bluuebunny/crossref_metadata_2025 huggingface dataset:
Deciphering the Genetic Crosstalk between Microglia and Oligodendrocyte Precursor Cells during Demyelination and Remyelination Using Transcriptomic Data
Authors: Enrich-Bengoa Jennifer , Manich Gemma , Dégano Irene R. , Perálvarez-Marín Alex
Published: November 2022

Demyelinating disorders show impaired remyelination due to failure in the differentiation of oligodendrocyte progenitor cells (OPCs) into mature myelin-forming oligodendrocytes, a process driven by microglia–OPC crosstalk. Through conducting a transcriptomic analysis of microarray studies on the demyelination–remyelination cuprizone model and using human samples of multiple sclerosis (MS), we identified molecules involved in this crosstalk. Differentially expressed genes (DEGs) of specific regions/cell types were detected in GEO transcriptomic raw data after cuprizone treatment and in MS samples, followed by functional analysis with GO terms and WikiPathways. Additionally, microglia–OPC crosstalk between microglia ligands, OPC receptors and target genes was examined with the NicheNet model. We identified 108 and 166 DEGs in the demyelinated corpus callosum (CC) at 2 and 4 weeks of cuprizone treatment; 427 and 355 DEGs in the remyelinated (4 weeks of cuprizone treatment + 14 days of normal diet) compared to 2- and 4-week demyelinated CC; 252 DEGs in MS samples and 2730 and 12 DEGs in OPC and microglia of 4-week demyelinated CC. At this time point, we found 95 common DEGs in the CC and OPCs, and one common DEG in microglia and OPCs, mostly associated with myelin and lipid metabolism. Crosstalk analysis identified 47 microglia ligands, 43 OPC receptors and 115 OPC target genes, all differentially expressed in cuprizone-treated samples and associated with myelination. Our differential expression pipeline identified demyelination/remyelination transcriptomic biomarkers in studies using diverse platforms and cell types/tissues. Cellular crosstalk analysis yielded novel markers of microglia ligands, OPC receptors and target genes.
Fabrication and In Vitro Characterization of Novel Hydroxyapatite Scaffolds 3D Printed Using Polyvinyl Alcohol as a Thermoplastic Binder
Authors: Thurzo Andrej , Gálfiová Paulína , Nováková Zuzana Varchulová , Polák Štefan , Varga Ivan , Strunga Martin , Urban Renáta , Surovková Jana , Leško Ľuboš , Hajdúchová Zora , Feranc Jozef , Janek Marian , Danišovič Ľuboš
Published: November 2022

This paper presents a proof-of-concept study on the biocolonization of 3D-printed hydroxyapatite scaffolds with mesenchymal stem cells (MSCs). Three-dimensional (3D) printed biomimetic bone structure made of calcium deficient hydroxyapatite (CDHA) intended as a future bone graft was made from newly developed composite material for FDM printing. The biopolymer polyvinyl alcohol serves in this material as a thermoplastic binder for 3D molding of the printed object with a passive function and is completely removed during sintering. The study presents the material, the process of fused deposition modeling (FDM) of CDHA scaffolds, and its post-processing at three temperatures (1200, 1300, and 1400 °C), as well it evaluates the cytotoxicity and biocompatibility of scaffolds with MTT and LDH release assays after 14 days. The study also includes a morphological evaluation of cellular colonization with scanning electron microscopy (SEM) in two different filament orientations (rectilinear and gyroid). The results of the MTT assay showed that the tested material was not toxic, and cells were preserved in both orientations, with most cells present on the material fired at 1300 °C. Results of the LDH release assay showed a slight increase in LDH leakage from all samples. Visual evaluation of SEM confirmed the ideal post-processing temperature of the 3D-printed FDM framework for samples fired at 1300 °C and 1400 °C, with a porosity of 0.3 mm between filaments. In conclusion, the presented fabrication and colonization of CDHA scaffolds have great potential to be used in the tissue engineering of bones.
Identification and Expression Analysis of the C-TERMINALLY ENCODED PEPTIDE Family in Pisum sativum L.
Authors: Lebedeva Maria A. , Gancheva Maria S. , Kulaeva Olga A. , Zorin Evgeny A. , Dobychkina Daria A. , Romanyuk Daria A. , Sulima Anton S. , Zhukov Vladimir A. , Lutova Lyudmila A.
Published: November 2022

The C-TERMINALLY ENCODED PEPTIDE(CEP) peptides play crucial roles in plant growth and response to environmental factors. These peptides were characterized as positive regulators of symbiotic nodule development in legume plants. However, little is known about the CEP peptide family in pea. Here, we discovered in pea genome 21 CEP genes (PsCEPs), among which three genes contained additional conserved motifs corresponding to the PIP (PAMP-induced secreted peptides) consensus sequences. We characterized the expression patterns of pea PsCEP genes based on transcriptomic data, and for six PsCEP genes with high expression levels in the root and symbiotic nodules the detailed expression analysis at different stages of symbiosis and in response to nitrate treatment was performed. We suggest that at least three PsCEP genes, PsCEP1, PsCEP7 and PsCEP2, could play a role in symbiotic nodule development, whereas the PsCEP1 and PsCEP13 genes, downregulated by nitrate addition, could be involved in regulation of nitrate-dependent processes in pea. Further functional studies are required to elucidate the functions of these PsCEP genes.
Evaluation of HIF-1 Involvement in the BDNF and ProBDNF Signaling Pathways among Obstructive Sleep Apnea Patients
Authors: Gabryelska Agata , Sochal Marcin
Published: November 2022

Obstructive Sleep Apnea (OSA) is a chronic condition characterized by intermittent hypoxia associated with multiple comorbidities, including psychiatric disorders, such as depression, insomnia, and cognitive impairment. The brain-derived neurotrophic factor (BDNF) and proBDNF singling pathways have been shown to be involved in this group of diseases. Furthermore, their expression might be affected by hypoxia-inducible factor 1 (HIF-1), which is an oxygen sensitive transcription factor due to its alpha subunit. Therefore, this study aimed to evaluate the association between HIF-1α, BDNF, and proBDNF protein levels among OSA patients. This study included 40 individuals who underwent polysomnography (PSG) and were divided into the OSA group (n = 20; AHI ≥ 30) and healthy control (n = 20; AHI < 5) based on the apnea–hypopnea index (AHI). All participants had their peripheral blood collected in the evening before and the morning after the PSG. BDNF, proBDNF, and HIF-1α protein concertation measurements were performed using ELISA. No differences were found in BDNF, proBDNF, and HIF-1α protein levels between OSA and the control group, both in the evening and in the morning. In the OSA group, i.e., the linear regression model, the morning BDNF protein level was predicted by age (ß = −0.389, p = 0.023) and the mean SpO2 of desaturations during sleep (ß = −0.577, p = 0.002). This model accounted for 63.3% of the variability in the morning BDNF protein level (F = 14.639, p < 0.001). The morning proBDNF protein level was predicted by age (ß = −0.395, p = 0.033) and HIF-1α morning protein level (ß = −3.192, p = 0.005). This model accounted for 52.4% of the variability in the morning BDNF protein level (F = 9.355, p = 0.002). The obtained results suggest that the HIF-1 transcription factor might be involved in the pathway activated by proBDNF, which may have protective properties from hypoxia in OSA patients.
Effects of Pro-Inflammatory Cytokines on Hepatic Metabolism in Primary Human Hepatocytes
Authors: Gramignoli Roberto , Ranade Aarati R. , Venkataramanan Raman , Strom Stephen C.
Published: November 2022

Three decades of hepatocyte transplantation have confirmed such a cell-based approach as an adjunct or alternative treatment to solid organ transplantation. Donor cell survival and engraftment were indirectly measured by hepatospecific secretive or released metabolites, such as ammonia metabolism in urea cycle defects. In cases of sepsis or viral infection, ammonia levels can significantly and abruptly increase in these recipients, erroneously implying rejection. Pro-inflammatory cytokines associated with viral or bacterial infections are known to affect many liver functions, including drug-metabolizing enzymes and hepatic transport activities. We examined the influence of pro-inflammatory cytokines in primary human hepatocytes, isolated from both normal donors or patients with metabolic liver diseases. Different measures of hepatocyte functions, including ammonia metabolism and phase 1–3 metabolism, were performed. All the hepatic functions were profoundly and significantly suppressed after exposure to concentrations of from 0.1 to 10 ng/mL of different inflammatory cytokines, alone and in combination. Our data indicate that, like phase I metabolism, suppression of phase II/III and ammonia metabolism occurs in hepatocytes exposed to pro-inflammatory cytokines in the absence of cell death. Such inflammatory events do not necessarily indicate a rejection response or loss of the cell graft, and these systemic inflammatory signals should be carefully considered when the immunosuppressant regiment is reduced or relieved in a hepatocyte transplantation recipient in response to such alleged rejection.
Liquid Crystalline Nanoparticles Conjugated with Dexamethasone Prevent Cisplatin Ototoxicity In Vitro
Authors: Valente Filippo , Simoni Edi , Gentilin Erica , Martini Alessandro , Zanoletti Elisabetta , Marioni Gino , Nicolai Piero , Astolfi Laura
Published: November 2022

The conjugation of drugs with nanoparticles represents an innovative approach for controlled and targeted administration of therapeutic agents. Nanoparticle-based systems have been tested for the inner ear therapy, increasing the drug diffusion and being detected in all parts of the cochlea when locally applied near the round window. In this study, glycerol monooleate liquid crystalline NanoParticles were conjugated with Dexamethasone (NPD), a hydrophobic drug already used for inner ear treatments but defective in solubility and bioavailability. NPD has been tested in vitro in the cell line OC-k3, a model of sensory cells of the inner ear, and the therapeutic efficacy has been evaluated against cisplatin, a chemotherapeutic compound known to induce ototoxicity. After comparing the physical chemical characteristics of NPD to the equivalent naïve nanoparticles, an initial investigation was carried out into the nanoparticle’s uptake in OC-k3 cells, which takes place within a few hours of treatment without causing toxic damage up to a concentration of 50 µg/mL. The NPD delivered the dexamethasone inside the cells at a significantly increased rate compared to the equivalent free drug administration, increasing the half-life of the therapeutic compound within the cell. Concerning the co-treatment with cisplatin, the NPD significantly lowered the cisplatin cytotoxicity after 48 h of administration, preventing cell apoptosis. To confirm this result, also cell morphology, cell cycle and glucocorticoids receptor expression were investigated. In conclusion, the NPD system has thus preliminarily shown the potential to improve the therapeutic efficacy of treatments delivered in the inner ear and prevent drug-induced ototoxicity.
Blockade of c-Met-Mediated Signaling Pathways by E7050 Suppresses Growth and Promotes Apoptosis in Multidrug-Resistant Human Uterine Sarcoma Cells
Authors: Huang Tsung-Teng , Chen Chuan-Mu , Lan Ying-Wei , Lin Song-Shu , Choo Kong-Bung , Chong Kowit-Yu
Published: November 2022

E7050 is a potent inhibitor of c-Met receptor tyrosine kinase and has potential for cancer therapy. However, the underlying molecular mechanism involved in the anti-cancer property of E7050 has not been fully elucidated. The main objective of this study was to investigate the anti-tumor activity of E7050 in multidrug-resistant human uterine sarcoma MES-SA/Dx5 cells in vitro and in vivo, and to define its mechanisms. Our results revealed that E7050 reduced cell viability of MES-SA/Dx5 cells, which was associated with the induction of apoptosis and S phase cell cycle arrest. Additionally, E7050 treatment significantly upregulated the expression of Bax, cleaved PARP, cleaved caspase-3, p21, p53 and cyclin D1, while it downregulated the expression of survivin and cyclin A. On the other hand, the mechanistic study demonstrated that E7050 inhibited the phosphorylation of c-Met, Src, Akt and p38 in HGF-stimulated MES-SA/Dx5 cells. Further in vivo experiments showed that treatment of athymic nude mice carrying MES-SA/Dx5 xenograft tumors with E7050 remarkably suppressed tumor growth. E7050 treatment also decreased the expression of Ki-67 and p-Met, and increased the expression of cleaved caspase-3 in MES-SA/Dx5 tumor sections. Therefore, E7050 is a promising drug that can be developed for the treatment of multidrug-resistant uterine sarcoma.
Effect of Isoleucine and Added Valine on Performance, Nutrients Digestibility and Gut Microbiota Composition of Pigs Fed with Very Low Protein Diets
Authors: Goodarzi Parniyan , Wileman Caitlyn Marie , Habibi Mohammad , Walsh Katherine , Sutton Julia , Shili Cedrick Ndhumba , Chai Jianmin , Zhao Jiangchao , Pezeshki Adel
Published: November 2022

Little is known whether a combination Ile and added Val improves the growth of pigs offered very low protein (VLP) diets through changes in nutrients digestibility and gut microbiota. The objective of this study was to investigate the effect of a mixture of Val above and Ile at NRC levels on growth, nutrient digestibility and gut microbiota in pigs fed with VLP diets. Forty, weaned piglets were assigned to: positive control: normal-protein-diet; negative control (NC): VLP diet supplemented with first four limiting amino acids; VA: NC with Val above NRC; IL: NC with Ile at NRC level; VAIL: NC with Val above and Ile at NRC levels. While both VAIL and VA groups completely recovered the inhibitory effects of VLP diets on feed intake, only VAIL partially recovered the negative effects of VLP diets on growth performance. VAIL and VA increased the thermal radiation and decreased the digestibility of nitrogen. NC increased the relative abundance of Pasteurellaceae and Enterobacteriaceae in the colon. VAIL had a higher abundance of colonic Actinobacteria, Enterococcus, and Brevibacillus and the colon content of VA was more enriched with Mogibacterium. Overall, VAIL partially improved the growth performance which is likely linked with alterations in gut microbiota composition.
Low-Intensity Pulsed Ultrasound Counteracts Advanced Glycation End Products-Induced Corpus Cavernosal Endothelial Cell Dysfunction via Activating Mitophagy
Authors: Chen Yuzhuo , Xiao Ming , Zhao Liangyu , Huang Yongquan , Lin Yuhong , Xie Ting , Tian Jiali , Wang Qi , Tang Yuxin , Su Zhongzhen
Published: November 2022

Injury to corpus cavernosal endothelial cells (CCECs) is an important pathological basis of diabetes mellitus-induced erectile dysfunction (DMED), while low-intensity pulsed ultrasound (LIPUS) has been shown to improve erectile function in DMED. To further understand its therapeutic mechanism of action, in this study, we first demonstrated increased apoptosis and shedding in the CCECs of DMED patients, accompanied by significant mitochondrial injury by immunohistochemistry and electron microscopy of corpus cavernosum tissue. Next, we used advanced glycation end products (AGEs) to simulate the diabetic environment in vitro and found that AGES damaged mitochondria and inhibited angiogenesis in CCECs in a dose-dependent manner, while LIPUS treatment significantly reversed its effects. Mechanistic studies based on transcriptome sequencing showed that LIPUS significantly up-regulated LC3 and PARKIN protein levels in mitochondria, promoted mitophagy, and affected mitochondrial dynamics and reactive oxygen species (ROS) production. In addition, the protective effects of LIPUS were abrogated when mitophagy was inhibited by 3-methyladenine. In summary, LIPUS exerted potent inhibitory effects on AGES-induced CCEC failure via mitophagy, providing a theoretical basis for DMED treatment that encompasses the protection of endothelial structure and function.
Calix[4]arene Polyamine Triazoles: Synthesis, Aggregation and DNA Binding
Authors: Burilov Vladimir , Makarov Egor , Mironova Diana , Sultanova Elza , Bilyukova Islamiya , Akyol Kevser , Evtugyn Vladimir , Islamov Daut , Usachev Konstantin , Mukhametzyanov Timur , Solovieva Svetlana , Antipin Igor
Published: November 2022

Artificial gene delivery systems are in great demand from both scientific and practical biomedical points of view. In this paper, we present the synthesis of a new click chemistry calix[4]arene precursor with free lower rim and new water-soluble calixarene triazoles with 12 amino-groups on the upper rim (one with free phenol hydroxyl groups and two another containing four butyl or tetradecyl fragments). Aggregation in the series of amino-triazole calixarenes of different lipophilicity (calixarene with free phenol hydroxyl groups or butyl and tetradecyl fragments on the lower rim) was studied using dynamic light scattering and fluorescent pyrene probe. It was found that calix[4]arene with a free lower rim, like alkyl-substituted butyl calix[4]arene, forms stable submicron aggregates 150–200 nm in size, while the more lipophilic tetradecyl –substituted calix[4]arene forms micellar aggregates19 nm in size. Using UV-Vis spectroscopy, fluorimetry and CD, it was shown that amino-triazole calix[4]arenes bind to calf thymus DNA by classical intercalation. According to DLS and TEM data, all studied macrocycles cause significant DNA compaction, forming stable nanoparticles 50–20 nm in size. Among all studied calix[4]arenes the most lipophilic tetradecyl one proved to be the best for both binding and compaction of DNA.
Transient Retention of Photoreceptor Outer Segments in Matrigel-Embedded Retinal Organoids
Authors: Berber Patricia , Bondarenko Sofiia , Michaelis Lisa , Weber Bernhard Heinrich Friedrich
Published: November 2022

Retinal organoids (ROs) are three-dimensional retinal tissues, which are differentiated in vitro from induced pluripotent stem cells (iPSC), ultimately forming all main retinal cell types under defined culture conditions. ROs show several highly specialized retinal features, including the outgrowth of photoreceptor outer segments (OSs). In vivo, the photoreceptor OSs are enveloped and maintained by protrusions of retinal pigment epithelium (RPE) cells, the so-called apical microvilli, while ROs fail to recapitulate this critical interaction in culture development. Here, we define specific co-culture conditions aiming to compensate for the missing physical proximity of RPE and OSs in RO development. Accordingly, functional RPE cells and ROs were differentiated simultaneously from the same iPSC clone, the former resulting in byproduct RPE or bRPE cells. While some co-culture approaches indicated a temporary functional interaction between bRPE and RO photoreceptors, they did not improve the photoreceptor histoarchitecture. In contrast, embedding ROs in a basement membrane extract without bRPE cells showed a robust improvement in the rate of photoreceptor OS retention. RO embedding is a quick and easy method that greatly enhances the preservation of photoreceptor OSs, an important structure for modelling retinal diseases with the involvement of photoreceptors.
Transformation of Corn Stover into Furan Aldehydes by One-Pot Reaction with Acidic Lithium Bromide Solution
Authors: Gao Meixiang , Xin Qi , Sun Wan , Xiao Jiaqi , Lu Xianqin
Published: November 2022

Currently, the production of furan aldehydes from raw biomass suffers from low furfural yield and high energy consumption. In this study, a recyclable and practical method was explored for the preparation of furfural from corn stover by the one-pot reaction by acidic lithium bromide solution (ALBS) without pretreatment and enzymolysis. In the ALBS reaction, the furan aldehydes were generated by the degradation of lignocellulose; however, the products were unstable and were further dehydrated to form humins. So, dehydration reaction was inhibited in this study, and the high yield of furan aldehydes was obtained, in which 2.94 g/L of furfural and 2.78 g/L of 5-hydroxymethyl furfural (5-HMF) were generated with high solid loading (10 wt%), the presence of commercial catalyst ZSM-5 and co-solvent tetrahydrofuran (THF) at 140 °C for 200 min. Via this method, almost 100% of hemicellulose was transformed to furfural, and 40.71% of cellulose was transformed to 5-HMF, which was based on the theoretical yield of HMF (8.35 g) from glucose (29.30 g) produced from cellulose. After the reaction, the catalyst ZSM-5 was the main component in the solid residue and kept a suitable performance. THF azeotrope was easily separated from the slurry by evaporation. During the removal of THF, lignin was precipitated from the liquid phase and showed lower molecular weight and abundant active groups, which was a potential feedstock for producing valuable aromatics and polymers. Thus, in a one-pot reaction, the ideal yield of furan aldehydes from raw biomass was obtained on a lab scale, and the catalyst, THF, and LiBr were easily recycled, which provided an option to realize the economical production of sustainable furan aldehydes from raw biomass.
A Discovery-Based Metabolomic Approach Using UPLC-Q-TOF-MS/MS Reveals Potential Antimalarial Compounds Present in Artemisia annua L.
Authors: Shi Henan , Wang Zhuqing , Xu Fujie , Li Jialin , Li Jing , Wang Manyuan
Published: November 2022

In 1972, Nobel laureate Youyou Tu’s research team conducted clinical trials on the dried material of Artemisia annua L. from Beijing extracted by ether and then treated with alkali (called “ether neutral dry”), which showed that artemisinin was not the only antimalarial component contained. The biosynthesis of sesquiterpenoids in A. annua has increased exponentially after unremitting cultivation efforts, and the plant resources are now quite different from those in the 1970s. In consideration of emerging artemisinin resistance, it is of great theoretical and practical value to further study the antimalarial activity of A. annua and explore its causes. The purpose of this study is to clarify scientific questions, such as “What ingredients are synergistic with artemisinin in A. annua?”, and “Are there non-artemisinin antimalarial ingredients in A. annua?”. In this paper, Beijing wild A. annua was used as a control and two representative cultivation species of A. annua were selected to evaluate the antimalarial activity of the herbal medicine. The antimalarial activity of different extracts on mice was studied using the Peters’ four-day suppressive test. UPLC-Q-TOF-MS was used to obtain mass spectrum data for all samples, and a UNIFI platform was used for identification. A multivariate statistical method was used to screen the different compounds with positive correlations. The antimalarial activity of different components from the ether extract and alkali treatments was determined and antimalarial components other than artemisinin were obtained. A total of 24 flavonoids, 68 sesquiterpenoids and 21 other compounds were identified. Compounds associated with differential antimalarial activity were identified. The material basis for the antimalarial activity of A. annua was clarified. The antimalarial components of A. annua include two categories: first, artemisinin and non-artemisinin antimalarial active components, of which the non-artemisinin antimalarial active components may include 5α-hydroperoxy-eudesma-4(15),11-diene; second, several antimalarial synergistic ingredients in A. annua, including arteanniun B, arteanniun B analogues and polymethoxy flavonoids.
Fisetin Modulates Toll-like Receptor-Mediated Innate Antiviral Response in Chikungunya Virus-Infected Hepatocellular Carcinoma Huh7 Cells
Authors: Lani Rafidah , Teoh Boon-Teong , Sam Sing-Sin , AbuBakar Sazaly , Hassandarvish Pouya
Published: November 2022

In the chronic phase of chikungunya virus (CHIKV) infection, excessive inflammation manifests as incapacitating joint pain and prolonged arthritis. Arthritis resulted from a large influx of infiltrating immune cells driven by pro-inflammatory cytokines and chemokines originating from the toll-like receptor (TLR)-mediated innate antiviral response. This study investigated fisetin’s ability to modulate TLR-mediated antiviral responses against CHIKV in Huh7 cells. The CHIKV inhibitory potential of fisetin was assessed by plaque-forming unit assay, virus yield reduction assay, and bright-field microscopy (cytopathic effect, immunofluorescence). Fisetin’s modulatory potential on TLR-mediated antiviral response was evaluated by immunofluorescence assay (expression of TLR proteins), qRT-PCR (mRNA level of antiviral genes), human cytokine array, and the immunoblotting of key transcription factors. The present study showed fisetin induced the expression of the antiviral genes at an early time-point by promoting the phosphorylation of IRF3 and IRF7. Fisetin reduced excessive inflammatory cytokine responses in CHIKV-infected Huh7 cells by impeding the over-phosphorylation of NF-κB. Fisetin also reduced CHIKV-induced cytopathic effects in CHIKV-infected Huh7 cells. Altogether, our study suggests that fisetin modulates TLR-mediated antiviral responses by affecting the CHIKV-induced inflammatory responses.
Three-Dimensional Ternary rGO/VS2/WS2 Composite Hydrogel for Supercapacitor Applications
Authors: Magdum Sahil S. , Thangarasu Sadhasivam , Oh Tae Hwan
Published: November 2022

In recent years, the development of lightweight electrode materials with excellent performance (energy density versus power density) has increased the number of uses for supercapacitors. Creating three-dimensional skeletal network structures with excellent specific capacitance and high energy density is still challenging. This study utilized a straightforward one-pot hydrothermal technique to construct a supercapacitor based on hydrogel 3D skeletal networks comprising rGO nanosheets with VS2/WS2 nanoparticles. The rGO appeared as flakes and layers, interconnected in nature, allowing for more ion transport pathways and a larger active surface area for EDLC performance. The heterostructured VS2 and WS2 nanoparticles were homogeneously anchored to the rGO layers and were porous in the hydrogel structure. The functioning rGO, rGO-VS2, and rGO-VS2-WS2 composite hydrogel electrodes were created without a binder on the Ni foam current collector using a hydraulic press. The rGO-VS2-WS2 composite hydrogel electrode showed excellent supercapacitor performance of 220 F g−1 at 1 A g−1 in 3M KOH electrolyte, which was more than those of the GO (158 F g−1) and rGO-VS2 (199 F g−1) hydrogels under similar conditions. Hydrogel electrodes made of rGO-VS2-WS2 had a power density of 355 Whkg−1 and a high energy density of 30.55 Whkg−1. It maintained a high energy density of up to 21.11 W/kg−1, even at a high power density of 3454 W/kg−1. Given the 3D shape and the excellent surface properties of rGO nanosheets with VS2 and WS2 nanoparticles as the hydrogel, this electrode has essential properties that make it a good choice for making high-performance capacitors.
Weather Sensitivity of Sugar Bait Trapping of Nocturnal Moths: A Case Study from Northern Europe
Authors: Fetnassi Nidal , Ude Kadri , Kull Ain , Tammaru Toomas
Published: November 2022

Assemblages of insects need to be quantitatively sampled in the context of various research questions. Light trapping is the most widely used method for sampling nocturnal Lepidoptera. Attracting moths to sugar baits offers a viable alternative. However, this method is rarely used in professional research despite its popularity among amateur lepidopterists. As the activity of insects is strongly dependent on ambient conditions, the sensitivity of any trapping method to weather parameters needs to be known for the quantitative interpretation of trapping results. In the present paper, we report data on the weather dependence of moth catches obtained by automatic bait traps. The study was performed in Estonia, representing the European hemiboreal forest zone. Portable weather stations set up next to each of the traps were used for collecting weather data. Both abundance and diversity of the moths in the catches depended strongly positively on temperature and negatively on air humidity. Diversity was also negatively correlated with air pressure and positively with the change in pressure during the night. The results show that in situ recording of weather parameters in connection to insect trapping provides useful insights for the study of insect behaviour and the interpretation of the results of monitoring projects.
Atrial Fibrillation in Heart Failure with Preserved Left Ventricular Systolic Function: Distinct Elevated Risk for Cardiovascular Outcomes in Women Compared to Men
Authors: Omar Alaa Mabrouk Salem , Rahman Mohamed Ahmed Abdel , Rifaie Osama , Bella Jonathan N.
Published: November 2022

Background: Heart failure with preserved ejection fraction (HFpEF) is prevalent in women and is associated with atrial fibrillation (AF). However, sex associations in AF-related HFpEF are not well explored. Aim: We studied differences between men and women with and without AF-related HFpEF symptoms on left ventricular (LV) geometry and diastolic dysfunction (DD) and their effect on cardiovascular events. Methods: Retrospectively, HFpEF patients with and without a history of AF referred for echocardiography were studied. Echocardiographic assessments were focused on LV geometry and diastolic functions. Patients were followed for the occurrence of cardiac events defined as death and cardiac hospitalization. Results: We studied 556 patients [age: 66.7 ± 17 years, 320 (58%) women, 91 (16%) AF]. Compared to HFpEF without AF (HFpEF-AF), HFpEF with AF patients (HFpEF+AF) were older (76 ± 13.8 vs. 64.9 ± 17.3 years, p < 0.001), had more risk factors, comorbidities, left ventricular hypertrophy (32 vs. 13%, p < 0.001), higher relative wall thickness (0.50 ± 0.14 vs. 0.44 ± 0.15, p < 0.001), and DD (56 vs. 30%, all p < 0.001). HFpEF+AF women had the worst clinical, LV geometric, and diastolic functional profiles and highest rates of cardiovascular outcomes compared to HFpEF+AF men and were the only group to predict outcomes (HR: 2.7, 95%CI: 1.4–5.1), while HFpEF-AF women were a low-risk group; HFpEF+AF and HFpEF-AF men had intermediate cardiovascular outcomes which were confirmed after propensity score matching. Conclusions: Among patients with HFpEF, women with AF had more abnormal LV geometry and diastolic function and had an increased risk of adverse cardiovascular outcomes independent of traditional risk factors, comorbidities, and baseline diastolic function.
Lost in Translation: Evaluation of Subcutaneous Interferon-β Treatment for SARS-CoV-2 Infection in Real Life
Authors: Casado José L. , Vizcarra Pilar , Del Rey José M. , Soriano María Cruz , Rodriguez-Dominguez Mario , Manzano Luis , Acero Julio , Palomar-Fernandez Carmen , Vallejo Alejandro ,   on behalf of the COVID-19 IRYCIS Team
Published: November 2022

Despite in vitro activity of interferon-β (IFN-β) against SARS-CoV-2 infection, its clinical efficacy remains controversial. We evaluated the impact of IFN-β treatment in a cohort of 3590 patients hospitalized with COVID-19 during March–April 2020. The primary endpoint was a composed variable of admission to intensive care unit (ICU)/death. Overall, 153 patients (4%) received IFN-β. They were significantly more severely ill, with a worse clinical and analytical situation, explaining a higher ICU admission (30% vs. 17%; p < 0.01), and a shorter time to the composed variable. In a Cox regression analysis, older age, lymphopenia, renal failure, or increased neutrophil-to-lymphocyte ratio were associated with a greater hazard ratio (HR) of admission at ICU/death. Notably, the HR of IFN-β for the outcome variable was no longer significant after adjustment (HR, 1.03; 95% CI, 0.82–1.30), and different sensitivity analysis (early IFN use, ICU admission) showed no changes in the estimates. A propensity score matching analysis showed no association of IFN-β therapy and outcome. In conclusion, in this large cohort of hospitalized COVID-19 patients, IFN-β was used mainly in patients with advanced disease, reflecting an important bias of selection. After adjusting by severity, IFN-β was not associated with a higher rate of ICU admission or mortality.
A Life-Threating Postpartum Atypical Hemolytic-Uremic Syndrome with Multiorgan Involvement
Authors: Sarno Laura , Conca Paolo , Capuano Alfredo , Tarantino Giovanni , Russo Domenico , Guida Maurizio
Published: November 2022

Atypical Hemolytic Uremic Syndrome is a very rare condition that can be triggered in predisposed patients. It can remain undiagnosed and can result in a life-threatening event or permanent renal failure. We report a case of a 36-year-old pregnant woman who developed atypical hemolytic uremic syndrome postpartum. She underwent an emergency caesarean section due to abruptio placenta, and she developed biochemical alterations suggestive of a thrombotic microangiopathy. Due to worsening of renal function after plasma exchange therapy, we decided to start therapy with eculizumab. Therapy was carried out with a weekly dose of 900 mg IV for five weeks. An improvement of clinical and biochemical parameters was rapidly observed, and her renal function completely recovered. The therapy was continued for six months, with a dose of 1200 mg of eculizumab every two weeks. One year after discontinuation of the therapy, her blood pressure and renal function were still normal. Our case confirms that it is important to promptly identify a pregnancy-related thrombotic microangiopathy and that early therapy can be life-saving for the patient and can preserve renal function, avoiding dialysis.
Macro- and Microvascular Function in Middle-Aged Individuals with Low Cardiovascular Disease Risk
Authors: Patel Sunni , Shokr Hala , Greenstein Adam , Gherghel Doina
Published: November 2022

Aims: To investigate the microvascular function in apparently healthy individuals showing signs of early macrovascular endothelial dysfunction. Methods: Healthy participants aged between 30–55 years were recruited for the present study. Baseline measurements included body-mass index (BMI), waist-to-hip ratio (WHR), 24-h blood pressure, as well as fasted venous glucose, triglycerides (TG) and cholesterol (HDL, LDL and total). Brachial artery reactivity was measured using the flow-mediated dilation (FMD) technique and retinal vessel reactivity was assessed by using the Dynamic Retinal Vessel Analyser (DVA) in all individuals. The enrolled participants were separated in two groups, based on either a reduced (group 1: <5%—n = 53) or a normal FMD response (group 2: 7–10%—n = 47). Results: Individuals exhibiting reduced FMD responses showed a reduced baseline-corrected microvascular arterial dilation response to flickering light (p = 0.039). In addition, they also exhibited a reduced arteriolar maximum dilation (p = 0.034), as well as a longer dilation reaction time (p = 0.048) and a lower dilation amplitude (p = 0.042) when compared to those with normal FMD values. Conclusion: In otherwise healthy middle-aged individuals, early signs of vascular dysfunction are reflected simultaneously at both macro- and microvascular levels.
Respiratory Health Inequities among Children and Young Adults with Cerebral Palsy in Aotearoa New Zealand: A Data Linkage Study
Authors: Sorhage Alexandra , Keenan Samantha , Chong Jimmy , Byrnes Cass , Blackmore Amanda Marie , Mackey Anna , Hill Timothy , Han Dug Yeo , Stott Ngaire Susan
Published: November 2022

(1) Background: Respiratory disease is a leading cause of morbidity, mortality, and poor quality of life in children with cerebral palsy (CP). This study describes the prevalence of CP-related respiratory disease and the non-modifiable risk factors for respiratory-related hospital admissions in the Aotearoa New Zealand population. (2) Methods: New Zealand Cerebral Palsy Register (NZCPR) participant data and de-identified data from the National Minimum Dataset and Pharmaceutical Dispensing Collections were linked to identify all respiratory-related hospital admissions and respiratory illness-related antibiotic exposure over 5 years in individuals with CP (0–26 years). (3) Results: Risk factors for respiratory-related hospital admissions included being classified Gross Motor Function Classification System (GMFCS) IV or V compared to GMFCS I [OR = 4.37 (2.90–6.58), p < 0.0001; OR = 11.8 (7.69–18.10), p < 0.0001, respectively,]; having ≥2 antibiotics dispensed per year [OR = 4.42 (3.01–6.48), p < 0.0001]; and being of Māori ethnicity [OR = 1.47 (1.13–1.93), p < 0.0047]. Māori experienced health inequities compared to non-Māori, with greater functional disability, and also experienced greater antibiotic dispensing than the general population. (4) Conclusion: Māori children and young adults have a higher risk of respiratory-related illness. Priority should be given to the screening for potentially modifiable risk factors for all children with CP from diagnosis onwards in a way that ensures Māori health equity.
Is There an Added Neonatal Risk in Vacuum-Assisted Deliveries with Nuchal Cord?
Authors: Schreiber Hanoch , Cohen Gal , Mevorach Nir , Shavit Maya , Kovo Michal , Biron-Shental Tal , Markovitch Ofer
Published: November 2022

This retrospective cohort study assessed the association between nuchal cord and adverse outcomes during vacuum-assisted delivery (VAD). Women with singleton pregnancies, 34–41-weeks gestation, who underwent VAD, from 2014 to 2020 were included. The primary outcome was umbilical cord pH ≤ 7.1. Secondary outcomes were neonatal intensive care unit admission, Apgar scores, pH < 7.15, subgaleal hematoma, shoulder dystocia and third/fourth-degree perineal tear. Outcomes were compared between neonates with (1059/3754, 28.2%) or without (71.8%) nuchal cord after VAD. No difference in cord pH ≤ 7.1 was found between groups. The nuchal cord group had a lower rate of nulliparity (729 (68.8%) vs. 2004 (74.4%), p = 0.001) and higher maternal BMI (23.6 ± 4.3 vs. 23.1 ± 5, p = 0.017). Nuchal cord was associated with higher rates of induction (207 (19.5%) vs. 431 (16%), p = 0.009) and lower birthweights (3185 ± 413 vs. 3223 ± 436 g, p = 0.013). The main indication for VAD in 830 (80.7%) of the nuchal cord group was non-reassuring fetal heart rate (NRFHR) vs. 1989 (75.6%) controls (p = 0.004). The second stage was shorter in the nuchal cord group (128 ± 81 vs. 141 ± 80 min, p < 0.001). Multivariate regression found nulliparity, induction and birthweight as independent risk factors for nuchal cord VAD. Although induction and NRFHR rates were higher in VAD with nuchal cord, the rate of umbilical cord acidemia was not.
Metal Allergy: State-of-the-Art Mechanisms, Biomarkers, Hypersensitivity to Implants
Authors: Zemelka-Wiacek Magdalena
Published: November 2022

Metal allergy is mainly an environmental disorder which can cause allergic contact dermatitis. Environmental metal exposures include jewelry, everyday metal items, mobile phones, leather, metal-rich food and implants, including stents or anchors. While consumer exposure is liable for the majority of metal hypersensitivity cases, the significance of occupational exposure to metals remains relevant. Although the most common metal allergens are nickel, chromium, and cobalt; however, lately, gold, palladium, titanium, and some others have also attracted attention. This review highlights advances in metal allergy mechanisms, biomarkers for potential patients’ stratification as well as biological treatments. The most recent evidence of human exposure to metal for risk assessment is discussed, as well as the relationship between the occurrence of metal hypersensitivity and implanted devices, including non-characteristic symptoms. The latest data on the diagnosis of metal hypersensitivity are also reported.
Clinical Efficacy, Tolerability and Safety of a New Multiple-Action Eyedrop in Subjects with Moderate to Severe Dry Eye
Authors: Roszkowska Anna Maria , Inferrera Leandro , Spinella Rosaria , Postorino Elisa Imelde , Gargano Romana , Oliverio Giovanni Wiliam , Aragona Pasquale
Published: November 2022

Background: To assess the clinical efficacy, tolerability and safety of a new-generation ophthalmic solution containing cross-linked hyaluronic acid 0.15% trehalose 3%, liposomes 1% and sterylamine 0.25% (Trimix® Off Health Italia, Firenze, Italy) (CXHAL) versus trehalose 3% (Thealoz®, Thea Pharmaceuticals, Clermont-Ferrand, France) (TRS) in subjects with moderate to severe dry eye disease (DED). Patients and methods: In this prospective, observational cohort study, 41 subjects with moderate to severe dry eye were enrolled and divided into two age- and sex-matched groups. Group 1 was treated with CXHA eye drops, and group 2 was treated with TRS eye drops four times daily for 2 months. All subjects were evaluated at baseline (V0) and at day 60 ± 3 (V1). The examination comprised Best Corrected Visual Acuity (BCVA) and Symptom Assessment in Dry Eye (SANDE). Tear osmolarity was evaluated using the TearLab Osmolarity System®; Keratograph 5M (Oculus, Wetzlar, Germany) was performed to assess tear meniscus height (TMH), fluorescein tear break-up time (TBUT) and corneal and conjunctival fluorescein staining and meibography; furthermore, slit lamp evaluation was performed for eyelid erythema and edema, conjunctival chemosis and hyperemia and Meibomian gland secretion quality. Results: All patients completed the treatment. BCVA remained stable in both groups, and no adverse events were reported. After 2 months, both groups showed statistically significant improvements for SANDE (p = 0.001 and p = 0.012, respectively), TBUT values (p < 0.001 and p < 0.001, respectively) and staining (p = 0.004 and p = 0.001, respectively) as compared to baseline values. Group 1 showed a statistically significant improvement in SANDE frequency and tear osmolarity (p = 0.02 and p = 0.001, respectively), whereas chemosis was significantly reduced in group 2. The amount of TBUT improvement was statistically higher in group 1 compared to that in group 2 (p = 0.041). Conclusion: A new-generation multiple-action ophthalmic solution was safe and clinically effective in the treatment of moderate and severe dry eye, with significant improvements in the main ocular surface parameters.
Practice of Awake Prone Positioning in Critically Ill COVID-19 Patients—Insights from the PRoAcT–COVID Study
Authors: Stilma Willemke , Valk Christel M. A. , van Meenen David M. P. , Morales Luis , Remmelzwaal Daantje , Myatra Sheila N. , Artigas Antonio , Neto Ary Serpa , Paulus Frederique , Schultz Marcus J.
Published: November 2022

We describe the incidence, practice and associations with outcomes of awake prone positioning in patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19) in a national multicenter observational cohort study performed in 16 intensive care units in the Netherlands (PRoAcT–COVID-study). Patients were categorized in two groups, based on received treatment of awake prone positioning. The primary endpoint was practice of prone positioning. Secondary endpoint was ‘treatment failure’, a composite of intubation for invasive ventilation and death before day 28. We used propensity matching to control for observed confounding factors. In 546 patients, awake prone positioning was used in 88 (16.1%) patients. Prone positioning started within median 1 (0 to 2) days after ICU admission, sessions summed up to median 12.0 (8.4–14.5) hours for median 1.0 day. In the unmatched analysis (HR, 1.80 (1.41–2.31); p < 0.001), but not in the matched analysis (HR, 1.17 (0.87–1.59); p = 0.30), treatment failure occurred more often in patients that received prone positioning. The findings of this study are that awake prone positioning was used in one in six COVID-19 patients. Prone positioning started early, and sessions lasted long but were often discontinued because of need for intubation.
Surgical Site Infection in Cardiac Surgery
Authors: Zukowska Agnieszka , Zukowski Maciej
Published: November 2022

Surgical site infections (SSIs) are one of the most significant complications in surgical patients and are strongly associated with poorer prognosis. Due to their aggressive character, cardiac surgical procedures carry a particular high risk of postoperative infection, with infection incidence rates ranging from a reported 3.5% and 26.8% in cardiac surgery patients. Given the specific nature of cardiac surgical procedures, sternal wound and graft harvesting site infections are the most common SSIs. Undoubtedly, DSWIs, including mediastinitis, in cardiac surgery patients remain a significant clinical problem as they are associated with increased hospital stay, substantial medical costs and high mortality, ranging from 3% to 20%. In SSI prevention, it is important to implement procedures reducing preoperative risk factors, such as: obesity, hypoalbuminemia, abnormal glucose levels, smoking and S. aureus carriage. For decolonisation of S. aureus carriers prior to cardiac surgery, it is recommended to administer nasal mupirocin, together with baths using chlorhexidine-based agents. Perioperative management also involves antibiotic prophylaxis, surgical site preparation, topical antibiotic administration and the maintenance of normal glucose levels. SSI treatment involves surgical intervention, NPWT application and antibiotic therapy
Hemoadsorption in Complex Cardiac Surgery—A Single Center Experience
Authors: Manohar Murali , Jawali Vivek , Neginahal Siddu , GT Sudarshan , Muniraj Geetha , Chakravarthy Murali
Published: November 2022

(1) Background: Cardiac surgery may evoke a generalized inflammatory response, typically magnified in complex, combined, redo, and emergency procedures with long aortic cross-clamp times. Various treatment options have been introduced to help regain control over post-cardiac surgery hyper-inflammation, including hemoadsorptive immunomodulation with CytoSorb®. (2) Methods: We conducted a single-center retrospective observational study of patients undergoing complex cardiac surgery. Patients intra-operatively treated with CytoSorb® were compared to a control group. The primary outcome was the change in the vasoactive-inotropic score (VIS) from pre-operatively to post-operatively. (3) Results: A total of 52 patients were included in the analysis, where 23 were treated with CytoSorb® (CS) and 29 without (controls). The mean VIS increase from pre-operative to post-operative values was significantly lower in the CS group compared to the control group (3.5 vs. 5.5, respectively, p = 0.05). In-hospital mortality in the control group was 20.7% (6 patients) and 9.1% (2 patients) in the CS group (p = 0.26). Lactate level changes were comparable, and the median intensive care unit and hospital lengths of stay were similar between groups. (4) Conclusions: Despite notable imbalances between the groups, the signals revealed point toward better hemodynamic stability with CytoSorb® hemoadsorption in complex cardiac surgery and a trend of lower mortality.