bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine Learning of Spatial Data
Authors: Nikparvar Behnam , Thill Jean-Claude
Published: September 2021

Properties of spatially explicit data are often ignored or inadequately handled in machine learning for spatial domains of application. At the same time, resources that would identify these properties and investigate their influence and methods to handle them in machine learning applications are lagging behind. In this survey of the literature, we seek to identify and discuss spatial properties of data that influence the performance of machine learning. We review some of the best practices in handling such properties in spatial domains and discuss their advantages and disadvantages. We recognize two broad strands in this literature. In the first, the properties of spatial data are developed in the spatial observation matrix without amending the substance of the learning algorithm; in the other, spatial data properties are handled in the learning algorithm itself. While the latter have been far less explored, we argue that they offer the most promising prospects for the future of spatial machine learning.
A Geometric Layout Method for Synchronous Pseudolite Positioning Systems Based on a New Weighted HDOP
Authors: Zhao Xinyang , Shuai Qiangqiang , Li Guangchen , Lu Fangzhou , Zhu Bocheng
Published: September 2021

The positioning accuracy of a ground-based system in an indoor environment is closely related to the geometric configuration of pseudolites. This paper presents a simple closed-form equation for computing the weighted horizontal dilution of precision (WHDOP) with four eigenvalues, which can reduce the amount of calculation. By comparing the result of WHDOP with traditional matrix inversion operation, the effectiveness of WHDOP of the proposed simple calculation method is analyzed. The proposed WHDOP has a linear relationship with the actual static positioning result error in an indoor environment proved by the Pearson analysis method. Twenty positioning points are randomly selected, and the positioning variance and WHDOP of each positioning point have been calculated. The correlation coefficient of WHDOP and the positioning variance is calculated to be 0.82. A pseudolite system layout method based on a simulated annealing algorithm is proposed by using WHDOP, instead of Geometric dilution of precision (GDOP). In this paper, the constraints of time synchronization are discussed. In wireless connection system, the distance between master station and slave station should be kept within a certain range. Specifically, for a given indoor scene, many positioning target points are randomly generated in this area by using the Monte Carlo method. The mean WHDOP value of all positioning points corresponding to the synchronous pseudolite layout is used as the objective function. The results of brute force search are compared with the method, which proves the accuracy of the new algorithm.
Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer
Authors: Al-Bari Md. Abdul Alim , Ito Yuko , Ahmed Samrein , Radwan Nada , Ahmed Hend S. , Eid Nabil
Published: September 2021

Macro-autophagy (autophagy) is a highly conserved eukaryotic intracellular process of self-digestion caused by lysosomes on demand, which is upregulated as a survival strategy upon exposure to various stressors, such as metabolic insults, cytotoxic drugs, and alcohol abuse. Paradoxically, autophagy dysfunction also contributes to cancer and aging. It is well known that regulating autophagy by targeting specific regulatory molecules in its machinery can modulate multiple disease processes. Therefore, autophagy represents a significant pharmacological target for drug development and therapeutic interventions in various diseases, including cancers. According to the framework of autophagy, the suppression or induction of autophagy can exert therapeutic properties through the promotion of cell death or cell survival, which are the two main events targeted by cancer therapies. Remarkably, natural products have attracted attention in the anticancer drug discovery field, because they are biologically friendly and have potential therapeutic effects. In this review, we summarize the up-to-date knowledge regarding natural products that can modulate autophagy in various cancers. These findings will provide a new position to exploit more natural compounds as potential novel anticancer drugs and will lead to a better understanding of molecular pathways by targeting the various autophagy stages of upcoming cancer therapeutics.
The miR-133a, TPM4 and TAp63γ Role in Myocyte Differentiation Microfilament Remodelling and Colon Cancer Progression
Authors: Caporali Sabrina , Calabrese Cosimo , Minieri Marilena , Pieri Massimo , Tarantino Umberto , Marini Mario , D’Ottavio Stefano , Angeletti Silvia , Mauriello Alessandro , Cortese Claudio , Bernardini Sergio , Terrinoni Alessandro
Published: September 2021

MicroRNAs (miRNAs) play an essential role in the regulation of a number of physiological functions. miR-133a and other muscular miRs (myomiRs) play a key role in muscle cell growth and in some type of cancers. Here, we show that miR133a is upregulated in individuals that undertake physical exercise. We used a skeletal muscle differentiation model to dissect miR-133a’s role and to identify new targets, identifying Tropomyosin-4 (TPM4). This protein is expressed during muscle differentiation, but importantly it is an essential component of microfilament cytoskeleton and stress fibres formation. The microfilament scaffold remodelling is an essential step in cell transformation and tumour progression. Using the muscle system, we obtained valuable information about the microfilament proteins, and the knowledge on these molecular players can be transferred to the cytoskeleton rearrangement observed in cancer cells. Further investigations showed a role of TPM4 in cancer physiology, specifically, we found that miR-133a downregulation leads to TPM4 upregulation in colon carcinoma (CRC), and this correlates with a lower patient survival. At molecular level, we demonstrated in myocyte differentiation that TPM4 is positively regulated by the TA isoform of the p63 transcription factor. In muscles, miR-133a generates a myogenic stimulus, reducing the differentiation by downregulating TPM4. In this system, miR-133a counteracts the differentiative TAp63 activity. Interestingly, in CRC cell lines and in patient biopsies, miR-133a is able to regulate TPM4 activity, while TAp63 is not active. The downregulation of the miR leads to TPM4 overexpression, this modifies the architecture of the cell cytoskeleton contributing to increase the invasiveness of the tumour and associating with a poor prognosis. These results add data to the interesting question about the link between physical activity, muscle physiology and protection against colorectal cancer. The two phenomena have in common the cytoskeleton remodelling, due to the TPM4 activity, that is involved in stress fibres formation.
Changes in Locomotor Activity and Oxidative Stress-Related Factors after the Administration of an Amino Acid Mixture by Generation and Age
Authors: Ahn Yejin , Hong Ki-Bae , Kim Suhyeon , Suh Hyung Joo , Jo Kyungae
Published: September 2021

Amino acids, as nutrients, are expected to improve sleep disorders. This study aimed to evaluate the generation- and age-dependent sleep-improving effects of γ-aminobutyric acid (GABA) and 5-hydroxytryptophan (5-HTP) coadministration. The differentially expressed genes and generation-related behavior after the administration of a GABA/5-HTP mixture were measured in a Drosophila model, while age-related changes in gene expression and oxidative stress-related parameters were measured in a mouse model. The GABA/5-HTP-treated group showed significant behavioral changes compared to the other groups. Sequencing revealed that the GABA/5-HTP mixture influenced changes in nervous system-related genes, including those involved in the regulation of the expression of behavioral and synaptic genes. Additionally, total sleep time increased with age, and nighttime sleep time in the first- and third-generation flies was significantly different from that of the control groups. The GABA/5-HTP mixture induced significant changes in the expression of sleep-related receptors in both models. Furthermore, the GABA/5-HTP mixture reduced levels of ROS and ROS reaction products in an age-dependent manner. Therefore, the increase in behavioral changes caused by GABA/5-HTP mixture administration was effective in eliminating ROS activity across generations and ages.
A Body of Circumstantial Evidence for the Irreversible Ectonucleotidase Inhibitory Action of FSCPX, an Agent Known as a Selective Irreversible A1 Adenosine Receptor Antagonist So Far
Authors: Viczjan Gabor , Erdei Tamas , Ovari Ignac , Lampe Nora , Szekeres Reka , Bombicz Mariann , Takacs Barbara , Szilagyi Anna , Zsuga Judit , Szilvassy Zoltan , Juhasz Bela , Gesztelyi Rudolf
Published: September 2021

In previous studies using isolated, paced guinea pig left atria, we observed that FSCPX, known as a selective A1 adenosine receptor antagonist, paradoxically increased the direct negative inotropic response to A1 adenosine receptor agonists (determined using concentration/effect (E/c) curves) if NBTI, a nucleoside transport inhibitor, was present. Based on mathematical modeling, we hypothesized that FSCPX blunted the cardiac interstitial adenosine accumulation in response to nucleoside transport blockade, probably by inhibiting CD39 and/or CD73, which are the two main enzymes of the interstitial adenosine production in the heart. The goal of the present study was to test this hypothesis. In vitro CD39 and CD73 inhibitor assays were carried out; furthermore, E/c curves were constructed in isolated, paced rat and guinea pig left atria using adenosine, CHA and CPA (two A1 adenosine receptor agonists), FSCPX, NBTI and NBMPR (two nucleoside transport inhibitors), and PSB-12379 (a CD73 inhibitor), measuring the contractile force. We found that FSCPX did not show any inhibitory effect during the in vitro enzyme assays. However, we successfully reproduced the paradox effect of FSCPX in the rat model, mimicked the “paradox” effect of FSCPX with PSB-12379, and demonstrated the lipophilia of FSCPX, which could explain the negative outcome of inhibitor assays with CD39 and CD73 dissolved in a water-based solution. Taken together, these three pieces of indirect evidence are strong enough to indicate that FSCPX possesses an additional action besides the A1 adenosine receptor antagonism, which action may be the inhibition of an ectonucleotidase. Incidentally, we found that POM-1 inhibited CD73, in addition to CD39.
Searching for Biological Function of the Mysterious PA2504 Protein from Pseudomonas aeruginosa
Authors: Drabinska Joanna , Steczkiewicz Kamil , Kujawa Martyna , Kraszewska Elżbieta
Published: September 2021

For nearly half of the proteome of an important pathogen, Pseudomonas aeruginosa, the function has not yet been recognised. Here, we characterise one such mysterious protein PA2504, originally isolated by us as a sole partner of the RppH RNA hydrolase involved in transcription regulation of multiple genes. This study aims at elucidating details of PA2504 function and discussing its implications for bacterial biology. We show that PA2504 forms homodimers and is evenly distributed in the cytoplasm of bacterial cells. Molecular modelling identified the presence of a Tudor-like domain in PA2504. Transcriptomic analysis of a ΔPA2504 mutant showed that 42 transcripts, mainly coding for proteins involved in sulphur metabolism, were affected by the lack of PA2504. In vivo crosslinking of cellular proteins in the exponential and stationary phase of growth revealed several polypeptides that bound to PA2504 exclusively in the stationary phase. Mass spectrometry analysis identified them as the 30S ribosomal protein S4, the translation elongation factor TufA, and the global response regulator GacA. These results indicate that PA2504 may function as a tether for several important cellular factors.
Current and Future Treatments in Primary Ciliary Dyskinesia
Authors: Paff Tamara , Omran Heymut , Nielsen Kim G. , Haarman Eric G.
Published: September 2021

Primary ciliary dyskinesia (PCD) is a rare genetic ciliopathy in which mucociliary clearance is disturbed by the abnormal motion of cilia or there is a severe reduction in the generation of multiple motile cilia. Lung damage ensues due to recurrent airway infections, sometimes even resulting in respiratory failure. So far, no causative treatment is available and treatment efforts are primarily aimed at improving mucociliary clearance and early treatment of bacterial airway infections. Treatment guidelines are largely based on cystic fibrosis (CF) guidelines, as few studies have been performed on PCD. In this review, we give a detailed overview of the clinical studies performed investigating PCD to date, including three trials and several case reports. In addition, we explore precision medicine approaches in PCD, including gene therapy, mRNA transcript and read-through therapy.
A New Perspective on Cancer Therapy: Changing the Treaded Path?
Authors: Baidoo Juliet N. E. , Mukherjee Sumit , Kashfi Khosrow , Banerjee Probal
Published: September 2021

During the last decade, we have persistently addressed the question, “how can the innate immune system be used as a therapeutic tool to eliminate cancer?” A cancerous tumor harbors innate immune cells such as macrophages, which are held in the tumor-promoting M2 state by tumor-cell-released cytokines. We have discovered that these tumor-associated macrophages (TAM) are repolarized into the nitric oxide (NO)-generating tumoricidal M1 state by the dietary agent curcumin (CC), which also causes recruitment of activated natural killer (NK) cells and cytotoxic T (Tc) cells into the tumor, thereby eliminating cancer cells as well as cancer stem cells. Indications are that this process may be NO-dependent. Intriguingly, the maximum blood concentration of CC in mice never exceeds nanomolar levels. Thus, our results submit that even low, transient levels of curcumin in vivo are enough to cause repolarization of the TAM and recruitment NK cells as well as Tc cells to eliminate the tumor. We have observed this phenomenon in two cancer models, glioblastoma and cervical cancer. Therefore, this approach may yield a general strategy to fight cancer. Our mechanistic studies have so far implicated induction of STAT-1 in this M2→M1 switch, but further studies are needed to understand the involvement of other factors such as the lipid metabolites resolvins in the CC-evoked anticancer pathways.
PI3K/PTEN/AKT Signaling Pathways in Germ Cell Development and Their Involvement in Germ Cell Tumors and Ovarian Dysfunctions
Authors: De Felici Massimo , Klinger Francesca Gioia
Published: September 2021

Several studies indicate that the PI3K/PTEN/AKT signaling pathways are critical regulators of ovarian function including the formation of the germ cell precursors, termed primordial germ cells, and the follicular pool maintenance. This article reviews the current state of knowledge of the functional role of the PI3K/PTEN/AKT pathways during primordial germ cell development and the dynamics of the ovarian primordial follicle reserve and how dysregulation of these signaling pathways may contribute to the development of some types of germ cell tumors and ovarian dysfunctions.
Anaesthesia-Induced Transcriptomic Changes in the Context of Renal Ischemia Uncovered by the Use of a Novel Clamping Device
Authors: Verney Charles , Legouis David , Placier Sandrine , Migeon Tiffany , Bonnin Philippe , Buob David , Hadchouel Juliette , Galichon Pierre
Published: September 2021

Ischemia is a common cause of acute kidney injury worldwide, frequently occurring in patients undergoing cardiac surgery or admitted to the intensive care unit (ICU). Thus, ischemia-reperfusion injury (IRI) remains one of the main experimental models for the study of kidney diseases. However, the classical technique, based on non-traumatic surgical clamps, suffers from several limitations. It does not allow the induction of multiple episodes of acute kidney injury (AKI) in the same animal, which would be relevant from a human perspective. It also requires a deep and long sedation, raising the question of potential anaesthesia-related biases. We designed a vascular occluding device that can be activated remotely in conscious mice. We first assessed the intensity and the reproducibility of the acute kidney injury induced by this new device. We finally investigated the role played by the anaesthesia in the IRI models at the histological, functional and transcriptomic levels. We showed that this technique allows the rapid induction of renal ischemia in a repeatable and reproducible manner, breaking several classical limitations. In addition, we used its unique specificities to highlight the renal protective effect conferred by the anaesthesia, related to the mitigation of the IRI transcriptomic program.
Evaluating Neuroprotective Effects of Uridine, Erythropoietin, and Therapeutic Hypothermia in a Ferret Model of Inflammation-Sensitized Hypoxic-Ischemic Encephalopathy
Authors: Corry Kylie A. , White Olivia R. , Shearlock AnnaMarie E. , Moralejo Daniel H. , Law Janessa B. , Snyder Jessica M. , Juul Sandra E. , Wood Thomas R.
Published: September 2021

Perinatal hypoxic-ischemic (HI) brain injury, often in conjunction with an inflammatory insult, is the most common cause of death or disability in neonates. Therapeutic hypothermia (TH) is the standard of care for HI encephalopathy in term and near-term infants. However, TH may not always be available or efficacious, creating a need for novel or adjunctive neurotherapeutics. Using a near-term model of inflammation-sensitized HI brain injury in postnatal day (P) 17 ferrets, animals were randomized to either the control group (n = 43) or the HI-exposed groups: saline vehicle (Veh; n = 42), Ur (uridine monophosphate, n = 23), Epo (erythropoietin, n = 26), or TH (n = 24) to test their respective therapeutic effects. Motor development was assessed from P21 to P42 followed by analysis of cortical anatomy, ex vivo MRI, and neuropathology. HI animals took longer to complete the motor assessments compared to controls, which was exacerbated in the Ur group. Injury resulted in thinned white matter tracts and narrowed cortical sulci and gyri, which was mitigated in Epo-treated animals in addition to normalization of cortical neuropathology scores to control levels. TH and Epo treatment also resulted in region-specific improvements in diffusion parameters on ex vivo MRI; however, TH was not robustly neuroprotective in any behavioral or neuropathological outcome measures. Overall, Ur and TH did not provide meaningful neuroprotection after inflammation-sensitized HI brain injury in the ferret, and Ur appeared to worsen outcomes. By comparison, Epo appears to provide significant, though not complete, neuroprotection in this model.
Pharmacological Characterization of Low Molecular Weight Biased Agonists at the Follicle Stimulating Hormone Receptor
Authors: De Pascali Francesco , Ayoub Mohammed Akli , Benevelli Riccardo , Sposini Silvia , Lehoux Jordan , Gallay Nathalie , Raynaud Pauline , Landomiel Flavie , Jean-Alphonse Frédéric , Gauthier Christophe , Pellissier Lucie P. , Crépieux Pascale , Poupon Anne , Inoue Asuka , Joubert Nicolas , Viaud-Massuard Marie-Claude , Casarini Livio , Simoni Manuela , Hanyaloglu Aylin C. , Nataraja Selva G. , Yu Henry N. , Palmer Stephen S. , Yvinec Romain , Reiter Eric
Published: September 2021

Follicle-stimulating hormone receptor (FSHR) plays a key role in reproduction through the activation of multiple signaling pathways. Low molecular weight (LMW) ligands composed of biased agonist properties are highly valuable tools to decipher complex signaling mechanisms as they allow selective activation of discrete signaling cascades. However, available LMW FSHR ligands have not been fully characterized yet. In this context, we explored the pharmacological diversity of three benzamide and two thiazolidinone derivatives compared to FSH. Concentration/activity curves were generated for Gαs, Gαq, Gαi, β-arrestin 2 recruitment, and cAMP production, using BRET assays in living cells. ERK phosphorylation was analyzed by Western blotting, and CRE-dependent transcription was assessed using a luciferase reporter assay. All assays were done in either wild-type, Gαs or β-arrestin 1/2 CRISPR knockout HEK293 cells. Bias factors were calculated for each pair of read-outs by using the operational model. Our results show that each ligand presented a discrete pharmacological efficacy compared to FSH, ranging from super-agonist for β-arrestin 2 recruitment to pure Gαs bias. Interestingly, LMW ligands generated kinetic profiles distinct from FSH (i.e., faster, slower or transient, depending on the ligand) and correlated with CRE-dependent transcription. In addition, clear system biases were observed in cells depleted of either Gαs or β-arrestin genes. Such LMW properties are useful pharmacological tools to better dissect the multiple signaling pathways activated by FSHR and assess their relative contributions at the cellular and physio-pathological levels.
Effects of SGLT2 Inhibitors beyond Glycemic Control—Focus on Myocardial SGLT1
Authors: Sayour Alex , Ruppert Mihály , Oláh Attila , Benke Kálmán , Barta Bálint , Zsáry Eszter , Merkely Béla , Radovits Tamás
Published: September 2021

Selective sodium–glucose cotransporter 2 (SGLT2) inhibitors reduced the risk of hospitalization for heart failure in patients with or without type 2 diabetes (T2DM) in large-scale clinical trials. The exact mechanism of action is currently unclear. The dual SGLT1/2 inhibitor sotagliflozin not only reduced hospitalization for HF in patients with T2DM, but also lowered the risk of myocardial infarction and stroke, suggesting a possible additional benefit related to SGLT1 inhibition. In fact, several preclinical studies suggest that SGLT1 plays an important role in cardiac pathophysiological processes. In this review, our aim is to establish the clinical significance of myocardial SGLT1 inhibition through reviewing basic research studies in the context of SGLT2 inhibitor trials.
The Role of Sonic Hedgehog in Human Holoprosencephaly and Short-Rib Polydactyly Syndromes
Authors: Loo Christine K. C. , Pearen Michael A. , Ramm Grant A.
Published: September 2021

The Hedgehog (HH) signalling pathway is one of the major pathways controlling cell differentiation and proliferation during human development. This pathway is complex, with HH function influenced by inhibitors, promotors, interactions with other signalling pathways, and non-genetic and cellular factors. Many aspects of this pathway are not yet clarified. The main features of Sonic Hedgehog (SHH) signalling are discussed in relation to its function in human development. The possible role of SHH will be considered using examples of holoprosencephaly and short-rib polydactyly (SRP) syndromes. In these syndromes, there is wide variability in phenotype even with the same genetic mutation, so that other factors must influence the outcome. SHH mutations were the first identified genetic causes of holoprosencephaly, but many other genes and environmental factors can cause malformations in the holoprosencephaly spectrum. Many patients with SRP have genetic defects affecting primary cilia, structures found on most mammalian cells which are thought to be necessary for canonical HH signal transduction. Although SHH signalling is affected in both these genetic conditions, there is little overlap in phenotype. Possible explanations will be canvassed, using data from published human and animal studies. Implications for the understanding of SHH signalling in humans will be discussed.
Impact of DICER1 and DROSHA on the Angiogenic Capacity of Human Endothelial Cells
Authors: Braun Heike , Hauke Michael , Ripperger Anne , Ihling Christian , Fuszard Matthew , Eckenstaler Robert , Benndorf Ralf A.
Published: September 2021

RNAi-mediated knockdown of DICER1 and DROSHA, enzymes critically involved in miRNA biogenesis, has been postulated to affect the homeostasis and the angiogenic capacity of human endothelial cells. To re-evaluate this issue, we reduced the expression of DICER1 or DROSHA by RNAi-mediated knockdown and subsequently investigated the effect of these interventions on the angiogenic capacity of human umbilical vein endothelial cells (HUVEC) in vitro (proliferation, migration, tube formation, endothelial cell spheroid sprouting) and in a HUVEC xenograft assay in immune incompetent NSGTM mice in vivo. In contrast to previous reports, neither knockdown of DICER1 nor knockdown of DROSHA profoundly affected migration or tube formation of HUVEC or the angiogenic capacity of HUVEC in vivo. Furthermore, knockdown of DICER1 and the combined knockdown of DICER1 and DROSHA tended to increase VEGF-induced BrdU incorporation and induced angiogenic sprouting from HUVEC spheroids. Consistent with these observations, global proteomic analyses showed that knockdown of DICER1 or DROSHA only moderately altered HUVEC protein expression profiles but additively reduced, for example, expression of the angiogenesis inhibitor thrombospondin-1. In conclusion, global reduction of miRNA biogenesis by knockdown of DICER1 or DROSHA does not inhibit the angiogenic capacity of HUVEC. Further studies are therefore needed to elucidate the influence of these enzymes in the context of human endothelial cell-related angiogenesis.
Mechanisms of DNA Methylation in Virus-Host Interaction in Hepatitis B Infection: Pathogenesis and Oncogenetic Properties
Authors: Zhang Dake , Guo Shicheng , Schrodi Steven J.
Published: September 2021

Hepatitis B virus (HBV), the well-studied oncovirus that contributes to the majority of hepatocellular carcinomas (HCC) worldwide, can cause a severe inflammatory microenvironment leading to genetic and epigenetic changes in hepatocyte clones. HBV replication contributes to the regulation of DNA methyltransferase gene expression, particularly by X protein (HBx), and subsequent methylation changes may lead to abnormal transcription activation of adjacent genes and genomic instability. Undoubtedly, the altered expression of these genes has been known to cause diverse aspects of infected hepatocytes, including apoptosis, proliferation, reactive oxygen species (ROS) accumulation, and immune responses. Additionally, pollutant-induced DNA methylation changes and aberrant methylation of imprinted genes in hepatocytes also complicate the process of tumorigenesis. Meanwhile, hepatocytes also contribute to epigenetic modification of the viral genome to affect HBV replication or viral protein production. Meanwhile, methylation levels of HBV integrants and surrounding host regions also play crucial roles in their ability to produce viral proteins in affected hepatocytes. Both host and viral changes can provide novel insights into tumorigenesis, individualized responses to therapeutic intervention, disease progress, and early diagnosis. As such, DNA methylation-mediated epigenetic silencing of cancer-related genes and viral replication is a compelling therapeutic goal to reduce morbidity and mortality from liver cancer caused by chronic HBV infection. In this review, we summarize the most recent research on aberrant DNA methylation associated with HBV infection, which is involved in HCC development, and provide an outlook on the future direction of the research.
Advanced Fusion and Empirical Mode Decomposition-Based Filtering Methods for Breathing Rate Estimation from Seismocardiogram Signals
Authors: Kozia Christina , Herzallah Randa
Published: September 2021

Breathing Rate (BR), an important deterioration indicator, has been widely neglected in hospitals due to the requirement of invasive procedures and the need for skilled nurses to be measured. On the other hand, biomedical signals such as Seismocardiography (SCG), which measures heart vibrations transmitted to the chest-wall, can be used as a non-invasive technique to estimate the BR. This makes SCG signals a highly appealing way for estimating the BR. As such, this work proposes three novel methods for extracting the BR from SCG signals. The first method is based on extracting respiration-dependent features such as the fundamental heart sound components, S1 and S2 from the SCG signal. The second novel method investigates for the first time the use of data driven methods such as the Empirical Mode Decomposition (EMD) method to identify the respiratory component from an SCG signal. Finally, the third advanced method is based on fusing frequency information from the respiration signals that result from the aforementioned proposed methods and other standard methods. The developed methods in this paper are then evaluated on adult recordings from the combined measurement of ECG, the Breathing and Seismocardiograms database. Both fusion and EMD filter-based methods outperformed the individual methods, giving a mean absolute error of 1.5 breaths per minute, using a one-minute window of data.
A Buffer Management Algorithm Based on Dynamic Marking Threshold to Restrain MicroBurst in Data Center Network
Authors: Yu Yan , Jiang Xianliang , Jin Guang , Gao Zihang , Li Penghui
Published: September 2021

The data center has become the infrastructure of most Internet services, and its network carries different types of business flow, such as query, data backup, control information, etc. At the same time, the throughput-sensitive large flows occupy a lot of bandwidth, resulting in the small flow’s longer completion time, finally affecting the performance of the applications. Recent proposals consider only dynamically adjusting the ECN threshold or reversing the ECN packet priority. This paper combines these two improvements and presents the HDCQ method for coordinating data center queuing, separating large and small flows, and scheduling in order to ensure flow completion time. It uses the ECN mechanism to design load-adaptive marking threshold update algorithms for small flows to prevent micro-bursts from occurring. At the same time, packets marked with ECN or ACK are raised in priority, prompting these packets to be fed back to the sender as soon as possible, effectively reducing the TCP control loop delay. Extensive experimental analysis on the network simulator (NS-2) shows that the HDCQ algorithm has better performance in the face of micro-burst traffic, reducing the average flow completion time by up to 24% compared with the PIAS.
A Pest or Otherwise? Encounter of Oryctes rhinoceros (Coleoptera: Scarabaeidae) with Persistent Organic Pollutants
Authors: Shen Meng-Wei , Chen Hung-Chuan , Chen Shyi-Tien
Published: September 2021

The potential use of invertebrates as bioreactors to treat environmental pollutants is promising and of great interest. Three types of the persistent organic pollutants (POPs), namely pentachlorophenol (PCP), PAHs (naphthalene and phenanthrene) and dieldrin (DLN), were spiked in soil and treated by using Oryctes rhinoceros larvae, a known pest of coconut trees in southeast Asia, and also the indicators of POP toxicity and the fate and degradability of the ingested POPs were assessed. The larvae were tested at various levels of the POPs and went through an acclimation process. Without acclimation, the tolerance limits of the larvae toward PCP, PAHs and DLN were 200, 100 and 0.1 mg/kg-soil, respectively, yet with acclimation, the tolerance levels increased to 800, 400 and 0.5 mg/kg-soil, respectively. Biodegradation rates of all the tested POPs were >90% by week 2, with <5% and nearly 0% remaining in the feces and body of the larvae, respectively. The results suggest that the use of the beetle larvae in soil POP decontamination is doable.
Assessment of Physical Activity Using Waist-Worn Accelerometers in Hospitalized Heart Failure Patients and Its Relationship with Kansas City Cardiomyopathy Questionnaire
Authors: Shiraishi Yasuyuki , Niimi Nozomi , Goda Ayumi , Takei Makoto , Kimura Takehiro , Kohno Takashi , Kawana Masataka , Fukuda Keiichi , Kohsaka Shun
Published: September 2021

The health benefits of physical activity have been widely recognized, yet there is limited information on associations between accelerometer-related parameters and established patient-reported health status. This study investigated the association between the waist-worn accelerometer measurements, cardiopulmonary exercise testing (CPX), and results of the Kansas City Cardiomyopathy Questionnaire (KCCQ) in heart failure (HF) patients hospitalized for acute decompensation. A total of 31 patients were enrolled and wore a validated three-axis accelerometer for 2 weeks and completed the short version of the KCCQ after removing the device. Daily step counts, exercise time (metabolic equivalents × hours), and %sedentary time (sedentary time/device-equipped time) were measured. Among the measured parameters, the best correlation was observed between %sedentary time and the KCCQ overall and clinical summary scores (r = −0.65 and −0.65, each p < 0.001). All of the individual domains of the KCCQ (physical limitation, symptom frequency, and quality of life), with the exception of the social limitation domain, showed moderate correlations with %sedentary time. Finally, oxygen consumption assessed by CPX demonstrated only weak associations with the accelerometer-measured parameters. An accelerometer could complement the KCCQ results in accurately assessing the physical activity in HF patients immediately after hospitalization, albeit its correlation with CPX was at most moderate.
Outcomes of Endoscopic Ultrasound-Guided Biliary Drainage in a General Hospital for Patients with Endoscopic Retrograde Cholangiopancreatography-Difficult Transpapillary Biliary Drainage
Authors: Kuraoka Naosuke , Hashimoto Satoru , Matsui Shigeru , Terai Shuji
Published: September 2021

Endoscopic ultrasound-guided biliary drainage (EUS-BD) has been developed as an alternative treatment for percutaneous transhepatic biliary drainage for patients with bile duct stenosis. At specialized hospitals, the high success rate and effectiveness of EUS-BD as primary drainage has been reported. However, the procedure is highly technical and difficult, and it has not been generally performed. In this study, we retrospectively examined the effectiveness of EUS-BD in ERCP-difficult patients with distal bile duct stenosis. We retrospectively examined 24 consecutive cases in which EUS-BD was performed at our hospital for distal bile duct stenosis from October 2018 to December 2020. EUS-guided choledochoduodenostomy (EUS-CDS) was selected for cases that could be approached from the duodenal bulb, and EUS-HGS was selected for other cases. In the EUS-CDS and EUS-HGS groups, the technical success rates were 83.3% (10/12] and 91.7% (11/12], respectively. An adverse event occurred in one case in the EUS-CDS group, which developed severe biliary peritonitis. The stent patency period was 91 and 101 days in the EUS-CDS and EUS-HGS groups, respectively. EUS-BD for ERCP-difficult patients with distal bile duct stenosis is considered to be an effective alternative for biliary drainage that can be performed not only in specialized hospitals but also in general hospitals.
Real-World Data from a Multi-Center Study: Insights to Psoriatic Arthritis Care
Authors: Batko Bogdan , Kucharz Eugeniusz , Stajszczyk Marcin , Brzosko Marek , Samborski Włodzimierz , Żuber Zbigniew
Published: September 2021

Introduction: Real-world data indicate disparities in biologic access across Europe. Objectives: To describe the national structure of PsA care in Poland, with a particular focus on the population of inadequate responders (IRs) and difficulties associated with biologic therapy access. Methods: A pool of rheumatologic and dermatologic care centers was created based on National Health Fund contract lists (n = 841), from which 29 rheumatologic and 10 dermatologic centers were sampled randomly and successfully met the inclusion criterium. Additionally, 33 tertiary care centers were recruited. For successful center recruitment, one provider had to recruit at least one patient that met the criteria for one of the four pre-defined clinical subgroups, in which all patients had to have active PsA and IR status to at least 2 conventional synthetic disease-modifying drugs (csDMARDs). Self-assessment questionnaires were distributed among physicians and their patients. Results: Barriers to biologic DMARD (bDMARD) treatment are complex and include stringency of reimbursement criteria, health care system, logistic/organizational, and personal choice factors. For patients who are currently bDMARD users, the median waiting time from the visit, at which the reimbursement procedure was initiated, to the first day of bDMARD admission was 9 weeks (range 2–212; 32% < 4 weeks, 29% 5–12 weeks, 26% 13–28 weeks, 13% with >28 weeks delay). Out of all inadequate responder groups, bDMARD users are the only group with “good” therapeutic situation and satisfaction with therapy. Patient satisfaction with therapy is not always concordant with physician assessment of therapeutic status. Conclusions: Despite the fact that over a decade has passed since the introduction of biologic agents, in medium welfare countries such as Poland, considerable healthcare system barriers to biologic access are present. Out of different IR populations, patient satisfaction with treatment is often discordant with physician assessment of disease status.
Atrial Fibrillation and Clinical Outcomes in a Cohort of Hospitalized Patients with Sars-Cov-2 Infection and Chronic Kidney Disease
Authors: Genovesi Simonetta , Rebora Paola , Occhino Giuseppe , Rossi Emanuela , Maloberti Alessandro , Belli Michele , Bonfanti Paolo , Giannattasio Cristina , Rossetti Claudio , Epis Oscar Massimiliano , Ughi Nicola , Valsecchi Maria Grazia
Published: September 2021

The aim of the study was to investigate the role of chronic kidney disease (CKD) on in-hospital mortality and on incident atrial fibrillation (AF) in patients infected with SARS-CoV-2. The incidence of acute kidney injury (AKI) was also investigated. Multivariable regression models were used to assess the association between renal function groups (estimated Glomerular Filtration Rate, eGFR, >60 mL/min, 30–59 mL/min, <30 mL/min) and in-hospital all-cause mortality and incident AF and AKI. A cohort of 2816 patients admitted in one year for COVID-19 disease in two large hospitals was analyzed. The independent predictors of mortality were severe CKD [HR 1.732 (95%CI 1.264–2.373)], older age [HR 1.054 (95%CI 1.044–1.065)], cerebrovascular disease [HR 1.335 (95%CI (1.016–1.754)], lower platelet count [HR 0.997 (95%CI 0.996–0.999)], higher C-reactive protein [HR 1.047 (95%CI 1.035–1.058)], and higher plasma potassium value 1.374 (95%CI 1.139–1.658). When incident AKI was added to the final survival model, it was associated with higher mortality [HR 2.202 (1.728–2.807)]. Incident AF was more frequent in patients with CKD, but in the multivariable model only older age was significantly related with a higher incidence of AF [OR 1.036 (95%CI 1.022–1.050)]. Incident AF was strongly associated with the onset of AKI [HR 2.619 (95%CI 1.711–4.009)]. In this large population of COVID-19 patients, the presence of severe CKD was an independent predictor of in-hospital mortality. In addition, patients who underwent AKI during hospitalization had a doubled risk of death. Incident AF became more frequent as eGFR decreased and it was significantly associated with the onset of AKI.
HIV and Antiretroviral Therapy Are Independently Associated with Cardiometabolic Variables and Cardiac Electrical Activity in Adults from the Western Cape Region of South Africa
Authors: Williams Cassidy , Kamau Festus , Everson Frans , Kgokane Boipelo , De Boever Patrick , Goswami Nandu , Webster Ingrid , Strijdom Hans
Published: September 2021

Cardiovascular-related complications are on the rise in people with HIV/AIDS (PWH); however, the relationship among HIV and antiretroviral therapy (ART)-related parameters, cardiovascular risk, and cardiac electrical activity in PWH remain poorly studied, especially in sub-Saharan African populations. We investigated whether HIV and ART are associated with cardiometabolic and cardiac electrical activity in PWH from Worcester in the Western Cape Province, South Africa. This was a cross-sectional study with HIV-negative (HIV−, n = 24) and HIV-positive on ART (HIV+/ART+, n = 63) participants. We obtained demographic, lifestyle, and medical history data and performed anthropometric, clinical assessments, and blood/urine biochemistry. We performed multiple stepwise linear regression analyses to determine independent associations among HIV, ART, cardiometabolic, and electrocardiographic (ECG) variables. HIV+/ART+ independently associated with a lower body mass index (p = 0.004), elevated gamma-glutamyl transferase levels (β: 0.333 (0.130–0.573); p = 0.002), and elevated alanine aminotransferase levels (β: 0.427 (0.224–0.629); p < 0.001) compared to HIV−. Use of second-line ART was positively associated with high-sensitivity C-reactive protein (p = 0.002). Although ECG parameters did not differ between HIV− and HIV+/ART+, viral load positively associated with p-wave duration (0.306 (0.018–0.594); p = 0.038), and longer HIV duration (≥5 years) with ST-interval (0.270 (0.003–0.537); p = 0.047) after adjusting for confounding factors. Our findings suggest that HIV and ART are associated with mixed effects on this population’s cardiometabolic profile and cardiac electrical activity, underpinning the importance of cardiovascular risk monitoring in PWH.
Corneal Higher-Order Aberrations after Microhook ab Interno Trabeculotomy and Goniotomy with the Kahook Dual Blade: Preliminary Early 3-Month Results
Authors: Onoe Hiromitsu , Hirooka Kazuyuki , Okumichi Hideaki , Murakami Yumiko , Kiuchi Yoshiaki
Published: September 2021

We examined postoperative corneal higher-order aberrations (HOAs) present after combined phacoemulsification with either microhook ab interno trabeculotomy (μLOT-Phaco) or goniotomy, using the Kahook Dual Blade (KDB-Phaco). Retrospective study: A total of 45 eyes underwent μLOT-Phaco and KDB-Phaco (LOT-Phaco) procedures, with 21 eyes that underwent cataract surgery alone used as controls. Visual acuity and corneal HOAs, coma-like aberrations, and spherical-like aberrations were analyzed before and at 1, 2, and 3 months after the surgeries. Risk factors that could potentially influence HOAs were evaluated. No significant postoperative changes were noted for corneal HOAs, coma-like aberrations, and spherical-like aberrations after cataract surgery alone. The mean corneal HOAs, coma-like aberrations, and spherical-like aberrations were 0.222 ± 0.115 μm, 0.203 ± 0.113 μm, and 0.084 ± 0.043 μm at baseline and 0.326 ± 0.195 μm (p < 0.001), 0.302 ± 0.289 μm (p = 0.03), and 0.150 ± 0.115 μm (p < 0.001) at 3 months after LOT-Phaco, respectively. Results of the analysis for risk factors suggested that a longer incision in Schlemm’s canal could influence corneal HOAs, coma-like aberrations, and spherical-like aberrations after LOT-Phaco. Although no significant postoperative changes were observed in corneal HOAs and coma-like or spherical-like aberrations after cataract surgery alone, a significant increase in corneal HOAs and coma-like or spherical-like aberrations remained after the LOT-Phaco procedure.
Ribophorin II Overexpression Is Associated with Poor Response to Induction Chemotherapy with Docetaxel, Cisplatin, and Fluorouracil in P16-Negative Locally Advanced Head and Neck Squamous Cell Carcinoma
Authors: Chen Wei-Shan , Luo Sheng-Dean , Chiu Tai-Jan , Wang Yu-Ming , Chen Wei-Chih , Chien Chih-Yen , Fang Fu-Min , Huang Tai-Lin , Li Shau-Hsuan
Published: September 2021

This study aims to evaluate the relationship between human ribophorin II (RPN2) and the effect of treatment using induction therapy with docetaxel, cisplatin, and fluorouracil (TPF) for p-16 negative locally advanced head and neck squamous cell carcinoma (HNSCC). A total of 203 patients with locally advanced p-16 negative HNSCC who received induction chemotherapy with TPF at the Kaohsiung Chang Gung Memorial Hospital between 2009 and 2014 were enrolled. Immunohistochemistry (IHC) for RPN2 was examined and correlated with treatment outcome. Our study showed that RPN2 overexpression was significantly correlated with a poor response to induction chemotherapy with TPF. Both RPN2 overexpression and clinical N1 to N3 stages represented adverse prognostic factors for progression-free survival (PFS) and overall survival (OS). RPN2 might be a predictive marker for treatment response to induction chemotherapy. Further clinical trials are needed to determine the therapeutic significance of RPN2 in patients with HNSCC.
Eye Tracking and an A/B Split Test for Social Media Marketing Optimisation: The Connection between the User Profile and Ad Creative Components
Authors: Nichifor Eliza , Lixăndroiu Radu Constantin , Chițu Ioana Bianca , Brătucu Gabriel , Sumedrea Silvia , Maican Cătălin Ioan , Tecău Alina Simona
Published: September 2021

In the era of digitally dominated competition, where the effectiveness of Facebook ads prompts the social media marketing strategy, new opportunities arise for most industries. In this context, this study aims to discover and summarize the key optimisations regarding the creative ad components needed to run highly personalized ads based on a user profile. The participants were Facebook users between the ages of 18 and 65+ who were interested in dental services. Qualitative methods were adopted in order to discover suitable options for professionals to grow their business. In the first stage, the A/B split test using the Facebook Ads manager labelled the most effective creative component. In the second stage, an eye-tracking experiment generated 30 heatmaps that showed the differences between the segments. The results show solutions for attracting users by increasing the level of personalization of the ads. They are more beneficial for social media campaigns aimed at brand awareness targeting women and showing them a happy human face. When the target audience is men, technical details are preferred in order for the ad to become more attractive for them. This study enriches the literature and empowers professionals to deploy social media marketing growth strategies to attract users and make them convert to their full potential.
COVID-19 Pandemic, Urban Resilience and Real Estate Prices: The Experience of Cities in the Yangtze River Delta in China
Authors: Tian Chuanhao , Peng Xintian , Zhang Xiang
Published: September 2021

The COVID-19 pandemic has severely impacted the urban real estate market around the world. This study regards the impact of the pandemic as a quasi-natural experiment, using the Difference in Difference model (DID) to examine the short-term impact of this severe public health crisis on the residential land and housing markets in the Yangtze River Delta. The study found that the COVID-19 pandemic has had a significant inhibitory effect on the average price of urban residential land and houses in the Yangtze River Delta. Although the currency oversupply has caused real estate prices in all cities to rise, the price of urban residential land decreased by 13.7% for each additional unit of epidemic severity. The greater the city’s resilience to the pressure of the COVID-19 pandemic, the faster its residential land prices will recover. Empirical research on the new house samples confirmed this conclusion. Local governments should continue to improve their ability to manage abnormal conditions, not only to prevent the spread of the epidemic, but also to gradually promote the recovery of the urban economy, strengthen urban resilience to better respond to health crises, and achieve sustainable urban development.