bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic Factors in Eutopic Endometrium in Women with Endometriosis and Infertility
Authors: Adamczyk Magdalena , Wender-Ozegowska Ewa , Kedzia Malgorzata
Published: March 2022

Eutopic endometrium in patients with endometriosis is characterized by aberrant expression of essential genes during the implantation window. It predisposes to disturbance of endometrial receptivity. The pathomechanism of implantation failures in women with endometriosis remains unclear. This paper aims to summarize the knowledge on epigenetic mechanisms in eutopic endometrium in the group of patients with both endometriosis and infertility. The impaired DNA methylation patterns of gene promoter regions in eutopic tissue was established. The global profile of histone acetylation and methylation and the analysis of selected histone modifications showed significant differences in the endometrium of women with endometriosis. Aberrant expression of the proposed candidate genes may promote an unfavorable embryonic implantation environment of the endometrium due to an immunological dysfunction, inflammatory reaction, and apoptotic response in women with endometriosis. The role of the newly discovered proteins regulating gene expression, i.e., TET proteins, in endometrial pathology is not yet completely known. The cells of the eutopic endometrium in women with endometriosis contain a stable, impaired methylation pattern and a histone code. Medication targeting critical genes responsible for the aberrant gene expression pattern in eutopic endometrium may help treat infertility in women with endometriosis.
The Activity of Ten Natural Extracts Combined in a Unique Blend to Maintain Cholesterol Homeostasis—In Vitro Model
Authors: Ruga Sara , Galla Rebecca , Penna Claudia , Molinari Claudio , Uberti Francesca
Published: March 2022

Background: Hypercholesterolemia is a major cause of cardiovascular disease and statins, the HMGCoA inhibitors, are the most prescribed drugs. Statins reduce the production of hepatic cholesterol, leading to greater expression of the LDL receptor and greater absorption of circulating LDL, reducing peripheral LDL levels. Unfortunately, statins are believed to induce myopathy and other severe diseases. To overcome this problem, safe nutraceuticals with the same activity as statins could hold great promise in the prevention and treatment of hypercholesterolemia. In this study, the anti-cholesterol efficacy of a new nutraceutical, called Esterol10®, was evaluated. Methods: HepG2 cells were used to study the biological mechanisms exerted by Esterol10® analyzing different processes involved in cholesterol metabolism, also comparing data with Atorvastatin. Results: Our results indicate that Esterol10® leads to a reduction in total hepatocyte cholesterol and an improvement in the biosynthesis of free cholesterol and bile acids. Furthermore, the anti-cholesterol activity of Esterol10® was also confirmed by the modulation of the LDL receptor and by the accumulation of lipids, as well as by the main intracellular pathways involved in the metabolism of cholesterol. Conclusions: Esterol10® is safe and effective with anti-cholesterol activity, potentially providing an alternative therapy to those based on statins for hypercholesterolemia disease.
Identification of Tumor-Suppressive miR-30e-3p Targets: Involvement of SERPINE1 in the Molecular Pathogenesis of Head and Neck Squamous Cell Carcinoma
Authors: Minemura Chikashi , Asai Shunichi , Koma Ayaka , Kase-Kato Ikuko , Tanaka Nozomi , Kikkawa Naoko , Kasamatsu Atsushi , Yokoe Hidetaka , Hanazawa Toyoyuki , Uzawa Katsuhiro , Seki Naohiko
Published: March 2022

Recently, our studies revealed that some passenger strands of microRNAs (miRNAs) were closely involved in cancer pathogenesis. Analysis of miRNA expression signatures showed that the expression of miR-30e-3p (the passenger strand of pre-miR-30e) was significantly downregulated in cancer tissues. In this study, we focused on miR-30e-3p (the passenger strand of pre-miR-30e). We addressed target genes controlled by miR-30e-3p that were closely associated with the molecular pathogenesis of head and neck squamous cell carcinoma (HNSCC). Ectopic expression assays demonstrated that the expression of miR-30e-3p attenuated cancer cell malignant phenotypes (e.g., cell proliferation, migration, and invasive abilities). Our analysis of miR-30e-3p targets revealed that 11 genes (ADA, CPNE8, C14orf126, ERGIC2, HMGA2, PLS3, PSMD10, RALB, SERPINE1, SFXN1, and TMEM87B) were expressed at high levels in HNSCC patients. Moreover, they significantly predicted the short survival of HNSCC patients based on 5-year overall survival rates (p < 0.05) in The Cancer Genome Atlas (TCGA). Among these targets, SERPINE1 was found to be an independent prognostic factor for patient survival (multivariate Cox regression; hazard ratio = 1.6078, p < 0.05). Aberrant expression of SERPINE1 was observed in HNSCC clinical samples by immunohistochemical analysis. Functional assays by targeting SERPINE1 expression revealed that the malignant phenotypes (e.g., proliferation, migration, and invasion abilities) of HNSCC cells were suppressed by the silencing of SERPINE1 expression. Our miRNA-based approach will accelerate our understanding of the molecular pathogenesis of HNSCC.
A Wide-Proteome Analysis to Identify Molecular Pathways Involved in Kidney Response to High-Fat Diet in Mice
Authors: Dozio Elena , Maffioli Elisa , Vianello Elena , Nonnis Simona , Grassi Scalvini Francesca , Spatola Leonardo , Roccabianca Paola , Tedeschi Gabriella , Corsi Romanelli Massimiliano Marco
Published: March 2022

The etiopathogenesis of obesity-related chronic kidney disease (CKD) is still scarcely understood. To this aim, we assessed the effect of high-fat diet (HF) on molecular pathways leading to organ damage, steatosis, and fibrosis. Six-week-old male C57BL/6N mice were fed HF diet or normal chow for 20 weeks. Kidneys were collected for genomic, proteomic, histological studies, and lipid quantification. The main findings were as follows: (1) HF diet activated specific pathways leading to fibrosis and increased fatty acid metabolism; (2) HF diet promoted a metabolic shift of lipid metabolism from peroxisomes to mitochondria; (3) no signs of lipid accumulation and/or fibrosis were observed, histologically; (4) the early signs of kidney damage seemed to be related to changes in membrane protein expression; (5) the proto-oncogene MYC was one of the upstream transcriptional regulators of changes occurring in protein expression. These results demonstrated the potential usefulness of specific selected molecules as early markers of renal injury in HF, while histomorphological changes become visible later in obesity-related CDK. The integration of these information with data from biological fluids could help the identification of biomarkers useful for the early detection and prevention of tissue damage in clinical practice.
Behavioral Neuroscience in the Era of Genomics: Tools and Lessons for Analyzing High-Dimensional Datasets
Authors: Bentzur Assa , Alon Shahar , Shohat-Ophir Galit
Published: March 2022

Behavioral neuroscience underwent a technology-driven revolution with the emergence of machine-vision and machine-learning technologies. These technological advances facilitated the generation of high-resolution, high-throughput capture and analysis of complex behaviors. Therefore, behavioral neuroscience is becoming a data-rich field. While behavioral researchers use advanced computational tools to analyze the resulting datasets, the search for robust and standardized analysis tools is still ongoing. At the same time, the field of genomics exploded with a plethora of technologies which enabled the generation of massive datasets. This growth of genomics data drove the emergence of powerful computational approaches to analyze these data. Here, we discuss the composition of a large behavioral dataset, and the differences and similarities between behavioral and genomics data. We then give examples of genomics-related tools that might be of use for behavioral analysis and discuss concepts that might emerge when considering the two fields together.
NSAIDs Induce Proline Dehydrogenase/Proline Oxidase-Dependent and Independent Apoptosis in MCF7 Breast Cancer Cells
Authors: Kazberuk Adam , Chalecka Magda , Palka Jerzy , Bielawska Katarzyna , Surazynski Arkadiusz
Published: March 2022

Non-steroidal anti-inflammatory drugs (NSAIDs) are considered in cancer therapy for their inhibitory effect on cyclooxygenase-2 (COX-2), which is overexpressed in most cancers. However, we found that NSAIDs as ligands of peroxisome proliferator-activated receptor-γ (PPARγ)-induced apoptosis independent of the COX-2 inhibition, and the process was mediated through activation of proline dehydrogenase/proline oxidase (PRODH/POX)-dependent generation of reactive oxygen species (ROS). This mitochondrial enzyme converts proline to ∆1-pyrroline-5-carboxylate (P5C) during which ATP or ROS is generated. To confirm the role of PRODH/POX in the mechanism of NSAID-induced apoptosis we obtained an MCF7 CRISPR/Cas9 PRODH/POX knockout breast cancer cell model (MCF7POK-KO). Interestingly, the studied NSAIDs (indomethacin and diclofenac) in MCF7POK-KO cells contributed to a more pronounced pro-apoptotic phenotype of the cells than in PRODH/POX-expressing MCF7 cells. The observed effect was independent of ROS generation, but it was related to the energetic disturbances in the cells as shown by an increase in the expression of AMPKα (sensor of cell energy status), GLUD1/2 (proline producing enzyme from glutamate), prolidase (proline releasing enzyme), PPARδ (growth supporting transcription factor) and a decrease in the expression of proline cycle enzymes (PYCR1, PYCRL), mammalian target of rapamycin (mTOR), and collagen biosynthesis (the main proline utilizing process). The data provide evidence that the studied NSAIDs induce PRODH/POX-dependent and independent apoptosis in MCF7 breast cancer cells.
Endogenous Opioids and Their Role in Stem Cell Biology and Tissue Rescue
Authors: Petrocelli Giovannamaria , Pampanella Luca , Abruzzo Provvidenza M. , Ventura Carlo , Canaider Silvia , Facchin Federica
Published: March 2022

Opioids are considered the oldest drugs known by humans and have been used for sedation and pain relief for several centuries. Nowadays, endogenous opioid peptides are divided into four families: enkephalins, dynorphins, endorphins, and nociceptin/orphanin FQ. They exert their action through the opioid receptors (ORs), transmembrane proteins belonging to the super-family of G-protein-coupled receptors, and are expressed throughout the body; the receptors are the δ opioid receptor (DOR), μ opioid receptor (MOR), κ opioid receptor (KOR), and nociceptin/orphanin FQ receptor (NOP). Endogenous opioids are mainly studied in the central nervous system (CNS), but their role has been investigated in other organs, both in physiological and in pathological conditions. Here, we revise their role in stem cell (SC) biology, since these cells are a subject of great scientific interest due to their peculiar features and their involvement in cell-based therapies in regenerative medicine. In particular, we focus on endogenous opioids’ ability to modulate SC proliferation, stress response (to oxidative stress, starvation, or damage following ischemia–reperfusion), and differentiation towards different lineages, such as neurogenesis, vasculogenesis, and cardiogenesis.
Identification of New QTLs for Dietary Fiber Content in Aegilops biuncialis
Authors: Ivanizs László , Marcotuli Ilaria , Rakszegi Marianna , Kalapos Balázs , Szőke-Pázsi Kitti , Farkas András , Türkösi Edina , Gaál Eszter , Kruppa Klaudia , Kovács Péter , Darkó Éva , Szakács Éva , Said Mahmoud , Cápal Petr , Doležel Jaroslav , Gadaleta Agata , Molnár István
Published: March 2022

Grain dietary fiber content is an important health-promoting trait of bread wheat. A dominant dietary fiber component of wheat is the cell wall polysaccharide arabinoxylan and the goatgrass Aegilops biuncialis has high β-glucan content, which makes it an attractive gene source to develop wheat lines with modified fiber composition. In order to support introgression breeding, this work examined genetic variability in grain β-glucan, pentosan, and protein content in a collection of Ae. biuncialis. A large variation in grain protein and edible fiber content was revealed, reflecting the origin of Ae. biuncialis accessions from different eco-geographical habitats. Association analysis using DArTseq-derived SNPs identified 34 QTLs associated with β-glucan, pentosan, water-extractable pentosan, and protein content. Mapping the markers to draft chromosome assemblies of diploid progenitors of Ae. biuncialis underlined the role of genes on chromosomes 1Mb, 4Mb, and 5Mb in the formation of grain β-glucan content, while other QTLs on chromosome groups 3, 6, and 1 identified genes responsible for total- and water-extractable pentosan content. Functional annotation of the associated marker sequences identified fourteen genes, nine of which were identified in other monocots. The QTLs and genes identified in the present work are attractive targets for chromosome-mediated gene transfer to improve the health-promoting properties of wheat-derived foods.
VCAM-1 Targeted Lipopolyplexes as Vehicles for Efficient Delivery of shRNA-Runx2 to Osteoblast-Differentiated Valvular Interstitial Cells; Implications in Calcific Valve Disease Treatment
Authors: Voicu Geanina , Rebleanu Daniela , Mocanu Cristina Ana , Tanko Gabriela , Droc Ionel , Uritu Cristina Mariana , Pinteala Mariana , Manduteanu Ileana , Simionescu Maya , Calin Manuela
Published: March 2022

Calcific aortic valve disease (CAVD) is a progressive inflammatory disorder characterized by extracellular matrix remodeling and valvular interstitial cells (VIC) osteodifferentiation leading to valve leaflets calcification and impairment movement. Runx2, the master transcription factor involved in VIC osteodifferentiation, modulates the expression of other osteogenic molecules. Previously, we have demonstrated that the osteoblastic phenotypic shift of cultured VIC is impeded by Runx2 silencing using fullerene (C60)-polyethyleneimine (PEI)/short hairpin (sh)RNA-Runx2 (shRunx2) polyplexes. Since the use of polyplexes for in vivo delivery is limited by their instability in the plasma and the non-specific tissue interactions, we designed and obtained targeted, lipid-enveloped polyplexes (lipopolyplexes) suitable for (1) systemic administration and (2) targeted delivery of shRunx2 to osteoblast-differentiated VIC (oVIC). Vascular cell adhesion molecule (VCAM)-1 expressed on the surface of oVIC was used as a target, and a peptide with high affinity for VCAM-1 was coupled to the surface of lipopolyplexes encapsulating C60-PEI/shRunx2 (V-LPP/shRunx2). We report here that V-LPP/shRunx2 lipopolyplexes are cyto- and hemo-compatible and specifically taken up by oVIC. These lipopolyplexes are functional as they downregulate the Runx2 gene and protein expression, and their uptake leads to a significant decrease in the expression of osteogenic molecules (OSP, BSP, BMP-2). These results identify V-LPP/shRunx2 as a new, appropriately directed vehicle that could be instrumental in developing novel strategies for blocking the progression of CAVD using a targeted nanomedicine approach.
Phenotypical Conversions of Dermal Adipocytes as Pathophysiological Steps in Inflammatory Cutaneous Disorders
Authors: Kruglikov Ilja L. , Zhang Zhuzhen , Scherer Philipp E.
Published: March 2022

Adipocytes from the superficial layer of subcutaneous adipose tissue undergo cyclic de- and re-differentiation, which can significantly influence the development of skin inflammation under different cutaneous conditions. This inflammation can be connected with local loading of the reticular dermis with lipids released due to de-differentiation of adipocytes during the catagen phase of the hair follicle cycle. Alternatively, the inflammation parallels a widespread release of cathelicidin, which typically takes place in the anagen phase (especially in the presence of pathogens). Additionally, trans-differentiation of dermal adipocytes into myofibroblasts, which can occur under some pathological conditions, can be responsible for the development of collateral scarring in acne. Here, we provide an overview of such cellular conversions in the skin and discuss their possible involvement in the pathophysiology of inflammatory skin conditions, such as acne and psoriasis.
Mesenchymal Stem Cell-Derived Extracellular Vesicles and Their Therapeutic Use in Central Nervous System Demyelinating Disorders
Authors: Allegretta Caterina , D’Amico Emanuele , Manuti Virginia , Avolio Carlo , Conese Massimo
Published: March 2022

Autoimmune demyelinating diseases—including multiple sclerosis, neuromyelitis optica spectrum disorder, anti-myelin oligodendrocyte glycoprotein-associated disease, acute disseminated encephalomyelitis, and glial fibrillary acidic protein (GFAP)-associated meningoencephalomyelitis—are a heterogeneous group of diseases even though their common pathology is characterized by neuroinflammation, loss of myelin, and reactive astrogliosis. The lack of safe pharmacological therapies has purported the notion that cell-based treatments could be introduced to cure these patients. Among stem cells, mesenchymal stem cells (MSCs), obtained from various sources, are considered to be the ones with more interesting features in the context of demyelinating disorders, given that their secretome is fully equipped with an array of anti-inflammatory and neuroprotective molecules, such as mRNAs, miRNAs, lipids, and proteins with multiple functions. In this review, we discuss the potential of cell-free therapeutics utilizing MSC secretome-derived extracellular vesicles—and in particular exosomes—in the treatment of autoimmune demyelinating diseases, and provide an outlook for studies of their future applications.
Crocetin Prolongs Recovery Period of DSS-Induced Colitis via Altering Intestinal Microbiome and Increasing Intestinal Permeability
Authors: Feng Peishi , Li Qiaoqiao , Liu Ling , Wang Siyu , Wu Zhipeng , Tao Yi , Huang Pan , Wang Ping
Published: March 2022

Crocetin is one of the major active constituents of saffron (Crocus sativus L.) which has a reputation for facilitating blood circulation and dispersing blood stasis in traditional Chinese medicine. However, there is little evidence showing the relationship between crocetin intake and the risk of gastrointestinal diseases such as colitis. In order to investigate the effect of crocetin on the regulation of intestinal barrier function and intestinal microbiota composition, mice were treated with crocetin after 3% dextran sulfate sodium (DSS) administration for one week. We found that crocetin intake at 10 mg/kg aggravated colitis in mice, showing increased weight loss and more serious histological abnormalities compared with the DSS group. The 16s rDNA sequencing analysis of the feces samples showed that mice treated with 10 mg/kg crocetin had lower species diversity and richness than those treated with DSS. At the genus level, a higher abundance of Akkermansia and Mediterraneibacter, and a lower abundance of Muribaculaceae, Dubosiella, Paramuribaculum, Parasutterella, Allobaculum, Duncaniella, Candidatus Stoquefichus, and Coriobacteriaceae UCG-002 were observed in the crocetin group. Untargeted metabolomic analyses revealed that crocetin reduced the levels of primary and secondary bile acids such as 12-ketodeoxycholic acid, 7-ketodeoxycholic acid, 3-sulfodeoxycholic acid, 6-ethylchenodeoxycholic acid, chenodeoxycholate, glycochenodeoxycholate-7-sulfate, glycocholate, and sulfolithocholic acid in the colon. In conclusion, crocetin intake disturbed intestinal homeostasis and prolonged recovery of colitis by promoting inflammation and altering gut microbiota composition and its metabolic products in mice. Our findings suggest that patients with gastrointestinal diseases such as inflammatory bowel disease should use crocetin with caution.
Negative Elongation Factor (NELF) Inhibits Premature Granulocytic Development in Zebrafish
Authors: Huang Mengling , Ahmed Abrar , Wang Wei , Wang Xue , Ma Cui , Jiang Haowei , Li Wei , Jing Lili
Published: March 2022

Gene expression is tightly regulated during hematopoiesis. Recent studies have suggested that RNA polymerase II (Pol II) promoter proximal pausing, a temporary stalling downstream of the promoter region after initiation, plays a critical role in regulating the expression of various genes in metazoans. However, the function of proximal pausing in hematopoietic gene regulation remains largely unknown. The negative elongation factor (NELF) complex is a key factor important for this proximal pausing. Previous studies have suggested that NELF regulates granulocytic differentiation in vitro, but its in vivo function during hematopoiesis remains uncharacterized. Here, we generated the zebrafish mutant for one NELF complex subunit Nelfb using the CRISPR-Cas9 technology. We found that the loss of nelfb selectively induced excessive granulocytic development during primitive and definitive hematopoiesis. The loss of nelfb reduced hematopoietic progenitor cell formation and did not affect erythroid development. Moreover, the accelerated granulocytic differentiation and reduced progenitor cell development could be reversed by inhibiting Pol II elongation. Further experiments demonstrated that the other NELF complex subunits (Nelfa and Nelfe) played similar roles in controlling granulocytic development. Together, our studies suggested that NELF is critical in controlling the proper granulocytic development in vivo, and that promoter proximal pausing might help maintain the undifferentiated state of hematopoietic progenitor cells.
Isoprene Emission Influences the Proteomic Profile of Arabidopsis Plants under Well-Watered and Drought-Stress Conditions
Authors: Mancini Ilaria , Domingo Guido , Bracale Marcella , Loreto Francesco , Pollastri Susanna
Published: March 2022

Isoprene is a small lipophilic molecule synthesized in plastids and abundantly released into the atmosphere. Isoprene-emitting plants are better protected against abiotic stresses, but the mechanism of action of isoprene is still under debate. In this study, we compared the physiological responses and proteomic profiles of Arabidopsis which express the isoprene synthase (ISPS) gene and emit isoprene with those of non-emitting plants under both drought-stress (DS) and well-watered (WW) conditions. We aimed to investigate whether isoprene-emitting plants displayed a different proteomic profile that is consistent with the metabolic changes already reported. Only ISPS DS plants were able to maintain the same photosynthesis and fresh weight of WW plants. LC–MS/MS-based proteomic analysis revealed changes in protein abundance that were dependent on the capacity for emitting isoprene in addition to those caused by the DS. The majority of the proteins changed in response to the interaction between DS and isoprene emission. These include proteins that are associated with the activation of secondary metabolisms leading to ABA, trehalose, and proline accumulations. Overall, our proteomic data suggest that isoprene exerts its protective mechanism at different levels: under drought stress, isoprene affects the abundance of chloroplast proteins, confirming a strong direct or indirect antioxidant action and also modulates signaling and hormone pathways, especially those controlling ABA synthesis. Unexpectedly, isoprene also alters membrane trafficking.
The Diversity of Aphidlion-like Larvae over the Last 130 Million Years
Authors: Haug Joachim T. , Linhart Simon , Haug Gideon T. , Gröhn Carsten , Hoffeins Christel , Hoffeins Hans-Werner , Müller Patrick , Weiterschan Thomas , Wunderlich Jörg , Haug Carolin
Published: March 2022

Aphidlions are larvae of certain lacewings (Neuroptera), and more precisely larvae of the groups Chrysopidae, green lacewings, and Hemerobiidae, brown lacewings. The name ‘aphidlion’ originates from their ecological function as specialised predators of aphids. Accordingly, they also play an economic role as biological pest control. Aphidlions have, mostly, elongated spindle-shaped bodies, and similarly to most lacewing larvae they are equipped with a pair of venom-injecting stylets. Fossils interpreted as aphidlions are known to be preserved in amber from the Cretaceous (130 and 100 million years ago), the Eocene (about 35 million years ago) and the Miocene (about 15 million years ago) ages. In this study, new aphidlion-like larvae are reported from Cretaceous amber from Myanmar (about 100 million years old) and Eocene Baltic amber. The shapes of head and stylets were compared between the different time slices. With the newly described fossils and specimens from the literature, a total of 361 specimens could be included in the analysis: 70 specimens from the Cretaceous, 5 from the Eocene, 3 from the Miocene, 188 extant larvae of Chrysopidae, and 95 extant larvae of Hemerobiidae. The results indicate that the diversity of head shapes remains largely unchanged over time, yet there is a certain increase in the diversity of head shapes in the larvae of Hemerobiidae. In certain other groups of Neuroptera, a distinct decrease in the diversity of head shapes in larval stages was observed.
Full-Length Transcriptome Sequencing-Based Analysis of Pinus sylvestris var. mongolica in Response to Sirex noctilio Venom
Authors: Gao Chenglong , Ren Lili , Wang Ming , Wang Zhengtong , Fu Ningning , Wang Huiying , Shi Juan
Published: March 2022

Sirex noctilio is a major international quarantine pest that recently emerged in northeast China to specifically invade conifers. During female oviposition, venom is injected into the host together with its symbiotic fungus to alter the normal Pinus physiology and weaken or even kill the tree. In China, the Mongolian pine (Pinus sylvestris var. mongolica), an important wind-proof and sand-fixing species, is the unique host of S. noctilio. To explore the interplay between S. noctilio venom and Mongolian pine, we performed a transcriptome comparative analysis of a 10-year-old Mongolian pine after wounding and inoculation with S. noctilio venom. The analysis was performed at 12 h, 24 h and 72 h. PacBio ISO-seq was used and integrated with RNA-seq to construct an accurate full-length transcriptomic database. We obtained 52,963 high-precision unigenes, consisting of 48,654 (91.86%) unigenes that were BLASTed to known sequences in the public database and 4309 unigenes without any annotation information, which were presumed to be new genes. The number of differentially expressed genes (DEGs) increased with the treatment time, and the DEGs were most abundant at 72 h. A total of 706 inoculation-specific DEGs (475 upregulated and 231 downregulated) and 387 wounding-specific DEGs (183 upregulated and 204 downregulated) were identified compared with the control. Under venom stress, we identified 6 DEGs associated with reactive oxygen species (ROS) and 20 resistance genes in Mongolian pine. Overall, 52 transcription factors (TFs) were found under venom stress, 45 of which belonged to the AP2/ERF TF family and were upregulated. A total of 13 genes related to the photosystem, 3 genes related photo-regulation, and 9 TFs were identified under wounding stress. In conclusion, several novel putative genes were found in Mongolian pine by PacBio ISO seq. Meanwhile, we also identified various genes that were resistant to S. noctilio venom, such as GAPDH, GPX, CAT, FL2, CERK1, and HSP83A, etc.
Metabolomics Reveals Changes in Metabolite Profiles among Pre-Diapause, Diapause and Post-Diapause Larvae of Sitodiplosis mosellana (Diptera: Cecidomyiidae)
Authors: Huang Qitong , Ma Qian , Li Fangxiang , Zhu-Salzman Keyan , Cheng Weining
Published: March 2022

Sitodiplosis mosellana, a notorious pest of wheat worldwide, copes with temperature extremes during harsh summers and winters by entering obligatory diapause as larvae. However, the metabolic adaptive mechanism underlying this process is largely unknown. In this study, we performed a comparative metabolomics analysis on S. mosellana larvae at four programmed developmental stages, i.e., pre-diapause, diapause, low temperature quiescence and post-diapause development. In total, we identified 54 differential metabolites based on pairwise comparisons of the four groups. Of these metabolites, 37 decreased in response to diapause, including 4 TCA cycle intermediates (malic acid, citric acid, fumaric acid, α-ketoglutaric acid), 2 saturated fatty acids (palmitic acid, stearic acid) and most amino acids. In contrast, nine metabolites, including trehalose, glycerol, mannitol, proline, alanine, oleic acid and linoleic acid were significantly higher in both the diapause and quiescent stages than the other two stages. In addition to two of them (trehalose, proline), glutamine was also significantly highest in the cold quiescence stage. These elevated metabolites could function as cryoprotectants and/or energy reserves. These findings suggest that the reduced TCA cycle activity and elevated biosynthesis of functional metabolites are most likely responsible for maintaining low metabolic activity and cold tolerance during diapause, which is crucial for the survival and post-diapause development of this pest.
Prohibitin 1 Regulates Inflammatory Mediators and Reactive Oxygen Species in Retinal Endothelial Cells
Authors: Liu Li , Jiang Youde , Steinle Jena J.
Published: March 2022

Diabetic retinopathy is associated with increased inflammatory mediator levels. In these studies, we focused on prohibitin 1. We performed western blotting for retinal lysates from diabetic mice and Epac1 floxed and cdh5Cre-Epac1 mice. We also grew primary retinal endothelial cells (REC) in normal (5 mM) and high (25 mM) glucose, and treated some cells with an Epac 1 agonist or prohibitin 1 siRNA. Western blotting was done to confirm knockdown of prohibitin 1 and Epac 1 agonism. We measured the tumor necrosis factor alpha (TNFα), interleukin-1-beta (IL-1β), phosphorylated prohibitin 1, phosphorylated nuclear factor kappa beta (NFkB), high mobility group box 1 (HMGB1) and reactive oxygen species (ROS) levels in REC after transfection with prohibitin 1 siRNA. Results showed that high glucose increased the inflammatory mediators, as well as HMGB1 and ROS. The levels of ROS, HMGB1, and inflammatory pathways were all reduced after cells were transfected with prohibitin 1 siRNA. Epac1 reduced prohibitin 1 phosphorylation. In conclusion, decreased prohibitin 1 significantly reduced the inflammatory mediator and ROS levels in REC. Epac1 regulates the prohibitin 1 levels in REC.
Head-to-Head Comparison between 18F-FES PET/CT and 18F-FDG PET/CT in Oestrogen Receptor-Positive Breast Cancer: A Systematic Review and Meta-Analysis
Authors: Piccardo Arnoldo , Fiz Francesco , Treglia Giorgio , Bottoni Gianluca , Trimboli Pierpaolo
Published: March 2022

18F-FDG PET/CT is a powerful diagnostic tool in breast cancer (BC). However, it might have a reduced sensitivity in differentiated, oestrogen receptor-positive (ER+) BC. In this setting, specific molecular imaging with fluorine-oestradiol (18F-FES) PET/CT could help in overcoming these limitations; however, the literature on the diagnostic accuracy of this method is limited. We therefore planned this systematic review and meta-analysis to compare 18F-FDG and 18F-FES PET/CT in ER+ BC patients. We performed a literature search to identify all studies performing a head-to-head comparison between the two methods; we excluded review articles, preclinical studies, case reports and small case series. Finally, seven studies were identified (overall: 171 patients; range: 7–49 patients). A patients-based analysis (PBA) showed that 18F-FDG and 18F-FES PET/CT had a similar high pooled sensitivity (97% and 94%, respectively) at the lesion-based analysis (LBA), 18F-FES performed slightly better than 18F-FDG (pooled sensitivity: 95% vs. 85%, respectively). Moreover, when we considered only the studies dealing with the restaging setting (n = 3), this difference in sensitivity was even more marked (98% vs. 81%, respectively). In conclusion, both tracers feature an excellent sensitivity in ER+ BC; however, 18F-FES PET/CT could be preferred in the restaging setting.
The Telecardiology Revolution: From Emergency Management to Daily Clinical Practice
Authors: De Bonis Silvana , Salerno Nadia , Bisignani Antonio , Verta Antonella , Capristo Cristina , Capristo Antonio , Sosto Gennaro , Sorrentino Sabato , Bisignani Giovanni
Published: March 2022

Aims: Telecardiology is one of the most widespread applications of telemedicine. We aimed to report the design and development of a telecardiology system in the sanitary district of Cosenza, one of the largest in Italy, with a complex orography, and healthcare reorganization needs, for the management of the emergency network and daily clinical practice. Methods: Our telecardiology network connects 8 hospitals, 9 first aid centers, 20 local 118-EMS stations, 1 helicopter station, 8 hospital emergency departments, 59 hospital departments, and 3 catheterization laboratories. All data are centralized on a dedicated server, accessible from any location for real-time assessment. The quality, source, and timing of the electrocardiograms transmitted were evaluated. Results: From October 2015 to December 2019, a total of 389,970 ECGs were transmitted. The quality of ECGs was optimal in 52%, acceptable in 42%, and poor in 6% of the cases. The number of poor-quality ECGs was only 3% in the last 2 years. Out of the total, 145,097 (37.2%) were transmitted from the emergency departments and 5318 (1.4%) from the 118-EMS. Of interest, a sizable part of the ECG was related to routine clinical practice, comprising 110,556 (28.3%) from the cardiology department and 79,256 (20.3%) from other noncardiovascular departments. Finally, the average reporting time was significantly decreased compared to reporting times without a telecardiology system (5–10 vs. 45–90 min). Conclusion: Our telecardiology system provides efficient cardiology assistance for all types, settings, and phases of cardiovascular diseases.
Low Five-Minute Apgar Score and Neurological Morbidities: Does Prematurity Modify the Association?
Authors: Wainstock Tamar , Sheiner Eyal
Published: March 2022

(1) Background: We aimed to study whether a low 5 min Apgar score is associated with pediatric neurological morbidities throughout childhood. (2) Methods: A population-based retrospective cohort study was conducted. The exposed group was defined as offspring with a 5 min Apgar score <7, and the remaining offspring served as the comparison group. The primary outcome was defined as pediatric hospitalizations with any neurological morbidity. Multivariable survival models were used to evaluate the association between the exposure and outcome while adjusting for potential confounders. Additional models were used to study this association separately among term- and preterm-born offspring. (3) Results: The study population included 349,385 singletons born between the years 1991 and 2021, 0.6% (n = 2030) of whom had a 5 min Apgar score <7 (exposed). The cohort was followed for up to 18 years (median ~ 10.6). The incidence of neurological morbidity-related hospitalizations was higher among the exposed group versus the unexposed group (11.3% versus 7.5%, hazard ratio = 1.84; 95%CI 1.58–2.13). A low 5 min Apgar score remained a significant risk factor for neurological hospitalizations after adjusting for preterm delivery, maternal age, hypertension during pregnancy, gestational diabetes mellitus, chorioamnionitis, and delivery mode (adjusted hazard ratio = 1.61; 95%CI 1.39–1.87). However, after modeling term and preterm offspring separately, a low 5 min Apgar score was independently associated with neurological hospitalizations only among offspring born at term (adjusted hazard ratio = 1.16; 95%CI 0.87–1.55 and 1.70; 95%CI 1.42–2.02 for preterm and term offspring, respectively). (4) Conclusions: A low 5 min Apgar score is independently associated with childhood neurological morbidity, specifically among term-born offspring. Although not designed to identify risk for long-term health complications, Apgar scores may be a marker of risk for short- and long-term neurological morbidities among term newborns.
Radiographic Outcomes of Ganz versus Modified Triple Osteotomies in Femoral Head Medialization and Coverage in Acetabular Dysplasia
Authors: Hsu Jui-Yo , Lee Chia-Che , Lin Sheng-Chieh , Wang Ting-Ming , Kuo Ken N. , Wu Kuan-Wen
Published: March 2022

Variable techniques in periacetabular osteotomy have been formulated for the treatment of acetabular dysplasia. However, few studies have compared the radiographic outcomes between different osteotomy types. This study compared modified triple innominate (MTI) osteotomy and Ganz osteotomy with respect to radiographic outcomes. Patients receiving MTI osteotomies and Ganz osteotomies at any time between 2006 and 2018 in a tertiary medical centre were recruited. Only patients with unilateral osteotomies were recruited to eliminate potential influence from the contralateral hip following periacetabular osteotomy. Patients having hip-joint dislocation, receiving simultaneous proximal femoral osteotomy, or having fewer than 2 years of follow-up were excluded. The radiographic parameters of preoperative and postoperative anteroposterior radiographs of the pelvis were measured, and Sharp’s angle (SA), the lateral centre-edge angle (CE angle), the femoral head extrusion index (FHEI), and the centre-head distance discrepancy (CHDD) were included for comparison. Among 55 participants, 23 received MTI osteotomies and 32 received Ganz osteotomies. The mean age at which patients underwent surgery was 21.9 years in the Ganz osteotomy group and 21.1 years in the MTI group. The mean follow-up length was 2.5 years. The preoperative radiographic parameters between groups differed only slightly and nonsignificantly. Both groups exhibited significantly improved SA, LCEA, and FHEI after surgery. The Ganz osteotomy group exhibited more favourable postoperative FHEI (13.5 vs. 24.3, p < 0.0001), CHDD (3.7 vs. 11.5, p < 0.0001), Sharp angle (45.0 vs. 41.8, p = 0.0489) and CE angles (28.3 vs. 21.1, p = 0.029) compared with the MTI osteotomy group. Notably, CHDD became better and worse following Ganz and MTI osteotomies, respectively; this suggests that the femoral head is pushed laterally in modified triple osteotomy. With respect to femoral head coverage and the medialization of the femoral head, Ganz osteotomy exhibits more favourable corrections in postoperative radiographic parameters than does MTI osteotomy.
Prevention of Abdominal Bulging Using Onlay Dermal Autografts from Discarded Zone IV TRAM Flap Tissue
Authors: Lee Won Seob , Park Seong Oh , Kim Il-Kug
Published: March 2022

While the transverse rectus abdominis myocutaneous (TRAM) flap is a popular option for abdominal-based breast reconstruction, abdominal wall morbidities such as bulging or hernia remain a concern. Here, we introduced a surgical technique for reinforcing the abdominal wall using an onlay autograft obtained from discarded zone IV tissue following a primary closure. We compared abdominal wall morbidities between patients receiving an onlay graft and those receiving primary closure only. We retrospectively reviewed the medical charts of patients who underwent breast reconstruction using a TRAM flap between December 2018 and May 2021. Additionally, we assessed donor-site morbidities based on physical examination. Of the 79 patients included, 38 had received a dermal graft and 41 had not. Donor-site morbidities occurred in 10 (24.5%) and 1 (2.6%) patients, and bulging occurred in 8 (19.5%) and 1 (2.6%) patients in the primary closure and dermal autograft groups, respectively. A statistically significant difference in the incidence of bulging was observed between the groups (p = 0.030). In conclusion, the introduction of a dermal autograft after primary closure can successfully ameliorate morbidities at the TRAM flap site.
Waste to Energy Onboard Cruise Ships: A New Paradigm for Sustainable Cruising
Authors: Toneatti Luca , Deluca Claudio , Fraleoni Morgera Alessandro , Piller Marzio , Pozzetto Dario
Published: March 2022

The newest cruise ships can guest a constantly increasing number of passengers and concentrate their environmental impact on the limited areas interested by their path. The generated solid waste contributes significantly to this impact; therefore, we propose an innovative solution for recovering embedded energy from that garbage. In more detail, we study the feasibility of an absorption plant able to exploit the residual energy of the flue gas of the ship’s incinerator. No payload space shall be sacrificed to install the considered absorption plant. Furthermore, it can be integrated with the existing plants providing for a limited number of heat exchangers. The recovered energy can be used to control the temperature of the refrigerated storerooms; operating simultaneously with, or in place of the existing compression vapors system already installed; it allows a reduction of the CO2 emissions and of fuel consumption. We show that the proposed approach can be applied to a variety of cruise ships, independently of their tonnage or passenger capacity.
Beyond Fake News and Fact-Checking: A Special Issue to Understand the Political, Social and Technological Consequences of the Battle against Misinformation and Disinformation
Authors: Rúas Araujo José , Wihbey John P. , Barredo-Ibáñez Daniel
Published: March 2022

Disinformation, hoaxes and false news are part of our daily lives and have numerous antecedents throughout history, and there have been many authors who have described the parallel between communication theories and propaganda theories (Barredo Ibáñez 2021) [...]
COVID-19—A Black Swan for Foreign Direct Investment: Evidence from European Countries
Authors: Hysa Eglantina , Imeraj Erinda , Feruni Nerajda , Panait Mirela , Vasile Valentina
Published: March 2022

This study aims to reconsider the role of foreign direct investment determinants for European national development and to analyze the impacts of the pandemic situation caused by COVID-19. Foreign direct investment is a source of development; therefore, this study includes empirical applications, specifically the random effect model, for EU countries, during the pandemic period. This study provides some valuable conclusions regarding the changes caused by the main determinants of foreign direct investment, such as unemployment, interest rates, economic growth, inflation, and business confidence. Additionally, the proxies of COVID-19 are the number of cases and number of deaths, both appearing to positively contribute to FDI outflow, the former with a higher impact than the latter. Based on the availability of the data, this paper deals with 22 European Union countries for Q1, Q2, and Q3 of 2020. Data for all the chosen variables were not available for the fourth quarter (Q4); thus, this period was not considered, which constitutes a limitation of this study, but confirms the need for robust FDI inflows to support the sustainable post-pandemic development recovery of less-developed EU countries. As the need for external funding sources, i.e., FDI inflow, grows in times of crisis, governments should take suitable measures to uplift the confidence of socially responsible foreign investors during difficult times generated by black swan events. There is almost no detailed research regarding the impact of COVID-19 on FDI flows received by European Union countries.
Sensitivity of Machine Learning Approaches to Fake and Untrusted Data in Healthcare Domain
Authors: Marulli Fiammetta , Marrone Stefano , Verde Laura
Published: March 2022

Machine Learning models are susceptible to attacks, such as noise, privacy invasion, replay, false data injection, and evasion attacks, which affect their reliability and trustworthiness. Evasion attacks, performed to probe and identify potential ML-trained models’ vulnerabilities, and poisoning attacks, performed to obtain skewed models whose behavior could be driven when specific inputs are submitted, represent a severe and open issue to face in order to assure security and reliability to critical domains and systems that rely on ML-based or other AI solutions, such as healthcare and justice, for example. In this study, we aimed to perform a comprehensive analysis of the sensitivity of Artificial Intelligence approaches to corrupted data in order to evaluate their reliability and resilience. These systems need to be able to understand what is wrong, figure out how to overcome the resulting problems, and then leverage what they have learned to overcome those challenges and improve their robustness. The main research goal pursued was the evaluation of the sensitivity and responsiveness of Artificial Intelligence algorithms to poisoned signals by comparing several models solicited with both trusted and corrupted data. A case study from the healthcare domain was provided to support the pursued analyses. The results achieved with the experimental campaign were evaluated in terms of accuracy, specificity, sensitivity, F1-score, and ROC area.
Conflict Analysis of Physical Industrial Land Development Policy Using Game Theory and Graph Model for Conflict Resolution in Markazi Province
Authors: Aghmashhadi Amir H. , Zahedi Samaneh , Kazemi Azadeh , Fürst Christine , Cirella Giuseppe T.
Published: March 2022

Industrial growth and development are among the integral components of economic development in developing countries such as Iran. Markazi province in the central part of Iran is one of the most prone areas for industrial progress due to its geopolitical location, proximity to the capital and major cities, and access via Iran’s western corridor. Over the last few decades, the concentration of major industries in combination with a lack of environmental safeguards have led to major environmental concerns, such that the province’s industrial development faces serious challenges going forward. This paper analyzes how to resolve these challenges through strategic analysis of stakeholder interactions using a Graph Model for Conflict Resolution, i.e., a non-cooperative model of game theory. Results indicate that, from a strategic point of view, the main cause of the conflict is over physical industrial land development in Markazi province by way of rationality and organizational benefits from stakeholders. It was shown that the insistence from the Industry and Mining Organization on industrial development and the Department of Environment on the preservation of natural resources and the environment, on the one hand, and the prevention of their further destruction, on the other, have made it difficult to find a cooperative solution. The findings further unveiled that in a non-cooperative scenario (i.e., the current situation), the equilibrium point of the conflict is status 16 (i.e., among the 18 situations) and no unilateral progression from either party can be detected. Via the equilibrium point, if the current preferences of the parties cannot be resolved, the conflict will remain at a deadlock leaving the environment at risk of further degradation.
The Interpretation of Implicit Arguments in Paraguayan Guaraní
Authors: Tonhauser Judith
Published: March 2022

Paraguayan Guaraní allows for implicit arguments, that is, arguments that are neither cross-referenced on the verb nor realized by an independent noun phrase. Building on prior description of the distribution of implicit arguments in the language, this paper describes the interpretations such arguments can receive. Specifically, the paper shows that implicit arguments in Paraguayan Guaraní can receive elided and existential interpretations, in addition to the anaphoric interpretation described in prior work.