bluuebunny/crossref_metadata_2025 huggingface dataset:
Reliability of IMU-Derived Static Balance Parameters in Neurological Diseases
Authors: Hansen Clint , Beckbauer Maximilian , Romijnders Robbin , Warmerdam Elke , Welzel Julius , Geritz Johanna , Emmert Kirsten , Maetzler Walter
Published: March 2021

Static balance is a commonly used health measure in clinical practice. Usually, static balance parameters are assessed via force plates or, more recently, with inertial measurement units (IMUs). Multiple parameters have been developed over the years to compare patient groups and understand changes over time. However, the day-to-day variability of these parameters using IMUs has not yet been tested in a neurogeriatric cohort. The aim of the study was to examine day-to-day variability of static balance parameters of five experimental conditions in a cohort of neurogeriatric patients using data extracted from a lower back-worn IMU. A group of 41 neurogeriatric participants (age: 78 ± 5 years) underwent static balance assessment on two occasions 12–24 h apart. Participants performed a side-by-side stance, a semi-tandem stance, a tandem stance on hard ground with eyes open, and a semi-tandem assessment on a soft surface with eyes open and closed for 30 s each. The intra-class correlation coefficient (two-way random, average of the k raters’ measurements, ICC2, k) and minimal detectable change at a 95% confidence level (MDC95%) were calculated for the sway area, velocity, acceleration, jerk, and frequency. Velocity, acceleration, and jerk were calculated in both anterior-posterior (AP) and medio-lateral (ML) directions. Nine to 41 participants could successfully perform the respective balance tasks. Considering all conditions, acceleration-related parameters in the AP and ML directions gave the highest ICC results. The MDC95% values for all parameters ranged from 39% to 220%, with frequency being the most consistent with values of 39–57%, followed by acceleration in the ML (43–55%) and AP direction (54–77%). The present results show moderate to poor ICC and MDC values for IMU-based static balance assessment in neurogeriatric patients. This suggests a limited reliability of these tasks and parameters, which should induce a careful selection of potential clinically relevant parameters.
The Role of Circulating Biomarkers in Peripheral Arterial Disease
Authors: Saenz-Pipaon Goren , Martinez-Aguilar Esther , Orbe Josune , González Miqueo Arantxa , Fernandez-Alonso Leopoldo , Paramo Jose Antonio , Roncal Carmen
Published: March 2021

Peripheral arterial disease (PAD) of the lower extremities is a chronic illness predominantly of atherosclerotic aetiology, associated to traditional cardiovascular (CV) risk factors. It is one of the most prevalent CV conditions worldwide in subjects >65 years, estimated to increase greatly with the aging of the population, becoming a severe socioeconomic problem in the future. The narrowing and thrombotic occlusion of the lower limb arteries impairs the walking function as the disease progresses, increasing the risk of CV events (myocardial infarction and stroke), amputation and death. Despite its poor prognosis, PAD patients are scarcely identified until the disease is advanced, highlighting the need for reliable biomarkers for PAD patient stratification, that might also contribute to define more personalized medical treatments. In this review, we will discuss the usefulness of inflammatory molecules, matrix metalloproteinases (MMPs), and cardiac damage markers, as well as novel components of the liquid biopsy, extracellular vesicles (EVs), and non-coding RNAs for lower limb PAD identification, stratification, and outcome assessment. We will also explore the potential of machine learning methods to build prediction models to refine PAD assessment. In this line, the usefulness of multimarker approaches to evaluate this complex multifactorial disease will be also discussed.
Understanding the Molecular Basis of 5-HT4 Receptor Partial Agonists through 3D-QSAR Studies
Authors: Castro-Alvarez Alejandro , Chávez-Ángel Emigdio , Nelson Ronald
Published: March 2021

Alzheimer’s disease (AD) is a neurodegenerative disorder whose prevalence has an incidence in senior citizens. Unfortunately, current pharmacotherapy only offers symptom relief for patients with side effects such as bradycardia, nausea, and vomiting. Therefore, there is a present need to provide other therapeutic alternatives for treatments for these disorders. The 5-HT4 receptor is an attractive therapeutic target since it has a potential role in central and peripheral nervous system disorders such as AD, irritable bowel syndrome, and gastroparesis. Quantitative structure-activity relationship analysis of a series of 62 active compounds in the 5-HT4 receptor was carried out in the present work. The structure-activity relationship was estimated using three-dimensional quantitative structure-activity relationship (3D-QSAR) techniques based on these structures’ field molecular (force and Gaussian field). The best force-field QSAR models achieve a value for the coefficient of determination of the training set of R2training = 0.821, and for the test set R2test = 0.667, while for Gaussian-field QSAR the training and the test were R2training = 0.898 and R2test = 0.695, respectively. The obtained results were validated using a coefficient of correlation of the leave-one-out cross-validation of Q2LOO = 0.804 and Q2LOO = 0.886 for force- and Gaussian-field QSAR, respectively. Based on these results, novel 5-HT4 partial agonists with potential biological activity (pEC50 8.209–9.417 for force-field QSAR and 9.111–9.856 for Gaussian-field QSAR) were designed. In addition, for the new analogues, their absorption, distribution, metabolism, excretion, and toxicity properties were also analyzed. The results show that these new derivatives also have reasonable pharmacokinetics and drug-like properties. Our findings suggest novel routes for the design and development of new 5-HT4 partial agonists.
Vitamin D Deficiency Induces Chronic Pain and Microglial Phenotypic Changes in Mice
Authors: Alessio Nicola , Belardo Carmela , Trotta Maria Consiglia , Paino Salvatore , Boccella Serena , Gargano Francesca , Pieretti Gorizio , Ricciardi Flavia , Marabese Ida , Luongo Livio , Galderisi Umberto , D’Amico Michele , Maione Sabatino , Guida Francesca
Published: March 2021

The bioactive form of vitamin D, 1,25-dihydroxyvitamin D (1,25D3), exerts immunomodulatory actions resulting in neuroprotective effects potentially useful against neurodegenerative and autoimmune diseases. In fact, vitamin D deficiency status has been correlated with painful manifestations associated with different pathological conditions. In this study, we have investigated the effects of vitamin D deficiency on microglia cells, as they represent the main immune cells responsible for early defense at central nervous system (CNS), including chronic pain states. For this purpose, we have employed a model of low vitamin D intake during gestation to evaluate possible changes in primary microglia cells obtained from postnatal day(P)2-3 pups. Afterwards, pain measurement and microglia morphological analysis in the spinal cord level and in brain regions involved in the integration of pain perception were performed in the parents subjected to vitamin D restriction. In cultured microglia, we detected a reactive—activated and proliferative—phenotype associated with intracellular reactive oxygen species (ROS) generation. Oxidative stress was closely correlated with the extent of DNA damage and increased β-galactosidase (B-gal) activity. Interestingly, the incubation with 25D3 or 1,25D3 or palmitoylethanolamide, an endogenous ligand of peroxisome proliferator-activated-receptor-alpha (PPAR-α), reduced most of these effects. Morphological analysis of ex-vivo microglia obtained from vitamin-D-deficient adult mice revealed an increased number of activated microglia in the spinal cord, while in the brain microglia appeared in a dystrophic phenotype. Remarkably, activated (spinal) or dystrophic (brain) microglia were detected in a prominent manner in females. Our data indicate that vitamin D deficiency produces profound modifications in microglia, suggesting a possible role of these cells in the sensorial dysfunctions associated with hypovitaminosis D.
Silencing of Sphingosine kinase 1 Affects Maturation Pathways in Mouse Neonatal Cardiomyocytes
Authors: Jozefczuk Ewelina , Szczepaniak Piotr , Guzik Tomasz Jan , Siedlinski Mateusz
Published: March 2021

Sphingosine kinase-1 (Sphk1) and its product, sphingosine-1-phosphate (S1P) are important regulators of cardiac growth and function. Numerous studies have reported that Sphk1/S1P signaling is essential for embryonic cardiac development and promotes pathological cardiac hypertrophy in adulthood. However, no studies have addressed the role of Sphk1 in postnatal cardiomyocyte (CM) development so far. The present study aimed to assess the molecular mechanism(s) by which Sphk1 silencing might influence CMs development and hypertrophy in vitro. Neonatal mouse CMs were transfected with siRNA against Sphk1 or negative control, and subsequently treated with 1 µM angiotensin II (AngII) or a control buffer for 24 h. The results of RNASeq analysis revealed that diminished expression of Sphk1 significantly accelerated neonatal CM maturation by inhibiting cell proliferation and inducing developmental pathways in the stress (AngII-induced) conditions. Importantly, similar effects were observed in the control conditions. Enhanced maturation of Sphk1-lacking CMs was further confirmed by the upregulation of the physiological hypertrophy-related signaling pathway involving Akt and downstream glycogen synthase kinase 3 beta (Gsk3β) downregulation. In summary, we demonstrated that the Sphk1 silencing in neonatal mouse CMs facilitated their postnatal maturation in both physiological and stress conditions.
Model of Environmental Membrane Field for Transmembrane Proteins
Authors: Roterman Irena , Stapor Katarzyna , Fabian Piotr , Konieczny Leszek , Banach Mateusz
Published: March 2021

The water environment determines the activity of biological processes. The role of such an environment interpreted in the form of an external field expressed by the 3D Gaussian distribution in the fuzzy oil drop model directs the folding process towards the generation of a centrally located hydrophobic core with the simultaneous exposure of polar residues on the surface. In addition to proteins soluble in the water environment, there is a significant group of membrane proteins that act as receptors or channels, including ion channels in particular. The change of the polar (water) environment into a highly hydrophobic (membrane) environment is quite radical, resulting in a different hydrophobicity distribution within the membrane protein. Modification of the notation of the force field expressing the presence of the hydrophobic environment has been proposed in this work. A modified fuzzy oil drop model with its adaptation to membrane proteins was used to interpret the structure of membrane proteins–mechanosensitive channel. The modified model was also used to describe the so-called negative cases—i.e., for water-soluble proteins with a clear distribution consistent with the fuzzy oil drop model.
Insights into the Role of the Microbiota and of Short-Chain Fatty Acids in Rubinstein–Taybi Syndrome
Authors: Di Fede Elisabetta , Ottaviano Emerenziana , Grazioli Paolo , Ceccarani Camilla , Galeone Antonio , Parodi Chiara , Colombo Elisa Adele , Bassanini Giulia , Fazio Grazia , Severgnini Marco , Milani Donatella , Verduci Elvira , Vaccari Thomas , Massa Valentina , Borghi Elisa , Gervasini Cristina
Published: March 2021

The short-chain fatty acid butyrate, produced by the gut microbiota, acts as a potent histone deacetylase (HDAC) inhibitor. We assessed possible ameliorative effects of butyrate, relative to other HDAC inhibitors, in in vitro and in vivo models of Rubinstein–Taybi syndrome (RSTS), a severe neurodevelopmental disorder caused by variants in the genes encoding the histone acetyltransferases CBP and p300. In RSTS cell lines, butyrate led to the patient-specific rescue of acetylation defects at subtoxic concentrations. Remarkably, we observed that the commensal gut microbiota composition in a cohort of RSTS patients is significantly depleted in butyrate-producing bacteria compared to healthy siblings. We demonstrate that the effects of butyrate and the differences in microbiota composition are conserved in a Drosophila melanogaster mutant for CBP, enabling future dissection of the gut–host interactions in an in vivo RSTS model. This study sheds light on microbiota composition in a chromatinopathy, paving the way for novel therapeutic interventions.
Molecular Signatures of Natural Killer Cells in CMV-Associated Anterior Uveitis, A New Type of CMV-Induced Disease in Immunocompetent Individuals
Authors: Yawata Nobuyo , Shirane Mariko , Woon Kaing , Lim Xinru , Tanaka Hidenori , Kawano Yoh-Ichi , Yawata Makoto , Chee Soon-Phaik , Siak Jay , Sonoda Koh-Hei
Published: March 2021

Cytomegalovirus (CMV) causes clinical issues primarily in immune-suppressed conditions. CMV-associated anterior uveitis (CMV-AU) is a notable new disease entity manifesting recurrent ocular inflammation in immunocompetent individuals. As patient demographics indicated contributions from genetic background and immunosenescence as possible underlying pathological mechanisms, we analyzed the immunogenetics of the cohort in conjunction with cell phenotypes to identify molecular signatures of CMV-AU. Among the immune cell types, natural killer (NK) cells are main responders against CMV. Therefore, we first characterized variants of polymorphic genes that encode differences in CMV-related human NK cell responses (Killer cell Immunoglobulin-like Receptors (KIR) and HLA class I) in 122 CMV-AU patients. The cases were then stratified according to their genetic features and NK cells were analyzed for human CMV-related markers (CD57, KLRG1, NKG2C) by flow cytometry. KIR3DL1 and HLA class I combinations encoding strong receptor–ligand interactions were present at substantially higher frequencies in CMV-AU. In these cases, NK cell profiling revealed expansion of the subset co-expressing CD57 and KLRG1, and together with KIR3DL1 and the CMV-recognizing NKG2C receptor. The findings imply that a mechanism of CMV-AU pathogenesis likely involves CMV-responding NK cells co-expressing CD57/KLRG1/NKG2C that develop on a genetic background of KIR3DL1/HLA-B allotypes encoding strong receptor–ligand interactions.
Rare Variants in Autophagy and Non-Autophagy Genes in Late-Onset Pompe Disease: Suggestions of Their Disease-Modifying Role in Two Italian Families
Authors: Napolitano Filomena , Bruno Giorgia , Terracciano Chiara , Franzese Giuseppina , Palomba Nicole , Scotto di Carlo Federica , Signoriello Elisabetta , De Blasiis Paolo , Navarro Stefano , Gialluisi Alessandro , Melone Mariarosa , Sampaolo Simone , Esposito Teresa
Published: March 2021

Pompe disease is an autosomal recessive disorder caused by a deficiency in the enzyme acid alpha-glucosidase. The late-onset form of Pompe disease (LOPD) is characterized by a slowly progressing proximal muscle weakness, often involving respiratory muscles. In LOPD, the levels of GAA enzyme activity and the severity of the clinical pictures may be highly variable among individuals, even in those who harbour the same combination of GAA mutations. The result is an unpredictable genotype–phenotype correlation. The purpose of this study was to identify the genetic factors responsible for the progression, severity and drug response in LOPD. We report here on a detailed clinical, morphological and genetic study, including a whole exome sequencing (WES) analysis of 11 adult LOPD siblings belonging to two Italian families carrying compound heterozygous GAA mutations. We disclosed a heterogeneous pattern of myopathic impairment, associated, among others, with cardiac defects, intracranial vessels abnormality, osteoporosis, vitamin D deficiency, obesity and adverse response to enzyme replacement therapy (ERT). We identified deleterious variants in the genes involved in autophagy, immunity and bone metabolism, which contributed to the severity of the clinical symptoms observed in the LOPD patients. This study emphasizes the multisystem nature of LOPD and highlights the polygenic nature of the complex phenotype disclosed in these patients.
Altered Task-Evoked Corticolimbic Responsivity in Generalized Anxiety Disorder
Authors: Kim Nayoung , Kim M. Justin
Published: March 2021

Generalized anxiety disorder (GAD) is marked by uncontrollable, persistent worry and exaggerated response to uncertainty. Here, we review and summarize the findings from the GAD literature that employs functional neuroimaging methods. In particular, the present review focuses on task-based blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies. We find that select brain regions often regarded as a part of a corticolimbic circuit (e.g., amygdala, anterior cingulate cortex, prefrontal cortex) are consistently targeted for a priori hypothesis-driven analyses, which, in turn, shows varying degrees of abnormal BOLD responsivity in GAD. Data-driven whole-brain analyses show the insula and the hippocampus, among other regions, to be affected by GAD, depending on the task used in each individual study. Overall, while the heterogeneity of the tasks and sample size limits the generalizability of the findings thus far, some promising convergence can be observed in the form of the altered BOLD responsivity of the corticolimbic circuitry in GAD.
Pharmacological Effects of Guava (Psidium guajava L.) Seed Polysaccharides: GSF3 Inhibits PC-3 Prostate Cancer Cell Growth through Immunotherapy In Vitro
Authors: Lin Hsiao-Chien , Lin Jin-Yuarn
Published: March 2021

The inhibitory effects of purified fractions isolated from guava seed polysaccharides (GSPS) including guava seed polysaccharide fraction 1 (GSF1), GSF2, and GSF3 on prostate cancer cells remain unclear. To clarify the anti-prostate cancer potential, GSPS, GSF1, GSF2, and GSF3 were isolated using Sepharose 6B gel filtration chromatography to assay their inhibitory effects on prostate PC-3 cell growth with direct action or indirect immunotherapy using either splenocyte conditioned media (SCM) or macrophage conditioned media (MCM). Correlations between cytokine profiles in the conditioned media and pro-apoptotic gene expression levels in the corresponding treated PC-3 cells were analyzed. Results showed that GSPS, GSF1, GSF2, and GSF3, particularly GSF3, through either direct action or indirect treatments using SCM or MCM, significantly (p < 0.05) inhibited PC-3 cell growth. GSF3 direct treatments increased pro-apoptotic Bax/anti-apoptotic Bcl-2 mRNA expression ratios in corresponding treated PC-3 cells. Either SCM or MCM cultured with GSF3 increased Fas mRNA expression levels in corresponding treated PC-3 cells. Both Th2-polarized and anti-inflammatory cytokine IL-10 either secreted in SCM or MCM were positively correlated with Fas mRNA expression levels in corresponding treated PC-3 cells. Our results suggest that GSF3 is a potent biological response modifier to decrease PC-3 cell growth through inducing apoptosis.
Elucidation of the Clustered Nano-Architecture of Radiation-Induced DNA Damage Sites and Surrounding Chromatin in Cancer Cells: A Single Molecule Localization Microscopy Approach
Authors: Hausmann Michael , Falk Martin , Neitzel Charlotte , Hofmann Andreas , Biswas Abin , Gier Theresa , Falkova Iva , Heermann Dieter W. , Hildenbrand Georg
Published: March 2021

In cancer therapy, the application of (fractionated) harsh radiation treatment is state of the art for many types of tumors. However, ionizing radiation is a “double-edged sword”—it can kill the tumor but can also promote the selection of radioresistant tumor cell clones or even initiate carcinogenesis in the normal irradiated tissue. Individualized radiotherapy would reduce these risks and boost the treatment, but its development requires a deep understanding of DNA damage and repair processes and the corresponding control mechanisms. DNA double strand breaks (DSBs) and their repair play a critical role in the cellular response to radiation. In previous years, it has become apparent that, beyond genetic and epigenetic determinants, the structural aspects of damaged chromatin (i.e., not only of DSBs themselves but also of the whole damage-surrounding chromatin domains) form another layer of complex DSB regulation. In the present article, we summarize the application of super-resolution single molecule localization microscopy (SMLM) for investigations of these structural aspects with emphasis on the relationship between the nano-architecture of radiation-induced repair foci (IRIFs), represented here by γH2AX foci, and their chromatin environment. Using irradiated HeLa cell cultures as an example, we show repair-dependent rearrangements of damaged chromatin and analyze the architecture of γH2AX repair clusters according to topological similarities. Although HeLa cells are known to have highly aberrant genomes, the topological similarity of γH2AX was high, indicating a functional, presumptively genome type-independent relevance of structural aspects in DSB repair. Remarkably, nano-scaled chromatin rearrangements during repair depended both on the chromatin domain type and the treatment. Based on these results, we demonstrate how the nano-architecture and topology of IRIFs and chromatin can be determined, point to the methodological relevance of SMLM, and discuss the consequences of the observed phenomena for the DSB repair network regulation or, for instance, radiation treatment outcomes.
Discovery of Hyperactive Antifreeze Protein from Phylogenetically Distant Beetles Questions Its Evolutionary Origin
Authors: Arai Tatsuya , Yamauchi Akari , Miura Ai , Kondo Hidemasa , Nishimiya Yoshiyuki , Sasaki Yuji C. , Tsuda Sakae
Published: March 2021

Beetle hyperactive antifreeze protein (AFP) has a unique ability to maintain a supercooling state of its body fluids, however, less is known about its origination. Here, we found that a popular stag beetle Dorcus hopei binodulosus (Dhb) synthesizes at least 6 isoforms of hyperactive AFP (DhbAFP). Cold-acclimated Dhb larvae tolerated −5 °C chilled storage for 24 h and fully recovered after warming, suggesting that DhbAFP facilitates overwintering of this beetle. A DhbAFP isoform (~10 kDa) appeared to consist of 6−8 tandem repeats of a 12-residue consensus sequence (TCTxSxNCxxAx), which exhibited 3 °C of high freezing point depression and the ability of binding to an entire surface of a single ice crystal. Significantly, these properties as well as DNA sequences including the untranslated region, signal peptide region, and an AFP-encoding region of Dhb are highly similar to those identified for a known hyperactive AFP (TmAFP) from the beetle Tenebrio molitor (Tm). Progenitor of Dhb and Tm was branched off approximately 300 million years ago, so no known evolution mechanism hardly explains the retainment of the DNA sequence for such a lo­ng divergence period. Existence of unrevealed gene transfer mechanism will be hypothesized between these two phylogenetically distant beetles to acquire this type of hyperactive AFP.
Understanding the Future Prospects of Synergizing Minimally Invasive Transforaminal Lumbar Interbody Fusion Surgery with Ceramics and Regenerative Cellular Therapies
Authors: Lo Wen-Cheng , Tsai Lung-Wen , Yang Yi-Shan , Chan Ryan Wing Yuk
Published: March 2021

Transforaminal lumber interbody fusion (TLIF) is the last resort to address the lumber degenerative disorders such as spondylolisthesis, causing lower back pain. The current surgical intervention for these abnormalities includes open TLIF. However, in recent years, minimally invasive TLIF (MIS-TLIF) has gained a high momentum, as it could minimize the risk of infection, blood loss, and post-operative complications pertaining to fusion surgery. Further advancement in visualizing and guiding techniques along with grafting cage and materials are continuously improving the safety and efficacy of MIS-TLIF. These assistive techniques are also playing a crucial role to increase and improve the learning curve of surgeons. However, achieving an appropriate output through TLIF still remains a challenge, which might be synergized through 3D-printing and tissue engineering-based regenerative therapy. Owing to their differentiation potential, biomaterials such as stem/progenitor cells may contribute to restructuring lost or damaged tissues during MIS-TLIF, and this therapeutic efficacy could be further supplemented by platelet-derived biomaterials, leading to improved clinical outcomes. Thus, based on the above-mentioned strategies, we have comprehensively summarized recent developments in MIS-TLIF and its possible combinatorial regenerative therapies for rapid and long-term relief.
Collagen I Modifies Connexin-43 Hemichannel Activity via Integrin α2β1 Binding in TGFβ1-Evoked Renal Tubular Epithelial Cells
Authors: Potter Joe A. , Price Gareth W. , Cliff Chelsy L. , Green Colin R. , Squires Paul E. , Hills Claire E.
Published: March 2021

Chronic Kidney Disease (CKD) is associated with sustained inflammation and progressive fibrosis, changes that have been linked to altered connexin hemichannel-mediated release of adenosine triphosphate (ATP). Kidney fibrosis develops in response to increased deposition of extracellular matrix (ECM), and up-regulation of collagen I is an early marker of renal disease. With ECM remodeling known to promote a loss of epithelial stability, in the current study we used a clonal human kidney (HK2) model of proximal tubular epithelial cells to determine if collagen I modulates changes in cell function, via connexin-43 (Cx43) hemichannel ATP release. HK2 cells were cultured on collagen I and treated with the beta 1 isoform of the pro-fibrotic cytokine transforming growth factor (TGFβ1) ± the Cx43 mimetic Peptide 5 and/or an anti-integrin α2β1 neutralizing antibody. Phase microscopy and immunocytochemistry observed changes in cell morphology and cytoskeletal reorganization, whilst immunoblotting and ELISA identified changes in protein expression and secretion. Carboxyfluorescein dye uptake and biosensing measured hemichannel activity and ATP release. A Cytoselect extracellular matrix adhesion assay assessed changes in cell-substrate interactions. Collagen I and TGFβ1 synergistically evoked increased hemichannel activity and ATP release. This was paralleled by changes to markers of tubular injury, partly mediated by integrin α2β1/integrin-like kinase signaling. The co-incubation of the hemichannel blocker Peptide 5, reduced collagen I/TGFβ1 induced alterations and inhibited a positive feedforward loop between Cx43/ATP release/collagen I. This study highlights a role for collagen I in regulating connexin-mediated hemichannel activity through integrin α2β1 signaling, ahead of establishing Peptide 5 as a potential intervention.
A Data-Driven Framework for Coding the Intent and Extent of Political Tweeting, Disinformation, and Extremism
Authors: Hashemi Mahdi
Published: March 2021

Disinformation campaigns on online social networks (OSNs) in recent years have underscored democracy’s vulnerability to such operations and the importance of identifying such operations and dissecting their methods, intents, and source. This paper is another milestone in a line of research on political disinformation, propaganda, and extremism on OSNs. A total of 40,000 original Tweets (not re-Tweets or Replies) related to the U.S. 2020 presidential election are collected. The intent, focus, and political affiliation of these political Tweets are determined through multiple discussions and revisions. There are three political affiliations: rightist, leftist, and neutral. A total of 171 different classes of intent or focus are defined for Tweets. A total of 25% of Tweets were left out while defining these classes of intent. The purpose is to assure that the defined classes would be able to cover the intent and focus of unseen Tweets (Tweets that were not used to determine and define these classes) and no new classes would be required. This paper provides these classes, their definition and size, and example Tweets from them. If any information is included in a Tweet, its factuality is verified through valid news sources and articles. If any opinion is included in a Tweet, it is determined that whether or not it is extreme, through multiple discussions and revisions. This paper provides analytics with regard to the political affiliation and intent of Tweets. The results show that disinformation and extreme opinions are more common among rightists Tweets than leftist Tweets. Additionally, Coronavirus pandemic is the topic of almost half of the Tweets, where 25.43% of Tweets express their unhappiness with how Republicans have handled this pandemic.
ThriftyNets: Convolutional Neural Networks with Tiny Parameter Budget
Authors: Coiffier Guillaume , Boukli Hacene Ghouthi , Gripon Vincent
Published: March 2021

Deep Neural Networks are state-of-the-art in a large number of challenges in machine learning. However, to reach the best performance they require a huge pool of parameters. Indeed, typical deep convolutional architectures present an increasing number of feature maps as we go deeper in the network, whereas spatial resolution of inputs is decreased through downsampling operations. This means that most of the parameters lay in the final layers, while a large portion of the computations are performed by a small fraction of the total parameters in the first layers. In an effort to use every parameter of a network at its maximum, we propose a new convolutional neural network architecture, called ThriftyNet. In ThriftyNet, only one convolutional layer is defined and used recursively, leading to a maximal parameter factorization. In complement, normalization, non-linearities, downsamplings and shortcut ensure sufficient expressivity of the model. ThriftyNet achieves competitive performance on a tiny parameters budget, exceeding 91% accuracy on CIFAR-10 with less than 40 k parameters in total, 74.3% on CIFAR-100 with less than 600 k parameters, and 67.1% On ImageNet ILSVRC 2012 with no more than 4.15 M parameters. However, the proposed method typically requires more computations than existing counterparts.
Artificial Intelligence (AI)-Empowered Echocardiography Interpretation: A State-of-the-Art Review
Authors: Akkus Zeynettin , Aly Yousof H. , Attia Itzhak Z. , Lopez-Jimenez Francisco , Arruda-Olson Adelaide M. , Pellikka Patricia A. , Pislaru Sorin V. , Kane Garvan C. , Friedman Paul A. , Oh Jae K.
Published: March 2021

Echocardiography (Echo), a widely available, noninvasive, and portable bedside imaging tool, is the most frequently used imaging modality in assessing cardiac anatomy and function in clinical practice. On the other hand, its operator dependability introduces variability in image acquisition, measurements, and interpretation. To reduce these variabilities, there is an increasing demand for an operator- and interpreter-independent Echo system empowered with artificial intelligence (AI), which has been incorporated into diverse areas of clinical medicine. Recent advances in AI applications in computer vision have enabled us to identify conceptual and complex imaging features with the self-learning ability of AI models and efficient parallel computing power. This has resulted in vast opportunities such as providing AI models that are robust to variations with generalizability for instantaneous image quality control, aiding in the acquisition of optimal images and diagnosis of complex diseases, and improving the clinical workflow of cardiac ultrasound. In this review, we provide a state-of-the art overview of AI-empowered Echo applications in cardiology and future trends for AI-powered Echo technology that standardize measurements, aid physicians in diagnosing cardiac diseases, optimize Echo workflow in clinics, and ultimately, reduce healthcare costs.
Assessment of Gastrointestinal Autonomic Dysfunction: Present and Future Perspectives
Authors: Kornum Ditte S. , Terkelsen Astrid J. , Bertoli Davide , Klinge Mette W. , Høyer Katrine L. , Kufaishi Huda H. A. , Borghammer Per , Drewes Asbjørn M. , Brock Christina , Krogh Klaus
Published: March 2021

The autonomic nervous system delicately regulates the function of several target organs, including the gastrointestinal tract. Thus, nerve lesions or other nerve pathologies may cause autonomic dysfunction (AD). Some of the most common causes of AD are diabetes mellitus and α-synucleinopathies such as Parkinson’s disease. Widespread dysmotility throughout the gastrointestinal tract is a common finding in AD, but no commercially available method exists for direct verification of enteric dysfunction. Thus, assessing segmental enteric physiological function is recommended to aid diagnostics and guide treatment. Several established assessment methods exist, but disadvantages such as lack of standardization, exposure to radiation, advanced data interpretation, or high cost, limit their utility. Emerging methods, including high-resolution colonic manometry, 3D-transit, advanced imaging methods, analysis of gut biopsies, and microbiota, may all assist in the evaluation of gastroenteropathy related to AD. This review provides an overview of established and emerging assessment methods of physiological function within the gut and assessment methods of autonomic neuropathy outside the gut, especially in regards to clinical performance, strengths, and limitations for each method.
Treatment of Achilles Tendinopathy in Recreational Runners with Peritendinous Hyaluronic Acid Injections: A Viscoelastometric, Functional, and Biochemical Pilot Study
Authors: Gervasi Marco , Barbieri Elena , Capparucci Italo , Annibalini Giosuè , Sisti Davide , Amatori Stefano , Carrabs Vittoria , Valli Giacomo , Donati Zeppa Sabrina , Rocchi Marco Bruno Luigi , Stocchi Vilberto , Sestili Piero
Published: March 2021

Background: Achilles tendinopathy (AT) affects ca. 10 million recreational runners in Europe; the practice of hyaluronic acid (HA) infiltration is being increasingly adopted. The aim of this pilot study was to monitor the effects of a three-local time-spaced injections regimen of HA in the treatment of AT in middle-aged runners combining for the first time viscoelastometric, biochemical, and functional methodologies with routine clinical examinations. Methods: Eight male runners (Age 49.3 ± 3.9), diagnosed for unilateral AT, were given three ultrasound (US) guided peritendinous HA injections at the baseline (T0) and every fifteenth day with a follow-up on the forty-fifth day (T1, T2, and T3). At all-time points patients were assessed for viscoelastic tone and stiffness, maximal voluntary isometric contraction (MVIC), and pain level (Likert scale 0–5). The peritendinous effusions of the injured tendon were collected at T0 and T2 to quantify the volume variations and the IL-1β and MMP-3 levels. Results: At T0 MVIC and pain score were significantly lower and higher, respectively, in injured tendons. The volume, IL-1β and MMP-3 levels decreased in the course of treatment and the clinical endpoints ameliorated over time. Tone, stiffness, and functional performance also varied significantly at T2 and T3, as compared to T0. Conclusions: The sequential peritendinous injections of HA were effective in the amelioration of the clinical symptoms, as well as of the functional and viscoelastic state associated with AT. The determination of the viscoelastometric state may help to precisely evaluate the healing process in AT patients.
“It Should Have Been Given Sooner, and We Should Not Have to Fight for It”: A Mixed-Methods Study of the Experience of Diagnosis and Early Management of Cerebral Palsy
Authors: Williams Sîan A , Alzaher Woroud , Mackey Anna , Hogan Amy , Battin Malcolm , Sorhage Alexandra , Stott N Susan
Published: March 2021

Listening to the family experience is integral to identifying areas of strength and for improvement in health service delivery around diagnosis and early management of cerebral palsy (CP). Families of children with a diagnosis of CP were invited to complete a purpose-developed electronic survey that included items around the timing of diagnosis, their experiences and satisfaction. It also allowed families to expand on their experiences through free text. Of the 57 families responding, 49% of children functioned at Gross Motor Function Classification System (GMFCS) levels I or II, 8% at GMFCS level III and 23% at GMFCS levels IV or V. 51% of participants were satisfied or very satisfied with the diagnosis experience, 18% were neutral about the experience and 31% were dissatisfied or very dissatisfied. Though the findings of this study may be subject to selection bias, perceived delays in the receipt of diagnosis of CP appeared common with 60% of participants indicating concerns about their child by <6 months of age but only 21% provided with a diagnosis of CP <6 months of age. Approximately 18% of families experienced a delay of more than 12 months. Thirty-four (61%) participants noted a delay between referrals to a service and receipt of service management/therapy. Common themes impacting on families’ experience in the diagnosis and health service delivery journey related to provision of information, and the style of communication, with both direct and ongoing communication styles common for greater family satisfaction. Overall, families desired the diagnosis experience to be informative and timely, with early follow up support and assistance with health sector navigation.
Internet of Things: A Review on Theory Based Impedance Matching Techniques for Energy Efficient RF Systems
Authors: Couraud Benoit , Vauche Remy , Daskalakis Spyridon Nektarios , Flynn David , Deleruyelle Thibaut , Kussener Edith , Assimonis Stylianos
Published: March 2021

Within an increasingly connected world, the exponential growth in the deployment of Internet of Things (IoT) applications presents a significant challenge in power and data transfer optimisation. Currently, the maximization of Radio Frequency (RF) system power gain depends on the design of efficient, commercial chips, and on the integration of these chips by using complex RF simulations to verify bespoke configurations. However, even if a standard 50Ω transmitter’s chip has an efficiency of 90%, the overall power efficiency of the RF system can be reduced by 10% if coupled with a standard antenna of 72Ω. Hence, it is necessary for scalable IoT networks to have optimal RF system design for every transceiver: for example, impedance mismatching between a transmitter’s antenna and chip leads to a significant reduction of the corresponding RF system’s overall power efficiency. This work presents a versatile design framework, based on well-known theoretical methods (i.e., transducer gain, power wave approach, transmission line theory), for the optimal design in terms of power delivered to a load of a typical RF system, which consists of an antenna, a matching network, a load (e.g., integrated circuit) and transmission lines which connect all these parts. The aim of this design framework is not only to reduce the computational effort needed for the design and prototyping of power efficient RF systems, but also to increase the accuracy of the analysis, based on the explanatory analysis within our design framework. Simulated and measured results verify the accuracy of this proposed design framework over a 0–4 GHz spectrum. Finally, a case study based on the design of an RF system for Bluetooth applications demonstrates the benefits of this RF design framework.
Hemocyte Health Status Based on Four Biomarkers to Assess Recovery Capacity in American Lobster (Homarus americanus) after Exposure to Marine Diesel and Diluted Bitumen
Authors: Berthod Camille , Bénard-Déraspe Marie-Hélène , Laplante Jean-François , Lemaire Nicolas , Nadeau Madeleine , Toupoint Nicolas , Triffault-Bouchet Gaëlle , Saint-Louis Richard
Published: March 2021

The growing transportation of petroleum products pose a significant risk of marine diesel or diluted bitumen (dilbit) spills at sea. Despite the economic importance of the American lobster, there have been few studies assessing the impact study of such a spill on their population. In the lobster industry, lobster quality is monitored according to the Brix index of hemolymph. In our research, the effectiveness of three other biomarkers operative in the industry was assessed in hemolymph during contamination (over 96 h) by marine diesel and dilbit (Cold Lake Blend; CLB), as well as in the subsequent recovery period, according to two temperature cycles. At the end of the experiment, chemical and tainting assays were performed. Our results demonstrate that, among the four tested biomarkers, lysosomal stability and ethoxyresorufin O-deethylase (EROD) induction exhibit higher sensitivity. Increasing the temperature did not shorten the recovery period. Viability cellular impacts were greater in lobsters exposed to dilbit than that in those exposed to marine diesel. Marine diesel exposure appears to be more problematic for the lobster fishery, as the cooked lobster meat still presented a hydrocarbon odor even after 3 months of live holding. Finally, the high PAH concentrations measured in lobster eggs suggest potential adverse transgenerational effects of marine diesel exposure.
Associations between Cryptococcus Genotypes, Phenotypes, and Clinical Parameters of Human Disease: A Review
Authors: Montoya Marhiah C. , Magwene Paul M. , Perfect John R.
Published: March 2021

The genus Cryptococcus contains two primary species complexes that are significant opportunistic human fungal pathogens: C. neoformans and C. gattii. In humans, cryptococcosis can manifest in many ways, but most often results in either pulmonary or central nervous system disease. Patients with cryptococcosis can display a variety of symptoms on a spectrum of severity because of the interaction between yeast and host. The bulk of our knowledge regarding Cryptococcus and the mechanisms of disease stem from in vitro experiments and in vivo animal models that make a fair attempt, but do not recapitulate the conditions inside the human host. To better understand the dynamics of initiation and progression in cryptococcal disease, it is important to study the genetic and phenotypic differences in the context of human infection to identify the human and fungal risk factors that contribute to pathogenesis and poor clinical outcomes. In this review, we summarize the current understanding of the different clinical presentations and health outcomes that are associated with pathogenicity and virulence of cryptococcal strains with respect to specific genotypes and phenotypes.
A Medium-Term Field Experiment to Study the Effect of Managing Soil Chemical Properties on Fusarium Wilt in Banana (Musa AAA)
Authors: Segura M. Rafael A. , Stoorvogel Jetse J. , Blanco R. Fabio A. , Sandoval F. Jorge A.
Published: March 2021

Fusarium oxysporum f. sp. cubense (Foc) is a soil-borne fungus causing Fusarium wilt (FW) in banana. It is practically impossible to eradicate Foc in soils. Our understanding of soil–Foc–banana interactions is hampered by inconsistent research results caused by agro-ecological variability and the complexity of the soil system. This study aimed to evaluate the options to manage soil chemical properties to reduce disease expression and maintain banana production. The expression of FW (Foc Race 1) and the agronomic performance of the Gros Michel (Musa AAA) banana were evaluated in two medium-term factorial field experiments at representative locations in the Costa Rican banana region. In the experiments, five soil chemical properties (pH, N, Ca, Mg, and Mn) were managed to achieve a low and a high level. Plant mortality caused by FW, soil fertility, plant nutrition, and agronomic performance were monitored during four crop cycles. After the first crop cycle, the treatments started to present differences in plant mortality. There was a significant rise of plant mortality after the second crop cycle resulting in a cumulative plant mortality exceeding 60% in both experiments. A lower soil pH consistently resulted in significantly higher plant mortality. The interactions between soil properties (pH-N, pH-CaMg, pH-Mn, N-Mn, and CaMg-Mn) also influenced plant mortality. Soil N was the most significant treatment affecting leaf nutrient concentrations, bunch weight, and clusters per bunch. The experiments confirmed the potential role of soil management in FW expression in banana. Our results suggest that the management of soil chemical properties in the conditions here studied may help to reduce the expression rate of FW, but not to control the disease in the long run.
A Network of Pathways Controlling Cellular Homeostasis Affects the Onset of Senescence in Podospora anserina
Authors: Osiewacz Heinz D. , Schürmanns Lea
Published: March 2021

Research on Podospora anserina unraveled a network of molecular pathways affecting biological aging. In particular, a number of pathways active in the control of mitochondria were identified on different levels. A long-known key process active during aging of P. anserina is the age-related reorganization of the mitochondrial DNA (mtDNA). Mechanisms involved in the stabilization of the mtDNA lead to lifespan extension. Another critical issue is to balance mitochondrial levels of reactive oxygen species (ROS). This is important because ROS are essential signaling molecules, but at increased levels cause molecular damage. At a higher level of the network, mechanisms are active in the repair of damaged compounds. However, if damage passes critical limits, the corresponding pathways are overwhelmed and impaired molecules as well as those present in excess are degraded by specific enzymes or via different forms of autophagy. Subsequently, degraded units need to be replaced by novel functional ones. The corresponding processes are dependent on the availability of intact genetic information. Although a number of different pathways involved in the control of cellular homeostasis were uncovered in the past, certainly many more exist. In addition, the signaling pathways involved in the control and coordination of the underlying pathways are only initially understood. In some cases, like the induction of autophagy, ROS are active. Additionally, sensing and signaling the energetic status of the organism plays a key role. The precise mechanisms involved are elusive and remain to be elucidated.
Effects of CYP3A5 Polymorphism on Rapid Progression of Chronic Kidney Disease: A Prospective, Multicentre Study
Authors: Lee Fei Yee , Islahudin Farida , Ali Nasiruddin Aina Yazrin , Abdul Gafor Abdul Halim , Wong Hin-Seng , Bavanandan Sunita , Mohd Saffian Shamin , Md Redzuan Adyani , Mohd Tahir Nurul Ain , Makmor-Bakry Mohd
Published: March 2021

Personalised medicine is potentially useful to delay the progression of chronic kidney disease (CKD). The aim of this study was to determine the effects of CYP3A5 polymorphism in rapid CKD progression. This multicentre, observational, prospective cohort study was performed among adult CKD patients (≥18 years) with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, who had ≥4 outpatient, non-emergency eGFR values during the three-year study period. The blood samples collected were analysed for CYP3A5*3 polymorphism. Rapid CKD progression was defined as eGFR decline of >5 mL/min/1.73 m2/year. Multiple logistic regression was then performed to identify the factors associated with rapid CKD progression. A total of 124 subjects consented to participate. The distribution of the genotypes adhered to the Hardy–Weinberg equilibrium (X2 = 0.237, p = 0.626). After adjusting for potential confounding factors via multiple logistic regression, the factors associated with rapid CKD progression were CYP3A5*3/*3 polymorphism (adjusted Odds Ratio [aOR] 4.190, 95% confidence interval [CI]: 1.268, 13.852), adjustments to antihypertensives, young age, dyslipidaemia, smoking and use of traditional/complementary medicine. CKD patients should be monitored closely for possible factors associated with rapid CKD progression to optimise clinical outcomes. The CYP3A5*3/*3 genotype could potentially be screened among CKD patients to offer more individualised management among these patients.