bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Mitochondrial Alterations in Aicardi–Goutières Patients Mutated in RNASEH2A and RNASEH2B Genes
Authors: Dragoni Francesca , Garau Jessica , Sproviero Daisy , Orcesi Simona , Varesio Costanza , De Siervi Silvia , Gagliardi Stella , Cereda Cristina , Pansarasa Orietta
Published: November 2022

Aicardi–Goutières syndrome (AGS) is a rare encephalopathy characterized by neurological and immunological features. Mitochondrial dysfunctions may lead to mitochondrial DNA (mtDNA) release and consequent immune system activation. We investigated the role of mitochondria and mtDNA in AGS pathogenesis by studying patients mutated in RNASEH2B and RNASEH2A genes. Lymphoblastoid cell lines (LCLs) from RNASEH2A- and RNASEH2B-mutated patients and healthy control were used. Transmission Electron Microscopy (TEM) and flow cytometry were used to assess morphological alterations, reactive oxygen species (ROS) production and mitochondrial membrane potential variations. Seahorse Analyzer was used to investigate metabolic alterations, and mtDNA oxidation and VDAC1 oligomerization were assessed by immunofluorescence. Western blot and RT-qPCR were used to quantify mtTFA protein and mtDNA release. Morphological alterations of mitochondria were observed in both mutated LCLs, and loss of physiological membrane potential was mainly identified in RNASEH2A LCLs. ROS production and 8-oxoGuanine levels were increased in RNASEH2B LCLs. Additionally, the VDAC1 signal was increased, suggesting a mitochondrial pore formation possibly determining mtDNA release. Indeed, higher cytoplasmic mtDNA levels were found in RNASEH2B LCLs. Metabolic alterations confirmed mitochondrial damage in both LCLs. Data highlighted mitochondrial alterations in AGS patients’ LCLs suggesting a pivotal role in AGS pathogenesis.
New TMA (4,6,4′-Trimethyl angelicin) Analogues as Anti-Inflammatory Agents in the Treatment of Cystic Fibrosis Lung Disease
Authors: Tupini Chiara , Chilin Adriana , Rossi Alice , De Fino Ida , Bragonzi Alessandra , D’Aversa Elisabetta , Cosenza Lucia Carmela , Vaccarin Christian , Sacchetti Gianni , Borgatti Monica , Tamanini Anna , Dechecchi Maria Cristina , Sanvito Francesca , Gambari Roberto , Cabrini Giulio , Lampronti Ilaria
Published: November 2022

A series of new-generation TMA (4,6,4′-trimethyl angelicin) analogues was projected and synthetized in order to ameliorate anti-inflammatory activity, with reduced or absent toxicity. Since the NF-κB transcription factor (TF) plays a critical role in the expression of IL-8 (Interluekin 8), a typical marker of lung inflammation in Cystic Fibrosis (CF), the use of agents able to interfere with the NF-κB pathway represents an interesting therapeutic strategy. Through preliminary EMSA experiments, we identified several new TMA derivatives able to inhibit the NF-κB/DNA complex. The selected active molecules were then analyzed to evaluate the anti-inflammatory effect using both Pseudomonas aeruginosa (PAO1) infection and TNF-alpha stimulus on the CF IB3-1 cell line. It was demonstrated that mainly two TMA analogues, GY971a mesylate salt (6-p-minophenyl-4,4′-dimethyl-angelicin) and GY964 (4-phenyl-6,4′-dimethyl-angelicin), were able to decrease the IL-8 gene expression. At the same time, these molecules were found to have no pro-apoptotic, mutagenic and phototoxic effects, facilitating our decision to test the efficacy in vivo by using a mouse model of acute P. aeruginosa lung infection. The anti-inflammatory effect of GY971a was confirmed in vivo; this derivative was able to deeply decrease the total number of inflammatory cells, the neutrophil count and the cytokine/chemokine profile in the P. aeruginosa acute infection model, without evident toxicity. Considering all the obtained and reported in vitro and in vivo pre-clinical results, GY971a seems to have interesting anti-inflammatory effects, modulating the NF-κB pathway, as well as the starting lead compound TMA, but without side effects.
DNA Sequence-Dependent Properties of Nucleosome Positioning in Regions of Distinct Chromatin States in Mouse Embryonic Stem Cells
Authors: Liu Guoqing , Zhang Zhi , Dong Biyu , Liu Jia
Published: November 2022

Chromatin architecture is orchestrated, and plays crucial roles during the developmental process by regulating gene expression. In embryonic stem cells (ESCs), three types of chromatin states, including active, repressive and poised states, were previously identified and characterized with specific chromatin modification marks and different transcription activity, but it is largely unknown how nucleosomes are organized in these chromatin states. In this study, by using a DNA deformation energy model, we investigated the sequence-dependent nucleosome organization within the chromatin states in mouse ESCs. The results revealed that: (1) compared with poised genes, active genes are characterized with a higher level of nucleosome occupancy around their transcription start sites (TSS) and transcription termination sites (TTS), and both types of genes do not have a nucleosome-depleted region at their TTS, contrasting with the MNase-seq based result; (2) based on our previous DNA bending energy model, we developed an improved model capable of predicting both rotational positioning and nucleosome occupancy determined by a chemical mapping approach; (3) DNA bending-energy-based analyses demonstrated that the fragile nucleosomes positioned at both gene ends could be explained largely by enhanced rotational positioning signals encoded in DNA, but nucleosome phasing around the TSS of active genes was not determined by sequence preference; (4) the nucleosome occupancy landscape around the binding sites of some developmentally important transcription factors known to bind with different chromatin contexts, was also successfully predicted; (5) the difference of nucleosome occupancy around the TSS between CpG-rich and CpG-poor promoters was partly captured by our sequence-dependent model. Taken together, by developing an improved deformation-energy-based model, we revealed some sequence-dependent properties of the nucleosome arrangements in regions of distinct chromatin states in mouse ESCs.
Modeling RTT Syndrome by iPSC-Derived Neurons from Male and Female Patients with Heterogeneously Severe Hot-Spot MECP2 Variants
Authors: Perego Sara , Alari Valentina , Pietra Gianluca , Lamperti Andrea , Vimercati Alessandro , Camporeale Nicole , Garzo Maria , Cogliati Francesca , Milani Donatella , Vignoli Aglaia , Peron Angela , Larizza Lidia , Pizzorusso Tommaso , Russo Silvia
Published: November 2022

Rett syndrome caused by MECP2 variants is characterized by a heterogenous clinical spectrum accounted for in 60% of cases by hot-spot variants. Focusing on the most frequent variants, we generated in vitro iPSC-neurons from the blood of RTT girls with p.Arg133Cys and p.Arg255*, associated to mild and severe phenotype, respectively, and of an RTT male harboring the close to p.Arg255*, p.Gly252Argfs*7 variant. Truncated MeCP2 proteins were revealed by Western blot and immunofluorescence analysis. We compared the mutant versus control neurons at 42 days for morphological parameters and at 120 days for electrophysiology recordings, including girls’ isogenic clones. A precocious reduced morphological complexity was evident in neurons with truncating variants, while in p.Arg133Cys neurons any significant differences were observed in comparison with the isogenic wild-type clones. Reduced nuclear size and branch number show up as the most robust biomarkers. Patch clamp recordings on mature neurons allowed the assessment of cell biophysical properties, V-gated currents, and spiking pattern in the mutant and control cells. Immature spiking, altered cell capacitance, and membrane resistance of RTT neurons, were particularly pronounced in the Arg255* and Gly252Argfs*7 mutants. The overall results indicate that the specific markers of in vitro cellular phenotype mirror the clinical severity and may be amenable to drug testing for translational purposes.
From Nucleus to Membrane: A Subcellular Map of the N-Acetylation Machinery in Plants
Authors: Pożoga Marlena , Armbruster Laura , Wirtz Markus
Published: November 2022

N-terminal acetylation (NTA) is an ancient protein modification conserved throughout all domains of life. N-terminally acetylated proteins are present in the cytosol, the nucleus, the plastids, mitochondria and the plasma membrane of plants. The frequency of NTA differs greatly between these subcellular compartments. While up to 80% of cytosolic and 20–30% of plastidic proteins are subject to NTA, NTA of mitochondrial proteins is rare. NTA alters key characteristics of proteins such as their three-dimensional structure, binding properties and lifetime. Since the majority of proteins is acetylated by five ribosome-bound N-terminal acetyltransferases (Nats) in yeast and humans, NTA was long perceived as an exclusively co-translational process in eukaryotes. The recent characterization of post-translationally acting plant Nats, which localize to the plasma membrane and the plastids, has challenged this view. Moreover, findings in humans, yeast, green algae and higher plants uncover differences in the cytosolic Nat machinery of photosynthetic and non-photosynthetic eukaryotes. These distinctive features of the plant Nat machinery might constitute adaptations to the sessile lifestyle of plants. This review sheds light on the unique role of plant N-acetyltransferases in development and stress responses as well as their evolution-driven adaptation to function in different cellular compartments.
Probiogenomic In-Silico Analysis and Safety Assessment of Lactiplantibacillus plantarum DJF10 Strain Isolated from Korean Raw Milk
Authors: Kandasamy Sujatha , Yoo Jayeon , Yun Jeonghee , Lee Kil-Ho , Kang Han-Byul , Kim Ji-Eun , Oh Mi-Hwa , Ham Jun-Sang
Published: November 2022

The whole genome sequence of Lactiplantibacillus plantarum DJF10, isolated from Korean raw milk, is reported, along with its genomic analysis of probiotics and safety features. The genome consists of 29 contigs with a total length of 3,385,113 bp and a GC content of 44.3%. The average nucleotide identity and whole genome phylogenetic analysis showed the strain belongs to Lactiplantibacillus plantarum with 99% identity. Genome annotation using Prokka predicted a total of 3235 genes, including 3168 protein-coding sequences (CDS), 59 tRNAs, 7 rRNAs and 1 tmRNA. The functional annotation results by EggNOG and KEGG showed a high number of genes associated with genetic information and processing, transport and metabolism, suggesting the strain’s ability to adapt to several environments. Various genes conferring probiotic characteristics, including genes related to stress adaptation to the gastrointestinal tract, biosynthesis of vitamins, cell adhesion and production of bacteriocins, were identified. The CAZyme analysis detected 98 genes distributed under five CAZymes classes. In addition, several genes encoding carbohydrate transport and metabolism were identified. The genome also revealed the presence of insertion sequences, genomic islands, phage regions, CRISPR-cas regions, and the absence of virulence and toxin genes. However, the presence of hemolysin and antibiotic-resistance-related genes detected in the KEGG search needs further experimental validation to confirm the safety of the strain. The presence of two bacteriocin clusters, sactipeptide and plantaricin J, as detected by the BAGEL 4 webserver, confer the higher antimicrobial potential of DJF10. Altogether, the analyses in this study performed highlight this strain’s functional characteristics. However, further in vitro and in vivo studies are required on the safety assurance and potential application of L. plantarum DJF10 as a probiotic agent.
HeLa Cervical Cancer Cells Are Maintained by Nephronophthisis 3-Associated Primary Cilium Formation via ROS-Induced ERK and HIF-1α Activation under Serum-Deprived Normoxic Condition
Authors: Lee Jae-Wook , Cho Jun-Yeong , Thuy Pham Xuan , Moon Eun-Yi
Published: November 2022

The primary cilium (PC) is a microtubule-based antenna-like organelle projecting from the surface of the cell membrane. We previously reported that PC formation could be regulated by nephronophthisis 3 (NPHP3) expression followed by its interaction with thymosin β4. Here, we investigated whether cancer cell viability is regulated by NPHP3-mediated PC formation. The total and viable cell number were reduced by incubating cells under serum deprivation (SD) without fetal bovine serum (-FBS). PC frequency was increased by SD which enhanced NPHP3 expression and hypoxia inducible factor (HIF)-1α. The role of HIF-1α on NPHP3 expression and PC formation was confirmed by the binding of HIF-1α to the NPHP3 promoter and siRNA-based inhibition of HIF-1α (siHIF-1α), respectively. HIF-1α-stabilizing dimethyloxallyl glycine (DMOG) and hypoxic conditions increased NPHP3 expression and PC formation. In addition, as SD elevated the reactive oxygen species (ROS), PC frequency and NPHP3 expression were inhibited by a treatment with N-acetylcysteine (NAC), a ROS scavenger. PC formation was increased by H2O2 treatment, which was inhibited by siHIF-1α. The inhibition of ERK with P98059 decreased the frequency of PC formation and NPHP3 expression. Cell viability was reduced by a treatment with ciliobrevin A (CilioA) to inhibit PC formation, which was re-affirmed by using PC-deficient IFT88−/− cells. Taken together, the results imply that PC formation in cancer cells could be controlled by NPHP3 expression through ROS-induced HIF-1α and ERK activation under SD conditions. It suggests that cancer cell viability under SD conditions could be maintained by NPHP3 expression to regulate PC formation.
Genome-Wide Identification and Analysis of FKBP Gene Family in Wheat (Triticum asetivum)
Authors: Ge Qiang , Peng Peipei , Cheng Mingyue , Meng Yanjun , Cao Yuan , Zhang Shuya , Long Yu , Li Gezi , Kang Guozhang
Published: November 2022

FK506-binding protein (FKBP) genes have been found to play vital roles in plant development and abiotic stress responses. However, limited information is available about this gene family in wheat (Triticum aestivum L.). In this study, a total of 64 FKBP genes were identified in wheat via a genome-wide analysis involving a homologous search of the latest wheat genome data, which was unevenly distributed in 21 chromosomes, encoded 152 to 649 amino acids with molecular weights ranging from 16 kDa to 72 kDa, and was localized in the chloroplast, cytoplasm, nucleus, mitochondria, peroxisome and endoplasmic reticulum. Based on sequence alignment and phylogenetic analysis, 64 TaFKBPs were divided into four different groups or subfamilies, providing evidence of an evolutionary relationship with Aegilops tauschii, Brachypodium distachyon, Triticum dicoccoides, Arabidopsis thaliana and Oryza sativa. Hormone-related, abiotic stress-related and development-related cis-elements were preferentially presented in promoters of TaFKBPs. The expression levels of TaFKBP genes were investigated using transcriptome data from the WheatExp database, which exhibited tissue-specific expression patterns. Moreover, TaFKBPs responded to drought and heat stress, and nine of them were randomly selected for validation by qRT-PCR. Yeast cells expressing TaFKBP19-2B-2 or TaFKBP18-6B showed increased influence on drought stress, indicating their negative roles in drought tolerance. Collectively, our results provide valuable information about the FKBP gene family in wheat and contribute to further characterization of FKBPs during plant development and abiotic stress responses, especially in drought stress.
Sex Differences in Neuropathy: The Paradigmatic Case of MetFormin
Authors: De Angelis Federica , Vacca Valentina , Tofanicchio Jessica , Strimpakos Georgios , Giacovazzo Giacomo , Pavone Flaminia , Coccurello Roberto , Marinelli Sara
Published: November 2022

As a widely prescribed anti-diabetic drug, metformin has been receiving novel attention for its analgesic potential. In the study of the complex etiology of neuropathic pain (NeP), male and female individuals exhibit quite different responses characterized by higher pain sensitivity and greater NeP incidence in women. This “gender gap” in our knowledge of sex differences in pain processing strongly limits the sex-oriented treatment of patients suffering from NeP. Besides, the current investigation of the analgesic potential of metformin has not addressed the “gender gap” problem. Hence, this study focuses on metformin and sex-dependent analgesia in a murine model of NeP induced by chronic constriction injury of the sciatic nerve. We investigated sexual dimorphism in signaling pathways involved by 7 days of metformin administration, such as changes in AMP-activated protein kinase and the positive regulation of autophagy machinery, discovering that metformin affected in a sexually dimorphic manner the immunological and inflammatory response to nerve lesion. These effects were complemented by morphological and adaptive changes occurring after peripheral nerve injury. Altogether these data can contribute to explaining a number of potential mechanisms responsible for the complete recovery from NeP found in male mice, as opposed to the failure of long-lasting recovery in female animals.
Electrolyzed–Reduced Water: Review II: Safety Concerns and Effectiveness as a Source of Hydrogen Water
Authors: LeBaron Tyler W. , Sharpe Randy , Ohno Kinji
Published: November 2022

Many studies demonstrate the safety of alkaline-electrolyzed–reduced water (ERW); however, several animal studies have reported significant tissue damage and hyperkalemia after drinking ERW. The mechanism responsible for these results remains unknown but may be due to electrode degradation associated with the production of higher pH, in which platinum nanoparticles and other metals that have harmful effects may leach into the water. Clinical studies have reported that, when ERW exceeds pH 9.8, some people develop dangerous hyperkalemia. Accordingly, regulations on ERW mandate that the pH of ERW should not exceed 9.8. It is recommended that those with impaired kidney function refrain from using ERW without medical supervision. Other potential safety concerns include impaired growth, reduced mineral, vitamin, and nutrient absorption, harmful bacterial overgrowth, and damage to the mucosal lining causing excessive thirst. Since the concentration of H2 in ERW may be well below therapeutic levels, users are encouraged to frequently measure the H2 concentration with accurate methods, avoiding ORP or ORP-based H2 meters. Importantly, although, there have been many people that have used high-pH ERW without any issues, additional safety research on ERW is warranted, and ERW users should follow recommendations to not ingest ERW above 9.8 pH.
hgtseq: A Standard Pipeline to Study Horizontal Gene Transfer
Authors: Carpanzano Simone , Santorsola Mariangela ,   nf-core community, Lescai Francesco
Published: November 2022

Horizontal gene transfer (HGT) is well described in prokaryotes: it plays a crucial role in evolution, and has functional consequences in insects and plants. However, less is known about HGT in humans. Studies have reported bacterial integrations in cancer patients, and microbial sequences have been detected in data from well-known human sequencing projects. Few of the existing tools for investigating HGT are highly automated. Thanks to the adoption of Nextflow for life sciences workflows, and to the standards and best practices curated by communities such as nf-core, fully automated, portable, and scalable pipelines can now be developed. Here we present nf-core/hgtseq to facilitate the analysis of HGT from sequencing data in different organisms. We showcase its performance by analysing six exome datasets from five mammals. Hgtseq can be run seamlessly in any computing environment and accepts data generated by existing exome and whole-genome sequencing projects; this will enable researchers to expand their analyses into this area. Fundamental questions are still open about the mechanisms and the extent or role of horizontal gene transfer: by releasing hgtseq we provide a standardised tool which will enable a systematic investigation of this phenomenon, thus paving the way for a better understanding of HGT.
O-GlcNAcylation of SIRT1 Protects against Cold Stress-Induced Skeletal Muscle Damage via Amelioration of Mitochondrial Homeostasis
Authors: Cao Yu , Zhang Meng , Li Ye , Lu Jingjing , Zhou Wanhui , Li Xiaoshuang , Shi Hao , Xu Bin , Li Shize
Published: November 2022

Cold stress disturbs cellular metabolic and energy homeostasis, which is one of the causes of stress-induced illnesses. O-GlcNAcylation is a nutrient-sensing pathway involved in a myriad of cellular processes. It plays a key role in metabolic homeostasis. Nevertheless, a specific sensing mechanism linking skeletal muscle to O-GlcNAcylation in cold stress is unknown. In this study, O-GlcNAcylation of SIRT1 was targeted to explore the mechanism of skeletal muscle adaptation to cold stress. Ogt mKO aggravated skeletal muscle fibrosis induced by cold stress. At the same time, Ogt gene deletion accelerated the homeostasis imbalance and oxidative stress of skeletal muscle mitochondria induced by cold stress. In vitro results showed that inhibition of SIRT1’s O-GlcNAcylation accelerated mild hypothermia induced mitochondrial homeostasis in mouse myogenic cells (C2C12 cells). However, overexpression of SIRT1’s O-GlcNAcylation improved the above phenomena. Thus, these results reveal a protective role of OGT-SIRT1 in skeletal muscle’s adaptation to cold stress, and our findings will provide new avenues to combat stress-induced diseases.
Bifunctional Temperature and Oxygen Dual Probe Based on Anthracene and Europium Complex Luminescence
Authors: Gálico Diogo Alves , Mazali Italo Odone , Sigoli Fernando Aparecido
Published: November 2022

In this work, we synthesized a polydimethylsiloxane membrane containing two emitter groups chemically attached to the membrane structure. For this, we attached the anthracene group and the [Eu(bzac)3] complex as blue and red emitters, respectively, in the matrix via hydrosilylation reactions. The synthesized membrane can be used as a bifunctional temperature and oxygen ratiometric optical probe by analyzing the effects that temperature changes and oxygen levels produce on the ratio of anthracene and europium(III) emission components. As a temperature probe, the system is operational in the 203–323 K range, with an observed maximum relative sensitivity of 2.06% K−1 at 290 K and temperature uncertainties below 0.1 K over all the operational range. As an oxygen probe, we evaluated the ratiometric response at 25, 30, 35, and 40 °C. These results show an interesting approach to obtaining bifunctional ratiometric optical probes and also suggest the presence of an anthracene → europium(III) energy transfer, even though there is no chemical bonding between species.
The Black Box of Cellular and Molecular Events of Plasmodium vivax Merozoite Invasion into Reticulocytes
Authors: Molina-Franky Jessica , Reyes César , Picón Jaimes Yelson Alejandro , Kalkum Markus , Patarroyo Manuel Alfonso
Published: November 2022

Plasmodium vivax is the most widely distributed malaria parasite affecting humans worldwide, causing ~5 million cases yearly. Despite the disease’s extensive burden, there are gaps in the knowledge of the pathophysiological mechanisms by which P. vivax invades reticulocytes. In contrast, this crucial step is better understood for P. falciparum, the less widely distributed but more often fatal malaria parasite. This discrepancy is due to the difficulty of studying P. vivax’s exclusive invasion of reticulocytes, which represent 1–2% of circulating cells. Its accurate targeting mechanism has not yet been clarified, hindering the establishment of long-term continuous in vitro culture systems. So far, only three reticulocyte invasion pathways have been characterised based on parasite interactions with DARC, TfR1 and CD98 host proteins. However, exposing the parasite’s alternative invasion mechanisms is currently being considered, opening up a large field for exploring the entry receptors used by P. vivax for invading host cells. New methods must be developed to ensure better understanding of the parasite to control malarial transmission and to eradicate the disease. Here, we review the current state of knowledge on cellular and molecular mechanisms of P. vivax’s merozoite invasion to contribute to a better understanding of the parasite’s biology, pathogenesis and epidemiology.
A Changing Light Environment Induces Significant Lateral CO2 Diffusion within Maize Leaves
Authors: Wu Han-Yu , Zou Qing-Qing , Ji Wen-Tao , Wang Ying-Wei , Zhang Wang-Feng , Jiang Chuang-Dao
Published: November 2022

A leaf structure with high porosity is beneficial for lateral CO2 diffusion inside the leaves. However, the leaf structure of maize is compact, and it has long been considered that lateral CO2 diffusion is restricted. Moreover, lateral CO2 diffusion is closely related to CO2 pressure differences (ΔCO2). Therefore, we speculated that enlarging the ΔCO2 between the adjacent regions inside maize leaves may result in lateral diffusion when the diffusion resistance is kept constant. Thus, the leaf structure and gas exchange of maize (C4), cotton (C3), and other species were explored. The results showed that maize and sorghum leaves had a lower mesophyll porosity than cotton and cucumber leaves. Similar to cotton, the local photosynthetic induction resulted in an increase in the ΔCO2 between the local illuminated and the adjacent unilluminated regions, which significantly reduced the respiration rate of the adjacent unilluminated region. Further analysis showed that when the adjacent region in the maize leaves was maintained under a steady high light, the photosynthesis induction in the local regions not only gradually reduced the ΔCO2 between them but also progressively increased the steady photosynthetic rate in the adjacent region. Under field conditions, the ΔCO2, respiration, and photosynthetic rate of the adjacent region were also markedly changed by fluctuating light in local regions in the maize leaves. Consequently, we proposed that enlarging the ΔCO2 between the adjacent regions inside the maize leaves results in the lateral CO2 diffusion and supports photosynthesis in adjacent regions to a certain extent under fluctuating light.
Mosquitoes and Mosquito-Borne Diseases in Vietnam
Authors: Huynh Ly Na , Tran Long Bien , Nguyen Hong Sang , Ho Van Hoang , Parola Philippe , Nguyen Xuan Quang
Published: November 2022

Mosquito-borne diseases pose a significant threat to humans in almost every part of the world. Key factors such as global warming, climatic conditions, rapid urbanisation, frequent human relocation, and widespread deforestation significantly increase the number of mosquitoes and mosquito-borne diseases in Vietnam, and elsewhere around the world. In southeast Asia, and notably in Vietnam, national mosquito control programmes contribute to reducing the risk of mosquito-borne disease transmission, however, malaria and dengue remain a threat to public health. The aim of our review is to provide a complete checklist of all Vietnamese mosquitoes that have been recognised, as well as an overview of mosquito-borne diseases in Vietnam. A total of 281 mosquito species of 42 subgenera and 22 genera exist in Vietnam. Of those, Anopheles, Aedes, and Culex are found to be potential vectors for mosquito-borne diseases. Major mosquito-borne diseases in high-incidence areas of Vietnam include malaria, dengue, and Japanese encephalitis. This review may be useful to entomological researchers for future surveys of Vietnamese mosquitoes and to decision-makers responsible for vector control tactics.
Personalised Treatment in Aortic Stenosis: A Patient-Tailored Transcatheter Aortic Valve Implantation Approach
Authors: Mitsis Andreas , Yuan Xun , Eftychiou Christos , Avraamides Panayiotis , Nienaber Christoph A.
Published: November 2022

Transcatheter aortic valve replacement (TAVI) has become a game changer in the management of severe aortic stenosis shifting the concept from inoperable or high-risk patients to intermediate or low surgical-risk individuals. Among devices available nowadays, there is no clear evidence that one device is better than the other or that one device is suitable for all patients. The selection of the optimal TAVI valve for every patient represents a challenging process for clinicians, given a large number of currently available devices. Consequently, understanding the advantages and disadvantages of each valve and personalising the valve selection based on patient-specific clinical and anatomical characteristics is paramount. This review article aims to both analyse the available devices in the presence of specific clinical and anatomic features and offer guidance to select the most suitable valve for a given patient.
Identification of Hub Genes in the Remodeling of Non-Infarcted Myocardium Following Acute Myocardial Infarction
Authors: Wang Lingxiao , Zhang Yan , Yu Mengjie , Yuan Wuzhou
Published: November 2022

(1) Background: There are few diagnostic and therapeutic targets for myocardial remodeling in the salvageable non-infarcted myocardium. (2) Methods: Hub genes were identified through comprehensive bioinformatics analysis (GSE775, GSE19322, and GSE110209 from the gene expression omnibus (GEO) database) and the biological functions of hub genes were examined by gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Furthermore, the differential expression of hub genes in various cell populations between the acute myocardial infarction (AMI) and sham-operation groups was analyzed by processing scRNA data (E-MTAB-7376 from the ArrayExpress database) and RNA-seq data (GSE183168). (3) Results: Ten strongly interlinked hub genes (Timp1, Sparc, Spp1, Tgfb1, Decr1, Vim, Serpine1, Serpina3n, Thbs2, and Vcan) were identified by the construction of a protein–protein interaction network from 135 differentially expressed genes identified through comprehensive bioinformatics analysis and their reliability was verified using GSE119857. In addition, the 10 hub genes were found to influence the ventricular remodeling of non-infarcted tissue by modulating the extracellular matrix (ECM)-mediated myocardial fibrosis, macrophage-driven inflammation, and fatty acid metabolism. (4) Conclusions: Ten hub genes were identified, which may provide novel potential targets for the improvement and treatment of AMI and its complications.
COVID-19 Infection in Rheumatic Patients on Chronic Antimalarial Drugs: A Systematic Review and Meta-Analysis
Authors: Landsteiner de Sampaio Amêndola Isabela , Aires Pinheiro Jonathan , Póvoa Pedro , Cés de Souza Dantas Vicente , Serafim Rodrigo Bernardo
Published: November 2022

The ongoing chronic use of hydroxychloroquine or chloroquine (HCQ/CQ) in rheumatic patients might impact their outcomes after a SARS-CoV-2 infection. Therefore, we sought to assess the mortality in rheumatic patients with chronic HCQ/CQ use who developed a COVID-19 infection through a comparison between individuals chronically using HCQ/CQ with those not taking these drugs. We performed a systematic review and meta-analysis of studies on PubMed, Embase, and Cochrane Central. We included full-length reports, prospective observational cohorts, and clinical trials of adult patients (aged ≥ 18 years) who were diagnosed with a COVID-19 infection. Case studies, case series, letters, comments, and editorials were excluded. The main outcome was all-cause mortality. This study is registered with PROSPERO (CRD42022341678). We identified 541 studies, of which 20 studies were included, comprising 236,997 patients. All-cause mortality was significantly lower in patients with prior chronic use of HCQ/CQ compared to those with no previous usage (OR 0.76; 95% CI 0.62–0.94; p = 0.01). There was a considerably lower incidence of hospitalization among patients with chronic HCQ/CQ use compared to their counterparts without HCQ/CQ usage (OR 0.80; 95% CI 0.65–0.99; p = 0.04). All-cause mortality and hospitalization were significantly lower in rheumatic patients with chronic HCQ/CQ use who developed a COVID-19 infection.
Sufentanil vs. Dexmedetomidine as Neuraxial Adjuvants in Cesarean Section: A Mono-Centric Retrospective Comparative Study
Authors: Coviello Antonio , Iacovazzo Carmine , D’Abrunzo Anella , Ianniello Marilena , Frigo Maria Grazia , Marra Annachiara , Buonanno Pasquale , Barone Maria Silvia , Servillo Giuseppe , Vargas Maria
Published: November 2022

Spinal anesthesia is the best choice for caesarean delivery. This technique is characterized by a complete and predictable nerve block with a fast onset and few complications. Several intrathecal adjuvants are used in order to improve the quality and duration of anesthesia and reduce its side effects. Sixty-two patients who underwent caesarean delivery under spinal anesthesia were included in this medical records review. In this retrospective study, after adopting exclusion criteria, we assessed 24 patients who received Hyperbaric Bupivacaine 0.5% 10 mg and dexmedetomidine 10 μg (G1), and 28 patients who received an institutional standard treatment with Hyperbaric Bupivacaine 0.5% 10 mg and sufentanil 5 μg (G2). We evaluated the difference in terms of motor and sensory block, postoperative pain, and adverse effects during the first 24 h following delivery and neonatal outcome. Our study found that the sufentanil group had a significantly lower requirement for analgesia than the dexmedetomidine group. Postoperative pain, assessed with the VAS scale, was stronger in G1 than in G2 (4 ± 2 vs. 2 ± 1, p-value < 0.01). Differences between the two groups regarding the intraoperative degree of motor and sensory block, motor recovery time, and neonatal Apgar scores were not noticed. Pruritus and shivering were observed only in G2. Itching and shivering did not occur in the dexmedetomidine group. Postoperative analgesia was superior in the sufentanil group, but the incidence of side effects was higher. Adjuvant dexmedetomidine prevented postoperative shivering.
Clinical Heterogeneity, Unmet Needs and Long-Term Outcomes in Patients with Systemic Lupus Erythematosus
Authors: Sjöwall Christopher , Parodis Ioannis
Published: November 2022

The clinical presentation of systemic lupus erythematosus (SLE) is highly heterogeneous, ranging from mild disease limited to skin and joint involvement to life-threatening conditions with renal impairment, severe cytopenias, central nervous system disease, and thromboembolic events [...]
Long-Term Outcomes following Common Femoral Endarterectomy
Authors: Hashimoto Takuya , Yamamoto Satoshi , Kimura Masaru , Sano Masaya , Sato Osamu , Deguchi Juno
Published: November 2022

Thromboendarterectomy of the common femoral artery (CFA) for occlusive disease is a crucial procedure in vascular surgery. As an outcome reference for emerging endovascular procedures and new devices, we need more robust evidence of the outcome of this gold standard technique. The purpose of this study was to report 10-year results after femoral endarterectomy (FEA). A retrospective review of medical records at our institution identified eighty consecutive patients (91 limbs) who underwent FEA for CFA lesions. Indications for FEA included 50 limbs (55%) for intermittent claudication (IC) and 39 limbs (43%) with chronic limb-threatening ischemia (CLTI). Two limbs (2%) underwent FEA to prevent hemodynamic steal during extra-anatomical bypass. Adjunctive procedures included endovascular therapy in 32%. CFAs were closed with patch angioplasty in 44%. With a mean follow-up period of 39 months, the survival rates at 3 and 8 years were 85% and 77%, respectively. Limb salvage rates were 92% and 87%. Primary patencies were 98% and 84%. Freedom from target lesion revascularization was 95% at 3 years and 91% at 8 years. Our findings support the durability of FEA, with comparable long-term procedural results in CLTI patients as well as IC patients. Since the FEA is a gate maneuver for hybrid revascularization in CLTI patients, our findings support a strategy combining open and endovascular approaches. Femoral endarterectomy remains a durable solution for common femoral occlusive disease in IC and CLTI in the era of endovascular therapy.
Association of Proton Pump Inhibitor Prophylaxis on Clinical Outcome in Acute Ischemic Stroke in China: A Multicenter Retrospective Cohort Study
Authors: Fang Lei , Zhong Wansi , Gong Xiaoxian , Chen Zhicai , Chen Yi , Yan Shenqiang , Lou Min
Published: November 2022

Background: Overtreatment with proton pump inhibitors (PPIs) in acute ischemic stroke (AIS) patients continues to grow. We aimed to investigate the frequency of PPI prophylaxis without an appropriate indication in AIS patients in China and clarify the association between PPI prophylaxis and long-term prognosis. Methods: Based on a multicenter stroke registry database, neurological outcomes, stroke events, recurrent ischemic strokes, and all-cause death were compared between patients with and without PPI prophylaxis. Results: A total of 4542 AIS were included, and 3335 (73.4%) received PPI prophylaxis. Patients with PPI prophylaxis were more likely to have a poor outcome at 1 year than those without PPI prophylaxis (33.3% vs. 25.8%, OR 1.321; 95% CI 1.102–1.584; p = 0.003). No significant differences were found in all-cause death, stroke event, or recurrent ischemic stroke at 1 year between the two groups. After propensity score matching, PPI prophylaxis was still independently associated with a higher rate of poor outcome (30.9% vs. 25.8%, OR 1.432; 95% CI 1.151–1.780; p = 0.001). Sensitivity analysis also showed that PPI prophylaxis increased the rate of a poor outcome in minor strokes or at different durations of PPI prophylaxis. Conclusions: Approximately 3/4 of AIS patients were given PPI prophylaxis during hospitalization, which was associated with a poor long-term outcome.
Cerebral Small Vessel Diseases and Outcomes for Acute Ischemic Stroke Patients after Endovascular Therapy
Authors: Zhao Yixin , Ning Yuye , Lei Lei , Yuan Huijie , Liu Hui , Luo Guogang , Wei Meng , Li Yongxin
Published: November 2022

The correlation between cerebral small vessel disease (CSVD) and the outcomes of acute ischemic stroke (AIS) patients after endovascular therapy (EVT) remains elusive. We aimed to investigate the effect of combined white matter hyperintensities (WMH) and enlarged perivascular spaces (EPVS) as detected in magnetic resonance imaging (MRI) at baseline on clinical outcomes in patients with AIS who underwent EVT. AIS patients that experienced EVT were retrospectively analyzed in this single-center study. Using MRIs taken prior to EVT, we rated WMH and EPVS as the burden of CSVD and dichotomized the population into two groups: absent-to-moderate and severe. Neurological outcome was assessed at day 90 with a modified Rankin Scale (mRS). Symptomatic intracerebral hemorrhage (sICH), early neurological deterioration (END), malignant cerebral edema (MCE), and hospital death were secondary outcomes. Of the 100 patients (64.0% male; mean age 63.71 ± 11.79 years), periventricular WMHs (28%), deep WMHs (41%), EPVS in basal ganglia (53%), and EPVS in centrum semiovale (73%) were observed. In addition, 69% had an absent-to-moderate total CSVD burden and 31.0% had a severe burden. The severe CSVD was not substantially linked to either the primary or secondary outcomes. Patients with AIS who underwent EVT had an elevated risk (OR: 7.89, 95% CI: 1.0, 62.53) of END if they also had EPVS. When considering WMH and EPVS together as a CSVD burden, there seemed to be no correlation between severe CSVD burden and sICH, END, or MCE following EVT for AIS patients. Further studies are warranted to clarify the relationship between CSVD burden and the occurrence, progression, and prognosis of AIS.
Adverse Cardiovascular Events in Non-Traumatic Intracranial Hemorrhage and Ischemic Stroke Survivors
Authors: Pasi Marco , Boulouis Grégoire , Bisson Arnaud , Herbert Julien , Bodin Alexandre , Cordonnier Charlotte , Lip Gregory Y. H. , Fauchier Laurent
Published: November 2022

Background: We aimed to evaluate different measures of adverse cardiovascular events between non-traumatic intracranial hemorrhage (ICrH) and ischemic stroke (IS) survivors with and without atrial fibrillation (AF). Methods: Using a national hospitalization database we compared incidences and risks of all-cause in-hospital death, cardiovascular death, non-cardiovascular death, MACE-HF (in-hospital cardiovascular death, myocardial infarction, IS or new-onset heart failure [HF]) between ICrH and IS survivors with and without AF. Propensity-score matching was also performed. Results: We identified 40,523 survivors of IS and 12,028 survivors of an ICrH without AF, and 20,449 IS survivors and 3574 ICrH survivors with AF. In unadjusted, adjusted and matched analyses, ICrH patients without AF had a higher risk of all-cause in-hospital death (Hazard Ratio (HR; for matched analyses) 1.80; 95% confidence interval (CI) 1.74–1.86), cardiovascular death (HR; 2.79; CI 2.64–2.94), MACE-HF (HR 1.97; CI 1.89–2.06) and new cerebrovascular events (HR 1.75; CI 1.57–1.96) but with lower risk of myocardial infarction (HR 0.81; CI 0.70–0.94), major bleeding (HR 0.92; CI 0.87–0.98) and new onset HF (HR 0.85; CI 0.79–0.91) compared to IS survivors without AF. Similar results were found for ICrH and IS survivors with AF except for myocardial infarction (HR 1.05; CI 0.79–1.34) and new onset HF (HR 0.94; CI 0.84–1.06) that were similar between the two groups. Conclusions: Adverse cardiovascular events are more frequent in ICrH survivors compared to IS survivors. New onset HF is a relatively frequent event after ICrH, especially in those patients with comorbid atrial fibrillation.
Angina in 2022: Current Perspectives
Authors: Manfredi Roberto , Verdoia Monica , Compagnucci Paolo , Barbarossa Alessandro , Stronati Giulia , Casella Michela , Dello Russo Antonio , Guerra Federico , Ciliberti Giuseppe
Published: November 2022

Angina is the main symptom of ischemic heart disease; mirroring a mismatch between oxygen supply and demand. Epicardial coronary stenoses are only responsible for nearly half of the patients presenting with angina; whereas in several cases; symptoms may underlie coronary vasomotor disorders; such as microvascular dysfunction or epicardial spasm. Various medications have been proven to improve the prognosis and quality of life; representing the treatment of choice in stable angina and leaving revascularization only in particular coronary anatomies or poorly controlled symptoms despite optimal medical therapy. Antianginal medications aim to reduce the oxygen supply-demand mismatch and are generally effective in improving symptoms; quality of life; effort tolerance and time to ischemia onset and may improve prognosis in selected populations. Since antianginal medications have different mechanisms of action and side effects; their use should be tailored according to patient history and potential drug-drug interactions. Angina with non-obstructed coronary arteries patients should be phenotyped with invasive assessment and treated accordingly. Patients with refractory angina represent a higher-risk population in which some therapeutic options are available to reduce symptoms and improve quality of life; but robust data from large randomized controlled trials are still lacking.
A Development of New Material for 4D Printing and the Material Properties Comparison between the Conventional and Stereolithography Polymerised NVCL Hydrogels
Authors: Zhuo Shuo , Geever Luke M. , Halligan Elaine , Tie Billy Shu Hieng , Breheny Colette
Published: November 2022

The term 4D printing refers to the idea that the shape or properties of a printed object can be changed when an external stimulus is applied. In this contribution, a temperature-responsive polymer Poly (N-vinyl caprolactam) (PNVCL), which is normally prepared via radical free polymerization, was used to justify the 4D printing concept. As a result, by using a Stereolithography (SLA) 3D printer, 4D prints were successfully prepared. These prints were able to demonstrate intelligent and reversible expansion/shrinkage behaviour as the temperature increases and decreases. Additionally, in order to examine the differences in chemical structure, thermal properties, mechanical properties, and swelling behaviours of the photopolymerised and printed parts, a series of characterisation tests, including Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), goniometry, tensile test, gel fraction measurement and pulsatile swelling study were performed on this study. In conclusion, the differences between polymerisation methods are significant; despite their chemical structures and thermal properties being similar, there were significant differences with regard to tensile properties, swellability and wettability of samples. The implications of conducting this study are remarkable, not only in providing a new way of preparing NVCL, but also in demonstrating the possibility of using 4D printed NVCL for practical applications.
Framework for Process Analysis of Maritime Accidents Caused by the Unsafe Acts of Seafarers: A Case Study of Ship Collision
Authors: Wang Ying , Fu Shanshan
Published: November 2022

Accurately describing and evaluating the effects of unsafe acts on maritime accidents is critical to establishing practical accident prevention and control options. This paper proposes a framework for the probabilistic analysis of maritime accidents caused by seafarers’ unsafe acts by incorporating a navigation simulation and dynamic Bayesian network (DBN) modeling. First, the unsafe acts of seafarers are identified according to an in-depth analysis of global maritime investigation reports. Then, a navigation simulation experiment is designed to collect the ship-handling data of seafarers during hazardous accident scenarios. Consequently, a dynamic probabilistic model is proposed using a DBN to describe the phases of maritime accidents based on the navigation simulation experiment data. Furthermore, an evolution analysis of maritime accidents is conducted to explore the causal chain of such accidents through sensitivity analysis. The typical navigational accident-collision is chosen as the case to interpret the proposed framework, considering the formation process of ship collision risks, from the occurrence of ship collision risk (phase 1) to the close-quarters situation (phase 2) and to immediate danger (phase 3). This framework is applied to explore the causal chain of collision accidents caused by the unsafe acts of seafarers.
Wave Motion and Seabed Response around a Vertical Structure Sheltered by Submerged Breakwaters with Fabry–Pérot Resonance
Authors: Jiang Lai , Zhang Jisheng , Tong Linlong , Guo Yakun , He Rui , Sun Ke
Published: November 2022

This paper presents the results from a numerical simulation study to investigate wave trapping by a series of trapezoidal porous submerged breakwaters near a vertical breakwater, as well as the seabed response around the vertical breakwater. An integrated model, based on the volume-averaged Reynolds-averaged Navier–Stokes (VARANS) equations is developed to simulate the flow field, while the dynamic Biot’s equations are used for simulating the wave-induced seabed response. The reflection of the wave energy over the submerged breakwaters, caused by the vertical breakwater, can be reserved, indicating that the existence of the submerged breakwaters in the front of the vertical breakwater can either provide shelter or worsen the hazards to the vertical breakwater. Numerical examples show two different modes under the Fabry–Pérot (F–P) resonance condition of the wave transformation, namely the wave reflection (Mode 1) and the wave trapping (Mode 2). The distance between the submerged breakwaters and the vertical breakwater, is a key parameter dominating the local hydrodynamic process and the resultant dynamic stresses around the vertical breakwater. The numerical results indicated that more submerged breakwaters and a higher porosity of submerged breakwaters will obviously dissipate more wave energy, and hence induce a smaller wave force on the rear vertical breakwater and liquefaction area around the vertical breakwater.