bluuebunny/crossref_metadata_2025 huggingface dataset:
Revealing Natural Intracellular Peptides in Gills of Seahorse Hippocampus reidi
Authors: Correa Claudia Neves , Fiametti Louise Oliveira , de Barros Gabriel Marques , de Castro Leandro Mantovani
Published: February 2023

The seahorse is a marine teleost fish member of the Syngnathidae family that displays a complex variety of morphological and reproductive behavior innovations and has been recognized for its medicinal importance. In the Brazilian ichthyofauna, the seahorse Hippocampus reidi is among the three fish species most used by the population in traditional medicine. In this study, a protocol was performed based on fast heat inactivation of proteases plus liquid chromatography coupled to mass spectrometry to identify native peptides in gills of seahorse H. reidi. The MS/MS spectra obtained from gills allowed the identification of 1080 peptides, of which 1013 peptides were present in all samples and 67 peptide sequences were identified in an additional LC-MS/MS run from an alkylated and reduced pool of samples. The majority of peptides were fragments of the internal region of the amino acid sequence of the precursor proteins (67%), and N- and C-terminal represented 18% and 15%, respectively. Many peptide sequences presented ribosomal proteins, histones and hemoglobin as precursor proteins. In addition, peptide fragments from moronecidin-like protein, described with antimicrobial activity, were found in all gill samples of H. reidi. The identified sequences may reveal new bioactive peptides.
A 20-Year Longitudinal Study of Plasma Chitotriosidase Activity in Treated Gaucher Disease Type 1 and 3 Patients—A Qualitative and Quantitative Approach
Authors: Szymańska-Rożek Paulina , Czartoryska Barbara , Kleinotiene Grazina , Lipiński Patryk , Tylki-Szymańska Anna , Ługowska Agnieszka
Published: February 2023

Chitotriosidase is an enzyme produced and secreted in large amounts by activated macrophages, especially macrophages loaded with phagocytozed glycosphingolipid in Gaucher disease. Macrophages phagocytose decayed blood cells that contain a lot of sphingolipid-rich cell membranes. In Gaucher disease, due to a deficit in beta-glucocerebrosidase activity, the phagocytozed substrate glucocerebroside cannot undergo further catabolism. In such a situation, macrophages secrete chitotriosidase in proportion to the degree of overload. Gaucher disease (GD) is a recessively inherited disorder resulting in storage of glucosylceramide (GlcCer) in lysosomes of tissue macrophages. It is directly caused by the deficiency of beta-glucocerebrosidase (GBA) activity. Chitotriosidase has been measured systematically each year in the same group of 49 patients with type 1 and 3 GD for over 20 years. Our analysis showed that chitotriosidase is very sensitive biomarker to enzyme replacement therapy (ERT). The response to treatment introduction is of an almost immediate nature, lowering pathologically high chitotriosidase levels by a factor of 2 in a time scale of 8 months, on average. Long term enzyme replacement therapy (ERT) brings chitotriosidase activity close to reference values. Finally, reducing the dose of ERT quickly boosts chitotriosidase activity, but restoring the initial dose of treatment brings chitotriosidase level of activity back onto the decreasing time trajectory.
Integrative Multiomics Analysis of the Heat Stress Response of Enterococcus faecium
Authors: Wang Li , Qiao Lin , Li Aike , Chen Lixian , He Beibei , Liu Gang , Wang Weiwei , Fang Jun
Published: February 2023

A continuous heat-adaptation test was conducted for one Enterococcus faecium (E. faecium) strain wild-type (WT) RS047 to obtain a high-temperature-resistant strain. After domestication, the strain was screened with a significantly higher ability of heat resistance. which is named RS047-wl. Then a multi-omics analysis of transcriptomics and metabolomics was used to analyze the mechanism of the heat resistance of the mutant. A total of 98 differentially expressed genes (DEGs) and 115 differential metabolites covering multiple metabolic processes were detected in the mutant, which indicated that the tolerance of heat resistance was regulated by multiple mechanisms. The changes in AgrB, AgrC, and AgrA gene expressions were involved in quorum-sensing (QS) system pathways, which regulate biofilm formation. Second, highly soluble osmotic substances such as putrescine, spermidine, glycine betaine (GB), and trehalose-6P were accumulated for the membrane transport system. Third, organic acids metabolism and purine metabolism were down-regulated. The findings can provide target genes for subsequent genetic modification of E. faecium, and provide indications for screening heat-resistant bacteria, so as to improve the heat-resistant ability of E. faecium for production.
Industrial Production of Proteins with Pichia pastoris—Komagataella phaffii
Authors: Barone Giovanni Davide , Emmerstorfer-Augustin Anita , Biundo Antonino , Pisano Isabella , Coccetti Paola , Mapelli Valeria , Camattari Andrea
Published: February 2023

Since the mid-1960s, methylotrophic yeast Komagataella phaffii (previously described as Pichia pastoris) has received increasing scientific attention. The interest for the industrial production of proteins for different applications (e.g., feed, food additives, detergent, waste treatment processes, and textile) is a well-consolidated scientific topic, and the importance for this approach is rising in the current era of environmental transition in human societies. This review aims to summarize fundamental and specific information in this scientific field. Additionally, an updated description of the relevant products produced with K. phaffii at industrial levels by a variety of companies—describing how the industry has leveraged its key features, from products for the ingredients of meat-free burgers (e.g., IMPOSSIBLE™ FOODS, USA) to diabetes therapeutics (e.g., Biocon, India)—is provided. Furthermore, active patents and the typical workflow for industrial protein production with this strain are reported.
Role of IL-6/STAT3 Axis in Resistance to Cisplatin in Gastric Cancers
Authors: Laurino Simona , Brancaccio Mariarita , Angrisano Tiziana , Calice Giovanni , Russi Sabino , Mazzone Pellegrino , Di Paola Giuseppina , Aieta Michele , Grieco Vitina , Bianchino Gabriella , Falco Geppino , Notarangelo Tiziana
Published: February 2023

Gastric cancer, the second most common cause of death worldwide, is characterized by poor prognosis and low responsiveness to chemotherapy. Indeed, multidrug resistance, based mainly on cellular and molecular factors, remains one of the most limiting factors of the current approach to gastric cancer (GC) therapy. We employed a comprehensive gene expression analysis through data mining of publicly available databases to assess the role of the signal transducer and activator of transcription 3 (STAT3) in gastric cancer drug efficiency. It has been proposed that gastric cancer cells are less sensitive to these drugs because they develop resistance to these agents through activating alternative signalling pathways responsible for overcoming pharmacological inhibition. Our study evaluated the hypothesis that activating STAT3 signalling in response to cisplatin reduces the reaction to the drug. Consistent with this hypothesis, inhibition of interleukin 6 (IL-6)/STAT3 in combination therapy with cisplatin prevented both STAT3 activation and more lethality than induction by a single agent. The data suggest that the IL-6/STAT3 axis block associated with cisplatin treatment may represent a strategy to overcome resistance.
Protective Potential of β-Hydroxybutyrate against Glucose-Deprivation-Induced Neurotoxicity Involving the Modulation of Autophagic Flux and the Monomeric Aβ Level in Neuro-2a Cells
Authors: Chiang Yi-Fen , Nguyen Ngan Thi Kim , Hsia Shih-Min , Chen Hsin-Yuan , Lin Shyh-Hsiang , Lin Ching-I
Published: February 2023

Hypoglycemia has been known as a potential contributory factor to neurodegenerative diseases, such as Alzheimer’s disease. There may be shared pathogenic mechanisms underlying both conditions, and the ketone body, β-hydroxybutyrate (BHB), as an alternative substrate for glucose may exert neuroprotection against hypoglycemia-induced injury. To investigate this, Neuro-2a cells were subjected to a 24 h period of glucose deprivation with or without the presence of BHB. Cell viability, reactive oxygen species (ROS) production, apoptosis, autophagy, and adenosine triphosphate (ATP) and beta-amyloid peptide (Aβ) levels were evaluated. The results show that Neuro-2a cells deprived of glucose displayed a significant loss of cell survival with a corresponding decrease in ATP levels, suggesting that glucose deprivation was neurotoxic. This effect was likely attributed to the diverse mechanisms including raised ROS, defective autophagic flux and reduced basal Aβ levels (particularly monomeric Aβ). The presence of BHB could partially protect against the loss of cell survival induced by glucose deprivation. The mechanisms underlying the neuroprotective actions of BHB might be mediated, at least in part, through restoring ATP, and modulating ROS production, autophagy flux efficacy and the monomeric Aβ level. Results imply that a possible link between the basal monomeric Aβ and glucose deprivation neurotoxicity, and treatments designed for the prevention of energy impairment, such as BHB, may be beneficial for rescuing surviving cells in relation to neurodegeneration.
An Artificial Placenta Experimental System in Sheep: Critical Issues for Successful Transition and Survival up to One Week
Authors: Eixarch Elisenda , Illa Miriam , Fucho Raquel , Rezaei Kambiz , Hawkins-Villarreal Ameth , Bobillo-Pérez Sara , Randanne Paula C. , Moran Miguel , Chorda Marina , Sanchez-Martinez Sergio , de Roo-Puente Yolanda J. D. , Velilla Maria del Mar , del Rio Ruth , Gallego Marc , Sanin-Ramirez Daniel , Narvaez Victor , Crispi Fatima , Bonet-Carne Elisenda , Gratacos Eduard
Published: February 2023

Objective: To describe the development of an artificial placenta (AP) system in sheep with learning curve and main bottlenecks to allow survival up to one week. Methods: A total of 28 fetal sheep were transferred to an AP system at 110–115 days of gestation. The survival goal in the AP system was increased progressively in three consecutive study groups: 1–3 h (n = 8), 4–24 h (n = 10) and 48–168 h (n = 10). Duration of cannulation procedure, technical complications, pH, lactate, extracorporeal circulation (EC) circuit flows, fetal heart rate, and outcomes across experiments were compared. Results: There was a progressive reduction in cannulation complications (75%, 50% and 0%, p = 0.004), improvement in initial pH (7.20 ± 0.06, 7.31 ± 0.04 and 7.33 ± 0.02, p = 0.161), and increment in the rate of experiments reaching survival goal (25%, 70% and 80%, p = 0.045). In the first two groups, cannulation accidents, air bubbles in the extracorporeal circuit, and thrombotic complications were the most common cause of AP system failure. Conclusions: Achieving a reproducible experimental setting for an AP system is extremely challenging, time- and effort-consuming, and requires a highly multidisciplinary team. As a result of the learning curve, we achieved reproducible transition and survival up to 7 days. Extended survival requires improving instrumentation with custom-designed devices.
The Usefulness of Nanotechnology in Improving the Prognosis of Lung Cancer
Authors: Bordeianu Gabriela , Filip Nina , Cernomaz Andrei , Veliceasa Bogdan , Hurjui Loredana Liliana , Pinzariu Alin Constantin , Pertea Mihaela , Clim Andreea , Marinca Mihai Vasile , Serban Ionela Lacramioara
Published: February 2023

Lung cancer remains a major public health problem both in terms of incidence and specific mortality despite recent developments in terms of prevention, such as smoking reduction policies and clinical management advances. Better lung cancer prognosis could be achieved by early and accurate diagnosis and improved therapeutic interventions. Nanotechnology is a dynamic and fast-developing field; various medical applications have been developed and deployed, and more exist as proofs of concepts or experimental models. We aim to summarize current knowledge relevant to the use of nanotechnology in lung cancer management. Starting from the chemical structure-based classification of nanoparticles, we identify and review various practical implementations roughly organized as diagnostic or therapeutic in scope, ranging from innovative contrast agents to targeted drug carriers. Available data are presented starting with standards of practice and moving to highly experimental methods and proofs of concept; particularities, advantages, limits and future directions are explored, focusing on the potential impact on lung cancer clinical prognosis.
HDL-Based Therapy: Vascular Protection at All Stages
Authors: Poznyak Anastasia V. , Sukhorukov Vasily N. , Eremin Ilya I. , Nadelyaeva Irina I. , Gutyrchik Nikita A. , Orekhov Alexander N.
Published: February 2023

It is known that lipid metabolism disorders are involved in a wide range of pathologies. These pathologies include cardiovascular, metabolic, neurodegenerative diseases, and even cancer. All these diseases lead to serious health consequences, which makes it impossible to ignore them. Unfortunately, these diseases most often have a complex pathogenesis, which makes it difficult to study them and, in particular, diagnose and treat them. HDL is an important part of lipid metabolism, performing many functions under normal conditions. One of such functions is the maintaining of the reverse cholesterol transport. These functions are also implicated in pathology development. Thus, HDL contributes to vascular protection, which has been demonstrated in various conditions: Alzheimer’s disease, atherosclerosis, etc. Many studies have shown that serum levels of HDL cholesterol correlate negatively with CV risk. With these data, HDL-C is a promising therapeutic target. In this manuscript, we reviewed HDL-based therapeutic strategies that are currently being used or may be developed soon.
Cardioprotective Effects of a Selective c-Jun N-terminal Kinase Inhibitor in a Rat Model of Myocardial Infarction
Authors: Plotnikov Mark B. , Chernysheva Galina A. , Smol’yakova Vera I. , Aliev Oleg I. , Fomina Tatyana I. , Sandrikina Lyubov A. , Sukhodolo Irina V. , Ivanova Vera V. , Osipenko Anton N. , Anfinogenova Nina D. , Khlebnikov Andrei I. , Atochin Dmitriy N. , Schepetkin Igor A. , Quinn Mark T.
Published: February 2023

Activation of c-Jun N-terminal kinases (JNKs) is involved in myocardial injury, left ventricular remodeling (LV), and heart failure (HF) after myocardial infarction (MI). The aim of this research was to evaluate the effects of a selective JNK inhibitor, 11H-indeno [1,2-b]quinoxalin-11-one oxime (IQ-1), on myocardial injury and acute myocardial ischemia/reperfusion (I/R) in adult male Wistar rats. Intraperitoneal administration of IQ-1 (25 mg/kg daily for 5 days) resulted in a significant decrease in myocardial infarct size on day 5 after MI. On day 60 after MI, a significant (2.6-fold) decrease in LV scar size, a 2.2-fold decrease in the size of the LV cavity, a 2.9-fold decrease in the area of mature connective tissue, and a 1.7-fold decrease in connective tissue in the interventricular septum were observed compared with the control group. The improved contractile function of the heart resulted in a significant (33%) increase in stroke size, a 40% increase in cardiac output, a 12% increase in LV systolic pressure, a 28% increase in the LV maximum rate of pressure rise, a 45% increase in the LV maximum rate of pressure drop, a 29% increase in the contractility index, a 14% increase in aortic pressure, a 2.7-fold decrease in LV end-diastolic pressure, and a 4.2-fold decrease in LV minimum pressure. We conclude that IQ-1 has cardioprotective activity and reduces the severity of HF after MI.
Design for Robustness: Bio-Inspired Perspectives in Structural Engineering
Authors: Kiakojouri Foad , De Biagi Valerio , Abbracciavento Lorenza
Published: February 2023

Bio-inspired solutions are widely adopted in different engineering disciplines. However, in structural engineering, these solutions are mainly limited to bio-inspired forms, shapes, and materials. Nature is almost completely neglected as a source of structural design philosophy. This study lists and discusses several bio-inspired solutions classified into two main classes, i.e., compartmentalization and complexity, for structural robustness design. Different examples are provided and mechanisms are categorized and discussed in detail. Some provided ideas are already used in the current structural engineering research and practice, usually without focus on their bio-analogy. These solutions are revisited and scrutinized from a bio-inspired point of view, and new aspects and possible improvements are suggested. Moreover, novel bio-inspired concepts including delayed compartmentalization, active compartmentalization, compartmentalization in intact parts, and structural complexity are also propounded for structural design under extreme loading conditions.
Capabilities of Double-Resonance LPG and SPR Methods for Hypersensitive Detection of SARS-CoV-2 Structural Proteins: A Comparative Study
Authors: Eftimov Tinko , Genova-Kalou Petia , Dyankov Georgi , Bock Wojtek J. , Mankov Vihar , Shoar Ghaffari Sanaz , Veselinov Petar , Arapova Alla , Makouei Somayeh
Published: February 2023

The danger of the emergence of new viral diseases and their rapid spread demands apparatuses for continuous rapid monitoring in real time. This requires the creation of new bioanalytical methods that overcome the shortcomings of existing ones and are applicable for point-of-care diagnostics. For this purpose, a variety of biosensors have been developed and tested in proof-of-concept studies, but none of them have been introduced for commercial use so far. Given the importance of the problem, in this study, long-period grating (LPG) and surface plasmon resonance (SPR) biosensors, based on antibody detection, were examined, and their capabilities for SARS-CoV-2 structural proteins detection were established. Supersensitive detections of structural proteins in the order of several femtomoles were achieved by the LPG method, while the SPR method demonstrated a sensitivity of about one hundred femtomoles. The studied biosensors are compatible in sensitivity with ELISA and rapid antigen tests but, in contrast, they are quantitative, which makes them applicable for acute SARS-CoV-2 infection detection, especially during the early stages of viral replication.
Upper-Arm Photoplethysmographic Sensor with One-Time Calibration for Long-Term Blood Pressure Monitoring
Authors: Wang Ching-Fu , Wang Ting-Yun , Kuo Pei-Hsin , Wang Han-Lin , Li Shih-Zhang , Lin Chia-Ming , Chan Shih-Chieh , Liu Tzu-Yu , Lo Yu-Chun , Lin Sheng-Huang , Chen You-Yin
Published: February 2023

Wearable cuffless photoplethysmographic blood pressure monitors have garnered widespread attention in recent years; however, the long-term performance values of these devices are questionable. Most cuffless blood pressure monitors require initial baseline calibration and regular recalibrations with a cuffed blood pressure monitor to ensure accurate blood pressure estimation, and their estimation accuracy may vary over time if left uncalibrated. Therefore, this study assessed the accuracy and long-term performance of an upper-arm, cuffless photoplethysmographic blood pressure monitor according to the ISO 81060-2 standard. This device was based on a nonlinear machine-learning model architecture with a fine-tuning optimized method. The blood pressure measurement protocol followed a validation procedure according to the standard, with an additional four weekly blood pressure measurements over a 1-month period, to assess the long-term performance values of the upper-arm, cuffless photoplethysmographic blood pressure monitor. The results showed that the photoplethysmographic signals obtained from the upper arm had better qualities when compared with those measured from the wrist. When compared with the cuffed blood pressure monitor, the means ± standard deviations of the difference in BP at week 1 (baseline) were −1.36 ± 7.24 and −2.11 ± 5.71 mmHg for systolic and diastolic blood pressure, respectively, which met the first criterion of ≤5 ± ≤8.0 mmHg and met the second criterion of a systolic blood pressure ≤ 6.89 mmHg and a diastolic blood pressure ≤ 6.84 mmHg. The differences in the uncalibrated blood pressure values between the test and reference blood pressure monitors measured from week 2 to week 5 remained stable and met both criteria 1 and 2 of the ISO 81060-2 standard. The upper-arm, cuffless photoplethysmographic blood pressure monitor in this study generated high-quality photoplethysmographic signals with satisfactory accuracy at both initial calibration and 1-month follow-ups. This device could be a convenient and practical tool to continuously measure blood pressure over long periods of time.
Social Touch Reduces Pain Perception—An fMRI Study of Cortical Mechanisms
Authors: Savallampi Mattias , Maallo Anne M. S. , Shaikh Sumaiya , McGlone Francis , Bariguian-Revel Frédérique J. , Olausson Håkan , Boehme Rebecca
Published: February 2023

Unmyelinated low-threshold mechanoreceptors (C-tactile, CT) in the human skin are important for signaling information about hedonic aspects of touch. We have previously reported that CT-targeted brush stroking by means of a robot reduces experimental mechanical pain. To improve the ecological validity of the stimulation, we developed standardized human–human touch gestures for signaling attention and calming. The attention gesture is characterized by tapping of the skin and is perceived as neither pleasant nor unpleasant, i.e., neutral. The calming gesture is characterized by slow stroking of the skin and is perceived as moderately to very pleasant. Furthermore, the attention (tapping) gesture is ineffective, whereas the calming (stroking) gesture is effective in activating CT-afferents. We conducted an fMRI study (n = 32) and capitalized on the previous development of touch gestures. We also developed an MR compatible stimulator for high-precision mechanical pain stimulation of the thenar region of the hand. Skin-to-skin touching (stroking or tapping) was applied and was followed by low and high pain. When the stroking gesture preceded pain, the pain was rated as less intense. When the tapping gesture preceded the pain, the pain was rated as more intense. Individual pain perception related to insula activation, but the activation was not higher for stroking than for tapping in any brain area during the stimulation period. However, during the evaluation period, stronger activation in the periaqueductal gray matter was observed after calming touch compared to after tapping touch. This finding invites speculation that human–human gentle skin stroking, effective in activating CT-afferents, reduced pain through neural processes involving CT-afferents and the descending pain pathway.
Overlapping between Wound Healing Occurring in Tumor Growth and in Central Nervous System Neurodegenerative Diseases
Authors: Ribatti Domenico , Benagiano Vincenzo , Guidolin Diego
Published: February 2023

Wound healing is characterized by the formation of a granulation tissue consisting of inflammatory cells, newly formed blood vessels, and fibroblasts embedded in a loose collagenous extracellular matrix. Tumors behave as wounds that fail to heal. Neuronal loss in neurodegenerative disease is associated with the synthesis and release of new components of the extracellular matrix by activated fibroblasts and astrocytes. This condition is responsible for a perpetuation of the wound healing state and constitutes a condition very similar to that which occurs during tumor progression. The aim of this article is to emphasize and compare the role of wound healing in two different pathological conditions, namely tumor growth and central nervous system neurodegenerative diseases. Both are conditions in which wounds fail to heal, as occurs in physiological conditions.
An Efficient Framework to Detect Intracranial Hemorrhage Using Hybrid Deep Neural Networks
Authors: Rajagopal Manikandan , Buradagunta Suvarna , Almeshari Meshari , Alzamil Yasser , Ramalingam Rajakumar , Ravi Vinayakumar
Published: February 2023

Intracranial hemorrhage (ICH) is a serious medical condition that necessitates a prompt and exhaustive medical diagnosis. This paper presents a multi-label ICH classification issue with six different types of hemorrhages, namely epidural (EPD), intraparenchymal (ITP), intraventricular (ITV), subarachnoid (SBC), subdural (SBD), and Some. A patient may experience numerous hemorrhages at the same time in some situations. A CT scan of a patient’s skull is used to detect and classify the type of ICH hemorrhage(s) present. First, our model determines whether there is a hemorrhage or not; if there is a hemorrhage, the model attempts to identify the type of hemorrhage(s). In this paper, we present a hybrid deep learning approach that combines convolutional neural network (CNN) and Long-Short Term Memory (LSTM) approaches (Conv-LSTM). In addition, to propose viable solutions for the problem, we used a Systematic Windowing technique with a Conv-LSTM. To ensure the efficacy of the proposed model, experiments are conducted on the RSNA dataset. The suggested model provides higher sensitivity (93.87%), specificity (96.45%), precision (95.21%), and accuracy (95.14%). In addition, the obtained F1 score results outperform existing deep neural network-based algorithms.
Qualitative Evaluation of Intracranial Pressure Slopes in Patients Undergoing Brain Death Protocol
Authors: Ideta Mylena Miki Lopes , Oliveira Louise Makarem , Gonçalves Daniel Buzaglo , Paschoalino Mylla Christie , Carvalho Nise Alessandra Carvalho , Della Coletta Marcus Vinicius , Paiva Wellingson , Brasil Sérgio , Amorim Robson Luís Oliveira de
Published: February 2023

Background: Due to the importance of not mistaking when determining the brain death (BD) diagnostic, reliable confirmatory exams should be performed to enhance its security. This study aims to evaluate the intracranial pressure (ICP) pulse morphology behavior in brain-dead patients through a noninvasive monitoring system. Methods: A pilot case-control study was conducted in adults that met the BD national protocol criteria. Quantitative parameters from the ICP waveforms, such as the P2/P1 ratio, time-to-peak (TTP) and pulse amplitude (AMP) were extracted and analyzed comparing BD patients and health subjects. Results: Fifteen patients were included, and 6172 waveforms were analyzed. ICP waveforms presented substantial differences amidst BD patients when compared to the control group, especially AMP, which had lower values in patients diagnosed with BD (p < 0.0001) and the TTP median (p < 0.00001), but no significance was found for the P2/P1 ratio (p = 0.8). The area under curve for combination of parameters on the BD prediction was 0.77. Conclusions: In this exploratory study, noninvasive ICP waveforms have shown potential as a screening method in patients with suspected brain death. Future studies should be carried out in a larger population.
Enhanced Targeted Delivery of Minocycline via Transferrin Conjugated Albumin Nanoparticle Improves Neuroprotection in a Blast Traumatic Brain Injury Model
Authors: Perumal Venkatesan , Ravula Arun Reddy , Agas Agnieszka , Gosain Aakaash , Aravind Aswati , Sivakumar Ponnurengam Malliappan , I Shanmuga Sundari , Sambath Karthik , Vijayaraghavalu Sivakumar , Chandra Namas
Published: February 2023

Traumatic brain injury (TBI) is a major source of death and disability worldwide as a result of motor vehicle accidents, falls, attacks and bomb explosions. Currently, there are no FDA-approved drugs to treat TBI patients predominantly because of a lack of appropriate methods to deliver drugs to the brain for therapeutic effect. Existing clinical and pre-clinical studies have shown that minocycline’s neuroprotective effects either through high plasma protein binding or an increased dosage requirement have resulted in neurotoxicity. In this study, we focus on the formulation, characterization, in vivo biodistribution, behavioral improvements, neuroprotective effect and toxicity of transferrin receptor-targeted (tf) conjugated minocycline loaded albumin nanoparticles in a blast-induced TBI model. A novel tf conjugated minocycline encapsulated albumin nanoparticle was developed, characterized and quantified using a validated HPLC method as well as other various analytical methods. The results of the nanoformulation showed small, narrow hydrodynamic size distributions, with high entrapment, loading efficiencies and sustained release profiles. Furthermore, the nanoparticle administered at minimal doses in a rat model of blast TBI was able to cross the blood–brain barrier, enhanced nanoparticle accumulation in the brain, improved behavioral outcomes, neuroprotection, and reduced toxicity compared to free minocycline. Hence, tf conjugated minocycline loaded nanoparticle elicits a neuroprotective effect and can thus offer a potential therapeutic effect.
Neural Correlates of Delay Discounting in the Light of Brain Imaging and Non-Invasive Brain Stimulation: What We Know and What Is Missed
Authors: Moro Andrea Stefano , Saccenti Daniele , Ferro Mattia , Scaini Simona , Malgaroli Antonio , Lamanna Jacopo
Published: February 2023

In decision making, the subjective value of a reward declines with the delay to its receipt, describing a hyperbolic function. Although this phenomenon, referred to as delay discounting (DD), has been extensively characterized and reported in many animal species, still, little is known about the neuronal processes that support it. Here, after drawing a comprehensive portrait, we consider the latest neuroimaging and lesion studies, the outcomes of which often appear contradictory among comparable experimental settings. In the second part of the manuscript, we focus on a more recent and effective route of investigation: non-invasive brain stimulation (NIBS). We provide a comprehensive review of the available studies that applied transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) to affect subjects’ performance in DD tasks. The aim of our survey is not only to highlight the superiority of NIBS in investigating DD, but also to suggest targets for future experimental studies, since the regions considered in these studies represent only a fraction of the possible ones. In particular, we argue that, based on the available neurophysiological evidence from lesion and brain imaging studies, a very promising and underrepresented region for future neuromodulation studies investigating DD is the orbitofrontal cortex.
Executive Profile of the Logopenic Variant of Primary Progressive Aphasia: Comparison with the Semantic and Non-Fluent Variants and Alzheimer’s Disease
Authors: Basaglia-Pappas Sandrine , Laurent Bernard , Getenet Jean-Claude , Boulangé Anne , Rendón de laCruz Aurelia , Simoes Loureiro Isabelle , Lefebvre Laurent
Published: February 2023

The logopenic variant of primary progressive aphasia (lvPPA) shows different features from the non-fluent (nfvPPA) and semantic (svPPA) variants of PPA. Although language impairments remain the core symptoms, studies have highlighted the presence of executive disorders at the onset of the disease. Nevertheless, the results are contradictory, particularly in lvPPA. The aim of this study was to explore the executive profile of lvPPA. We compared executive functioning in lvPPA with the other two variants of PPA, Alzheimer’s disease (AD) and a cognitively healthy group. In total, 70 patients with PPA, 32 patients with AD, and 41 healthy controls were included. They underwent a comprehensive executive battery assessing short-term and working memory, inhibition, flexibility, planning, and initiation. The analyses showed significant differences between the lvPPA group and the control group, except on visuospatial spans and the Stroop test, and between the lvPPA group and the other PPA groups and the AD group for several tasks. Thus, this research highlighted the existence of an executive dysfunction from the onset of the disease in lvPPA but also in the other two variants of PPA.
A Comparative Study of the Impact of NO-Related Agents on MK-801- or Scopolamine-Induced Cognitive Impairments in the Morris Water Maze
Authors: Cieślik Paulina , Borska Magdalena , Wierońska Joanna Monika
Published: February 2023

Learning and memory deficits accompany numerous brain dysfunctions, including schizophrenia and Alzheimer’s disease (AD), and many studies point to the role of nitric oxide (NO) in these processes. The present investigations constitute the follow-up of our previous research, in which we investigated the activity of NO releasers and a selective inhibitor of neuronal NO synthase (nNOS) to prevent short-term memory deficits in novel object recognition and T-maze. Here, the ability of the compounds to prevent the induction of long-term memory deficits by MK-801 or scopolamine administration was investigated. The Morris Water Maze test, a reliable and valid test of spatial learning and memory, was used, in which escape latency in the acquisition phase and nine different parameters in the retention phase were measured. A fast NO releaser (spermine NONOate), a slow NO releaser (DETA NONOate), and a nNOS inhibitor, N(ω)-propyl-L-arginine (NPLA), were used. The compounds were administered i.p. at a dose range of 0.05–0.5 mg/kg. All compounds prevented learning deficits in the acquisition phase and reversed reference memory deficits in the retention phase of the scopolamine-treated mice. Spermine NONOate was the least effective. In contrast, the drugs poorly antagonised MK-801-induced deficits, and only the administration of DETA NONOate induced some improvements in the retention trial.
Assessing Stress Levels, Predictors and Management Strategies of Inmates at Ankaful Prison Complex in the Central Region, Ghana
Authors: Ansah Edward W. , Addae Jennifer , Hagan John E. , Baidoo Michael A.
Published: February 2023

Background: Stress among prison inmates is a neglected psychological health issue, but this phenomenon seems worse in Ghana’s prisons. This study examined the stress levels, predictors and management strategies utilized among inmates at Ankaful Prison Complex. Method: This survey sampled 1160 inmates using the census approach at the Ankaful Prison Complex with a self-developed questionnaire for the data collection. Frequency counts, one-way ANOVA, and multiple regression analysis were applied to the data. Results: The findings indicate that more than half of the inmates were moderately or highly stressed. Specifically, inmates at the Maximum Security Prison were the most stressed, followed by Annex Prison, Communicable Disease Prison, and the least, Main Camp Prison inmates. Inmate engagement in exercises, sporting activities, visit and chat with colleagues, and family connectedness outside the prison were stress-management strategies. Inmates’ self-reported stress levels were influenced by the prison of custody and state of depression. Conclusion: The moderate to high stress levels identified among inmates of Ankaful Prison Complex are influenced by person–environment factors. Management of the Ankaful Prison Complex is encouraged to initiate health screening services for inmates on common mental health challenges such as stress and to promote functional stress reduction interventions to improve prisoners’ mental health and overall well-being.
State Anxiety and Procrastination: The Moderating Role of Neuroendocrine Factors
Authors: Barel Efrat , Shahrabani Shosh , Mahagna Lila , Massalha Refaat , Colodner Raul , Tzischinsky Orna
Published: February 2023

Procrastination is prevalent among students, as well as the general population, and has negative impacts on various domains. Several models aimed to understand factors associated with procrastination, with some suggesting that anxiety plays a significant role. Biological factors have been shown to contribute to individual differences in procrastination; however, little attention has been paid to the role of neuroendocrine factors on procrastination. The primary question addressed in the present study is whether neuroendocrine factors (testosterone and cortisol) moderate the association between state anxiety and procrastination. Eighty-eight participants (29 men; 32 women using oral contraceptives; and 27 women not using oral contraceptives and in their luteal phase) were tested for biomarkers and completed questionnaires. Results show that state anxiety is positively correlated with procrastination. Furthermore, testosterone levels moderate the correlation between state anxiety and procrastination. As testosterone levels drop, the positive correlation between state anxiety and procrastination becomes stronger, but when testosterone levels are higher, no significant association between state anxiety and procrastination is found. Cortisol levels do not moderate the relationship between state anxiety and procrastination. The role of neuroendocrine factors for psychological outcomes is discussed.
Basic Analysis of the Correlation between the Accessibility and Utilization Activation of Public Libraries in Seoul: Focusing on Location and Subway Factors
Authors: Zhao Xiaolong , Hong Kwanseon
Published: February 2023

In the past, the utilization rate of public libraries in Seoul could be estimated based on their accessibility. However, several issues emerge if we apply this correlation to the present day. Therefore, we re-examined the causal relationship between accessibility and the utilization rate of public libraries to provide directions for improving the use of public libraries in densely populated cities with growing cultural demand. After investigating the utilization rate of public libraries in Seoul from 2015 to 2019, the degree of utilization activation (DUA) was set as the dependent variable, and the integration of public libraries (derived by the quantification of urban space with space syntax) was set as the independent variable. A hypothesis was established to examine the causal relationship using statistical techniques. According to the results, the derived index values had independence and normality, but the accessibility index of public libraries did not exhibit a causal relationship with DUA. It was verified that the causal relationship recognized in the past (where accessibility was the sole predictor of utilization rate) cannot be applied to public libraries in the present day. Modern factors affecting DUA may involve either user motivation or the recent developments in public libraries compared to the past.
Experimental Validation and Numerical Analysis of a High-Performance Blast Energy-Absorbing System for Building Structures
Authors: Gomes Gabriel de Jesus , Lúcio Valter José da Guia , Cismaşiu Corneliu , Mingote José Luis
Published: February 2023

The paper presents a full-scale blast testing experimental campaign conducted on an energyabsorbing connector comprising thin-walled inversion tubes as kernel elements mounted in a façade protective panel. LS-DYNA finite element predictions of the global and local deformation/inversion of the panel/connectors compared reasonably well with the experimental observations. After validation, the numerical model was used to analyze the response of a simple idealized reinforced concrete structure under three blast-loading scenarios: the first two scenarios produce, approximately, the same impulse but are significantly different in terms of load duration and overpressures, and represent a far-field and a near-field scenario (1600 kg TNT at 20 m (i) and 150 kg TNT at 5 m (ii), respectively); the third scenario is more demanding, and consists in a half standoff distance of the second (150 kg TNT at 2.5 m (iii)). These numerical simulations allow to assess the effect of standoff distance and blast loading on the effectiveness of the protective system. One may conclude that the introduction of EACs strongly limits the forces imparted to the protected structure, reducing significantly the corresponding energy absorption demand. Comparing the energy absorbed by the structure in different scenarios, with and without the protective system (8 × ϕ64 × 2 mm), one can see that these reductions can reach, respectively 67%, 72% and 68% in the far-field, near-field and very near-field explosions.
Effect of Interior Space and Window Geometry on Daylighting Performance for Terrace Classrooms of Universities in Severe Cold Regions: A Case Study of Shenyang, China
Authors: Jia Yingjie , Liu Zheming , Fang Yaoxuan , Zhang Huiying , Zhao Caiyi , Cai Xuqiang
Published: February 2023

Good daylighting performance positively affects students’ physical and mental health, learning efficiency, and the building’s energy-saving capability. Due to the terrace classroom having ample space, large capacity, the ability to avoid obstructing sight, and the ability to meet various use needs, it is the most important place in university buildings. However, research on the daylighting performance of university terrace classrooms is limited, leading to a lack of quantitative guidance in early design stages. This study aims to explore the effects of interior space and window geometry of terrace classrooms in universities in severe cold regions on daylighting performance. This research took Shenyang as an example; spatial daylight autonomy (sDA300,50%) and useful daylight illuminance (UDI100–2000) were selected as daylighting performance evaluation indices. Based on the Grasshopper parametric platform, the simulation was carried out using Ladybug and Honeybee plugins. Correlation and regression analyses revealed the relationship between interior space and window geometry parameters and the evaluation indices. The results showed the following: window-to-floor ratio (WFR), classroom height (Htc), window height (Hw), window-to-wall ratio (WWR), classroom width (Wtc), and window width (Ww) have positive effects on improving the daylight sufficiency of the terrace classrooms facing each orientation, and the degree of the effect decreases in order. To ensure the overall daylighting performance, the Wtc can be maximized. The width of walls between windows for south-facing and west-facing classrooms should be 0.9 m. The WWR and WFR for south-facing classrooms should be 0.3–0.5 and 0.11–0.14, respectively. The WWR and WFR for north-facing classrooms should be 0.6–0.7 and 0.14–0.20, respectively. Prediction models are established for the sDA300,50% and UDI100–2000 of the terrace classrooms facing each orientation.
Sensory Design in the Birth Environment: Learning from Existing Case Studies
Authors: Bellini Elena , Macchi Alessia , Setola Nicoletta , Lindahl Göran
Published: February 2023

Studies have shown how built environments for hospitals can influence psychological and physiological conditions and status for childbearing women. Sensory attributes of birth spaces can enhance comfort, feelings of wellbeing, and, to some extent, clinical outcomes. Recently, some case studies of multisensory rooms for the birth environment have been developed based on, e.g., Snoezelen room examples. The aim of this research is to develop an overview of how sensory aspects for birth environments are designed, used, and tested in current and recent studies. Case studies were selected according to sensory aspect significance, observing space factors, and relationship with the experience and comfort of users (women, partners, midwives). All case studies were analysed to collect information about the design and validation process. The collected data were organised in categories and compared for the selected case studies. Main findings were summarised in tables with the aim of underlining how sensory design processes and projects can positively influence comfort for birthing. Conclusions about how to bring forward the issue of sensory design so that it can be used and applied to support childbearing women is discussed.
Seismic Response and Damage Analysis of Shield Tunnel with Lateral Karst Cavity under Oblique SV Waves
Authors: Li Mingda , Meng Kang , Zhou Jing
Published: February 2023

The dynamic effects of the lateral karst cavity on the shield tunnels under different incident angles of seismic waves are investigated by numerical analysis in this paper, based on the Dalian Metro Line 5 project. The viscous-spring artificial boundary is applied and verified to guarantee the accuracy of seismic input. A simplified finite element model of shield tunnel is established based on the equivalent bending stiffness model. This paper compares the seismic response characteristics and damage states of the tunnel under different incident angles by analyzing the axial deformation, stress distribution, and damage severity, respectively. A new damage state classification criterion is proposed by introducing the relationship between cracks and tensile damage. The results show that the tunnel’s affected scope by the lateral karst cavity is twice the cavity diameter. As the incident angle increases, the tunnel’s displacement and stress increase and show the structural spatial difference, and the tunnel’s damage state is increasingly severe. The displacement and stress reach the max values when the incident angle is 30°. The cracks along the axial direction extend on the outer surface of the vault and bottom, and the crack width is greater than 0.2 mm, as that angle is 30°. The damage severity at the tunnel’s central zone is minimum along axial directions during seismic action, while the damage concentration occurs on the bottom at the end of seismic. The lateral karst cavity plays an energy dissipation and vibration reduction role to a certain extent, but it also aggravates the local damage. This paper can serve as a reference for the seismic design of tunnels in karst regions.
Prediction of the Debonding Failure of Beams Strengthened with FRP through Machine Learning Models
Authors: Hu Tianyu , Zhang Hong , Zhou Jianting
Published: February 2023

Plate end (PE) debonding and intermediate crack (IC) debonding are the two main failure modes of beams strengthened with fiber-reinforced polymer (FRP) in flexure. Therefore, it is essential to clarify the force state of the structure when debonding occurs in strengthened beams. This paper collected 229 beams with debonding failure as the database, of which 128 were PE debonding and 101 were IC debonding. Correlation and grey correlation analysis were used to establish the indicator systems for predicting PE and IC debonding and to identify the critical indicators among them. Five machine learning models, linear regression, ridge regression, decision trees, random forests, and back propagation (BP) neural networks, were used to build the two debonding prediction models. Optimization of the best prediction among the five machine learning models took place using the Dung Beetle Optimizer (DBO) algorithm, which has competitive performance with state-of-the-art optimization approaches in terms of convergence rate, solution accuracy, and stability. Finally, the optimal prediction model was compared with the models suggested by codes, and it was found that the established model can well predict PE and IC debonding.