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PLOS ONE Alerts: New Articles

accelerating the publication of peer-reviewed science

Updated: 2018-04-24T23:23:46Z


(XML) Correction: Acral melanoma detection using a convolutional neural network for dermoscopy images


by Chanki Yu, Sejung Yang, Wonoh Kim, Jinwoong Jung, Kee-Yang Chung, Sang Wook Lee, Byungho Oh


(XML) Correction: Controversy matters: Impacts of topic and solution controversy on the perceived credibility of a scientist who advocates


by Lindsey Beall, Teresa A. Myers, John E. Kotcher, Emily K. Vraga, Edward W. Maibach


(XML) Correction: A prophylactic multivalent vaccine against different filovirus species is immunogenic and provides protection from lethal infections with Ebolavirus and Marburgvirus species in non-human primates


by Benoit Callendret, Jort Vellinga, Kerstin Wunderlich, Ariane Rodriguez, Robin Steigerwald, Ulrike Dirmeier, Cedric Cheminay, Ariane Volkmann, Trevor Brasel, Ricardo Carrion, Luis D. Giavedoni, Jean L. Patterson, Chad E. Mire, Thomas W. Geisbert, Jay W. Hooper, Mo Weijtens, Jutta Hartkoorn-Pasma, Jerome Custers, Maria Grazia Pau, Hanneke Schuitemaker, Roland Zahn


(XML) Correction: Pilates training improves 5-km run performance by changing metabolic cost and muscle activity in trained runners


by Paula Finatto, Edson Soares Da Silva, Alexandre B. Okamura, Bruna P. Almada, Jorge L. L. Storniolo, Henrique B. Oliveira, Leonardo A. Peyré-Tartaruga


(XML) Elevated CO2 accelerates polycyclic aromatic hydrocarbon accumulation in a paddy soil grown with rice


by Fuxun Ai, Nico Eisenhauer, Yuwei Xie, Jianguo Zhu, Alexandre Jousset, Wenchao Du, Ying Yin, Xiaowei Zhang, Rong Ji, Hongyan Guo

The concentration of atmospheric carbon dioxide (CO2) and polycyclic aromatic hydrocarbons (PAHs) contents in the environment have been rising due to human activities. Elevated CO2 (eCO2) levels have been shown to affect plant physiology and soil microbes, which may alter the degradation of organic pollutants. Here, we study the effect of eCO2 on PAH accumulation in a paddy soil grown with rice. We collected soil and plant samples after rice harvest from a free-air CO2 enrichment (FACE) system, which had already run for more than 15 years. Our results show that eCO2 increased PAH concentrations in the soil, and we link this effect to a shift in soil microbial community structure and function. Elevated CO2 changed the composition of soil microbial communities, especially by reducing the abundance of some microbial groups driving PAH degradation. Our study indicates that elevated CO2 levels may weaken the self-cleaning ability of soils related to organic pollutants. Such changes in the function of soil microbial communities may threaten the quality of crops, with unknown implications for food safety and human health in future climate scenarios.(image)

(XML) Characterization of Transglutaminase 2 activity inhibitors in monocytes in vitro and their effect in a mouse model for multiple sclerosis


by Navina L. Chrobok, John G. J. M. Bol, Cornelis A. Jongenelen, John J. P. Brevé, Said El Alaoui, Micha M. M. Wilhelmus, Benjamin Drukarch, Anne-Marie van Dam

The neurodegenerative disease multiple sclerosis (MS) is pathologically characterized by the massive influx of immune cells into the central nervous system. This contributes to demyelination and axonal damage which causes symptoms such as motor and cognitive dysfunctions. The migration of leukocytes from the blood vessel is orchestrated by a multitude of factors whose determination is essential in reducing cellular influx in MS patients and the experimental autoimmune encephalomyelitis (EAE) animal model. The here studied enzyme tissue Transglutaminase (TG2) is present intracellularly, on the cell surface and extracellularly. There it contributes to cellular adhesion and migration via its transamidation activity and possibly by facilitating cellular interaction with the extracellular matrix. Previous data from our group showed reduced motor symptoms and cellular infiltration after using a pharmacological TG2 transamidation activity inhibitor in a rat EAE model. However, it remained elusive if the cross-linking activity of the enzyme resulted in the observed effects. To follow-up, we now characterized two new small molecule TG2 activity inhibitors, BJJF078 and ERW1041E. Both compounds are potent inhibitor of recombinant human and mouse Transglutaminase enzyme activity, mainly TG2 and the close related enzyme TG1. In addition they did not affect the binding of TG2 to the extracellular matrix substrate fibronectin, a process via which TG2 promotes cellular adhesion and migration. We found, that ERW1041E but not BJJF078 resulted in reduced EAE disease motor-symptoms while neither caused apparent changes in pathology (cellular influx), Transglutaminase activity or expression of inflammation related markers in the spinal cord, compared to vehicle treated controls. Although we cannot exclude issues on bioavailability and in vivo efficacy of the used compounds, we hypothesize that extracellular TG1/TG2 activity is of greater importance than (intra-)cellular activity in mouse EAE pathology.(image)

(XML) Effects of bioturbation on environmental DNA migration through soil media


by Christopher M. Prosser, Bryan M. Hedgpeth

Extracting and identifying genetic material from environmental media (i.e. water and soil) presents a unique opportunity for researchers to assess biotic diversity and ecosystem health with increased speed and decreased cost as compared to traditional methods (e.g. trapping). The heterogeneity of soil mineralogy, spatial and temporal variations however present unique challenges to sampling and interpreting results. Specifically, fate/transport of genetic material in the terrestrial environment represents a substantial data gap. Here we investigate to what degree, benthic fauna transport genetic material through soil. Using the red worm (Eisenia fetida), we investigate how natural movement through artificial soil affect the transport of genetic material. All experiments were run in Frabill® Habitat® II worm systems with approximately 5 cm depth of artificial soil. We selected an “exotic” source of DNA not expected to be present in soil, zebrafish (Danio rerio) tissue. Experiment groups contained homogenized zebrafish tissue placed in a defined location combined with a varying number of worms (10, 30 or 50 worms per experimental group). Experimental groups comprised two controls and three treatment groups (representing different worm biomass) in triplicate. A total of 210 soil samples were randomly collected over the course of 15 days to investigate the degree of genetic transfer, and the rate of detection. Positive detections were identified in 14% - 38% of samples across treatment groups, with an overall detection rate of 25%. These findings highlight two important issues when utilizing environmental DNA for biologic assessments. First, benthic fauna are capable of redistributing genetic material through a soil matrix. Second, despite a defined sample container and abundance of worm biomass, as many as 86% of the samples were negative. This has substantial implications for researchers and managers who wish to interpret environmental DNA results from terrestrial systems. Studies such as these will aid in future study protocol design and sample collection methodology.(image)

(XML) Improvement of kynurenine aminotransferase-II inhibitors guided by mimicking sulfate esters


by Gayan S. Jayawickrama, Alireza Nematollahi, Guanchen Sun, William Bret Church

The mammalian kynurenine aminotransferase (KAT) enzymes are a family of related isoforms that are pyridoxal 5’-phosphate-dependent, responsible for the irreversible transamination of kynurenine to kynurenic acid. Kynurenic acid is implicated in human diseases such as schizophrenia where it is found in elevated levels and consequently KAT-II, as the isoform predominantly responsible for kynurenic acid production in the brain, has been targeted for the development of specific inhibitors. One class of compounds that have also shown inhibitory activity towards the KAT enzymes are estrogens and their sulfate esters. Estradiol disulfate in particular is very strongly inhibitory and it appears that the 17-sulfate makes a significant contribution to its potency. The work here demonstrates that the effect of this moiety can be mirrored in existing KAT-II inhibitors, from the development of two novel inhibitors, JN-01 and JN-02. Both inhibitors were based on NS-1502 (IC50: 315 μM), but the deliberate placement of a sulfonamide group significantly improved the potency of JN-01 (IC50: 73.8 μM) and JN-02 (IC50: 112.8 μM) in comparison to the parent compound. This 3–4 fold increase in potency shows the potential of these moieties to be accommodated in the KAT-II active site and the effect they can have on improving inhibitors, and the environments in the KAT-II have been suitably modelled using docking calculations.(image)

(XML) Comparison of a new biometer using swept-source optical coherence tomography and a conventional biometer using partial coherence interferometry


by Tomoaki Higashiyama, Hazuki Mori, Fumi Nakajima, Masahito Ohji

The aim of this study was to compare the axial lengths (ALs) using a new biometer with swept-source optical coherence tomography (Argos) versus ALs using a conventional biometer with partial coherence interferometry (IOL Master, version 5). The ALs in 48 eyes of 48 cataract patients were measured with Argos using refractive indexes that correspond to the particular tissue and with IOL Master using a single refractive index. The eyes were divided into three subgroups by AL length: short-AL group (n = 16), <23.27 mm; intermediate-AL group (n = 16), 23.27–24.03 mm; long-AL group (n = 16), ≥24.04 mm. The ALs (mm) measured with the Argos and IOL Master biometers, respectively, were 22.77 ± 0.43 and 22.74 ± 0.44, 23.63 ± 0.21 and 23.62 ± 0.21, and 26.00 ± 1.61 and 26.05 ± 1.64 in the short-, intermediate-, and long-AL groups, respectively. The mean ALs with the Argos biometer were longer than those with the IOL Master biometer in the short-AL group (P = 0.002) There was no significant difference in the intermediate-AL groups (P = 0.14). In contrast, the mean ALs with the Argos biometer were shorter than those with the IOL Master biometer in the long-AL group (P < 0.001). Differences between the ALs measured with the two biometers were statistically significant in short- and long-AL subgroups. However, the differences might not be clinically significant.(image)

(XML) Relative age effects in international age group championships: A study of Spanish track and field athletes


by Javier Brazo-Sayavera, María Asunción Martínez-Valencia, Lisa Müller, Georgios Andronikos, Russell J. J. Martindale

The relative age effect is a well-researched phenomenon, however there is still a dearth of understanding in track and field and female sport. This study investigated the role of relative age on selection for international competition of Spanish age group athletes between 2006–2014. Six hundred and forty two athletes competed for Spain at U20 or U18 age group international competition (n = 359 males; 283 females) across 9 years. The birthdates of these athletes were compared against the population of registered athletes at that time (14,502 males; 10,096 females). The results highlighted the influential role of relative age on selection to these opportunities. In line with previous research, this effect was mediated by age and gender, with stronger effects for both males and younger athletes (U18). The data best supported the ‘maturation-selection’ hypothesis as a mechanism for RAEs. These results highlight the need to carefully consider the role and need for international competitive opportunities at different age groups. A number of possible context relevant solutions are discussed, including correction adjustments techniques and competition structure within track and field.(image)

(XML) Glycan modifications to the gp120 immunogens used in the RV144 vaccine trial improve binding to broadly neutralizing antibodies


by Rachel C. Doran, Gwen P. Tatsuno, Sara M. O’Rourke, Bin Yu, David L. Alexander, Kathryn A. Mesa, Phillip W. Berman

To date, the RV144 HIV vaccine trial has been the only study to show that immunization can confer protection from HIV infection. While encouraging, the modest 31.2% (P = 0.04) efficacy achieved in this study left significant room for improvement, and created an incentive to optimize the AIDSVAX B/E vaccine immunogens to increase the level of vaccine efficacy. Since the completion of the RV144 trial, our understanding of the antigenic structure of the HIV envelope protein, gp120, and of the specificity of broadly neutralizing monoclonal antibodies (bN-mAbs) that bind to it, has significantly improved. In particular, we have learned that multiple families of bN-mAbs require specific oligomannose glycans for binding. Both of the monomeric gp120 immunogens (MN- and A244-rgp120) in the AIDSVAX B/E vaccine used in the RV144 trial were enriched for glycans containing high levels of sialic acid, and lacked critical N-linked glycosylation sites required for binding by several families of bN-mAbs. The absence of these epitopes may have contributed to the low level of efficacy achieved in this study. In this report, we describe our efforts to improve the antigenic structure of the rgp120 immunogens used in the vaccine by optimizing glycan-dependent epitopes recognized by multiple bN-mAbs. Our results demonstrated that by shifting the location of one PNGS in A244-rgp120, and by adding two PNGS to MN-rgp120, in conjunction with the production of both proteins in a cell line that favors the incorporation of oligomannose glycans, we could significantly improve the binding by three major families of bN-mAbs. The immunogens described here represent a second generation of gp120-based vaccine immunogens that exhibit potential for use in RV144 follow-up studies.(image)

(XML) Inbreeding estimates in human populations: Applying new approaches to an admixed Brazilian isolate


by Renan B. Lemes, Kelly Nunes, Juliana E. P. Carnavalli, Lilian Kimura, Regina C. Mingroni-Netto, Diogo Meyer, Paulo A. Otto

The analysis of genomic data (~400,000 autosomal SNPs) enabled the reliable estimation of inbreeding levels in a sample of 541 individuals sampled from a highly admixed Brazilian population isolate (an African-derived quilombo in the State of São Paulo). To achieve this, different methods were applied to the joint information of two sets of markers (one complete and another excluding loci in patent linkage disequilibrium). This strategy allowed the detection and exclusion of markers that biased the estimation of the average population inbreeding coefficient (Wright’s fixation index FIS), which value was eventually estimated as around 1% using any of the methods we applied. Quilombo demographic inferences were made by analyzing the structure of runs of homozygosity (ROH), which were adapted to cope with a highly admixed population with a complex foundation history. Our results suggest that the amount of ROH <2Mb of admixed populations should be somehow proportional to the genetic contribution from each parental population.(image)

(XML) Higher expression of miR-133b is associated with better efficacy of erlotinib as the second or third line in non-small cell lung cancer patients


by Alessandra Bisagni, Maria Pagano, Sally Maramotti, Francesca Zanelli, Martina Bonacini, Elena Tagliavini, Luca Braglia, Massimiliano Paci, Andrea Mozzarelli, Stefania Croci

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (gefitinib, erlotinib and afatinib) are indicated as first-line therapy in patients with non-small cell lung cancer (NSCLC) whose tumors harbor activating mutations in the EGFR gene. Erlotinib is also used in second and third-line therapy for patients whose tumors have wild type EGFR but to date there are no validated biomarkers useful to identify which patients may benefit from this treatment. The expression level of four miRNAs: miR-133b, -146a, -7 and -21 which target EGFR was investigated by real-time PCR in tumor specimens from NSCLC patients treated with erlotinib administered as the second or third line. We found that miR-133b expression level better discriminated responder from non-responder patients to erlotinib. Higher levels of miR-133b in NSCLCs were associated with longer progression-free survival time of patients. Functional analyses on miR-133b through transfection of a miR-133b mimic in A549 and H1299 NSCLC cell lines indicated that increasing miR-133b expression level led to a decreased cell growth and altered morphology but did not affect sensitivity to erlotinib. The detection of miR-133b expression levels in tumors help in the identification of NSCLC patients with a better prognosis and who are likely to benefit from second and third-line therapy with erlotinib.(image)

(XML) On the advancement of highly cited research in China: An analysis of the Highly Cited database


by John Tianci Li

This study investigates the progress of highly cited research in China from 2001 to 2016 through the analysis of the Highly Cited database. The Highly Cited database, compiled by Clarivate Analytics, is comprised of the world’s most influential researchers in the 22 Essential Science Indicator fields as catalogued by the Web of Science. The database is considered an international standard for the measurement of national and institutional highly cited research output. Overall, we found a consistent and substantial increase in Highly Cited Researchers from China during the timespan. The Chinese institutions with the most Highly Cited Researchers- the Chinese Academy of Sciences, Tsinghua University, Peking University, Zhejiang University, the University of Science and Technology of China, and BGI Shenzhen- are all top ten universities or primary government research institutions. Further evaluation of separate fields of research and government funding data from the National Natural Science Foundation of China revealed disproportionate growth efficiencies among the separate divisions of the National Natural Science Foundation. The most development occurred in the fields of Chemistry, Materials Sciences, and Engineering, whereas the least development occurred in Economics and Business, Health Sciences, and Life Sciences.(image)

(XML) The benefit of quality control charts (QCC) for routine quantitative BCR-ABL1 monitoring in chronic myeloid leukemia


by Birgit Spiess, Nicole Naumann, Norbert Galuschek, Sébastien Rinaldetti, Ute Kossak-Roth, Irina Tarnopolscaia, Elena Felde, Alice Fabarius, Wolf-Karsten Hofmann, Susanne Saußele, Wolfgang Seifarth

Quantitative real-time polymerase chain reaction (qRT-PCR) is state of the art in molecular monitoring of minimal residual disease in chronic myeloid leukemia (CML). In this context, maintenance of assay fidelity and detection of technical inaccuracy are crucial. Beside multiple common negative controls for the clinical sample preparations, quality control charts (QCC) are a common validation tool to sustain high process quality by continuously recording of qRT-PCR control parameters. Here, we report on establishment and benefit of QCC in qRT-PCR-based CML diagnostics. The absolute quantification of BCR-ABL1 fusion transcripts in patient samples is based on coamplification of a serially diluted reference plasmid (pME-2). For QCC establishment the measured Ct values of each pME-2 standard dilution (4–400,000) of a test set resembling 21 sequential qRT-PCR experiments were recorded and statistically evaluated. Test set data were used for determination of warning limits (mean +/- 2-fold standard deviation) and control (intervention) limits (mean +/- 3-fold standard deviation) to allow rapid detection of defined out-of-control situations which may require intervention. We have retrospectively analyzed QCC data of 282 sequential qRT-PCR experiments (564 reactions). Data evaluation using QCCs revealed three out-of-control situations that required intervention like experiment repeats, renewal of pME-2 standards, replacement of reagents or personnel re-training. In conclusion, with minimal more effort and hands-on time QCC rank among the best tools to grant high quality and reproducibility in CML routine molecular diagnosis.(image)

(XML) Electrocardiogram-synchronized pulsatile extracorporeal life support preserves left ventricular function and coronary flow in a porcine model of cardiogenic shock


by Petr Ostadal, Mikulas Mlcek, Holger Gorhan, Ivo Simundic, Svitlana Strunina, Matej Hrachovina, Andreas Krüger, Dagmar Vondrakova, Marek Janotka, Pavel Hala, Martin Mates, Martin Ostadal, James C. Leiter, Otomar Kittnar, Petr Neuzil


Veno-arterial extracorporeal life support (ECLS) is increasingly being used to treat rapidly progressing or severe cardiogenic shock. However, it has been repeatedly shown that increased afterload associated with ECLS significantly diminishes left ventricular (LV) performance. The objective of the present study was to compare LV function and coronary flow during standard continuous-flow ECLS support and electrocardiogram (ECG)-synchronized pulsatile ECLS flow in a porcine model of cardiogenic shock.


Sixteen female swine (mean body weight 45 kg) underwent ECLS implantation under general anesthesia and artificial ventilation. Subsequently, acute cardiogenic shock, with documented signs of tissue hypoperfusion, was induced by initiating global myocardial hypoxia. Hemodynamic cardiac performance variables and coronary flow were then measured at different rates of continuous or pulsatile ECLS flow (ranging from 1 L/min to 4 L/min) using arterial and venous catheters, a pulmonary artery catheter, an LV pressure-volume loop catheter, and a Doppler coronary guide-wire.


Myocardial hypoxia resulted in declines in mean cardiac output to 1.7±0.7 L/min, systolic blood pressure to 64±22 mmHg, and LV ejection fraction (LVEF) to 22±7%. Synchronized pulsatile flow was associated with a significant reduction in LV end-systolic volume by 6.2 mL (6.7%), an increase in LV stroke volume by 5.0 mL (17.4%), higher LVEF by 4.5% (18.8% relative), cardiac output by 0.37 L/min (17.1%), and mean arterial pressure by 3.0 mmHg (5.5%) when compared with continuous ECLS flow at all ECLS flow rates (P<0.05). At selected ECLS flow rates, pulsatile flow also reduced LV end-diastolic pressure, end-diastolic volume, and systolic pressure. ECG-synchronized pulsatile flow was also associated with significantly increased (7% to 22%) coronary flow at all ECLS flow rates.


ECG-synchronized pulsatile ECLS flow preserved LV function and coronary flow compared with standard continuous-flow ECLS in a porcine model of cardiogenic shock.


(XML) Discrimination and prediction of the origin of Chinese and Korean soybeans using Fourier transform infrared spectrometry (FT-IR) with multivariate statistical analysis


by Byeong-Ju Lee, Yaoyao Zhou, Jae Soung Lee, Byeung Kon Shin, Jeong-Ah Seo, Doyup Lee, Young-Suk Kim, Hyung-Kyoon Choi

The ability to determine the origin of soybeans is an important issue following the inclusion of this information in the labeling of agricultural food products becoming mandatory in South Korea in 2017. This study was carried out to construct a prediction model for discriminating Chinese and Korean soybeans using Fourier-transform infrared (FT-IR) spectroscopy and multivariate statistical analysis. The optimal prediction models for discriminating soybean samples were obtained by selecting appropriate scaling methods, normalization methods, variable influence on projection (VIP) cutoff values, and wave-number regions. The factors for constructing the optimal partial-least-squares regression (PLSR) prediction model were using second derivatives, vector normalization, unit variance scaling, and the 4000–400 cm–1 region (excluding water vapor and carbon dioxide). The PLSR model for discriminating Chinese and Korean soybean samples had the best predictability when a VIP cutoff value was not applied. When Chinese soybean samples were identified, a PLSR model that has the lowest root-mean-square error of the prediction value was obtained using a VIP cutoff value of 1.5. The optimal PLSR prediction model for discriminating Korean soybean samples was also obtained using a VIP cutoff value of 1.5. This is the first study that has combined FT-IR spectroscopy with normalization methods, VIP cutoff values, and selected wave-number regions for discriminating Chinese and Korean soybeans.(image)

(XML) Pathogenic adaptations of Colletotrichum fungi revealed by genome wide gene family evolutionary analyses


by Xiaofei Liang, Bo Wang, Qiuyue Dong, Lingnan Li, Jeffrey A. Rollins, Rong Zhang, Guangyu Sun

The fungal genus Colletotrichum contains hemibiotrophic phytopathogens being highly variable in host and tissue specificities. We sequenced a C. fructicola genome (1104–7) derived from an isolate of apple in China and compared it with the reference genome (Nara_gc5) derived from an isolate of strawberry in Japan. Mauve alignment and BlastN search identified 0.62 Mb lineage-specific (LS) genomic regions in 1104–7 with a length criterion of 10 kb. Genes located within LS regions evolved more dynamically, and a strongly elevated proportion of genes were closely related to non-Colletotrichum sequences. Two LS regions, containing nine genes in total, showed features of fungus-to-fungus horizontal transfer supported by both gene order collinearity and gene phylogeny patterns. We further compared the gene content variations among 13 Colletotrichum and 11 non-Colletotrichum genomes by gene function annotation, OrthoMCL grouping and CAFE analysis. The results provided a global evolutionary picture of Colletotrichum gene families, and identified a number of strong duplication/loss events at key phylogenetic nodes, such as the contraction of the detoxification-related RTA1 family in the monocot-specializing graminicola complex and the expansions of several ammonia production-related families in the fruit-infecting gloeosporioides complex. We have also identified the acquirement of a RbsD/FucU fucose transporter from bacterium by the Colletotrichum ancestor. In sum, this study summarized the pathogenic evolutionary features of Colletotrichum fungi at multiple taxonomic levels and highlights the concept that the pathogenic successes of Colletotrichum fungi require shared as well as lineage-specific virulence factors.(image)

(XML) Liver disease burden and required treatment expenditures for hepatitis C virus (HCV) infection in Thailand: Implications for HCV elimination in the new therapeutic era, a population-based study


by Rujipat Wasitthankasem, Preeyaporn Vichaiwattana, Nipaporn Siripon, Nawarat Posuwan, Chompoonut Auphimai, Sirapa Klinfueng, Napha Thanetkongtong, Viboonsak Vuthitanachot, Supapith Saiyatha, Chaiwat Thongmai, Saowakon Sochoo, Natnada Pongsuwan, Kittiyod Poovorawan, Pisit Tangkijvanich, Yong Poovorawan

The prevalence of hepatitis C virus (HCV) infection has been decreasing globally, but the growing effects of HCV-related morbidity and mortality remain of concern. Advances in curative medicine, involving direct-acting antivirals (DAAs), have led many countries to aim to eradicate HCV. Information on epidemiology and disease burden is essential for national policy development. Thus, this study aimed to determine the HCV-related hepatic disease burden in areas of Thailand with high and average HCV prevalence in order to extrapolate the viral burden across Thailand. Patients previously diagnosed as positive for anti-HCV antibodies were recruited to assess chronic HCV infection (CHC) status, liver function, HCV-RNA level and hepatic fibrosis. The number of patients eligible for Universal Health Coverage (UC) scheme and the approximately required expenditure on interferon (IFN)-based treatment were estimated. In areas of both high (12%) and average (2%) HCV viremic prevalence, over half of the patients (52.2% to 62.5%) had advanced liver fibrosis (F3 and F4). A striking percentage of patients with F4 (38.9%) were found in the high-prevalence area, while comparable proportions of advanced liver fibrosis presented in the two areas and disease burden peaked at 50–59 years. Under the current UC program treatment scenario, 78–83% of CHC patients with stage F2–F4 fibrosis were eligible for treatment. The estimated expenditure required for overall CHC treatment across the whole country was 1,240 million USD at this current status, but the declining cost of generic DAA-based therapy may reduce the requirement to <90 million USD. This study provides information on the estimated number of CHC patients, liver disease burden and expenditure requirements for Thailand. To eliminate HCV by 2030, proactive government strategies raising public health to minimize transmission and emphasizing targeted screen-and-treatment programs, novel therapeutic guideline development for decentralizing treatment, and effective budget allocation are urgently needed.(image)

(XML) Cerebral desaturation in heart failure: Potential prognostic value and physiologic basis


by Yu-Jen Chen, Jong-Shyan Wang, Chih-Chin Hsu, Pyng-Jing Lin, Feng-Chun Tsai, Ming-Shien Wen, Chi-Tai Kuo, Shu-Chun Huang

Cerebral tissue oxygen saturation (SctO2) reflects cerebral perfusion and tissue oxygen consumption, which decline in some patients with heart failure with reduced ejection fraction (HFrEF) or stroke, especially during exercise. Its physiologic basis and clinical significance remain unclear. We aimed to investigate the association of SctO2 with oxygen transport physiology and known prognostic factors during both rest and exercise in patients with HFrEF or stroke. Thirty-four HFrEF patients, 26 stroke patients, and 17 healthy controls performed an incremental cardiopulmonary exercise test using a bicycle ergometer. Integrated near-infrared spectroscopy and automatic gas analysis were used to measure cerebral tissue oxygenation and cardiac and ventilatory parameters. We found that SctO2 (rest; peak) were significantly lower in the HFrEF (66.3±13.3%; 63.4±13.8%,) than in the stroke (72.1±4.2%; 72.7±4.5%) and control (73.1±2.8%; 72±3.2%) groups. In the HFrEF group, SctO2 at rest (SctO2rest) and peak SctO2 (SctO2peak) were linearly correlated with brain natriuretic peptide (BNP), peak oxygen consumption (V˙O2peak), and oxygen uptake efficiency slope (r between -0.561 and 0.677, p < 0.001). Stepwise linear regression showed that SctO2rest was determined by partial pressure of end-tidal carbon dioxide at rest (PETCO2rest), hemoglobin, and mean arterial pressure at rest (MAPrest) (adjusted R = 0.681, p < 0.05), while SctO2peak was mainly affected by peak carbon dioxide production (V˙CO2peak) (adjusted R = 0.653, p < 0.05) in patients with HFrEF. In conclusion, the study delineates the relationship of cerebral saturation and parameters associated with oxygen delivery. Moreover, SctO2peak and SctO2rest are correlated with some well-recognized prognostic factors in HFrEF, suggesting its potential prognostic value.(image)

(XML) Nitrogen diagnosis based on dynamic characteristics of rice leaf image


by Yuanyuan Sun, Shaochun Zhu, Xuan Yang, Melanie Valerie Weston, Ke Wang, Zhangquan Shen, Hongwei Xu, Lisu Chen

Digital image processing is widely used in the non-destructive diagnosis of plant nutrition. Previous plant nitrogen diagnostic studies have mostly focused on characteristics of the rice canopy or leaves at some specific points in time, with the long sampling intervals unable to provide detailed and specific “dynamic features.” According to plant growth mechanisms, the dynamic changing rate in leaf shape and color differ between different nitrogen supplements. Therefore, the objective of this study was to diagnose nitrogen stress levels by analyzing the dynamic characteristics of rice leaves. Scanning technology was implemented to collect rice leaf images every 3 days, with the characteristics of the leaves from different leaf positions extracted utilizing MATLAB. Newly developed shape characteristics such as etiolation area (EA) and etiolation degree (ED), in addition to shape (area, perimeter) and color characteristics (green, normalized red index, etc.), were used to quantify the process of leaf change. These characteristics allowed sensitive indices to be established for further model validation. Our results indicate that the changing rates in dynamic characteristics, in particular the shape characteristics of the first incomplete leaf (FIL) and the characteristics of the 3rd leaf (leaf color and etiolation indices), expressed obvious distinctions among different nitrogen treatments. Consequently, we achieved acceptable diagnostic accuracy (training accuracy 77.3%, validation accuracy 64.4%) by using the FIL at six days after leaf emergence, and the new shape characteristics developed in this article (ED and EA) also showed good performance in nitrogen diagnosis. Based on the aforementioned results, dynamic analysis is valuable not only in further studies but also in practice.(image)

(XML) Support amongst UK pig farmers and agricultural stakeholders for the use of food losses in animal feed


by Erasmus K. H. J. zu Ermgassen, Moira Kelly, Eleanor Bladon, Ramy Salemdeeb, Andrew Balmford

While food losses (foods which were intended for human consumption, but which ultimately are not directly eaten by people) have been included in animal feed for millennia, the practice is all but banned in the European Union. Amid recent calls to promote a circular economy, we conducted a survey of pig farmers (n = 82) and other agricultural stakeholders (n = 81) at a UK agricultural trade fair on their attitudes toward the use of food losses in pig feed, and the potential relegalisation of swill (the use of cooked food losses as feed). While most respondents found the use of feeds containing animal by-products or with the potential for intra-species recycling (i.e. pigs eating pork products) to be less acceptable than feeds without, we found strong support (>75%) for the relegalisation of swill among both pig farmers and other stakeholders. We fit multi-hierarchical Bayesian models to understand people’s position on the relegalisation of swill, finding that respondents who were concerned about disease control and the perception of the pork industry supported relegalisation less, while people who were concerned with farm financial performance and efficiency or who thought that swill would benefit the environment and reduce trade-deficits, were more supportive. Our results provide a baseline estimate of support amongst the large-scale pig industry for the relegalisation of swill, and suggest that proponents for its relegalisation must address concerns about disease control and the consumer acceptance of swill-fed pork.(image)

(XML) Ankylosing spondylitis disease activity score is related to NSAID use, especially in patients treated with TNF-α inhibitors


by Marlies J. G. Carbo, Anneke Spoorenberg, Fiona Maas, Elisabeth Brouwer, Reinhard Bos, Hendrika Bootsma, Eveline van der Veer, Freke Wink, Suzanne Arends


Non-steroidal anti-inflammatory drugs (NSAIDs) are regarded as the cornerstone of conventional treatment for AS. However little is known about concomitant NSAID use during treatment (with TNF-α inhibitors) in daily clinical practice.

Methods and findings

Consecutive patients from the GLAS cohort were included. NSAID use and ASAS-NSAID index were evaluated at group level and at individual patient level during 52 weeks of follow-up. Analyses were stratified for treatment regimen. Generalized estimating equations (GEE) was used to evaluate NSAID use in relation to assessments of disease activity over time. In patients starting TNF-α inhibitors (n = 254), 79% used NSAIDs at baseline and this proportion decreased significantly to 38% at 52 weeks. ASAS-NSAID index also decreased significantly from median 65 to 0. In patients on conventional treatment (n = 139), 74% used NSAIDs at baseline with median ASAS-NSAID index of 50 and this remained stable during follow-up. At each follow-up visit, approximately half of the patients changed their type or dose of NSAIDs. GEE analysis over time showed that NSAID use was associated with AS disease activity score (p<0.05). This relation was more pronounced in patients treated with TNF-α inhibitors compared to conventional treatment (B = 0.825 vs. B = 0.250).


In this observational cohort of established AS patients, there was no difference in baseline NSAID use between patients with and without indication for TNF-α inhibitors. NSAID use decreased significantly after starting TNF-α inhibitors. During conventional treatment, NSAID use remained stable at group level. However, NSAID use changed frequently at individual patient level and was significantly associated with disease activity.


(XML) Experimental autoimmune encephalomyelitis (EAE) up-regulates the mitochondrial activity and manganese superoxide dismutase (MnSOD) in the mouse renal cortex


by Balamurugan Packialakshmi, Xiaoming Zhou

Increases of the activity of mitochondrial electron transport chain generally lead to increases of production of ATP and reactive oxygen species (ROS) as by-products. MnSOD is the first line of defense against the stress induced by mitochondrial ROS. Our previous studies demonstrated that EAE progression increased Na,K-ATPase activity in the mouse kidney cortex. Since mitochondria are the major source of ATP, our present studies were sought to determine whether EAE progression increased mitochondrial activity. We found that severe EAE increased mitochondrial complex II and IV activities without significantly affecting complex I activity with corresponding increases of ROS in the isolated mitochondria and native kidney cortex. Severe EAE augmented both cytosolic and mitochondrial MnSOD protein levels and activities and decreased the specific activity of mitochondrial MnSOD when the total mitochondrial MnSOD activity was normalized to the protein level. Using HEK293 cells as a model free of interference from immune reactions, we found that activation of Na,K-ATPase by monensin for 24 hours increased complex II activity, mitochondrial ROS and MnSOD protein abundance, and decreased the specific activity of the mitochondrial MnSOD. Inhibition of Na,K-ATPase by ouabain or catalase attenuated the effects of monensin on the mitochondrial complex II activity, ROS, MnSOD protein level and specific activity. Kockdown of MnSOD by RNAi reduced the mitochondrial ability to generate ATP. In conclusion, EAE increases mitochondrial activity possibly to meet the energy demand from increased Na,K-ATPase activity. EAE increases mitochondrial MnSOD protein abundance to compensate for the loss of the specific activity of the enzyme, thus minimizing the harmful effects of ROS.(image)

(XML) Effect of monotherapy with darunavir/cobicistat on viral load and semen quality of HIV-1 patients


by Miguel A. López-Ruz, Miguel A. López-Zúñiga, María Carmen Gonzalvo, Antonio Sampedro, Juan Pasquau, Carmen Hidalgo, Javier Rosario, Jose Antonio Castilla

Many patients previously using darunavir/ritonavir (DRV/r) (800/100mg) have switched to darunavir/cobicistat (DRV/C) (800/150 mg) either as part of triple therapy (ART) or as monotherapy with DRV (mDRV). The latter approach continues to be used in some countries for patients receiving long-term treatment. However, to date, the behaviour of DRV/C in the seminal compartment has not been analysed. This study explores how the combination behaves in monotherapy, with respect to the control of viral load and seminal quality. To this end, we studied 20 patients who were treated with mDRV/C after previous treatment with mDRV/r for at least 24 weeks. A viral load control in seminal plasma similar to that published in the literature was observed after 24 weeks of treatment with mDRV/C (viral load positivity in 20% of patients). Similarly, semen quality was confirmed (70% normozoospermic) in patients treated with this formulation, as has previously been reported for ART and mDRV/r. The DRV levels measured in seminal plasma were above EC50, regardless of whether the seminal viral load was positive or negative. We conclude that this mDRV/C co-formulation behaves like mDRV/r in seminal plasma in terms of viral load control and semen quality.(image)

(XML) Estimation of the marginal effect of regular drug use on multiple sclerosis in the Iranian population


by Ibrahim Abdollahpour, Saharnaz Nedjat, Mohammad Ali Mansournia, Tibor Schuster

There are only few reports regarding the role of lifetime drug or substance use in multiple sclerosis (MS) etiology. In this study, we investigated the potential effect of drug or substance exposure on the onset of MS diagnosis. We conducted a population-based incident case control study in Tehran. Cases (n = 547) were 15–50 years old persons with MS identified from the Iranian Multiple Sclerosis Society (IMSS) register during August 7, 2013, and November 17, 2015. Population-based controls (n = 1057) were 15–50 years old and were recruited by random digit telephone dialing. Inverse-probability-of-treatment weighing (IPTW) using two sets of propensity scores (PSs) was used to estimate marginal incidence odds ratios (ORs) for MS contrasting pre-specified substance use. The estimated marginal OR was 6.03 (95% confidence interval: 3.54;10.3, using trimmed weights at the 95th percentile of the stabilized weight distribution) in both IPTW analyses comparing lifetime substance use (opioids, cannabis, inhalants, hallucinogens and stimulants) for at least one time monthly during a six-months or longer period vs. no such history of drug use. Subject to limitation of causal claims based on case-control studies, this study suggests that monthly drug or substance use for a period of at least six consecutive months, may increase the risk of MS by factor 3.5 or higher.(image)