bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of Transmissible Gastroenteritis Virus (TGEV): A Codon Usage Perspective
Authors: Cheng Saipeng , Wu Huiguang , Chen Zhenhai
Published: October 2020

Transmissible gastroenteritis virus (TGEV) is a coronavirus associated with diarrhea and high mortality in piglets. To gain insight into the evolution and adaptation of TGEV, a comprehensive analysis of phylogeny and codon usage bias was performed. The phylogenetic analyses of maximum likelihood and Bayesian inference displayed two distinct genotypes: genotypes I and II, and genotype I was classified into subtypes Ia and Ib. The compositional properties revealed that the coding sequence contained a higher number of A/U nucleotides than G/C nucleotides, and that the synonymous codon third position was A/U-enriched. The principal component analysis based on the values of relative synonymous codon usage (RSCU) showed the genotype-specific codon usage patterns. The effective number of codons (ENC) indicated moderate codon usage bias in the TGEV genome. Dinucleotide analysis showed that CpA and UpG were over-represented and CpG was under-represented in the coding sequence of the TGEV genome. The analyses of Parity Rule 2 plot, ENC-plot, and neutrality plot displayed that natural selection was the dominant evolutionary driving force in shaping codon usage preference in genotypes Ia and II. In addition, natural selection played a major role, while mutation pressure had a minor role in driving the codon usage bias in genotype Ib. The codon adaptation index (CAI), relative codon deoptimization index (RCDI), and similarity index (SiD) analyses suggested that genotype I might be more adaptive to pigs than genotype II. Current findings contribute to understanding the evolution and adaptation of TGEV.
Hijacking of Lipid Droplets by Hepatitis C, Dengue and Zika Viruses—From Viral Protein Moonlighting to Extracellular Release
Authors: Cloherty Alexandra P.M. , Olmstead Andrea D. , Ribeiro Carla M.S. , Jean François
Published: October 2020

Hijacking and manipulation of host cell biosynthetic pathways by human enveloped viruses are essential for the viral lifecycle. Flaviviridae members, including hepatitis C, dengue and Zika viruses, extensively manipulate host lipid metabolism, underlining the importance of lipid droplets (LDs) in viral infection. LDs are dynamic cytoplasmic organelles that can act as sequestration platforms for a unique subset of host and viral proteins. Transient recruitment and mobilization of proteins to LDs during viral infection impacts host-cell biological properties, LD functionality and canonical protein functions. Notably, recent studies identified LDs in the nucleus and also identified that LDs are transported extracellularly via an autophagy-mediated mechanism, indicating a novel role for autophagy in Flaviviridae infections. These developments underline an unsuspected diversity and localization of LDs and potential moonlighting functions of LD-associated proteins during infection. This review summarizes recent breakthroughs concerning the LD hijacking activities of hepatitis C, dengue and Zika viruses and potential roles of cytoplasmic, nuclear and extracellular LD-associated viral proteins during infection.
Insights on the Functional Interaction between Group 1 Metabotropic Glutamate Receptors (mGluRI) and ErbB Receptors
Authors: Ledonne Ada , Mercuri Nicola B.
Published: October 2020

It is well-appreciated that phosphorylation is an essential post-translational mechanism of regulation for several proteins, including group 1 metabotropic glutamate receptors (mGluRI), mGluR1, and mGluR5 subtypes. While contributions of various serine/threonine protein kinases on mGluRI modulation have been recognized, the functional role of tyrosine kinases (TKs) is less acknowledged. Here, while describing current evidence supporting that mGluRI are targets of TKs, we mainly focus on the modulatory roles of the ErbB tyrosine kinases receptors—activated by the neurotrophic factors neuregulins (NRGs)—on mGluRI function. Available evidence suggests that mGluRI activity is tightly dependent on ErbB signaling, and that ErbB’s modulation profoundly influences mGluRI-dependent effects on neurotransmission, neuronal excitability, synaptic plasticity, and learning and memory processes.
Chromosome Painting in Cultivated Bananas and Their Wild Relatives (Musa spp.) Reveals Differences in Chromosome Structure
Authors: Šimoníková Denisa , Němečková Alžběta , Čížková Jana , Brown Allan , Swennen Rony , Doležel Jaroslav , Hřibová Eva
Published: October 2020

Edible banana cultivars are diploid, triploid, or tetraploid hybrids, which originated by natural cross hybridization between subspecies of diploid Musa acuminata, or between M. acuminata and diploid Musa balbisiana. The participation of two other wild diploid species Musa schizocarpa and Musa textilis was also indicated by molecular studies. The fusion of gametes with structurally different chromosome sets may give rise to progenies with structural chromosome heterozygosity and reduced fertility due to aberrant chromosome pairing and unbalanced chromosome segregation. Only a few translocations have been classified on the genomic level so far, and a comprehensive molecular cytogenetic characterization of cultivars and species of the family Musaceae is still lacking. Fluorescence in situ hybridization (FISH) with chromosome-arm-specific oligo painting probes was used for comparative karyotype analysis in a set of wild Musa species and edible banana clones. The results revealed large differences in chromosome structure, discriminating individual accessions. These results permitted the identification of putative progenitors of cultivated clones and clarified the genomic constitution and evolution of aneuploid banana clones, which seem to be common among the polyploid banana accessions. New insights into the chromosome organization and structural chromosome changes will be a valuable asset in breeding programs, particularly in the selection of appropriate parents for cross hybridization.
Emerging Links between Control of Mitochondrial Protein ATAD3A and Cancer
Authors: Lang Liwei , Loveless Reid , Teng Yong
Published: October 2020

Spanning from the mitochondria’s outer surface to the inner membrane, the nuclear-encoded protein ATAD3A maintains vital roles in regulating mitochondrial dynamics, homeostasis, metabolism, and interactions with the endoplasmic reticulum. Recently, elevated levels of ATAD3A have been reported in several types of cancer and to be tightly correlated with cancer development and progression, including increased cancer cell potential of proliferation, metastasis, and resistance to chemotherapy and radiotherapy. In the current review, we reveal ATAD3A as the link between mitochondrial functions and cancer biology and the accumulating evidence presenting ATAD3A as an attractive target for the development of novel cancer therapy to inhibit aberrant cancer metabolism and progression.
Increased Skeletal Muscle Fiber Cross-Sectional Area, Muscle Phenotype Shift, and Altered Insulin Signaling in Rat Hindlimb Muscles in a Prenatally Androgenized Rat Model for Polycystic Ovary Syndrome
Authors: DeChick Auryana , Hetz Rebecca , Lee Jack , Speelman Diana L.
Published: October 2020

Women with polycystic ovary syndrome (PCOS) are reported to have greater lean mass and insulin resistance. To examine muscular changes in a prenatally androgenized (PNA) rat model for PCOS, Sprague–Dawley rats were exposed to 5 mg testosterone or vehicle daily on gestational days 16–19. At 15 weeks of age, endurance on a rota-rod treadmill was measured. At 16 weeks of age, fasting blood glucose and insulin, hindlimb skeletal muscle mass, muscle fiber cross-sectional area (CSA) and composition, and intra- and peri-muscular lipid droplets were examined. Expression of mitochondrial marker ATP synthase and insulin signaling proteins were also investigated. Compared with controls, PNA female rats demonstrated greater total body and hindlimb muscle weights, greater muscle fiber CSA, and trending reduced time on the rota-rod. An increase in fibers co-expressing the slow and fast isoforms of myosin (90 vs. 86%, p < 0.05) and greater expression of ATP synthase (6-fold, p < 0.005) were observed in the gastrocnemius (GN) muscle. More lipid content was observed in GN and tibialis anterior (TA) muscles. PNA rats had elevated fasting serum insulin (1.9 vs. 1.2 ng/mL, p < 0.005) but comparable fasting glucose. Expression of total and Ser636/9-phosphorylated IRS1 were altered in PNA rat hindlimb muscles. Together, skeletal muscle alterations in hindlimb muscles of a PNA rat model for PCOS may represent consequences of, or adaptations to, insulin resistance in this model.
Thermodynamics and Kinetics of Glycolytic Reactions. Part II: Influence of Cytosolic Conditions on Thermodynamic State Variables and Kinetic Parameters
Authors: Vogel Kristina , Greinert Thorsten , Reichard Monique , Held Christoph , Harms Hauke , Maskow Thomas
Published: October 2020

For systems biology, it is important to describe the kinetic and thermodynamic properties of enzyme-catalyzed reactions and reaction cascades quantitatively under conditions prevailing in the cytoplasm. While in part I kinetic models based on irreversible thermodynamics were tested, here in part II, the influence of the presumably most important cytosolic factors was investigated using two glycolytic reactions (i.e., the phosphoglucose isomerase reaction (PGI) with a uni-uni-mechanism and the enolase reaction with an uni-bi-mechanism) as examples. Crowding by macromolecules was simulated using polyethylene glycol (PEG) and bovine serum albumin (BSA). The reactions were monitored calorimetrically and the equilibrium concentrations were evaluated using the equation of state ePC-SAFT. The pH and the crowding agents had the greatest influence on the reaction enthalpy change. Two kinetic models based on irreversible thermodynamics (i.e., single parameter flux-force and two-parameter Noor model) were applied to investigate the influence of cytosolic conditions. The flux-force model describes the influence of cytosolic conditions on reaction kinetics best. Concentrations of magnesium ions and crowding agents had the greatest influence, while temperature and pH-value had a medium influence on the kinetic parameters. With this contribution, we show that the interplay of thermodynamic modeling and calorimetric process monitoring allows a fast and reliable quantification of the influence of cytosolic conditions on kinetic and thermodynamic parameters.
Sarcopenia Induced by Chronic Liver Disease in Mice Requires the Expression of the Bile Acids Membrane Receptor TGR5
Authors: Abrigo Johanna , Campos Fabián , Gonzalez Francisco , Aguirre Francisco , Gonzalez Andrea , Huerta-Salgado Camila , Conejeros Sabrina , Simon Felipe , Arrese Marco , Cabrera Daniel , Elorza Alvaro A. , Cabello-Verrugio Claudio
Published: October 2020

Sarcopenia is a condition of muscle dysfunction, commonly associated with chronic liver disease (CLD), characterized by a decline in muscle strength, the activation of the ubiquitin-proteasome system (UPS), and oxidative stress. We recently described a murine model of CLD-induced sarcopenia by intake of hepatotoxin 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), which presents an increase in plasma bile acids (BA). BA induced skeletal muscle atrophy through a mechanism dependent on the Takeda G protein-coupled receptor 5 (TGR5) receptor. In the present study, we evaluated the role of TGR5 signaling in the development of sarcopenia using a model of DDC-induced CLD in C57BL6 wild-type (WT) mice and mice deficient in TGR5 expression (TGR5−/− mice). The results indicate that the decline in muscle function and contractibility induced by the DDC diet is dependent on TGR5 expression. TGR5 dependence was also observed for the decrease in fiber diameter and sarcomeric proteins, as well as for the fast-to-slow shift in muscle fiber type. UPS overactivation, indicated by increased atrogin-1/MAFbx (atrogin-1) and muscle RING-finger protein-1 (MuRF-1) protein levels and oxidative stress, was abolished in tibialis anterior muscles from TGR5−/− mice. Our results collectively suggest that all sarcopenia features induced by the DDC-supplemented diet in mice are dependent on TGR5 receptor expression.
Kynurenine Promotes RANKL-Induced Osteoclastogenesis In Vitro by Activating the Aryl Hydrocarbon Receptor Pathway
Authors: Eisa Nada H. , Reddy Sakamuri V. , Elmansi Ahmed M. , Kondrikova Galina , Kondrikov Dmitry , Shi Xing-Ming , Novince Chad M. , Hamrick Mark W. , McGee-Lawrence Meghan E. , Isales Carlos M. , Fulzele Sadanand , Hill William D.
Published: October 2020

There is increasing evidence of the involvement of the tryptophan metabolite kynurenine (KYN) in disrupting osteogenesis and contributing to aging-related bone loss. Here, we show that KYN has an effect on bone resorption by increasing osteoclastogenesis. We have previously reported that in vivo treatment with KYN significantly increased osteoclast number lining bone surfaces. Here, we report the direct effect of KYN on receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis in Raw 264.7 macrophage cells, and we propose a potential mechanism for these KYN-mediated effects. We show that KYN/RANKL treatment results in enhancement of RANKL-induced osteoclast differentiation. KYN drives upregulation and activation of the key osteoclast transcription factors, c-fos and NFATc1 resulting in an increase in the number of multinucleated TRAP+ osteoclasts, and in hydroxyapatite bone resorptive activity. Mechanistically, the KYN receptor, aryl hydrocarbon receptor (AhR), plays an important role in the induction of osteoclastogenesis. We show that blocking AhR signaling using an AhR antagonist, or AhR siRNA, downregulates the KYN/RANKL-mediated increase in c-fos and NFATc1 and inhibits the formation of multinucleated TRAP + osteoclasts. Altogether, this work highlights that the novelty of the KYN and AhR pathways might have a potential role in helping to regulate osteoclast function with age and supports pursuing additional research to determine if they are potential therapeutic targets for the prevention or treatment of osteoporosis.
Focus on Biochemical and Clinical Predictors of Response to Immune Checkpoint Inhibitors in Metastatic Urothelial Carcinoma: Where Do We Stand?
Authors: Roviello Giandomenico , Catalano Martina , Nobili Stefania , Santi Raffaella , Mini Enrico , Nesi Gabriella
Published: October 2020

Urothelial bladder cancer is one of the most lethal cancers worldwide with barely 5% five-year survival in patients with metastatic disease. Intravesical immunotherapy with Bacillus Calmette-Guérin and platinum-based chemotherapy are currently the standard of care for non-muscle invasive and advanced or metastatic urothelial cancer (mUC), respectively. Recently, a subset of patients with locally advanced or mUC has shown to be responsive to immune checkpoint inhibitors (ICIs), e.g., the anti-cytotoxic T-lymphocyte-associated protein 4 and programmed cell death -1/programmed death-ligand1 (PD-1/PD-L1) antibodies. Due to the relevant clinical benefit of immunotherapy for mUC, in 2016, the United States Food and Drug Administration (FDA) approved five immunotherapeutic agents as second-line or first-line treatments for patients with advanced bladder cancer who did not profit from or were ineligible for standard therapy. In this review, we discuss the role of immunotherapy in bladder cancer and recent clinical applications of PD-1/PD-L1 blockade in mUC. Furthermore, we evaluate a variable response rate to ICIs treatment and outline potential biomarkers predictive of immunotherapy response.
Molecular Mechanisms of Sex-Related Differences in Arthritis and Associated Pain
Authors: Kim Ju-Ryoung , Kim Hyun Ah
Published: October 2020

Clinical conditions leading to chronic pain show important sex-related differences in the prevalence, severity, and degree of functional disability. Decades of epidemiological and clinical studies have demonstrated that women are more sensitive to pain than men. Arthritis, including rheumatoid arthritis (RA) and osteoarthritis (OA), is much more prevalent in females and accounts for the majority of pain arising from musculoskeletal conditions. It is therefore important to understand the mechanisms governing sex-dependent differences in chronic pain, including arthritis pain. However, research into the mechanisms underlying the sex-related differences in arthritis-induced pain is still in its infancy due to the bias in biomedical research performed largely in male subjects and animals. In this review, we discuss current advances in both clinical and preclinical research regarding sex-related differences in the development or severity of arthritis and associated pain. In addition, sex-related differences in biological and molecular mechanisms underlying the pathogenesis of arthritis pain, elucidated based on clinical and preclinical findings, are reviewed.
Mitocans Revisited: Mitochondrial Targeting as Efficient Anti-Cancer Therapy
Authors: Dong Lanfeng , Gopalan Vinod , Holland Olivia , Neuzil Jiri
Published: October 2020

Mitochondria are essential cellular organelles, controlling multiple signalling pathways critical for cell survival and cell death. Increasing evidence suggests that mitochondrial metabolism and functions are indispensable in tumorigenesis and cancer progression, rendering mitochondria and mitochondrial functions as plausible targets for anti-cancer therapeutics. In this review, we summarised the major strategies of selective targeting of mitochondria and their functions to combat cancer, including targeting mitochondrial metabolism, the electron transport chain and tricarboxylic acid cycle, mitochondrial redox signalling pathways, and ROS homeostasis. We highlight that delivering anti-cancer drugs into mitochondria exhibits enormous potential for future cancer therapeutic strategies, with a great advantage of potentially overcoming drug resistance. Mitocans, exemplified by mitochondrially targeted vitamin E succinate and tamoxifen (MitoTam), selectively target cancer cell mitochondria and efficiently kill multiple types of cancer cells by disrupting mitochondrial function, with MitoTam currently undergoing a clinical trial.
Regulation of Male Fertility by the Renin-Angiotensin System
Authors: Gianzo Marta , Subirán Nerea
Published: October 2020

The renin-angiotensin system (RAS) is a peptidic system known mainly for its roles in the maintenance of blood pressure and electrolyte and fluid homeostasis. However, several tissues and cells have been described to possess an intrinsic RAS that acts locally through different paracrine and autocrine mechanisms. In the male reproductive system, several components of this system have been observed in various organs and tissues, such as the testes, spermatozoa and seminal fluid. Some functions attributed to this local RAS are maintenance of seminal plasma electrolytes, regulation of steroidogenesis and spermatogenesis, and sperm functions. However, their specific actions in these locations are not fully understood. Therefore, a deep knowledge of the functions of the RAS at both the testicular and seminal levels could clarify its roles in male infertility and sperm physiology, and the different RAS elements could be used to design tools enabling the diagnosis and/or treatment of male infertility.
The Mechanism of Bisdemethoxycurcumin Enhances Conventional Antibiotics against Methicillin-Resistant Staphylococcus aureus
Authors: Wang Shu , Kim Min-Chul , Kang Ok-Hwa , Kwon Dong-Yeul
Published: October 2020

Methicillin-resistant Staphylococcus aureus (MRSA) infection has posed a serious threat to public health, therefore, the development of new antibacterial drugs is imperative. Bisdemethoxycurcumin (BDMC) is a curcumin analog that exists in nature and possesses extensive pharmacological actions. This review focuses on investigating the antibacterial activity of BDMC alone or in combination with three antibiotics against MRSA. We determined the minimal inhibitory concentration of BDMC, with a broth microdilution assay, and the value against all six strains was 7.8 μg/mL. The synergistic effect of BDMC combined with the antibiotics was determined using a checkerboard dilution test and a time–kill curve assay. The results showed that the antimicrobial effect of BDMC combined with antibiotics was superior to treatment with that of a single agent alone. We examined the antibacterial activity of BDMC in the presence of a membrane-permeabilizing agent and an ATPase-inhibiting agent, respectively. In addition, we analyzed the mecA transcription gene and the penicillin-binding protein 2a (PBP2a) level of MRSA treated with BDMC by quantitative RT-PCR or Western blot assay. The gene transcription and the protein level were significantly inhibited. This study demonstrated that BDMC has potent antibacterial activity, and proved that BDMC may be a potential natural modulator of antibiotics.
Outage Analysis of Relay-Assisted NOMA in Cooperative Cognitive Radio Networks with SWIPT
Authors: Tang Kun , Liao Shaowei
Published: October 2020

In this paper, we investigate a relay-assisted cooperative spectrum sharing for the considered non-orthogonal multiple access (NOMA) scheme in cognitive radio networks, where the relay node assists the base station (BS) to transmit the superimposed composite signal to two receivers by utilizing an amplified-and-forward (AF) technique with simultaneous wireless information and power transfer (SWIPT). The exact expressions for outage probabilities of two receivers are derived in closed forms. Moreover, a joint optimization of power allocation and the proportion of information splitting for energy harvesting is proposed in terms of energy efficiency (EE) maximization under required data reliability. Simulation results validate the analytical results since the analytical results match well with simulation results and demonstrate the performance advantages of the proposed scheme over other schemes and direct transmission.
Low Seroprevalence of SARS-CoV-2 Antibodies during Systematic Antibody Screening and Serum Responses in Patients after COVID-19 in a German Transplant Center
Authors: Choi Mira , Bachmann Friederike , Naik Marcel Ganesh , Duettmann Wiebke , Duerr Michael , Zukunft Bianca , Schwarz Tatjana , Corman Victor Max , Liefeldt Lutz , Budde Klemens , Halleck Fabian
Published: October 2020

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 denotes a global health issue. Data regarding COVID-19 incidence in kidney transplant recipients (KTR) are sparse. From 19 March to 19 May 2020, we performed a systematic screening for COVID-19 in KTR. Tests included serum analysis for SARS-CoV-2 antibodies using S protein-based immunofluorescence, anti-SARS-CoV-2 S1 immunoglobulin G (IgG) and immunoglobulin A (IgA) enzyme-linked immunosorbent assays (ELISA), and/or quantitative reverse transcription polymerase chain reaction (qRT-PCR) from nasal-throat swabs. Outpatient serum samples from KTR with PCR confirmed COVID-19, and swab samples from recipients (+donors) undergoing kidney transplantation were analyzed. Out of 223 samples from outpatients, 13 patients were positive with solely anti-SARS-CoV-2-IgA and 3 with both anti-IgA and anti-IgG. In total, 53 patients were symptomatic in the past, but positive results could be found in both symptomatic and asymptomatic patients. After an in depth analysis using immunofluorescence and neutralization tests in 2 KTR, recent COVID-19 infection remained highly suspicious. Apart from outpatient visits, only 5 out of 2044 KTR were symptomatic and tested positive via PCR, of which 4 recovered and one died. All patients showed seroconversion during the course of the disease. This study demonstrated a low seroprevalence in a German KTR cohort, and seroconversion of IgA and IgG after COVID-19 could be demonstrated. Effective containment strategies enabled us to continue our transplant program.
Functional Recovery in Parkinson’s Disease: Current State and Future Perspective
Authors: Bacanoiu Manuela Violeta , Mititelu Radu Razvan , Danoiu Mircea , Olaru Gabriela , Buga Ana Maria
Published: October 2020

Parkinson’s disease (PD) is one of the most frequent neurodegenerative disorders, affecting not only the motor function but also limiting the autonomy of affected people. In the last decade, the physical exercises of different intensities carried out by kinetic therapeutic activities, by robotic technologies or with the participation of sensory cues, have become increasingly appreciated in the management of Parkinson’s disease impairments. The aim of this paper was to evaluate the impact of physical exercises with and without physical devices on the motor and cognitive variables of PD patients. In order to achieve our objectives, we performed a systematic review of available original articles based on the impact of kinetic therapeutic activity. Through the search strategy, we selected original papers that were laboriously processed using characteristics related to physical therapy, or the tools used in physiological and psychological rehabilitation strategies for PD patients. In this study, we presented the most current intervention techniques in the rehabilitation programs of patients with Parkinson’s disease, namely the use of assisted devices, virtual imagery or the performing of physical therapies that have the capacity to improve walking deficits, tremor and bradykinesia, to reduce freezing episodes of gait and postural instability, or to improve motor and cognitive functions.
Adult Diabetes and Prediabetes Prevalence in Kuwait: Data from the Cross-Sectional Kuwait Diabetes Epidemiology Program
Authors: Alkandari Abdullah , Alarouj Monira , Elkum Naser , Sharma Prem , Devarajan Sriraman , Abu-Farha Mohamed , Al-Mulla Fahd , Tuomilehto Jaakko , Bennakhi Abdullah
Published: October 2020

Background: This study aimed to estimate the prevalence of diabetes and prediabetes in adults in Kuwait. Methods: The Kuwait Diabetes Epidemiology Program was a nationally representative, cross-sectional study of diabetes and obesity in Kuwait conducted between 2011 and 2014. The survey sampled 4937 adults in Kuwait aged 20 years or more and recorded participants’ demographics, behaviours, medical history, physical measurements and blood biochemical measurements. Prediabetes was defined as fasting plasma glucose between 6.1 and 6.9 mmol/L or HbA1c between 6 and 6.4% (42–47 mmol/mol). Diabetes was defined as self-reported history with prescribed glucose-lowering medication or FPG ≥7mmol/L or HbA1c level ≥6.5% (≥48 mmol/mol). Results: The overall adjusted prevalence of diabetes was 19.1%. The overall adjusted prevalence of prediabetes was 13.5%. Diabetes prevalence was 5.4%, 14.2%, 38.7% and 64.8% in adults aged 20–29, 30–44, 45–59 and 60 years or more, respectively. Diabetes prevalence was 22.4% in men and 14.4% in women. Prediabetes prevalence was 14.8% in men and 11.5% in women. In Kuwaitis, diabetes and prediabetes prevalence was 21.8% and 11.1%, respectively, while prevalence in non-Kuwaitis was 18.2% for diabetes and 14.3% for prediabetes. Conclusion: These findings illustrate the severe public health challenge posed by diabetes in Kuwait.
Daytime Neurophysiological Hyperarousal in Chronic Insomnia: A Study of qEEG
Authors: Oh Da Young , Park Su Mi , Choi Sung Won
Published: October 2020

Background: The hyperarousal model demonstrates that instability of sleep-wake regulation leads to insomnia symptoms and various neurophysiological hyperarousal states. Previous studies have shown that hyperarousal states that appear in chronic insomnia patients are not limited to sleep at nighttime but are stable characteristics that extend into the daytime. However, this phenomenon is mainly measured at bedtime, so it hard to determine whether it is maintained throughout a 24 h cycle or if it just appears at bedtime. Methods: We examined the resting state qEEG (quantitative electroencephalogram) and ECG (electrocardiogram) of chronic insomnia patients (n = 24) compared to good sleepers (n = 22) during the daytime. Results: As compared with controls, participants with insomnia showed a clearly high beta band activity in eyes closed condition at all brain areas. They showed a low frequency band at the frontal area; high frequency bands at the central and parietal areas were found in eyes open condition. Significantly higher heart rates were also found in the chronic insomnia group. Conclusion: These findings suggest that chronic insomnia patients were in a state of neurophysiological hyperarousal during the middle of the day due to abnormal arousal regulation.
Cell-Free DNA in the Investigation of Miscarriage
Authors: Colley Emily , Devall Adam J. , Williams Helen , Hamilton Susan , Smith Paul , Morgan Neil V. , Quenby Siobhan , Coomarasamy Arri , Allen Stephanie
Published: October 2020

Approximately one in four pregnancies result in pregnancy loss, and ~50% of these miscarriages are caused by chromosomal abnormalities. Genetic investigations are recommended after three consecutive miscarriages on products of conception (POC) tissue. Cell-free DNA (cfDNA) has been utilised for prenatal screening, but very little work has been carried out in nonviable pregnancies. We investigated the use of cfDNA from maternal blood to identify chromosomal abnormalities in miscarriage. One hundred and two blood samples from women experiencing a first trimester miscarriage were collected and stored. The mean gestational age was 7.1 weeks (range: 5–11 weeks). In this research, samples without a genetic test result from POC were not analysed. CfDNA was extracted and analysed using a modified commercial genome-wide non-invasive prenatal test. No results were provided to the patient. In 57 samples, cytogenetic results from POC analysis were available. Chromosomal abnormalities were identified in 47% (27/57) of POC analyses, and cfDNA analysis correctly identified 59% (16/27) of these. In total, 75% (43/57) of results were correctly identified. The average cfDNA fetal fraction was 6% (2–19%). In conclusion, cfDNA can be used to detect chromosomal abnormalities in miscarriages where the ‘fetal fraction’ is high enough; however, more studies are required to identify variables that can affect the overall results.
Short Term Presence of Subretinal Fluid in Central Serous Chorioretinopathy Affects Retinal Thickness and Function
Authors: Gawęcki Maciej , Jaszczuk Agnieszka , Grzybowski Andrzej
Published: October 2020

Background: Acute central serous chorioretinopathy (CSCR), with subretinal fluid (SRF) resolving spontaneously within a few months from disease onset, has been considered as a benign and self-limiting disease for many years. This study sought to discover if a short presence of SRF can result in morphological and functional damage to the retina. Materials and methods: The study included patients treated by subthreshold diode micropulse laser (SDM) application for acute CSCR at the Dobry Wzrok Ophthalmological Clinic between January 2018 and November 2019. Inclusion criteria were: first episode of CSCR; duration of symptoms of two months or less; complete resolution of subretinal fluid (SRF) after a single session of SDM; and a lack of any retinal pathology, previous CSCR episode, significant anisometropia or amblyopia in the collateral eye. Fifteen patients fulfilled the inclusion criteria, including 13 males and two females aged 42.3 ± 9.5 years. The mean duration of symptoms before treatment was 4.7 ± 1.3 weeks on average. Baseline and follow-up examinations were performed in both the affected and collateral eyes and included best-corrected visual acuity (BCVA); spectral-domain optical coherent tomography measurements such as central retinal thickness (CRT) and minimal foveal thickness (MFT) (at the follow-up visit only); fluorescein angiography (at presentation only) and fundus autofluorescence. The first follow-up visit, when the total resolution of SRF was noted, was conducted between 8 and 12 weeks after SDM. Results: Resolved CSCR eyes had significantly poorer BCVA, CRT, and MFT findings in comparison with healthy collateral eyes (respectively, 0.11 +/− 0.1 vs. 0.01 +/− 0.04 logMAR; 238.80 +/− 23.39 vs. 264.87 +/− 21.22 µm and 178.93 +/− 16.88 vs. 199.47 +/− 17.87 µm) despite the short period of CSCR duration (maximum of 14 ± 2.15 weeks on average). Conclusion: Short presence of SRF typical for acute CSCR can affect retinal function and morphology resulting in poorer visual outcome.
Use of a Holistic Design and Manufacturing Approach to Implement Optimized Additively Manufactured Mould Inserts for the Production of Injection-Moulded Thermoplastics
Authors: Papadakis Loucas , Avraam Stelios , Photiou Demetris , Masurtschak Simona , Pereira Falcón Juan Carlos
Published: October 2020

Injection moulding is one the most familiar processes for manufacturing of plastic parts by injecting molten thermoplastic polymers into a metallic mould. The cycle time of this process consists of the phases of injection, packing, cooling, and ejection of the final product. Shortening of cycle time is a key consideration to increase productivity. Therefore, in this manuscript the adoption of additively manufactured mould inserts with conformal cooling channels by means of selective laser melting (SLM) with the aim to reduce process cycles is presented. The design and manufacture of a mould insert with conformal cooling channels for producing pressure fitting thermoplastic parts is described. Numerical analysis of the injection process and simulation of shape distortions after SLM were conducted providing useful results for the design and manufacture of the mould insert. The results of the numerical analyses are compared with experimental 3D geometrical data of the additively manufactured mould insert. Temperature measurements during the real injection moulding process demonstrating promising findings. The adoption of the introduced method for the series production of injection moulded thermoplastics proves a shortening of cycle times of up to 32% and a final product shape quality improvement of up to 77% when using mould inserts with conformal cooling channels over the conventional mould inserts.
On the Fabrication of Metallic Single Crystal Turbine Blades with a Commentary on Repair via Additive Manufacturing
Authors: Angel Nicole Marie , Basak Amrita
Published: October 2020

The turbine section of aircraft engines (both commercial and military) is an example of one of the most hostile environments as the components in this section typically operate at upwards of 1650 °C in the presence of corrosive and oxidative gases. The blades are at the heart of the turbine section as they extract energy from the hot gases to generate work. The turbine blades are typically fabricated using investment casting, and depending on the casting complexity, they generally display one of the three common microstructures (i.e., equiaxed or polycrystalline, directionally solidified, and single crystal). Single crystal casting is exotic as several steps of the casting process are traditionally hands-on. Due to the complex production process involving several prototyping iterations, the blade castings have a significant cost associated with them. For example, a set of 40 single crystal turbine blades costs above USD 600,000 and requires 60–90 weeks for production. Additionally, if the components suffer from material loss due to prolonged service or manufacturing defects, the traditional manufacturing methods cannot restore the parent metallurgy at the damage locations. Hence, there is a significant interest in developing additive manufacturing (AM) technologies that can repair the single crystal turbine blades. Despite the blades’ criticality in aircraft propulsion, there is currently no review article that summarizes the metallurgy, production process, failure mechanisms, and AM-based repair methods of the single crystal turbine blades. To address this existing gap, this review paper starts with a discussion on the composition of the single crystal superalloys, describes the traditional fabrication methods for the metallic single crystal turbine blades, estimates the material and energy loss when the blades are scrapped or reverted, and provides a summary of the AM technologies that are currently being investigated for their repair potential. In conclusion, based on the literature reviewed, this paper identifies new avenues for research and development approaches for advancing the fabrication and repair of single crystal turbine blades.
Multi-AUVs Cooperative Target Search Based on Autonomous Cooperative Search Learning Algorithm
Authors: Liu Yuan , Wang Min , Su Zhou , Luo Jun , Xie Shaorong , Peng Yan , Pu Huayan , Xie Jiajia , Zhou Rui
Published: October 2020

As a new type of marine unmanned intelligent equipment, autonomous underwater vehicle (AUV) has been widely used in the field of ocean observation, maritime rescue, mine countermeasures, intelligence reconnaissance, etc. Especially in the underwater search mission, the technical advantages of AUV are particularly obvious. However, limited operational capability and sophisticated mission environments are also difficulties faced by AUV. To make better use of AUV in the search mission, we establish the DMACSS (distributed multi-AUVs collaborative search system) and propose the ACSLA (autonomous collaborative search learning algorithm) integrated into the DMACSS. Compared with the previous system, DMACSS adopts a distributed control structure to improve the system robustness and combines an information fusion mechanism and a time stamp mechanism, making each AUV in the system able to exchange and fuse information during the mission. ACSLA is an adaptive learning algorithm trained by the RL (Reinforcement learning) method with a tailored design of state information, reward function, and training framework, which can give the system optimal search path in real-time according to the environment. We test DMACSS and ACSLA in the simulation test. The test results demonstrate that the DMACSS runs stably, the search accuracy and efficiency of ACSLA outperform other search methods, thus better realizing the cooperation between AUVs, making the DMACSS find the target more accurately and faster.
Assessing the Impacts of Agriculture and Its Trade on Philippine Biodiversity
Authors: Ortiz Andrea Monica D. , Torres Justine Nicole V.
Published: October 2020

Many Philippine species are at risk of extinction because of habitat loss and degradation driven by agricultural land use and land-use change. The Philippines is one of the world’s primary banana and pineapple producers. The input-intensive style of plantation agriculture for these typically exported crops has many adverse effects on the environment. While global studies have attempted to understand the biodiversity impacts of agricultural goods, there are few studies that have investigated the Philippines specifically. In this study, Philippine policies and data are investigated to better characterize the nexus between agriculture, biodiversity, and trade. An analysis of key national policies highlights that more stringent definitions and protections for biodiversity are needed to recognize the increasing roles that agricultural production, and importantly, its global trade, have on threatened Philippine species. A geographical analysis shows that many banana and pineapple plantations in Mindanao and their surrounding agricultural impact zones overlap with ecologically important areas, such as Protected Areas and Important Bird Areas. Overlaps of recorded species occurrence are observed within the immediate zones surrounding 250 plantations for banana and pineapple in Mindanao, with 83 threatened species of Philippine fauna and tree at risk of exposure to the impacts of intensive agriculture.
The Value Assessment and Planning of Industrial Mining Heritage as a Tourism Attraction: The Case of Las Médulas Cultural Space
Authors: Caamaño-Franco Iria , Suárez María
Published: October 2020

This article analyzes the heritage construction process or “heritagization” of Las Médulas gold mines, a prime example of how Spain’s mining heritage has been reused for tourism purposes. Based on a methodology combined documentary analysis and fieldwork, informal interviews with territorial actors and surveys targeting residents, this study addresses the complexities of integrating this cultural landscape into a tourism development strategy and analyzes the support and impacts perceived by the local population. The information gathered in this research is intended to facilitate the development of adequate planning and generate recommendations to mitigate the debate that has surrounded Las Médulas and confronted its stakeholders for years. The results show that the existence of multiple agents and institutions acting on the destination leads to problems of management and collaboration. In addition, the local population’s lack of involvement and awareness is also hindering integral tourism planning. There are a number of positive impacts mainly related to the increase in the tourist value of the image of the area and its historical and cultural heritage, as well as the consequences of financial management for tourism, which also help to predict the levels of support of residents to the tourist development of Las Médulas.
Differences in the Soil Quality Index for Two Contrasting Mediterranean Landscapes in Southern Spain
Authors: Sillero-Medina José A. , Hueso-González Paloma , Ruiz-Sinoga José D.
Published: October 2020

Soil quality indexes (SQIs) are very useful in assessing the status and edaphic health of soils. This is particularly the case in the Mediterranean area, where successive torrential rainfall episodes give rise to erosion and soil degradation processes; these are being exacerbated by the current climate crisis. The objective of this study was to analyze the soil quality in two contrasting Mediterranean watersheds in the province of Malaga (Spain): the middle and upper watersheds of the Rio Grande (sub-humid conditions) and the Benamargosa River (semi-arid conditions). Field soil sampling was carried out at representative sites, and the soils were subsequently analyzed for various edaphic properties in the laboratory. From the resulting data, the mean values have been grouped and reclassified, and, based on a multicriteria evaluation, an SQI for the study region was generated. The results show that there are major differences between the two watersheds, with optimal soil quality values being found in the Rio Grande watershed (very high soil quality—34.26%), but more unfavorable values occurring throughout most of the Benamargosa River watershed (very low soil quality—63.33%). Thus, these results have been subjected to a validation process in the field.
A Regression-Based Procedure for Markov Transition Probability Estimation in Land Change Modeling
Authors: Eastman J. Ronald , He Jiena
Published: October 2020

Land change models commonly model the expected quantity of change as a Markov chain. Markov transition probabilities can be estimated by tabulating the relative frequency of change for all transitions between two dates. To estimate the appropriate transition probability matrix for any future date requires the determination of an annualized matrix through eigendecomposition followed by matrix powering. However, the technique yields multiple solutions, commonly with imaginary parts and negative transitions, and possibly with no non-negative real stochastic matrix solution. In addition, the computational burden of the procedure makes it infeasible for practical use with large problems. This paper describes a Regression-Based Markov (RBM) approximation technique based on quadratic regression of individual transitions that is shown to always yield stochastic matrices, with very low error characteristics. Using land cover data for the 48 conterminous US states, median errors in probability for the five states with the highest rates of transition were found to be less than 0.00001 and the maximum error of 0.006 was of the same order of magnitude experienced by the commonly used compromise of forcing small negative transitions estimated by eigendecomposition to 0. Additionally, the technique can solve land change modeling problems of any size with extremely high computational efficiency.
The Effect of Instructed Second Language Learning on the Acoustic Properties of First Language Speech
Authors: Dmitrieva Olga , Jongman Allard , Sereno Joan A.
Published: October 2020

This paper reports on a comprehensive phonetic study of American classroom learners of Russian, investigating the influence of the second language (L2) on the first language (L1). Russian and English productions of 20 learners were compared to 18 English monolingual controls focusing on the acoustics of word-initial and word-final voicing. The results demonstrate that learners’ Russian was acoustically different from their English, with shorter voice onset times (VOTs) in [−voice] stops, longer prevoicing in [+voice] stops, more [−voice] stops with short lag VOTs and more [+voice] stops with prevoicing, indicating a degree of successful L2 pronunciation learning. Crucially, learners also demonstrated an L1 phonetic change compared to monolingual English speakers. Specifically, the VOT of learners’ initial English voiceless stops was shortened, indicating assimilation with Russian, while the frequency of prevoicing in learners’ English was decreased, indicating dissimilation with Russian. Word-final, the duration of preceding vowels, stop closures, frication, and voicing during consonantal constriction all demonstrated drift towards Russian norms of word-final voicing neutralization. The study confirms that L2-driven phonetic changes in L1 are possible even in L1-immersed classroom language learners, challenging the role of reduced L1 use and highlighting the plasticity of the L1 phonetic system.
Diversity, Composition and Functional Inference of Gut Microbiota in Indian Cabbage white Pieris canidia (Lepidoptera: Pieridae)
Authors: Wang Ying , Zhu Jianqing , Fang Jie , Shen Li , Ma Shuojia , Zhao Zimiao , Yu Weidong , Jiang Weibin
Published: October 2020

We characterized the gut microbial composition and relative abundance of gut bacteria in the larvae and adults of Pieris canidia by 16S rRNA gene sequencing. The gut microbiota structure was similar across the life stages and sexes. The comparative functional analysis on P. canidia bacterial communities with PICRUSt showed the enrichment of several pathways including those for energy metabolism, immune system, digestive system, xenobiotics biodegradation, transport, cell growth and death. The parameters often used as a proxy of insect fitness (development time, pupation rate, emergence rate, adult survival rate and weight of 5th instars larvae) showed a significant difference between treatment group and untreated group and point to potential fitness advantages with the gut microbiomes in P. canidia. These data provide an overall view of the bacterial community across the life stages and sexes in P. canidia.