bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging Drug Targets for Endometriosis
Authors: Dolmans Marie-Madeleine , Donnez Jacques
Published: November 2022

Endometriosis is a chronic inflammatory disease causing distressing symptoms and requiring a life-long management strategy. The objective of this review is to evaluate endometriosis-related pathways and identify novel therapies to treat it. We focused on the crucial role of inflammation and inflammatory molecules in order to define new perspectives for non-hormonal treatment of the disease by targeting inflammation, nuclear factor kappa B and cytokines, or reactive oxygen species, apoptotic and autophagic pathways, regulators of epithelial-mesenchymal transition, and angiogenesis and neuroangiogenesis. Novel non-steroidal therapies targeting these pathways for endometriosis were explored, but multiple challenges remain. While numerous agents have been investigated in preclinical trials, few have reached the clinical testing stage because of use of inappropriate animal models, with no proper study design or reporting of preclinical strategies. Targeting estrogens is still the best way to control endometriosis progression and inflammation.
Hypoxia in A Patient with Anti-p200 Pemphigoid under Combined Dapsone and Pantoprazole Treatment
Authors: Lang Sebastian , Sänger Philipp Wilhelm , Kocina Sandra , von Loeffelholz Christian
Published: November 2022

A 70-year-old male patient was admitted to our dermatology outpatient clinic with newly developed personality changes and signs of hypoxemia. His anti-p200 Pemphigoid was treated with Dapsone for a few weeks. Due to generalized tonic-clonic seizure with a subsequent Glasgow Coma Scale of 5 points and a peripheral oxygen saturation not exceeding 88% under conditions of high-flow nasal cannula, he was intubated by the emergency team and transferred to the intensive care unit. Comprehensive tests were performed, but Dapsone-induced methemoglobinemia remained the exclusive explanation for the observed scenario, although arterial MetHb analysis showed a peak value of only 6%. The patient recovered shortly after repeated infusions of Methylene blue and Ascorbate, and cessation of Dapsone. We provide an overview of the pathophysiology, diagnostic procedures, and possible explanations for this case of Dapsone-induced methaemoglobinaemia. In conclusion, our case report provides evidence that even mild chronic methemglobinemia can induce severe clinical symptoms.
Arrhythmias after SARS-CoV-2 Vaccination in Patients with a Cardiac Implantable Electronic Device: A Multicenter Study
Authors: Sangpornsuk Naruepat , Rungpradubvong Voravut , Tokavanich Nithi , Srisomwong Sathapana , Ananwattanasuk Teetouch , Teerawongsakul Padoemwut , Kerr Stephen J. , Suwanwalaikorn Mathurin , Jongnarangsin Krit , Chokesuwattanaskul Ronpichai
Published: November 2022

One of the most concerning adverse events related to the SARS-CoV-2 vaccination is arrhythmia. To ascertain the relationship between vaccination and arrhythmic events, we studied the occurrence of arrhythmia in patients with cardiac implantable electronic devices (CIEDs) before and after a SARS-CoV-2 vaccination. Patients with CIEDs aged ≥18 who visited the CIED clinic at King Chulalongkorn Memorial Hospital and Vajira hospital from August 2021 to February 2022 were included. Information about the SARS-CoV-2 vaccination and side effects was obtained. One hundred eighty patients were included in our study, which compared the incidence of arrhythmias in the 14 days post-vaccination to the 14 days before vaccination. The median age was 70 years. The number of patients who received one, two, and three doses of the vaccine was 180, 88, and 4, respectively. ChAdOx1 was the primary vaccine used in our institutes, accounting for 86% of vaccinations. The vaccination was significantly associated with a 73% increase incidence of supraventricular tachycardia (SVT). In an adjusted model, factors associated with the incidence of SVT were the post-vaccination period, female sex, increasing BMI, chronic kidney disease, and a history of atrial fibrillation. Increased ventricular arrhythmia (VA) episodes were also associated with the post-vaccination period, female sex, decreasing BMI, and chronic kidney disease, but to a lesser degree than those with SVT episodes. No life-threatening arrhythmia was noted in this study. In conclusion, the incidence of arrhythmia in patients implanted with CIEDs was significantly increased after the SARS-CoV-2 vaccination.
Artificial Intelligence for Early Detection of Chest Nodules in X-ray Images
Authors: Chiu Hwa-Yen , Peng Rita Huan-Ting , Lin Yi-Chian , Wang Ting-Wei , Yang Ya-Xuan , Chen Ying-Ying , Wu Mei-Han , Shiao Tsu-Hui , Chao Heng-Sheng , Chen Yuh-Min , Wu Yu-Te
Published: November 2022

Early detection increases overall survival among patients with lung cancer. This study formulated a machine learning method that processes chest X-rays (CXRs) to detect lung cancer early. After we preprocessed our dataset using monochrome and brightness correction, we used different kinds of preprocessing methods to enhance image contrast and then used U-net to perform lung segmentation. We used 559 CXRs with a single lung nodule labeled by experts to train a You Only Look Once version 4 (YOLOv4) deep-learning architecture to detect lung nodules. In a testing dataset of 100 CXRs from patients at Taipei Veterans General Hospital and 154 CXRs from the Japanese Society of Radiological Technology dataset, the sensitivity of the AI model using a combination of different preprocessing methods performed the best at 79%, with 3.04 false positives per image. We then tested the AI by using 383 sets of CXRs obtained in the past 5 years prior to lung cancer diagnoses. The median time from detection to diagnosis for radiologists assisted with AI was 46 (3–523) days, longer than that for radiologists (8 (0–263) days). The AI model can assist radiologists in the early detection of lung nodules.
Whole Exome Sequencing Identifies PHF14 Mutations in Neurocytoma and Predicts Responsivity to the PDGFR Inhibitor Sunitinib
Authors: Zhang Dongyun , Yong William H. , Movassaghi Masoud , Rodriguez Fausto J. , Yang Issac , McKeever Paul , Qian Jiang , Li Jian Yi , Mao Qinwen , Newell Kathy L. , Green Richard M. , Welsh Cynthia T. , Heaney Anthony P.
Published: November 2022

Neurocytomas are rare low-grade brain tumors predominantly affecting young adults, but their cellular origin and molecular pathogenesis is largely unknown. We previously reported a sellar neurocytoma that secreted excess arginine vasopressin causing syndrome of inappropriate anti-diuretic hormone (SIADH). Whole exome sequencing in 21 neurocytoma tumor tissues identified somatic mutations in the plant homeodomain finger protein 14 (PHF14) in 3/21 (14%) tumors. Of these mutations, two were missense mutations and 4 caused splicing site losses, resulting in PHF14 dysfunction. Employing shRNA-mediated knockdown and CRISPR/Cas9-based knockout approaches, we demonstrated that loss of PHF14 increased proliferation and colony formation in five different human, mouse and rat mesenchymal and differentiated cell lines. Additionally, we demonstrated that PHF14 depletion resulted in upregulation of platelet derived growth factor receptor-alpha (PDGFRα) mRNA and protein in neuroblastoma SHSY-5Y cells and led to increased sensitivity to treatment with the PDGFR inhibitor Sunitinib. Furthermore, in a neurocytoma primary culture harboring splicing loss PHF14 mutations, overexpression of wild-type PHF14 and sunitinib treatment inhibited cell proliferation. Nude mice, inoculated with PHF14 knockout SHSY-5Y cells developed earlier and larger tumors than control cell-inoculated mice and Sunitinib administration caused greater tumor suppression in mice harboring PHF-14 knockout than control SHSY-5Y cells. Altogether our studies identified mutations of PHF14 in 14% of neurocytomas, demonstrate it can serve as an alternative pathway for certain cancerous behavior, and suggest a potential role for Sunitinib treatment in some patients with residual/recurrent neurocytoma.
Immunotherapy against the Cystine/Glutamate Antiporter xCT Improves the Efficacy of APR-246 in Preclinical Breast Cancer Models
Authors: Barutello Giuseppina , Di Lorenzo Antonino , Gasparetto Alessandro , Galiazzi Chiara , Bolli Elisabetta , Conti Laura , Cavallo Federica
Published: November 2022

Breast cancer is the most frequent cancer in women. Despite recent clinical advances, new therapeutic approaches are still required. The cystine-glutamate antiporter xCT, encoded by the SLC7A11 gene, which imports cystine in exchange with glutamate, is a potentially new target for breast cancer therapy, being involved in tumor cell redox balance and resistance to therapies. xCT expression is regulated by the oncosuppressor p53, which is mutated in many breast cancers. Indeed, mutant p53 (mut-p53) can induce xCT post-transcriptional down modulation, rendering mut-p53 tumors susceptible to oxidative damage. Interestingly, the drug APR-246, developed to restore the wild-type function of p53 in tumors harboring its mutation, alters the cell redox balance in a p53-independent way, possibly rendering the cells more sensitive to xCT inhibition. Here, we propose a combinatorial treatment based on xCT immunetargeting and APR-246 treatment as a strategy for tackling breast cancer. We demonstrate that combining the inhibition of xCT with the APR-246 drug significantly decreased breast cancer cell viability in vitro and induced apoptosis and affected cancer stem cells’ self-renewal compared to the single treatments. Moreover, the immunetargeting of xCT through DNA vaccination in combination with APR-246 treatment synergistically hinders tumor progression and prevents lung metastasis formation in vivo. These effects can be mediated by the production of anti-xCT antibodies that are able to induce the antibody dependent cellular cytotoxicity of tumor cells. Overall, we demonstrate that DNA vaccination against xCT can synergize with APR-246 treatment and enhance its therapeutic effect. Thus, APR-246 treatment in combination with xCT immunetargeting may open new perspectives in the management of breast cancer.
Urinary Cysteinyl Leukotrienes as Biomarkers of Endothelial Activation, Inflammation and Oxidative Stress and Their Relationship with Organ Dysfunction in Human Septic Shock
Authors: Reina-Couto Marta , Santos-Oliveira Marisa , Pereira-Terra Patrícia , Silva-Pereira Carolina , Quelhas-Santos Janete , Duarte Álvaro , Martins Sandra , Serrão Paula , Dias Cláudia Camila , Morato Manuela , Guimarães João T. , Roncon-Albuquerque Roberto , Paiva José-Artur , Albino-Teixeira António , Sousa Teresa
Published: November 2022

Cysteinyl leukotrienes (CysLT) are potent vascular leakage-promoting agents but have been scarcely explored in human septic shock (SS). We evaluated CysLT at admission and during hospitalization and their correlation with endothelial dysfunction, inflammation, oxidative stress, the renin–angiotensin–aldosterone system, and cardiac, renal, respiratory, and hepatic parameters in SS patients. Blood and spot-urine samples were collected at days 1–2 (admission), 3–4, and 5–8 in SS patients (n = 13) and at a single time point in controls (n = 22). Urinary CysLT (u-CysLT) and isoprostanes, plasma, and urinary angiotensinogen, serum myeloperoxidase, and IL-10 were quantified by ELISA. Serum intercellular-adhesion molecule-1, vascular cell-adhesion molecule-1, E-selectin, tumor necrosis factor-α, IL-1β, and IL-6 were measured by multiplex immunoassays. Routine markers were evaluated using automated analyzers. At admission, SS patients had increased u-CysLT, endothelial activation, inflammation, oxidative stress, and plasma and urinary angiotensinogen, as well as cardiac, respiratory, hepatic, and renal injury/dysfunction. There were no changes in u-CysLT during hospitalization. Both correlation and multivariate analyses showed positive relationships of u-CysLT with endothelial activation, inflammation, oxidative stress, proteinuria, and hepatic injury/dysfunction markers. These results suggest that u-CysLT may be potential non-invasive biomarkers for monitoring the pathophysiological mechanisms underlying SS, as well as putative therapeutic targets.
New Insights into Molecular Mechanisms of Chronic Kidney Disease
Authors: Frąk Weronika , Kućmierz Joanna , Szlagor Magdalena , Młynarska Ewelina , Rysz Jacek , Franczyk Beata
Published: November 2022

Chronic kidney disease (CKD) is a major public health problem with a developing incidence and prevalence. As a consequence of the growing number of patients diagnosed with renal dysfunction leading to the development of CKD, it is particularly important to explain the mechanisms of its underlying causes. In our paper, we discuss the molecular mechanisms of the development and progression of CKD, focusing on oxidative stress, the role of the immune system, neutrophil gelatinase-associated lipocalin, and matrix metalloproteinases. Moreover, growing evidence shows the importance of the role of the gut–kidney axis in the maintenance of normal homeostasis and of the dysregulation of this axis in CKD. Further, we discuss the therapeutic potential and highlight the future research directions for the therapeutic targeting of CKD. However, additional investigation is crucial to improve our knowledge of CKD progression and, more importantly, accelerate basic research to improve our understanding of the mechanism of pathophysiology.
BDNF Spinal Overexpression after Spinal Cord Injury Partially Protects Soleus Neuromuscular Junction from Disintegration, Increasing VAChT and AChE Transcripts in Soleus but Not Tibialis Anterior Motoneurons
Authors: Głowacka Anna , Ji Benjun , Szczepankiewicz Andrzej Antoni , Skup Małgorzata , Gajewska-Woźniak Olga
Published: November 2022

After spinal cord transection (SCT) the interaction between motoneurons (MNs) and muscle is impaired, due to reorganization of the spinal network after a loss of supraspinal inputs. Rats subjected to SCT, treated with intraspinal injection of a AAV-BDNF (brain-derived neurotrophic factor) construct, partially regained the ability to walk. The central effects of this treatment have been identified, but its impact at the neuromuscular junction (NMJ) has not been characterized. Here, we compared the ability of NMJ pre- and postsynaptic machinery in the ankle extensor (Sol) and flexor (TA) muscles to respond to intraspinal AAV-BDNF after SCT. The gene expression of cholinergic molecules (VAChT, ChAT, AChE, nAChR, mAChR) was investigated in tracer-identified, microdissected MN perikarya, and in muscle fibers with the use of qPCR. In the NMJs, a distribution of VAChT, nAChR and Schwann cells was studied by immunofluorescence, and of synaptic vesicles and membrane active zones by electron microscopy. We showed partial protection of the Sol NMJs from disintegration, and upregulation of the VAChT and AChE transcripts in the Sol, but not the TA MNs after spinal enrichment with BDNF. We propose that the observed discrepancy in response to BDNF treatment is an effect of difference in the TrkB expression setting BDNF responsiveness, and of BDNF demands in Sol and TA muscles.
Volatilomics as an Emerging Strategy to Determine Potential Biomarkers of Female Infertility: A Pilot Study
Authors: Brinca Ana Teresa , Anjos Ofélia , Alves Maria Manuel Casteleiro , Sousa Ângela , Oliani António Hélio , Breitenfeld Luiza , Passarinha Luís A. , Ramalhinho Ana Cristina , Gallardo Eugenia
Published: November 2022

Due to its high prevalence, infertility has become a prominent public health issue, posing a significant challenge to modern reproductive medicine. Some clinical conditions that lead to female infertility include polycystic ovary syndrome (PCOS), endometriosis, and premature ovarian failure (POF). Follicular fluid (FF) is the biological matrix that has the most contact with the oocyte and can, therefore, be used as a predictor of its quality. Volatilomics has emerged as a non-invasive, straightforward, affordable, and simple method for characterizing various diseases and determining the effectiveness of their current therapies. In order to find potential biomarkers of infertility, this study set out to determine the volatomic pattern of the follicular fluid from patients with PCOS, endometriosis, and POF. The chromatographic data integration was performed through solid-phase microextraction (SPME), followed by gas chromatography–mass spectrometry (GC-MS). The findings pointed to specific metabolite patterns as potential biomarkers for the studied diseases. These open the door for further research into the relevant metabolomic pathways to enhance infertility knowledge and diagnostic tools. An extended investigation may, however, produce a new mechanistic understanding of the pathophysiology of the diseases.
Neuroimmunoendocrinology of SARS-CoV-2 Infection
Authors: Bellastella Giuseppe , Cirillo Paolo , Carbone Carla , Scappaticcio Lorenzo , Maio Antonietta , Botta Graziella , Tomasuolo Maria , Longo Miriam , Pontillo Alessandro , Bellastella Antonio , Esposito Katherine , De Bellis Annamaria
Published: November 2022

This review is aimed at illustrating and discussing the neuroimmune endocrinological aspects of the SARS-CoV-2 infection in light of the studies on this topic that have so far appeared in the literature. The most characteristic findings and pending controversies were derived by PubMed and Scopus databases. We included original and observational studies, reviews, meta-analysis, and case reports. The entry of the coronavirus into susceptible cells is allowed by the interaction with an ecto-enzyme located on human cells, the angiotensin-converting enzyme 2 (ACE2). SARS-CoV-2 also targets the central nervous system (CNS), including hypothalamic-pituitary structures, as their tissues express ACE2, and ACE2 mRNA expression in hypothalamus and pituitary gland cells has been confirmed in an autoptic study on patients who died of COVID 19. SARS-CoV-2 infection may cause central endocrine disorders in acute phase and in post-COVID period, particularly due to the effects of this virus at CNS level involving the hypothalamic-pituitary axis. The aggression to the hypothalamus-pituitary region may also elicit an autoimmune process involving this axis, responsible consequently for functional disorders of the satellite glands. Adrenal, thyroid and gonadal dysfunctions, as well as pituitary alterations involving GH and prolactin secretions, have so far been reported. However, the extent to which COVID-19 contributes to short- and long-term effects of infection to the endocrine system is currently being discussed and deserves further detailed research.
Emerging Multiplex Nucleic Acid Diagnostic Tests for Combating COVID-19
Authors: Akarapipad Patarajarin , Bertelson Elizabeth , Pessell Alexander , Wang Tza-Huei , Hsieh Kuangwen
Published: November 2022

The COVID-19 pandemic caused by SARS-CoV-2 has drawn attention to the need for fast and accurate diagnostic testing. Concerns from emerging SARS-CoV-2 variants and other circulating respiratory viral pathogens further underscore the importance of expanding diagnostic testing to multiplex detection, as single-plex diagnostic testing may fail to detect emerging variants and other viruses, while sequencing can be too slow and too expensive as a diagnostic tool. As a result, there have been significant advances in multiplex nucleic-acid-based virus diagnostic testing, creating a need for a timely review. This review first introduces frequent nucleic acid targets for multiplex virus diagnostic tests, then proceeds to a comprehensive and up-to-date overview of multiplex assays that incorporate various detection reactions and readout modalities. The performances, advantages, and disadvantages of these assays are discussed, followed by highlights of platforms that are amenable for point-of-care use. Finally, this review points out the remaining technical challenges and shares perspectives on future research and development. By examining the state of the art and synthesizing existing development in multiplex nucleic acid diagnostic tests, this review can provide a useful resource for facilitating future research and ultimately combating COVID-19.
Lateral Flow Microimmunoassay (LFµIA) for the Reliable Quantification of Allergen Traces in Food Consumables
Authors: Sena-Torralba Amadeo , Gabaldón-Atienza Javier , Cubells-Gómez Aitor , Casino Patricia , Maquieira Ángel , Morais Sergi
Published: November 2022

Quality assurance and food safety are of great concern within the food industry because of unknown quantities of allergens often present in food. Therefore, there is an ongoing need to develop rapid, sensitive, and easy to use methods that serve as an alternative to mass spectrometry and enzyme-linked immunosorbent assay (ELISA) for monitoring food safety. Lateral flow immunoassay is one of the most used point-of-need devices for clinical, environmental, and food safety applications. Compared to traditional methods, it appears to be a simple and fast alternative for detecting food allergens. However, its reliability is frequently questioned due to the lack of quantitative information. In this study, a lateral flow microimmunoassay (LFµIA) is presented that integrates up to 36 spots in microarray format in a single strip, providing semi-quantitative information about the level of allergens, positive and negative controls, internal calibration, and hook effect. The LFµIA has been evaluated for the on-site simultaneous and reliable quantification of almond and peanut allergens as a proof of concept, demonstrating high sensitivity (185 and 229 µg/kg, respectively), selectivity (77%), and accuracy (RSD 5–25%) when analyzing commercial allergen-suspicious food consumables.
Science vs. Conspiracy Theory about COVID-19: Need for Cognition and Openness to Experience Increased Belief in Conspiracy-Theoretical Postings on Social Media
Authors: Ozimek Phillip , Nettersheim Marie , Rohmann Elke , Bierhoff Hans-Werner
Published: November 2022

In the context of COVID-19 virus containment, there is a lack of acceptance of preventive measures in the population. The present work investigated which factors influence the belief in scientific propositions compared with belief in conspiracy theories. The focus here was on the determinants of conspiracy beliefs in the context of COVID-19 related media content. Using an online questionnaire (N = 175), results indicate that scientific compared to conspiracy-theoretical media content led to higher acceptance. Furthermore, need for cognition (NFC-K), a conspiracy-theoretical worldview (CMQ), and openness to experience (NEO-FFI) were positively associated with conspiracy beliefs derived from Facebook postings. In addition, a conspiracy-theoretical worldview was negatively associated with belief in scientific media content. Furthermore, agreeableness was unrelated to conspiracy beliefs, although it was positively associated with conspiracy-theoretical worldview. The results imply promising persuasion strategies for reducing conspiracy-theoretical beliefs and to increase the acceptance of preventive measures.
A New Explication of Minimum Variable Sets (MVS) for Building Energy Prediction Based on Building Performance Database
Authors: Zhu Mingya , Pan Yiqun , Lyu Yan , Huang Zhizhong , Li Pengcheng
Published: November 2022

Building energy simulation plays a significant role in buildings, with applications such as building performance evaluation, retrofit decisions and the optimization of building operations. However, the wide range of model inputs has limited much research into empirically customized case studies due to the insufficient availability of data inputs or the lack of systematic feature selection of key inputs. To address this gap, this study proposes the concept of minimum variable sets (MVSs) for building energy-prediction models to improve the general applicability of building energy prediction using forward simulation. An MVS, in this paper, refers to a variable set that contains the most indispensable energy-related variables/features for annual building energy prediction. This study developed MVSs for office buildings by applying feature engineering algorithms to a Building Performance Database (BPD), which was established by integrating the design of experiments (DoE) method with high-dimensional data-space metrics, as well as parallel simulation. Supervised feature dimension reduction methods and multiple statistical criteria were adopted to choose different numbers of indispensable variables from the primary 16 building variables. The hierarchical MVSs that consist of the selected variables are characterized by the most influential features for building energy prediction, with certain requirements for prediction accuracy. To further improve the feasibility of MVSs, this study utilized two separate office buildings located in Shanghai and California as validation cases and provided comparable prediction accuracies across different sizes of MVS. The results showed that the MVS that has 12 variables has higher prediction accuracy than that which has 9 variables, followed by that which has 7 variables. Finally, the quantitatively hierarchical correlations between different sizes of MVS with different prediction accuracies for annual building energy could provide potential support for reasonable decision-making regarding building energy model variables, especially when comprehensive consideration is needed of the limited cost and data availability, and the acceptable accuracy of building energy.
Building an Augmented Reality Experience on Top of a Smart Pavement Management System
Authors: Moradi Maryam , Assaf Gabriel J.
Published: November 2022

Pavement Management Systems (PMS) offers a systematic collection, storage, analysis, and modeling of road condition data to optimize resources across a road network. Adding artificial intelligence (AI) and augmented reality (AR) to PMS could improve their technical or visual aspects. This paper tries to identify a method to improve the understanding of the consequences of the city council’s decisions in the urban pavement management system field. This paper establishes the potential of AR. It provides future maintenance and rehabilitation (M&R) actions needed based on the recommendation of the future distress in the study area. The road cracks are discovered through technical analysis, and a CityEngine model is established based on the PMS results. Additionally, in terms of visualization, this paper’s unique feature delivers the result as an AR experience. Applying the Unity game engine and importing the built CityEngine model and the embedded textures as input empowered us to provide a dynamic product in terms of data and analysis and a real-time Decision Support System (DSS) for the final users. This paper concludes that researchers need many different modules to design and implement an efficient PMS to move toward a smart PMS. The smart city concept is meaningless without a tight collaboration between all distinctive parts of each urban infrastructure management system. Additionally, this paper attempts to provide answers for researchers and an outlook for future research, the development of the proposed method, and its application in other fields
Fault Assessment in Piezoelectric-Based Smart Strand Using 1D Convolutional Neural Network
Authors: Le Ba-Tung , Le Thanh-Cao , Luu Tran-Huu-Tin , Ho Duc-Duy , Huynh Thanh-Canh
Published: November 2022

The smart strand technique has been recently developed as a cost-effective prestress load monitoring solution for post-tensioned engineering systems. Nonetheless, during its lifetime under various operational and environmental conditions, the sensing element of the smart strand has the potential to fail, threatening its functionality and resulting in inaccurate prestress load estimation. This study analyzes the effect of potential failures in the smart strand on impedance characteristics and develops a 1D convolutional neural network (1D CNN) for automated fault diagnosis. Instead of using a realistic experimental structure for which transducer faults can be hard to control accurately, we adopt a well-established finite element model to conduct all experiments. The results show that the impedance characteristics of a damaged smart strand are relatively different from other piezoelectric active sensing devices. While the slope of the susceptance response is widely accepted as a promising fault indicator, this study shows that the resistance response is more favorable for the smart strand. The developed network can accurately diagnose the potential faults in a damaged smart strand with the highest testing accuracy of 94.1%. Since the network can autonomously learn damage-sensitive features without pre-processing, it shows great potential for embedding in impedance-based damage identification systems for real-time structural health monitoring.
Light-Activated Modified Arginine Carbon Dots as Antibacterial Particles
Authors: Suner Selin S. , Sahiner Mehtap , Yilmaz Aynur S. , Ayyala Ramesh S. , Sahiner Nurettin
Published: November 2022

Nitrogen-doped arginine carbon dots (Arg CDs) as light-sensitive antibacterial agents were prepared by using citric acid as the carbon source and arginine amino acid as the nitrogen source via a microwave-assisted synthesis method. Dynamic light scattering (DLS) measurements and TEM images revealed that the Arg CDs were in the 1–10 nm size range with a graphitic structure. To improve their antibacterial capability, the Arg CDs were modified with ethyleneimine (EDA), pentaethylenehexamine (PEHA), and polyethyleneimine (PEI) as different amine sources, and the zeta potential value of +2.8 ± 0.6 mV for Arg CDs was increased to +34.4 ± 4.1 mV for PEI-modified Arg CDs. The fluorescence intensity of the Arg CDs was significantly enhanced after the modification with EDA, and the highest antibacterial effect was observed for the PEI-modified Arg CDs. Furthermore, the photodynamic antibacterial capacity of bare and EDA-modified Arg CDs was determined upon light exposure to show their light-induced antibacterial effects. Photoexcited (315–400 nm, UVA, 300 W), EDA-modified Arg CDs at 5 mg/mL concentration were found to inhibit about 49 ± 7% of pathogenic bacteria, e.g., Escherichia coli, with 5 min of light exposure. Furthermore, the biocompatibilities of the bare and modified Arg CDs were also investigated with blood compatibility tests via hemolysis and blood clotting assays and cytotoxicity analysis on L929 fibroblast cells.
Reductive Catalytic Fractionation of Spruce Wood over Ru/C Bifunctional Catalyst in the Medium of Ethanol and Molecular Hydrogen
Authors: Taran Oxana P. , Miroshnikova Angelina V. , Baryshnikov Sergey V. , Kazachenko Aleksandr S. , Skripnikov Andrey M. , Sychev Valentin V. , Malyar Yuriy N. , Kuznetsov Boris N.
Published: November 2022

Reductive catalytic fractionation (RCF) has emerged as an effective lignin-first biorefinery strategy to depolymerize lignin into tractable fragments in high yields. Herein, we propose the RCF of spruce wood over a Ru/C bifunctional catalyst in the medium of ethanol and molecular hydrogen to produce monomeric phenolic compounds from lignin, polyols from hemicelluloses, and microcrystalline cellulose. This contribution attempts to elucidate the role of the Ru/C bifunctional catalysts characteristics. The results clarify the particular effect of the carbon support acidity, catalyst grain size, content and dispersion of Ru on the effectiveness of lignin and hemicelluloses extraction and the yields of liquid and gaseous products. The most efficient catalysts for RCF of spruce wood, providing high yields of the monomeric phenols, glycols, and solid product with content of cellulose up to 90 wt%, bear 3 wt% of Ru with a dispersion of 0.94 based on an acidic oxidized graphite-like carbon support Sibunit®, and having a grain size of 56–94 μm. The Ru/C catalysts intensify the reactions of hydrodeoxygenation of liquid products from lignin. The main phenolic monomers are 4-propyl guaiacol, 4-propenyl guaiacol, and 4-propanol guaiacol. We explored the effect of the process temperature and time on the yield and composition of the liquid, solid, and gaseous products of spruce wood RCF. The optimal trade-off between the yields of phenolic monomers (30.0 wt%). polyols (18.6 wt%) and the solid product containing 84.4 wt% of cellulose is reached at 225 °C and 3 h over the most acidic Ru/C catalyst.
A Colorimetric CO2 Hydration Assay for Facile, Accurate, and Precise Determination of Carbonic Anhydrase Activity
Authors: Kim Joo Hyun , Jo Byung Hoon
Published: November 2022

A simple, reliable, and universal method is demanded for routine determination of carbonic anhydrase (CA) activity, overcoming the limitations of previous assays that are inaccurate, complicated, expensive, or limited to a specific enzyme family. The most widely used Wilbur–Anderson assay was modified to improve the speed, accuracy, and precision by employing a temperature controllable UV/Vis spectrophotometer and the pH indicator phenol red. The experimental setting, measurement, and data analysis were facile and straightforward. The assay was validated using a commercially available bovine CA, showing that the obtained activity was directly proportional to the amount of enzyme. The measured activity (2540 WAU mg−1) agreed well with the previously reported data. The comparison results with esterase assay showed that the CO2 hydration assay should not be substituted by the esterase assay in the measurement of CA activity. The simple and reliable colorimetric method can be widely adopted for the routine determination of CO2 hydration activity, substituting for the traditional Wilbur–Anderson assay.
Dynamic Balance between PTH1R-Dependent Signal Cascades Determines Its Pro- or Anti-Osteogenic Effects on MSC
Authors: Kulebyakin Konstantin , Tyurin-Kuzmin Pyotr , Sozaeva Leila , Voloshin Nikita , Nikolaev Mikhail , Chechekhin Vadim , Vigovskiy Maxim , Sysoeva Veronika , Korchagina Elizaveta , Naida Daria , Vorontsova Maria
Published: November 2022

Parathyroid hormone (PTH) is one of the key regulators of calcium and phosphate metabolism in the body, controlling bone metabolism and ion excretion by the kidneys. At present, attempts to use PTH as a therapeutic agent have been associated with side-effects, the nature of which is not always clear and predictable. In addition, it is known that in vivo impairment of PTH post-receptor signaling is associated with atypical differentiation behavior not only of bone cells, but also of connective tissues, including adipose tissue. In this work, we studied the functional responses of multipotent mesenchymal stromal cells (MSCs) to the action of PTH at the level of single cells. We used MSCs isolated from the periosteum and subcutaneous adipose tissue to compare characteristics of cell responses to PTH. We found that the hormone can activate three key responses via its receptor located on the surface of MSCs: single transients of calcium, calcium oscillations, and hormone-activated smooth increase in intracellular calcium. These types of calcium responses led to principally different cellular responses of MSCs. The cAMP-dependent smooth increase of intracellular calcium was associated with pro-osteogenic action of PTH, whereas phospholipase C dependent calcium oscillations led to a decrease in osteogenic differentiation intensity. Different variants of calcium responses are in dynamic equilibrium. Suppression of one type of response leads to increased activation of another type and, accordingly, to a change in the effect of PTH on cell differentiation.
AV-101, a Pro-Drug Antagonist at the NMDA Receptor Glycine Site, Reduces L-Dopa Induced Dyskinesias in MPTP Monkeys
Authors: Bourque Mélanie , Grégoire Laurent , Patel Waseema , Dickens David , Snodgrass Ralph , Di Paolo Thérèse
Published: November 2022

N-methyl-D-aspartate (NMDA) receptors have been implicated in L-Dopa-induced dyskinesias (LID) in Parkinson’s disease patients, but the use of antagonists that directly inhibit this receptor is associated with severe side effects. L-4-chlorokynurenine (4-Cl-KYN or AV-101) is a pro-drug of 7-chlorokynurenic acid (7-Cl-KYNA), a potent and specific antagonist of the glycine (GlyB) co-agonist site of NMDA receptors. The 7-Cl-KYNA has limited ability to cross the blood–brain barrier, whereas AV-101 readily accesses the brain. We investigated if AV-101 reduces LID in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys while maintaining the antiparkinsonian activity of L-Dopa. A first pilot study using three dyskinetic MPTP monkeys showed that acute AV-101 treatment (250 and 450 mg/kg) reduced LID and maintained the antiparkinsonian activity of L-Dopa. The main study using six additional dyskinetic MPTP monkeys showed that repeated AV-101 treatment (250 mg/kg, b.i.d. for 4 consecutive days) maintained their L-Dopa antiparkinsonian response. We measured significantly less LID when AV-101 was combined with L-Dopa treatment. AV-101 alone or with L-Dopa had no non-motor adverse effects in MPTP monkeys. Our study showed antidyskinetic activity of AV-101 in MPTP monkeys was comparable to amantadine tested previously in our laboratory in this model. We observed no adverse effects with AV-101, which is an improvement over amantadine, with its known side effects.
Quantitative Measurements of Pharmacological and Toxicological Activity of Molecules
Authors: Kazakova Renata R. , Masson Patrick
Published: November 2022

Toxicity and pharmacological activity scales of molecules, in particular toxicants, xenobiotics, drugs, nutraceuticals, etc., are described by multiples indicators, and the most popular is the median lethal dose (LD50). At the molecular level, reversible inhibition or binding constants provide unique information on the potential activity of molecules. The important problem concerning the meaningfulness of IC50 for irreversible ligands/inhibitors is emphasized. Definitions and principles for determination of these quantitative parameters are briefly introduced in this article. Special attention is devoted to the relationships between these indicators. Finally, different approaches making it possible to link pharmacological and toxicological properties of molecules in terms of molecular interactions (or chemical reactions) with their biological targets are briefly examined. Experimental trends for future high-throughput screening of active molecules are pointed out.
Very Low Birth Weight Outcomes and Admission Temperature: Does Hyperthermia Matter?
Authors: Brophy Hannah , Tan Gaik Min , Yoxall Charles William
Published: November 2022

National and international recommendations for thermal care at preterm birth include recommendations to avoid hypothermia and hyperthermia. There is limited evidence demonstrating harm resulting from admission hyperthermia. Our aim was to assess the relationships between admission temperature and outcomes in very low birth weight (VLBW) babies in a unit with low rates of hypothermia and a higher rate of hyperthermia. This was an observational study based on routinely collected data including demographics, admission temperature, survival and major morbidity outcomes. Subjects were 1104 consecutive inborn VLBW babies admitted to a Neonatal Intensive Care Unit in United Kingdom between 2010 and 2017. Results: 155 (14%) of babies were hypothermic (<36.5 °C) with only 21 (1.9%) < 36 °C, and 254 (23%) of babies were hyperthermic (>37.5 °C). The rate of major abnormality on cranial ultrasound scan was increased in the hyperthermic babies compared to the normothermic babies (37/239 (15.5%) vs. 54/601 (9%), relative risk (95% CI) 1.723 (1.166 to 2.546), p = 0.006). There was no difference in survival or other major morbidity in the hyperthermic babies compared to the normothermic babies. There was no association between hypothermia and survival or any major morbidity, although this probably reflects the low power of the study given the low rates of significant hypothermia. Higher admission temperature was associated with an increase in the risk of major cranial ultrasound abnormality using multiple logistic regression analysis (p = 0.007) with an increased odds ratio (95% CI) of 1.48 (1.11 to 1.97) for each degree of increase. We conclude that admission hyperthermia is independently associated with an increased risk of preterm brain injury. It is not possible to state whether this is a causative association, or whether the association is a consequence of a shared aetiology of perinatal infection.
Usage of DNA Fingerprinting Technology to Check Sample Error and Contamination in Molecular Laboratories
Authors: Qin Dahui , Forster Mark , Gandhi Shital M. , Akabari Ratilal , Zheng Zhong , Lal Janella , Lovinger Katherine
Published: November 2022

Sample identification error is a severe medical error in clinical molecular diagnostic laboratories, which can lead to reporting the wrong results for the patient involved. Sample contamination can also lead to incorrect test reports. Avoiding sample identification error and sample contamination could be life-saving. Sample switch and sample contamination could happen on laboratory bench works, especially when pipetting into multi-well plates. It is difficult to realize such errors during laboratory bench work. Laboratory staff may not be aware of such an error when it happens. DNA fingerprinting technology can be used to determine sample identity and subsequently identify sample switch and sample contamination in the laboratory. Our laboratory has explored the usage of this technology in our quality control process and successfully established that DNA fingerprinting can be used to monitor sample switch and sample contamination in next-generation sequencing and BCR/ABL1 real-time PCR bench work.
Barriers and Facilitators to Conducting Oncology Clinical Trials in the UAE
Authors: Al-Shamsi Humaid O.
Published: November 2022

Cancer research and clinical trials are essential to improve cancer patients’ outcomes and advance the oncology field. The United Arab Emirates (UAE) has been lagging in cancer research with many barriers, including healthcare, institutional, regulatory, patient and community, the global oncology community, and the pharmaceutical industry. In this report, we try to address these challenges from our perspective. Making clinical trials accessible for cancer patients in the UAE requires a collaborative approach from all stakeholders and serious consideration for the greater cause to improve the patient’s outcome and contribute to the advancement of the cancer field worldwide. There has been significant support from the UAE government and the regulators in the UAE to facilitate and encourage research in general and cancer research in particular with recent initiatives and international collaborations. Private and public institutions must overcome their competitive moods and work together to strengthen the research network across the UAE and improve accrual for potential clinical trials. Public awareness and education must overcome long-standing perceptions about research and clinical trials in the UAE. The pharmaceutical industry must work closely with institutions across the UAE and support them in establishing accredited research programs and clinical trial units. The Emirates Oncology Society is establishing the Oncology Research Working Group to advocate and advance cancer research in the UAE. All stakeholders must be engaged to successfully implement impactful clinical trials in the UAE and the region.
Global Coasts: A Baroque Embarrassment of Riches
Authors: Schlacher Thomas A. , Maslo Brooke , de Schipper Matthieu A.
Published: November 2022

Coasts form the universal stage on which people interact with the global ocean. Our history is inextricably intertwined with the seashore, being a rich tapestry of archaeological sites that paint a vivid picture of people hunting, foraging, fishing and scavenging at the edge of the sea. Seascapes inspire diverse art forms celebrated through the ages. The world’s sandy beaches have a flummoxing duality of anthropocentric purpose—ranging from the horrors when being theatres of war to first love under a rising moon. ‘Man’s Love of the Sea’ continues to draw people towards the shore: the narrow coastal strip contains everything from holiday cottages to mega-cities. This coastal concentration of the human population is problematic when shorelines erode and move inland, a geological process fastened by climate change. Society’s response is often a heavy investment in coastal engineering to complement and enhance the natural storm protection capacity of beaches and dunes. The coast’s immense cultural, social, and economic significance are complemented by a wealth of natural riches. In the public’s eye, these ecological values can pale somewhat compared with more imminent ecosystem services, particularly protecting human properties from storm impacts. To re-balance the picture, here we illustrate how peer-reviewed science can be translated into ‘cool beach facts’, aimed at creating a broader environmental appreciation of ocean shores. The colourful kaleidoscope of coastal values faces a veritable array of anthropogenic stressors, from coastal armouring to environmental harm caused by off-road vehicles. Whilst these threats are not necessarily unique to coastal ecosystems, rarely do the winds of global change blow stiffer than at the edge of the sea, where millions of people have created their fragile homes on shifting sands now being increasingly eroded by rising seas. Natural shorelines accommodate such changing sea levels by moving landwards, a poignant and powerful reminder that protecting the remaining natural land is primus inter pares in coastal management. There is no doubt that coastal ecosystems and coastal communities face august trials to maintain essential ecosystem services in the face of global change. Whilst bureaucracies are not always well equipped to counteract environmental harm effectively, using measures carrying a social license, many communities and individuals have encouragingly deep values connected to living coastlines. Building on these values, and harnessing the fierce protective spirits of people, are pivotal to shaping fresh models that can enhance and re-build resilience for shores that will continue to be a ‘baroque embarrassment of coastal riches’.
Synthesis Optimization of Cadmium Carbonate Films as Potential Precursor to Produce CdSe, CdTe, and CdO Films
Authors: Heredia-Cancino J. A. , Mendoza-Peña K. J. , Higuera-Valenzuela H. J. , Soto B. M. Anahí , Ochoa-Landín R. , Castillo S. J.
Published: November 2022

Cadmium-derived materials are highly demanded for optoelectronics applications, and the scientific community has widely worked in different ways to develop them. In this research, the optimization of CdCO3 films using a chemical bath deposition (CBD) method at different deposition times (10, 11, and 12 h) is reported. The intention to optimize CdCO3 films is in order to propose it as a precursor to produce different types of cadmium-derived semiconductors such as CdSe, CdTe, and CdO. The obtained films were characterized by X-ray diffraction (XRD), Raman spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, optical absorption by diffuse reflectance, scanning electron microscopy (SEM), and energy-dispersive spectroscopy (EDS). The results provide evidence that CdCO3 films were effectively synthesized, featuring a rhombohedral crystalline structure with a preferential plane (104), and crystallite sizes were 65, 69, and 87 nm for the deposited samples at 10, 11, and 12 h, respectively. Surface morphology analysis revealed microstructures around 3–5 μm, with a deltoid shape, agglomerated and distributed randomly for all samples. The bandgap obtained was 3.78 eV for all samples.