bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Bradyrhizobium elkanii USDA61 Type III Effectors Determining Symbiosis with Vigna mungo
Authors: Nguyen Hien P. , Ratu Safirah T. N. , Yasuda Michiko , Teaumroong Neung , Okazaki Shin
Published: April 2020

Bradyrhizobium elkanii USDA61 possesses a functional type III secretion system (T3SS) that controls host-specific symbioses with legumes. Here, we demonstrated that B. elkanii T3SS is essential for the nodulation of several southern Asiatic Vigna mungo cultivars. Strikingly, inactivation of either Nod factor synthesis or T3SS in B. elkanii abolished nodulation of the V. mungo plants. Among the effectors, NopL was identified as a key determinant for T3SS-dependent symbiosis. Mutations of other effector genes, such as innB, nopP2, and bel2-5, also impacted symbiotic effectiveness, depending on host genotypes. The nopL deletion mutant formed no nodules on V. mungo, but infection thread formation was still maintained, thereby suggesting its pivotal role in nodule organogenesis. Phylogenetic analyses revealed that NopL was exclusively conserved among Bradyrhizobium and Sinorhizobium (Ensifer) species and showed a different phylogenetic lineage from T3SS. These findings suggest that V. mungo evolved a unique symbiotic signaling cascade that requires both NFs and T3Es (NopL).
Molecular Mechanism Underlying Mechanical Wounding-Induced Flavonoid Accumulation in Dalbergia odorifera T. Chen, an Endangered Tree That Produces Chinese Rosewood
Authors: Sun Ying , Gao Mei , Kang Seogchan , Yang Chengmin , Meng Hui , Yang Yun , Zhao Xiangsheng , Gao Zhihui , Xu Yanhong , Jin Yue , Zhao Xiaohong , Zhang Zheng , Han Jianping
Published: April 2020

Dalbergia odorifera, a critically endangered tree species, produces heartwood containing a vast variety of flavonoids. This heartwood, also known as Chinese rosewood, has high economic and medicinal value, but its formation takes several decades. In this study, we showed that discolored wood induced by pruning displays similar color, structure, and flavonoids content to those of natural heartwood, suggesting that wounding is an efficient method for inducing flavonoid production in D. odorifera. Transcriptome analysis was performed to investigate the mechanism underlying wounding-induced flavonoids production in D. odorifera heartwood. Wounding upregulated the expression of 90 unigenes, which covered 19 gene families of the phenylpropanoid and flavonoid pathways, including PAL, C4H, 4CL, CHS, CHI, 6DCS, F3’5’H, F3H, FMO, GT, PMAT, CHOMT, IFS, HI4’OMT, HID, IOMT, I2’H, IFR, and I3’H. Furthermore, 47 upregulated unigenes were mapped to the biosynthesis pathways for five signal molecules (ET, JA, ABA, ROS, and SA). Exogenous application of these signal molecules resulted in the accumulation of flavonoids in cell suspensions of D. odorifera, supporting their role in wounding-induced flavonoid production. Insights from this study will help develop new methods for rapidly inducing the formation of heartwood with enhanced medicinal value.
ATP2A2 SINE Insertion in an Irish Terrier with Darier Disease and Associated Infundibular Cyst Formation
Authors: Linek Monika , Doelle Maren , Leeb Tosso , Bauer Anina , Leuthard Fabienne , Henkel Jan , Bannasch Danika , Jagannathan Vidhya , Welle Monika M.
Published: April 2020

A 4-month-old female Irish Terrier presented with a well demarcated ulcerative and crusting lesion in the right ear canal. Histological analysis revealed epidermal hyperplasia with severe acantholysis affecting all suprabasal layers of the epidermis, which prompted a presumptive diagnosis of canine Darier disease. The lesion was successfully treated by repeated laser ablation of the affected epidermis. Over the course of three years, the dog additionally developed three dermal nodules of up to 4 cm in diameter that were excised and healed without complications. Histology of the excised tissue revealed multiple infundibular cysts extending from the upper dermis to the subcutis. The cysts were lined by squamous epithelium, which presented with abundant acantholysis of suprabasal keratinocytes. Infundibular cysts represent a novel finding not previously reported in Darier patients. Whole genome sequencing of the affected dog was performed, and the functional candidate genes for Darier disease (ATP2A2) and Hailey-Hailey disease (ATP2C1) were investigated. The analysis revealed a heterozygous SINE insertion into the ATP2A2 gene, at the end of intron 14, close to the boundary of exon 15. Analysis of the ATP2A2 mRNA from skin of the affected dog demonstrated a splicing defect and marked allelic imbalance, suggesting nonsense-mediated decay of the resulting aberrant transcripts. As Darier disease in humans is caused by haploinsufficiency of ATP2A2, our genetic findings are in agreement with the clinical and histopathological data and support the diagnosis of canine Darier disease.
Characterization of the IS200/IS605 Insertion Sequence Family in Halanaerobium Hydrogeniformans
Authors: Sadler Michael , R. Mormile Melanie , L. Frank Ronald
Published: April 2020

Mobile DNA elements play a significant evolutionary role by promoting genome plasticity. Insertion sequences are the smallest prokaryotic transposable elements. They are highly diverse elements, and the ability to accurately identify, annotate, and infer the full genomic impact of insertion sequences is lacking. Halanaerobium hydrogeniformans is a haloalkaliphilic bacterium with an abnormally high number of insertion sequences. One family, IS200/IS605, showed several interesting features distinct from other elements in this genome. Twenty-three loci harbor elements of this family in varying stages of decay, from nearly intact to an ends-only sequence. The loci were characterized with respect to two divergent open reading frames (ORF), tnpA and tnpB, and left and right ends of the elements. The tnpB ORF contains two nearly identical insert sequences that suggest recombination between tnpB ORF is occurring. From these results, insertion sequence activity can be inferred, including transposition capability and element interaction.
VviWRKY40, a WRKY Transcription Factor, Regulates Glycosylated Monoterpenoid Production by VviGT14 in Grape Berry
Authors: Li Xiangyi , He Lei , An Xiaohui , Yu Keji , Meng Nan , Duan Changqing , Pan Qiu-Hong
Published: April 2020

Glycosylated volatile precursors are important, particularly in wine grape berries, as they contribute to the final aroma in wines by releasing volatile aglycones during yeast fermentation and wine storage. Previous study demonstrated that VviGT14 was functioned as a critical monoterpene glucosyltransferase in grape berry, while the transcriptional regulation mechanism of VviGT14 was still unknown. Here we identified VviWRKY40 as a binding factor of VviGT14 promoter by both DNA pull-down and yeast one-hybrid screening, followed by a series of in vitro verification. VviWRKY40 expression pattern negatively correlated with that of VviGT14 in grape berries. And the suppressor role of VviWRKY40 was further confirmed by using the dual luciferase assay with Arabidopsis protoplast and grape cell suspension system. Furthermore, the grape suspension cell ABA treatment study showed that ABA downregulated VviWRKY40 transcript level but promoted that of VviGT14, indicating that VviWRKY40 was at the downstream of ABA signal transduction network to regulate monoterpenoid glycosylation. These data extend our knowledge of transcriptional regulation of VviGT14, and provide new targets for grape breeding to alter monoterpenoid composition.
Immediate Effects of Ankle–Foot Orthosis Using Wire on Static Balance of Patients with Stroke with Foot Drop: A Cross-Over Study
Authors: Lee Jung-Hoon , Choi Im-Rak , Choi Hyun-Su
Published: April 2020

The aim of this study was to investigate the immediate static balance effects of bare foot, UD-Flex ankle–foot orthosis (AFO), and AFO using wire (AOW) of patients with stroke with foot drop. Seventeen patients with stroke with foot drop (8 men and 9 women) were randomized to three conditions (bare foot, UD-Flex AFO, or AOW made with a flexible material). Static balance was assessed using the Zebris (Zebris GmbH, Isny, Germany) and BioRescue (RM Ingenierie, Rodez, France) pressure platform by a single examiner, who did not design the AOW. The order of testing with the equipment was random. The center of pressure path length (mm) measured using Zebris showed significant differences among the three conditions (bare foot, 484.47 ± 208.42; UD-Flex AFO, 414.59 ± 144.43; AOW, 318.29 ± 157.60) (p < 0.05). The bare-foot condition was not significantly different from the UD-Flex AFO condition (p > 0.05), but was significantly different from the AOW condition (p < 0.05). The surface area ellipse (mm2) measured using BioRescue showed significant differences among the three conditions (bare foot, 241.35 ± 153.76; UD-Flex AFO, 277.41 ± 381.83; AOW, 68.06 ± 48.98) (p < 0.05). The bare-foot condition was not significantly different from the UD-Flex AFO condition (p > 0.05), but the AOW condition was significantly different from the bare-foot (p < 0.05) and from the UD-Flex AFO conditions (p < 0.05). We suggest using the AOW made of flexible materials and wire instead of the UD-Flex AFO to improve immediate static balance of patients with stroke with foot drop after stroke. Further studies on the effects of dynamic balance and gait are required.
Prevalence of Physical Activity and Sedentary Behavior among Chinese Children and Adolescents: Variations, Gaps, and Recommendations
Authors: Shen Hejun , Yan Jin , Hong Jin-Tao , Clark Cain , Yang Xian-Nan , Liu Yang , Chen Si-Tong
Published: April 2020

Physical-activity (PA) and sedentary-behavior (SB) assessment is of particular importance in the promotion of health in young people. However, there is no comprehensive overview of PA and SB from national surveys among Chinese children and adolescents. Following a literature search for Chinese national health surveys, 11 papers from six national surveys were found. Of the included studies, the majority applied self-reported questionnaires to estimate the prevalence of PA and SB. Owing to different definitions of the prevalence of PA and SB and various measures, a large variation in prevalence of PA and SB was observed. Such variations were attributable to methodological and practical issues. This study highlights the current gaps in estimating the national prevalence of PA and SB among Chinese children and adolescents, which should be addressed. To improve the quality of PA and SB surveillance, standardized measurement protocols to estimate the prevalence of PA and SB more accurately among Chinese children and adolescents are urgently required.
Interventions to Improve the Quality of Life of Patients with Chronic Obstructive Pulmonary Disease: A Global Mapping During 1990–2018
Authors: Vu Giap Van , Ha Giang Hai , Nguyen Cuong Tat , Vu Giang Thu , Pham Hai Quang , Latkin Carl A. , Tran Bach Xuan , Ho Roger C. M. , Ho Cyrus S. H.
Published: April 2020

Chronic obstructive pulmonary disease (COPD) has been considered a significant health challenge globally in recent years, which affects different aspects of the quality-of-life (QoL). A review was conducted of research output, research topics, and landscape to have a global view of the papers mentioning the interventions to increase QoL of patients with COPD. A total of 3242 research items from Web of Science during the period 1990–2018 were downloaded and analyzed. Analyses based on the different levels of data and methods using using VOSviewer software tool (version 1.16.15, Centre for Science and Technology Studies (CWTS), Leiden University, Leiden, The Netherlands) and Latent Dirichlet allocation. By exploring the trends in research productivity and topics, an increase was found in the number of papers mentioning non-pharmacological interventions as well as mental health illness and QoL among patients with COPD. In conclusion, the research on the interventions to increase the QoL of patients with COPD has attracted scientists globally. It is suggested that more research should be conducted on the effectiveness of non-pharmacological therapies to increase QoL of patients with COPD that can be applied broadly in the community. The collaboration and support from developed countries to developing countries are needed to increase the QoL of people living with COPD.
Performance Comparison of Different Constructed Wetlands Designs for the Removal of Personal Care Products
Authors: Ilyas Huma , van Hullebusch Eric D.
Published: April 2020

This research investigates the performance of four types of constructed wetlands (CWs): free water surface CW (FWSCW), horizontal flow CW (HFCW), vertical flow CW (VFCW), and hybrid CW (HCW) for the removal of 20 personal care products (PCPs), based on secondary data compiled for 137 CWs reported in 39 peer reviewed journal papers. In spite of considerable variation in the re-moval efficiency of PCPs, CWs prove to be a promising treatment technology. The average removal efficiency of 15 widely studied PCPs ranged from 9.0% to 84%. Although CWs effectively reduced the environmental risks caused by many PCPs, triclosan was still classified under high risk category based on effluent concentration. Five other PCPs were classified under medium risk category (triclocarban > methylparaben > galaxolide > oxybenzone > methyl dihydrojasmonate). In most of the examined PCPs, adsorption and/or sorption is the most common removal mechanism followed by biodegradation and plant uptake. The comparatively better performance of HCW followed by VFCW, HFCW, and FWSCW might be due to the co-existence of aerobic and anaerobic conditions, and longer hydraulic retention time enhancing the removal of PCPs (e.g., triclosan, methyl dihydro-jasmonate, galaxolide, tonalide, and oxybenzone), which are removed under both conditions and by adsorption/sorption processes.
Concentration, Spatial Distribution, Contamination Degree and Human Health Risk Assessment of Heavy Metals in Urban Soils across China between 2003 and 2019—A Systematic Review
Authors: Tong Shuangmei , Li Hairong , Wang Li , Tudi Muyesaier , Yang Linsheng
Published: April 2020

This study provides an overview of the studies of heavy metal pollution regarding As, Cd, Cr, Hg, Pb, Cu, Zn and Ni in the urban soils throughout 71 cities of China, based on data from online literature, during the period 2003–2019. The concentrations, spatial distributions, contamination degrees and health risks of heavy metals in the urban soils were evaluated. The results demonstrated that the mean values of eight heavy metals all exceeded the soil background values in China, and the kriging interpolation method showed that the hot-spot cities with heavy metal contamination in urban soils were mainly concentrated in the southwest, southcentral, southeast coast, northcentral and northwest regions of China. The geoaccumulation index (Igeo) indicated that Hg and Cd were at moderate contamination levels and that the levels of the other six metals did not appear contamination. The pollution index (PI) showed that Cd and Hg reached high contamination levels, and the other metals reached moderate contamination levels. The integrated pollution index (IPI) and potential ecological risk index (PRI) indicated that the integral urban soils in the study areas ranked high contamination levels and moderate ecological risk degree, respectively, and Cd and Hg should be labeled as priority metals for control in the urban soils around China. The human health risk assessments for the heavy metals indicated that ingestion was the dominant exposure pathway for having adverse effects on human health. The mean Hazard index (HI) values of eight heavy metals all showed that adverse effects on human health were unlikely, and the mean carcinogenic (CR) values of As, Cr and Ni for children and adults all suggested an acceptable carcinogenic risk to human beings. In addition, children exposed to these heavy metals faced more serious non-carcinogenic and carcinogenic health threats compared to adults. The results could provide valuable information for demanding the better control of heavy metal pollution and mitigation of the adverse effects on residents by environmental regulators in national urban regions.
Assessing the Effect of the Chinese River Chief Policy for Water Pollution Control under Uncertainty—Using Chaohu Lake as a Case
Authors: Xu Xia , Wu Fengping , Zhang Lina , Gao Xin
Published: April 2020

The River Chief Policy (RCP) is an innovative water resource management system in China aimed at managing water pollution and improving water quality. Though the RCP has been piloted in some river basins of China, few scholars have studied the effects of the policy. We built a differential game model under random interference factors to compare the water pollution in Chaohu Lake under the RCP and without the RCP, and we explored the conditions to ensure the effectiveness of the RCP. The results showed that: (1) The average effect of water pollution control under the RCP was greater than under non-RCP; (2) the higher the rewarding excellence and punishing inferiority coefficient ( θ ) was, the better the water pollution control effect under the RCP; (3) the greater the random interference coefficient ( σ ) and rewarding excellence and punishing inferiority coefficient ( θ ) were, the bigger the fluctuation of the water pollution control effect was; (4) when using the stochastic differential game, when σ ≤ 0.0403 , θ ≥ 0.0063 , or σ > 0.0403 , θ ≥ 0.268 , the RCP must be effective for water pollution control. Therefore, we can theoretically adjust the rewarding excellence and punishing inferiority coefficient ( θ ) and the random interference coefficient ( σ ) to ensure the effective implementation of the RCP and achieve the purpose of water pollution control.
Patterns of Comorbidity in Hepatocellular Carcinoma: A Network Perspective
Authors: Mu Xiao-Min , Wang Wei , Jiang Yu-Ying , Feng Jia
Published: April 2020

Hepatocellular carcinoma (HCC) is a common and fatal cancer. People with HCC report higher odds of comorbidity compared with people without HCC. To explore the association between HCC and medical comorbidity, we used routinely collected clinical data and applied a network perspective. In the network perspective, we used correlation analysis and community detection tests that described direct relationships among comorbidities. We collected 14,891 patients with HCC living in Jilin Province, China, between 2016 and 2018. Cirrhosis was the most common comorbidity of HCC. Hypertension and renal cysts were more common in male patients, while chronic viral hepatitis C, hypersplenism, hypoproteinemia, anemia and coronary heart disease were more common in female patients. The proportion of chronic diseases in comorbidities increased with age. The main comorbidity patterns of HCC were: HCC, cirrhosis, chronic viral hepatitis B, portal hypertension, ascites and other common complications of cirrhosis; HCC, hypertension, diabetes mellitus, coronary heart disease and cerebral infarction; and HCC, hypoproteinemia, electrolyte disorders, gastrointestinal hemorrhage and hemorrhagic anemia. Our findings provide comprehensive information on comorbidity patterns of HCC, which may be used for the prevention and management of liver cancer.
TLR-4 Signaling vs. Immune Checkpoints, miRNAs Molecules, Cancer Stem Cells, and Wingless-Signaling Interplay in Glioblastoma Multiforme—Future Perspectives
Authors: Litak Jakub , Grochowski Cezary , Litak Joanna , Osuchowska Ida , Gosik Krzysztof , Radzikowska Elżbieta , Kamieniak Piotr , Rolinski Jacek
Published: April 2020

Toll-like-receptor (TLR) family members were detected in the central nervous system (CNS). TLR occurrence was noticed and widely described in glioblastomamultiforme (GBM) cells. After ligand attachment, TLR-4 reorients domains and dimerizes, activates an intracellular cascade, and promotes further cytoplasmatic signaling. There is evidence pointing at a strong relation between TLR-4 signaling and micro ribonucleic acid (miRNA) expression. The TLR-4/miRNA interplay changes typical signaling and encourages them to be a target for modern immunotherapy. TLR-4 agonists initiate signaling and promote programmed death ligand-1 (PD-1L) expression. Most of those molecules are intensively expressed in the GBM microenvironment, resulting in the autocrine induction of regional immunosuppression. Another potential target for immunotreatment is connected with limited TLR-4 signaling that promotes Wnt/DKK-3/claudine-5 signaling, resulting in a limitation of GBM invasiveness. Interestingly, TLR-4 expression results in bordering proliferative trends in cancer stem cells (CSC) and GBM. All of these potential targets could bring new hope for patients suffering from this incurable disease. Clinical trials concerning TLR-4 signaling inhibition/promotion in many cancers are recruiting patients. There is still a lot to do in the field of GBM immunotherapy.
Peroxisome Proliferator-Activated Receptor Gamma Modulator Promotes Neonatal Mouse Primordial Follicle Activation In Vitro
Authors: Yoon Sook Young , Kim Ran , Jang Hyunmee , Shin Dong Hyuk , Lee Jin Il , Seol Dongwon , Lee Dong Ryul , Chang Eun Mi , Lee Woo Sik
Published: April 2020

Peroxisome proliferator-activated receptor gamma (PPARγ) is known as a regulator of cellular functions, including adipogenesis and immune cell activation. The objectives of this study were to investigate the expression of PPARγ and identify the mechanism of primordial follicle activation via PPARγ modulators in mouse ovaries. We first measured the gene expression of PPARγ and determined its relationship with phosphatase and tensin homolog (PTEN), protein kinase B (AKT1), and forkhead box O3a (FOXO3a) expression in neonatal mouse ovaries. We then incubated neonatal mouse ovaries with PPARγ modulators, including rosiglitazone (a synthetic agonist of PPARγ), GW9662 (a synthetic antagonist of PPARγ), and cyclic phosphatidic acid (cPA, a physiological inhibitor of PPARγ), followed by transplantation into adult ovariectomized mice. After the maturation of the transplanted ovaries, primordial follicle growth activation, follicle growth, and embryonic development were evaluated. Finally, the delivery of live pups after embryo transfer into recipient mice was assessed. While PPARγ was expressed in ovaries from mice of all ages, its levels were significantly increased in ovaries from 20-day-old mice. In GW9662-treated ovaries in vitro, PTEN levels were decreased, AKT was activated, and FOXO3a was excluded from the nuclei of primordial follicles. After 1 month, cPA-pretreated, transplanted ovaries produced the highest numbers of oocytes and polar bodies, exhibited the most advanced embryonic development, and had the greatest blastocyst formation rate compared to the rosiglitazone- and GW9662-pretreated groups. Additionally, the successful delivery of live pups after embryo transfer into the recipient mice transplanted with cPA-pretreated ovaries was confirmed. Our study demonstrates that PPARγ participates in primordial follicle activation and development, possibly mediated in part by the PI3K/AKT signaling pathway. Although more studies are required, adapting these findings for the activation of human primordial follicles may lead to treatments for infertility that originates from poor ovarian reserves.
Hedgehog Signal Inhibitor GANT61 Inhibits the Malignant Behavior of Undifferentiated Hepatocellular Carcinoma Cells by Targeting Non-Canonical GLI Signaling
Authors: Harada Kensuke , Ohashi Ryuya , Naito Kyoko , Kanki Keita
Published: April 2020

The Hedgehog (HH)–GLI pathway plays an important role in cell dedifferentiation and is therefore pivotally involved in the malignant transformation of cancer cells. GANT61, a selective inhibitor of GLI1 and GLI2, was reported as a promising treatment for cancer in various tissues; however, the biological impact of GANT61 in hepatocellular carcinoma (HCC), especially in undifferentiated HCC cells, remains unclear. In this study, we investigated the antitumor effect of GANT61 using two undifferentiated hepatoma cell lines: HLE and HLF. Quantitative PCR and RT-PCR analyses revealed that these cells express GLI transcripts, showing mesenchymal phenotypes characterized by the loss of epithelial and hepatic markers and specific expression of epithelial–mesenchymal transition (EMT)-related genes. GANT61 significantly reduced the proliferation and cell viability after drug treatment using 5-FU and Mitomycin C. We showed that GLI transcript levels were down-regulated by the MEK inhibitor U0126 and the Raf inhibitor sorafenib, suggesting that non-canonical signaling including the Ras–Raf–MEK–ERK pathway is involved. Sphere formation and migration were significantly decreased by GANT61 treatment, and it is suggested that the underlying molecular mechanisms are the down-regulation of stemness-related genes (Oct4, Bmi1, CD44, and ALDH) and the EMT-related gene Snail1. The data presented here showed that direct inhibition of GLI might be beneficial for the treatment of dedifferentiated HCC.
Tyrosinase-Targeting Gallacetophenone Inhibits Melanogenesis in Melanocytes and Human Skin- Equivalents
Authors: Lee Ji Young , Lee Jooyun , Min Daejin , Kim Juewon , Kim Hyoung-June , No Kyoung Tai
Published: April 2020

Demands for safe depigmentation compounds are constantly increasing in the pharmaceutical and cosmetic industry, since the numerous relevant compounds reported to date have shown undesirable side effects or low anti-melanogenic effects. In this study, we reported three novel inhibitors of tyrosinase, which is the key enzyme in melanogenesis, identified using docking-based high throughput virtual screening of an in-house natural compound library followed by mushroom tyrosinase inhibition assay. Of the three compounds, gallacetophenone showed high anti-melanogenic effect in both human epidermal melanocytes and a 3D human skin model, MelanoDerm. The inhibitory effect of gallacetophenone on tyrosinase was elucidated by computational molecular modeling at the atomic level. Binding of gallacetophenone to the active site of tyrosinase was found to be stabilized by hydrophobic interactions with His367, Ile368, and Val377; hydrogen bonding with Ser380 and a water molecule bridging the copper ions. Thus, our results strongly suggested gallacetophenone as an anti-melanogenic ingredient that inhibits tyrosinase.
Sublethal Effects of Diamide Insecticides on Development and Flight Performance of Chloridea virescens (Lepidoptera: Noctuidae): Implications for Bt Soybean Refuge Area Management
Authors: Silva Barros Lucas , Takao Yamamoto Pedro , Merten Paul , Naranjo Steve E.
Published: April 2020

High-dose and refuge are the most important strategies for delaying resistance evolution in Bt crops. Insecticide sprays in refuge areas could be necessary and may limit refuge effectiveness. Here, we evaluated the sublethal effects of two diamide insecticides (chlorantraniliprole and flubendiamide) on Chloridea virescens life history traits and flight performance. Sublethal concentrations of chlorantraniliprole and flubendiamide increased larval and pre-pupal development times and decreased larval weight; flubendiamide increased pupal development times. Chlorantraniliprole increased adult male longevity and reduced female fertility, while flubendiamide reduced fecundity. Overall life table parameters were negatively impacted by both treatments. Males exposed to either insecticide showed significant reductions in flight duration and distance for unsustained flights (<30 min). The duration and distance of the first flights were reduced when exposed to chlorantraniliprole. Sustained flights (>30 min) were generally unaffected by insecticide exposure and both sexes flew >6400 m in a single flight. The sublethal effects of flubendiamide and chlorantraniliprole on C. virescens’ population dynamics could lead to generation asynchrony and provide insufficient susceptible moths when sprayed on refuge crops. However, the distance and duration of flight may still be sufficient to ensure mixing of potentially resistant and susceptible populations from refuge plots.
Effects of Sugammadex on Post-Operative Pulmonary Complications in Laparoscopic Gastrectomy: A Retrospective Cohort Study
Authors: Han Jiwon , Ryu Jung-Hee , Koo Bon-Wook , Nam Sun Woo , Cho Sang-Il , Oh Ah-Young
Published: April 2020

The use of sugammadex can reduce post-operative residual neuromuscular blockade, which is known to increase the risk of post-operative respiratory events. However, its effect on post-operative pulmonary complications is not obvious. This study was performed to evaluate the effects of sugammadex on post-operative pulmonary complications in patients undergoing laparoscopic gastrectomy between 2013 and 2017. We performed propensity score matching to correct for selection bias. Post-operative pulmonary complications (i.e., pneumonia, respiratory failure, pleural effusion, atelectasis, pneumothorax, and aspiration pneumonitis) were evaluated from the radiological and laboratory findings. We also evaluated admission to the intensive care unit after surgery, re-admission or an emergency room visit within 30 days after discharge, length of hospital stay, re-operation, and mortality within 90 days post-operatively as secondary outcomes. In the initial cohort of 3802 patients, 541 patients were excluded, and 1232 patients were analyzed after propensity score matching. In the matched cohort, pleural effusion was significantly reduced in the sugammadex group compared to the neostigmine group (neostigmine 23.4% vs. sugammadex 18%, p = 0.02). Other pulmonary complications and secondary outcomes were not significantly different between the groups. In comparison to neostigmine, the use of sugammadex was associated with a lower incidence of post-operative pleural effusion in laparoscopic gastrectomy.
Impact of Early C-Reactive Protein/Albumin Ratio on Intra-Hospital Mortality Among Patients with Spontaneous Intracerebral Hemorrhage
Authors: Bender Michael , Haferkorn Kristin , Friedrich Michaela , Uhl Eberhard , Stein Marco
Published: April 2020

Objective: The impact of increased C-reactive protein (CRP)/albumin ratio on intra-hospital mortality has been investigated among patients admitted to general intensive care units (ICU). However, it was not investigated among patients with spontaneous intracerebral hemorrhage (ICH). This study aimed to investigate the impact of CRP/albumin ratio on intra-hospital mortality in patients with ICH. Patients and Methods: This retrospective study was conducted on 379 ICH patients admitted between 02/2008 and 12/2017. Blood samples were drawn upon admission and the patients’ demographic, medical, and radiological data were collected. The identification of the independent prognostic factors for intra-hospital mortality was calculated using binary logistic regression and COX regression analysis. Results: Multivariate regression analysis shows that higher CRP/albumin ratio (odds ratio (OR) = 1.66, 95% confidence interval (CI) = 1.193–2.317, p = 0.003) upon admission is an independent predictor of intra-hospital mortality. Multivariate Cox regression analysis indicated that an increase of 1 in the CRP/albumin ratio was associated with a 15.3% increase in the risk of intra-hospital mortality (hazard ratio = 1.153, 95% CI = 1.005–1.322, p = 0.42). Furthermore, a CRP/albumin ratio cut-off value greater than 1.22 was associated with increased intra-hospital mortality (Youden’s Index = 0.19, sensitivity = 28.8, specificity = 89.9, p = 0.007). Conclusions: A CRP/albumin ratio greater than 1.22 upon admission was significantly associated with intra-hospital mortality in the ICH patients.
Which Child with Asthma is a Candidate for Biological Therapies?
Authors: Bush Andrew
Published: April 2020

In asthmatic adults, monoclonals directed against Type 2 airway inflammation have led to major improvements in quality of life, reductions in asthma attacks and less need for oral corticosteroids. The paediatric evidence base has lagged behind. All monoclonals currently available for children are anti-eosinophilic, directed against the T helper (TH2) pathway. However, in children and in low and middle income settings, eosinophils may have important beneficial immunological actions. Furthermore, there is evidence that paediatric severe asthma may not be TH2 driven, phenotypes may be less stable than in adults, and adult biomarkers may be less useful. Children being evaluated for biologicals should undergo a protocolised assessment, because most paediatric asthma can be controlled with low dose inhaled corticosteroid if taken properly and regularly. For those with severe therapy resistant asthma, and refractory asthma which cannot be addressed, the two options if they have TH2 inflammation are omalizumab and mepolizumab. There is good evidence of efficacy for omalizumab, particularly in those with multiple asthma attacks, but only paediatric safety, not efficacy, data for mepolizumab. There is an urgent need for efficacy data in children, as well as data on biomarkers to guide therapy, if the right children are to be treated with these powerful new therapies.
Dupilumab for the Treatment of Atopic Dermatitis in an Austrian Cohort-Real-Life Data Shows Rosacea-Like Folliculitis
Authors: Quint Tamara , Brunner Patrick M. , Sinz Christoph , Steiner Irene , Ristl Robin , Vigl Kornelia , Kimeswenger Susanne , Neubauer Katharina , Pirkhammer Detlev , Zikeli Martin , Hoetzenecker Wolfram , Reider Norbert , Bangert Christine
Published: April 2020

Dupilumab is the first biological treatment approved for moderate-to-severe atopic dermatitis (AD). Efficacy and safety have been demonstrated in clinical trials, but real-life data is still limited. The objective of this study was to retrospectively evaluate Dupilumab treatment in AD patients in a real-life clinical setting. Effectiveness and safety outcomes were collected at baseline and after 2, 6, 10, 24, 39, and 52 weeks by using clinical scores for disease activity, as well as serological markers. Ninety-four patients from five dermatological hospitals were included. After 24 weeks of treatment, the median Investigator Global Assessment (IGA) and Eczema Area and Severity Index (EASI) showed a significant reduction compared to baseline (3.9 ± 0.7 vs. 1.4 ± 0.8 and 26.5 ± 12.5 vs. 6.4 ± 6.5). Interestingly, we observed rosacea-like folliculitis as an unexpected side effect in 6.4% of patients. Dupilumab proves to be an effective and well-tolerated treatment under real-life conditions. The occurrence of rosacea-like folliculitis warrants further mechanistic investigation.
Speckle Tracking-Derived Left Atrial Stiffness Predicts Clinical Outcome in Heart Failure Patients with Reduced to Mid-Range Ejection Fraction
Authors: Bytyçi Ibadete , Dini Frank L. , Bajraktari Artan , Pugliese Nicola Riccardo , D’Agostino Andreina , Bajraktari Gani , Lindqvist Per , Henein Michael Y.
Published: April 2020

Background and Aim: Left atrial stiffness (LASt) is an important marker of cardiac function, especially in patients with heart failure (HF); it explains symptoms on the basis of pressure transfer to the pulmonary circulation. The aim of this study was to evaluate the relationship between LASt and cardiac events (CE) in HF patients with reduced to mid-range ejection fraction. Methods: The study included 215 consecutive ambulatory HF patients with ejection fraction (EF) < 50% (162 HF reduced EF and 53 HF mid-range EF) of mean age 66 ± 11 years and 24.4% females. Peak LA strain (PALS) was measured by speckle tracking echocardiography and E/e’ recorded from the apical four-chamber view. Non-invasive LASt was calculated using the equation: LASt = E/e’ ratio/PALS. Documented cardiac events (CE) were HF hospitalization and cardiac death. Results: During a median follow up of 41 ± 34 months, 65 patients (30%) had CE. In multivariate analysis model, only raised LV filling pressure (E/e’) (OR = 0.292, (95% CI 0.099 to 0.859), p = 0.02), peak pulmonary artery pressure (PAP) (OR = 1.050 (1.009 to 1.094), p = 0.01), PALS (OR = 0.932 (0.873 to 0.994), p = 0.02) and LASt (OR = 3.781 (1.144 to 5.122), p = 0.001) independently predicted CE. LASt ≥ 0.76% was the most powerful predictor of CE, with 80% sensitivity and 73% specificity (AUC 0.82, CI = 0.73 to 0.87, p < 0.001) followed by PALS ≤ 16%, with 74% sensitivity and 72% specificity (AUC 0.77, CI = 0.71 to 0.84, p < 0.001). These results were consistent irrespective of EF (p < 0.05). Conclusion: In this cohort of ambulatory HFrEF and HFmrEF patients, LASt proved the most powerful predictor of clinical outcome.
The Clinical Significance of PIWIL3 and PIWIL4 Expression in Pancreatic Cancer
Authors: Li Weiyao , Martinez-Useros Javier , Garcia-Carbonero Nuria , Fernandez-Aceñero Maria J. , Orta Alberto , Ortega-Medina Luis , Garcia-Botella Sandra , Perez-Aguirre Elia , Diez-Valladares Luis , Celdran Angel , García-Foncillas Jesús
Published: April 2020

P-element-induced wimpy testis (PIWI) proteins have been described in several cancers. PIWIL1 and PIWIL2 have been recently evaluated in pancreatic cancer, and elevated expression of PIWIL2 conferred longer survival to patients. However, PIWIL3’s and PIWIL4’s role in carcinogenesis is rather controversial, and their clinical implication in pancreatic cancer has not yet been investigated. In the present study, we evaluated PIWIL1, PIWIL2, PIWIL3 and PIWIL4 expression in pancreatic cancer-derived cell lines and in one non-tumor cell line as healthy control. Here, we show a differential expression in tumor and non-tumor cell lines of PIWIL3 and PIWIL4. Subsequently, functional experiments with PIWIL3 and/or PIWIL4 knockdown revealed a decrease in the motility ratio of tumor and non-tumor cell lines through downregulation of mesenchymal factors in pro of epithelial factors. We also observed that PIWIL3 and/or PIWIL4 silencing impaired undifferentiated phenotype and enhanced drug toxicity in both tumor- and non-tumor-derived cell lines. Finally, PIWIL3 and PIWIL4 evaluation in human pancreatic cancer samples showed that patients with low levels of PIWIL4 protein expression presented poor prognosis. Therefore, PIWIL3 and PIWIL4 proteins may play crucial roles to keep pancreatic cell homeostasis not only in tumors but also in healthy tissues.
Machine Learning and Virtual Reality on Body Movements’ Behaviors to Classify Children with Autism Spectrum Disorder
Authors: Alcañiz Raya Mariano , Marín-Morales Javier , Minissi Maria Eleonora , Teruel Garcia Gonzalo , Abad Luis , Chicchi Giglioli Irene Alice
Published: April 2020

Autism spectrum disorder (ASD) is mostly diagnosed according to behavioral symptoms in sensory, social, and motor domains. Improper motor functioning, during diagnosis, involves the qualitative evaluation of stereotyped and repetitive behaviors, while quantitative methods that classify body movements’ frequencies of children with ASD are less addressed. Recent advances in neuroscience, technology, and data analysis techniques are improving the quantitative and ecological validity methods to measure specific functioning in ASD children. On one side, cutting-edge technologies, such as cameras, sensors, and virtual reality can accurately detect and classify behavioral biomarkers, as body movements in real-life simulations. On the other, machine-learning techniques are showing the potential for identifying and classifying patients’ subgroups. Starting from these premises, three real-simulated imitation tasks have been implemented in a virtual reality system whose aim is to investigate if machine-learning methods on movement features and frequency could be useful in discriminating ASD children from children with typical neurodevelopment. In this experiment, 24 children with ASD and 25 children with typical neurodevelopment participated in a multimodal virtual reality experience, and changes in their body movements were tracked by a depth sensor camera during the presentation of visual, auditive, and olfactive stimuli. The main results showed that ASD children presented larger body movements than TD children, and that head, trunk, and feet represent the maximum classification with an accuracy of 82.98%. Regarding stimuli, visual condition showed the highest accuracy (89.36%), followed by the visual-auditive stimuli (74.47%), and visual-auditive-olfactory stimuli (70.21%). Finally, the head showed the most consistent performance along with the stimuli, from 80.85% in visual to 89.36% in visual-auditive-olfactory condition. The findings showed the feasibility of applying machine learning and virtual reality to identify body movements’ biomarkers that could contribute to improving ASD diagnosis.
Gene Expression Patterns Distinguish Mortality Risk in Patients with Postsurgical Shock
Authors: Martínez-Paz Pedro , Aragón-Camino Marta , Gómez-Sánchez Esther , Lorenzo-López Mario , Gómez-Pesquera Estefanía , López-Herrero Rocío , Sánchez-Quirós Belén , de la Varga Olga , Tamayo-Velasco Álvaro , Ortega-Loubon Christian , García-Morán Emilio , Gonzalo-Benito Hugo , Heredia-Rodríguez María , Tamayo Eduardo
Published: April 2020

Nowadays, mortality rates in intensive care units are the highest of all hospital units. However, there is not a reliable prognostic system to predict the likelihood of death in patients with postsurgical shock. Thus, the aim of the present work is to obtain a gene expression signature to distinguish the low and high risk of death in postsurgical shock patients. In this sense, mRNA levels were evaluated by microarray on a discovery cohort to select the most differentially expressed genes between surviving and non-surviving groups 30 days after the operation. Selected genes were evaluated by quantitative real-time polymerase chain reaction (qPCR) in a validation cohort to validate the reliability of data. A receiver-operating characteristic analysis with the area under the curve was performed to quantify the sensitivity and specificity for gene expression levels, which were compared with predictions by established risk scales, such as acute physiology and chronic health evaluation (APACHE) and sequential organ failure assessment (SOFA). IL1R2, CD177, RETN, and OLFM4 genes were upregulated in the non-surviving group of the discovery cohort, and their predictive power was confirmed in the validation cohort. This work offers new biomarkers based on transcriptional patterns to classify the postsurgical shock patients according to low and high risk of death. The results present more accuracy than other mortality risk scores.
Analyzing Impetus of Regenerative Cellular Therapeutics in Myocardial Infarction
Authors: Chang Ming-Long , Chiu Yu-Jui , Li Jian-Sing , Cheah Khoot-Peng , Lin Hsiu-Hu
Published: April 2020

Both vasculature and myocardium in the heart are excessively damaged following myocardial infarction (MI), hence therapeutic strategies for treating MI hearts should concurrently aim for true cardiac repair by introducing new cardiomyocytes to replace lost or injured ones. Of them, mesenchymal stem cells (MSCs) have long been considered a promising candidate for cell-based therapy due to their unspecialized, proliferative differentiation potential to specific cell lineage and, most importantly, their capacity of secreting beneficial paracrine factors which further promote neovascularization, angiogenesis, and cell survival. As a consequence, the differentiated MSCs could multiply and replace the damaged tissues to and turn into tissue- or organ-specific cells with specialized functions. These cells are also known to release potent anti-fibrotic factors including matrix metalloproteinases, which inhibit the proliferation of cardiac fibroblasts, thereby attenuating fibrosis. To achieve the highest possible therapeutic efficacy of stem cells, the other interventions, including hydrogels, electrical stimulations, or platelet-derived biomaterials, have been supplemented, which have resulted in a narrow to broad range of outcomes. Therefore, this article comprehensively analyzed the progress made in stem cells and combinatorial therapies to rescue infarcted myocardium.
Sexual Dimorphism of NAFLD in Adults. Focus on Clinical Aspects and Implications for Practice and Translational Research
Authors: Lonardo Amedeo , Suzuki Ayako
Published: April 2020

Nonalcoholic fatty liver disease (NAFLD) embraces the clinico-pathological consequences of hepatic lipotoxicity and is a major public health problem globally. Sexual dimorphism is a definite feature of most human diseases but, under this aspect, NAFLD lags behind other medical fields. Here, we aim at summarizing and critically discussing the most prominent sex differences and gaps in NAFLD in humans, with emphasis on those aspects which are relevant for clinical practice and translational research. Sexual dimorphism of NAFLD is covered with references to the following areas: disease prevalence and risk factors, pathophysiology, comorbidities, natural course and complications. Finally, we also discuss selected gender differences and whether sex-specific lifestyle changes should be adopted to contrast NAFLD in men and women.
Group IIA Secretory Phospholipase A2 Predicts Graft Failure and Mortality in Renal Transplant Recipients by Mediating Decreased Kidney Function
Authors: Annema Wijtske , de Boer Jan Freark , Dikkers Arne , Dimova Lidiya G. , van der Giet Markus , Bakker Stephan J.L. , Tietge Uwe J.F.
Published: April 2020

The acute phase protein group IIA secretory phospholipase A2 (sPLA2-IIA) has intrinsic proatherosclerotic properties. The present prospective cohort study investigated whether plasma sPLA2-IIA associates with graft failure, cardiovascular, and all-cause mortality in renal transplant recipients (RTRs), patients with accelerated atherosclerosis formation both systemically and within the graft. In 511 RTRs from a single academic center with stable graft function >1 year, baseline plasma sPLA2-IIA was determined by ELISA. Primary end points were death-censored graft failure and mortality (median follow-up, 7.0 years). Baseline sPLA2-IIA was higher in RTRs than in healthy controls (median 384 ng/dL (range 86–6951) vs. 185 ng/dL (range 104–271), p < 0.001). Kaplan–Meier analysis demonstrated increased risk for graft failure (p = 0.002), as well as cardiovascular (p < 0.001) and all-cause mortality (p < 0.001), with increasing sPLA2-IIA quartiles. Cox regression showed strong associations of sPLA2-IIA with increased risks of graft failure (hazard ratio (HR) = 1.42 (1.11–1.83), p = 0.006), as well as cardiovascular (HR = 1.48 (1.18−1.85), p = 0.001) and all-cause mortality (HR = 1.39 (1.17−1.64), p < 0.001), dependent on parameters of kidney function. Renal function during follow-up declined faster in RTRs with higher baseline sPLA2-IIA levels. In RTRs, sPLA2-IIA is a significant predictive biomarker for chronic graft failure, as well as overall and cardiovascular disease mortality dependent on kidney function. This dependency is conceivably explained by sPLA2-IIA impacting negatively on kidney function.
The Nitrogen Stress-Repressed sRNA NsrR1 Regulates Expression of all1871, a Gene Required for Diazotrophic Growth in Nostoc sp. PCC 7120
Authors: Álvarez-Escribano Isidro , Brenes-Álvarez Manuel , Olmedo-Verd Elvira , Vioque Agustín , Muro-Pastor Alicia M.
Published: April 2020

Small regulatory RNAs (sRNAs) are post-transcriptional regulators of bacterial gene expression. In cyanobacteria, the responses to nitrogen availability, that are mostly controlled at the transcriptional level by NtcA, involve also at least two small RNAs, namely NsiR4 (nitrogen stress-induced RNA 4) and NsrR1 (nitrogen stress-repressed RNA 1). Prediction of possible mRNA targets regulated by NsrR1 in Nostoc sp. PCC 7120 allowed, in addition to previously described nblA, the identification of all1871, a nitrogen-regulated gene encoding a protein of unknown function that we describe here as required for growth at the expense of atmospheric nitrogen (N2). We show that transcription of all1871 is induced upon nitrogen step-down independently of NtcA. All1871 accumulation is repressed by NsrR1 and its expression is stronger in heterocysts, specialized cells devoted to N2 fixation. We demonstrate specific interaction between NsrR1 and the 5′ untranslated region (UTR) of the all1871 mRNA, that leads to decreased expression of all1871. Because transcription of NsrR1 is partially repressed by NtcA, post-transcriptional regulation by NsrR1 would constitute an indirect way of NtcA-mediated regulation of all1871.