bluuebunny/crossref_metadata_2025 huggingface dataset:
The 2019 Philippine UHC Act, Pandemic Management and Implementation Implications in a Post-COVID-19 World: A Content Analysis
Authors: Bautista Maria Cristina G. , Acacio-Claro Paulyn Jean , Mendoza Nori Benjamin , Pulmano Christian , Estuar Maria Regina Justina , Dayrit Manuel M. , Festin Vincent Edward , Valera Madeleine , Sugon Quirino , Villamor Dennis Andrew
Published: August 2022

The 2019 Philippine Universal Health Care Act (Republic Act 11223) was set for implementation in January 2020 when disruptions brought on by the pandemic occurred. Will the provisions of the new UHC Act for an improved health system enable agile responses to forthcoming shocks, such as this COVID-19 pandemic? A content analysis of the 2019 Philippine UHC Act can identify neglected and leverage areas for systems’ improvement in a post-pandemic world. While content or document analysis is commonly undertaken as part of scoping or systematic reviews of a qualitative nature, quantitative analyses using a two-way mixed effects, consistency, multiple raters type of intraclass correlation coefficient (ICC) were applied to check for reliability and consistency of agreement among the study participants in the manual tagging of UHC components in the legislation. The intraclass correlation reflected the individuals’ consistency of agreement with significant reliability (0.939, p < 0.001). The assessment highlighted a centralized approach to implementation, which can set aside the crucial collaborations and partnerships demonstrated and developed during the pandemic. The financing for local governments was strengthened with a new ruling that could alter UHC integration tendencies. A smarter allocation of tax-based financing sources, along with strengthened information and communications systems, can confront issues of trust and accountability, amidst the varying capacities of agents and systems.
Integrating Post-Processing Kinematic (PPK)–Structure-from-Motion (SfM) with Unmanned Aerial Vehicle (UAV) Photogrammetry and Digital Field Mapping for Structural Geological Analysis
Authors: Cirillo Daniele , Cerritelli Francesca , Agostini Silvano , Bello Simone , Lavecchia Giusy , Brozzetti Francesco
Published: August 2022

We studied some exposures of the Roccacaramanico Conglomerate (RCC), a calcareous-clastic mega-bed intercalated within the Late Messinian–Early Pliocene pelitic succession of the La Queglia and Maiella tectonic units (central Apennines). The outcrops, localized in the overturned limb of a kilometric-scale syncline, show a complex array of fractures, including multiple systems of closely spaced cleavages, joints, and mesoscopic faults, which record the progressive deformation associated with the Late Pliocene thrusting. Due to the extent of the investigated sites and a large amount of data to collect, we applied a multi-methodology survey technique integrating unmanned aerial vehicle (UAV) technologies and digital mapping in the field. We reconstructed the 3D digital outcrop model of the RCC in the type area and defined the 3D pattern of fractures and their time–space relationships. The field survey played a pivotal role in determining the various sets of structures, their kinematics, the associated displacements, and relative chronology. The results unveiled the investigated area’s tectonic evolution and provide a deformation model that could be generalized in similar tectonic contexts. Furthermore, the methodology allows for evaluating the reliability of the applied remote survey techniques (i.e., using UAV) compared to those based on the direct measurements of structures using classic devices. Our purpose was to demonstrate that our multi-methodology approach can describe the tectonic evolution of the study area, providing consistent 3D data and using a few ground control points. Finally, we propose two alternative working methods and discuss their different fields of application.
MicroRNA-7a2 Contributes to Estrogen Synthesis and Is Modulated by FSH via the JNK Signaling Pathway in Ovarian Granulosa Cells
Authors: Li Liuhui , Zhang Jinglin , Lu Chenyang , Wang Bingjie , Guo Jiajia , Zhang Haitong , Cui Sheng
Published: August 2022

MicroRNA-7a2 (miR-7a2) plays fundamental roles in the female reproductive axis, and estrogen is indispensable for maintaining ovary function. However, the interaction between miR-7a2 and ovarian function is unclear. The present study aimed to determine whether and how miR-7a2 functions in estrogen synthesis. Firstly, the results verified that miR-7a was highly expressed in ovarian granulosa cells. The knockout (KO) of miR-7a2 caused infertility and abnormal ovarian function in mice. Concomitantly, the Cyp19a1 expression and estrogen synthesis were significantly inhibited, which was validated in primary granulosa cells. The mice transplanted with miR-7a2 KO ovaries showed similar results; however, estrogen supplementation reversed infertility. In the in vitro experiment, follicle-stimulating hormone (FSH) significantly improved the expression of miR-7a and Cyp19a1 and the synthesis of estrogen. However, the miR-7a2 KO markedly reversed the function of FSH. Also, FSH upregulated miR-7a by activating the (c-Jun N-terminal kinase) JNK signaling pathway. In addition, Golgi apparatus protein 1 (Glg1) was shown to be the target gene of miR-7a2. These findings indicated that miR-7a2 is essential for ovarian functions with respect to estrogen synthesis through the targeted inhibition of the expression of Glg1 and then promoting Cyp19a1 expression; the physiological process was positively regulated by FSH via the JNK signaling pathway in granulosa cells.
Downregulation of IL-8 and IL-10 by the Activation of Ca2+-Activated K+ Channel KCa3.1 in THP-1-Derived M2 Macrophages
Authors: Ohya Susumu , Matsui Miki , Kajikuri Junko , Kito Hiroaki , Endo Kyoko
Published: August 2022

THP-1-differentiated macrophages are useful for investigating the physiological significance of tumor-associated macrophages (TAMs). In the tumor microenvironment (TME), TAMs with the M2-like phenotype play a critical role in promoting cancer progression and metastasis by inhibiting the immune surveillance system. We examined the involvement of Ca2+-activated K+ channel KCa3.1 in TAMs in expressing pro-tumorigenic cytokines and angiogenic growth factors. In THP-1-derived M2 macrophages, the expression levels of IL-8 and IL-10 were significantly decreased by treatment with the selective KCa3.1 activator, SKA-121, without changes in those of VEGF and TGF-β1. Furthermore, under in vitro experimental conditions that mimic extracellular K+ levels in the TME, IL-8 and IL-10 levels were both significantly elevated, and these increases were reversed by combined treatment with SKA-121. Among several signaling pathways potentially involved in the transcriptional regulation of IL-8 and IL-10, respective treatments with ERK and JNK inhibitors significantly repressed their transcriptions, and treatment with SKA-121 significantly reduced the phosphorylated ERK, JNK, c-Jun, and CREB levels. These results strongly suggest that the KCa3.1 activator may suppress IL-10-induced tumor immune surveillance escape and IL-8-induced tumorigenicity and metastasis by inhibiting their production from TAMs through ERK-CREB and JNK-c-Jun cascades.
Targeting of a Conserved Epitope in Mouse and Human GPVI Differently Affects Receptor Function
Authors: Navarro Stefano , Starke Andreas , Heemskerk Johan W. M. , Kuijpers Marijke J. E. , Stegner David , Nieswandt Bernhard
Published: August 2022

Glycoprotein (GP) VI is the major platelet collagen receptor and a promising anti-thrombotic target. This was first demonstrated in mice using the rat monoclonal antibody JAQ1, which completely blocks the Collagen-Related Peptide (CRP)-binding site on mouse GPVI and efficiently inhibits mouse platelet adhesion, activation and aggregation on collagen. Here, we show for the first time that JAQ1 cross-reacts with human GPVI (huGPVI), but not with GPVI in other tested species, including rat, rabbit, guinea pig, swine, and dog. We further demonstrate that JAQ1 differently modulates mouse and human GPVI function. Similar to its effects on mouse GPVI (mGPVI), JAQ1 inhibits CRP-induced activation in human platelets, whereas, in stark contrast to mouse GPVI, it does not inhibit the adhesion, activation or aggregate formation of human platelets on collagen, but causes instead an increased response. This effect was also seen with platelets from newly generated human GPVI knockin mice (hGP6tg/tg). These results indicate that the binding of JAQ1 to a structurally conserved epitope in GPVI differently affects its function in human and mouse platelets.
High-Contrast Stimulation Potentiates the Neurotrophic Properties of Müller Cells and Suppresses Their Pro-Inflammatory Phenotype
Authors: Zloh Miloslav , Kutilek Patrik , Stofkova Andrea
Published: August 2022

High-contrast visual stimulation promotes retinal regeneration and visual function, but the underlying mechanism is not fully understood. Here, we hypothesized that Müller cells (MCs), which express neurotrophins such as brain-derived neurotrophic factor (BDNF), could be key players in this retinal plasticity process. This hypothesis was tested by conducting in vivo and in vitro high-contrast stimulation of adult mice and MCs. Following stimulation, we examined the expression of BDNF and its inducible factor, VGF, in the retina and MCs. We also investigated the alterations in the expression of VGF, nuclear factor kappa B (NF-κB) and pro-inflammatory mediators in MCs, as well as their capacity to proliferate and develop a neurogenic or reactive gliosis phenotype after high-contrast stimulation and treatment with BDNF. Our results showed that high-contrast stimulation upregulated BDNF levels in MCs in vivo and in vitro. The additional BDNF treatment significantly augmented VGF production in MCs and their neuroprotective features, as evidenced by increased MC proliferation, neurodifferentiation, and decreased expression of the pro-inflammatory factors and the reactive gliosis marker GFAP. These results demonstrate that high-contrast stimulation activates the neurotrophic and neuroprotective properties of MCs, suggesting their possible direct involvement in retinal neuronal survival and improved functional outcomes in response to visual stimulation.
Beyond NMDA Receptors: Homeostasis at the Glutamate Tripartite Synapse and Its Contributions to Cognitive Dysfunction in Schizophrenia
Authors: Bauminger Hagar , Gaisler-Salomon Inna
Published: August 2022

Cognitive deficits are core symptoms of schizophrenia but remain poorly addressed by dopamine-based antipsychotic medications. Glutamate abnormalities are implicated in schizophrenia-related cognitive deficits. While the role of the NMDA receptor has been extensively studied, less attention was given to other components that control glutamate homeostasis. Glutamate dynamics at the tripartite synapse include presynaptic and postsynaptic components and are tightly regulated by neuron–astrocyte crosstalk. Here, we delineate the role of glutamate homeostasis at the tripartite synapse in schizophrenia-related cognitive dysfunction. We focus on cognitive domains that can be readily measured in humans and rodents, i.e., working memory, recognition memory, cognitive flexibility, and response inhibition. We describe tasks used to measure cognitive function in these domains in humans and rodents, and the relevance of glutamate alterations in these domains. Next, we delve into glutamate tripartite synaptic components and summarize findings that implicate the relevance of these components to specific cognitive domains. These collective findings indicate that neuron–astrocyte crosstalk at the tripartite synapse is essential for cognition, and that pre- and postsynaptic components play a critical role in maintaining glutamate homeostasis and cognitive well-being. The contribution of these components to cognitive function should be considered in order to better understand the role played by glutamate signaling in cognition and develop efficient pharmacological treatment avenues for schizophrenia treatment-resistant symptoms.
Nanomaterials Used in Fluorescence Polarization Based Biosensors
Authors: Zhang Yingqi , Tang Howyn , Chen Wei , Zhang Jin
Published: August 2022

Fluorescence polarization (FP) has been applied in detecting chemicals and biomolecules for early-stage diagnosis, food safety analyses, and environmental monitoring. Compared to organic dyes, inorganic nanomaterials such as quantum dots have special fluorescence properties that can enhance the photostability of FP-based biosensing. In addition, nanomaterials, such as metallic nanoparticles, can be used as signal amplifiers to increase fluorescence polarization. In this review paper, different types of nanomaterials used in in FP-based biosensors have been reviewed. The role of each type of nanomaterial, acting as a fluorescent element and/or the signal amplifier, has been discussed. In addition, the advantages of FP-based biosensing systems have been discussed and compared with other fluorescence-based techniques. The integration of nanomaterials and FP techniques allows biosensors to quickly detect analytes in a sensitive and cost-effective manner and positively impact a variety of different fields including early-stage diagnoses.
Effects of MICU1-Mediated Mitochondrial Calcium Uptake on Energy Metabolism and Quality of Vitrified-Thawed Mouse Metaphase II Oocytes
Authors: Lan Tianyang , Zhang Kang , Lin Feifei , He Qifu , Wu Shenghui , Xu Zhiming , Zhang Yong , Quan Fusheng
Published: August 2022

Background: Oocyte vitrification has been widely used in the treatment of infertility and fertility preservation. However, vitrification-induced mitochondrial damage adversely affects oocyte development. Several studies have reported that mitochondrial calcium uptake protein 1 (MICU1) regulates the uptake of mitochondrial calcium by the mitochondrial calcium uniporter (MCU) and subsequently controls aerobic metabolism and oxidative stress in mitochondria, but research considering oocytes remains unreported. We evaluated whether the addition of MICU1 modulators enhances mitochondrial activity, pyruvate metabolism, and developmental competence after warming of MII oocytes. Methods: Retrieved MII oocytes of mice were classified as vitrified or control groups. After thawing, oocytes of vitrified group were cultured with or without DS16570511 (MICU1 inhibitor) and MCU-i4 (MICU1 activator) for 2 h. Results: Mitochondrial Ca2+ concentration, pyruvate dephosphorylation level, and MICU1 expression of MII oocytes were significantly increased after vitrification. These phenomena were further exacerbated by the addition of MCU-i4 and reversed by the addition of DS16570511 after warming. However, the mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) in vitrified-warmed MII oocytes drop significantly after vitrification, which was improved after MCU-i4 treatment and decreased significantly after DS16570511 treatment. The vitrification process was able to elicit a development competence reduction. After parthenogenetic activation, incubation of the thawed oocytes with MCU-i4 did not alter the cleavage and blastocyst rates. Moreover, incubation of the thawed oocytes with DS16570511 reduced the cleavage and blastocyst rates. Conclusions: MICU1-mediated increasing mitochondrial calcium uptake after vitrification of the MII oocytes promoted the pyruvate oxidation, and this process may maintain oocyte development competence by compensating for the consumption of ATP under stress state.
Lipolysis-Stimulated Lipoprotein Receptor Acts as Sensor to Regulate ApoE Release in Astrocytes
Authors: Herzine Ameziane , Sekkat Ghita , Kaminski Sandra , Calcagno Gaetano , Boschi-Muller Sandrine , Safi Hela , Corbier Catherine , Siest Sophie , Claudepierre Thomas , Yen Frances T.
Published: August 2022

Astroglia play an important role, providing de novo synthesized cholesterol to neurons in the form of ApoE-lipidated particles; disruption of this process can increase the risk of Alzheimer’s disease. We recently reported that glia-specific suppression of the lipolysis-stimulated lipoprotein receptor (LSR) gene leads to Alzheimer’s disease-like memory deficits. Since LSR is an Apo-E lipoprotein receptor, our objective of this study was to determine the effect of LSR expression modulation on cholesterol and ApoE output in mouse astrocytes expressing human ApoE3. qPCR analysis showed that siRNA-mediated lsr knockdown significantly increased expression of the genes involved in cholesterol synthesis, secretion, and metabolism. Analysis of media and lipoprotein fractions showed increased cholesterol and lipidated ApoE output in HDL-like particles. Further, lsr expression could be upregulated when astrocytes were incubated 5 days in media containing high levels (two-fold) of lipoprotein, or after 8 h treatment with 1 µM LXR agonist T0901317 in lipoprotein-deficient media. In both conditions of increased lsr expression, the ApoE output was repressed or unchanged despite increased abca1 mRNA levels and cholesterol production. We conclude that LSR acts as a sensor of lipoprotein content in the medium and repressor of ApoE release, while ABCA1 drives cholesterol efflux, thereby potentially affecting cholesterol load, ApoE lipidation, and limiting cholesterol trafficking towards the neuron.
Identification of Novel Inhibitors Targeting SGK1 via Ensemble-Based Virtual Screening Method, Biological Evaluation and Molecular Dynamics Simulation
Authors: Zhang Hui , Shen Chen , Zhang Hong-Rui , Qi Hua-Zhao , Hu Mei-Ling , Luo Qing-Qing
Published: August 2022

Serum and glucocorticoid-regulated kinase 1 (SGK1), as a serine threonine protein kinase of the AGC family, regulates different enzymes, transcription factors, ion channels, transporters, and cell proliferation and apoptosis. Inhibition of SGK1 is considered as a valuable approach for the treatment of various metabolic diseases. In this investigation, virtual screening methods, including pharmacophore models, Bayesian classifiers, and molecular docking, were combined to discover novel inhibitors of SGK1 from the database with 29,158 compounds. Then, the screened compounds were subjected to ADME/T, PAINS and drug-likeness analysis. Finally, 28 compounds with potential inhibition activity against SGK1 were selected for biological evaluation. The kinase inhibition activity test revealed that among these 28 hits, hit15 exhibited the highest inhibition activity against SGK1, which gave 44.79% inhibition rate at the concentration of 10 µM. In order to further investigate the interaction mechanism of hit15 and SGK1 at simulated physiological conditions, a molecular dynamics simulation was performed. The molecular dynamics simulation demonstrated that hit15 could bind to the active site of SGK1 and form stable interactions with key residues, such as Tyr178, ILE179, and VAL112. The binding free energy of the SGK1-hit15 was −48.90 kJ mol−1. Therefore, the identified hit15 with novel scaffold may be a promising lead compound for development of new SGK1 inhibitors for various diseases treatment.
Functional Precision Oncology: The Next Frontier to Improve Glioblastoma Outcome?
Authors: Panovska Dena , De Smet Frederik
Published: August 2022

Glioblastoma remains the most malignant and intrinsically resistant brain tumour in adults. Despite intensive research over the past few decades, through which numerous potentially druggable targets have been identified, virtually all clinical trials of the past 20 years have failed to improve the outcome for the vast majority of GBM patients. The observation that small subgroups of patients displayed a therapeutic response across several unsuccessful clinical trials suggests that the GBM patient population probably consists of multiple subgroups that probably all require a distinct therapeutic approach. Due to extensive inter- and intratumoral heterogeneity, assigning the right therapy to each patient remains a major challenge. Classically, bulk genetic profiling would be used to identify suitable therapies, although the success of this approach remains limited due to tumor heterogeneity and the absence of direct relationships between mutations and therapy responses in GBM. An attractive novel strategy aims at implementing methods for functional precision oncology, which refers to the evaluation of treatment efficacies and vulnerabilities of (ex vivo) living tumor cells in a highly personalized way. Such approaches are currently being implemented for other cancer types by providing rapid, translatable information to guide patient-tailored therapeutic selections. In this review, we discuss the current state of the art of transforming technologies, tools and challenges for functional precision oncology and how these could improve therapy selection for GBM patients.
HDAC8-Selective Inhibition by PCI-34051 Enhances the Anticancer Effects of ACY-241 in Ovarian Cancer Cells
Authors: Kim Ji Yoon , Han Seung Yoon , Yoo Jung , Kim Go Woon , Jeon Yu Hyun , Lee Sang Wu , Park Jongsun , Kwon So Hee
Published: August 2022

HDAC6 is overexpressed in ovarian cancer and is known to be correlated with tumorigenesis. Accordingly, ACY-241, a selective HDAC6 inhibitor, is currently under clinical trial and has been tested in combination with various drugs. HDAC8, another member of the HDAC family, has recently gained attention as a novel target for cancer therapy. Here, we evaluated the synergistic anticancer effects of PCI-34051 and ACY-241 in ovarian cancer. Among various ovarian cancer cells, PCI-34051 effectively suppresses cell proliferation in wild-type p53 ovarian cancer cells compared with mutant p53 ovarian cancer cells. In ovarian cancer cells harboring wild-type p53, PCI-34051 in combination with ACY-241 synergistically represses cell proliferation, enhances apoptosis, and suppresses cell migration. The expression of pro-apoptotic proteins is synergistically upregulated, whereas the expressions of anti-apoptotic proteins and metastasis-associated proteins are significantly downregulated in combination treatment. Furthermore, the level of acetyl-p53 at K381 is synergistically upregulated upon combination treatment. Overall, co-inhibition of HDAC6 and HDAC8 through selective inhibitors synergistically suppresses cancer cell proliferation and metastasis in p53 wild-type ovarian cancer cells. These results suggest a novel approach to treating ovarian cancer patients and the therapeutic potential in developing HDAC6/8 dual inhibitors.
An Extensive Study of Phenol Red Thread as a Novel Non-Invasive Tear Sampling Technique for Proteomics Studies: Comparison with Two Commonly Used Methods
Authors: Kecskeméti Gábor , Tóth-Molnár Edit , Janáky Tamás , Szabó Zoltán
Published: August 2022

Tear samples are considered in recent publications as easily, noninvasively collectible information sources for precision medicine. Their complex composition may aid the identification of biomarkers and the monitoring of the effectiveness of treatments for the eye and systemic diseases. Sample collection and processing are key steps in any analytical method, especially if subtle personal differences need to be detected. In this work, we evaluate the usability of a novel sample collection technique for human tear samples using phenol red threads (cotton thread treated with the pH indicator phenol red), which are efficiently used to measure tear volume in clinical diagnosis. The low invasiveness and low discomfort to the patients have already been demonstrated, but their applicability for proteomic sample collection has not yet been compared to other methods. We have shown, using various statistical approaches, the qualitative and quantitative differences in proteomic samples collected with this novel and two traditional methods using either glass capillaries or Schirmer’s paper strips. In all parameters studied, the phenol red threads proved to be equally or even more suitable than traditional methods. Based on detectability using different sampling methods, we have classified proteins in tear samples.
Delivery of Nucleotide Sugars to the Mammalian Golgi: A Very Well (un)Explained Story
Authors: Maszczak-Seneczko Dorota , Wiktor Maciej , Skurska Edyta , Wiertelak Wojciech , Olczak Mariusz
Published: August 2022

Nucleotide sugars (NSs) serve as substrates for glycosylation reactions. The majority of these compounds are synthesized in the cytoplasm, whereas glycosylation occurs in the endoplasmic reticulum (ER) and Golgi lumens, where catalytic domains of glycosyltransferases (GTs) are located. Therefore, translocation of NS across the organelle membranes is a prerequisite. This process is thought to be mediated by a group of multi-transmembrane proteins from the SLC35 family, i.e., nucleotide sugar transporters (NSTs). Despite many years of research, some uncertainties/inconsistencies related with the mechanisms of NS transport and the substrate specificities of NSTs remain. Here we present a comprehensive review of the NS import into the mammalian Golgi, which consists of three major parts. In the first part, we provide a historical view of the experimental approaches used to study NS transport and evaluate the most important achievements. The second part summarizes various aspects of knowledge concerning NSTs, ranging from subcellular localization up to the pathologies related with their defective function. In the third part, we present the outcomes of our research performed using mammalian cell-based models and discuss its relevance in relation to the general context.
Face Identification Using Data Augmentation Based on the Combination of DCGANs and Basic Manipulations
Authors: Ammar Sirine , Bouwmans Thierry , Neji Mahmoud
Published: August 2022

Recently, Deep Neural Networks (DNNs) have become a central subject of discussion in computer vision for a broad range of applications, including image classification and face recognition. Compared to existing conventional machine learning methods, deep learning algorithms have shown prominent performance with high accuracy and speed. However, they always require a large amount of data to achieve adequate robustness. Furthermore, additional samples are time-consuming and expensive to collect. In this paper, we propose an approach that combines generative methods and basic manipulations for image data augmentations and the FaceNet model with Support Vector Machine (SVM) for face recognition. To do so, the images were first preprocessed by a Deep Convolutional Generative Adversarial Net (DCGAN) to generate samples having realistic properties inseparable from those of the original datasets. Second, basic manipulations were applied on the images produced by DCGAN in order to increase the amount of training data. Finally, FaceNet was employed as a face recognition model. FaceNet detects faces using MTCNN, 128-D face embedding is computed to quantify each face, and an SVM was used on top of the embeddings for classification. Experiments carried out on the LFW and VGG image databases and ChokePoint video database demonstrate that the combination of basic and generative methods for augmentation boosted face recognition performance, leading to better recognition results.
SL: A Reference Smartness Level Scale for Smart Artifacts
Authors: Costa Nuno , Rodrigues Nuno , Seco Maria Alexandra , Pereira António
Published: August 2022

During the last two decades, many products, research projects and prototypes were announced with different characteristics and capabilities, all adopting the “smart” qualifier word. If a smartness property could not be defined simply as true or false, defining a suitable range was not an easy task. This issue led to the proposal of some classification models, frameworks and taxonomies for project classifications, but none of them provide a clear and pragmatic smartness scale able to classify smart artifacts and serve as a reference. This paper aims to propose a smartness scale to help research and non-research communities to better quantify and easily understand the features and autonomy of smart artifacts. The proposed smartness scale considers the main function of physical-device components in smart systems. The provided smartness scale is based on a uni-dimensional typology that defines 12 different smartness levels, created based on our definition of “smart artifact” and by following an evolutionary set of capabilities ranging from traceable-only and sensing-capable artifacts to autonomous, adaptable and self-driven artifacts. In order to show the feasibility of the proposed smartness scale, an analytic model was defined and applied to several research- and market-based artifacts tagged as smart in order to extract their smartness levels.
Synthesis, Characterization, Computational and Biological Activity of Some Schiff Bases and Their Fe, Cu and Zn Complexes
Authors: Al-Shboul Tareq M. A. , El-khateeb Mohammad , Obeidat Zaid H. , Ababneh Taher S. , Al-Tarawneh Suha S. , Al Zoubi Mazhar S. , Alshaer Walhan , Abu Seni Anas , Qasem Taqwa , Moriyama Hayato , Yoshida Yukihiro , Kitagawa Hiroshi , Jazzazi Taghreed M. A.
Published: August 2022

Four new symmetrical Schiff bases derived from 2,2′-diamino-6,6′-dibromo-4,4′-dimethyl-1,1′-biphenyl or 2,2′-diamino-4,4′-dimethyl-1,1′-biphenyl, and 3,5-dichloro- or 5-nitro-salicylaldehyde, were synthesized and reacted with copper-, iron- and zinc-acetate, producing the corresponding complexes. The Schiff bases and their metal complexes were characterized by 1H-, 13C-NMR, IR and UV-Vis spectroscopy and elemental analysis. The structures of one Schiff base and the two zinc complexes were resolved by X-ray structure determination. Density functional theory (DFT) calculations at the B3LYP/6-31G(d) level of the latter compounds were carried out to optimize and examine their molecular geometries. The biomedical applications of the Schiff bases and their complexes were investigated as anticancer or antimicrobial agents.
Functional Asymmetries Routing the Mating Behavior of the Rusty Grain Beetle, Cryptolestes ferrugineus (Stephens) (Coleoptera: Laemophloeidae)
Authors: Boukouvala Maria C. , Kavallieratos Nickolas G. , Canale Angelo , Benelli Giovanni
Published: August 2022

The rusty grain beetle, Cryptolestes ferrugineus (Stephens) (Coleoptera: Laemophloeidae), is a serious secondary pest of stored and processed food commodities. In the present study, we investigated the lateralization of males during courtship and mating, attempting to understand if it can be linked with a high likelihood of successful copulation. Most males exhibited left-biased (41%) approaches towards females, and turned 180° to their left, with 37% mating success. Right-biased males (i.e., approaching from the right and then turning 180°) were fewer than left-biased ones; 26% out of 34% managed to copulate with females. Only 9% out of 13% and 7% out of 11% of the back side- and front side-approaching males succeeded in mating, respectively. Directional asymmetries in approaching a potential mate, as well as the laterality of side-biased turning 180°, significantly affected male copulation success, with left-biased males achieving higher mating success if compared to right-biased males. Copula duration was significantly lower for left-biased-approaching males (1668.0 s) over the others (i.e., 1808.1, 1767.9 and 1746.9 for right-biased, front and back side-males, respectively). Left-biased males performed shorter copulation attempts and copula compared to right-biased males. Overall, our study adds basic knowledge to the lateralized behavioral displays during courtship and copula of C. ferrugineus.
The Immunohistochemical Assessment of Neoangiogenesis Factors in Squamous Cell Carcinomas and Their Precursors in the Skin
Authors: Daneluzzi Cloé , Seyed Jafari Seyed Morteza , Hunger Robert , Bossart Simon
Published: August 2022

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer. Well-limited forms can be easily treated with excision, but locally advanced cancers can, unfortunately, progress to metastasis. However, it is difficult to establish the prognosis for cutaneous squamous cell carcinoma and its potential to metastasize. Therefore, this study aimed to evaluate neoangiogenesis in cSCC, as it plays a major role in the dissemination of neoplasia. A literature review was performed on selected neoangiogenic factors (VEGF, ANG1/2, Notch1, CD31/34/105, EGF, etc.). Most of them, including VEGF, EGFR, and CD105, had more elevated levels in the advanced stages of the lesion. The same is true for Notch1, p53, and TGFβ, which are the most frequently mutated tumor suppressors in this type of skin cancer. In addition, the inhibition of some of these markers, using Ang1 analogs, inhibitors of EGFR, TRAF6, or combined inhibitors of EGFR and IGF-IR, may lead to a decrease in tumor size. In conclusion, this literature review identified diagnostic and prognostic markers, as well as possible factors that can be used for the targeted therapy of spinaliomas.
Lower Levels of ABO Anti-A and Anti-B of IgM, IgG and IgA Isotypes in the Serum but Not the Saliva of COVID-19 Convalescents
Authors: Matzhold Eva M. , Körmöczi Günther F. , Banfi Chiara , Schönbacher Marlies , Drexler-Helmberg Camilla , Steinmetz Ivo , Berghold Andrea , Schlenke Peter , Wagner Gabriel E. , Stoisser Anja , Kleinhappl Barbara , Mayr Wolfgang R. , Wagner Thomas
Published: August 2022

Individuals with ABO type O, naturally possessing anti-A and anti-B antibodies in their serum, are underrepresented among patients infected with SARS-CoV-2 compared with healthy controls. The ABO antibodies might play a role in the viral transmission. Therefore, we aimed to quantify anti-A/anti-B, including their subclasses IgM, IgG and IgA, in the serum and saliva of Caucasians (n = 187) after mild COVID-19 to compare them with individuals who had never been infected with SARS-CoV-2. Two samples were collected within two months after the diagnosis (median days: 44) and two months later. ABO antibodies were determined by flow cytometry. Additionally, total IgA in saliva and antibodies specific to SARS-CoV-2 were tested by ELISA. COVID-19 convalescents had significantly lower levels of anti-A/anti-B IgM, IgG and IgA in their serum than control subjects (p < 0.001). Interestingly, no significant differences were observed in saliva. ABO antibody levels remained stable over the period considered. No relation of ABO to the level of SARS-CoV-2-specific antibodies was observed. Total IgA was lower in convalescents than in controls (p = 0.038). Whereas ABO antibodies in the saliva may not contribute to the pathogenesis of COVID-19, individual pre-existing high serum concentrations of anti-A/anti-B may have a protective effect against SARS-CoV-2 infection.
Emerging Role of FAPI PET Imaging for the Assessment of Benign Bone and Joint Diseases
Authors: Dondi Francesco , Albano Domenico , Treglia Giorgio , Bertagna Francesco
Published: August 2022

Positron emission tomography/computed tomography (PET/CT) is a hybrid imaging modality that has recently experienced a wide increase in its use and applications [...]
The Anemia Stress Index—Anemia, Transfusions, and Mortality in Patients with Continuous Flow Ventricular Assist Devices
Authors: Shore Supriya , Hanff Thomas C. , Mazurek Jeremy A. , Fox Arieh , Tanna Monique S. , Grandin Edward W. , Zhang Robert , Wald Joyce , Peters Carli , Acker Michael A. , Atluri Pavan , Rame J. Eduardo , Goldberg Lee R. , Jessup Mariell , Margulies Kenneth B. , Birati Edo Y.
Published: August 2022

We aimed to identify a simple metric accounting for peri-procedural hemoglobin changes, independent of blood product transfusion strategies, and assess its correlation with outcomes in patients undergoing left ventricular assist device (LVAD) implantation We included consecutive patients undergoing LVAD implantation at a single center between 10/1/2008 and 6/1/2014. The anemia stress index (ASI), defined as the sum of number of packed red blood cells transfused and the hemoglobin changes after LVAD implantation, was calculated for each patient at 24 h, discharge, and 3 months after LVAD implantation. Our cohort included 166 patients (80.1% males, mean age 56.3 ± 15.6 years) followed up for a median of 12.3 months. Increases in ASI per unit were associated with a higher hazard for all-cause mortality and early RV failure. The associations between the ASI and all-cause mortality persisted after multivariable adjustment, irrespective of when it was calculated (adjusted HR of 1.11, 95% CI 1.03–1.20 per unit increase in ASI). Similarly, ASI at 24 h after implant was associated with early RV failure despite multivariable adjustment (OR 1.09, 95% CI 1.05–1.14). We present a novel metric, the ASI, that is correlated with an increased risk for all-cause mortality and early RV failure in LVAD recipients.
Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn’s Disease Patients on Ustekinumab
Authors: Chaparro María , Baston-Rey Iria , Fernández Salgado Estela , González García Javier , Ramos Laura , Diz-Lois Palomares María Teresa , Argüelles-Arias Federico , Iglesias Flores Eva , Cabello Mercedes , Rubio Iturria Saioa , Núñez Ortiz Andrea , Charro Mara , Ginard Daniel , Dueñas Sadornil Carmen , Merino Ochoa Olga , Busquets David , Iyo Eduardo , Gutiérrez Casbas Ana , Ramírez de la Piscina Patricia , Boscá-Watts Marta Maia , Arroyo Maite , García María José , Hinojosa Esther , Gordillo Jordi , Martínez Montiel Pilar , Velayos Jiménez Benito , Quílez Ivorra Cristina , Vázquez Morón Juan María , Huguet José María , González-Lama Yago , Muñagorri Santos Ana Isabel , Amo Víctor Manuel , Martín Arranz María Dolores , Bermejo Fernando , Martínez Cadilla Jesús , Rubín de Célix Cristina , Fradejas Salazar Paola , López San Román Antonio , Jiménez Nuria , García-López Santiago , Figuerola Anna , Jiménez Itxaso , Martínez Cerezo Francisco José , Taxonera Carlos , Varela Pilar , de Francisco Ruth , Monfort David , Molina Arriero Gema , Hernández-Camba Alejandro , García Alonso Francisco Javier , Van Domselaar Manuel , Pajares-Villarroya Ramón , Núñez Alejandro , Rodríguez Moranta Francisco , Marín-Jiménez Ignacio , Robles Alonso Virginia , Martín Rodríguez María del Mar , Camo-Monterde Patricia , García Tercero Iván , Navarro-Llavat Mercedes , García Lara Arias , Hervías Cruz Daniel , Kloss Sebastian , Passey Alun , Novella Cynthia , Vispo Eugenia , Barreiro-de Acosta Manuel , Gisbert Javier P.
Published: August 2022

Ustekinumab has shown efficacy in Crohn’s Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients’ data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index ≤ 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission.
Fibrillatory Wave Amplitude Evolution during Persistent Atrial Fibrillation Ablation: Implications for Atrial Substrate and Fibrillation Complexity Assessment
Authors: Squara Fabien , Scarlatti Didier , Bun Sok-Sithikun , Moceri Pamela , Ferrari Emile , Meste Olivier , Zarzoso Vicente
Published: August 2022

Background. Fibrillatory Wave Amplitude (FWA) has been described as a non-invasive marker of atrial fibrillation (AF) complexity, and it predicts catheter ablation outcome. However, the actual determinants of FWA remain incompletely understood. Objective. To assess the respective implications of anatomical atrial substrate and AF spectral characteristics for FWA. Methods. Persistent AF patients undergoing radiofrequency catheter ablation were included. FWA was measured on 1-min ECG by TQ concatenation in Lead I, V1, V2, and V5 at baseline and immediately before AF termination. FWA evolution during ablation was compared to that of AF dominant frequency (DF) measured by Independent Component Analysis on 12-lead ECG. FWA was compared to the extent of endocardial low-voltage areas (LVA I < 10%; II 10–20%; III 20–30%; IV > 30%), to the surface of healthy left atrial tissue, and to P-wave amplitude in sinus rhythm. The predictive value of FWA for AF recurrence during follow-up was assessed. Results. We included 29 patients. FWA remained stable along ablation procedure with comparable values at baseline and before AF termination (Lead I p = 0.54; V1 p = 0.858; V2 p = 0.215; V5 p = 0.14), whereas DF significantly decreased (5.67 ± 0.68 vs. 4.95 ± 0.58 Hz, p < 0.001). FWA was higher in LVA-I than in LVA-II, -III, and -IV in Lead I and V5 (p = 0.02 and p = 0.01). FWA in V5 was strongly correlated with the surface of healthy left atrial tissue (R = 0.786; p < 0.001). FWA showed moderate to strong correlation to P-wave amplitude in all leads. Finally, FWA did not predict AF recurrence after a follow-up of 23.3 ± 9.8 months. Conclusions. These findings suggest that FWA is unrelated to AF complexity but is mainly determined by the amount of viable atrial myocytes. Therefore, FWA should only be referred as a marker of atrial tissue pathology.
The Association between Early Changes in Neutrophil-Lymphocyte Ratio and Survival in Patients Treated with Immunotherapy
Authors: Guven Deniz Can , Sahin Taha Koray , Erul Enes , Cakir Ibrahim Yahya , Ucgul Enes , Yildirim Hasan Cagri , Aktepe Oktay Halit , Erman Mustafa , Kilickap Saadettin , Aksoy Sercan , Yalcin Suayib
Published: August 2022

Dynamic changes in the blood-based biomarkers could be used as a prognostic biomarker in patients treated with immune checkpoint inhibitors (ICIs), although the data are limited. We evaluated the association between the neutrophil–lymphocyte ratio (NLR) and early NLR changes with survival in ICI-treated patients. We retrospectively evaluated the data of 231 patients with advanced-stage cancer. We recorded baseline clinical characteristics, baseline NLR and fourth-week NLR changes, and survival data. A compound prognostic score, the NLR2-CEL score, was developed with the following parameters: baseline NLR (<5 vs. ≥5), ECOG status (0 vs. ≥1), Charlson Comorbidity Index (CCI, <9 vs. ≥9), LDH (N vs. ≥ULN), and fourth-week NLR change (10% or over NLR increase). In the multivariable analyses, higher NLR (HR: 1.743, p = 0.002), 10% or over NLR increase in the fourth week of treatment (HR: 1.807, p = 0.001), higher ECOG performance score (HR: 1.552, p = 0.006), higher LDH levels (HR: 1.454, p = 0.017), and higher CCI (HR: 1.400, p = 0.041) were associated with decreased OS. Compared to patients with the lowest scores, patients in the highest score group had significantly lower OS (HR: 7.967, 95% CI: 3.531–17.979, p < 0.001) and PFS. The composite score had moderate success for survival prediction, with an AUC of 0.702 (95% CI: 0.626–0.779, p < 0.001). We observed significantly lower survival in patients with higher baseline NLR values and increased NLR values under treatment.
Myocardial Injuries in COVID-19: More Questions Than Answers
Authors: Bardaji Alfredo
Published: August 2022

At the end of 2019, the SARS-CoV-2 virus was reported to be responsible for the cases of pneumonia that had begun to appear a few months earlier in the Wuhan province of China [...]
Comparison between Automatic and Semiautomatic System for the 3D Echocardiographic Multiparametric Evaluation of RV Function and Dimension
Authors: Penso Marco , Ranalletta Remo Antonio , Pepi Mauro , Garlaschè Anna , Ali Sarah Ghulam , Fusini Laura , Mantegazza Valentina , Muratori Manuela , Maragna Riccardo , Tamborini Gloria
Published: August 2022

Background: The right ventricle (RV) plays a pivotal role in cardiovascular diseases and 3-dimensional echocardiography (3DE) has gained acceptance for the evaluation of RV volumes and function. Recently, a new artificial intelligence (AI)–based automated 3DE software for RV evaluation has been proposed and validated against cardiac magnetic resonance. The aims of this study were three-fold: (i) feasibility of the AI-based 3DE RV quantification, (ii) comparison with the semi-automatic 3DE method and (iii) assessment of 2-dimensional echocardiography (2DE) and strain measurements obtained automatically. Methods: A total of 203 subject (122 normal and 81 patients) underwent a 2DE and both the semi-automatic and automatic 3DE methods for Doppler standard, RV volumes and ejection fraction (RVEF) measurements. Results: The automatic 3DE method was highly feasible, faster than 2DE and semi-automatic 3DE and data obtained were comparable with traditional measurements. Both in normal subjects and patients, the RVEF was similar to the two 3DE methods and 2DE and strain measurements obtained by the automated system correlated very well with the standard 2DE and strain ones. Conclusions: results showed that rapid analysis and excellent reproducibility of AI-based 3DE RV analysis supported the routine adoption of this automated method in the daily clinical workflow.
Second-Generation Antipsychotics’ Effectiveness and Tolerability: A Review of Real-World Studies in Patients with Schizophrenia and Related Disorders
Authors: Fabrazzo Michele , Cipolla Salvatore , Camerlengo Alessio , Perris Francesco , Catapano Francesco
Published: August 2022

Despite methodological limitations, real-world studies might support clinicians by broadening the knowledge of antipsychotics’ (APs) effectiveness and tolerability in different clinical scenarios and complement clinical trials. We conducted an extensive literature search in the PubMed database to evaluate the effectiveness and tolerability profiles of second-generation antipsychotics (SGAs) from real-world studies to aid clinicians and researchers in selecting the proper treatment for patients with schizophrenia and related disorders. The present review evidenced that SGAs demonstrated superior effectiveness over first-generation antipsychotics (FGAs) in relapse-free survival and psychiatric hospitalization rate and for treating negative symptoms. Persistence and adherence to therapy were higher in SGAs than FGAs. Most studies concluded that switching to long-acting injectables (LAIs) was significantly associated with a lower treatment failure rate than monotherapy with oral SGAs. Considerable improvements in general functionality, subjective well-being, and total score on global satisfaction tests, besides improved personal and social performance, were reported in some studies on patients treated with LAI SGAs. Clozapine was also associated with the lowest rates of treatment failure and greater effectiveness over the other SGAs, although with more severe side effects. Effectiveness on primary negative symptoms and cognitive deficits was rarely measured in these studies. Based on the data analyzed in the present review, new treatments are needed with better tolerability and improved effectiveness for negative, affective, and cognitive symptoms.