bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression Analysis of Zinc Transporters in Nervous Tissue Cells Reveals Neuronal and Synaptic Localization of ZIP4
Authors: De Benedictis Chiara A. , Haffke Claudia , Hagmeyer Simone , Sauer Ann Katrin , Grabrucker Andreas M.
Published: April 2021

In the last years, research has shown that zinc ions play an essential role in the physiology of brain function. Zinc acts as a potent neuromodulatory agent and signaling ions, regulating healthy brain development and the function of both neurons and glial cells. Therefore, the concentration of zinc within the brain and its cells is tightly controlled. Zinc transporters are key regulators of (extra-) cellular zinc levels, and deregulation of zinc homeostasis and zinc transporters has been associated with neurodegenerative and neuropsychiatric disorders. However, to date, the presence of specific family members and their subcellular localization within brain cells have not been investigated in detail. Here, we analyzed the expression of all zinc transporters (ZnTs) and Irt-like proteins (ZIPs) in the rat brain. We further used primary rat neurons and rat astrocyte cell lines to differentiate between the expression found in neurons or astrocytes or both. We identified ZIP4 expressed in astrocytes but significantly more so in neurons, a finding that has not been reported previously. In neurons, ZIP4 is localized to synapses and found in a complex with major postsynaptic scaffold proteins of excitatory synapses. Synaptic ZIP4 reacts to short-term fluctuations in local zinc levels. We conclude that ZIP4 may have a so-far undescribed functional role at excitatory postsynapses.
Current Understanding of Leaf Senescence in Rice
Authors: Lee Sichul , Masclaux-Daubresse Celine
Published: April 2021

Leaf senescence, which is the last developmental phase of plant growth, is controlled by multiple genetic and environmental factors. Leaf yellowing is a visual indicator of senescence due to the loss of the green pigment chlorophyll. During senescence, the methodical disassembly of macromolecules occurs, facilitating nutrient recycling and translocation from the sink to the source organs, which is critical for plant fitness and productivity. Leaf senescence is a complex and tightly regulated process, with coordinated actions of multiple pathways, responding to a sophisticated integration of leaf age and various environmental signals. Many studies have been carried out to understand the leaf senescence-associated molecular mechanisms including the chlorophyll breakdown, phytohormonal and transcriptional regulation, interaction with environmental signals, and associated metabolic changes. The metabolic reprogramming and nutrient recycling occurring during leaf senescence highlight the fundamental role of this developmental stage for the nutrient economy at the whole plant level. The strong impact of the senescence-associated nutrient remobilization on cereal productivity and grain quality is of interest in many breeding programs. This review summarizes our current knowledge in rice on (i) the actors of chlorophyll degradation, (ii) the identification of stay-green genotypes, (iii) the identification of transcription factors involved in the regulation of leaf senescence, (iv) the roles of leaf-senescence-associated nitrogen enzymes on plant performance, and (v) stress-induced senescence. Compiling the different advances obtained on rice leaf senescence will provide a framework for future rice breeding strategies to improve grain yield.
Back to the Origins: Background and Perspectives of Grapevine Domestication
Authors: Grassi Fabrizio , De Lorenzis Gabriella
Published: April 2021

Domestication is a process of selection driven by humans, transforming wild progenitors into domesticated crops. The grapevine (Vitis vinifera L.), besides being one of the most extensively cultivated fruit trees in the world, is also a fascinating subject for evolutionary studies. The domestication process started in the Near East and the varieties obtained were successively spread and cultivated in different areas. Whether the domestication occurred only once, or whether successive domestication events occurred independently, is a highly debated mystery. Moreover, introgression events, breeding and intense trade in the Mediterranean basin have followed, in the last thousands of years, obfuscating the genetic relationships. Although a succession of studies has been carried out to explore grapevine origin and different evolution models are proposed, an overview of the topic remains pending. We review here the findings obtained in the main phylogenetic and genomic studies proposed in the last two decades, to clarify the fundamental questions regarding where, when and how many times grapevine domestication took place. Finally, we argue that the realization of the pan-genome of grapes could be a useful resource to discover and track the changes which have occurred in the genomes and to improve our understanding about the domestication.
Inherited Platelet Disorders: An Updated Overview
Authors: Palma-Barqueros Verónica , Revilla Nuria , Sánchez Ana , Zamora Cánovas Ana , Rodriguez-Alén Agustín , Marín-Quílez Ana , González-Porras José Ramón , Vicente Vicente , Lozano María Luisa , Bastida José María , Rivera José
Published: April 2021

Platelets play a major role in hemostasis as ppwell as in many other physiological and pathological processes. Accordingly, production of about 1011 platelet per day as well as appropriate survival and functions are life essential events. Inherited platelet disorders (IPDs), affecting either platelet count or platelet functions, comprise a heterogenous group of about sixty rare diseases caused by molecular anomalies in many culprit genes. Their clinical relevance is highly variable according to the specific disease and even within the same type, ranging from almost negligible to life-threatening. Mucocutaneous bleeding diathesis (epistaxis, gum bleeding, purpura, menorrhagia), but also multisystemic disorders and/or malignancy comprise the clinical spectrum of IPDs. The early and accurate diagnosis of IPDs and a close patient medical follow-up is of great importance. A genotype–phenotype relationship in many IPDs makes a molecular diagnosis especially relevant to proper clinical management. Genetic diagnosis of IPDs has been greatly facilitated by the introduction of high throughput sequencing (HTS) techniques into mainstream investigation practice in these diseases. However, there are still unsolved ethical concerns on general genetic investigations. Patients should be informed and comprehend the potential implications of their genetic analysis. Unlike the progress in diagnosis, there have been no major advances in the clinical management of IPDs. Educational and preventive measures, few hemostatic drugs, platelet transfusions, thrombopoietin receptor agonists, and in life-threatening IPDs, allogeneic hematopoietic stem cell transplantation are therapeutic possibilities. Gene therapy may be a future option. Regular follow-up by a specialized hematology service with multidisciplinary support especially for syndromic IPDs is mandatory.
Tryptophanyl-tRNA Synthetase as a Potential Therapeutic Target
Authors: Ahn Young Ha , Oh Se-Chan , Zhou Shengtao , Kim Tae-Don
Published: April 2021

Tryptophanyl-tRNA synthetase (WRS) is an essential enzyme that catalyzes the ligation of tryptophan (Trp) to its cognate tRNAtrp during translation via aminoacylation. Interestingly, WRS also plays physiopathological roles in diseases including sepsis, cancer, and autoimmune and brain diseases and has potential as a pharmacological target and therapeutic. However, WRS is still generally regarded simply as an enzyme that produces Trp in polypeptides; therefore, studies of the pharmacological effects, therapeutic targets, and mechanisms of action of WRS are still at an emerging stage. This review summarizes the involvement of WRS in human diseases. We hope that this will encourage further investigation into WRS as a potential target for drug development in various pathological states including infection, tumorigenesis, and autoimmune and brain diseases.
Effects of SARS-CoV-2 on Cardiovascular System: The Dual Role of Angiotensin-Converting Enzyme 2 (ACE2) as the Virus Receptor and Homeostasis Regulator-Review
Authors: Aleksova Aneta , Gagno Giulia , Sinagra Gianfranco , Beltrami Antonio Paolo , Janjusevic Milijana , Ippolito Giuseppe , Zumla Alimuddin , Fluca Alessandra Lucia , Ferro Federico
Published: April 2021

Angiotensin-converting enzyme 2 (ACE2) is the entry receptor for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of Coronavirus Disease-2019 (COVID-19) in humans. ACE-2 is a type I transmembrane metallocarboxypeptidase expressed in vascular endothelial cells, alveolar type 2 lung epithelial cells, renal tubular epithelium, Leydig cells in testes and gastrointestinal tract. ACE2 mediates the interaction between host cells and SARS-CoV-2 spike (S) protein. However, ACE2 is not only a SARS-CoV-2 receptor, but it has also an important homeostatic function regulating renin-angiotensin system (RAS), which is pivotal for both the cardiovascular and immune systems. Therefore, ACE2 is the key link between SARS-CoV-2 infection, cardiovascular diseases (CVDs) and immune response. Susceptibility to SARS-CoV-2 seems to be tightly associated with ACE2 availability, which in turn is determined by genetics, age, gender and comorbidities. Severe COVID-19 is due to an uncontrolled and excessive immune response, which leads to acute respiratory distress syndrome (ARDS) and multi-organ failure. In spite of a lower ACE2 expression on cells surface, patients with CVDs have a higher COVID-19 mortality rate, which is likely driven by the imbalance between ADAM metallopeptidase domain 17 (ADAM17) protein (which is required for cleavage of ACE-2 ectodomain resulting in increased ACE2 shedding), and TMPRSS2 (which is required for spike glycoprotein priming). To date, ACE inhibitors and Angiotensin II Receptor Blockers (ARBs) treatment interruption in patients with chronic comorbidities appears unjustified. The rollout of COVID-19 vaccines provides opportunities to study the effects of different COVID-19 vaccines on ACE2 in patients on treatment with ACEi/ARB.
Supramolecular Polymorphism of (G4C2)n Repeats Associated with ALS and FTD
Authors: Potrč Melani , Sebastián Nerea , Škarabot Miha , Drevenšek-Olenik Irena , Spindler Lea
Published: April 2021

Guanine-rich DNA sequences self-assemble into highly stable fourfold structures known as DNA-quadruplexes (or G-quadruplexes). G-quadruplexes have furthermore the tendency to associate into one-dimensional supramolecular aggregates termed G-wires. We studied the formation of G-wires in solutions of the sequences d(G4C2)n with n = 1, 2, and 4. The d(G4C2)n repeats, which are associated with some fatal neurological disorders, especially amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), represent a challenging research topic due to their extensive structural polymorphism. We used dynamic light scattering (DLS) to measure translational diffusion coefficients and consequently resolve the length of the larger aggregates formed in solution. We found that all three sequences assemble into longer structures than previously reported. The d(G4C2) formed extremely long G-wires with lengths beyond 80 nm. The d(G4C2)2 formed a relatively short stacked dimeric quadruplex, while d(G4C2)4 formed multimers corresponding to seven stacked intramolecular quadruplexes. Profound differences between the multimerization properties of the investigated sequences were also confirmed by the AFM imaging of surface films. We propose that π-π stacking of the basic G-quadruplex units plays a vital role in the multimerization mechanism, which might be relevant for transformation from the regular medium-length to disease-related long d(G4C2)n repeats.
Supramolecular Nanofibers from Collagen-Mimetic Peptides Bearing Various Aromatic Groups at N-Termini via Hierarchical Self-Assembly
Authors: Koga Tomoyuki , Kingetsu Shinya , Higashi Nobuyuki
Published: April 2021

Self-assembly of artificial peptides has been widely studied for constructing nanostructured materials, with numerous potential applications in the nanobiotechnology field. Herein, we report the synthesis and hierarchical self-assembly of collagen-mimetic peptides (CMPs) bearing various aromatic groups at the N-termini, including 2-naphthyl, 1-naphtyl, anthracenyl, and pyrenyl groups, into nanofibers. The CMPs (R-(GPO)n: n > 4) formed a triple helix structure in water at 4 °C, as confirmed via CD analyses, and their conformations were more stable with increasing hydrophobicity of the terminal aromatic group and peptide chain length. The resulting pre-organized triple helical CMPs showed diverse self-assembly into highly ordered nanofibers, reflecting their slight differences in hydrophobic/hydrophilic balance and configuration of aromatic templates. TEM analysis demonstrated that 2Np-CMPn (n = 6 and 7) and Py-CMP6 provided well-developed natural collagen-like nanofibers and An-CMPn (n = 5–7) self-assembled into rod-like micelle fibers. On the other hand, 2Np-CMP5 and 1Np-CMP6 were unable to form nanofibers under the same conditions. Furthermore, the Py-CMP6 nanofiber was found to encapsulate a guest hydrophobic molecule, Nile red, and exhibited unique emission behavior based on the specific nanostructure. In addition to the ability of CMPs to bind small molecules, their controlled self-assembly enables their versatile utilization in drug delivery and wavelength-conversion nanomaterials.
Cell Lysis Directed by SulA in Response to DNA Damage in Escherichia coli
Authors: Murata Masayuki , Nakamura Keiko , Kosaka Tomoyuki , Ota Natsuko , Osawa Ayumi , Muro Ryunosuke , Fujiyama Kazuya , Oshima Taku , Mori Hirotada , Wanner Barry L. , Yamada Mamoru
Published: April 2021

The SOS response is induced upon DNA damage and the inhibition of Z ring formation by the product of the sulA gene, which is one of the LexA-regulated genes, allows time for repair of damaged DNA. On the other hand, severely DNA-damaged cells are eliminated from cell populations. Overexpression of sulA leads to cell lysis, suggesting SulA eliminates cells with unrepaired damaged DNA. Transcriptome analysis revealed that overexpression of sulA leads to up-regulation of numerous genes, including soxS. Deletion of soxS markedly reduced the extent of cell lysis by sulA overexpression and soxS overexpression alone led to cell lysis. Further experiments on the SoxS regulon suggested that LpxC is a main player downstream from SoxS. These findings suggested the SulA-dependent cell lysis (SDCL) cascade as follows: SulA→SoxS→LpxC. Other tests showed that the SDCL cascade pathway does not overlap with the apoptosis-like and mazEF cell death pathways.
The Roles of Nitric Oxide Synthase/Nitric Oxide Pathway in the Pathology of Vascular Dementia and Related Therapeutic Approaches
Authors: Zhu Han-Yan , Hong Fen-Fang , Yang Shu-Long
Published: April 2021

Vascular dementia (VaD) is the second most common form of dementia worldwide. It is caused by cerebrovascular disease, and patients often show severe impairments of advanced cognitive abilities. Nitric oxide synthase (NOS) and nitric oxide (NO) play vital roles in the pathogenesis of VaD. The functions of NO are determined by its concentration and bioavailability, which are regulated by NOS activity. The activities of different NOS subtypes in the brain are partitioned. Pathologically, endothelial NOS is inactivated, which causes insufficient NO production and aggravates oxidative stress before inducing cerebrovascular endothelial dysfunction, while neuronal NOS is overactive and can produce excessive NO to cause neurotoxicity. Meanwhile, inflammation stimulates the massive expression of inducible NOS, which also produces excessive NO and then induces neuroinflammation. The vicious circle of these kinds of damage having impacts on each other finally leads to VaD. This review summarizes the roles of the NOS/NO pathway in the pathology of VaD and also proposes some potential therapeutic methods that target this pathway in the hope of inspiring novel ideas for VaD therapeutic approaches.
Advances in the Development Ubiquitin-Specific Peptidase (USP) Inhibitors
Authors: Chen Shiyao , Liu Yunqi , Zhou Huchen
Published: April 2021

Ubiquitylation and deubiquitylation are reversible protein post-translational modification (PTM) processes involving the regulation of protein degradation under physiological conditions. Loss of balance in this regulatory system can lead to a wide range of diseases, such as cancer and inflammation. As the main members of the deubiquitinases (DUBs) family, ubiquitin-specific peptidases (USPs) are closely related to biological processes through a variety of molecular signaling pathways, including DNA damage repair, p53 and transforming growth factor-β (TGF-β) pathways. Over the past decade, increasing attention has been drawn to USPs as potential targets for the development of therapeutics across diverse therapeutic areas. In this review, we summarize the crucial roles of USPs in different signaling pathways and focus on advances in the development of USP inhibitors, as well as the methods of screening and identifying USP inhibitors.
Liquid Biomarkers for Improved Diagnosis and Classification of CNS Tumors
Authors: Bunda Severa , Zuccato Jeffrey A. , Voisin Mathew R. , Wang Justin Z. , Nassiri Farshad , Patil Vikas , Mansouri Sheila , Zadeh Gelareh
Published: April 2021

Liquid biopsy, as a non-invasive technique for cancer diagnosis, has emerged as a major step forward in conquering tumors. Current practice in diagnosis of central nervous system (CNS) tumors involves invasive acquisition of tumor biopsy upon detection of tumor on neuroimaging. Liquid biopsy enables non-invasive, rapid, precise and, in particular, real-time cancer detection, prognosis and treatment monitoring, especially for CNS tumors. This approach can also uncover the heterogeneity of these tumors and will likely replace tissue biopsy in the future. Key components of liquid biopsy mainly include circulating tumor cells (CTC), circulating tumor nucleic acids (ctDNA, miRNA) and exosomes and samples can be obtained from the cerebrospinal fluid, plasma and serum of patients with CNS malignancies. This review covers current progress in application of liquid biopsies for diagnosis and monitoring of CNS malignancies.
Polymeric Scaffolds: Design, Processing, and Biomedical Application
Authors: Dobrzyński Piotr , Pamuła Elżbieta
Published: April 2021

Tissue engineering is a fascinating and multidisciplinary field of science [...]
BMP Signaling Interferes with Optic Chiasm Formation and Retinal Ganglion Cell Pathfinding in Zebrafish
Authors: Knickmeyer Max D. , Mateo Juan L. , Heermann Stephan
Published: April 2021

Decussation of axonal tracts is an important hallmark of vertebrate neuroanatomy resulting in one brain hemisphere controlling the contralateral side of the body and also computing the sensory information originating from that respective side. Here, we show that BMP interferes with optic chiasm formation and RGC pathfinding in zebrafish. Experimental induction of BMP4 at 15 hpf results in a complete ipsilateral projection of RGC axons and failure of commissural connections of the forebrain, in part as the result of an interaction with shh signaling, transcriptional regulation of midline guidance cues and an affected optic stalk morphogenesis. Experimental induction of BMP4 at 24 hpf, resulting in only a mild repression of forebrain shh ligand expression but in a broad expression of pax2a in the diencephalon, does not per se prevent RGC axons from crossing the midline. It nevertheless shows severe pathologies of RGC projections e.g., the fasciculation of RGC axons with the ipsilateral optic tract resulting in the innervation of one tectum by two eyes or the projection of RGC axons in the direction of the contralateral eye.
The Anti-Cancer Effects of a Zotarolimus and 5-Fluorouracil Combination Treatment on A549 Cell-Derived Tumors in BALB/c Nude Mice
Authors: Wu Ching-Feng , Wu Ching-Yang , Chiou Robin Y.-Y. , Yang Wei-Cheng , Lin Chuen-Fu , Wang Chao-Min , Hou Po-Hsun , Lin Tzu-Chun , Kuo Chan-Yen , Chang Geng-Ruei
Published: April 2021

Zotarolimus is a semi-synthetic derivative of rapamycin and a novel immunosuppressive agent used to prevent graft rejection. The pharmacological pathway of zotarolimus restricts the kinase activity of the mammalian target of rapamycin (mTOR), which potentially leads to reductions in cell division, cell growth, cell proliferation, and inflammation. These pathways have a critical influence on tumorigenesis. This study aims to examine the anti-tumor effect of zotarolimus or zotarolimus combined with 5-fluorouracil (5-FU) on A549 human lung adenocarcinoma cell line implanted in BALB/c nude mice by estimating tumor growth, apoptosis expression, inflammation, and metastasis. We established A549 xenografts in nude mice, following which we randomly divided the mice into four groups: control, 5-FU (100 mg/kg/week), zotarolimus (2 mg/kg/day), and zotarolimus combined with 5-FU. Compared the results with those for control mice, we found that mice treated with zotarolimus or zotarolimus combined with 5-FU retarded tumor growth; increased tumor apoptosis through the enhanced expression of cleaved caspase 3 and extracellular signal-regulated kinase (ERK) phosphorylation; decreased inflammation cytokines levels (e.g., IL-1β, TNF-α, and IL-6); reduced inflammation-related factors such as cyclooxygenase-2 (COX-2) protein and nuclear factor-κB (NF-κB) mRNA; enhanced anti-inflammation-related factors including IL-10 and inhibitor of NF-κB kinase α (IκBα) mRNA; and inhibited metastasis-related factors such as transforming growth factor β (TGF-β), CD44, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF). Notably, mice treated with zotarolimus combined with 5-FU had significantly retarded tumor growth, reduced tumor size, and increased tumor inhibition compared with the groups of mice treated with 5-FU or zotarolimus alone. The in vivo study confirmed that zotarolimus or zotarolimus combined with 5-FU could retard lung adenocarcinoma growth and inhibit tumorigenesis. Zotarolimus and 5-FU were found to have an obvious synergistic tumor-inhibiting effect on lung adenocarcinoma. Therefore, both zotarolimus alone and zotarolimus combined with 5-FU may be potential anti-tumor agents for treatment of human lung adenocarcinoma.
Artificial Intelligence in Bulk and Single-Cell RNA-Sequencing Data to Foster Precision Oncology
Authors: Del Giudice Marco , Peirone Serena , Perrone Sarah , Priante Francesca , Varese Fabiola , Tirtei Elisa , Fagioli Franca , Cereda Matteo
Published: April 2021

Artificial intelligence, or the discipline of developing computational algorithms able to perform tasks that requires human intelligence, offers the opportunity to improve our idea and delivery of precision medicine. Here, we provide an overview of artificial intelligence approaches for the analysis of large-scale RNA-sequencing datasets in cancer. We present the major solutions to disentangle inter- and intra-tumor heterogeneity of transcriptome profiles for an effective improvement of patient management. We outline the contributions of learning algorithms to the needs of cancer genomics, from identifying rare cancer subtypes to personalizing therapeutic treatments.
Modeling Neurotransmission: Computational Tools to Investigate Neurological Disorders
Authors: Gandolfi Daniela , Boiani Giulia Maria , Bigiani Albertino , Mapelli Jonathan
Published: April 2021

The investigation of synaptic functions remains one of the most fascinating challenges in the field of neuroscience and a large number of experimental methods have been tuned to dissect the mechanisms taking part in the neurotransmission process. Furthermore, the understanding of the insights of neurological disorders originating from alterations in neurotransmission often requires the development of (i) animal models of pathologies, (ii) invasive tools and (iii) targeted pharmacological approaches. In the last decades, additional tools to explore neurological diseases have been provided to the scientific community. A wide range of computational models in fact have been developed to explore the alterations of the mechanisms involved in neurotransmission following the emergence of neurological pathologies. Here, we review some of the advancements in the development of computational methods employed to investigate neuronal circuits with a particular focus on the application to the most diffuse neurological disorders.
The Role of Eph Receptors and Ephrins in Corneal Physiology and Diseases
Authors: Kaczmarek Radoslaw , Zimmer Katarzyna , Gajdzis Pawel , Gajdzis Malgorzata
Published: April 2021

The cornea, while appearing to be simple tissue, is actually an extremely complex structure. In order for it to retain its biomechanical and optical properties, perfect organization of its cells is essential. Proper regeneration is especially important after injuries and in the course of various diseases. Eph receptors and ephrin are mainly responsible for the proper organization of tissues as well as cell migration and communication. In this review, we present the current state of knowledge on the role of Eph and ephrins in corneal physiology and diseases, in particular, we focused on the functions of the epithelium and endothelium. Since the role of Eph and ephrins in the angiogenesis process has been well established, we also analyzed their influence on conditions with corneal neovascularization.
Evaluating the Potential of Using Spodoptera litura Eggs for Mass-Rearing Telenomus remus, a Promising Egg Parasitoid of Spodoptera frugiperda
Authors: Chen Wanbin , Li Yuyan , Wang Mengqing , Mao Jianjun , Zhang Lisheng
Published: April 2021

Although Telenomus remus, a promising parasitoid of Spodoptera frugiperda, had been successfully reared on the eggs of Corcyra cephalonica in some countries, reports from China have argued that it is infeasible. Notably, studies from China have indicated that Spodoptera litura eggs could be a candidate host. Therefore, to further evaluate the potential of using S. litura eggs as hosts, we compared the development and parasitism of T. remus on the eggs of S. frugiperda and S. litura at temperatures between 20–32 °C. Our results showed that T. remus developed successfully on both host eggs at all of the tested temperatures, and the developmental duration and thermal requirements at each stage were similar between the two host species. The number of parasitized eggs was greater for S. litura than for S. frugiperda. Meanwhile, the emergence rate exceeded 86.6%, and it was significantly higher for S. litura than that for S. frugiperda, except at 29 °C. This study is the first time estimating the thermal requirements of T. remus at each stage. Moreover, we also recorded the morphological characteristics of T. remus at each stage. Our results demonstrate that S. litura eggs are more suitable than S. frugiperda eggs as an alternative host for the mass-rearing of T. remus in China. Understanding the thermal requirements and biological parameters contributes greatly to predicting the generation time and providing a reference for the mass-rearing and storage of the parasitoid.
Designing Aedes (Diptera: Culicidae) Mosquito Traps: The Evolution of the Male Aedes Sound Trap by Iterative Evaluation
Authors: Staunton Kyran M. , Liu Jianyi , Townsend Michael , Desnoyer Mark , Howell Paul , Crawford Jacob E. , Xiang Wei , Snoad Nigel , Burkot Thomas R. , Ritchie Scott A.
Published: April 2021

Effective surveillance of Aedes aegypti (Linnaeus, Diptera: Culicidae) is critical to monitoring the impact of vector control measures when mitigating disease transmission by this species. There are benefits to deploying male-specific traps, particularly when a high level of catch-specificity is desired. Here, the rationale behind the developmental process of an entirely new trap which uses a sound lure to capture male Ae. aegypti, the male Aedes sound trap (MAST), is presented as a target product profile with findings from developmental trials of key trap components and performance. Trial results suggest that the presence of a black base associated with the trap influenced male catches as did variations in size of this base, to a degree. Trap entrance shape didn’t influence catch rates, but entrance size did. No significant differences in catch rates were found when sound lures were set to intermittent or continuous playbacks, at volumes between 63–74 dB or frequencies of 450 Hz compared to 500 Hz. Additionally, adult males aged 3 days post-eclosion, were less responsive to sound lures set to 500 Hz than those 4 or 6 days old. Lastly, almost no males were caught when the MAST directly faced continual winds of 1.5 ms−1, but males were captured at low rates during intermittent winds, or if the trap faced away from the wind. The developmental process to optimising this trap is applicable to the development of alternate mosquito traps beyond Aedes sound traps and provides useful information towards the improved surveillance of these disease vectors.
The Role of Cell Tracing and Fate Mapping Experiments in Cardiac Outflow Tract Development, New Opportunities through Emerging Technologies
Authors: Peterson Joshua C. , Kelder Tim P. , Goumans Marie José T. H. , Jongbloed Monique R. M. , DeRuiter Marco C.
Published: April 2021

Whilst knowledge regarding the pathophysiology of congenital heart disease (CHDs) has advanced greatly in recent years, the underlying developmental processes affecting the cardiac outflow tract (OFT) such as bicuspid aortic valve, tetralogy of Fallot and transposition of the great arteries remain poorly understood. Common among CHDs affecting the OFT, is a large variation in disease phenotypes. Even though the different cell lineages contributing to OFT development have been studied for many decades, it remains challenging to relate cell lineage dynamics to the morphologic variation observed in OFT pathologies. We postulate that the variation observed in cellular contribution in these congenital heart diseases might be related to underlying cell lineage dynamics of which little is known. We believe this gap in knowledge is mainly the result of technical limitations in experimental methods used for cell lineage analysis. The aim of this review is to provide an overview of historical fate mapping and cell tracing techniques used to study OFT development and introduce emerging technologies which provide new opportunities that will aid our understanding of the cellular dynamics underlying OFT pathology.
Proximal Row Carpectomy with Total Scapoidectomy vs. Conventional Carpal Resection for ReMotion Total Wrist Arthroplasty
Authors: Froschauer Stefan M. , Holzbauer Matthias , Hager Dietmar , Kwasny Oskar , Duscher Dominik
Published: April 2021

High complication rates in total wrist arthroplasty (TWA) still lead to controversy in the medical literature, and novel methods for complication reduction are warranted. In the present retrospective cohort study, we compare the outcomes of the proximal row carpectomy (PRC) method including total scaphoidectomy (n = 22) to the manufacturer’s conventional carpal resection (CCR) technique, which retains the distal pole of the scaphoid (n = 25), for ReMotion prosthesis implantation in non-rheumatoid patients. Mean follow-up was 65.8 ± 19.8 and 80.0 ± 28.7 months, respectively. Pre- and postoperative clinical assessment included wrist flexion-extension and radial-ulnar deviation; Disability of Arm, Shoulder, and Hand scores; and pain via visual analogue scale. At final follow-up, grip strength and satisfaction were evaluated. All complications, re-operations, and revision surgeries were noted. Clinical complications were significantly lower in the PRC group (p = 0.010). Radial impaction was detected as the most frequent complication in the CCR group (n = 10), while no PRC patients suffered from this complication (p = 0.0008). Clinical assessment, grip strength measurements, and the log rank test evaluating the re-operation as well as revision function showed no significant difference. All functional parameters significantly improved compared to preoperative values in both cohorts. In conclusion, we strongly recommend PRC for ReMotion prosthesis implantation.
Rota-Lithotripsy—A Novel Bail-Out Strategy for Calcified Coronary Lesions in Acute Coronary Syndrome. The First-in-Man Experience
Authors: Włodarczak Adrian , Rola Piotr , Barycki Mateusz , Kulczycki Jan Jakub , Szudrowicz Marek , Lesiak Maciej , Doroszko Adrian
Published: April 2021

Heavy calcification remains one of the greatest challenges in the treatment of coronary artery disease (CAD), especially in subjects with an acute coronary syndrome (ACS). In the present case series study of high-risk patients with ACS, including both STEMI and NSTEMI, we performed a rota-lithotripsy—a combination of rotational atherectomy with subsequent intravascular lithotripsy—as a novel bail-out strategy to facilitate stent delivery in a tortuous calcified coronary artery.
Using Machine Learning to Predict Invasive Bacterial Infections in Young Febrile Infants Visiting the Emergency Department
Authors: Chiu I-Min , Cheng Chi-Yung , Zeng Wun-Huei , Huang Ying-Hsien , Lin Chun-Hung Richard
Published: April 2021

Background: The aim of this study was to develop and evaluate a machine learning (ML) model to predict invasive bacterial infections (IBIs) in young febrile infants visiting the emergency department (ED). Methods: This retrospective study was conducted in the EDs of three medical centers across Taiwan from 2011 to 2018. We included patients age in 0–60 days who were visiting the ED with clinical symptoms of fever. We developed three different ML algorithms, including logistic regression (LR), supportive vector machine (SVM), and extreme gradient boosting (XGboost), comparing their performance at predicting IBIs to a previous validated score system (IBI score). Results: During the study period, 4211 patients were included, where 126 (3.1%) had IBI. A total of eight, five, and seven features were used in the LR, SVM, and XGboost through the feature selection process, respectively. The ML models can achieve a better AUROC value when predicting IBIs in young infants compared with the IBI score (LR: 0.85 vs. SVM: 0.84 vs. XGBoost: 0.85 vs. IBI score: 0.70, p-value < 0.001). Using a cost sensitive learning algorithm, all ML models showed better specificity in predicting IBIs at a 90% sensitivity level compared to an IBI score > 2 (LR: 0.59 vs. SVM: 0.60 vs. XGBoost: 0.57 vs. IBI score >2: 0.43, p-value < 0.001). Conclusions: All ML models developed in this study outperformed the traditional scoring system in stratifying low-risk febrile infants after the standardized sensitivity level.
The Serum Uric Acid Level Is Related to the More Severe Renal Histopathology of Female IgA Nephropathy Patients
Authors: Choi Won Jung , Hong Yu A , Min Ji Won , Koh Eun Sil , Kim Hyung Duk , Ban Tae Hyun , Kim Young Soo , Kim Yong Kyun , Shin Seok Joon , Kim Seok Young , Kim Young Ok , Yang Chul Woo , Chang Yoon-Kyung
Published: April 2021

Hyperuricemia is a significant risk factor for cardiovascular morbidity and chronic kidney disease progression. IgA nephropathy (IgAN) is a well-known primary glomerular nephropathy. Hyperuricemia is associated with a poor prognosis in IgAN patients. We evaluated the association of hyperuricemia with the histopathological severity of IgAN in male and female patients; 658 patients diagnosed with IgAN via kidney biopsy were initially included. Baseline patient data were collected by eight university hospitals affiliated with the College of Medicine of the Catholic University of Korea. Pathological features were independently evaluated by eight expert pathologists working in the hospitals, and the consensus was reached. Of the initial 658 patients, 517 were finally included (253 males and 264 females). Hyperuricemia was defined as a serum uric acid (UA) level >7.0 mg/dL for males and >5.6 mg/dL for females; 108 (42.7%) males and 95 (35.9%) females exhibited hyperuricemia. Compared to the patients with normal UA levels, the global glomerulosclerosis, segmental sclerosis, mesangial matrix expansion (MME), endocapillary proliferation (ECP), interstitial fibrosis (IF), and tubular atrophy (TA) scores were higher in hyperuricemic males and females. In multivariable linear regression, the serum UA level correlated significantly with the MME, ECP, IF, and TA scores of female IgAN patients only.
Detection of the Anaerobic Threshold in Endurance Sports: Validation of a New Method Using Correlation Properties of Heart Rate Variability
Authors: Rogers Bruce , Giles David , Draper Nick , Mourot Laurent , Gronwald Thomas
Published: April 2021

Past attempts to define an anaerobic threshold (AnT) have relied upon gas exchange kinetics, lactate testing and field-based evaluations. DFA a1, an index of heart rate (HR) variability (HRV) fractal correlation properties, has been shown to decrease with exercise intensity. The intent of this study is to investigate whether the AnT derived from gas exchange is associated with the transition from a correlated to uncorrelated random HRV pattern signified by a DFA a1 value of 0.5. HRV and gas exchange data were obtained from 15 participants during an incremental treadmill run. Comparison of the HR reached at the second ventilatory threshold (VT2) was made to the HR reached at a DFA a1 value of 0.5 (HRVT2). Based on Bland–Altman analysis and linear regression, there was strong agreement between VT2 and HRVT2 measured by HR (r = 0.78, p < 0.001). Mean VT2 was reached at a HR of 174 (±12) bpm compared to mean HRVT2 at a HR of 171 (±16) bpm. In summary, the HR associated with a DFA a1 value of 0.5 on an incremental treadmill ramp was closely related to that of the HR at the VT2 derived from gas exchange analysis. A distinct numerical value of DFA a1 representing an uncorrelated, random interbeat pattern appears to be associated with the VT2 and shows potential as a noninvasive marker for training intensity distribution and performance status.
Determination of the Round Window Niche Anatomy Using Cone Beam Computed Tomography Imaging as Preparatory Work for Individualized Drug-Releasing Implants
Authors: Matin Farnaz , Gao Ziwen , Repp Felix , John Samuel , Lenarz Thomas , Scheper Verena
Published: April 2021

Modern therapy of inner ear disorders is increasingly shifting to local drug delivery using a growing number of pharmaceuticals. Access to the inner ear is usually made via the round window membrane (RWM), located in the bony round window niche (RWN). We hypothesize that the individual shape and size of the RWN have to be taken into account for safe reliable and controlled drug delivery. Therefore, we investigated the anatomy and its variations. Cone beam computed tomography (CBCT) images of 50 patients were analyzed. Based on the reconstructed 3D volumes, individual anatomies of the RWN, RWM, and bony overhang were determined by segmentation using 3D SlicerTM with a custom build plug-in. A large individual anatomical variability of the RWN with a mean volume of 4.54 mm3 (min 2.28 mm3, max 6.64 mm3) was measured. The area of the RWM ranged from 1.30 to 4.39 mm2 (mean: 2.93 mm2). The bony overhang had a mean length of 0.56 mm (min 0.04 mm, max 1.24 mm) and the shape was individually very different. Our data suggest that there is a potential for individually designed and additively manufactured RWN implants due to large differences in the volume and shape of the RWN.
Improved Current Estimates from Spar Buoy-Mounted ADCP Measurement Station: A Case Study in the Ligurian Sea
Authors: Bordone Andrea , Ciuffardi Tiziana , Raiteri Giancarlo , Schirone Antonio , Bozzano Roberto , Pensieri Sara , Pennecchi Francesca , Picco Paola
Published: April 2021

Current measurements in the open sea are generally acquired by Acoustic Doppler Current Profilers (ADCPs). In the case of ADCPs mounted on spar buoy, current profiles require to be post-processed, to properly take into account the buoy influence: in fact, ADCP compass may reflect alterations induced by the metal structure of the buoy and apparent currents can occur due to the large displacement of the platform. Uncertainty analysis is finally required to properly consider both these effects and to compute robust velocity estimates. A new methodology is tested for a measurement station in the Ligurian Sea, where an ADCP was mounted on the surface buoy of the W1-M3A (Western 1 Mediterranean Moored Multisensor Array) oceanographic observatory, facing upwards at the depth of about 40 m. Marine current numerical models and historical data in the area have been used as a basis for comparison to test the consistency of the proposed method. A very good agreement is obtained. Only minor discrepancies are reported (e.g., monthly averages from the reference model slightly underestimate the west-east current component along the entire profile), but, in general, the application of the proposed methodology ensures that the spar buoy-mounted ADCP system is able to provide reliable measurements for oceanographic studies and validation of 3D hydrodynamic models.
Spatio-Temporal Hydrological Model Structure and Parametrization Analysis
Authors: Farrag Mostafa , Perez Gerald Corzo , Solomatine Dimitri
Published: April 2021

Many grid-based spatial hydrological models suffer from the complexity of setting up a coherent spatial structure to calibrate such a complex, highly parameterized system. There are essential aspects of model-building to be taken into account: spatial resolution, the routing equation limitations, and calibration of spatial parameters, and their influence on modeling results, all are decisions that are often made without adequate analysis. In this research, an experimental analysis of grid discretization level, an analysis of processes integration, and the routing concepts are analyzed. The HBV-96 model is set up for each cell, and later on, cells are integrated into an interlinked modeling system (Hapi). The Jiboa River Basin in El Salvador is used as a case study. The first concept tested is the model structure temporal responses, which are highly linked to the runoff dynamics. By changing the runoff generation model description, we explore the responses to events. Two routing models are considered: Muskingum, which routes the runoff from each cell following the river network, and Maxbas, which routes the runoff directly to the outlet. The second concept is the spatial representation, where the model is built and tested for different spatial resolutions (500 m, 1 km, 2 km, and 4 km). The results show that the spatial sensitivity of the resolution is highly linked to the routing method, and it was found that routing sensitivity influenced the model performance more than the spatial discretization, and allowing for coarser discretization makes the model simpler and computationally faster. Slight performance improvement is gained by using different parameters’ values for each cell. It was found that the 2 km cell size corresponds to the least model error values. The proposed hydrological modeling codes have been published as open-source.
Full Duplex Physical and MAC Layer-Based Underwater Wireless Communication Systems and Protocols: Opportunities, Challenges, and Future Directions
Authors: Songzuo Liu , Iqbal Basit , Khan Imran Ullah , Ahmed Niaz , Qiao Gang , Zhou Feng
Published: April 2021

Underwater wireless communication has gained a great deal of attention in the last couple of decades because of its applications in the military, industrial, and monitoring sectors. Despite the extreme physical and MAC layer difficulties, acoustics are used for various applications among the various modes of underwater communication technologies used. While significant research efforts have been made to address these issues, the bottleneck remains in achieving high bandwidth, high throughputs, and data rate. Researchers have begun to look into full duplex (FD) implementation to improve bandwidth efficiency and increase data rate and throughput. Users can send and receive data simultaneously over the FD links, maximizing bandwidth utilization and increasing throughput. As a result, we thoroughly reviewed various FD physical layered UWAC systems and MAC layered protocols for underwater communication. The various problems that the aforementioned systems and protocols have faced, as well as the solutions suggested in previous works to solve each problem, are also highlighted. Various metrics are used to compare the performance of various physical layered FD systems and FD MAC protocols. We also explore some of the open research questions in these FD-physical layered and MAC layered protocols, as well as future research directions. Based on ample information, we suggest a cross-layered architecture based on various IBFD-SI cancellations, DA-CSMA, and FD-MAC protocols. This review provides a broad view of the current FD physical and MAC layered protocols based on acoustic communication, as well as recommendations.
Multi-Platform, High-Resolution Study of a Complex Coastal System: The TOSCA Experiment in the Gulf of Trieste
Authors: Querin Stefano , Cosoli Simone , Gerin Riccardo , Laurent Célia , Malačič Vlado , Pristov Neva , Poulain Pierre-Marie
Published: April 2021

Although small in size, the Gulf of Trieste (GoT), a marginal coastal basin in the northern Adriatic Sea, is characterized by very complex dynamics and strong variability of its oceanographic conditions. In April–May 2012, a persistent, large-scale anticyclonic eddy was observed in the GoT. This event was captured by both High Frequency Radar (HFR) and Lagrangian drifter observations collected within the European MED TOSCA (Tracking Oil Spill and Coastal Awareness) project. The complexity of the system and the variety of forcing factors constitute major challenges from a numerical modeling perspective when it comes to simulating the observed features. In this study, we implemented a high-resolution hydrodynamic model in an attempt to reproduce and analyze the observed basin-wide eddy structure and determine its drivers. We adopted the Massachusetts Institute of Technology General Circulation Model (MITgcm), tailored for the GoT, nested into a large-scale simulation of the Adriatic Sea and driven by a tidal model, measured river freshwater discharge data and surface atmospheric forcing. Numerical results were qualitatively and quantitatively evaluated against HFR surface current maps, Lagrangian drifter trajectories and thermohaline data, showing good skills in reproducing the general circulation, but failing in accurately tracking the drifters. Model sensitivity to different forcing factors (wind, river and tides) was also assessed.