bluuebunny/crossref_metadata_2025 huggingface dataset:
JAK2 Phosphorylation Signals and Their Associated Cytokines Involved in Chronic Rhinosinusitis with Nasal Polyps and Correlated with Disease Severity
Authors: Lin Yu-Tsai , Chen Wei-Chih , Tsai Ming-Hsien , Chen Jing-Ying , Chien Chih-Yen , Huang Shun-Chen
Published: July 2021

Janus kinase 2 (JAK2) is a member of the JAK family that transduces cytokine-mediated signals via the JAKs/STATs (signal transducer and activator of transcription proteins) pathway, which plays an important role in many inflammatory diseases. This study investigates the association of p-JAK2 and JAK2-associated cytokines from nasal polyp (NP) tissue with disease severity, and evaluates the p-JAK2-mediated STATs in chronic rhinosinusitis (CRS) with NP. Sixty-one CRSwNP patients with nasal polyps undergoing endoscopic sinus surgery were enrolled, while the turbinate tissues from 26 nasal obstruction patients were examined as the control group. Elevated levels of p-JAK2 were detected in CRSwNP, and significantly correlated with scores of disease severity (LMK-CT, TPS, and SNOT-22). Expressions of the JAK2-associated cytokines, such as IL-5, IL-6, IL-13, G-CSF, and IFN-γ were significantly higher in CRSwNP than in the controls, while the levels of IL-5, IL-6, IL-13, or G-CSF had positive correlation with scores of disease severity. Moreover, markedly increased expression of p-STAT3 in CRSwNP was observed relative to the control. Taken together, these data showed that the JAK2-associated cytokines including IL-6 and G-CSF may stimulate JAK2 phosphorylation to activate p-STAT3, indicating an association with disease severity and supporting its development of JAK2 inhibitor as a potential therapeutic agent for CRS.
Intrinsic Disorder and Phosphorylation in BRCA2 Facilitate Tight Regulation of Multiple Conserved Binding Events
Authors: Julien Manon , Ghouil Rania , Petitalot Ambre , Caputo Sandrine M. , Carreira Aura , Zinn-Justin Sophie
Published: July 2021

The maintenance of genome integrity in the cell is an essential process for the accurate transmission of the genetic material. BRCA2 participates in this process at several levels, including DNA repair by homologous recombination, protection of stalled replication forks, and cell division. These activities are regulated and coordinated via cell-cycle dependent modifications. Pathogenic variants in BRCA2 cause genome instability and are associated with breast and/or ovarian cancers. BRCA2 is a very large protein of 3418 amino acids. Most well-characterized variants causing a strong predisposition to cancer are mutated in the C-terminal 700 residues DNA binding domain of BRCA2. The rest of the BRCA2 protein is predicted to be disordered. Interactions involving intrinsically disordered regions (IDRs) remain difficult to identify both using bioinformatics tools and performing experimental assays. However, the lack of well-structured binding sites provides unique functional opportunities for BRCA2 to bind to a large set of partners in a tightly regulated manner. We here summarize the predictive and experimental arguments that support the presence of disorder in BRCA2. We describe how BRCA2 IDRs mediate self-assembly and binding to partners during DNA double-strand break repair, mitosis, and meiosis. We highlight how phosphorylation by DNA repair and cell-cycle kinases regulate these interactions. We finally discuss the impact of cancer-associated variants on the function of BRCA2 IDRs and more generally on genome stability and cancer risk.
Adventitial Microcirculation Is a Major Target of SARS-CoV-2-Mediated Vascular Inflammation
Authors: Vasuri Francesco , Ciavarella Carmen , Collura Salvatore , Mascoli Chiara , Valente Sabrina , Degiovanni Alessio , Gargiulo Mauro , Capri Miriam , Pasquinelli Gianandrea
Published: July 2021

We report the case of a 77-year-old woman affected by coronavirus disease-19 (COVID-19) who developed an occlusive arterial disease of the lower limb requiring a left leg amputation. We studied the mechanisms of vascular damage by SARS-CoV-2 by means of a comprehensive multi-technique in situ analysis on the diseased popliteal arterial district, including immunohistochemistry (IHC), transmission electron microscopy (TEM) and miRNA analysis. At histological analyses, we observed a lymphocytic inflammatory infiltrate, oedema and endothelialitis of adventitial vasa vasorum while the media was normal and the intima had only minor changes. The vasa vasorum expressed the ACE2 receptor and factor VIII; compared with the controls, VEGFR2 staining was reduced. TEM analyses showed endothelial injury and numerous Weibel–Palade bodies in the cytoplasm. No coronavirus particle was seen. IL-6 protein and mRNA, together with miR-155-5p and miRs-27a-5p, which can target IL-6, were significantly increased compared with that in the controls. Our case report suggests an involvement of adventitial artery microcirculation by inflammation in the course of COVID-19. Without evident signs of current infection by SARS-CoV-2, endothelial cells show a spectrum of structural and functional alterations that can fuel the cardiovascular complications observed in people infected with SARS-CoV-2.
Relationship between Circulating PCSK9 and Markers of Subclinical Atherosclerosis—The IMPROVE Study
Authors: Coggi Daniela , Frigerio Beatrice , Bonomi Alice , Ruscica Massimiliano , Ferri Nicola , Sansaro Daniela , Ravani Alessio , Ferrante Palma , Damigella Manuela , Veglia Fabrizio , Capra Nicolò , Lupo Maria , Macchi Chiara , Savonen Kai , Silveira Angela , Kurl Sudhir , Giral Philippe , Pirro Matteo , Strawbridge Rona , Gigante Bruna , Smit Andries , Tremoli Elena , Amato Mauro , Baldassarre Damiano ,   on behalf of the IMPROVE Study Group
Published: July 2021

(1) Background and purpose: circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key regulators of cholesterol metabolism. Despite this, its role as a player in atherosclerosis development is still matter of debate. Here, we investigated the relationships between this protein and several markers of subclinical atherosclerosis. (2) Methods: the IMPROVE study enrolled 3703 European subjects (54–79 years; 48% men; with ≥3 vascular risk factors), asymptomatic for cardiovascular diseases. PCSK9 levels were measured by ELISA. B-mode ultrasound was used to measure markers of carotid subclinical atherosclerosis. (3) Results: in the crude analysis, PCSK9 levels were associated with several baseline measures of carotid intima-media thickness (cIMT) (all p < 0.0001); with cIMT change over time (Fastest-IMTmax-progr) (p = 0.01); with inter-adventitia common carotid artery diameter (ICCAD) (p < 0.0001); and with the echolucency (Grey Scale Median; GSM) of both carotid plaque and plaque-free common carotid IMT (both p < 0.0001). However, after adjustment for age, sex, latitude, and pharmacological treatment, all the afore-mentioned correlations were no longer statistically significant. The lack of correlation was also observed after stratification for sex, latitude, and pharmacological treatments. (4) Conclusions: in subjects who are asymptomatic for cardiovascular diseases, PCSK9 plasma levels do not correlate with vascular damage and/or subclinical atherosclerosis of extracranial carotid arteries.
Substance Use Outcomes from Two Formats of a Cognitive-Behavioral Intervention for Aggressive Children: Moderating Roles of Inhibitory Control and Intervention Engagement
Authors: Lochman John E. , Boxmeyer Caroline L. , Bui Chuong , Hakim Estephan , Jones Shannon , Kassing Francesca , McDonald Kristina , Powell Nicole , Qu Lixin , Dishion Thomas
Published: July 2021

Although cognitive-behavioral interventions have reduced the risk of substance use, little is known about moderating factors in children with disruptive behaviors. This study examined whether aggressive preadolescents’ inhibitory control and intervention engagement moderates the effect of group versus individual delivery on their substance use. Following screening for aggression in 4th grade, 360 children were randomly assigned to receive the Coping Power intervention in either group or individual formats. The sample was primarily African American (78%) and male (65%). Assessments were made of children’s self-reported substance use from preintervention through a six-year follow-up after intervention, parent-reported inhibitory control at preintervention, and observed behavioral engagement in the group intervention. Multilevel growth modeling found lower increases in substance use slopes for children with low inhibitory control receiving individual intervention, and for children with higher inhibitory control receiving group intervention. Children with low inhibitory control but who displayed more positive behavioral engagement in the group sessions had slower increases in their substance use than did similar children without positive engagement. Aggressive children’s level of inhibitory control can lead to tailoring of group versus individual delivery of intervention. Children’s positive behavioral engagement in group sessions is a protective factor for children with low inhibitory control.
Endogenous Expression of G-CSF in Rat Dorsal Root Ganglion Neurons after Nerve Injury
Authors: Yeh Chun-Chang , Yang Chih-Ping , Ma Kuo-Hsing , Shih Jui-Hu , Tseng Ching-San , Huang Yuahn-Sieh
Published: July 2021

Granulocyte colony-stimulating factor (G-CSF) has been reported to modulate pain function following nerve injury. However, the expression of endogenous G-CSF in the dorsal root ganglion (DRG) and the response to nerve injury remain unclear. In the present study, we demonstrated that G-CSF and G-CSFR are mainly expressed in both small- and medium-diameter DRG neurons in rats and are responsible for transmitting pain responses. G-CSF and G-CSFR were co-expressed in certain nociceptive DRG neurons. In addition, G-CSF was expressed in satellite glial cells around large-diameter DRG neurons. After sciatic nerve injury, the number of G-CSF-positive DRG neurons was increased in both the ipsilateral and contralateral lesion sites in rats. However, G-CSF expression in satellite glial cells was not affected by nerve injury. To clarify the role of G-CSF in pain, exogenous G-CSF was administered to a rat model of neuropathic pain induced by partial sciatic nerve transaction (PST). Our results indicate that treatment with G-CSF did not attenuate but exacerbated neuropathic pain. In summary, G-CSF may directly activate sensory neurons and contribute to nociceptive signaling.
Grief Iconography between Italians and Americans: A Comparative Study on How Mourning Is Visually Expressed on Social Media
Authors: Cupit Illene Noppe , Sapelli Paolo , Testoni Ines
Published: July 2021

As an innovative way to express grief, social media posts about the deceased have become fairly common. However, few studies have examined commonly posted grief photos. The purpose of the present study was to examine such pictures, as well as the motivations and reactions of those who posted them, among Italians and Americans. Surveys were sent to both Italian and US participants. The US group yielded 262 responses (mean age = 22 years; 81% female), and the Italian group yielded 51 (mean age = 32 years; 82% female). Several key issues emerged, such as the need for social media users to receive empathic support from other users, the desire to maintain continuing bonds, the wish to remember the deceased, and the desire to share beauty and symbolic pictures. The images were analyzed using content analysis. Both samples posted photos to remember, and to enhance their posts. A strong preference for pictures with a positive emotional connotation appeared, depicting the deceased in a conjoint appearance with the participant. The results suggest that the imagery used for the expression of grief in social media sites, an “iconography of grief”, is a popular means of expression for grievers across the two cultures.
Transition from Physical Design Studio to Emergency Virtual Design Studio. Available Teaching and Learning Methods and Tools—A Case Study
Authors: Komarzyńska-Świeściak Elżbieta , Adams Britt , Thomas Laura
Published: July 2021

At the core of architecture education are the design studio classes, where students test ideas, build physical models, and propose design projects in a shared creative environment. The COVID-19 pandemic in 2020 created a large disruption of this status quo and required a major shift in the whole experience of teaching and learning at design studios. Using a case study approach, the present paper describes the systematic process of translating Physical Design Studio into emergency Virtual Design Studio and how it has been perceived by students enrolled in the investigated courses. The focus was primarily on those tools and methods that were intended to compensate for traditional workshop methods (for example the tactile exercise of physical model making and pin-up board presentations). To meet this objective, available tools for performing Virtual Design Studio were assessed using experiences of Design Studio instructors on the one hand and students’ surveys on the other hand. The study’s results can be used as recommendations on how to optimally implement a transition from a Physical Design Studio environment to teaching a digital remote design studio. Furthermore, the results also add to creating design guidelines for setting up blended architecture education post-COVID-19.
Elevated Levels of CTRP1 in Obesity Contribute to Tumor Progression in a p53-Dependent Manner
Authors: Park Rackhyun , Jang Minsu , Park Yea-In , Park Yeonjeong , Namkoong Sim , Lee Jin I. , Park Junsoo
Published: July 2021

Mounting evidence supports the relationship between obesity and cancer. However, the molecular mechanisms linking obesity with cancer remain largely uninvestigated. In this study, we demonstrate that the expression of C1q/TNF-related protein 1 (CTRP1), an adiponectin paralogue, contributes to tumor growth by regulating the tumor suppressor p53. In our study, obese mice on a high-fat diet showed higher serum CTRP1 levels. Through in vitro experiments, we showed that the secreted form of CTRP1 in the culture medium decreased p53 expression and p53-dependent transcription in the cells. Moreover, CTRP1 treatment enhanced colony formation and cell migration. These results collectively suggest that elevated levels of CTRP1 in obesity significantly contribute to tumor progression.
Prognostic Impact of Immunoglobulin Kappa C (IGKC) in Early Breast Cancer
Authors: Schmidt Marcus , Edlund Karolina , Hengstler Jan G. , Heimes Anne-Sophie , Almstedt Katrin , Lebrecht Antje , Krajnak Slavomir , Battista Marco J. , Brenner Walburgis , Hasenburg Annette , Rahnenführer Jörg , Gehrmann Mathias , Kellokumpu-Lehtinen Pirkko-Liisa , Wirtz Ralph M. , Joensuu Heikki
Published: July 2021

We studied the prognostic impact of tumor immunoglobulin kappa C (IGKC) mRNA expression as a marker of the humoral immune system in the FinHer trial patient population, where 1010 patients with early breast cancer were randomly allocated to either docetaxel-containing or vinorelbine-containing adjuvant chemotherapy. HER2-positive patients were additionally allocated to either trastuzumab or no trastuzumab. Hormone receptor-positive patients received tamoxifen. IGKC was evaluated in 909 tumors using quantitative real-time polymerase chain reaction, and the influence on distant disease-free survival (DDFS) was examined using univariable and multivariable Cox regression and Kaplan–Meier estimates. Interactions were analyzed using Cox regression. IGKC expression, included as continuous variable, was independently associated with DDFS in a multivariable analysis also including age, molecular subtype, grade, and pT and pN stage (HR 0.930, 95% CI 0.870–0.995, p = 0.034). An independent association with DDFS was also found in a subset analysis of triple-negative breast cancers (TNBC) (HR 0.843, 95% CI 0.724–0.983, p = 0.029), but not in luminal (HR 0.957, 95% CI 0.867–1.056, p = 0.383) or HER2-positive (HR 0.933, 95% CI 0.826–1.055, p = 0.271) cancers. No significant interaction between IGKC and chemotherapy or trastuzumab administration was detected (Pinteraction = 0.855 and 0.684, respectively). These results show that humoral immunity beneficially influences the DDFS of patients with early TNBC.
Hyperthermic Intrathoracic Chemoperfusion for Malignant Pleural Mesothelioma: Systematic Review and Meta-Analysis
Authors: Järvinen Tommi , Paajanen Juuso , Ilonen Ilkka , Räsänen Jari
Published: July 2021

Malignant pleural mesothelioma (MPM) is an aggressive malignancy of the pleural lining with exceptionally poor survival. Hyperthermic intrathoracic chemoperfusion (HITHOC) is commonly used with surgery in limited disease. However, data on its effect on survival are limited. In this systematic review and meta-analysis, we analyzed a total of 11 observational articles. HITHOC was compared to control arm that did not receive HITHOC in three studies including 762 patients. The pooled analysis of these studies revealed an SMD of 0.24, with 95% CI of 0.06–0.41 favoring the HITHOC group, reaching statistical significance. The survival effect of HITHOC in epithelioid MPM vs. non-epithelioid MPM was analyzed in four studies. Pooled analysis showed an SMD of 0.79 (95% CI = 0.48–1.10) favoring epithelioid MPM. Based on available data, there seems to be a benefit with HITHOC in regards to overall survival in the treatment of all mesothelioma patients. Multicenter randomized controlled trials are needed to validate and standardize this treatment approach.
A Nationwide Study on the Impact of Routine Testing for EGFR Mutations in Advanced NSCLC Reveals Distinct Survival Patterns Based on EGFR Mutation Subclasses
Authors: Koopman Bart , Cajiao Garcia Betzabel N. , Kuijpers Chantal C. H. J. , Damhuis Ronald A. M. , van der Wekken Anthonie J. , Groen Harry J. M. , Schuuring Ed , Willems Stefan M. , van Kempen Léon C.
Published: July 2021

EGFR mutation analysis in non-small-cell lung cancer (NSCLC) patients is currently standard-of-care. We determined the uptake of EGFR testing, test results and survival of EGFR-mutant NSCLC patients in the Netherlands, with the overall objective to characterize the landscape of clinically actionable EGFR mutations and determine the role and clinical relevance of uncommon and composite EGFR mutations. Non-squamous NSCLC patients diagnosed in 2013, 2015 and 2017 were identified in the Netherlands Cancer Registry (NCR) and matched to the Dutch Pathology Registry (PALGA). Overall, 10,254 patients were included. Between 2013–2017, the uptake of EGFR testing gradually increased from 72.7% to 80.9% (p < 0.001). Multi-gene testing via next-generation sequencing (increased from 7.8% to 78.7% (p < 0.001), but did not affect the number of detected EGFR mutations (n = 925; 11.7%; 95% confidence interval (CI), 11.0–12.4) nor the distribution of variants. For patients treated with first-line EGFR inhibitors (n = 651), exon 19 deletions were associated with longer OS than L858R (HR 1.58; 95% CI, 1.30–1.92; p < 0.001) or uncommon, actionable variants (HR 2.13; 95% CI, 1.60–2.84; p < 0.001). Interestingly, OS for patients with L858R was similar to those with uncommon, actionable variants (HR 1.31; 95% CI, 0.98–1.75; p = 0.069). Our analysis indicates that grouping exon 19 deletions and L858R into one class of ‘common’ EGFR mutations in a clinical trial may mask the true activity of an EGFR inhibitor towards specific mutations.
Cellular Mechanisms of FGF-Stimulated Tissue Repair
Authors: Prudovsky Igor
Published: July 2021

Growth factors belonging to the FGF family play important roles in tissue and organ repair after trauma. In this review, I discuss the regulation by FGFs of the aspects of cellular behavior important for reparative processes. In particular, I focus on the FGF-dependent regulation of cell proliferation, cell stemness, de-differentiation, inflammation, angiogenesis, cell senescence, cell death, and the production of proteases. In addition, I review the available literature on the enhancement of FGF expression and secretion in damaged tissues resulting in the increased FGF supply required for tissue repair.
The RHO Family GTPases: Mechanisms of Regulation and Signaling
Authors: Mosaddeghzadeh Niloufar , Ahmadian Mohammad Reza
Published: July 2021

Much progress has been made toward deciphering RHO GTPase functions, and many studies have convincingly demonstrated that altered signal transduction through RHO GTPases is a recurring theme in the progression of human malignancies. It seems that 20 canonical RHO GTPases are likely regulated by three GDIs, 85 GEFs, and 66 GAPs, and eventually interact with >70 downstream effectors. A recurring theme is the challenge in understanding the molecular determinants of the specificity of these four classes of interacting proteins that, irrespective of their functions, bind to common sites on the surface of RHO GTPases. Identified and structurally verified hotspots as functional determinants specific to RHO GTPase regulation by GDIs, GEFs, and GAPs as well as signaling through effectors are presented, and challenges and future perspectives are discussed.
CD36 Signal Transduction in Metabolic Diseases: Novel Insights and Therapeutic Targeting
Authors: Karunakaran Udayakumar , Elumalai Suma , Moon Jun-Sung , Won Kyu-Chang
Published: July 2021

The cluster of differentiation 36 (CD36) is a scavenger receptor present on various types of cells and has multiple biological functions that may be important in inflammation and in the pathogenesis of metabolic diseases, including diabetes. Here, we consider recent insights into how the CD36 response becomes deregulated under metabolic conditions, as well as the therapeutic benefits of CD36 inhibition, which may provide clues for developing strategies aimed at the treatment or prevention of diabetes associated with metabolic diseases. To facilitate this process further, it is important to pinpoint regulatory mechanisms that are relevant under physiological and pathological conditions. In particular, understanding the mechanisms involved in dictating specific CD36 downstream cellular outcomes will aid in the discovery of potent compounds that target specific CD36 downstream signaling cascades.
The Influence of Virus Infection on Microglia and Accelerated Brain Aging
Authors: Filgueira Luis , Larionov Alexey , Lannes Nils
Published: July 2021

Microglia are the resident immune cells of the central nervous system contributing substantially to health and disease. There is increasing evidence that inflammatory microglia may induce or accelerate brain aging, by interfering with physiological repair and remodeling processes. Many viral infections affect the brain and interfere with microglia functions, including human immune deficiency virus, flaviviruses, SARS-CoV-2, influenza, and human herpes viruses. Especially chronic viral infections causing low-grade neuroinflammation may contribute to brain aging. This review elucidates the potential role of various neurotropic viruses in microglia-driven neurocognitive deficiencies and possibly accelerated brain aging.
Cryopreservation of Human Adipose Tissues and Adipose-Derived Stem Cells with DMSO and/or Trehalose: A Systematic Review
Authors: Crowley Conor A. , Smith William P. W. , Seah K. T. Matthew , Lim Soo-Keat , Khan Wasim S.
Published: July 2021

Adipose tissue senescence is implicated as a major player in obesity- and ageing-related disorders. There is a growing body of research studying relevant mechanisms in age-related diseases, as well as the use of adipose-derived stem cells in regenerative medicine. The cell banking of tissue by utilising cryopreservation would allow for much greater flexibility of use. Dimethyl sulfoxide (DMSO) is the most commonly used cryopreservative agent but is toxic to cells. Trehalose is a sugar synthesised by lower organisms to withstand extreme cold and drought that has been trialled as a cryopreservative agent. To examine the efficacy of trehalose in the cryopreservation of human adipose tissue, we conducted a systematic review of studies that used trehalose for the cryopreservation of human adipose tissues and adipose-derived stem cells. Thirteen articles, including fourteen studies, were included in the final review. All seven studies that examined DMSO and trehalose showed that they could be combined effectively to cryopreserve adipocytes. Although studies that compared nonpermeable trehalose with DMSO found trehalose to be inferior, studies that devised methods to deliver nonpermeable trehalose into the cell found it comparable to DMSO. Trehalose is only comparable to DMSO when methods are devised to introduce it into the cell. There is some evidence to support using trehalose instead of using no cryopreservative agent.
BNIP3-Dependent Mitophagy via PGC1α Promotes Cartilage Degradation
Authors: Kim Deokha , Song Jinsoo , Jin Eun-Jung
Published: July 2021

Since mitochondria are suggested to be important regulators in maintaining cartilage homeostasis, turnover of mitochondria through mitochondrial biogenesis and mitochondrial degradation may play an important role in the pathogenesis of osteoarthritis (OA). Here, we found that mitochondrial dysfunction is closely associated with OA pathogenesis and identified the peroxisome proliferator-activated receptor-gamma co-activator 1-alpha (PGC1α) as a potent regulator. The expression level of PGC1α was significantly decreased under OA conditions, and knockdown of PGC1α dramatically elevated the cartilage degradation by upregulating cartilage degrading enzymes and apoptotic cell death. Interestingly, the knockdown of PGC1α activated the parkin RBR E3 ubiquitin protein ligase (PRKN)-independent selective mitochondria autophagy (mitophagy) pathway through the upregulation of BCL2 and adenovirus E1B 19-kDa-interacting protein 3 (BNIP3). The overexpression of BNIP3 stimulated mitophagy and cartilage degradation by upregulating cartilage-degrading enzymes and chondrocyte death. We identified microRNA (miR)-126-5p as an upstream regulator for PGC1α and confirmed the direct binding between miR-126-5p and 3′ untranslated region (UTR) of PGC1α. An in vivo OA mouse model induced by the destabilization of medial meniscus (DMM) surgery, and the delivery of antago-miR-126 via intra-articular injection significantly decreased cartilage degradation. In sum, the loss of PGC1α in chondrocytes due to upregulation of miR-126-5p during OA pathogenesis resulted in the activation of PRKN-independent mitophagy through the upregulation of BNIP3 and stimulated cartilage degradation and apoptotic death of chondrocytes. Therefore, the regulation of PGC1α:BNIP3 mitophagy axis could be of therapeutic benefit to cartilage-degrading diseases.
Transcriptomic Profile Reveals Deregulation of Hearing-Loss Related Genes in Vestibular Schwannoma Cells Following Electromagnetic Field Exposure
Authors: Colciago Alessandra , Audano Matteo , Bonalume Veronica , Melfi Valentina , Mohamed Tasnim , Reid Adam J. , Faroni Alessandro , Greer Peter A. , Mitro Nico , Magnaghi Valerio
Published: July 2021

Hearing loss (HL) is the most common sensory disorder in the world population. One common cause of HL is the presence of vestibular schwannoma (VS), a benign tumor of the VIII cranial nerve, arising from Schwann cell (SC) transformation. In the last decade, the increasing incidence of VS has been correlated to electromagnetic field (EMF) exposure, which might be considered a pathogenic cause of VS development and HL. Here, we explore the molecular mechanisms underlying the biologic changes of human SCs and/or their oncogenic transformation following EMF exposure. Through NGS technology and RNA-Seq transcriptomic analysis, we investigated the genomic profile and the differential display of HL-related genes after chronic EMF. We found that chronic EMF exposure modified the cell proliferation, in parallel with intracellular signaling and metabolic pathways changes, mostly related to translation and mitochondrial activities. Importantly, the expression of HL-related genes such as NEFL, TPRN, OTOGL, GJB2, and REST appeared to be deregulated in chronic EMF exposure. In conclusion, we suggest that, at a preclinical stage, EMF exposure might promote the transformation of VS cells and contribute to HL.
Vitamin D Insufficiency Prior to Paediatric Liver Transplantation Is Associated with Early T-Cell Mediated Rejection
Authors: Rock Nathalie M. , Anghileri Elisa , Cousin Vladimir L. , Petit Laetitia-Marie , McLin Valérie A.
Published: July 2021

Objectives: T-cell mediated rejection (TCMR) can compromise long-term liver allograft survival. The immunomodulatory properties of vitamin D are increasingly recognized. We investigated whether perturbations in vitamin D metabolism prior to LT may predispose to TCMR in a representative cohort of paediatric LT recipients. Methods: In this retrospective single-center study of children who underwent liver transplantation between 2005 and 2017, we collected serum 25(OH) vitamin D levels and other parameters related to vitamin D metabolism. Post-transplant variables were collected from medical records during the first year following LT. Results: Eighty-two patients were included. Twenty-six (32%) developed TCMR, 52 (65%) presented at least one event of 25(OH) D insufficiency during the year before the transplant, while 23 (32%) had at least one documented elevated plasma parathyroid hormone level. Forty-six patients benefited from nutritional support (56%). The development of TCMR was associated with vitamin D insufficiency pre-LT (p = 0.01). No significant correlations were identified between PTH levels and incidence of TCMR. The association was stronger in patients transplanted for cholestatic diseases (p = 0.004). Conclusions: Vitamin D insufficiency before a liver transplant may be associated with TCMR during the first year post-LT. These findings warrant further investigation.
Airway Malacia: Clinical Features and Surgical Related Issues, a Ten-Year Experience from a Tertiary Pediatric Hospital
Authors: Ghezzi Michele , D’Auria Enza , Farolfi Andrea , Calcaterra Valeria , Zenga Alessandra , De Silvestri Annalisa , Pelizzo Gloria , Zuccotti Gian Vincenzo
Published: July 2021

Background: Few studies have been carried out with the aim of describing the clinical course and follow-up of patients with tracheomalacia. We aim to describe the symptoms at diagnosis and the post-treatment clinical course of patients affected by airway malacia. Methods: We retrospectively analyzed characteristics of pediatric patients with a diagnosis of airway malacia. Patients were classified into three groups: bronchomalacia (BM), tracheomalacia (TM) and tracheo-bronchomalacia (TBM). Demographic and clinical data, diagnostic work-up and surgical treatment were recorded. Results: 13/42 patients were affected by congenital syndromes (30.9%). Esophageal atresia with or without tracheal-esophageal fistula (EA/TEF) was detected in 7/42 patients (16.7%). Cardiovascular anomalies were found in 9/42 (21.4%) and idiopathic forms in 13/42 (30.9%). BM occurred in 7/42 (16.6%), TM in 23/42 (54.7%) and TBM in 12/42 (28.6%). At the diagnosis stage, a chronic cough was reported in 50% of cases with a higher prevalence in EA/TEF (p = 0.005). Surgery was performed in 16/42 (40%) of children. A chronic cough and acute respiratory failure were correlated to the need for surgery. During follow-up, there was no difference in persistence of symptoms between conservative vs surgical treatment (p = 0.47). Conclusion: the management of tracheomalacia remains a challenge for pediatricians. Clinical manifestations, such as a barking cough and acute respiratory failure may suggest the need for surgery. Follow-up is crucial, especially in those patients affected by comorbidities, so as to be able to manage effectively the possible persistence of symptoms, including those that may continue after surgical treatment.
Fluorescent Azobenzene-Containing Compounds: From Structure to Mechanism
Authors: Xue Lulu , Pan Ying , Zhang Shaohai , Chen Yinjie , Yu Haifeng , Yang Yonggang , Mo Lixin , Sun Zhicheng , Li Luhai , Yang Huai
Published: July 2021

The reversible photoisomerization of azobenzenes has been extensively studied to construct systems with optical responsiveness; however, this process limits the luminescence of these compounds. Recently, there have been many efforts to design and synthesize fluorescent azobenzene compounds, such as inhibition of electron transfer, inducing aggregation, and metal-enhancement, which make the materials ideal for application in fluorescence probes, light-emitting devices, molecular detection, etc. Herein, we review the recently reported progress in the development of various fluorescent azobenzenes and summarize the possible mechanism of their fluorescence emission. The potential applications of these materials are also discussed. Finally, in order to guide research in this field, the existing problems and future development prospects are discussed.
Black Coral Distribution in the Italian Seas: A Review
Authors: Ingrassia Michela , Di Bella Letizia
Published: July 2021

Antipatharian corals are important structural and complex members of benthic communities inhabiting the Italian seafloor. In this study, the distribution of black corals in Italy is reported and mapped for the first time. This review has permitted the identification of occurrences of such vulnerable marine ecosystems along the Italian coasts in a bathymetric range of 42 m to 790 m. Black corals appear to be most conspicuous and widely distributed in the mesophotic zone (from around 60 to 300 m depth), with a major occurrence on the rocky bottom and shoals. This review also highlights that these communities suffer direct damage from anthropogenic impacts (fishing activity and lost garbage). Finally, this study provides evidence that the reported Italian submarine sites associated with the occurrence of black corals probably represent only a small portion of their real distribution. This finding urges the need to increase monitoring efforts to support the protection and the conservation of these pristine species assemblages.
Diversity and Abundance of Roadkilled Bats in the Brazilian Atlantic Forest
Authors: Damásio Lucas , Ferreira Laís Amorim , Pimenta Vinícius Teixeira , Paneto Greiciane Gaburro , dos Santos Alexandre Rosa , Ditchfield Albert David , Bergallo Helena Godoy , Banhos Aureo
Published: July 2021

Faunal mortality from roadkill has a negative impact on global biodiversity, and bats are among the roadkilled animals. In South America, the Atlantic Forest covers southeastern Brazil, a region which sustains a large bat diversity. In this biome, the Sooretama reserves are crossed by the federal highway BR-101, one of the busiest in Brazil. We analyzed bats roadkilled along the 25 km stretch of highway that crosses the Sooretama reserves. Data were collected between the years 2010 and 2015. In total, 773 individuals distributed among 47 bat species were roadkilled during this period. The insectivorous feeding guild was the most affected, accounting for 25 species and 74% of the recorded roadkill, and those flying in the open area were the most frequently roadkilled (41.9%). Bat mortality rates did not differ between months of the year. However, the relation between rainy days and roadkill was negative. Monitoring by foot was more efficient than by car for detection of bat carcasses. Radars with a speed limit below 60 km/h reduced the rates of roadkill. The diversity of deceased bats found in this study represents 40% of the known species in the Atlantic Forest, and is the largest among current studies of species killed on highways globally. The present study raises concerns about the high diversity and abundance of roadkilled insectivorous bats and the conservation of these animals in the Neotropical region.
The Influence of the Exclusion of Central Necrosis on [18F]FDG PET Radiomic Analysis
Authors: Noortman Wyanne A. , Vriens Dennis , Mooij Charlotte D. Y. , Slump Cornelis H. , Aarntzen Erik H. , van Berkel Anouk , Timmers Henri J. L. M. , Bussink Johan , Meijer Tineke W. H. , de Geus-Oei Lioe-Fee , van Velden Floris H. P.
Published: July 2021

Background: Central necrosis can be detected on [18F]FDG PET/CT as a region with little to no tracer uptake. Currently, there is no consensus regarding the inclusion of regions of central necrosis during volume of interest (VOI) delineation for radiomic analysis. The aim of this study was to assess how central necrosis affects radiomic analysis in PET. Methods: Forty-three patients, either with non-small cell lung carcinomas (NSCLC, n = 12) or with pheochromocytomas or paragangliomas (PPGL, n = 31), were included retrospectively. VOIs were delineated with and without central necrosis. From all VOIs, 105 radiomic features were extracted. Differences in radiomic features between delineation methods were assessed using a paired t-test with Benjamini–Hochberg multiple testing correction. In the PPGL cohort, performances of the radiomic models to predict the noradrenergic biochemical profile were assessed by comparing the areas under the receiver operating characteristic curve (AUC) for both delineation methods. Results: At least 65% of the features showed significant differences between VOIvital-tumour and VOIgross-tumour (65%, 79% and 82% for the NSCLC, PPGL and combined cohort, respectively). The AUCs of the radiomic models were not significantly different between delineation methods. Conclusion: In both tumour types, almost two-third of the features were affected, demonstrating that the impact of whether or not to include central necrosis in the VOI on the radiomic feature values is significant. Nevertheless, predictive performances of both delineation methods were comparable. We recommend that radiomic studies should report whether or not central necrosis was included during delineation.
Predicting Hemodynamic Failure Development in PICU Using Machine Learning Techniques
Authors: Comoretto Rosanna , Azzolina Danila , Amigoni Angela , Stoppa Giorgia , Todino Federica , Wolfler Andrea , Gregori Dario ,   on behalf of the TIPNet Study Group
Published: July 2021

The present work aims to identify the predictors of hemodynamic failure (HF) developed during pediatric intensive care unit (PICU) stay testing a set of machine learning techniques (MLTs), comparing their ability to predict the outcome of interest. The study involved patients admitted to PICUs between 2010 and 2020. Data were extracted from the Italian Network of Pediatric Intensive Care Units (TIPNet) registry. The algorithms considered were generalized linear model (GLM), recursive partition tree (RPART), random forest (RF), neural networks models, and extreme gradient boosting (XGB). Since the outcome is rare, upsampling and downsampling algorithms have been applied for imbalance control. For each approach, the main performance measures were reported. Among an overall sample of 29,494 subjects, only 399 developed HF during the PICU stay. The median age was about two years, and the male gender was the most prevalent. The XGB algorithm outperformed other MLTs in predicting HF development, with a median ROC measure of 0.780 (IQR 0.770–0.793). PIM 3, age, and base excess were found to be the strongest predictors of outcome. The present work provides insights for the prediction of HF development during PICU stay using machine-learning algorithms.
GaborPDNet: Gabor Transformation and Deep Neural Network for Parkinson’s Disease Detection Using EEG Signals
Authors: Loh Hui Wen , Ooi Chui Ping , Palmer Elizabeth , Barua Prabal Datta , Dogan Sengul , Tuncer Turker , Baygin Mehmet , Acharya U. Rajendra
Published: July 2021

Parkinson’s disease (PD) is globally the most common neurodegenerative movement disorder. It is characterized by a loss of dopaminergic neurons in the substantia nigra of the brain. However, current methods to diagnose PD on the basis of clinical features of Parkinsonism may lead to misdiagnoses. Hence, noninvasive methods such as electroencephalographic (EEG) recordings of PD patients can be an alternative biomarker. In this study, a deep-learning model is proposed for automated PD diagnosis. EEG recordings of 16 healthy controls and 15 PD patients were used for analysis. Using Gabor transform, EEG recordings were converted into spectrograms, which were used to train the proposed two-dimensional convolutional neural network (2D-CNN) model. As a result, the proposed model achieved high classification accuracy of 99.46% (±0.73) for 3-class classification (healthy controls, and PD patients with and without medication) using tenfold cross-validation. This indicates the potential of proposed model to simultaneously automatically detect PD patients and their medication status. The proposed model is ready to be validated with a larger database before implementation as a computer-aided diagnostic (CAD) tool for clinical-decision support.
Design of a 20 T Class REBCO Insert in a 15 T Low Temperature Superconducting Magnet
Authors: Shao Liangjun , Zhang Xintao , Yan Yufan , Wang Haoyuan , Liu Huajun , Qu Timing
Published: July 2021

A 20 T REBCO insert magnet has been designed considering a 15 T/150 mm background field generated by an LTS magnet. A two-nested-coil structure was chosen. The target of this project is to generate a 20 T/80 mm user field by inserting the outer MI-REBCO coil (Coil 2) first, then try to reach 35 T by inserting the inner NI-REBCO test coil (Coil 1). Coil 2 will be wound by copper packed, 185-μm thick REBCO tapes co-wound with 50-μm thick Hastelloy tapes. Coil 1 will be no-insulated wound by 65-μm thick REBCO tapes. Two mechanical models were built to estimate the stress distribution inside the HTS coils during operation. The influence of the screening current distribution on stress was discussed. The unbalanced force caused by the coil misalignment was also simulated. The 20 T HTS insert magnet is planned to be built and tested in 2021. The progress of coil winding and preliminary test results at 77 K were presented.
Secure Watermarking Schemes and Their Approaches in the IoT Technology: An Overview
Authors: Wazirali Raniyah , Ahmad Rami , Al-Amayreh Ahmed , Al-Madi Mohammad , Khalifeh Ala’
Published: July 2021

Information security is considered one of the most important issues in various infrastructures related to the field of data communication where most of the modern studies focus on finding effective and low-weight secure approaches. Digital watermarking is a trend in security techniques that hides data by using data embedding and data extraction processes. Watermarking technology is integrated into different frames without adding an overheard as in the conventional encryption. Therefore, it is efficient to be used in data encryption for applications that run over limited resources such as the Internet of Things (IoT). In this paper, different digital watermarking algorithms and approaches are presented. Additionally, watermarking requirements and challenges are illustrated in detail. Moreover, the common architecture of the watermarking system is described. Furthermore, IoT technology and its challenges are highlighted. Finally, the paper provides the motivations, objectives and applications of the recent secure watermarking techniques in IoT and summarises them into one table. In addition, the paper highlights the potential to apply the modified watermark algorithms to secure IoT networks.
Experimental and Simulation-Based Performance Analysis of a Computed Torque Control (CTC) Method Running on a Double Rotor Aeromechanical Testbed
Authors: Varga Árpád , Eigner György , Rudas Imre , Tar József Kázmér
Published: July 2021

Concept of closed loop control appears in many fields of engineering sciences, where the output quantity of some physical system must be forced to follow some prescribed function over time, e.g., when a robotic arm endpoint must track a desired trajectory or path given as timed series of spatial coordinates. The classic approach for solving this kind of problem involves a PID compensation block, and the necessary input signal for keeping the controlled process in the vicinity of the desired trajectory is calculated as the weighted sum of momentary deviation, deviation integral, and deviation derivative relative to the reference path. However, despite the obvious advantages, practical usability, and simplicity of the PID controllers, their performance is limited when they are utilized for controlling nonlinear systems. Even with linear systems, their proper operation requires an accurate system model and precise tuning process for finding the best weight values for the proportional, integral, and derivative effects, and the planned closed loop behavior might change significantly as the parameters of the controlled plant change over time. In this article, a computed torque-based controller is presented, which has only one adjustable parameter ensuring precise trajectory tracking even with significantly alternated model constants. The practical usability of the offered algorithm is evaluated and verified by simulations and experiments performed on a simple mechanical bi-rotor testbed playing the role of controlled plant.
Modeling the Diameter Distribution of Mixed Uneven-Aged Stands in the South Western Carpathians in Romania
Authors: Ciceu Albert , Pitar Diana , Badea Ovidiu
Published: July 2021

Tree diameter measurements are repetitive, time-consuming, and laborious but necessary to obtain the diameter distribution of the stands. Tree diameter distribution provides much of the information necessary for sustainable management and can be predicted with high accuracy, thus saving time and financial resources. Permanent sample plots that belong to a permanent sampling network located in a protected area in the South Western Carpathians in Romania were used in this study. We compared two theoretical distribution functions and predicted or recovered their parameters using parameter prediction and parameter recovery methods. Five modeling approaches based on maximum likelihood and the method of moments were used to predict the diameter distribution of unmanaged mixed uneven-aged stands. Parameter recovery methods outperformed parameter prediction methods while the left-truncated Weibull distribution outperformed the complete Weibull distribution. The accuracy obtained by the best modeling approach measured by the relative root mean squared error (%RMSE) reaches up to 12.6% when the sums of the diameters are raised to the third power and only 0.02% and 4.8% for the sums of the second powers and the sum of the diameters respectively. This research is the first of this kind in Romania and can serve as an example of alternative solutions to the yield tables in estimating the volume of mixed uneven-aged stands and can be easily implemented into forest growth models to predict the diameter distribution in the absence of tree lists.