bluuebunny/crossref_metadata_2025 huggingface dataset:
News about the Role of Fluid and Imaging Biomarkers in Neurodegenerative Diseases
Authors: Meldolesi Jacopo
Published: March 2021

Biomarkers are molecules that are variable in their origin, nature, and mechanism of action; they are of great relevance in biology and also in medicine because of their specific connection with a single or several diseases. Biomarkers are of two types, which in some cases are operative with each other. Fluid biomarkers, started around 2000, are generated in fluid from specific proteins/peptides and miRNAs accumulated within two extracellular fluids, either the central spinal fluid or blood plasma. The switch of these proteins/peptides and miRNAs, from free to segregated within extracellular vesicles, has induced certain advantages including higher levels within fluids and lower operative expenses. Imaging biomarkers, started around 2004, are identified in vivo upon their binding by radiolabeled molecules subsequently revealed in the brain by positron emission tomography and/or other imaging techniques. A positive point for the latter approach is the quantitation of results, but expenses are much higher. At present, both types of biomarker are being extensively employed to study Alzheimer’s and other neurodegenerative diseases, investigated from the presymptomatic to mature stages. In conclusion, biomarkers have revolutionized scientific and medical research and practice. Diagnosis, which is often inadequate when based on medical criteria only, has been recently improved by the multiplicity and specificity of biomarkers. Analogous results have been obtained for prognosis. In contrast, improvement of therapy has been limited or fully absent, especially for Alzheimer’s in which progress has been inadequate. An urgent need at hand is therefore the progress of a new drug trial design together with patient management in clinical practice.
The Therapeutic Potential of Carnosine/Anserine Supplementation against Cognitive Decline: A Systematic Review with Meta-Analysis
Authors: Caruso Giuseppe , Godos Justyna , Castellano Sabrina , Micek Agnieszka , Murabito Paolo , Galvano Fabio , Ferri Raffaele , Grosso Giuseppe , Caraci Filippo
Published: March 2021

Carnosine is a natural occurring endogenous dipeptide that was proposed as an anti-aging agent more than 20 years ago. Carnosine can be found at low millimolar concentrations at brain level and different preclinical studies have demonstrated its antioxidant, anti-inflammatory, and anti-aggregation activity with neuroprotective effects in animal models of Alzheimer’s disease (AD). A selective deficit of carnosine has also been linked to cognitive decline in AD. Different clinical studies have been conducted to evaluate the impact of carnosine supplementation against cognitive decline in elderly and AD subjects. We conducted a systematic review with meta-analysis, in accordance with the PRISMA guidelines coupled to the PICOS approach, to investigate the therapeutic potential of carnosine against cognitive decline and depressive symptoms in elderly subjects. We found five studies matching the selection criteria. Carnosine/anserine was administered for 12 weeks at a dose of 1 g/day and improved global cognitive function, whereas no effects were detected on depressive symptoms. These data suggest a preliminary evidence of clinical efficacy of carnosine against cognitive decline both in elderly subjects and mild cognitive impairment (MCI) patients, although larger and long-term clinical studies are needed in MCI patients (with or without depression) to confirm the therapeutic potential of carnosine.
Automatic Premature Ventricular Contraction Detection Using Deep Metric Learning and KNN
Authors: Yu Junsheng , Wang Xiangqing , Chen Xiaodong , Guo Jinglin
Published: March 2021

Premature ventricular contractions (PVCs), common in the general and patient population, are irregular heartbeats that indicate potential heart diseases. Clinically, long-term electrocardiograms (ECG) collected from the wearable device is a non-invasive and inexpensive tool widely used to diagnose PVCs by physicians. However, analyzing these long-term ECG is time-consuming and labor-intensive for cardiologists. Therefore, this paper proposed a simplistic but powerful approach to detect PVC from long-term ECG. The suggested method utilized deep metric learning to extract features, with compact intra-product variance and separated inter-product differences, from the heartbeat. Subsequently, the k-nearest neighbors (KNN) classifier calculated the distance between samples based on these features to detect PVC. Unlike previous systems used to detect PVC, the proposed process can intelligently and automatically extract features by supervised deep metric learning, which can avoid the bias caused by manual feature engineering. As a generally available set of standard test material, the MIT-BIH (Massachusetts Institute of Technology-Beth Israel Hospital) Arrhythmia Database is used to evaluate the proposed method, and the experiment takes 99.7% accuracy, 97.45% sensitivity, and 99.87% specificity. The simulation events show that it is reliable to use deep metric learning and KNN for PVC recognition. More importantly, the overall way does not rely on complicated and cumbersome preprocessing.
Glycated Hemoglobin and Methods for Its Point of Care Testing
Authors: Pohanka Miroslav
Published: March 2021

Glycated hemoglobin (HbA1c) is a product of the spontaneous reaction between hemoglobin and elevated glucose levels in the blood. It is included among the so-called advanced glycation end products, of which is the most important for the clinical diagnosis of diabetes mellitus, and it can serve as an alternative to glycemia measurement. Compared to the diagnosis of diabetes mellitus by glycemia, the HbA1c level is less influenced by a short-term problem with diabetes compensation. Mass spectroscopy and chromatographic techniques are among the standard methods of HbA1c level measurement. Compared to glycemia measurement, there is lack of simple methods for diabetes mellitus diagnosis by means of the HbA1c assay using a point-of-care test. This review article is focused on the surveying of facts about HbA1c and its importance in diabetes mellitus diagnosis, and surveying standard methods and new methods suitable for the HbA1c assay under point-of-care conditions. Various bioassays and biosensors are mentioned and their specifications are discussed.
The Role of Cancer Stem Cells in Colorectal Cancer: From the Basics to Novel Clinical Trials
Authors: Hervieu Céline , Christou Niki , Battu Serge , Mathonnet Muriel
Published: March 2021

The treatment options available for colorectal cancer (CRC) have increased over the years and have significantly improved the overall survival of CRC patients. However, the response rate for CRC patients with metastatic disease remains low and decreases with subsequent lines of therapy. The clinical management of patients with metastatic CRC (mCRC) presents a unique challenge in balancing the benefits and harms while considering disease progression, treatment-related toxicities, drug resistance and the patient’s overall quality of life. Despite the initial success of therapy, the development of drug resistance can lead to therapy failure and relapse in cancer patients, which can be attributed to the cancer stem cells (CSCs). Thus, colorectal CSCs (CCSCs) contribute to therapy resistance but also to tumor initiation and metastasis development, making them attractive potential targets for the treatment of CRC. This review presents the available CCSC isolation methods, the clinical relevance of these CCSCs, the mechanisms of drug resistance associated with CCSCs and the ongoing clinical trials targeting these CCSCs. Novel therapeutic strategies are needed to effectively eradicate both tumor growth and metastasis, while taking into account the tumor microenvironment (TME) which plays a key role in tumor cell plasticity.
The Chicken Chorioallantoic Membrane Tumor Assay as a Relevant In Vivo Model to Study the Impact of Hypoxia on Tumor Progression and Metastasis
Authors: Harper Kelly , Yatsyna Anna , Charbonneau Martine , Brochu-Gaudreau Karine , Perreault Alexis , Jeldres Claudio , McDonald Patrick P. , Dubois Claire M.
Published: March 2021

Hypoxia in the tumor microenvironment is a negative prognostic factor associated with tumor progression and metastasis, and therefore represents an attractive therapeutic target for anti-tumor therapy. To test the effectiveness of novel hypoxia-targeting drugs, appropriate preclinical models that recreate tumor hypoxia are essential. The chicken ChorioAllantoic Membrane (CAM) assay is increasingly used as a rapid cost-effective in vivo drug-testing platform that recapitulates many aspects of human cancers. However, it remains to be determined whether this model recreates the hypoxic microenvironment of solid tumors. To detect hypoxia in the CAM model, the hypoxic marker pimonidazole was injected into the vasculature of tumor-bearing CAM, and hypoxia-dependent gene expression was analyzed. We observed that the CAM model effectively supports the development of hypoxic zones in a variety of human tumor cell line-derived and patient’s tumor fragment-derived xenografts. The treatment of both patient and cell line-derived CAM xenografts with modulators of angiogenesis significantly altered the formation of hypoxic zones within the xenografts. Furthermore, the changes in hypoxia translated into modulated levels of chick liver metastasis as measured by Alu-based assay. These findings demonstrate that the CAM xenograft model is a valuable in vivo platform for studying hypoxia that could facilitate the identification and testing of drugs targeting this tumor microenvironment.
Development of Novel Follicular Thyroid Cancer Models Which Progress to Poorly Differentiated and Anaplastic Thyroid Cancer
Authors: Caperton Caitlin O. , Jolly Lee Ann , Massoll Nicole , Bauer Andrew J. , Franco Aime T.
Published: March 2021

Recent developments in thyroid cancer research have been hindered by a lack of validated in vitro models, allowing for preclinical experimentation and the screening of prospective therapeutics. The goal of this work is to develop and characterize three novel follicular thyroid cancer (FTC) cell lines developed from relevant animal models. These cell lines recapitulate the genetics and histopathological features of FTC, as well as progression to a poorly differentiated state. We demonstrate that these cell lines can be used for a variety of in vitro applications and maintain the potential for in vivo transplantation into immunocompetent hosts. Further, cell lines exhibit differing degrees of dysregulated growth and invasive behavior that may help define mechanisms of pathogenesis underlying the heterogeneity present in the patient population. We believe these novel cell lines will provide powerful tools for investigating the molecular basis of thyroid cancer progression and lead to the development of more personalized diagnostic and treatment strategies.
Dual Targeting of CDK4/6 and cMET in Metastatic Uveal Melanoma
Authors: Ohara Masahiro , Saito Kengo , Kageyama Ken , Terai Mizue , Cheng Hanyin , Aplin Andrew E. , Sato Takami
Published: March 2021

Uveal melanoma (UM) is the most common cancer of the eye in adults. Up to 50% of UM patients subsequently develop metastases, especially in the liver. It has been reported that the retinoblastoma (RB) pathway is deregulated in more than 90% of UM despite the rarity of mutations in the RB1 gene itself. CDK4/6 inhibition (CDK4/6i) is a rational strategy for treatment of UM. In this report, we investigated the antiproliferative activity of a selective CDK4/6 inhibitor on metastatic UM. A CDK4/6 inhibitor suppressed UM cell lines growth in in vitro and in vivo experiments. Hepatocyte growth factor (HGF) decreased the effect of CDK4/6 inhibitor on metastatic UM cell lines. When CDK4/6i was combined with cMET inhibitor, enhanced growth suppression was observed in metastatic UM tumors grown in human-HGF knock-in xenograft mouse models. HGF is enriched in the liver and the majority of liver metastases from UM express activated forms of cMET; therefore, signaling through cMET could contribute to the resistance mechanisms against CDK4/6i, especially in UM patients with hepatic metastasis. Together, these results provide a rationale for the use of cMET inhibitor in combination with a CDK4/6 inhibitor for the treatment of metastatic UM.
Baseline Hedgehog Pathway Activation and Increase of Plasma Wnt1 Protein Are Associated with Resistance to Immune Checkpoint Inhibitors in Advanced Non-Small-Cell Lung Cancer
Authors: Mehlman Camille , Takam Kamga Paul , Costantini Adrien , Julié Catherine , Dumenil Coraline , Dumoulin Jennifer , Ouaknine Julia , Giraud Violaine , Chinet Thierry , Emile Jean-François , Giroux Leprieur Etienne
Published: March 2021

Hedgehog (Hh) and Wingless-type (Wnt) pathways are associated with resistance to immune checkpoint inhibitors (ICIs) in preclinical studies. This study aimed to assess the association between expression and activation levels of Wnt and Sonic Hedgehog (Shh) pathways and resistance to ICIs in advanced NSCLC patients treated with ICI. Hh and Wnt pathways activation was assessed by immunohistochemistry (Gli1 and beta-catenin) on corresponding tumor tissues, and by plasma concentrations of Shh and Wnt (Wnt1, Wnt2 and Wnt3) at ICI introduction and at the first clinical evaluation. Sixty-three patients were included, with 36 patients (57.1%) with available tissue. Response rate was lower in Gli1+ NSCLC (20.0%) compared to Gli1 negative (Gli-) NSCLC (55.6%) (p = 0.015). Rate of primary resistance was 69.8%, vs. 31.2%, respectively (p = 0.04), and median progression-free survival (PFS) was 1.9 months (interquartile range (IQR) 1.2–5.7) vs. 6.1 months (1.6–26.0), respectively (p = 0.08). Median PFS and overall survival were shorter in case of increase of Wnt1 concentration during ICI treatment compared to other patients: 3.9 months vs. 11.2 months (p = 0.008), and 15.3 months vs. not reached (p = 0.003). In conclusion, baseline activation of Hh pathway and increase of Wnt1 concentrations during ICI treatment were associated with poor outcome in NSCLC patients treated with ICIs.
Metabolic Health Together with a Lipid Genetic Risk Score Predicts Survival of Small Cell Lung Cancer Patients
Authors: Fernández Lara P. , Merino María , Colmenarejo Gonzalo , Moreno Rubio Juan , González Pessolani Tais , Reglero Guillermo , Casado Enrique , Sereno María , Ramírez de Molina Ana
Published: March 2021

Small cell lung cancer (SCLC) prognosis is the poorest of all types of lung cancer. Its clinical management remains heterogeneous and therefore, the capability to predict survival would be of great clinical value. Metabolic health (MH) status and lipid metabolism are two relevant factors in cancer prevention and prognosis. Nevertheless, their contributions in SCLC outcome have not yet been analyzed. We analyzed MH status and a transcriptomic panel of lipid metabolism genes in SCLC patients, and we developed a predictive genetic risk score (GRS). MH and two lipid metabolism genes, racemase and perilipin 1, are biomarkers of SCLC survival (HR = 1.99 (CI95%: 1.11–3.61) p = 0.02, HR = 0.36 (CI95%: 0.19–0.67), p = 0.03 and HR = 0.21 (CI95%: 0.09–0.47), respectively). Importantly, a lipid GRS of these genes predict better survival (c-index = 0.691). Finally, in a Cox multivariate regression model, MH, lipid GRS and smoking history are the main predictors of SCLC survival (c-index = 0.702). Our results indicate that the control of MH, lipid gene expression and environmental factors associated with lifestyle is crucial for increased SCLC survival. Here, we propose for the first time, a metabolic precision approach for SCLC patients.
Fighting Drug Resistance through the Targeting of Drug-Tolerant Persister Cells
Authors: De Conti Giulia , Dias Matheus Henrique , Bernards René
Published: March 2021

Designing specific therapies for drug-resistant cancers is arguably the ultimate challenge in cancer therapy. While much emphasis has been put on the study of genetic alterations that give rise to drug resistance, much less is known about the non-genetic adaptation mechanisms that operate during the early stages of drug resistance development. Drug-tolerant persister cells have been suggested to be key players in this process. These cells are thought to have undergone non-genetic adaptations that enable survival in the presence of a drug, from which full-blown resistant cells may emerge. Such initial adaptations often involve engagement of stress response programs to maintain cancer cell viability. In this review, we discuss the nature of drug-tolerant cancer phenotypes, as well as the non-genetic adaptations involved. We also discuss how malignant cells employ homeostatic stress response pathways to mitigate the intrinsic costs of such adaptations. Lastly, we discuss which vulnerabilities are introduced by these adaptations and how these might be exploited therapeutically.
Engineering Metabolism of Chimeric Antigen Receptor (CAR) Cells for Developing Efficient Immunotherapies
Authors: Mangal Joslyn L. , Handlos Jamie L. , Esrafili Arezoo , Inamdar Sahil , Mcmillian Sidnee , Wankhede Mamta , Gottardi Riccardo , Acharya Abhinav P.
Published: March 2021

Chimeric antigen receptor (CAR) T cell-based therapies have shown tremendous advancement in clinical and pre-clinical studies for the treatment of hematological malignancies, such as the refractory of pre-B cell acute lymphoblastic leukemia (B-ALL), chronic lymphocytic leukemia (CLL), and large B cell lymphoma (LBCL). However, CAR T cell therapy for solid tumors has not been successful clinically. Although, some research efforts, such as combining CARs with immune checkpoint inhibitor-based therapy, have been used to expand the application of CAR T cells for the treatment of solid tumors. Importantly, further understanding of the coordination of nutrient and energy supplies needed for CAR T cell expansion and function, especially in the tumor microenvironment (TME), is greatly needed. In addition to CAR T cells, there is great interest in utilizing other types of CAR immune cells, such as CAR NK and CAR macrophages that can infiltrate solid tumors. However, the metabolic competition in the TME between cancer cells and immune cells remains a challenge. Bioengineering technologies, such as metabolic engineering, can make a substantial contribution when developing CAR cells to have an ability to overcome nutrient-paucity in the solid TME. This review introduces technologies that have been used to generate metabolically fit CAR-immune cells as a treatment for hematological malignancies and solid tumors, and briefly discusses the challenges to treat solid tumors with CAR-immune cells.
Investigation of Co3O4 and LaCoO3 Interaction by Performing N2O Decomposition Tests under Co3O4-CoO Transition Temperature
Authors: Iwanek (nee Wilczkowska) Ewa M. , Liotta Leonarda F. , Pantaleo Giuseppe , Krawczyk Krzysztof , Gdyra Ewa , Petryk Jan , Sobczak Janusz W. , Kaszkur Zbigniew
Published: March 2021

The research presented in this paper addresses the question: How does the addition of a small amount of LaCoO3 impact the activity of a Co3O4 catalyst? By testing such a catalyst in N2O decomposition under conditions at which the thermal decomposition of Co3O4 to CoO is possible, one gains unique insight into how the two phases interact. The activity of such a catalyst increases in the entire studied temperature range, unlike the activity of the undoped cobalt catalyst which is lower at 850 °C than at 800 °C due to the reduction of Co3O4 to CoO. XRD measurements showed that CoO was also the main cobalt oxide present in the Co3.5La catalyst after operating at 850 °C, as did the XPS measurements, but there was no drop of activity associated with this change. The influence of NO, O2 and H2O on the activity of the new catalyst, Co3.5La, was determined. Lack of positive effect of NO, a known oxygen scavenger, on the activity was noticed at all temperatures, showing that the effect of LaCoO3 is probably due to increased oxygen desorption. Temperature programed oxidation (TPO) tests showed that the beneficial effects of the presence of LaCoO3 on the activity of cobalt oxide at 850 °C were probably caused by enhanced diffusion of O2− anions through the entire catalyst, which facilitates desorption of oxygen molecules from the surface.
Theoretical Study on Epoxide Ring-opening in CO2/Epoxide Copolymerization Catalyzed by Bifunctional Salen-Type Cobalt(III) Complexes: Influence of Stereoelectronic Factors
Authors: Dyduch Karol , Roznowska Aleksandra , Srebro-Hooper Monika , Lee Bun Yeoul , Michalak Artur
Published: March 2021

Propylene oxide (PO) binding and ring-opening reaction with the bifunctional CO2/epoxide copolymerization catalyst, based on the Co(III)-salcy complex including two quaternary ammonium salts with n-butyl substituents (N+-chains) were investigated by Density Functional Theory (DFT) calculations and compared with the model systems without the N+-chains. The importance of the different possible stereoisomers and the stereoselectivity of these processes for (S)- and (R)-enantiomers of PO were considered. To explore the conformational space for the real catalyst, a complex approach, developed previously was applied. The calculations for the model systems directly demonstrate that PO-ring opening proceeds preferentially in trans catalysts’ configuration and no participation of cis-β isomers is viable; nucleophilic attack at the methylene-carbon atom is preferred over that at methine-carbon atom. For the real bifunctional catalyst, with the (S,S)-configuration of cyclohexane, the results indicate a preference of (R)-PO ring-opening over (S)-PO ring-opening (ca. 6:5). Concerning stereoisomers resulting from the orientation of N+-chains in the real catalyst, different groups of structures participate in the ring-opening reaction for (R)-PO, and different for (S)-PO. The high population of nonreactive complexes of (R)-PO may be the key factor responsible for decreasing the activity of the analyzed catalyst in the epoxide ring-opening reaction.
One-Pot Synthesis of Ultra-Small Pt Dispersed on Hierarchical Zeolite Nanosheet Surfaces for Mild Hydrodeoxygenation of 4-Propylphenol
Authors: Wetchasat Piraya , Salakhum Saros , Imyen Thidarat , Suttipat Duangkamon , Wannapakdee Wannaruedee , Ketkaew Marisa , Prasertsab Anittha , Kidkhunthod Pinit , Witoon Thongthai , Wattanakit Chularat
Published: March 2021

The rational design of ultra-small metal clusters dispersed on a solid is of crucial importance in modern nanotechnology and catalysis. In this contribution, the concept of catalyst fabrication with a very ultra-small size of platinum nanoparticles supported on a hierarchical zeolite surface via a one-pot hydrothermal system was demonstrated. Combining the zeolite gel with ethylenediaminetetraacetic acid (EDTA) as a ligand precursor during the crystallization process, it allows significant improvement of the metal dispersion on a zeolite support. To illustrate the beneficial effect of ultra-small metal nanoparticles on a hierarchical zeolite surface as a bifunctional catalyst, a very high catalytic performance of almost 100% of cycloalkane product yield can be achieved in the consecutive mild hydrodeoxygenation of 4-propylphenol, which is a lignin-derived model molecule. This instance opens up perspectives to improve the efficiency of a catalyst for the sustainable conversion of biomass-derived compounds to fuels.
Modulation of Endosome Function, Vesicle Trafficking and Autophagy by Human Herpesviruses
Authors: Tognarelli Eduardo I. , Reyes Antonia , Corrales Nicolás , Carreño Leandro J. , Bueno Susan M. , Kalergis Alexis M. , González Pablo A.
Published: March 2021

Human herpesviruses are a ubiquitous family of viruses that infect individuals of all ages and are present at a high prevalence worldwide. Herpesviruses are responsible for a broad spectrum of diseases, ranging from skin and mucosal lesions to blindness and life-threatening encephalitis, and some of them, such as Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein–Barr virus (EBV), are known to be oncogenic. Furthermore, recent studies suggest that some herpesviruses may be associated with developing neurodegenerative diseases. These viruses can establish lifelong infections in the host and remain in a latent state with periodic reactivations. To achieve infection and yield new infectious viral particles, these viruses require and interact with molecular host determinants for supporting their replication and spread. Important sets of cellular factors involved in the lifecycle of herpesviruses are those participating in intracellular membrane trafficking pathways, as well as autophagic-based organelle recycling processes. These cellular processes are required by these viruses for cell entry and exit steps. Here, we review and discuss recent findings related to how herpesviruses exploit vesicular trafficking and autophagy components by using both host and viral gene products to promote the import and export of infectious viral particles from and to the extracellular environment. Understanding how herpesviruses modulate autophagy, endolysosomal and secretory pathways, as well as other prominent trafficking vesicles within the cell, could enable the engineering of novel antiviral therapies to treat these viruses and counteract their negative health effects.
Daratumumab in the Treatment of Light-Chain (AL) Amyloidosis
Authors: Palladini Giovanni , Milani Paolo , Malavasi Fabio , Merlini Giampaolo
Published: March 2021

Systemic light-chain (AL) amyloidosis is caused by a small B cell, most commonly a plasma cell (PC), clone that produces toxic light chains (LC) that cause organ dysfunction and deposits in tissues. Due to the production of amyloidogenic, misfolded LC, AL PCs display peculiar biologic features. The small, indolent plasma cell clone is an ideal target for anti-CD38 immunotherapy. A recent phase III randomized study showed that in newly diagnosed patients, the addition of daratumumab to the standard of care increased the rate and depth of the hematologic response and granted more frequent organ responses. In the relapsed/refractory setting, daratumumab alone or as part of combination regimens gave very promising results. It is likely that daratumumab-based regimens will become new standards of care in AL amyloidosis. Another anti-CD38 monoclonal antibody, isatuximab, is at an earlier stage of development as a treatment for AL amyloidosis. The ability to target CD38 on the amyloid PC offers new powerful tools to treat AL amyloidosis. Future studies should define the preferable agents to combine with daratumumab upfront and in the rescue setting and assess the role of maintenance. In this review, we summarize the rationale for using anti-CD38 antibodies in the treatment of AL amyloidosis.
Quantitative Optical Coherence Tomography Angiography (OCTA) Parameters in a Black Diabetic Population and Correlations with Systemic Diseases
Authors: Shaw Lincoln T. , Khanna Saira , Chun Lindsay Y. , Dimitroyannis Rose C. , Rodriguez Sarah H. , Massamba Nathalie , Hariprasad Seenu M. , Skondra Dimitra
Published: March 2021

This is a cross-sectional, prospective study of a population of black diabetic participants without diabetic retinopathy aimed to investigate optical coherence tomography angiography (OCTA) characteristics and correlations with systemic diseases in this population. These parameters could serve as novel biomarkers for microvascular complications; especially in black populations which are more vulnerable to diabetic microvascular complications. Linear mixed models were used to obtain OCTA mean values ± standard deviation and analyze statistical correlations to systemic diseases. Variables showing significance on univariate mixed model analysis were further analyzed with multivariate mixed models. 92 eyes of 52 black adult subjects were included. After multivariate analysis; signal strength intensity (SSI) and heart disease had statistical correlations to superficial capillary plexus vessel density in our population. SSI and smoking status had statistical correlations to deep capillary plexus vessel density in a univariate analysis that persisted in part of the imaging subset in a multivariate analysis. Hyperlipidemia; hypertension; smoking status and pack-years; diabetes duration; creatinine; glomerular filtration rate; total cholesterol; hemoglobin A1C; and albumin-to-creatinine ratio were not significantly associated with any OCTA measurement in multivariate analysis. Our findings suggest that OCTA measures may serve as valuable biomarkers to track systemic vascular functioning in diabetes mellitus in black patients.
Language and Communication in Preschool Children with Autism and Other Developmental Disorders
Authors: Torrens Vicenç , Ruiz Cristina
Published: March 2021

In this research, we studied the language and communication skills of preschool children with a diagnosis of autistic syndrome disorder (ASD) (n = 51) compared to children with other developmental disorders (DD) (n = 42), using direct measures and parental reports when assessing the development of language and communication. As a novelty, this research studied a sample of children with low language and communication skills. We found a high correlation between direct measures and parental reports for both populations. Therefore, we propose that combining the information supplied by direct measures together with that supplied by parental reports would be a suitable strategy for language assessment in these populations. In addition, the results show a delay in language comprehension with respect to language production in children with ASD, along with many difficulties with non-verbal communication, compared to children with other developmental disorders (DD). We also found significant differences between both groups with respect to lexical categories. The differences in language and communication profiles of children with ASD compared to children with other DD might have some implications for diagnoses and language intervention in these populations.
Novel Approaches to Combat Medical Device-Associated BioFilms
Authors: Li Xin , Sun Luyao , Zhang Peng , Wang Yang
Published: March 2021

Biofilms are aggregates formed as a protective survival state by microorganisms to adapt to the environment and can be resistant to antimicrobial agents and host immune responses due to chemical or physical diffusion barriers, modified nutrient environments, suppression of the growth rate within biofilms, and the genetic adaptation of cells within biofilms. With the widespread use of medical devices, medical device-associated biofilms continue to pose a serious threat to human health, and these biofilms have become the most important source of nosocomial infections. However, traditional antimicrobial agents cannot completely eliminate medical device-associated biofilms. New strategies for the treatment of these biofilms and targeting biofilm infections are urgently required. Several novel approaches have been developed and identified as effective and promising treatments. In this review, we briefly summarize the challenges associated with the treatment of medical device-associated biofilm infections and highlight the latest promising approaches aimed at preventing or eradicating these biofilms.
β-Lactoglobulin Adsorption Layers at the Water/Air Surface: 5. Adsorption Isotherm and Equation of State Revisited, Impact of pH
Authors: Gochev Georgi G. , Kovalchuk Volodymyr I. , Aksenenko Eugene V. , Fainerman Valentin B. , Miller Reinhard
Published: March 2021

The theoretical description of the adsorption of proteins at liquid/fluid interfaces suffers from the inapplicability of classical formalisms, which soundly calls for the development of more complicated adsorption models. A Frumkin-type thermodynamic 2-d solution model that accounts for nonidealities of interface enthalpy and entropy was proposed about two decades ago and has been continuously developed in the course of comparisons with experimental data. In a previous paper we investigated the adsorption of the globular protein β-lactoglobulin at the water/air interface and used such a model to analyze the experimental isotherms of the surface pressure, Π(c), and the frequency-, f-, dependent surface dilational viscoelasticity modulus, E(c)f, in a wide range of protein concentrations, c, and at pH 7. However, the best fit between theory and experiment proposed in that paper appeared incompatible with new data on the surface excess, Γ, obtained from direct measurements with neutron reflectometry. Therefore, in this work, the same model is simultaneously applied to a larger set of experimental dependences, e.g., Π(c), Γ(c), E(Π)f, etc., with E-values measured strictly in the linear viscoelasticity regime. Despite this ambitious complication, a best global fit was elaborated using a single set of parameter values, which well describes all experimental dependencies, thus corroborating the validity of the chosen thermodynamic model. Furthermore, we applied the model in the same manner to experimental results obtained at pH 3 and pH 5 in order to explain the well-pronounced effect of pH on the interfacial behavior of β-lactoglobulin. The results revealed that the propensity of β-lactoglobulin globules to unfold upon adsorption and stretch at the interface decreases in the order pH 3 > pH 7 > pH 5, i.e., with decreasing protein net charge. Finally, we discuss advantages and limitations in the current state of the model.
Dynamic Pricing Recognition on E-Commerce Platforms with VAR Processes
Authors: Faehnle Alexander , Guidolin Mariangela
Published: March 2021

In an environment such as e-commerce, characterized by the presence of numerous agents, competition based on product characteristics is a very important aspect. This paper proposes a model based on vector autoregressive processes (VAR) and Lasso penalization to detect and examine the dynamics that govern real-time price competition in electronic marketplaces. Employing this model, an empirical study was performed on the price trends of smartphone models on the major electronic sales platforms of the Italian market. The proposed model detects real-time price variations in single vendors, based on the variations of their direct competitors. The statistical method adopted in this analysis may be useful for e-commerce companies that conduct market analyses of competitors’ pricing strategies.
First Case Report of Maternal Mosaic Tetrasomy 9p Incidentally Detected on Non-Invasive Prenatal Testing
Authors: Shu Wendy , Cheng Shirley S. W. , Xue Shuwen , Chan Lin Wai , Soong Sung Inda , Kan Anita Sik Yau , Cheung Sunny Wai Hung , Choy Kwong Wai
Published: March 2021

Tetrasomy 9p (ORPHA:3390) is a rare syndrome, hallmarked by growth retardation; psychomotor delay; mild to moderate intellectual disability; and a spectrum of skeletal, cardiac, renal and urogenital defects. Here we present a Chinese female with good past health who conceived her pregnancy naturally. Non-invasive prenatal testing (NIPT) showed multiple chromosomal aberrations were consistently detected in two sampling times, which included elevation in DNA from chromosome 9p. Amniocentesis was performed and sent for chromosomal microarray, which was normal. Maternal karyotype revealed that mos 47,XX,+dic(9;9)(q21.1;q21.1)(24)/46,XX(9) presents mosaic tetrasomy for the short arm of chromosome 9p and is related to the NIPT results showing elevation in DNA from chromosome 9p. The pregnancy was uneventful, and the patient was delivered at term. Maternal samples were obtained at two different time points after delivery showed the same multiple chromosomal aberrations detected during pregnancy. This is a first report on an unusual case of mosaic isodicentric tetrasomy 9p in a healthy adult with normal intellect. With widespread adoption of NIPT for screening fetal aneuploidy and genome-wide copy number changes, a rise in incidental detection of maternal rare genetic syndrome will bring challenges in our current approach to genetic counselling and prenatal diagnosis.
Novel Homozygous Mutations in the Genes TGM1, SULT2B1, SPINK5 and FLG in Four Families Underlying Congenital Ichthyosis
Authors: Fozia Fozia , Nazli Rubina , Alam Khan Sher , Bari Ahmed , Nasir Abdul , Ullah Riaz , Mahmood Hafiz Majid , Sohaib Muhammad , Alobaid Abdulrahman , Ansari Siddique A. , Basit Sulman , Khan Saadullah
Published: March 2021

Background: Ichthyoses are a large group of hereditary cornification disorders, which are both clinically and etiologically heterogeneous and affect mostly all the skin surface of the patients. Ichthyosis has its origin in an ancient Greek word “ichthys” meaning fish, this is because the ichthyosis patients have dry, thickened, and scaly skin. There is an excess accumulation of epidermal cells resulting in the appearance of continuous and widespread scales on the body. There are many varieties of ichthyosis with a broad spectrum of intensity, severity, and associated symptoms, most of them are extremely rare. Ichthyosis vulgaris is the most frequently occurring type of ichthyoses. Method: The present study consists of four Pakistani ichthyosis families (A, B, C, and D). Whole exome sequencing (WES) approach was used to identify the pathogenic sequence variants in probands. The segregation of these variants in other participants was confirmed by Sanger sequencing. Results: Total four variants including, two splice site (TGM1: c.2088 + 1G > A) and (SPINK5: c.882 + 1G > T), a missense (SULT2B1: c.419C > T; p. Ala140Val), and a nonsense (FLG: c.6109C > T; p. Arg2037Ter) variant were identified in families A, C, B, and D, respectively, as causative mutations responsible for ichthyosis in these families. Conclusion: Our study unravels the molecular etiology of the four Pakistani ichthyosis families and validates the involvement of TGM1, SULT2B1, SPINK5, and FLG, in the etiology of different forms of ichthyosis. In addition, this study also aims to give a detailed clinical report of the studied ichthyosis families.
Theory of Effective Stress in Soil and Rock and Implications for Fracturing Processes: A Review
Authors: Guerriero Vincenzo , Mazzoli Stefano
Published: March 2021

The effective stress principle (ESP) plays a basic role in geology and engineering problems as it is involved in fundamental issues concerning strain and failure of rock and soil, as well as of other porous materials such as concrete, metal powders, biological tissues, etc. Although since its introduction in the 1920s the main ESP aspects have been unravelled and theoretically derived, these do not appear to have been always entirely perceived by many in the science community dealing with ESP-related topics but having little familiarity with the complex theories of porous media and poroelasticity. The purpose of this review is to provide a guidance for the reader who needs an updated overview of the different theoretical and experimental approaches to the ESP and related topics over the past century, with particular reference to geological fracturing processes. We begin by illustrating, after some introductive historical remarks, the basic theory underlying the ESP, based on theory of elasticity methods. Then the different ESP-related theories and experimental results, as well as main interpretations of rock jointing and fracturing phenomena, are discussed. Two main classical works are then revisited, and a rigorous ESP proof is derived. Such a proof is aimed at geologists, engineers and geophysicists to become more familiar with theories of porous media and poroelasticity, being based on the classical theory of elasticity. The final part of this review illustrates some still open issues about faulting and hydraulic fracturing in rocks.
The Vocational School of Sintra and Its Contribution to Heritage Education
Authors: Cardeira Ana Mafalda , Frade Marta
Published: March 2021

This paper aims to share the experience acquired with students of the 3rd year (namely the 12th grade of the Portuguese educational system) at the Vocational School for the Recovery of Heritage of Sintra in the Course of Studies for Conservation and Restoration Assistants in the field of Plaster Restoration, in the classes of Work-Related Training and Analytical Methods of Examination and Laboratory Analysis, by carrying out theoretical-practical work and training in a work context specifically focused on Portuguese heritage, demonstrating how practical classes motivate students and prepare them for future professional work. This vocational course helps students to reflect and question themselves on the role of “looking” at heritage. Thus, its cross information, both interdisciplinary and from the historical-artistic context of the monument, will provide a better perspective over its materiality and its use. In situ learning awakens students to the reality of work. The notion that they are helping to maintain the memory of ancestors credits them and gives them confidence in their work. After presenting their Final Year Projects, they look at heritage with a more awakened vision. With this, they have the perception that they have contributed to the reconstruction of memory, their cultural heritage.
Likely Geographic Distributional Shifts among Medically Important Tick Species and Tick-Associated Diseases under Climate Change in North America: A Review
Authors: Alkishe Abdelghafar , Raghavan Ram K. , Peterson Andrew T.
Published: March 2021

Ticks rank high among arthropod vectors in terms of numbers of infectious agents that they transmit to humans, including Lyme disease, Rocky Mountain spotted fever, Colorado tick fever, human monocytic ehrlichiosis, tularemia, and human granulocytic anaplasmosis. Increasing temperature is suspected to affect tick biting rates and pathogen developmental rates, thereby potentially increasing risk for disease incidence. Tick distributions respond to climate change, but how their geographic ranges will shift in future decades and how those shifts may translate into changes in disease incidence remain unclear. In this study, we have assembled correlative ecological niche models for eight tick species of medical or veterinary importance in North America (Ixodes scapularis, I. pacificus, I. cookei, Dermacentor variabilis, D. andersoni, Amblyomma americanum, A. maculatum, and Rhipicephalus sanguineus), assessing the distributional potential of each under both present and future climatic conditions. Our goal was to assess whether and how species’ distributions will likely shift in coming decades in response to climate change. We interpret these patterns in terms of likely implications for tick-associated diseases in North America.
Validation of a Fast and Accurate Magnetic Tracker Operating in the Environmental Field
Authors: Biancalana Valerio , Cecchi Roberto , Chessa Piero , Mandalà Marco , Bevilacqua Giuseppe , Dancheva Yordanka , Vigilante Antonio
Published: March 2021

We characterize the performance of a system based on a magnetoresistor array. This instrument is developed to map the magnetic field, and to track a dipolar magnetic source in the presence of a static homogeneous field. The position and orientation of the magnetic source with respect to the sensor frame is retrieved together with the orientation of the frame with respect to the environmental field. A nonlinear best-fit procedure is used, and its precision, time performance, and reliability are analyzed. This analysis is performed in view of the practical application for which the system is designed that is an eye-tracking diagnostics and rehabilitative tool for medical purposes, which require high speed (≥100 Sa/s) and sub-millimetric spatial resolution. A throughout investigation on the results makes it possible to list several observations, suggestions, and hints, which will be useful in the design of similar setups.
Editorial for the Special Issue on Discontinuous Fiber Composites, Volume II
Authors: Kuhn Christoph , Osswald Tim A.
Published: March 2021

This Special Issue on discontinuous fiber composites and its published papers, like its predecessor, give the polymer engineer and scientist an insight into challenges and research topics in the field of discontinuous fiber-reinforced composites [...]
Detecting and Locating Passive Video Forgery Based on Low Computational Complexity Third-Order Tensor Representation
Authors: Alsakar Yasmin M. , Mekky Nagham E. , Hikal Noha A.
Published: March 2021

Great attention is paid to detecting video forgeries nowadays, especially with the widespread sharing of videos over social media and websites. Many video editing software programs are available and perform well in tampering with video contents or even creating fake videos. Forgery affects video integrity and authenticity and has serious implications. For example, digital videos for security and surveillance purposes are used as evidence in courts. In this paper, a newly developed passive video forgery scheme is introduced and discussed. The developed scheme is based on representing highly correlated video data with a low computational complexity third-order tensor tube-fiber mode. An arbitrary number of core tensors is selected to detect and locate two serious types of forgeries which are: insertion and deletion. These tensor data are orthogonally transformed to achieve more data reductions and to provide good features to trace forgery along the whole video. Experimental results and comparisons show the superiority of the proposed scheme with a precision value of up to 99% in detecting and locating both types of attacks for static as well as dynamic videos, quick-moving foreground items (single or multiple), zooming in and zooming out datasets which are rarely tested by previous works. Moreover, the proposed scheme offers a reduction in time and a linear computational complexity. Based on the used computer’s configurations, an average time of 35 s. is needed to detect and locate 40 forged frames out of 300 frames.
LCTC Ships Concept Design in the North Europe- Mediterranean Transport Scenario Focusing on Intact Stability Issues
Authors: Degan Germano , Braidotti Luca , Marinò Alberto , Bucci Vittorio
Published: March 2021

In late years, the size of RoRo cargo ships has continuously increased, leading to the so-called Large Car Truck Carriers (LCTC). The design of these vessels introduced new challenges that shall be considered during the ship design since the conceptual stage, which has a very strong impact on the technical and economic performances of the vessel during all its life-cycle. In this work, the concept design of an LCTC is presented based on Multi-Attribute Decision Making (MADM). A large set of design alternatives have been generated and compared in order to find out the most promising feasible designs. The proposed approach is based on a Mathematical Design Model (MDM) capable to assess all the main technical and economic characteristics for each design. Among the others, here focus has been done on the ship stability to assure the compliance with statutory rules within the MDM. A new stability metamodel has been developed capable to define the cross curves of stability at the concept design stage. The proposed MADM methodology has been applied to North Europe-Mediterranean transport scenario highlighting the impact of main particulars describing hull geometry on the technical and economic performances of an LCTC ship.
Marine Engines Performance and Emissions
Authors: Galdo María Isabel Lamas
Published: March 2021

Marine engines are key components in most ships [...]