bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Challenges and Prospects of Indonesian Non-Timber Forest Products (NTFPs): A Review
Authors: Pasaribu Gunawan , Winarni Ina , Gusti Raden Esa Pangersa , Maharani Rizki , Fernandes Andrian , Harianja Alfonsus Hasudungan , Saragih Grace Serepina , Turjaman Maman , Tampubolon Agustinus Panusunan , Kuspradini Harlinda , Lukmandaru Ganis , Njurumana Gerson Ndawa , Sukito Agus , Aswandi Aswandi , Kholibrina Cut Rizlani
Published: December 2021

Non-Timber Forest Products (NTFPs) management can lead to various benefits for community livelihood and forest sustainability. However, such management has not been carried out optimally and sustainably in Indonesia, due to various limiting factors including ineffective policies, undeveloped cultivation technologies, and inadequate innovation in processing technologies. Further, the diversity of NTFPs species requires that policy-makers determine the priority species to be developed. Agarwood (Aquilaria spp. and Gyrinops spp.), benzoin (Styrax spp.), sandalwood (Santalum album L.), and cajuput (Melaleuca cajuputi Powell) are aromatic NTFPs species in Indonesia that forest-dwellers have utilized across generations. This paper reviews the current governance, cultivation systems, processing and valuation, and benefits and uses of these species. We also highlights the future challenges and prospects of these NTFPs species, which are expected to be useful in designing NTFPs governance, in order to maximize the associated benefits for the farmers and all related stakeholders.
Effects of Thermal and High-Pressure Processing on Quality Features and the Volatile Profiles of Cloudy Juices Obtained from Golden Delicious, Pinova, and Red Delicious Apple Cultivars
Authors: Liberatore Claudia Maria , Cirlini Martina , Ganino Tommaso , Rinaldi Massimiliano , Tomaselli Silvia , Chiancone Benedetta
Published: December 2021

In this study, juices extracted from three apple cultivars (Golden Delicious, Pinova, and Red Delicious) were stabilized by means of thermal treatment (TT) and high-pressure processing (HPP, 600 MPa 3 min); pH, total titratable acidity, total soluble solids content, color, and viscosity, as well as volatile profile, were investigated. Qualitative characteristics (pH, titratable acidity, colorimetric parameters, viscosity, and volatile profile) results were significantly influenced by both cultivars and treatments; for example, juice viscosity greatly increased after HPP treatment for Golden Delicious, and after both TT and HPP for Pinova, while no influence of stabilization treatment was registered for Red Delicious juices. Regarding the volatile profile, for Golden Delicious cultivar, HPP treatment determined an increase in volatile compounds for most of the classes considered, leading to a supposed quality implementation. For the other two cultivars, the stabilization treatment that better preserved the volatile profile was the HPP one, even if the results were quite similar to the thermal treatment. Further studies are needed to evaluate different time/pressure combinations that could give better results, depending on the specific apple cultivar.
Non-Invasive Methods for Predicting the Quality of Processed Horticultural Food Products, with Emphasis on Dried Powders, Juices and Oils: A Review
Authors: Okere Emmanuel Ekene , Arendse Ebrahiema , Nieuwoudt Helene , Fawole Olaniyi Amos , Perold Willem Jacobus , Opara Umezuruike Linus
Published: December 2021

This review covers recent developments in the field of non-invasive techniques for the quality assessment of processed horticultural products over the past decade. The concept of quality and various quality characteristics related to evaluating processed horticultural products are detailed. A brief overview of non-invasive methods, including spectroscopic techniques, nuclear magnetic resonance, and hyperspectral imaging techniques, is presented. This review highlights their application to predict quality attributes of different processed horticultural products (e.g., powders, juices, and oils). A concise summary of their potential commercial application for quality assessment, control, and monitoring of processed agricultural products is provided. Finally, we discuss their limitations and highlight other emerging non-invasive techniques applicable for monitoring and evaluating the quality attributes of processed horticultural products. Our findings suggest that infrared spectroscopy (both near and mid) has been the preferred choice for the non-invasive assessment of processed horticultural products, such as juices, oils, and powders, and can be adapted for on-line quality control. Raman spectroscopy has shown potential in the analysis of powdered products. However, imaging techniques, such as hyperspectral imaging and X-ray computed tomography, require improvement on data acquisition, processing times, and reduction in the cost and size of the devices so that they can be adopted for on-line measurements at processing facilities. Overall, this review suggests that non-invasive techniques have the potential for industrial application and can be used for quality assessment.
The Influence of Socioeconomic Status on the Prognosis and Profile of Patients Admitted for Acute Heart Failure during COVID-19 Pandemic: Overestimated Aspects or a Multifaceted Hydra of Cardiovascular Risk Factors?
Authors: Miftode Radu-Stefan , Costache Irina-Iuliana , Cianga Petru , Petris Antoniu Octavian , Cianga Corina-Maria , Maranduca Minela-Aida , Miftode Ionela-Larisa , Constantinescu Daniela , Timpau Amalia-Stefana , Crisan Adrian , Mitu Ovidiu , Haba Mihai Stefan Cristian , Stafie Celina-Silvia , Șerban Ionela-Lacramioara
Published: December 2021

Background: Heart failure (HF) is a complex clinical syndrome that represents a great burden on public health systems due to its increased prevalence, disability and mortality rates. There are multiple triggers that can induce or aggravate a preexisting HF, socioeconomic status (SES) emerging as one of the most common modifiable risk factors. Our study aimed to analyze the influence of certain SES indicators on the outcome, clinical aspects and laboratory parameters of patients with HF in North-Eastern Romania, as well as their relationship with other traditional cardiovascular risk factors. Methods: We conducted a prospective, single-center study comprising 120 consecutively enrolled patients admitted for acute HF. The evaluation of individual SES was based upon a standard questionnaire and evidence from official documents. Results: the patients’ age ranged between 18 and 94 years; Out of 120 patients, 49 (40.8%) were women and 71 (59.2%) were men, residing in rural 59 (49.2%) or urban 61 (50.8%) areas. 14.2% were university graduates, while 15.8% had only attended primary school. The majority of the patients are or were employed in the service sector (54.5%), followed by industry (29.2%) and agriculture (20%). The mean monthly income was 306.1 ± 177.4 euro, while the mean hospitalization cost was 2471.8 ± 2073.8 euro per patient. The individual income level was positively correlated with urban area of residence, adequate household sanitation facilities and healthcare access, and negatively associated with advanced age and previous hospitalizations due to HF. However, the individual financial situation was also positively correlated with the increased prevalence of certain cardiovascular risk factors, such as arterial hypertension, anemia or obesity, but not with total cholesterol or male gender. Concerning the direct impact of a poor economic status upon prognosis in the setting of acute HF, our results showed no statistically significant differences concerning the in-hospital or at 1-month follow-up mortality rates. Rather than inducing a direct impact on the short-term outcome, these findings concerning SES indicators are meant to enhance the implementation of policies aimed to provide adequate healthcare for people from all social layers, with a primary focus on modifiable cardiovascular risk factors.
Health Problems and the Use of Medications and Traditional Therapies among Chinese Immigrants Living in Spain
Authors: Badanta Bárbara , Rodríguez-Burbano Aura Yolima , López-Tarrida Angeles C. , Vega-Escaño Juan , Lucchetti Giancarlo , Barrientos-Trigo Sergio , de Diego-Cordero Rocío
Published: December 2021

In this study, we investigate the health problems and the use of medications and traditional therapies among Chinese immigrants in the Southern region of Spain. A qualitative study using semi-structured interviews and including 133 immigrants and 7 stakeholders was conducted in 2017. Transcription, literal reading, and theoretical categorization were performed, and a narrative content analysis was carried out. The most common health problems were musculoskeletal (28.6%) and allergies (25.6%) related to work activity and unhealthy lifestyles. Key informants also reported gastric problems, stress, and changes in eating habits, mostly related to their work activity. For these problems, a large number of traditional remedies (herbs, diet therapy, acupuncture, vitamins, etc.) were used, usually combined with pharmaceutical drugs used for colds, flu, general malaise (29%), pain and fever (23%), and allergy drugs (9.2%). Chinese immigrants reported health conditions associated with their working conditions and life habits in Spain, using Traditional Chinese Medicine instead of pharmacological drugs. Understanding these health problems and promoting awareness towards traditional therapies in the healthcare system may help to design public policies and Health Promotion strategies targeting this group.
Growth Hormone and the Human Hair Follicle
Authors: Horesh Elijah J. , Chéret Jérémy , Paus Ralf
Published: December 2021

Ever since the discoveries that human hair follicles (HFs) display the functional peripheral equivalent of the hypothalamic-pituitary-adrenal axis, exhibit elements of the hypothalamic-pituitary-thyroid axis, and even generate melatonin and prolactin, human hair research has proven to be a treasure chest for the exploration of neurohormone functions. However, growth hormone (GH), one of the dominant neurohormones of human neuroendocrine physiology, remains to be fully explored in this context. This is interesting since it has long been appreciated clinically that excessive GH serum levels induce distinct human skin pathology. Acromegaly, or GH excess, is associated with hypertrichosis, excessive androgen-independent growth of body hair, and hirsutism in females, while dysfunctional GH receptor-mediated signaling (Laron syndrome) is associated with alopecia and prominent HF defects. The outer root sheath keratinocytes have recently been shown to express functional GH receptors. Furthermore, and contrary to its name, recombinant human GH is known to inhibit female human scalp HFs’ growth ex vivo, likely via stimulating the expression of the catagen-inducing growth factor, TGF-β2. These limited available data encourage one to systematically explore the largely uncharted role of GH in human HF biology to uncover nonclassical functions of this core neurohormone in human skin physiology.
The Protective Mechanism of Deuterated Linoleic Acid Involves the Activation of the Ca2+ Signaling System of Astrocytes in Ischemia In Vitro
Authors: Turovsky Egor A. , Varlamova Elena G. , Gudkov Sergey V. , Plotnikov Egor Y.
Published: December 2021

Ischemia-like (oxygen-glucose deprivation, OGD) conditions followed by reoxygenation (OGD/R) cause massive death of cerebral cortex cells in culture as a result of the induction of necrosis and apoptosis. Cell death occurs as a result of an OGD-induced increase in Ca2+ ions in the cytosol of neurons and astrocytes, an increase in the expression of genes encoding proapoptotic and inflammatory genes with suppression of protective genes. The deuterated form of linoleic polyunsaturated fatty acid (D4-Lnn) completely inhibits necrosis and greatly reduces apoptotic cell death with an increase in the concentration of fatty acid in the medium. It was shown for the first time that D4-Lnn, through the activation of the phosphoinositide calcium system of astrocytes, causes their reactivation, which correlates with the general cytoprotective effect on the cortical neurons and astrocytes in vitro. The mechanism of the cytoprotective action of D4-Lnn involves the inhibition of the OGD-induced calcium ions, increase in the cytosolic and reactive oxygen species (ROS) overproduction, the enhancement of the expression of protective genes, and the suppression of damaging proteins.
Nicotinamide Mononucleotide Prevents Free Fatty Acid-Induced Reduction in Glucose Tolerance by Decreasing Insulin Clearance
Authors: Nahle Ashraf , Joseph Yemisi Deborah , Pereira Sandra , Mori Yusaku , Poon Frankie , Ghadieh Hilda E. , Ivovic Aleksandar , Desai Tejas , Ghanem Simona S. , Asalla Suman , Muturi Harrison T. , Jentz Emelien M. , Joseph Jamie W. , Najjar Sonia M. , Giacca Adria
Published: December 2021

The NAD-dependent deacetylase SIRT1 improves β cell function. Accordingly, nicotinamide mononucleotide (NMN), the product of the rate-limiting step in NAD synthesis, prevents β cell dysfunction and glucose intolerance in mice fed a high-fat diet. The current study was performed to assess the effects of NMN on β cell dysfunction and glucose intolerance that are caused specifically by increased circulating free fatty acids (FFAs). NMN was intravenously infused, with or without oleate, in C57BL/6J mice over a 48-h-period to elevate intracellular NAD levels and consequently increase SIRT1 activity. Administration of NMN in the context of elevated plasma FFA levels considerably improved glucose tolerance. This was due not only to partial protection from FFA-induced β cell dysfunction but also, unexpectedly, to a significant decrease in insulin clearance. However, in conditions of normal FFA levels, NMN impaired glucose tolerance due to decreased β cell function. The presence of this dual action of NMN suggests caution in its proposed therapeutic use in humans.
Development of Computational Approaches with a Fragment-Based Drug Design Strategy: In Silico Hsp90 Inhibitors Discovery
Authors: León Roberto , Soto-Delgado Jorge , Montero Elizabeth , Vargas Matías
Published: December 2021

A semi-exhaustive approach and a heuristic search algorithm use a fragment-based drug design (FBDD) strategy for designing new inhibitors in an in silico process. A deconstruction reconstruction process uses a set of known Hsp90 ligands for generating new ones. The deconstruction process consists of cutting off a known ligand in fragments. The reconstruction process consists of coupling fragments to develop a new set of ligands. For evaluating the approaches, we compare the binding energy of the new ligands with the known ligands.
How the Innate Immune DNA Sensing cGAS–STING Pathway Is Involved in Autophagy
Authors: Zheng Wanglong , Xia Nengwen , Zhang Jiajia , Chen Nanhua , Meurens François , Liu Zongping , Zhu Jianzhong
Published: December 2021

The cGAS–STING pathway is a key component of the innate immune system and exerts crucial roles in the detection of cytosolic DNA and invading pathogens. Accumulating evidence suggests that the intrinsic cGAS–STING pathway not only facilitates the production of type I interferons (IFN-I) and inflammatory responses but also triggers autophagy. Autophagy is a homeostatic process that exerts multiple effects on innate immunity. However, systematic evidence linking the cGAS–STING pathway and autophagy is still lacking. Therefore, one goal of this review is to summarize the known mechanisms of autophagy induced by the cGAS–STING pathway and their consequences. The cGAS–STING pathway can trigger canonical autophagy through liquid-phase separation of the cGAS–DNA complex, interaction of cGAS and Beclin-1, and STING-triggered ER stress–mTOR signaling. Furthermore, both cGAS and STING can induce non-canonical autophagy via LC3-interacting regions and binding with LC3. Subsequently, autophagy induced by the cGAS–STING pathway plays crucial roles in balancing innate immune responses, maintaining intracellular environmental homeostasis, alleviating liver injury, and limiting tumor growth and transformation.
A Rat Model of Post-Traumatic Stress Syndrome Causes Phenotype-Associated Morphological Changes and Hypofunction of the Adrenal Gland
Authors: Tseilikman Vadim , Komelkova Maria , Kondashevskaya Marina V. , Manukhina Eugenia , Downey H. Fred , Chereshnev Valerii , Chereshneva Margarita , Platkovskii Pavel , Goryacheva Anna , Pashkov Anton , Fedotova Julia , Tseilikman Olga , Maltseva Natalya , Cherkasova Olga , Steenblock Charlotte , Bornstein Stefan R. , Ettrich Barbara , Chrousos George P. , Ullmann Enrico
Published: December 2021

Background: Rats exposed to chronic predator scent stress mimic the phenotype of complex post-traumatic stress disorder (PTSD) in humans, including altered adrenal morphology and function. High- and low-anxiety phenotypes have been described in rats exposed to predator scent stress (PSS). This study aimed to determine whether these high- and low-anxiety phenotypes correlate with changes in adrenal histomorphology and corticosteroid production. Methods: Rats were exposed to PSS for ten days. Thirty days later, the rats’ anxiety index (AI) was assessed with an elevated plus-maze test. Based on differences in AI, the rats were segregated into low- (AI ≤ 0.8, n = 9) and high- (AI > 0.8, n = 10) anxiety phenotypes. Plasma corticosterone (CORT) concentrations were measured by ELISA. Adrenal CORT, desoxyCORT, and 11-dehydroCORT were measured by high-performance liquid chromatography. After staining with hematoxylin and eosin, adrenal histomorphometric changes were evaluated by measuring the thickness of the functional zones of the adrenal cortex. Results: Decreased plasma CORT concentrations, as well as decreased adrenal CORT, desoxyCORT and 11-dehydroCORT concentrations, were observed in high- but not in low-anxiety phenotypes. These decreases were associated with increases in AI. PSS led to a significant decrease in the thickness of the zona fasciculata and an increase in the thickness of the zona intermedia. The increase in the thickness of the zona intermedia was more pronounced in low-anxiety than in high-anxiety rats. A decrease in the adrenal capsule thickness was observed only in low-anxiety rats. The nucleus diameter of cells in the zona fasciculata of high-anxiety rats was significantly smaller than that of control or low-anxiety rats. Conclusion: Phenotype-associated changes in adrenal function and histomorphology were observed in a rat model of complex post-traumatic stress disorder.
Preparation of Antimicrobial Coatings from Cross-Linked Copolymers Containing Quaternary Dodecyl-Ammonium Compounds
Authors: Druvari Denisa , Antonopoulou Aggeliki , Lainioti Georgia C. , Vlamis-Gardikas Alexios , Bokias Georgios , Kallitsis Joannis K.
Published: December 2021

One of the concerns today’s societies face is the development of resistant pathogenic microorganisms. The need to tackle this problem has driven the development of innovative antimicrobial materials capable of killing or inhibiting the growth of microorganisms. The present study investigates the dependence of the antimicrobial activity and solubility properties on the hydrophilicity/hydrophobicity ratio of antimicrobial coatings based on quaternary ammonium compounds. In this line, suitable hydrophilic and hydrophobic structural units were selected for synthesizing the antimicrobial copolymers poly(4-vinylbenzyl dimethyldodecylammonium chloride-co-acrylic acid), P(VBCDDA-co-AA20) and poly(dodecyltrimethylammonium 4-styrene sulfonate-co-glycidyl methacrylate), P(SSAmC12-co-GMA20), bearing an alkyl chain of 12 carbons either through covalent bonding or through electrostatic interaction. The cross-linking reaction of the carboxylic group of acrylic acid (AA) with the epoxide group of glycidyl methacrylate (GMA) of these two series of reactive antimicrobial copolymers was explored in blends, obtained through solution casting after curing at various temperatures. The release of the final products in pure water and NaCl 1 M solutions (as analyzed by gravimetry and total organic carbon, TOC/total nitrogen, TN analyses), could be controlled by the coating composition. The cross-linked polymeric membranes of composition 60/40 w/w % ratios led to 97.8 and 99.7% mortality for Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), respectively, whereas the coating 20/80 w/w % resulted in 96.6 and 99.8% cell reduction. Despite the decrease in hydrophobicity (from a 16- to a 12-carbon alkyl chain), the new materials maintained the killing efficacy, while at the same time resulting in increased release to the aqueous solution.
A Deep Exon Cryptic Splice Site Promotes Aberrant Intron Retention in a Von Willebrand Disease Patient
Authors: Conboy John G.
Published: December 2021

A translationally silent single nucleotide mutation in exon 44 (E44) of the von Willebrand factor (VWF) gene is associated with inefficient removal of intron 44 in a von Willebrand disease (VWD) patient. This intron retention (IR) event was previously attributed to reordered E44 secondary structure that sequesters the normal splice donor site. We propose an alternative mechanism: the mutation introduces a cryptic splice donor site that interferes with the function of the annotated site to favor IR. We evaluated both models using minigene splicing reporters engineered to vary in secondary structure and/or cryptic splice site content. Analysis of splicing efficiency in transfected K562 cells suggested that the mutation-generated cryptic splice site in E44 was sufficient to induce substantial IR. Mutations predicted to vary secondary structure at the annotated site also had modest effects on IR and shifted the balance of residual splicing between the cryptic site and annotated site, supporting competition among the sites. Further studies demonstrated that introduction of cryptic splice donor motifs at other positions in E44 did not promote IR, indicating that interference with the annotated site is context dependent. We conclude that mutant deep exon splice sites can interfere with proper splicing by inducing IR.
Interaction of KRSR Peptide with Titanium Dioxide Anatase (100) Surface: A Molecular Dynamics Simulation Study
Authors: Tarjányi Tamás , Bogár Ferenc , Minarovits Janos , Gajdács Márió , Tóth Zsolt
Published: December 2021

Due to its tensile strength and excellent biocompatibility, titanium (Ti) is commonly used as an implant material in medicine and dentistry. The success of dental implants depends on the formation of a contact between the oxidized surface of Ti implant and the surrounding bone tissue. The adsorption of proteins and peptides to the implant surface allows the bone-forming osteoblast cells to adhere to such modified surfaces. Recently, it has been observed that tetrapeptide KRSR (Lys-Arg-Ser-Arg) functionalization could promote osteoblast adhesion to implant surfaces. This may facilitate the establishment of an efficient bone-to implant contact and improve implant stability during the healing process. GROMACS, a molecular dynamics software package was used to perform a 200 ns simulation of adsorption of the KRSR peptide to the TiO2 (anatase) surface in an aqueous environment. The molecule conformations were mapped with Replica Exchange Molecular Dynamics (REMD) simulations to assess the possible peptide conformations on the anatase surface, and the umbrella sampling method was used to calculate the binding energy of the most common conformation. The simulations have shown that the KRSR peptide migrates and attaches to the surface in a stable position. The dominant amino acid residue interacting with the TiO2 surface was the N-terminal charged lysine (K) residue. REMD indicated that there is a distinct conformation that is taken by the KRSR peptide. In this conformation the surface interacts only with the lysine residue while the ser (S) and arg (R) residues interact with water molecules farther from the surface. The binding free energy of the most common conformation of KRSR peptide to the anatase (100) surface was ΔG = −8.817 kcal/mol. Our result suggests that the N-terminal lysine residue plays an important role in the adhesion of KRSR to the TiO2 surface and may influence the osseointegration of dental implants.
Drug Discovery for Mycobacterium tuberculosis Using Structure-Based Computer-Aided Drug Design Approach
Authors: Ejalonibu Murtala A. , Ogundare Segun A. , Elrashedy Ahmed A. , Ejalonibu Morufat A. , Lawal Monsurat M. , Mhlongo Ndumiso N. , Kumalo Hezekiel M.
Published: December 2021

Developing new, more effective antibiotics against resistant Mycobacterium tuberculosis that inhibit its essential proteins is an appealing strategy for combating the global tuberculosis (TB) epidemic. Finding a compound that can target a particular cavity in a protein and interrupt its enzymatic activity is the crucial objective of drug design and discovery. Such a compound is then subjected to different tests, including clinical trials, to study its effectiveness against the pathogen in the host. In recent times, new techniques, which involve computational and analytical methods, enhanced the chances of drug development, as opposed to traditional drug design methods, which are laborious and time-consuming. The computational techniques in drug design have been improved with a new generation of software used to develop and optimize active compounds that can be used in future chemotherapeutic development to combat global tuberculosis resistance. This review provides an overview of the evolution of tuberculosis resistance, existing drug management, and the design of new anti-tuberculosis drugs developed based on the contributions of computational techniques. Also, we show an appraisal of available software and databases on computational drug design with an insight into the application of this software and databases in the development of anti-tubercular drugs. The review features a perspective involving machine learning, artificial intelligence, quantum computing, and CRISPR combination with available computational techniques as a prospective pathway to design new anti-tubercular drugs to combat resistant tuberculosis.
Lipids and Trehalose Actively Cooperate in Heat Stress Management of Schizosaccharomyces pombe
Authors: Péter Mária , Gudmann Péter , Kóta Zoltán , Török Zsolt , Vígh László , Glatz Attila , Balogh Gábor
Published: December 2021

Homeostatic maintenance of the physicochemical properties of cellular membranes is essential for life. In yeast, trehalose accumulation and lipid remodeling enable rapid adaptation to perturbations, but their crosstalk was not investigated. Here we report about the first in-depth, mass spectrometry-based lipidomic analysis on heat-stressed Schizosaccharomyces pombe mutants which are unable to synthesize (tps1Δ) or degrade (ntp1Δ) trehalose. Our experiments provide data about the role of trehalose as a membrane protectant in heat stress. We show that under conditions of trehalose deficiency, heat stress induced a comprehensive, distinctively high-degree lipidome reshaping in which structural, signaling and storage lipids acted in concert. In the absence of trehalose, membrane lipid remodeling was more pronounced and increased with increasing stress dose. It could be characterized by decreasing unsaturation and increasing acyl chain length, and required de novo synthesis of stearic acid (18:0) and very long-chain fatty acids to serve membrane rigidification. In addition, we detected enhanced and sustained signaling lipid generation to ensure transient cell cycle arrest as well as more intense triglyceride synthesis to accommodate membrane lipid-derived oleic acid (18:1) and newly synthesized but unused fatty acids. We also demonstrate that these changes were able to partially substitute for the missing role of trehalose and conferred measurable stress tolerance to fission yeast cells.
The Paradigm Change of IL-33 in Vascular Biology
Authors: Demyanets Svitlana , Stojkovic Stefan , Huber Kurt , Wojta Johann
Published: December 2021

In this review, we focus on the actual understanding of the role of IL-33 in vascular biology in the context of the historical development since the description of IL-33 as a member of IL-1 superfamily and the ligand for ST2 receptor in 2005. We summarize recent data on the biology, structure and signaling of this dual-function factor with both nuclear and extracellular cytokine properties. We describe cellular sources of IL-33, particularly within vascular wall, changes in its expression in different cardio-vascular conditions and mechanisms of IL-33 release. Additionally, we summarize the regulators of IL-33 expression as well as the effects of IL-33 itself in cells of the vasculature and in monocytes/macrophages in vitro combined with the consequences of IL-33 modulation in models of vascular diseases in vivo. Described in murine atherosclerosis models as well as in macrophages as an atheroprotective cytokine, extracellular IL-33 induces proinflammatory, prothrombotic and proangiogenic activation of human endothelial cells, which are processes known to be involved in the development and progression of atherosclerosis. We, therefore, discuss that IL-33 can possess both protective and harmful effects in experimental models of vascular pathologies depending on experimental conditions, type and dose of administration or method of modulation.
Spherical Silica Functionalized by 2-Naphthalene Methanol Luminophores as a Phosphorescence Sensor
Authors: Laskowska Magdalena , Nowak Anna , Dulski Mateusz , Weigl Peter , Blochowicz Thomas , Laskowski Łukasz
Published: December 2021

Photoluminescence is known to have huge potential for applications in studying biological systems. In that respect, phosphorescent dye molecules open the possibility to study the local slow solvent dynamics close to hard and soft surfaces and interfaces using the triplet state (TSD: triplet state solvation dynamics). However, for that purpose, probe molecules with efficient phosphorescence features are required with a fixed location on the surface. In this article, a potential TSD probe is presented in the form of a nanocomposite: we synthesize spherical silica particles with 2-naphthalene methanol molecules attached to the surface with a predefined surface density. The synthesis procedure is described in detail, and the obtained materials are characterized employing transmission electron microscopy imaging, Raman, and X-ray photoelectron spectroscopy. Finally, TSD experiments are carried out in order to confirm the phosphorescence properties of the obtained materials and the route to develop phosphorescent sensors at silica surfaces based on the presented results is discussed.
Peptides Bearing Multiple Post-Translational Modifications as Antigenic Targets for Severe Rheumatoid Arthritis Patients
Authors: García-Moreno Cristina , Gómara María J. , Castellanos-Moreira Raúl , Sanmartí Raimon , Haro Isabel
Published: December 2021

Rheumatoid arthritis (RA) is characterized by the presence of autoantibodies that are of paramount importance for the diagnosis and prognosis of the disease and have been implicated in its pathogenesis. Proteins resulting from post-translational modifications (PTMs) are capable of triggering autoimmune responses important for the development of RA. In this work, we investigate serum antibody reactivity in patients with an established RA against a panel of chimeric peptides derived from fibrin and filaggrin proteins and bearing from one to three PTMs (citrullination, carbamylation and acetylation) by home-designed ELISA tests (anti-AMPA autoantibodies). The role of anti-AMPAs as biomarkers linked to the presence of a more severe RA phenotype (erosive disease with radiological structural damage) and to the presence of interstitial lung disease (ILD), a severe extra-articular manifestation in RA patients entailing a high mortality, was also analyzed. In general, the association with the clinical phenotype of RA was confirmed with the different autoantibodies, and especially for IgA and IgM isotypes. The prevalence of severe joint damage was only statistically significant for the IgG isotype when working with the peptide bearing three PTMs. Furthermore, the median titers were significantly higher in patients with RA-ILD, a finding not observed for the IgG isotype when working with the single- and double-modified peptides.
Direct vs. Video-Laryngoscopy for Intubation by Paramedics of Simulated COVID-19 Patients under Cardiopulmonary Resuscitation: A Randomized Crossover Trial
Authors: Gadek Leszek , Szarpak Lukasz , Konge Lars , Dabrowski Marek , Telecka-Gadek Dominika , Maslanka Maciej , Drela Wiktoria Laura , Jachowicz Marta , Iskrzycki Lukasz , Bialka Szymon , Peacock Frank William , Smereka Jacek
Published: December 2021

A safe way of securing the airway with an endotracheal tube is one of the priorities of an advanced cardiovascular life support algorithm for suspected or confirmed COVID-19 patients. The aim of this study was to compare intubation success rates (ISR) and intubation time (IT) of different laryngoscopes for simulated COVID-19 patients under cardiopulmonary resuscitation. The study was designed as a prospective, randomized, crossover trial. Fifty four active paramedics performed endotracheal intubation with a Macintosh direct laryngoscope (MAC) and McGrath videolaryngoscope (McGrath) with and without personal protective equipment (PPE). Without PPE, ISRs were 87% and 98% for MAC and McGrath, respectively (p = 0.32). ITs were 22.5 s (IQR: 19–26) and 19.5 s (IQR: 17–21) for MAC and McGrath, respectively (p = 0.005). With PPE, first-pass ISR were 30% and 89% with MAC and McGrath, respectively (p < 0.001). The overall success rates were 83% vs. 100% (p = 0.002). Median ITs were 34.0 s (IQR: 29.5–38.5) and 24.8 s (IQR: 21–29) for MAC and McGrath, respectively (p < 0.001). In conclusion, the McGrath videolaryngoscope appears to possess significant advantages over the Macintosh direct laryngoscope when used by paramedics in suspected or confirmed COVID-19 intubation scenarios.
Deep Learning to Distinguish ABCA4-Related Stargardt Disease from PRPH2-Related Pseudo-Stargardt Pattern Dystrophy
Authors: Miere Alexandra , Zambrowski Olivia , Kessler Arthur , Mehanna Carl-Joe , Pallone Carlotta , Seknazi Daniel , Denys Paul , Amoroso Francesca , Petit Eric , Souied Eric H.
Published: December 2021

(1) Background: Recessive Stargardt disease (STGD1) and multifocal pattern dystrophy simulating Stargardt disease (“pseudo-Stargardt pattern dystrophy”, PSPD) share phenotypic similitudes, leading to a difficult clinical diagnosis. Our aim was to assess whether a deep learning classifier pretrained on fundus autofluorescence (FAF) images can assist in distinguishing ABCA4-related STGD1 from the PRPH2/RDS-related PSPD and to compare the performance with that of retinal specialists. (2) Methods: We trained a convolutional neural network (CNN) using 729 FAF images from normal patients or patients with inherited retinal diseases (IRDs). Transfer learning was then used to update the weights of a ResNet50V2 used to classify the 370 FAF images into STGD1 and PSPD. Retina specialists evaluated the same dataset. The performance of the CNN and that of retina specialists were compared in terms of accuracy, sensitivity, and precision. (3) Results: The CNN accuracy on the test dataset of 111 images was 0.882. The AUROC was 0.890, the precision was 0.883 and the sensitivity was 0.883. The accuracy for retina experts averaged 0.816, whereas for retina fellows it averaged 0.724. (4) Conclusions: This proof-of-concept study demonstrates that, even with small databases, a pretrained CNN is able to distinguish between STGD1 and PSPD with good accuracy.
Association of Insulin Resistance with Vascular Ageing in a General Caucasian Population: An EVA Study
Authors: Gómez-Sánchez Leticia , Gómez-Sánchez Marta , Lugones-Sánchez Cristina , Tamayo-Morales Olaya , González-Sánchez Susana , Rodríguez-Sánchez Emiliano , García-Ortiz Luis , Gómez-Marcos Manuel A. ,   on behalf of the EVA Investigators
Published: December 2021

The data on the relationship between insulin resistance and vascular ageing are limited. The aim of this study was to explore the association of different indices of insulin resistance with vascular ageing in an adult Caucasian population without cardiovascular disease. We selected 501 individuals without cardiovascular disease (mean age: 55.9 years, 50.3% women) through random sampling stratified by sex and age. Arterial stiffness was evaluated by measuring the carotid-to-femoral pulse wave velocity (cfPWV) and brachial-to-ankle pulse wave velocity (baPWV). The participants were classified into three groups according to the degree of vascular ageing: early vascular ageing (EVA), normal vascular ageing (NVA) and healthy vascular ageing (HVA). Insulin resistance was evaluated with the homeostatic model assessment of insulin resistance (HOMA-IR) and another five indices. The prevalence of HVA and EVA was 8.4% and 21.4%, respectively, when using cfPWV, and 7.4% and 19.2%, respectively, when using baPWV. The deterioration of vascular ageing, with both measurements, presented as an increase in all the analysed indices of insulin resistance. In the multiple regression analysis and logistic regression analysis, the indices of insulin resistance showed a positive association with cfPWV and baPWV and with EVA.
Potential Applications of Computational Fluid Dynamics for Predicting Hemolysis in Mitral Paravalvular Leaks
Authors: Kozłowski Michał , Wojtas Krzysztof , Orciuch Wojciech , Jędrzejek Marek , Smolka Grzegorz , Wojakowski Wojciech , Makowski Łukasz
Published: December 2021

Paravalvular leaks (PVLs) may lead to hemolysis. In vitro shear stress forces above 300 Pa cause erythrocyte destruction. PVL channel dimensions may determine magnitude of shear stress forces that affect erythrocytes; however, this has not been tested. It remains unclear how different properties of PVL channels contribute to presence of hemolysis. A model of a left ventricle was created based on data from computer tomography with Slicer software PVLs of various shapes and sizes were introduced. Blood flow was simulated using ANSYS Fluent software. The following variables were examined: wall shear stress, shear stress in fluid, volume of PVL channel with shear stress exceeding 300 Pa, and duration of exposure of erythrocytes to shear stress values above 300 Pa. In all models, shear stress forces exceeded 300 Pa. Shear stress increased with blood flow rates and cross-sectional areas of any PVL. There was no linear relationship between cross-sectional area of a PVL and volume of a PVL channel with shear stress > 300 Pa. Blood flow through mitral PVLs is associated with shear stress above 300 Pa. Cross-sectional area of a PVL does not correlate with volume of a PVL channel with shear stress > 300 Pa and duration of exposure of erythrocytes to shear stress > 300 Pa.
Prevalence and Predisposing Factors for Recurrence after Hallux Valgus Surgery: A Systematic Review and Meta-Analysis
Authors: Ezzatvar Yasmin , López-Bueno Laura , Fuentes-Aparicio Laura , Dueñas Lirios
Published: December 2021

Recurrence is a frequent and undesirable outcome after hallux valgus (HV) surgery. However, the prevalence of HV recurrence and the pre- and postoperatory factors associated with it have not been adequately studied. This study aimed to quantify the prevalence rate of HV recurrence and to analyze its predisposing factors. MEDLINE and EMBASE databases were systematically searched for observational studies including individuals undergoing HV surgical correction. The random-effects restricted maximum likelihood model was used to estimate the pooled effect size (correlation coefficient (r)). Twenty-three studies were included, yielding a total of 2914 individuals. Pooled prevalence of HV recurrence was 24.86% (95% confidence interval (CI), 19.15 to 30.57, I2 = 91.92%, p = 0.00). Preoperative HV angle (HVA) (r = 0.29; 95% CI, 0.14 to 0.43) and preoperative intermetatarsal angle (IMA) (r = 0.13; 95% CI, 0.00 to 0.27) showed a moderate positive relationship with recurrence. Postoperative HVA (r = 0.57; 95% CI, 0.21 to 0.94) and sesamoid position (r = 0.46; 95% CI, 0.31 to 0.60) showed strong relationships with recurrence. In conclusion, preoperative HVA, IMA, and postoperative HVA and sesamoid position are significant risk factors for HV recurrence, and the association of these factors with recurrence is affected by age.
Low Screening Rates Despite a High Prevalence of Significant Liver Fibrosis in People with Diabetes from Primary and Secondary Care
Authors: Dobbie Laurence J. , Kassab Mohamed , Davison Andrew S. , Grace Pete , Cuthbertson Daniel J. , Hydes Theresa J.
Published: December 2021

Diabetes is a driver of non-alcoholic fatty liver disease (NAFLD) and fibrosis. We determine current practices in examining liver fibrosis in people with diabetes and record prevalence levels in primary and secondary care. We extracted HbA1c results ≥48 mmol/mol to identify people with diabetes, then examined the proportion who had AST, ALT, and platelets results, facilitating calculation of non-invasive fibrosis tests (NIT), or an enhanced liver fibrosis score. Fibrosis markers were requested in only 1.49% (390/26,090), of which 29.7% (n = 106) had evidence of significant fibrosis via NIT. All patients at risk of fibrosis had undergone transient elastography (TE), biopsy or imaging. TE and biopsy data showed that 80.6% of people with raised fibrosis markers had confirmed significant fibrosis. We also show that fibrosis levels as detected by NIT are marginally lower in patients treated with newer glucose lowering agents (sodium-glucose transporter protein 2 inhibitors, dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists). In conclusion by utilising a large consecutively recruited dataset we demonstrate that liver fibrosis is infrequently screened for in patients with diabetes despite high prevalence rates of advanced fibrosis. This highlights the need for cost-effectiveness analyses to support the incorporation of widespread screening into national guidelines and the requirement for healthcare practitioners to incorporate NAFLD screening into routine diabetes care.
Long-Term Preservation of Renal Function in Septic Shock Burn Patients Requiring Renal Replacement Therapy for Acute Kidney Injury
Authors: Mariano Filippo , De Biase Consuelo , Hollo Zsuzsanna , Deambrosis Ilaria , Davit Annalisa , Mella Alberto , Bergamo Daniela , Maffei Stefano , Rumbolo Francesca , Papaleo Alberto , Stella Maurizio , Biancone Luigi
Published: December 2021

Background. The real impact of septic shock-associated acute kidney injury (AKI) on the long-term renal outcome is still debated, and little is known about AKI-burn patients. In a cohort of burn survivors treated by continuous renal replacement therapy (CRRT) and sorbent technology (CPFA-CRRT), we investigated the long-term outcome of glomerular and tubular function. Methods. Out of 211 burn patients undergoing CRRT from 2001 to 2017, 45 survived, 40 completed the clinical follow-up (cumulative observation period 4067 months, median 84 months, IR 44-173), and 30 were alive on 31 December 2020. Besides creatinine and urine albumin, in the 19 patients treated with CPFA-CRRT, we determined the normalized GFR by 99mTc-DTPA (NRI-GFR) and studied glomerular and tubular urine protein markers. Results. At the follow-up endpoint, the median plasma creatinine and urine albumin were 0.99 (0.72–1.19) and 0.0 mg/dL (0.0–0.0), respectively. NRI-GFR was 103.0 mL/min (93.4–115). Four patients were diabetic, and 22/30 presented at least one risk factor for chronic disease (hypertension, dyslipidemia, and overweight). Proteinuria decreased over time, from 0.47 g/day (0.42–0.52) at 6 months to 0.134 g/day (0.09–0.17) at follow-up endpoint. Proteinuria positively correlated with the peak of plasma creatinine (r 0.6953, p 0.006) and the number of CRRT days (r 0.5650, p 0.035) during AKI course, and negatively with NRI–GFR (r −0.5545, p 0.049). In seven patients, urine protein profile showed a significant increase of glomerular marker albumin and glomerular/tubular index. Conclusions. Burn patients who experienced septic shock and AKI treated with CRRT had a long-term expectation of preserved renal function. However, these patients were more predisposed to microalbuminuria, diabetes, and the presence of risk factors for intercurrent comorbidities and chronic renal disease.
Association of Genes of the NO Pathway with Altitude Disease and Hypoxic Pulmonary Hypertension
Authors: Hannemann Juliane , Siques Patricia , Schmidt-Hutten Lena , Zummack Julia , Brito Julio , Böger Rainer
Published: December 2021

Chronic intermittent hypoxia leads to high-altitude pulmonary hypertension, which is associated with high asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthesis. Therefore, we aimed to understand the relation of single nucleotide polymorphisms in this pathway to high-altitude pulmonary hypertension (HAPH). We genotyped 69 healthy male Chileans subjected to chronic intermittent hypoxia. Acclimatization to altitude was determined using the Lake Louise Score and the presence of acute mountain sickness. Echocardiography was performed after six months in 24 individuals to estimate pulmonary arterial pressure. The minor allele of dimethylarginine dimethylaminohydrolase (DDAH)1 rs233112 was associated with high-baseline plasma ADMA concentration, while individuals homozygous for the major allele of DDAH2 rs805304 had a significantly greater increase in ADMA during chronic intermittent hypoxia. The major allele of alanine glyoxylate aminotransferase-2 (AGXT2) rs37369 was associated with a greater reduction of plasma symmetric dimethylarginine (SDMA). Several genes were associated with high-altitude pulmonary hypertension, and the nitric oxide synthase (NOS)3 and DDAH2 genes were related to acute mountain sickness. In conclusion, DDAH1 determines baseline plasma ADMA, while DDAH2 modulates ADMA increase in hypoxia. AGXT2 may be up-regulated in hypoxia. Genomic variation in the dimethylarginine pathway affects the development of HAPH and altitude acclimatization.
Healing of Chronic Wounds with Platelet-Derived Growth Factors from Single Donor Platelet-Rich Plasma following One Freeze-Thaw Cycle. A Cross-Sectional Study
Authors: Vidán-Estévez Vidán-Estévez , Sánchez-Herráez Sánchez-Herráez , Escalante-Barrigón Escalante-Barrigón , Seco-Calvo Seco-Calvo
Published: December 2021

Chronic non-healing wounds (CNHWs) may be associated with trauma or idiopathic in nature and are difficult to treat. Our objective was to assess the use of platelet-derived growth factor (PDGF) from single-donor platelets (al-PRP), using one freeze-thaw cycle, for treating CNHWs. We conducted a cross-sectional study. A total of 23 CNHWs being treated with al-PRP. The al-PRP treatment can be considered successful in well over half (n = 13, 56.5%) of the wounds. We found that all the wounds treated for up to 7 weeks showed partial or complete healing, while those treated for between 8 and 12 weeks did not show healing, healing again being successful in cases in which treatment was extended to more than 13 weeks (85.7%). Using chi-square tests, this relationship was found to be highly significant (p < 0.001, chi2 = 19.51; p value = 0.00006). Notably, Cramer’s V coefficient was very high (0.921), indicating that the effect size of PRP treatment duration on healing is very large (84.8%). We could suggest that the use of al-PRP in the healing of CNHWs is a promising approach. Further studies with larger sample sizes and long follow-ups are needed to obtain multivariate models to explain which factors favour the healing of ulcers treated with PRP