bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Angiogenesis by Exosomes Secreted by Adipose-Derived Stem Cells upon Lipopolysaccharide Stimulation
Authors: Wu Shao-Chun , Kuo Pao-Jen , Rau Cheng-Shyuan , Huang Lien-Hung , Lin Chia-Wei , Wu Yi-Chan , Wu Chia-Jung , Tsai Chia-Wen , Hsieh Ting-Min , Liu Hang-Tsung , Huang Chun-Ying , Hsieh Ching-Hua
Published: August 2021

Exosomes secreted by adipose-derived stem cells (ADSCs) enhance angiogenesis and wound healing. However, in clinical settings, wounds may be infected by various bacteria or pathogens. We investigated whether human ADSCs stimulated with lipopolysaccharide (LPS) secrete exosomes (ADSC-LPS-exo) that augment the angiogenesis of human umbilical vein endothelial cells (HUVECs). ExoQuick-TC exosome precipitation solution was used to purify exosomes from human ADSC culture media in the presence or absence of 1 µg/mL LPS treatment for 24 h. The uptake of ADSC-LPS-exo significantly induced the activation of cAMP response element binding protein (CREB), activating protein 1 (AP-1), and nuclear factor-κB (NF-κB) signaling pathways and increased the migration of and tube formation in HUVECs. RNA interference with CREB, AP-1, or NF-κB1 significantly reduced the migration of and tube formation in HUVECs treated with ADSC-LPS-exo. An experiment with an antibody array for 25 angiogenesis-related proteins revealed that only interleukin-8 expression was significantly upregulated in HUVECs treated with ADSC-LPS-exo. In addition, proteomic analysis revealed that eukaryotic translation initiation factor 4E, amyloid beta A4 protein, integrin beta-1, and ras-related C3 botulinum toxin substrate 1 may be potential candidates involved in ADSC-LPS-exo-mediated enhanced angiogenesis.
Screening Anti-Inflammatory Effects of Flavanones Solutions
Authors: Bustos-Salgado Paola , Andrade-Carrera Berenice , Domínguez-Villegas Valeri , Díaz-Garrido Natalia , Rodríguez-Lagunas María J. , Badía Josefa , Baldomà Laura , Mallandrich Mireia , Calpena-Campmany Ana , Garduño-Ramírez María Luisa
Published: August 2021

There are a large number of remedies in traditional medicine focused on relieving pain and inflammation. Flavanones have been a potential source in the search for leading compounds and biologically active components, and they have been the focus of much research and development in recent years. Eysenhardtia platycarpa is used in traditional medicine for the treatment of kidney diseases, bladder infections, and diabetes mellitus. Many compounds have been isolated from this plant, such as flavones, flavanones, phenolic compounds, triterpenoid acids, chalcones, sugars, and fatty acids, among others. In this paper, natural flavanone 1 (extracted from Eysenhardtia platycarpa) as lead compound and flavanones 1a–1d as its structural analogues were screened for anti-inflammatory activity using Molinspiration® and PASS Online in a computational study. The hydro alcoholic solutions (FS) of flavanones 1, 1a–1d (FS1, FS1a–FS1d) were also assayed to investigate their in vivo anti-inflammatory cutaneous effect using two experimental models, a rat ear edema induced by arachidonic acid (AA) and a mouse ear edema induced by 12-O-tetradecanoylphorbol acetate (TPA). Histological studies and analysis of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 were also assessed in AA-inflamed rat ear tissue. The results showed that the flavanone hydro alcoholic solutions (FS) caused edema inhibition in both evaluated models. This study suggests that the evaluated flavanones will be effective when used in the future in skin pathologies with inflammation, with the results showing 1b and 1d to be the best.
Modulation of PTPN2/22 Function by Spermidine in CRISPR-Cas9-Edited T-Cells Associated with Crohn’s Disease and Rheumatoid Arthritis
Authors: Shaw Ameera M. , Qasem Ahmad , Naser Saleh A.
Published: August 2021

Crohn’s Disease (CD) and Rheumatoid Arthritis (RA) share some single nucleotide polymorphisms (SNPs) in protein tyrosine phosphatase non-receptor types 2 and 22 (PTPN2/22). Recently, we reported that clinical samples from CD and RA patients associated with PTPN2:rs478582 or PTPN22:rs2476601 genotypes were linked to overactive immune response and exacerbation of inflammation. Here, we investigated in vitro the effects of these SNPs in Jurkat T-cells using CRISPR-Cas9. All cells were evaluated for PTPN22/22 loss of function and effects on cell response. We measured gene expression via RT-qPCR and cytokines by ELISA. We also measured cell proliferation using a BrdU labeling proliferation ELISA, and T-cell activation using CD-25 fluorescent immunostaining. In PTPN2 SNP-edited cells, PTPN2 expression decreased by 3.2-fold, and proliferation increased by 10.2-fold compared to control. Likewise, expression of PTPN22 decreased by 2.4-fold and proliferation increased by 8.4-fold in PTPN22 SNP-edited cells. IFN-γ and TNF-α secretions increased in both edited cell lines. CD25 expression (cell activation) was 80.32% in PTPN2 SNP-edited cells and 85.82% in PTPN22 SNP-edited cells compared to 70.48% in unedited Jurkat T-cells. Treatment of PTPN2 and PTPN22-edited cells with a maximum 20 μM spermidine restored PTPN2/22 expression and cell response including cell proliferation, activation, and cytokines secretion. Most importantly, the effect of spermidine on edited cells restored normal expression and secretion of IFN-γ and TNF-α. The data clearly demonstrated that edited SNPs in PTPN2 or PTPN22 were associated with reduced gene expression, which resulted in an increase in cell proliferation and activation and overactive immune response. The data validated our earlier observations in CD and RA clinical samples. Surprisingly, spermidine restored PTPN2/22 expression in edited Jurkat T-cells and the consequent beneficial effect on cell response and inflammation. The study supports the use of polyamines dietary supplements for management of CD and in RA patients.
Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy
Authors: Kryczka Jolanta , Kryczka Jakub , Czarnecka-Chrebelska Karolina H. , Brzeziańska-Lasota Ewa
Published: August 2021

Cancer cells utilise several mechanisms to increase their survival and progression as well as their resistance to anticancer therapy: deregulation of growth regulatory pathways by acquiring grow factor independence, immune system suppression, reducing the expression of antigens activating T lymphocyte cells (mimicry), induction of anti-apoptotic signals to counter the action of drugs, activation of several DNA repair mechanisms and driving the active efflux of drugs from the cell cytoplasm, and epigenetic regulation by microRNAs (miRNAs). Because it is commonly diagnosed late, lung cancer remains a major malignancy with a low five-year survival rate; when diagnosed, the cancer is often highly advanced, and the cancer cells may have acquired drug resistance. This review summarises the main mechanisms involved in cisplatin resistance and interactions between cisplatin-resistant cancer cells and the tumour microenvironment. It also analyses changes in the gene expression profile of cisplatin sensitive vs. cisplatin-resistant non-small cell lung cancer (NSCLC) cellular model using the GSE108214 Gene Expression Omnibus database. It describes a protein-protein interaction network that indicates highly dysregulated TP53, MDM2, and CDKN1A genes as they encode the top networking proteins that may be involved in cisplatin tolerance, these all being upregulated in cisplatin-resistant cells. Furthermore, it illustrates the multifactorial nature of cisplatin resistance by examining the diversity of dysregulated pathways present in cisplatin-resistant NSCLC cells based on KEGG pathway analysis.
Role of Activating Transcription Factor 4 in Murine Choroidal Neovascularization Model
Authors: Yasuda Hiroto , Tanaka Miruto , Nishinaka Anri , Nakamura Shinsuke , Shimazawa Masamitsu , Hara Hideaki
Published: August 2021

Neovascular age-related macular degeneration (nAMD) featuring choroidal neovascularization (CNV) is the principal cause of irreversible blindness in elderly people in the world. Integrated stress response (ISR) is one of the intracellular signals to be adapted to various stress conditions including endoplasmic reticulum (ER) stress. ISR signaling results in the upregulation of activating transcription factor 4 (ATF4), which is a mediator of ISR. Although recent studies have suggested ISR contributes to the progression of some age-related disorders, the effects of ATF4 on the development of CNV remain unclear. Here, we performed a murine model of laser-induced CNV and found that ATF4 was highly expressed in endothelial cells of the blood vessels of the CNV lesion site. Exposure to integrated stress inhibitor (ISRIB) reduced CNV formation, vascular leakage, and the upregulation of vascular endothelial growth factor (VEGF) in retinal pigment epithelium (RPE)-choroid-sclera complex. In human retinal microvascular endothelial cells (HRMECs), ISRIB reduced the level of ATF4 and VEGF induced by an ER stress inducer, thapsigargin, and recombinant human VEGF. Moreover, ISRIB decreased the VEGF-induced cell proliferation and migration of HRMECs. Collectively, our findings showed that pro-angiogenic effects of ATF4 in endothelial cells may be a potentially therapeutic target for patients with nAMD.
Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease
Authors: Lin Peiya , Niimi Hiromi , Ohsugi Yujin , Tsuchiya Yosuke , Shimohira Tsuyoshi , Komatsu Keiji , Liu Anhao , Shiba Takahiko , Aoki Akira , Iwata Takanori , Katagiri Sayaka
Published: August 2021

Periodontitis is an inflammatory disease characterized by the destruction of the periodontium. In the last decade, a new murine model of periodontitis has been widely used to simulate alveolar bone resorption and periodontal soft tissue destruction by ligation. Typically, 3-0 to 9-0 silks are selected for ligation around the molars in mice, and significant bone loss and inflammatory infiltration are observed within a week. The ligature-maintained period can vary according to specific aims. We reviewed the findings on the interaction of systemic diseases with periodontitis, periodontal tissue destruction, the immunological and bacteriological responses, and new treatments. In these studies, the activation of osteoclasts, upregulation of pro-inflammatory factors, and excessive immune response have been considered as major factors in periodontal disruption. Multiple genes identified in periodontal tissues partly reflect the complexity of the pathogenesis of periodontitis. The effects of novel treatment methods on periodontitis have also been evaluated in a ligature-induced periodontitis model in mice. This model cannot completely represent all aspects of periodontitis in humans but is considered an effective method for the exploration of its mechanisms. Through this review, we aimed to provide evidence and enlightenment for future studies planning to use this model.
The Role of Antimicrobial Peptides in Preterm Birth
Authors: Son Ga-Hyun , Lee Jae-Jun , Kim Youngmi , Lee Keun-Young
Published: August 2021

Antimicrobial peptides (AMPs) are short cationic amphipathic peptides with a wide range of antimicrobial properties and play an important role in the maintenance of immune homeostasis by modulating immune responses in the reproductive tract. As intra-amniotic infection and microbial dysbiosis emerge as common causes of preterm births (PTBs), a better understanding of the AMPs involved in the development of PTB is essential. The altered expression of AMPs has been reported in PTB-related clinical presentations, such as preterm labor, intra-amniotic infection/inflammation, premature rupture of membranes, and cervical insufficiency. Moreover, it was previously reported that dysregulation of AMPs may affect the pregnancy prognosis. This review aims to describe the expression of AMPs associated with PTBs and to provide new perspectives on the role of AMPs in PTB.
Cellular Therapy for the Treatment of Paediatric Respiratory Disease
Authors: Brennan Laura C. , O’Sullivan Andrew , MacLoughlin Ronan
Published: August 2021

Respiratory disease is the leading cause of death in children under the age of 5 years old. Currently available treatments for paediatric respiratory diseases including bronchopulmonary dysplasia, asthma, cystic fibrosis and interstitial lung disease may ameliorate symptoms but do not offer a cure. Cellular therapy may offer a potential cure for these diseases, preventing disease progression into adulthood. Induced pluripotent stem cells, mesenchymal stromal cells and their secretome have shown great potential in preclinical models of lung disease, targeting the major pathological features of the disease. Current research and clinical trials are focused on the adult population. For cellular therapies to progress from preclinical studies to use in the clinic, optimal cell type dosage and delivery methods need to be established and confirmed. Direct delivery of these therapies to the lung as aerosols would allow for lower doses with a higher target efficiency whilst avoiding potential effect of systemic delivery. There is a clear need for research to progress into the clinic for the treatment of paediatric respiratory disease. Whilst research in the adult population forms a basis for the paediatric population, varying disease pathology and anatomical differences in paediatric patients means a paediatric-centric approach must be taken.
In Vivo Matrigel Plug Assay as a Potent Method to Investigate Specific Individual Contribution of Angiogenesis to Blood Flow Recovery in Mice
Authors: Aref Zeen , Quax Paul H. A.
Published: August 2021

Neovascularization restores blood flow recovery after ischemia in peripheral arterial disease. The main two components of neovascularization are angiogenesis and arteriogenesis. Both of these processes contribute to functional improvements of blood flow after occlusion. However, discriminating between the specific contribution of each process is difficult. A frequently used model for investigating neovascularization is the murine hind limb ischemia model (HLI). With this model, it is difficult to determine the role of angiogenesis, because usually the timing for the sacrifice of the mice is chosen to be optimal for the analysis of arteriogenesis. More importantly, the occurring angiogenesis in the distal calf muscles is probably affected by the proximally occurring arteriogenesis. Therefore, to understand and subsequently intervene in the process of angiogenesis, a model is needed which investigates angiogenesis without the influence of arteriogenesis. In this study we evaluated the in vivo Matrigel plug assay in genetic deficient mice to investigate angiogenesis. Mice deficient for interferon regulatory factor (IRF)3, IRF7, RadioProtective 105 (RP105), Chemokine CC receptor CCR7, and p300/CBP-associated factor (PCAF) underwent the in vivo Matrigel model. Histological analysis of the Matrigel plugs showed an increased angiogenesis in mice deficient of IRF3, IRF7, and RP105, and a decreased angiogenesis in PCAF deficient mice. Our results also suggest an involvement of CCR7 in angiogenesis. Comparing our results with results of the HLI model found in the literature suggests that the in vivo Matrigel plug assay is superior in evaluating the angiogenic response after ischemia.
Strategies to Improve the Antitumor Effect of γδ T Cell Immunotherapy for Clinical Application
Authors: Miyashita Masatsugu , Shimizu Teruki , Ashihara Eishi , Ukimura Osamu
Published: August 2021

Human γδ T cells show potent cytotoxicity against various types of cancer cells in a major histocompatibility complex unrestricted manner. Phosphoantigens and nitrogen-containing bisphosphonates (N-bis) stimulate γδ T cells via interaction between the γδ T cell receptor (TCR) and butyrophilin subfamily 3 member A1 (BTN3A1) expressed on target cells. γδ T cell immunotherapy is classified as either in vivo or ex vivo according to the method of activation. Immunotherapy with activated γδ T cells is well tolerated; however, the clinical benefits are unsatisfactory. Therefore, the antitumor effects need to be increased. Administration of γδ T cells into local cavities might improve antitumor effects by increasing the effector-to-target cell ratio. Some anticancer and molecularly targeted agents increase the cytotoxicity of γδ T cells via mechanisms involving natural killer group 2 member D (NKG2D)-mediated recognition of target cells. Both the tumor microenvironment and cancer stem cells exert immunosuppressive effects via mechanisms that include inhibitory immune checkpoint molecules. Therefore, co-immunotherapy with γδ T cells plus immune checkpoint inhibitors is a strategy that may improve cytotoxicity. The use of a bispecific antibody and chimeric antigen receptor might be effective to overcome current therapeutic limitations. Such strategies should be tested in a clinical research setting.
HOXB8 Counteracts MAPK/ERK Oncogenic Signaling in a Chicken Embryo Model of Neoplasia
Authors: Wilmerding Axelle , Bouteille Lauranne , Rinaldi Lucrezia , Caruso Nathalie , Graba Yacine , Delfini Marie-Claire
Published: August 2021

HOX transcription factors are members of an evolutionarily conserved family of proteins required for the establishment of the anteroposterior body axis during bilaterian development. Although they are often deregulated in cancers, the molecular mechanisms by which they act as oncogenes or tumor suppressor genes are only partially understood. Since the MAPK/ERK signaling pathway is deregulated in most cancers, we aimed at apprehending if and how the Hox proteins interact with ERK oncogenicity. Using an in vivo neoplasia model in the chicken embryo consisting in the overactivation of the ERK1/2 kinases in the trunk neural tube, we analyzed the consequences of the HOXB8 gain of function at the morphological and transcriptional levels. We found that HOXB8 acts as a tumor suppressor, counteracting ERK-induced neoplasia. The HOXB8 tumor suppressor function relies on a large reversion of the oncogenic transcriptome induced by ERK. In addition to showing that the HOXB8 protein controls the transcriptional responsiveness to ERK oncogenic signaling, our study identified new downstream targets of ERK oncogenic activation in an in vivo context that could provide clues for therapeutic strategies.
A Survey on Sentiment Analysis and Opinion Mining in Greek Social Media
Authors: Alexandridis Georgios , Varlamis Iraklis , Korovesis Konstantinos , Caridakis George , Tsantilas Panagiotis
Published: August 2021

As the amount of content that is created on social media is constantly increasing, more and more opinions and sentiments are expressed by people in various subjects. In this respect, sentiment analysis and opinion mining techniques can be valuable for the automatic analysis of huge textual corpora (comments, reviews, tweets etc.). Despite the advances in text mining algorithms, deep learning techniques, and text representation models, the results in such tasks are very good for only a few high-density languages (e.g., English) that possess large training corpora and rich linguistic resources; nevertheless, there is still room for improvement for the other lower-density languages as well. In this direction, the current work employs various language models for representing social media texts and text classifiers in the Greek language, for detecting the polarity of opinions expressed on social media. The experimental results on a related dataset collected by the authors of the current work are promising, since various classifiers based on the language models (naive bayesian, random forests, support vector machines, logistic regression, deep feed-forward neural networks) outperform those of word or sentence-based embeddings (word2vec, GloVe), achieving a classification accuracy of more than 80%. Additionally, a new language model for Greek social media has also been trained on the aforementioned dataset, proving that language models based on domain specific corpora can improve the performance of generic language models by a margin of 2%. Finally, the resulting models are made freely available to the research community.
Cell Line Platforms Support Research into Arthropod Immunity
Authors: Goodman Cynthia L. , Kang David S. , Stanley David
Published: August 2021

Innate immune responses are essential to maintaining insect and tick health and are the primary defense against pathogenic viruses, bacteria, and fungi. Cell line research is a powerful method for understanding how invertebrates mount defenses against pathogenic organisms and testing hypotheses on how these responses occur. In particular, immortal arthropod cell lines are valuable tools, providing a tractable, high-throughput, cost-effective, and consistent platform to investigate the mechanisms underpinning insect and tick immune responses. The research results inform the controls of medically and agriculturally important insects and ticks. This review presents several examples of how cell lines have facilitated research into multiple aspects of the invertebrate immune response to pathogens and other foreign agents, as well as comments on possible future research directions in these robust systems.
Comparative Transcriptome Analysis Reveals bmo-miR-6497-3p Regulate Circadian Clock Genes during the Embryonic Diapause Induction Process in Bivoltine Silkworm
Authors: Liu Lulu , Zhang Pan , Gao Qiang , Feng Xiaoge , Han Lan , Zhang Fengbin , Bai Yanmin , Han Minjin , Hu Hai , Dai Fangyin , Zhang Gaojun , Tong Xiaoling
Published: August 2021

Diapause is one of the survival strategies of insects for confronting adverse environmental conditions. Bombyx mori displays typical embryonic diapause, and offspring diapause depends on the incubation environment of the maternal embryo in the bivoltine strains of the silkworm. However, the molecular mechanisms of the diapause induction process are still poorly understood. In this study, we compared the differentially expressed miRNAs (DEmiRs) in bivoltine silkworm embryos incubated at diapause- (25 °C) and non-diapause (15 °C)-inducing temperatures during the blastokinesis (BK) and head pigmentation (HP) phases using transcriptome sequencing. There were 411 known miRNAs and 71 novel miRNAs identified during the two phases. Among those miRNAs, there were 108 and 74 DEmiRs in the BK and HP groups, respectively. By the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the predicted target genes of the DEmiRs, we found that aside from metabolism, the targets were also enriched in phototransduction-fly and insect hormone biosynthesis in the BK group and the HP group, respectively. Dual luciferase reporter assay illustrated that bmo-miR-6497-3p directly regulated Bmcycle and subsequently regulated the expression of circadian genes. These results imply that microRNAs, as vitally important regulators, respond to different temperatures and participate in the diapause induction process across species.
Capsella bursa-pastoris Is a Key Overwintering Plant for Aphids in the Mediterranean Region
Authors: Satar Serdar , Kavallieratos Nickolas G. , Tüfekli Mustafa , Satar Gül , Athanassiou Christos G. , Papanikolaou Nikos E. , Karacaoğlu Mehmet , Özdemir Işıl , Starý Petr
Published: August 2021

The reproduction of aphids depends to a great extent on their host plants, an integration that impacts on the successful expansion of overwintering populations. Therefore, a survey was conducted to evaluate the globally distributed Capsella bursa-pastoris as an overwintering host of economically important aphid species, their parasitoids and hyperparasitoids in the southern and western regions of Turkey from November to March in 2006 to 2013. During this survey, 395 samples of C. bursa-pastoris were collected with 25 aphid species recorded. Among aphids that feed on this host, Myzus persicae, Aphis gossypii, Rhopalosiphum padi, Aphis fabae, Aphis craccivora, Lipaphis erysimi, and Brevicoryne brassicae were the most frequently recorded. In total, 10,761 individual parasitoids were identified. Binodoxys angelicae, Aphidius colemani, Aphidius matricariae, Diaeretiella rapae, Ephedrus persicae, and Lysiphlebus confusus were the most abundant aphidiines that emerged from the aphids collected from C. bursa-pastoris. Alloxysta spp. (Hymenoptera: Cynipoidea), Chalcidoidea (unidentified at genus level), and Dendrocerus spp. (Hymenoptera: Ceraphronoidea) were identified as hyperparasitoids on the parasitoids. These findings indicate that C. bursa-pastoris is a key non-agricultural plant that significantly contributes to the overwintering of numerous aphids and their parasitoids, which should be given serious consideration when biological control strategies are designed.
Genome-Wide Identification of Neuropeptides and Their Receptors in an Aphid Endoparasitoid Wasp, Aphidius gifuensi
Authors: Kong Xue , Li Zhen-Xiang , Gao Yu-Qing , Liu Fang-Hua , Chen Zhen-Zhen , Tian Hong-Gang , Liu Tong-Xian , Xu Yong-Yu , Kang Zhi-Wei
Published: August 2021

In insects, neuropeptides and their receptors not only play a critical role in insect physiology and behavior but also are the potential targets for novel pesticide discoveries. Aphidius gifuensis is one of the most important and widespread aphid parasitoids, and has been successfully used to control aphid. In the present work, we systematically identified neuropeptides and their receptors from the genome and head transcriptome of A. gifuensis. A total of 35 neuropeptide precursors and 49 corresponding receptors were identified. The phylogenetic analyses demonstrated that 35 of these receptors belong to family-A, four belong to family-B, two belong to leucine-rich repeat-containing GPCRs, four belong to receptor guanylyl cyclases, and four belong to receptor tyrosine kinases. Oral ingestion of imidacloprid significantly up-regulated five neuropeptide precursors and four receptors whereas three neuropeptide precursors and eight receptors were significantly down-regulated, which indicated that these neuropeptides and their receptors are potential targets of some commercial insecticides. The RT-qPCR results showed that dopamine receptor 1, dopamine receptor 2, octopamine receptor, allatostatin-A receptor, neuropeptides capa receptor, SIFamide receptor, FMRFamide receptor, tyramine receptor and short neuropeptide F predominantly were expressed in the head whilst the expression of ion transport peptide showed widespread distribution in various tissues. The high expression levels of these genes suggest their important roles in the central nervous system. Taken together, our study provides fundamental information that may further our understanding of neuropeptidergic signaling systems in the regulation of the physiology and behavior of solitary wasps. Furthermore, this information could also aid in the design and discovery of specific and environment-friendly insecticides.
Poor Correction Capacity of Preexisting Ankle Valgus Deformity after Total Knee Arthroplasty
Authors: Shih Han-Ting , Liao Wei-Jen , Tu Kao-Chang , Lee Cheng-Hung , Tang Shih-Chieh , Wang Shun-Ping
Published: August 2021

This study investigated the differences in ankle alignment changes after TKA in patients with varying preexisting ankle deformities. We retrospectively examined 90 knees with osteoarthritis and varus deformity in 78 patients who underwent TKA. Preoperative and postoperative radiographic parameters were analyzed. According to their preexisting ankle deformity, patients were assigned to the valgus or varus group. Overall, 14 (15.6%) cases were of preoperative valgus ankle deformity; the remainder were of preoperative varus ankle deformity. Hip–knee–ankle angle (HKA), tibial plafond–ground angle (PGA), and talus–ground angle (TGA) all exhibited significant correction in both groups; however, tibial plafond–talus angle (PTA) and superior space of ankle joint (SS) only changed in the varus group. The median PTA and SS significantly decreased from 1.2° to 0.3° (p < 0.001) and increased from 2.5 to 2.6 mm (p = 0.013), respectively. Notably, ∆PTA positively correlated with ∆HKA in the varus group (r = 0.247, p = 0.032) but not in the valgus group. Between-group differences in postoperative PTA (p < 0.001) and ∆PTA (p < 0.001) were significant. The degree of ankle alignment correction after TKA differed between patients with preexisting varus and valgus ankle deformities. TKA could not effectively correct the preexisting ankle valgus malalignment.
Clinical Management of Moyamoya Patients
Authors: Canavero Isabella , Vetrano Ignazio Gaspare , Zedde Marialuisa , Pascarella Rosario , Gatti Laura , Acerbi Francesco , Nava Sara , Ferroli Paolo , Parati Eugenio Agostino , Bersano Anna
Published: August 2021

Moyamoya angiopathy (MMA) is a peculiar cerebrovascular condition characterized by progressive steno-occlusion of the terminal part of the internal carotid arteries (ICAs) and their proximal branches, associated with the development of a network of fragile collateral vessels at the base of the brain. The diagnosis is essentially made by radiological angiographic techniques. MMA is often idiopathic (moyamoya disease-MMD); conversely, it can be associated with acquired or hereditary conditions (moyamoya Syndrome-MMS); however, the pathophysiology underlying either MMD or MMS has not been fully elucidated to date, and this poor knowledge reflects uncertainties and heterogeneity in patient management. MMD and MMS also have similar clinical expressions, including, above all, ischemic and hemorrhagic strokes, then headaches, seizures, cognitive impairment, and movement disorders. The available treatment strategies are currently shared between idiopathic MMD and MMS, including pharmacological and surgical stroke prevention treatments and symptomatic drugs. No pharmacological treatment able to reverse the progressive disappearance of the ICAs has been found to date in both idiopathic and syndromic cases. Antithrombotic agents are usually prescribed in ischemic MMA, although the coexisting hemorrhagic risk should be considered. Surgical revascularization techniques, which are currently the best available treatment in symptomatic MMA, are associated with good long-term outcomes and reduced ischemic and hemorrhagic risks. Given the lack of dedicated randomized clinical trials, current treatment is mainly based on observational studies and physicians’ and surgeons’ expertise.
Lessons Learned from 30 Years of Transverse Myocutaneous Gracilis Flap Breast Reconstruction: Historical Appraisal and Review of the Present Literature and 300 Cases
Authors: Weitgasser Laurenz , Mahrhofer Maximilian , Schwaiger Karl , Bachleitner Kathrin , Russe Elisabeth , Wechselberger Gottfried , Schoeller Thomas
Published: August 2021

Background: Happy 30th birthday to the transverse myocutaneous gracilis (TMG) flap. Since 1991 the TMG flap has been used to reconstruct a wide variety of defects and became a workhorse flap and reliable alternative to the deep inferior epigastric perforator (DIEP) flap in many breast reconstruction services worldwide. This manuscript sheds light on the history and success of the TMG flap by critically reviewing the present literature and a series of 300 patients receiving a breast reconstruction. Patients and Methods: The present literature and history of the TMG flap was reviewed and a retrospective double center cohort study of 300 free TMG free flaps for autologous breast reconstruction was conducted. Patient demographics, perioperative data, and post-operative complications were recorded and compared with literature findings. Results: Mean flap weight was 320 g. Mean pedicle length was 70 mm. Complications included 19 (6.3%) flap loss. 10 patients (3.3%) had postoperative cellulitis and 28 (9.3%) wound healing disturbance of the donor site. Conclusion: Recipient and donor site complications were comparable to other free flaps used for breast reconstruction. A low BMI or the lack of an abdominal based donor site do not represent a limitation for breast reconstruction and can be overcome using the TMG flap.
Influence of the Human Development Index on the Maternal–Perinatal Morbidity and Mortality of Pregnant Women with SARS-CoV-2 Infection: Importance for Personalized Medical Care
Authors: Cuñarro-López Yolanda , Larroca Santiago García-Tizón , Pintado-Recarte Pilar , Hernández-Martín Concepción , Prats-Rodríguez Pilar , Cano-Valderrama Óscar , Cueto-Hernández Ignacio , Ruiz-Labarta Javier , Muñoz-Chápuli María del Mar , Martínez-Pérez Óscar , Ortega Miguel A. , De León-Luis Juan Antonio
Published: August 2021

Coronavirus disease-19 (COVID-19) is perhaps the most worrisome pandemic in the 21st century, having entailed devastating consequences for the whole society during the last year. Different studies have displayed an existing association between pregnancy and COVID-19 severity due to the various physiological changes that occur during gestation. Recent data identified maternal country of origin as an important determinant of COVID-19 presentation in pregnant women. However, the explanation of this fact remains to be fully elucidated. Therefore, the purpose of this work is to analyze the possible relationship between Human Development Index (HDI) of maternal country of origin with the morbimortality of pregnant women and their newborns. Here, we conducted a multicentric, ambispective, observational case-control study (1:1 ratio) and compare with the HDI of each country (group 1—very high HDI, group 2—high HDI, group 3—medium HDI, and group 4—low HDI). In total, 1347 pregnant women with confirmed SARV-CoV-2 infection (cases) were enrolled, and each was paired with one control to give a total number of 2694 participants from 81 tertiary care centers. Among the women with SARS-CoV-2 infection, more cases were produced of perinatal mortality, overall maternal morbidity, COVID-19 maternal morbidity, C-sections, hypertensive maternal morbidity, and perinatal morbidity. Our results described an inverse association between HDI and maternofetal morbidity and mortality. Moreover, the countries with an HDI lower than 1 showed higher rates of patients with maternal COVID-19-related morbidity (6.0% vs. 2.4%, p < 0.001), a need for oxygen therapy (4.7% vs. 1.8%, p < 0.001), and maternal ICU admission (2.6% vs. 1.0%, p = 0.007). Compared to other risk factors such as overweight, obesity, preexisting and obstetric comorbidities, HDI emerged as an independent risk factor explaining much of the increased maternal–perinatal morbidity and mortality detected in our group of cases. Further research is needed to establish to confirm the real impact of this factor and its components on pregnancy outcomes.
Clinical Characteristics and Outcomes of Adults with Nephrotic Syndrome Due to Minimal Change Disease
Authors: Lionaki Sophia , Mantios Evangelos , Tsoumbou Ioanna , Marinaki Smaragdi , Makris George , Liapis George , Vergandis Chrysovalantis , Boletis Ioannis
Published: August 2021

Purpose: Minimal change disease (MCD) is considered a relatively benign glomerulopathy, as it rarely progresses to end-stage kidney disease. The aim of this study was to describe the characteristics and outcomes of adults with MCD and identify potential risk factors for relapse. Patients & Methods: We retrospectively studied a cohort of adults with biopsy-proven MCD in terms of clinical features and treatment outcomes. Baseline characteristics and outcomes were recorded and predictors of relapse were analyzed using logistic regression multivariate analysis. Results: 59 patients with adult-onset primary MCD with nephrotic syndrome were included. Mean serum creatinine at diagnosis was 0.8 mg/dL (±2.5) and estimated GFR (eGFR) was 87 mL/min/1.73 m2 (±29.5). Mean serum albumin was 2.5 g/dL (±0.8) and 24 h proteinuria 6.8 g (±3.7). Microscopic hematuria was detected in 35 (58.5%) patients. 42 patients received prednisone alone, six patients received prednisone plus cyclophosphamide, five patients received prednisone plus cyclosporine, one patient received prednisone plus rituximab and five patients did not receive immunosuppression at all since they achieved spontaneous remission. During a mean follow up time of 34.7(22.1) months, 46.1% of patients experienced at least one episode of relapse. The mean age of patients who did not experience a relapse was significantly higher than that of patients who relapsed while relapsers had a significantly longer duration of 24 h proteinuria prior to biopsy compared to non-relapsers. Overall, 10% of patients experienced acute kidney injury while the mean eGFR at the end was 82 mL/min/1.73 m2 (±29.1) and one patient ended up in chronic dialysis. Overall, the proportion of non-relapsers, who experienced acute kidney injury (17%) was significantly higher than the one recorded among relapsers (0%).Conclusion: In this series of patients, almost 46% of adult-onset nephrotic MCD patients experienced a relapse, although their renal progression was rare. Younger onset age was an independent risk factor for relapse in adult-onset MCD patients.
Protocol Biopsies on de novo Renal-Transplants at 3 Months after Surgery: Impact on 5-Year Transplant Survival
Authors: Terrec Florian , Noble Johan , Naciri-Bennani Hamza , Malvezzi Paolo , Janbon Bénédicte , Emprou Camille , Giovannini Diane , Rostaing Lionel , Jouve Thomas
Published: August 2021

Background: In many centers, a protocol kidney biopsy (PKB) is performed at 3 months post-transplantation (M3), without a demonstrated benefit on death-censored graft survival (DCGS). In this study, we compared DCGS between kidney transplant recipients undergoing a PKB or without such biopsy while accounting for the obvious indication bias. Methods: In this retrospective, single-center study conducted between 2007 and 2013, we compared DCGS with respect to the availability and features of a PKB. We built a propensity score (PS) to account for PKB indication likelihood and adjusted the DCGS analysis on PKB availability and the PS. Results: A total of 615 patients were included: 333 had a PKB, 282 did not. In bivariate Kaplan–Meier survival analysis, adjusting for the availability of a PKB and for the PS, a PKB was associated with a better 5-year DCGS independently of the PS (p < 0.001). Among the PKB+ patients, 87 recipients (26%) had IF/TA > 0. Patients with an IF/TA score of 3 had the worst survival. A total of 144 patients (44%) showed cv lesions. Patients with cv2 and cv3 lesions had the worst 5-year DCGS. Conclusions: A M3 PKB was associated with improved graft survival independently of potential confounders. These results could be explained by the early treatment of subclinical immunological events. It could be due to better management of the immunosuppressive regimen.
The Use of Adipose-Derived Stem Cells (ADSCs) and Stromal Vascular Fraction (SVF) in Skin Scar Treatment—A Systematic Review of Clinical Studies
Authors: Stachura Albert , Paskal Wiktor , Pawlik Weronika , Mazurek Maciej J. , Jaworowski Janusz
Published: August 2021

In recent years, lipofilling became a popular scar treatment method. Its beneficial outcomes have been partly attributed to the regenerative capacity of adipose-derived stem cells (ADSCs), suspended in an extracellular matrix—the stromal vascular fraction (SVF). The aim of this review was to verify if existing data support the clinical use of ADSC-related interventions in scar treatment. A systematic search of the literature was performed in July 2020 in five databases (Medline, Cochrane, Web of Science, Scopus and Embase). Articles written in English, except for reviews, letters and editorials, were identified and screened for eligibility. We looked for reports of any outcomes in scars treated with ADSCs or SVF. Data from selected articles were extracted and the quality of each study was assessed. Five hundred and fourteen studies were identified in the primary search, of which nineteen were eventually included in the systematic review. Extracted data pointed to beneficial microscopic, functional and aesthetic outcomes in a total of 665 patients. Six studies included comparative interventions—platelet-rich plasma or CO2 fractional laser. Collected data give low-to-average quality evidence for beneficial effects of ADSC-related interventions in scar treatment. Some studies suggest that these interventions are noninferior to PRP or fractional CO2 laser.
Relationship between Psoriasis and Prevalence of Cardiovascular Disease in 88 Japanese Patients
Authors: Yamazaki Fumikazu , Takehana Kazuya , Tanaka Akihiro , Son Yonsu , Ozaki Yoshio , Tanizaki Hideaki
Published: August 2021

Psoriasis is a systemic inflammatory disease known to affect survival in the presence of cerebral or cardiovascular comorbidities. However, no clear guidelines have been defined regarding the extent of vascular lesion testing that should be performed in patients with psoriasis. We therefore performed coronary computed tomography angiography (CCTA) in 88 Japanese patients with psoriasis who visited Kansai Medical University Hospital between 2015 and 2019 and determined the ankle–brachial pressure index (ABI) for 44 of these patients. CCTA abnormalities were found in 39 of the 88 patients, and a need for treatment was identified in 14 patients. The prevalence of cardiovascular lesions in these patients was 15.9%, significantly higher than that in the healthy Japanese population (6.38% according to the Suita Study). In the 44 patients with results for both ABI and CCTA, the rates of CCTA vascular lesions were significantly higher in cases with ABIs indicating hard vessels or above than in cases with supple, normal, or slightly stiff vessels. This is the first report to show a correlation between CCTA and ABI in psoriasis patients. ABI was considered useful as a preliminary test before CCTA. The univariate analysis of the abnormal and normal CCTA groups showed that the prevalence differed significantly among patients with psoriatic arthritis, erythrodermic psoriasis, older age, pre-existing conditions, drinking, and hypertension. The multivariate analysis showed correlations with arthritic or erythrodermic psoriasis.
Risks of Recurrent Cardiovascular Events and Mortality in 1-Year Survivors of Acute Myocardial Infarction Implanted with Newer-Generation Drug-Eluting Stents
Authors: Lim Sungmin , Choo Eun Ho , Choi Ik Jun , Lee Kwan Yong , Lee Su Nam , Hwang Byung-Hee , Kim Chan Joon , Park Mahn-Won , Lee Jong-Min , Park Chul Soo , Kim Hee-Yeol , Yoo Ki-Dong , Jeon Doo Soo , Youn Ho Joong , Chung Wook Sung , Kim Min Chul , Jeong Myung Ho , Yim Hyeon Woo , Ahn Youngkeun , Chang Kiyuk
Published: August 2021

Current treatments for acute myocardial infarction (AMI) have dramatically improved clinical outcomes during the first year after AMI. Less is known, however, about the subsequent risks of recurrent cardiovascular events and mortality in patients who survive 1 year after AMI. The purpose of the present study is to evaluate long-term clinical outcomes in 1-year AMI survivors who were implanted with newer-generation drug-eluting stents (DESs) since 2010. The COREA-AMI (CardiOvascular Risk and idEntificAtion of potential high-risk population in AMI) registry consecutively enrolled AMI patients who underwent percutaneous coronary intervention (PCI), and patients who received newer-generation DESs since 2010 were analyzed. The primary endpoint was major adverse cardiovascular events (MACEs), and secondary endpoint was all-cause mortality. Of 6242 AMI patients, 5397 were alive 1 year after the index procedure. The cumulative incidence of MACEs and all-cause death 1 to 7 years after AMI were 28.4% (annually 4–6%) and 20.2% (annually 3–4%), respectively. Multivariate analysis showed that uncontrolled systolic blood pressure (SBP) and serum low-density lipoprotein cholesterol (LDL-C) concentration, as well as traditional risk factors, were associated with MACEs and all-cause death. Recurrent non-fatal myocardial infarction, ischemic stroke, and bleeding events within 1 year were significantly associated with all-cause death. The risks of adverse cardiovascular events and death remain high in AMI patients more than 1 year after the index PCI with newer-generation DESs. Traditional risk factors, uncontrolled SBP and LDL-C, and non-fatal adverse events within 1 year after the index procedure strongly influence long-term clinical outcomes.
A Reperfusion BOLD-MRI Tissue Perfusion Protocol Reliably Differentiate Patients with Peripheral Arterial Occlusive Disease from Healthy Controls
Authors: Törngren Kristina , Eriksson Stefanie , Arvidsson Jonathan , Falkenberg Mårten , Johnsson Åse A. , Sjöberg Carl , Lagerstrand Kerstin , Nordanstig Joakim
Published: August 2021

There is no established technique that directly quantifies lower limb tissue perfusion. Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) is an MRI technique that can determine skeletal muscle perfusion. BOLD-MRI relies on magnetic differences of oxygenated and deoxygenated hemoglobin, and regional changes in oxy/deoxyhemoglobin ratio can be recorded by T2* weighted MRI sequences. We aimed to test whether BOLD-MRI can differentiate lower limb tissue perfusion in peripheral arterial occlusive disease (PAOD) patients and healthy controls. Twenty-two PAOD patients and ten healthy elderly volunteers underwent lower limb BOLD-MRI. Reactive hyperemia was provoked by transient cuff compression and images of the gastrocnemius and soleus muscles were continuously acquired at rest, during ischemia and reperfusion. Key BOLD parameters were baseline T2* absolute value and time to T2* peak value after cuff deflation (TTP). Correlations between imaging parameters and ankle-brachial index (ABI) was investigated. The mean TTP was considerably prolonged in PAOD patients compared to healthy controls (m. gastrocnemius: 111 ± 46 versus 48 ± 22 s, p = 0.000253; m. soleus: 100 ± 42 versus 41 ± 30 s, p = 0.000216). Both gastrocnemius and soleus TTP values correlated strongly with ABI (−0.82 and −0.78, p < 0.01). BOLD-MRI during reactive hyperemia differentiated most PAOD patients from healthy controls. TTP was the most decisive parameter and strongly correlated with the ABI.
Immunomodulatory Effect of Withania somnifera (Ashwagandha) Extract—A Randomized, Double-Blind, Placebo Controlled Trial with an Open Label Extension on Healthy Participants
Authors: Tharakan Ajit , Shukla Himanshu , Benny Irin Rosanna , Tharakan Matthan , George Lekha , Koshy Santhosh
Published: August 2021

The immunomodulatory effect of Withania somnifera (WS) extract was tested in healthy adults. In this randomized placebo-controlled double-blinded study, subjects were allocated either 60 mg WS extract or placebo. It consists of a blinded 30-day period and an open-label extension study of another 30 days with crossover of only placebo to test. After the 30-day blinded study period, the WS test group reported significant increase (p < 0.05) in Ig’s (IgA, IgM, IgG, IgG2, IgG3 and IgG4), Cytokines (IFN-γ, IL4), TBNK (CD45+, CD3+, CD4+, CD8+, CD19+, NK cells) whereas in the placebo group TBNK cells showed significant decrease (p < 0.05) and Ig’s and cytokines showed no change (p > 0.05). In the extension period on day 60, the subjects on placebo who were crossed over to the WS test group showed significant increase (p < 0.05) in Ig’s, cytokines and TBNK cells and the subjects who continued on the WS group showed a further significant improvement (p < 0.05) in Ig’s, cytokines and TBNK cells. There were no adverse events reported in the study. WS extract significantly improved the immune profile of healthy subjects by modulating the innate and adaptive immune systems. Boosting the immune system of people at risk of infection and during widespread infections can be targeted with WS extract.