bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Dietary Multienzyme Complex Supplementation on Growth Performance, Digestive Capacity, Histomorphology, Blood Metabolites and Hepatic Glycometabolism in Snakehead (Channa argus)
Authors: Ding Xiaoqing , Nie Xinzheng , Yuan Chunchun , Jiang Lai , Ye Wenxin , Qian Lichun
Published: February 2022

The present study evaluated the impact of dietary multienzyme complex (MEC) supplementation on growth performance, digestive enzyme activity, histomorphology, serum metabolism and hepatopancreas glycometabolism in snakeheads (Channa argus). A total of 600 fish (initial weight, 69.70 ± 0.30 g) were randomly divided into four groups. Four diets were formulated: (1) control (basic diet); (2) E1 (400 U kg−1 amylase, 150 U kg−1 acid protease, 1900 U kg−1 neutral protease and basic diet); (3) E2 (800 U kg−1 amylase, 300 U kg−1 acid protease, 3800 U kg−1 neutral protease and basic diet); and (4) E3 (1200 U kg−1 amylase, 450 U kg−1 acid protease, 5700 U kg−1 neutral protease and basic diet). The results show that the E2 group increased the specific growth rate, weight gain rate and the final body weight, as well as decreasing the blood urea nitrogen, alanine aminotransferase and triglyceride. The mRNA levels and activities of digestive enzymes and key glucose metabolism enzymes in the hepatopancreas were enhanced in snakeheads fed the MEC. Meanwhile, moderate MEC diet (E2 groups) supplementation improved digestive tract morphology, increased the glycogen in the hepatopancreas and the lipids in the dorsal muscle. Moreover, plasma metabolomics revealed differential metabolites mainly involved in amino acid metabolism. These findings suggest that dietary supplementation with the MEC improved growth performance, digestive tract morphology, gene expression and the activity of digestive enzymes, enhanced the glycolysis-gluconeogenesis and amino acid metabolism of snakeheads, and the optimal composition of the MEC was group E2.
Clostridioides Difficile Enteritis: Case Report and Literature Review
Authors: Klimko Artsiom , Tieranu Cristian George , Curte Ana-Maria , Preda Carmen Monica , Tieranu Ioana , Olteanu Andrei Ovidiu , Ionescu Elena Mirela
Published: February 2022

Background: Clostridioides Difficile is a well-known pathogen causing diarrhea of various degrees of severity through associated infectious colitis. However, there have been reports of infectious enteritis mainly in patients with ileostomy, causing dehydration through high-output volume; Case presentation: We report the case of a 46-year-old male patient, malnourished, who presented with high-output ileostomy following a recent hospitalization where he had suffered an ileo-colic resection with ileal and transverse colon double ostomy, for stricturing Crohn’s disease. Clostridioides Difficile toxin A was identified in the ileal output confirming the diagnosis of acute enteritis. Treatment with oral Vancomycin was initiated with rapid reduction of the ileostomy output volume; Conclusion: We report a case of Clostridioides Difficile enteral infection as a cause for high-output ileostomy, successfully treated with oral Vancomycin. We also review the existing literature data regarding this specific localized infection.
Preliminary Application of the Algorithm Highlighting Petroglyph Patterns
Authors: Wojcicki Piotr , Korga Sylwester , Milosz Marek
Published: February 2022

One of the greatest problems in the field of cultural heritage is the process of material destruction of monuments. In most cases, the cause is operational or random wear. Such processes can be slowed down or eliminated thanks to the maintenance process. The most dangerous processes of monument wear and tear are those in which historical objects are exposed to environmental impact. Cycles of weather changes have a particularly negative impact on objects of this type. These types of objects are significantly damaged and are the most difficult to scan. The research work included the scanning of such an object and attempts were made to digitise the point cloud. The monument selected for the model laser scanning was a rock petroglyph located on the slope of the Chatkal mountain near the town of Tashkent in Uzbekistan. The article describes the process of digitally recording a historic object with the use of the Artec Eva scanner. The process of data acquisition from points in space and the processes of highlighting petroglyphs are described. The highlighted model was obtained using proprietary software created for this purpose by the authors of the article. As a result, data were saved which would be difficult to save and read using the previously used 3D scanning techniques. The obtained data can be made available to recipients in the form of exhibits in virtual museums.
Numerical Analysis for Elucidating the Effect of Tunnel Excavation in Gravel-Mixed Ground
Authors: Hayashi Hisashi , Okazaki Yasuyuki , Sakai Daisuke , Morimoto Shingo , Shinji Masato
Published: February 2022

In tunnel construction in gravel-mixed ground, it is extremely important to predict the risk of gravel dropout and the accompanying large deformation of the substrate ground. The distribution and shape of gravel vary, and it is difficult to reproduce the situation depending on the individual site. Therefore, in this study, we created a model of the gravel-mixed ground using the Voronoi partition model. Then, by mathematical analysis, the gravel shape that appears in the actual phenomenon could be reproduced in consideration of randomness and inhomogeneity. In addition, it was clarified that the gravel extrusion phenomenon and the large deformation of the ground can be expressed.
System-Theoretic Process Analysis Based on SysML/MARTE and NuSMV
Authors: Zhong Deming , Sun Rui , Gong Haoyuan , Wang Tianhuai
Published: February 2022

Systems Theoretical Accident Model and Process (STAMP), which considers system safety as an emergent property of the system, is a more effective accident/loss causality model for modern complex systems. Based on STAMP, System Theoretical Process Analysis (STPA) has attracted increasing attention as a new approach to hazard analysis, and relevant international standards are being developed. However, STPA is mainly performed manually, leading to inefficiencies, and constructs models in non-standard language, hindering the integration with existing systems engineering. STPA-SN (STPA based on SysML/MARTE and NuSMV) is proposed to build model in SysML, describing the timing with MARTE (Modeling and Analysis of Real-Time and Embedded Systems), transform SysML model into NuSMV model and output loss scenarios automatically with model checker. An application example of STPA-SN is provided to demonstrate potentials for higher efficiency of analysis and for collaboration with SysML-based systems engineering.
Evaluation of the Factors Impacting the Water Pipe Leak Detection Ability of GPR, Infrared Cameras, and Spectrometers under Controlled Conditions
Authors: Aslam Huda , Mortula Md Maruf , Yehia Sherif , Ali Tarig , Kaur Manreet
Published: February 2022

Leakages from water distribution infrastructures are responsible for a considerable amount of water losses. Consequently, innovative, non-destructive techniques (NDT) of leakage detection for early recognition is vital. In this study, the leak detection abilities of Ground Penetration Radar (GPR), spectrometers, and infrared (IR) cameras were investigated, and the factors affecting the leak detection response were assessed. Three experimental setups were constructed to simulate underground pipes in dune sand. Three different pipe materials (PVC, PPR, and PE) were investigated under three levels of moisture content (MC; 2%, 5%, and 10%) and three types of leaks (hole, crack, and faulty joint). The IR camera was the most effective among the different NDTs used in this study. The IR camera detected all types of leaks at 2% and 5% MC but was inconclusive at 10% MC. Similarly, the GPR detected the leaks at 2% and 5% MC successfully but was inconclusive at 10% MC. Lastly, the spectrometer was the least reliable NDT to detect leaks. Results suggest that IR cameras and spectrometers that operate in the mid-IR range (5–25 µm) can detect leaks.
Recording of Long Low-Amplitude Bulk Elastic Waves in Transparent Solid Waveguides by Digital and Classical Holography
Authors: Belashov Andrey V. , Zhikhoreva Anna A. , Semenova Irina V.
Published: February 2022

In this paper we compare two implementations of the holographic technique for recording long, nonlinear, elastic waves of low amplitude in solid polymer waveguides: classical holographic interferometry and digital holography. Both implementations are realized in transmission configuration, with recording in the off-axis schematic. The advantages and disadvantages of these implementations are discussed as applied to the investigation of the evolution of shock waves and strain solitons in transparent solid waveguides.
Carotenoids in Fresh and Processed Food: Between Biosynthesis and Degradation
Authors: Crupi Pasquale
Published: February 2022

Currently, there is a general trend in food science to link food and health in line with consumers’ concern about what is in their food and how what they eat can promote well-being [...]
Utilization of Optical Tweezer Nanotechnology in Membrane Interaction Studies
Authors: Eechampati Arnith , de Silva Chamaree
Published: February 2022

Optical tweezers have been a fixture of microscopic cell manipulation since the 1990s. Arthur Ashkin’s seminal work has led to the advancement of optical tweezers as an effective tool for assay development in the fields of physics and nanotechnology. As an advanced application of cell manipulation, optical tweezers have facilitated the study of a multitude of cellular and molecular interactions within the greater field of nanotechnology. In the three decades since the optical tweezers’ rise to prominence, different and versatile assays have emerged that further explore the biochemical pathways integral for cell proliferation and communication. The most critical organelle implicated in the communication and protection of single cells includes the plasma membrane. In the past three decades, novel assays have emerged which examine the plasma membrane’s role in cell-to-cell interaction and the specific protein components that serve integral membrane functions for the cell as a whole. To further understand the extent to which optical tweezers have evolved as a critical tool for cellular membrane assessment within the field of nanotechnology, the various novel assays, including pulling, indentation, and stretching assays, will be reviewed in the current research sector.
Color of Tenement Houses Built in the 19th and Early 20th Centuries in Wroclaw (Poland)—Research, Restoration and Conservation
Authors: Nowakowski Przemyslaw
Published: February 2022

The article presents an analysis of the color evolution of tenement houses in Wroclaw in the 19th and early 20th centuries. Their various colors, confirmed by research, prove the term “Colorful Wroclaw”, appearing in the 1930s the architectural journals. The considerations were supported, i.e., by iconographic material presenting the varied colors of renovated tenement houses in Wroclaw. The aim of this analysis is to show the role of scientific and conservation research in restoring the historical value of buildings. Examples of tenement house restoration projects show the practical application of scientific research to formulate conservation guidelines and organize renovation work. Renovation work also requires traditional and increasingly modern construction techniques. These historical buildings belong to the country’s cultural heritage. They are usually entered into the Monuments Register and are subject to conservation protection. Restoring their former appearance and character is possible thanks to the participation of national and international institutions. It deals with supporting the flow of knowledge and financial resources. The following research methods were used: archival and literature studies, analytical studies of selected conservation techniques and stratigraphic studies of paint coatings, and case studies when discussing renovation projects for selected tenement houses.
Structure Calculations in Nd III and U III Relevant for Kilonovae Modelling
Authors: Silva Ricardo F. , Sampaio Jorge M. , Amaro Pedro , Flörs Andreas , Martínez-Pinedo Gabriel , Marques José P.
Published: February 2022

The detection of gravitational waves and electromagnetic signals from the neutron star merger GW170817 has provided evidence that these astrophysical events are sites where the r-process nucleosynthesis operates. The electromagnetic signal, commonly known as kilonova, is powered by the radioactive decay of freshly synthesized nuclei. However, its luminosity, colour and spectra depend on the atomic opacities of the produced elements. In particular, opacities of lanthanides and actinides elements, due to their large density of bound–bound transitions, are fundamental. The current work focuses on atomic structure calculations for lanthanide and actinide ions, which are important in kilonovae modelling of ejecta spectra. Calculations for Nd III and U III, two representative rare-earth ions, were achieved. Our aim is to provide valuable insights for future opacity calculations for all heavy elements. We noticed that the opacity of U III is about an order of magnitude greater than the opacity of Nd III due to a higher density of levels in the case of the actinide.
Role of Implantable Drug Delivery Devices with Dual Platform Capabilities in the Prevention and Treatment of Bacterial Osteomyelitis
Authors: Billings Caroline , Anderson David E.
Published: February 2022

As medicine advances and physicians are able to provide patients with innovative solutions, including placement of temporary or permanent medical devices that drastically improve quality of life of the patient, there is the persistent, recurring problem of chronic bacterial infection, including osteomyelitis. Osteomyelitis can manifest as a result of traumatic or contaminated wounds or implant-associated infections. This bacterial infection can persist as a result of inadequate treatment regimens or the presence of biofilm on implanted medical devices. One strategy to mitigate these concerns is the use of implantable medical devices that simultaneously act as local drug delivery devices (DDDs). This classification of device has the potential to prevent or aid in clearing chronic bacterial infection by delivering effective doses of antibiotics to the area of interest and can be engineered to simultaneously aid in tissue regeneration. This review will provide a background on bacterial infection and current therapies as well as current and prospective implantable DDDs, with a particular emphasis on local DDDs to combat bacterial osteomyelitis.
Nutrient Utilization during Male Maturation and Protein Digestion in the Oriental Hornet
Authors: Bodner Levona , Bouchebti Sofia , Watted Omar , Seltzer Rya , Drabkin Ariel , Levin Eran
Published: February 2022

Males of social Hymenoptera spend the first days following eclosion inside the nest before dispersing to find a young queen to mate with. During this period, they must acquire enough nutrients to enable their sexual maturation and store energy to sustain them through their nuptial journey. It was previously argued that adult hornets are unable to process dietary proteins and rely on the larvae to supply them with free amino acids and carbohydrates that they secrete via trophallaxis. Using isotopically enriched diets, we examined nutrient allocation and protein turnover in newly-emerged males of the Oriental hornet during their maturation period and tested the protein digestion capability in the presence and absence of larvae in both males and worker hornets. The results indicated that protein turnover in males occurs during the first days following eclosion, while carbohydrates are incorporated into body tissues at higher rates towards the end of the maturation period. Additionally, we found that males cannot digest protein and depend on larval secretions as a source of nutrition, while workers, in contrast to previous reports, can metabolize protein independently. Our findings demonstrate the contribution of adult male nutrition and larval secretions to colony fitness.
Comparison of the External Morphology of the Sternal Glands for Hornets in the Genus Vespa
Authors: Mattila Heather R. , Otis Gard W. , Billen Johan , Nguyen Lien T. P. , Shimano Satoshi
Published: February 2022

Many social wasps in the speciose subfamilies Polistinae and Vespinae have two sternal glands—the van der Vecht gland and the Richards gland—that are not found in other insects. The presence of these glands has been confirmed in only 6 of 22 hornet species (genus Vespa) and images of their fine structure have not been produced. Here; we characterize the external morphology associated with both glands for workers of nine Vespa species using scanning electron microscopy. All hornets had similar gland configurations; although gland-associated external features differed among species. Scaled for size, glands were equivalently sized for the giant hornets (V. mandarinia and V. soror) and their closest phylogenetic relatives (V. tropica and V. ducalis). Relative size of gland-associated structures was reduced by half for V. simillima; V. velutina; and V. affinis workers. The remaining species (V. crabro and V. analis) had intermediately sized features. Differences among species in external gland structure were best explained by selective pressures related to predatory behavior, rather than defense of nests against ants. However, a lack of information about how Vespa workers use their van der Vecht and Richards glands limits a comparative interpretation of the function of their external gland morphology.
Plasma Proteomic Changes of Atherosclerosis after Exercise in ApoE Knockout Mice
Authors: Liao Chen-Chung , Xu Jin-Wei , Huang Wen-Ching , Chang Hung-Chang , Tung Yu-Tang
Published: February 2022

Atherosclerosis is the preliminary cause of coronary artery disease, one of the diseases that account for the largest number of fatal mortalities. Physical activity is an effective strategy to restrain atherosclerosis from deterioration. Evidence indicated that changes in the proteomic profile are highly associated with atherosclerosis development, but the mechanism behind exercise for atherosclerosis amelioration has not yet been investigated from a proteomics perspective. Hence, the proteomic profiles could further elucidate the systematic effects of exercise intervention on ApoE knockout atherosclerotic model and high-fat-diet intervention. In the current study, Apoeem1Narl/Narl mice were randomly allocated into a normal diet (ND), Western diet (WD), and WD with 12-week exercise intervention (WD EX) groups. The plasma proteome between WD and WD EX groups demonstrate the significant difference, and ten major pathways, including cardiovascular disease (CVD)–hematological disease, inflammatory disease, infectious diseases, inflammatory response, cell-to-cell signaling and interaction, connective tissue disorders_inflammatory disease, metabolic disease_organismal injury and abnormalities, cell-to-cell signaling and interaction, connective tissue disorders_inflammatory disease, and endocrine system disorders_gastrointestinal disease, etc., were generated by the IPA analysis. The 15 proteins (MYOCD, PROS1, C2, SERPINA10, CRP, F5, C5, CFB, FGG, CFH, F12, PRDX2, PROZ, PPIA, and HABP2) critically involved in CVD–hematological disease pathway showed significant difference between WD and WD EX groups. In current study, exercise could significantly alleviate the significantly elevated C5 and inflammation induced by the WD group in accordance with amelioration of atherosclerosis. Therefore, exercise could mitigate chemotaxis through the modulation of the C5 level and innate immunity, thereby alleviating the pathogenesis of atherosclerosis in Western-diet-induced obese mice.
A New Approach to Inhibiting Triple-Negative Breast Cancer: In Vitro, Ex Vivo and In Vivo Antiangiogenic Effect of BthTx-II, a PLA2-Asp-49 from Bothrops jararacussu Venom
Authors: Van Petten de Vasconcelos Azevedo Fernanda , Lopes Daiana Silva , Zóia Mariana Alves Pereira , Correia Lucas Ian Veloso , Saito Natieli , Fonseca Belchiolina Beatriz , Polloni Lorena , Teixeira Samuel Cota , Goulart Luiz Ricardo , de Melo Rodrigues Ávila Veridiana
Published: February 2022

Phospholipases A2 (PLA2) represent a superfamily of enzymes widely distributed in living organisms, with a broad spectrum of pharmacological activities and therapeutic potential. Anti-angiogenic strategies have become one of the main tools in fighting cancer. In this sense, the present work reports the inhibition of tumor angiogenesis induced by Asp-49 BthTX-II using in vitro, ex vivo and in vivo approaches. We demonstrate that BthTx-II inhibited cell adhesion, proliferation, and migration of human umbilical vein endothelial cells (HUVEC), as well as caused a reduction in the levels of endothelial growth factor (VEGF) during in vitro angiogenesis assays. BthTx-II was also able to inhibit the sprouting angiogenic process, by the ex vivo germination assay of the aortic ring; in addition, this toxin inhibited the migration and proliferation of HUVEC in co-culture with triple-negative breast cancer cells (e.g., MDA-MB-231 cells). Finally, in vivo tumor suppression and anti-angiogenic activities were analyzed using MDA-MB-231 cells with Matrigel injected into the chorioallantoic membrane of chicken embryo (CAM) for 7 days treatment with BthTx-II, showing a considerable reduction in vessel caliber, on the size and weight of tumors. Together, these results suggest an important antiangiogenic and antitumor role for BthTx-II, as a potential prototype for the development of new tools and antitumor drugs in cancer therapy.
Venous Thromboembolism and Cancer: A Comprehensive Review from Pathophysiology to Novel Treatment
Authors: Canonico Mario Enrico , Santoro Ciro , Avvedimento Marisa , Giugliano Giuseppe , Mandoli Giulia Elena , Prastaro Maria , Franzone Anna , Piccolo Raffaele , Ilardi Federica , Cameli Matteo , Esposito Giovanni
Published: February 2022

Acute thrombotic events can unveil occult cancer, as they are its first manifestation in about 20 to 30% of all cases. Malignancy interacts in an intricate way with the hemostatic system, promoting both thrombosis and bleeding. The main pathway involved in these reactions involves the activation of tumor-associated procoagulant factors, which eventually results in clot formation. The clinical manifestation of cancer-related thrombotic events mainly involves the venous side, and manifests in a broad spectrum of conditions, including unusual sites of venous thrombosis. The selection of patients who have a balanced risk–benefit profile for management of anticoagulation is complex, given individual patient goals and preferences, different prognosis of specific cancers, common comorbidities, potential drug–drug interactions, underweight states, and the competing risks of morbidity and mortality. Anticoagulant treatment in cancer settings is broadly debated, considering the potential application of direct oral anticoagulants in both thromboprophylaxis and secondary prevention, having demonstrated its efficacy and safety compared to conventional treatment. This review aims to provide a brief overview of the pathophysiology and management of cancer-related thrombosis, summarizing the results obtained in recent clinical trials.
Biocides as Biomedicines against Foodborne Pathogenic Bacteria
Authors: Butucel Eugenia , Balta Igori , Ahmadi Mirela , Dumitrescu Gabi , Morariu Florica , Pet Ioan , Stef Lavinia , Corcionivoschi Nicolae
Published: February 2022

Biocides are currently considered the first line of defense against foodborne pathogens in hospitals or food processing facilities due to the versatility and efficiency of their chemical active ingredients. Understanding the biological mechanisms responsible for their increased efficiency, especially when used against foodborne pathogens on contaminated surfaces and materials, represents an essential first step in the implementation of efficient strategies for disinfection as choosing an unsuitable product can lead to antibiocide resistance or antibiotic–biocide cross-resistance. This review describes these biological mechanisms for the most common foodborne pathogens and focuses mainly on the antipathogen effect, highlighting the latest developments based on in vitro and in vivo studies. We focus on biocides with inhibitory effects against foodborne bacteria (e.g., Escherichia spp., Klebsiella spp., Staphylococcus spp., Listeria spp., Campylobacter spp.), aiming to understand their biological mechanisms of action by looking at the most recent scientific evidence in the field.
TDP-43 Pathology and Prionic Behavior in Human Cellular Models of Alzheimer’s Disease Patients
Authors: Cuevas Eva P. , Rodríguez-Fernández Alberto , Palomo Valle , Martínez Ana , Martín-Requero Ángeles
Published: February 2022

Alzheimer’s disease (AD) is a neurodegenerative disorder for which there is currently no effective treatment. Despite advances in the molecular pathology of the characteristic histopathological markers of the disease (tau protein and β-amyloid), their translation to the clinic has not provided the expected results. Increasing evidences have demonstrated the presence of aggregates of TDP-43 (TAR DNA binding protein 43) in the postmortem brains of patients diagnosed with AD. The present research is focused on of the study of the pathological role of TDP-43 in AD. For this purpose, immortalized lymphocytes samples from patients diagnosed with different severity of sporadic AD were used and the TDP-43 pathology was analyzed against controls, looking for differences in their fragmentation, phosphorylation and cellular location using Western blot and immunocytochemical techniques. The results revealed an increase in TDP-43 fragmentation, as well as increased phosphorylation and aberrant localization of TDP-43 in the cytosolic compartment of lymphocytes of patients diagnosed with severe AD. Moreover, a fragment of approximately 25 KD was found in the extracellular medium of cells derived from severe AD individuals that seem to have prion-like characteristics. We conclude that TDP-43 plays a key role in AD pathogenesis and its cell to cell propagation.
Placenta Accreta Spectrum Disorder Complicated with Endometriosis: Systematic Review and Meta-Analysis
Authors: Matsuzaki Shinya , Ueda Yutaka , Nagase Yoshikazu , Matsuzaki Satoko , Kakuda Mamoru , Kakuda Sahori , Sakaguchi Hitomi , Hisa Tsuyoshi , Kamiura Shoji
Published: February 2022

This study aimed to assess the relationship between placenta accreta spectrum disorder (PASD) and endometriosis. The relationships among pregnancy, assisted reproductive technology (ART), placenta previa, ART-conceived pregnancy and PASD were also determined. A systematic literature review was conducted using multiple computerized databases. Forty-eight studies (1990–2021) met the inclusion criteria. According to the adjusted pooled analysis (n = 3), endometriosis was associated with an increased prevalence of PASD (adjusted odds ratio [OR] 3.39, 95% confidence interval [CI] 1.96–5.87). In the included studies, the ART rate ranged from 18.2% to 37.2% for women with endometriosis. According to the adjusted pooled analysis, women who used ART were more likely to have placenta previa (n = 13: adjusted OR 2.96, 95%CI, 2.43–3.60) and PASD (n = 4: adjusted OR 3.54, 95%CI 1.86–6.76) than those who did not use ART. According to the sensitivity analysis using an unadjusted analysis accounting for the type of ART, frozen embryo transfer (ET) was associated with an increased risk of PASD (n = 4: OR 2.79, 95%CI, 1.22−6.37) compared to fresh ET. Endometriosis may be associated with an increased rate of PASD. Women with placenta previa complicated with endometriosis who conceived using frozen ET may be a high risk for PASD.
Involvement of Oxidative Stress in the Development of Subcellular Defects and Heart Disease
Authors: Dhalla Naranjan S. , Elimban Vijayan , Bartekova Monika , Adameova Adriana
Published: February 2022

It is now well known that oxidative stress promotes lipid peroxidation, protein oxidation, activation of proteases, fragmentation of DNA and alteration in gene expression for producing myocardial cell damage, whereas its actions for the induction of fibrosis, necrosis and apoptosis are considered to result in the loss of cardiomyocytes in different types of heart disease. The present article is focused on the discussion concerning the generation and implications of oxidative stress from various sources such as defective mitochondrial electron transport and enzymatic reactions mainly due to the activation of NADPH oxidase, nitric oxide synthase and monoamine oxidase in diseased myocardium. Oxidative stress has been reported to promote excessive entry of Ca2+ due to increased permeability of the sarcolemmal membrane as well as depressions of Na+-K+ ATPase and Na+-Ca2+ exchange systems, which are considered to increase the intracellular of Ca2+. In addition, marked changes in the ryanodine receptors and Ca2+-pump ATPase have been shown to cause Ca2+-release and depress Ca2+ accumulation in the sarcoplasmic reticulum as a consequence of oxidative stress. Such alterations in sarcolemma and sarcoplasmic reticulum are considered to cause Ca2+-handling abnormalities, which are associated with mitochondrial Ca2+-overload and loss of myofibrillar Ca2+-sensitivity due to oxidative stress. Information regarding the direct effects of different oxyradicals and oxidants on subcellular organelles has also been outlined to show the mechanisms by which oxidative stress may induce Ca2+-handling abnormalities. These observations support the view that oxidative stress plays an important role in the genesis of subcellular defects and cardiac dysfunction in heart disease.
An Artificial Intelligence-Enabled ECG Algorithm for the Prediction and Localization of Angiography-Proven Coronary Artery Disease
Authors: Huang Pang-Shuo , Tseng Yu-Heng , Tsai Chin-Feng , Chen Jien-Jiun , Yang Shao-Chi , Chiu Fu-Chun , Chen Zheng-Wei , Hwang Juey-Jen , Chuang Eric Y. , Wang Yi-Chih , Tsai Chia-Ti
Published: February 2022

(1) Background: The role of using artificial intelligence (AI) with electrocardiograms (ECGs) for the diagnosis of significant coronary artery disease (CAD) is unknown. We first tested the hypothesis that using AI to read ECG could identify significant CAD and determine which vessel was obstructed. (2) Methods: We collected ECG data from a multi-center retrospective cohort with patients of significant CAD documented by invasive coronary angiography and control patients in Taiwan from 1 January 2018 to 31 December 2020. (3) Results: We trained convolutional neural networks (CNN) models to identify patients with significant CAD (>70% stenosis), using the 12,954 ECG from 2303 patients with CAD and 2090 ECG from 1053 patients without CAD. The Marco-average area under the ROC curve (AUC) for detecting CAD was 0.869 for image input CNN model. For detecting individual coronary artery obstruction, the AUC was 0.885 for left anterior descending artery, 0.776 for right coronary artery, and 0.816 for left circumflex artery obstruction, and 1.0 for no coronary artery obstruction. Marco-average AUC increased up to 0.973 if ECG had features of myocardial ischemia. (4) Conclusions: We for the first time show that using the AI-enhanced CNN model to read standard 12-lead ECG permits ECG to serve as a powerful screening tool to identify significant CAD and localize the coronary obstruction. It could be easily implemented in health check-ups with asymptomatic patients and identifying high-risk patients for future coronary events.
A FRET-Based Biosensor for the Src N-Terminal Regulatory Element
Authors: Iruela Guillermo , Fernández Alejandro , Sagar Amin , Carvajal Francisco Javier , Bernadó Pau , Pons Miquel
Published: February 2022

In signaling proteins, intrinsically disordered regions often represent regulatory elements, which are sensitive to environmental effects, ligand binding, and post-translational modifications. The conformational space sampled by disordered regions can be affected by environmental stimuli and these changes trigger, vis a vis effector domain, downstream processes. The disordered nature of these regulatory elements enables signal integration and graded responses but prevents the application of classical approaches for drug screening based on the existence of a fixed three-dimensional structure. We have designed a genetically encodable biosensor for the N-terminal regulatory element of the c-Src kinase, the first discovered protooncogene and lead representative of the Src family of kinases. The biosensor is formed by two fluorescent proteins forming a FRET pair fused at the two extremes of a construct including the SH4, unique and SH3 domains of Src. An internal control is provided by an engineered proteolytic site allowing the generation of an identical mixture of the disconnected fluorophores. We show FRET variations induced by ligand binding. The biosensor has been used for a high-throughput screening of a library of 1669 compounds with seven hits confirmed by NMR.
The Impact of an Incidental Dose on Axillary Tumor Control and Toxicity in Localized Breast Cancer: A Retrospective Analysis
Authors: Schmitt Martin , Chambrelant Isabelle , Hong Chheang Parigna , Pflumio Carole , Hild Carole , Petit Thierry , Noël Georges
Published: February 2022

Purpose: The dosimetric analysis of the incidental axillary dose delivered to axillary lymph node levels I–III by different techniques of whole breast irradiation and the analysis of prognostic factors of axillary recurrence of breast cancer. Methods: We perform a retrospective analysis that includes 171 patients with localized breast carcinoma irradiated at Centre Paul Strauss. To be included in the study, patients had to have a histological confirmation of breast cancer diagnosis, surgical treatment without axillary lymph node dissection (ALND), whole breast irradiation without axillary irradiation by a specific field, and a treatment plan available. Results: Three patients had lymph node recurrence. There was no significant correlation between the maximal or mean dose delivered at the three axillary levels and the risk of axillary lymph node recurrence. There was no significant correlation between the irradiation technique and the risk of axillary lymph node recurrence. Two patients, both in the HT group, had lymphoedema. There was significantly more lymphoedema in the HT group than in the ST and IMRT groups (p < 0.048). The mean dose in level II was significantly higher in the group of patients with lymphoedema (3.45 Gy (1.08; 9.62) vs. 23.4 Gy (23.1; 23.6)) (p < 0.02). Conclusion: The irradiation technique has an influence on the incidental dose delivered to the axillary area, but has no influence on the risk of axillary recurrence. The risk of lymphoedema could be related to the use of HT and the mean dose delivered at level II.
Diagnostic Performance of Risk of Malignancy Algorithm (ROMA), Risk of Malignancy Index (RMI) and Expert Ultrasound Assessment in a Pelvic Mass Classified as Inconclusive by International Ovarian Tumour Analysis (IOTA) Simple Rules
Authors: Ngu Siew Fei , Chai Yu Ka , Choi Ka Man , Leung Tsin Wah , Li Justin , Kwok Gladys S. T. , Chu Mandy M. Y. , Tse Ka Yu , Cheung Vincent Y. T. , Ngan Hextan Y. S. , Chan Karen K. L.
Published: February 2022

The accurate prediction of malignancy for a pelvic mass detected on ultrasound allows for appropriate referral to specialised care. IOTA simple rules are one of the best methods but are inconclusive in 25% of cases, where subjective assessment by an expert sonographer is recommended but may not always be available. In the present paper, we evaluate the methods for assessing the nature of a pelvic mass, including IOTA with subjective assessment by expert ultrasound, RMI and ROMA. In particular, we investigate whether ROMA can replace expert ultrasound when IOTA is inconclusive. This prospective study involves one cancer centre and three general units. Women scheduled for an operation for a pelvic mass underwent a pelvic ultrasound pre-operatively. The final histology was obtained from the operative sample. The sensitivity, specificity and accuracy for each method were compared with the McNemar test. Of the 690 women included in the study, 171 (25%) had an inconclusive IOTA. In this group, expert ultrasound was more sensitive in diagnosing a malignant mass compared to ROMA (81% vs. 63%, p = 0.009) with no significant difference in the specificity or accuracy. All assessment methods involving IOTA had similar accuracies and were more accurate than RMI or ROMA alone. In conclusion, when IOTA was inconclusive, assessment by expert ultrasound was more sensitive than ROMA, with similar specificity.
The Landscape of PDK1 in Breast Cancer
Authors: Wang Na , Fu Jianjiang , Li Zhihua , Jiang Ningni , Chen Yanhong , Peng Juan
Published: February 2022

Given that 3-phosphoinositide-dependent kinase 1 (PDK1) plays a crucial role in the malignant biological behaviors of a wide range of cancers, we review the influence of PDK1 in breast cancer (BC). First, we describe the power of PDK1 in cellular behaviors and characterize the interaction networks of PDK1. Then, we establish the roles of PDK1 in carcinogenesis, growth and survival, metastasis, and chemoresistance in BC cells. More importantly, we sort the current preclinical or clinical trials of PDK1-targeted therapy in BC and find that, even though no selective PDK1 inhibitor is currently available for BC therapy, the combination trials of PDK1-targeted therapy and other agents have provided some benefit. Thus, there is increasing anticipation that PDK1-targeted therapy will have its space in future therapeutic approaches related to BC, and we hope the novel approaches of targeted therapy will be conducive to ameliorating the dismal prognosis of BC patients.
Gas Plasma Exposure of Glioblastoma Is Cytotoxic and Immunomodulatory in Patient-Derived GBM Tissue
Authors: Bekeschus Sander , Ispirjan Mikael , Freund Eric , Kinnen Frederik , Moritz Juliane , Saadati Fariba , Eckroth Jacqueline , Singer Debora , Stope Matthias B. , Wende Kristian , Ritter Christoph A. , Schroeder Henry W. S. , Marx Sascha
Published: February 2022

Glioblastoma multiforme (GBM) is the most common primary malignant adult brain tumor. Therapeutic options for glioblastoma are maximal surgical resection, chemotherapy, and radiotherapy. Therapy resistance and tumor recurrence demand, however, new strategies. Several experimental studies have suggested gas plasma technology, a partially ionized gas that generates a potent mixture of reactive oxygen species (ROS), as a future complement to the existing treatment arsenal. However, aspects such as immunomodulation, inflammatory consequences, and feasibility studies using GBM tissue have not been addressed so far. In vitro, gas plasma generated ROS that oxidized cells and led to a treatment time-dependent metabolic activity decline and G2 cell cycle arrest. In addition, peripheral blood-derived monocytes were co-cultured with glioblastoma cells, and immunomodulatory surface expression markers and cytokine release were screened. Gas plasma treatment of either cell type, for instance, decreased the expression of the M2-macrophage marker CD163 and the tolerogenic molecule SIGLEC1 (CD169). In patient-derived GBM tissue samples exposed to the plasma jet kINPen ex vivo, apoptosis was significantly increased. Quantitative chemokine/cytokine release screening revealed gas plasma exposure to significantly decrease 5 out of 11 tested chemokines and cytokines, namely IL-6, TGF-β, sTREM-2, b-NGF, and TNF-α involved in GBM apoptosis and immunomodulation. In summary, the immuno-modulatory and proapoptotic action shown in this study might be an important step forward to first clinical observational studies on the future discovery of gas plasma technology’s potential in neurosurgery and neuro-oncology especially in putative adjuvant or combinatory GBM treatment settings.
Use of Omics Technologies for the Detection of Colorectal Cancer Biomarkers
Authors: Alorda-Clara Marina , Torrens-Mas Margalida , Morla-Barcelo Pere Miquel , Martinez-Bernabe Toni , Sastre-Serra Jorge , Roca Pilar , Pons Daniel Gabriel , Oliver Jordi , Reyes Jose
Published: February 2022

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers with high mortality rates, especially when detected at later stages. Early detection of CRC can substantially raise the 5-year survival rate of patients, and different efforts are being put into developing enhanced CRC screening programs. Currently, the faecal immunochemical test with a follow-up colonoscopy is being implemented for CRC screening. However, there is still a medical need to describe biomarkers that help with CRC detection and monitor CRC patients. The use of omics techniques holds promise to detect new biomarkers for CRC. In this review, we discuss the use of omics in different types of samples, including breath, urine, stool, blood, bowel lavage fluid, or tumour tissue, and highlight some of the biomarkers that have been recently described with omics data. Finally, we also review the use of extracellular vesicles as an improved and promising instrument for biomarker detection.
Evaluating the Role of Hepatobiliary Phase of Gadoxetic Acid-Enhanced Magnetic Resonance Imaging in Predicting Treatment Impact of Lenvatinib and Atezolizumab plus Bevacizumab on Unresectable Hepatocellular Carcinoma
Authors: Sasaki Ryu , Nagata Kazuyoshi , Fukushima Masanori , Haraguchi Masafumi , Miuma Satoshi , Miyaaki Hisamitsu , Soyama Akihiko , Hidaka Masaaki , Eguchi Susumu , Shigeno Masaya , Yamashima Mio , Yamamichi Shinobu , Ichikawa Tatsuki , Kugiyama Yuki , Yatsuhashi Hiroshi , Nakao Kazuhiko
Published: February 2022

Background: Atezolizumab plus bevacizumab therapy has high response rates in patients with unresectable hepatocellular carcinoma (HCC). The hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) has been reported to be useful as an imaging biomarker for detecting β-catenin mutations. We evaluated whether the pretreatment of the hepatobiliary phase of EOB-MRI could predict the therapeutic effect of lenvatinib and atezolizumab plus bevacizumab. Methods: This study included 68 patients (lenvatinib group (n = 33) and atezolizumab plus bevacizumab group (n = 35)). The visual assessment and relative enhancement ratio (RER) of the largest HCC lesions were evaluated using the hepatobiliary phase of EOB-MRI. Results: The hyperintensity type (RER ≥ 0.9) was 18.2% in the lenvatinib group and 20.0% in the atezolizumab plus bevacizumab group. In the lenvatinib group, progression-free survival (PFS) was not different between the heterogeneous and homogenous types (p = 0.688) or between the hyperintensity and hypointensity types (p = 0.757). In the atezolizumab plus bevacizumab group, the heterogeneous type had significantly shorter PFS than the homogenous type (p = 0.007), and the hyperintensity type had significantly shorter PFS than the hypointensity type (p = 0.012). Conclusions: The hepatobiliary phase of EOB-MRI was useful for predicting the therapeutic effect of atezolizumab plus bevacizumab therapy on unresectable HCC.
On Optimal Barium Promoter Content in a Cobalt Catalyst for Ammonia Synthesis
Authors: Tarka Aleksandra , Zybert Magdalena , Ronduda Hubert , Patkowski Wojciech , Mierzwa Bogusław , Kępiński Leszek , Raróg-Pilecka Wioletta
Published: February 2022

High priority in developing an efficient cobalt catalyst for ammonia synthesis involves optimizing its composition in terms of the content of promoters. In this work, a series of cobalt catalysts doubly promoted with cerium and barium was prepared and tested in ammonia synthesis (H2/N2 = 3, 6.3 MPa, 400 °C). Barium content was studied in the range of 0–2.6 mmol gCo−1. Detailed characterization studies by nitrogen physisorption, SEM-EDX, XRPD, H2-TPR, and H2-TPD showed the impact of barium loading in CoCeBa catalysts on the physicochemical properties and activity of the catalysts. The most pronounced effect was observed in the development of the active phase surface, a differentiation of weakly and strongly binding sites on the catalyst surface and changes in cobalt surface activity (TOF). Barium content in the range of 1.1–1.6 mmol gCo−1 leads to obtaining a catalyst with the most favorable properties. Its excellent catalytic performance is ascribed to the appropriate Ba/Ce molar ratio, i.e., greater than unity, which results in not only a structural promotion of barium, but also a modifying action associated with the in-situ formation of the BaCeO3 phase.
Hematopoietic Cells from Pluripotent Stem Cells: Hope and Promise for the Treatment of Inherited Blood Disorders
Authors: Rao Ilaria , Crisafulli Laura , Paulis Marianna , Ficara Francesca
Published: February 2022

Inherited blood disorders comprise a large spectrum of diseases due to germline mutations in genes with key function in the hematopoietic system; they include immunodeficiencies, anemia or metabolic diseases. For most of them the only curative treatment is bone marrow transplantation, a procedure associated to severe complications; other therapies include red blood cell and platelet transfusions, which are dependent on donor availability. An alternative option is gene therapy, in which the wild-type form of the mutated gene is delivered into autologous hematopoietic stem cells using viral vectors. A more recent therapeutic perspective is gene correction through CRISPR/Cas9-mediated gene editing, that overcomes safety concerns due to insertional mutagenesis and allows correction of base substitutions in large size genes difficult to incorporate into vectors. However, applying this technique to genomic disorders caused by large gene deletions is challenging. Chromosomal transplantation has been proposed as a solution, using a universal source of wild-type chromosomes as donor, and induced pluripotent stem cells (iPSCs) as acceptor. One of the obstacles to be addressed for translating PSC research into clinical practice is the still unsatisfactory differentiation into transplantable hematopoietic stem or mature cells. We provide an overview of the recent progresses in this field and discuss challenges and potential of iPSC-based therapies for the treatment of inherited blood disorders.