostability of Novel Benzofuroxan Derivatives Containing Triazidoisobutyl Fragments
Authors: Chugunova Elena , Shaekhov Timur , Khamatgalimov Ayrat , Gorshkov Vladimir , Burilov Alexander
Published: January 2022

New derivatives of benzofuroxan containing triazidoisobutyl fragments, opening the way for the creation of highly effective compositions with an increased value of energy characteristics, were synthesized for the first time. Such compounds are also an excellent platform for further modification and for the preparation of new biologically-active compounds containing tetrazole and triazole fragments. Calculations of heats of formation performed with the DFT (density functional theory) method showed that the studied compounds are high-energetic density ones, the enthalpies of formation of which are comparable to the enthalpies of formation of similar benzofuroxan derivatives and exceeds experimental enthalpy of formation of CL-14 (5,7-diamino-4,6-dinitrobenzofuroxan). The analysis of DSC indicates a sufficiently high thermal stability of the synthesized azidobenzofuroxans, which are acceptable for their use as components in the creation of highly efficient compositions with an increased value of energy characteristics.
Extracellular Vesicles Derived from Human Liver Stem Cells Attenuate Chronic Kidney Disease Development in an In Vivo Experimental Model of Renal Ischemia and Reperfusion Injury
Authors: Bruno Stefania , Chiabotto Giulia , Cedrino Massimo , Ceccotti Elena , Pasquino Chiara , De Rosa Samuela , Grange Cristina , Tritta Stefania , Camussi Giovanni
Published: January 2022

The potential therapeutic effect of extracellular vesicles (EVs) that are derived from human liver stem cells (HLSCs) has been tested in an in vivo model of renal ischemia and reperfusion injury (IRI), that induce the development of chronic kidney disease (CKD). EVs were administered intravenously immediately after the IRI and three days later, then their effect was tested at different time points to evaluate how EV-treatment might interfere with fibrosis development. In IRI-mice that were sacrificed two months after the injury, EV- treatment decreased the development of interstitial fibrosis at the histological and molecular levels. Furthermore, the expression levels of pro-inflammatory genes and of epithelial–mesenchymal transition (EMT) genes were significantly reverted by EV-treatment. In IRI-mice that were sacrificed at early time points (two and three days after the injury), functional and histological analyses showed that EV-treatment induced an amelioration of the acute kidney injury (AKI) that was induced by IRI. Interestingly, at the molecular level, a reduction of pro-fibrotic and EMT-genes in sacrificed IRI-mice was observed at days two and three after the injury. These data indicate that in renal IRI, treatment with HLSC-derived EVs improves AKI and interferes with the development of subsequent CKD by modulating the genes that are involved in fibrosis and EMT.
Regulation of the Emissions of the Greenhouse Gas Nitrous Oxide by the Soybean Endosymbiont Bradyrhizobium diazoefficiens
Authors: Bueno Emilio , Mania Daniel , Mesa Socorro , Bedmar Eulogio J. , Frostegård Åsa , Bakken Lars R. , Delgado María J.
Published: January 2022

The greenhouse gas nitrous oxide (N2O) has strong potential to drive climate change. Soils are a major source of N2O, with microbial nitrification and denitrification being the primary processes involved in such emissions. The soybean endosymbiont Bradyrhizobium diazoefficiens is a model microorganism to study denitrification, a process that depends on a set of reductases, encoded by the napEDABC, nirK, norCBQD, and nosRZDYFLX genes, which sequentially reduce nitrate (NO3−) to nitrite (NO2−), nitric oxide (NO), N2O, and dinitrogen (N2). In this bacterium, the regulatory network and environmental cues governing the expression of denitrification genes rely on the FixK2 and NnrR transcriptional regulators. To understand the role of FixK2 and NnrR proteins in N2O turnover, we monitored real-time kinetics of NO3−, NO2−, NO, N2O, N2, and oxygen (O2) in a fixK2 and nnrR mutant using a robotized incubation system. We confirmed that FixK2 and NnrR are regulatory determinants essential for NO3− respiration and N2O reduction. Furthermore, we demonstrated that N2O reduction by B. diazoefficiens is independent of canonical inducers of denitrification, such as the nitrogen oxide NO3−, and it is negatively affected by acidic and alkaline conditions. These findings advance the understanding of how specific environmental conditions and two single regulators modulate N2O turnover in B. diazoefficiens.
The Thermodynamically Expensive Contribution of Three Calcium Sources to Somatic Release of Serotonin
Authors: De-Miguel Francisco F.
Published: January 2022

The soma, dendrites and axon of neurons may display calcium-dependent release of transmitters and peptides. Such release is named extrasynaptic for occurring in absence of synaptic structures. This review describes the cooperative actions of three calcium sources on somatic exocytosis. Emphasis is given to the somatic release of serotonin by the classical leech Retzius neuron, which has allowed detailed studies on the fine steps from excitation to exocytosis. Trains of action potentials induce transmembrane calcium entry through L-type channels. For action potential frequencies above 5 Hz, summation of calcium transients on individual action potentials activates the second calcium source: ryanodine receptors produce calcium-induced calcium release. The resulting calcium tsunami activates mitochondrial ATP synthesis to fuel transport of vesicles to the plasma membrane. Serotonin that is released maintains a large-scale exocytosis by activating the third calcium source: serotonin autoreceptors coupled to phospholipase C promote IP3 production. Activated IP3 receptors in peripheral endoplasmic reticulum release calcium that promotes vesicle fusion. The Swiss-clock workings of the machinery for somatic exocytosis has a striking disadvantage. The essential calcium-releasing endoplasmic reticulum near the plasma membrane hinders the vesicle transport, drastically reducing the thermodynamic efficiency of the ATP expenses and elevating the energy cost of release.
Acknowledgment to Reviewers of Immuno in 2021
Authors:   Immuno Editorial Office
Published: January 2022

Rigorous peer-reviews are the basis of high-quality academic publishing [...]
Neural Substrates of Transcutaneous Spinal Cord Stimulation: Neuromodulation across Multiple Segments of the Spinal Cord
Authors: Barss Trevor S. , Parhizi Behdad , Porter Jane , Mushahwar Vivian K.
Published: January 2022

Transcutaneous spinal cord stimulation (tSCS) has the potential to promote improved sensorimotor rehabilitation by modulating the circuitry of the spinal cord non-invasively. Little is currently known about how cervical or lumbar tSCS influences the excitability of spinal and corticospinal networks, or whether the synergistic effects of multi-segmental tSCS occur between remote segments of the spinal cord. The aim of this review is to describe the emergence and development of tSCS as a novel method to modulate the spinal cord, while highlighting the effectiveness of tSCS in improving sensorimotor recovery after spinal cord injury. This review underscores the ability of single-site tSCS to alter excitability across multiple segments of the spinal cord, while multiple sites of tSCS converge to facilitate spinal reflex and corticospinal networks. Finally, the potential and current limitations for engaging cervical and lumbar spinal cord networks through tSCS to enhance the effectiveness of rehabilitation interventions are discussed. Further mechanistic work is needed in order to optimize targeted rehabilitation strategies and improve clinical outcomes.
Hospital-Acquired Functional Decline and Clinical Outcomes in Older Cardiac Surgical Patients: A Multicenter Prospective Cohort Study
Authors: Morisawa Tomoyuki , Saitoh Masakazu , Otsuka Shota , Takamura Go , Tahara Masayuki , Ochi Yusuke , Takahashi Yo , Iwata Kentaro , Oura Keisuke , Sakurada Koji , Takahashi Tetsuya
Published: January 2022

This study aimed to determine the effect of hospital-acquired functional decline (HAFD) on prognosis, 1-year post-hospital discharge, of older patients who had undergone cardiac surgery in seven Japanese hospitals between June 2017 and June 2018. This multicenter prospective cohort study involved 247 patients with cardiac disease aged ≥65 years. HAFD was defined as a decrease in the short physical performance battery at hospital discharge compared with before surgery. Primary outcomes included a composite outcome of frailty severity, total mortality, and cardiovascular readmission 1-year post-hospital discharge. Secondary outcomes were changes in the total score and sub-item scores in the Ki-hon Checklist (KCL), assessed pre- and 1-year postoperatively. Poor prognostic outcomes were observed in 33% of patients, and multivariate analysis identified HAFD (odds ratio [OR] 3.43, 95% confidence interval [CI] 1.75–6.72, p < 0.001) and low preoperative gait speed (OR 2.47, 95% CI 1.18–5.17, p = 0.016) as independent predictors of poor prognosis. Patients with HAFD had significantly worse total KCL scores and subscale scores for instrumental activities of daily living, mobility, oral function, and depression at 1-year post-hospital discharge. HAFD is a powerful predictor of prognosis in older patients who have undergone cardiac surgery.
Characteristics and Outcomes of Intracranial Hemorrhage in Cancer Patients Visiting the Emergency Department
Authors: Qdaisat Aiham , Yeung Sai-Ching J. , Rojas Hernandez Cristhiam H. , Samudrala Pavani , Kamal Mona , Li Ziyi , Wechsler Adriana H.
Published: January 2022

Intracranial hemorrhage (ICH) is a dreaded complication of both cancer and its treatment. To evaluate the characteristics and clinical outcomes of cancer patients with ICH, we identified all patients with ICH who visited The University of Texas MD Anderson Cancer Center emergency department between 1 September 2006 and 16 February 2016. Clinical and radiologic data were collected and compared. Logistic regression analyses were used to determine the association between clinical variables and various outcomes. During the period studied, 704 confirmed acute ICH cases were identified. In-hospital, 7-day, and 30-day mortality rates were 15.1, 11.4, and 25.6%, respectively. Hypertension was most predictive of intensive care unit admission (OR = 1.52, 95% CI = 1.09–2.12, p = 0.013). Low platelet count was associated with both in-hospital mortality (OR = 0.96, 95% CI = 0.94–0.99, p = 0.008) and 30-day mortality (OR = 0.98, 95% CI = 0.96–1.00, p = 0.016). Radiologic findings, especially herniation and hydrocephalus, were strong predictors of short-term mortality. Among known risk factors of ICH, those most helpful in predicting cancer patient outcomes were hypertension, low platelet count, and the presence of hydrocephalus or herniation. Understanding how the clinical presentation, risk factors, and imaging findings correlate with patient morbidity and mortality is helpful in guiding the diagnostic evaluation and aggressiveness of care for ICH in cancer patients.
Perioperative Complications of Patients with SARS-CoV-2 Infection in Neurosurgery
Authors: Greuter Ladina , Zweifel Christian , Guzman Raphael , Soleman Jehuda
Published: January 2022

Background: The outbreak of coronavirus disease 2019 (COVID-19) has been rapidly evolving, resulting in a pandemic, with 270,031,622 infections according to the World Health Organization. Patients suffering from COVID-19 have also been described to suffer from neurologic and coagulopathic symptoms apart from the better-known flu-like symptoms. Some studies showed that patients suffering from COVID-19 were likely to developed intracranial hemorrhages. To our knowledge, only a few studies have investigated postoperative complications in COVID-19-positive neurosurgical patients and investigated the perioperative complications, either thrombotic or hemorrhagic, in patients with SARS-CoV-2 undergoing a neurosurgical intervention. Methods: We conducted a retrospective cohort study including patients from March 2020 to March 2021 undergoing neurosurgical interventions and suffering from COVID-19. Our primary outcome parameter was a hemorrhagic or thrombotic complication within 30 days after surgery. These outcomes were compared to those for a COVID-19-negative cohort of patients using propensity score matching. Results: We included ten COVID-19-positive patients with a mean age of 56.00 (±14.91) years. Twelve postoperative complications occurred in five patients. Three thrombotic complications (30%) were observed, with two cerebral sinus vein thromboses and one pulmonary embolus. Two patients suffered from a postoperative hemorrhagic complication (20%). The mean postoperative GCS was 14.30 (±1.57). COVID-19-positive patients showed a significantly higher rate of overall postoperative complications ((6 (60.0%) vs. 10 (19.2%), p = 0.021), thrombotic complications (3 (30.0%) vs. 1 (1.9%), p = 0.009), and mortality (2 (20.0%) vs. 0 (0.0%), p = 0.021) compared to the matched cohort of COVID-19-negative patients, treated at our institute before the SARS-CoV-2 pandemic. Conclusion: Patients undergoing neurosurgical operations with concomitant COVID-19 infection have higher rates of perioperative complications.
Optimizing Mandibular Advancement Maneuvers during Sleep Endoscopy with a Titratable Positioner: DISE-SAM Protocol
Authors: Fernández-Sanjuán Patricia , Arrieta Juan José , Sanabria Jaime , Alcaraz Marta , Bosco Gabriela , Pérez-Martín Nuria , Pérez Adriana , Carrasco-Llatas Marina , Moreno-Hay Isabel , Ríos-Lago Marcos , Lugo Rodolfo , O’Connor-Reina Carlos , Baptista Peter , Plaza Guillermo
Published: January 2022

Mandibular advancement devices (MAD) are an effective alternative treatment to CPAP. Different maneuvers were performed during drug sleep-induced endoscopy (DISE) to mimic the effect of MAD. Using the Selector Avance Mandibular (SAM) device, we aimed to identify MAD candidates during DISE using a titratable, reproducible, and measurable maneuver. This DISE-SAM protocol may help to find the relationship between the severity of the respiratory disorder and the degree of response and determine the advancement required to improve the collapsibility of the upper airway. Explorations were performed in 161 patients (132 males; 29 females) with a mean age of 46.81 (SD = 11.42) years, BMI of 27.90 (SD = 4.19) kg/m2, and a mean AHI of 26.51 (SD = 21.23). The results showed no relationship between severity and MAD recommendation. Furthermore, there was a weak positive relationship between the advancement required to obtain a response and the disease severity. Using the DISE-SAM protocol, the response and the range of mandibular protrusion were assessed, avoiding the interexaminer bias of the jaw thrust maneuver. We suggest prescribing MAD as a single, alternative, or multiple treatment approaches following the SAM recommendations in a personalized design.
Early N-Terminal Pro B-Type Natriuretic Peptide (NTproBNP) Plasma Values and Associations with Patent Ductus Arteriosus Closure and Treatment—An Echocardiography Study of Extremely Preterm Infants
Authors: Gudmundsdottir Anna , Bartocci Marco , Picard Oda , Ekström Joanna , Chakhunashvili Alexander , Bohlin Kajsa , Attner Caroline , Printz Gordana , Karlsson Mathias , Mohlkert Lilly-Ann , Karlén Jonna , Pegelow Halvorsen Cecilia , Edstedt Bonamy Anna-Karin
Published: January 2022

The aim was to investigate the association of gestational age (GA), echocardiographic markers and levels of plasma N-terminal pro-B-type natriuretic peptide (NTproBNP) with the closure rate of a haemodynamically significant patent ductus arteriosus (hsPDA). Ninety-eight Swedish extremely preterm infants, mean GA 25.7 weeks (standard deviation 1.3), born in 2012–2014, were assessed with echocardiography and for levels of NTproBNP. Thirty-three (34%) infants had spontaneous ductal closure within three weeks of age. Infants having spontaneous closure at seven days or less had significantly lower NTproBNP levels on day three, median 1810 ng/L (IQR 1760–6000 ng/L) compared with: infants closing spontaneously later, 10,900 ng/L (6120–19,200 ng/L); infants treated either with ibuprofen only, 14,600 ng/L (7740–28,100 ng/L); or surgery, 32,300 ng/L (29,100–35,000 ng/L). Infants receiving PDA surgery later had significantly higher NTproBNP values on day three than other infants. Day three NTproBNP cut-off values of 15,001–18,000 ng/L, predicted later PDA surgery, with an area under the curve in ROC analysis of 0.69 (0.54–0.83). In conclusion, the spontaneous PDA closure rate is relatively high in extremely preterm infants. Early NTproBNP levels can be used with GA in the management decisions of hsPDA.
Contemporary Ichthyological and Fisheries Research of Deepwater Fish: New Advances, Current Challenges, and Future Developments
Authors: Orlov Alexei M.
Published: January 2022

Deepwater fishes are a very diverse group of chondrichthyans and teleosts widely distributed in the world ocean from the Arctic to the Antarctic and inhabiting the water column and seabed of continental slopes, seamounts, and high seas usually at depths greater than 400 m [...]
Analysis of Vibration Characteristics of Podded Propulsor Shafting Based on Analytical Method
Authors: Tian Yaqi , Zhang Cong , Yang Lei , Ouyang Wu , Zhou Xincong
Published: January 2022

Podded propulsors are widely used in warships and cruise ships, which have a higher requirement of vibrational and acoustic design. Therefore, studying vibration characteristics and the transmission mechanism of podded propulsor shafting is significant for reducing vibration and ensuring the safe operation of ships. This paper establishes a model of podded propulsor shafting by analytical method. The shafting is simplified to a heterogeneous variable cross-section beam, while bearings are seen as springs. The podded propulsor shafting has one radial-thrust hybrid bearing and one radial bearing. The excitations from the propeller and cabin are considered. The influences of bearing stiffness, bearing location, and excitation on vibration characteristics of shafting are analyzed. The main conclusions are as follows: Based on the analysis of the area that resonance frequency is sensitive to the change of bearing stiffness, the resonance frequencies of the shafting can be adjusted to the proper range. The large span between hybrid bearing and radial bearing leads to low stiffness of shafting and low resonances frequencies. Under radial excitations, the low vibration always occurs at the hybrid bearing, motor shafting, or propeller end of shafting. This research provides theoretical support for the design and optimization of vibration reduction of podded propulsor shafting.
Photoaging Characteristics of Disposable Masks under UV Irradiation
Authors: Liu Xinhao , Cao Wei , Xie Linqing , Sun Chengjun , Jiang Fenghua
Published: January 2022

The global outbreak of Corona Virus Disease 2019 (COVID-19) has led to an extreme increase in the use of disposable masks. If the used disposable masks are not appropriately disposed of, they will enter the natural environment and lead to environmental pollution. In order to understand the impacts of disposable masks after being disposed of into the natural environment, aging experiments with simulated natural conditions were performed on the outer, inner, and middle layers of the masks to verify the aging characteristics of disposable masks. We analyzed the mechanical behavior, surface morphology, and Fourier Transform Infrared Spectroscopy (FT-IR) spectra of disposable masks treated with different levels of UV irradiation to understand the possible changes in the masks under UV. Results showed that the elongation at break, tensile strength, and maximum force of all three polypropylene (PP) mask layers decreased after UV irradiation, indicating chemical bond breakage. In the process of photoaging, each layer of the disposable masks showed a different degree of microscopic surface changes after UV irradiation, and these changes gradually intensified with the extension of UV exposure time. FT-IR results showed that functional groups, such as hydroxyl and carbonyl groups increased in each layer after UV irradiation. The results of this study support that, although the different layers of the disposable masks are all made of PP, they age differently in the environment. With the ever-increasing number of disposable masks in the environment, we need to further study the aging and degradation of disposable masks to better understand their potential impacts on the environment in the future.
Metagenomic Insights into the Structure of Microbial Communities Involved in Nitrogen Cycling in Two Integrated Multitrophic Aquaculture (IMTA) Ponds
Authors: Liu Qian , Li Junnan , Shan Hongwei , Xie Yicheng
Published: January 2022

The microbial structure and metabolic potential, particularly with regard to nitrogen (N) cycling, in integrated multitrophic aquaculture (IMTA) ponds with shrimp remain unclear. In this study, an analysis of microbial community taxonomic diversity and a metagenomic analysis of N-related genes were performed in a shrimp-crab pond (Penaeus japonicus-Portunus trituberculatus, SC) and a shrimp-crab-clam pond (P. japonicus-P. trituberculatus-Sinonovacula constricta, SCC) to evaluate microbial structure and N transformation capacities in these two shrimp IMTA ponds. The composition of the microbial communities was similar between SC and SCC, but the water and sediments shared few common members in either pond. The relative abundances of N cycling genes were significantly higher in sediment than in water in both SC and SCC, except for assimilatory nitrate reduction genes. The main drivers of the differences in the relative abundances of N cycling genes in SC and SCC were salinity and pH in water and the NO2− and NH4+ contents of pore water in sediment. These results indicate that the coculture of S. constricta in a shrimp-crab pond may result in decreased N cycling in sediment. The reduced N flux in the shrimp IMTA ponds primarily originates within the sediment, except for assimilatory nitrate reduction.
Tidal Turbine Apparatus Vibration and Its Effect on Power Production Measurement
Authors: Xu Yiyi , Zhao Jun , Sun Shuai , Liu Pengfei
Published: January 2022

The effect of vibration and oscillation of an instrumented testing apparatus on horizontal axis tidal turbine rotor energy generation performance was examined and analyzed. Enforcement struts and an accelerometer were installed to measure and record vibration during the test with and without struts. Three rotors with a solidity (i.e., expanded area ratio, EAR) of 0.25, 0.4, and 0.51 were tested to obtain the rotor energy generation performance data. The analysis of the results is focused on the rotor open-water performance, in terms of the drag and power coefficient, respectively. The results show the reduced overall oscillation/vibration achieved an improvement in the measured power coefficient of about 6% and the drag measurement improved by about 3%. The allowable inflow velocity was also extended from 2 to 4 m/s. These results indicate that the enhanced vibration reduction method is effective and necessary for tidal turbine apparatus and its instrumentation.
Numerical Study on the Turbulent Structure of Tsunami Bottom Boundary Layer Using the 2011 Tohoku Tsunami Waveform
Authors: Tinh Nguyen Xuan , Tanaka Hitoshi , Yu Xiping , Liu Guangwei
Published: January 2022

In this study, the tsunami-induced bottom boundary layer was investigated based on actual waveforms obtained by the GPS buoys along the coast of the Tohoku region during the 2011 Great East Japan Earthquake tsunami. The k-ω model was utilized for the numerical analysis in this study. As a result, the tsunami boundary layer thickness was found to be extremely thin compared to the water depth. The velocity distribution was similar to that of the bottom boundary layer under wind-generated waves. The flow regime is located in the transition from smooth turbulence to rough turbulence. Because of this, the gradient of the flow across the layer is much greater than the gradients in the steady flow direction. Therefore, the bottom friction is underestimated if the steady friction factor, such as in the Manning formula, is used. This study proposes a new simple method for calculating the bottom shear stress due to an irregular tsunami based on the wave friction law, and the k-ω model results are used to validate the proposed methods.