bluuebunny/crossref_metadata_2025 huggingface dataset:
Citrus Genetic Engineering for Disease Resistance: Past, Present and Future
Authors: Sun Lifang , Nasrullah  , Ke Fuzhi , Nie Zhenpeng , Wang Ping , Xu Jianguo
Published: October 2019

Worldwide, citrus is one of the most important fruit crops and is grown in more than 130 countries, predominantly in tropical and subtropical areas. The healthy progress of the citrus industry has been seriously affected by biotic and abiotic stresses. Several diseases, such as canker and huanglongbing, etc., rigorously affect citrus plant growth, fruit quality, and yield. Genetic engineering technologies, such as genetic transformation and genome editing, represent successful and attractive approaches for developing disease-resistant crops. These genetic engineering technologies have been widely used to develop citrus disease-resistant varieties against canker, huanglongbing, and many other fungal and viral diseases. Recently, clustered regularly interspaced short palindromic repeats (CRISPR)-based systems have made genome editing an indispensable genetic manipulation tool that has been applied to many crops, including citrus. The improved CRISPR systems, such as CRISPR/CRISPR-associated protein (Cas)9 and CRISPR/Cpf1 systems, can provide a promising new corridor for generating citrus varieties that are resistant to different pathogens. The advances in biotechnological tools and the complete genome sequence of several citrus species will undoubtedly improve the breeding for citrus disease resistance with a much greater degree of precision. Here, we attempt to summarize the recent successful progress that has been achieved in the effective application of genetic engineering and genome editing technologies to obtain citrus disease-resistant (bacterial, fungal, and virus) crops. Furthermore, we also discuss the opportunities and challenges of genetic engineering and genome editing technologies for citrus disease resistance.
Quercetin Directly Targets JAK2 and PKCδ and Prevents UV-Induced Photoaging in Human Skin
Authors: Shin Eun Ju , Lee Ji Su , Hong Seungpyo , Lim Tae-Gyu , Byun Sanguine
Published: October 2019

Quercetin is a naturally occurring polyphenol present in various fruits and vegetables. The bioactive properties of quercetin include anti-oxidative, anti-cancer, anti-inflammatory, and anti-diabetic effects. However, the effect of quercetin on skin aging and the direct molecular targets responsible have remained largely unknown. Herein, we investigated the protective effect of quercetin against UV-mediated skin aging and the molecular mechanisms responsible. Treatment with quercetin suppressed UV-induced matrix metalloproteinase-1 (MMP-1) and cyclooxygenase-2 (COX-2) expression and prevented UV-mediated collagen degradation in human skin tissues. Quercetin exerted potent inhibitory effects towards UV-induced activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB) activity. Further examination of the upstream signaling pathways revealed that quercetin can attenuate UV-mediated phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N terminal kinases (JNK), protein kinase B (Akt), and signal transducer and activator of transcription 3 (STAT3). Kinase assays using purified protein demonstrated that quercetin can directly inhibit protein kinase C delta (PKCδ) and Janus kinase 2 (JAK2) kinase activity. Quercetin was observed to bind to PKCδ and JAK2 in pull-down assays. These findings suggest that quercetin can directly target PKCδ and JAK2 in the skin to elicit protective effects against UV-mediated skin aging and inflammation. Our results highlight the potential use of quercetin as a natural agent for anti-skin aging applications.
Differential Expression of Neuroinflammatory mRNAs in the Rat Sciatic Nerve Following Chronic Constriction Injury and Pain-Relieving Nanoemulsion NSAID Delivery to Infiltrating Macrophages
Authors: Stevens Andrea , Liu Lu , Bertovich Dylan , Janjic Jelena , Pollock John
Published: October 2019

The neuroinflammatory response to peripheral nerve injury is associated with chronic pain and significant changes in the molecular expression profiles of mRNAs in neurons, glia and infiltrating immune cells. Chronic constriction injury (CCI) of the rat sciatic nerve provides an opportunity to mimic neuropathic injury and quantitatively assess behavior and differential gene expression in individual animals. Previously, we have shown that a single intravenous injection of nanoemulsion containing celecoxib (0.24 mg/kg) reduces inflammation of the sciatic nerve and relieves pain-like behavior for up to 6 days. Here, we use this targeted therapy to explore the impact on mRNA expression changes in both pain and pain-relieved states. Sciatic nerve tissue recovered from CCI animals is used to evaluate the mRNA expression profiles utilizing quantitative PCR. We observe mRNA changes consistent with the reduced recruitment of macrophages evident by a reduction in chemokine and cytokine expression. Furthermore, genes associated with adhesion of macrophages, as well as changes in the neuronal and glial mRNAs are observed. Moreover, genes associated with neuropathic pain including Maob, Grin2b/NMDAR2b, TrpV3, IL-6, Cacna1b/Cav2.2, Itgam/Cd11b, Scn9a/Nav1.7, and Tac1 were all found to respond to the celecoxib loaded nanoemulsion during pain relief as compared to those animals that received drug-free vehicle. These results demonstrate that by targeting macrophage production of PGE2 at the site of injury, pain relief includes partial reversal of the gene expression profiles associated with chronic pain.
The Hedgehog Signaling Pathway in Ischemic Tissues
Authors: Giarretta Igor , Gaetani Eleonora , Bigossi Margherita , Tondi Paolo , Asahara Takayuki , Pola Roberto
Published: October 2019

Hedgehog (Hh) proteins are prototypical morphogens known to regulate epithelial/mesenchymal interactions during embryonic development. In addition to its pivotal role in embryogenesis, the Hh signaling pathway may be recapitulated in post-natal life in a number of physiological and pathological conditions, including ischemia. This review highlights the involvement of Hh signaling in ischemic tissue regeneration and angiogenesis, with particular attention to the heart, the brain, and the skeletal muscle. Updated information on the potential role of the Hh pathway as a therapeutic target in the ischemic condition is also presented.
The Pivotal Role of TRP Channels in Homeostasis and Diseases throughout the Gastrointestinal Tract
Authors: Alaimo Alessandro , Rubert Josep
Published: October 2019

The transient receptor potential (TRP) channels superfamily are a large group of proteins that play crucial roles in cellular processes. For example, these cation channels act as sensors in the detection and transduction of stimuli of temperature, small molecules, voltage, pH, and mechanical constrains. Over the past decades, different members of the TRP channels have been identified in the human gastrointestinal (GI) tract playing multiple modulatory roles. Noteworthy, TRPs support critical functions related to the taste perception, mechanosensation, and pain. They also participate in the modulation of motility and secretions of the human gut. Last but not least, altered expression or activity and mutations in the TRP genes are often related to a wide range of disorders of the gut epithelium, including inflammatory bowel disease, fibrosis, visceral hyperalgesia, irritable bowel syndrome, and colorectal cancer. TRP channels could therefore be promising drug targets for the treatment of GI malignancies. This review aims at providing a comprehensive picture of the most recent advances highlighting the expression and function of TRP channels in the GI tract, and secondly, the description of the potential roles of TRPs in relevant disorders is discussed reporting our standpoint on GI tract–TRP channels interactions.
Immune Complexes Impaired Glomerular Endothelial Cell Functions in Lupus Nephritis
Authors: Wang Linlin , Law Helen Ka Wai
Published: October 2019

Lupus nephritis (LN) is one of the most common and severe complications of lupus. However, the mechanisms for renal damage have not been well elucidated. There are evidences show that glomerular endothelial cells (GECs) are damaged in LN. Immune complexes can deposit in subendothelial area and could affect GEC functions. In the present study, we used heat-aggregated gamma globulin (HAGG) to simulate immune complexes and investigated their effects on GEC functions. Our results revealed that HAGG impaired different aspect of the GEC functions. HAGG changed cell morphology, upregulated the expression of active caspase-3, inhibited angiogenesis, and increased NO production in GECs. These results provide new clues for the mechanisms of renal damage and the pathology of LN.
Lipophilicity Determination of Quaternary (Fluoro)Quinolones by Chromatographic and Theoretical Approaches
Authors: Ciura Krzesimir , Fedorowicz Joanna , Andrić Filip , Greber Katarzyna Ewa , Gurgielewicz Alina , Sawicki Wiesław , Sączewski Jarosław
Published: October 2019

Lipophilicity is a vital physicochemical parameter of a molecule, which affects several biological processes such as absorption, tissue distribution, and pharmacokinetic properties. In this study, evaluation of lipophilicities of a series of novel fluoroquinolone-Safirinium dye hybrids using chromatographic and computational methods is presented. Fluoroquinolone-Safirinium dye hybrids have been synthesized as new dual-acting hydrophilic antibacterial agents. Reversed phase thin-layer chromatography and micellar electrokinetic chromatography experiments were carried out. Furthermore, logP values of the target structures were predicted by means of different software platforms and algorithms. In order to assess similarities and dissimilarities of the obtained lipophilicity indexes, cluster analysis and sum of ranking differences were performed. The significant differences of calculated logP values (α = 0.05, p < 0.001) indicated that an experimental approach is necessary for lipophilicity prediction of this class of antibiotics. Chromatographic data indicated that the newly synthesized hybrid (fluoro)quinolone-based quaternary ammonium derivatives show less lipophilic character than the parent (fluoro)quinolones. Additionally, the chromatographically obtained lipophilicity indexes were evaluated for possible application in quantitative retention–activity relationships. The established lipophilicity models have the potential to predict antimicrobial activities of a series of quaternary (fluoro)quinolones against Bacillus subtilis, Escherichia coli, and Proteus vulgaris.
Understanding G Protein Selectivity of Muscarinic Acetylcholine Receptors Using Computational Methods
Authors: Santiago Luis , Abrol Ravinder
Published: October 2019

The neurotransmitter molecule acetylcholine is capable of activating five muscarinic acetylcholine receptors, M1 through M5, which belong to the superfamily of G-protein-coupled receptors (GPCRs). These five receptors share high sequence and structure homology; however, the M1, M3, and M5 receptor subtypes signal preferentially through the Gαq/11 subset of G proteins, whereas the M2 and M4 receptor subtypes signal through the Gαi/o subset of G proteins, resulting in very different intracellular signaling cascades and physiological effects. The structural basis for this innate ability of the M1/M3/M5 set of receptors and the highly homologous M2/M4 set of receptors to couple to different G proteins is poorly understood. In this study, we used molecular dynamics (MD) simulations coupled with thermodynamic analyses of M1 and M2 receptors coupled to both Gαi and Gαq to understand the structural basis of the M1 receptor’s preference for the Gαq protein and the M2 receptor’s preference for the Gαi protein. The MD studies showed that the M1 and M2 receptors can couple to both Gα proteins such that the M1 receptor engages with the two Gα proteins in slightly different orientations and the M2 receptor engages with the two Gα proteins in the same orientation. Thermodynamic studies of the free energy of binding of the receptors to the Gα proteins showed that the M1 and M2 receptors bind more strongly to their cognate Gα proteins compared to their non-cognate ones, which is in line with previous experimental studies on the M3 receptor. A detailed analysis of receptor–G protein interactions showed some cognate-complex-specific interactions for the M2:Gαi complex; however, G protein selectivity determinants are spread over a large overlapping subset of residues. Conserved interaction between transmembrane helices 5 and 6 far away from the G-protein-binding receptor interface was found only in the two cognate complexes and not in the non-cognate complexes. An analysis of residues implicated previously in G protein selectivity, in light of the cognate and non-cognate structures, shaded a more nuanced role of those residues in affecting G protein selectivity. The simulation of both cognate and non-cognate receptor–G protein complexes fills a structural gap due to difficulties in determining non-cognate complex structures and provides an enhanced framework to probe the mechanisms of G protein selectivity exhibited by most GPCRs.
Insights on Calcium-Dependent Protein Kinases (CPKs) Signaling for Abiotic Stress Tolerance in Plants
Authors: Atif Rana Muhammad , Shahid Luqman , Waqas Muhammad , Ali Babar , Rashid Muhammad Abdul Rehman , Azeem Farrukh , Nawaz Muhammad Amjad , Wani Shabir Hussain , Chung Gyuhwa
Published: October 2019

Abiotic stresses are the major limiting factors influencing the growth and productivity of plants species. To combat these stresses, plants can modify numerous physiological, biochemical, and molecular processes through cellular and subcellular signaling pathways. Calcium-dependent protein kinases (CDPKs or CPKs) are the unique and key calcium-binding proteins, which act as a sensor for the increase and decrease in the calcium (Ca) concentrations. These Ca flux signals are decrypted and interpreted into the phosphorylation events, which are crucial for signal transduction processes. Several functional and expression studies of different CPKs and their encoding genes validated their versatile role for abiotic stress tolerance in plants. CPKs are indispensable for modulating abiotic stress tolerance through activation and regulation of several genes, transcription factors, enzymes, and ion channels. CPKs have been involved in supporting plant adaptation under drought, salinity, and heat and cold stress environments. Diverse functions of plant CPKs have been reported against various abiotic stresses in numerous research studies. In this review, we have described the evaluated functions of plant CPKs against various abiotic stresses and their role in stress response signaling pathways.
Dynamic Regulation of miRNA Expression by Functionally Enhanced Placental Mesenchymal Stem Cells Promotes Hepatic Regeneration in a Rat Model with Bile Duct Ligation
Authors: Kim Jae , Jun Ji , Park Soo , Yang Seong , Bae Si , Kim Gi
Published: October 2019

Placenta-derived mesenchymal stem cells (PD-MSCs) were highlighted as therapeutic sources in several degenerative diseases. Recently, microRNAs(miRNAs) were found to mediate one of the therapeutic mechanisms of PD-MSCs in regenerative medicine. To enhance the therapeutic effects of PD-MSCs, we established functionally enhanced PD-MSCs with phosphatase of regenerating liver-1 overexpression (PRL-1(+)). However, the profile and functions of miRNAs induced by PRL-1(+) PD-MSCs in a rat model with hepatic failure prepared by bile duct ligation (BDL) remained unclear. Hence, the objectives of the present study were to analyze the expression of miRNAs and investigate their therapeutic mechanisms for hepatic regeneration via PRL-1(+) in a rat model with BDL. We selected candidate miRNAs based on microarray analysis. Under hypoxic conditions, compared with migrated naïve PD-MSCs, migrated PRL-1(+) PD-MSCs showed improved integrin-dependent migration ability through Ras homolog (RHO) family-targeted miRNA expression (e.g., hsa-miR-30a-5p, 340-5p, and 146a-3p). Moreover, rno-miR-30a-5p and 340-5p regulated engraftment into injured rat liver by transplanted PRL-1(+) PD-MSCs through the integrin family. Additionally, an increase in platelet-derived growth factor receptor A (PDGFRA) by suppressing rno-miR-27a-3p improved vascular structure in rat liver tissues after PRL-1(+) PD-MSC transplantation. Furthermore, decreased rno-miR-122-5p was significantly correlated with increased proliferation of hepatocytes in liver tissues by PRL-1(+) PD-MSCs by activating the interleukin-6 (IL-6) signaling pathway through the repression of rno-miR-21-5p. Taken together, these findings improve the understanding of therapeutic mechanisms based on miRNA-mediated stem-cell therapy in liver diseases.
Withania Somnifera (Ashwagandha) and Withaferin A: Potential in Integrative Oncology
Authors: Dutta Rinku , Khalil Roukiah , Green Ryan , Mohapatra Shyam S , Mohapatra Subhra
Published: October 2019

Ashwagandha (Withania Somnifera, WS), belonging to the family Solanaceae, is an Ayurvedic herb known worldwide for its numerous beneficial health activities since ancient times. This medicinal plant provides benefits against many human illnesses such as epilepsy, depression, arthritis, diabetes, and palliative effects such as analgesic, rejuvenating, regenerating, and growth-promoting effects. Several clinical trials of the different parts of the herb have demonstrated safety in patients suffering from these diseases. In the last two decades, an active component of Withaferin A (WFA) has shown tremendous cytotoxic activity suggesting its potential as an anti-carcinogenic agent in treatment of several cancers. In spite of enormous progress, a thorough elaboration of the proposed mechanism and mode of action is absent. Herein, we provide a comprehensive review of the properties of WS extracts (WSE) containing complex mixtures of diverse components including WFA, which have shown inhibitory properties against many cancers, (breast, colon, prostate, colon, ovarian, lung, brain), along with their mechanism of actions and pathways involved.
The Protective Role of Calbindin-D9k on Endoplasmic Reticulum Stress-Induced Beta Cell Death
Authors: Ahn Changhwan , Jung Eui-Man , An Beum-Soo , Hong Eui-Ju , Yoo Yeong-Min , Jeung Eui-Bae
Published: October 2019

Intracellular calcium ion content is tightly regulated for the maintenance of cellular functions and cell survival. Calbindin-D9k (CaBP-9k) is responsible for regulating the distribution of cytosolic free-calcium ions. In this study, we aimed to investigate the effect of CaBP-9k on cell survival in pancreatic beta cells. Six-month-old wildtype CaBP-9k, CaBP-28k, and CaBP-9k/28k knockout (KO) mice were used to compare the pathological phenotypes of calcium-binding protein-deleted mice. Subsequently, the endoplasmic reticulum (ER) stress reducer tauroursodeoxycholic acid (TUDCA) was administered to wildtype and CaBP-9k KO mice. In vitro assessment of the role of CaBP-9k was performed following CaBP-9k overexpression and treatment with the ER stress inducer thapsigargin. Six-month-old CaBP-9k KO mice showed reduced islet volume and up-regulation of cell death markers resulting from ER stress, which led to pancreatic beta cell death. TUDCA treatment recovered islet volume, serum insulin level, and abdominal fat storage by CaBP-9k ablation. CaBP-9k overexpression elevated insulin secretion and recovered thapsigargin-induced ER stress in the INS-1E cell line. The results of this study show that CaBP-9k can protect pancreatic beta cell survival from ER stress and contribute to glucose homeostasis, which can reduce the risk of type 1 diabetes and provide the molecular basis for calcium supplementation to diabetic patients.
Proposal of an Implementation Methodology of ICT Processes
Authors: Canedo Edna Dias , Parente da Costa Ruyther , Vieira Amaral Luis Henrique , Coutinho Moramay , Daniel Amvame Nze Georges , de Sousa Junior Rafael Timoteo
Published: October 2019

The challenge to enhance the use of Information Communication Technology (ICT) in the Brazilian Federal Public Administration involves not only technological issues but also staff training, adaptation to new culture, and understanding of processes. Furthermore, knowledge must be well aligned and articulated so that ICT resources are applied efficiently and effectively, meeting the needs of society, ensuring the provision of quality public service and, above all, providing better conditions for the exercise of functions performed by employees. This article presents an account of the implementation of the ICT processes in a State Company based on the ICT Governance Kit proposed for the Secretariat of Coordination and Governance of State Companies. During the execution of the case study, we surveyed the initial diagnosis of the processes performed by the State, as well as brainstormings and semi-structured interviews to help the implementation process. The diagnosis made it possible to identify the level of maturity of the existing ICT processes in the State and to verify if they were being carried out in the best possible way. The driving dynamics worked as a pilot, allowing the exchange of knowledge between teams, improvements suggestion in some processes of the Kit and the definition of a proposed methodology for the implementation of the Kit that could serve as a model to be used by other States which will implement the Kit. Lastly, the processes contemplated in the Kit were considered adherent by the execution team (State employees specialists in ICT Governance who participated in the implementation process), and the suggested artifacts were validated.
Efficient Detection of Ventricular Late Potentials on ECG Signals Based on Wavelet Denoising and SVM Classification
Authors: Giorgio Agostino , Rizzi Maria , Guaragnella Cataldo
Published: October 2019

The analysis of cardiac signals is still regarded as attractive by both the academic community and industry because it helps physicians in detecting abnormalities and improving the diagnosis and therapy of diseases. Electrocardiographic signal processing for detecting irregularities related to the occurrence of low-amplitude waveforms inside the cardiac signal has a considerable workload as cardiac signals are heavily contaminated by noise and other artifacts. This paper presents an effective approach for the detection of ventricular late potential occurrences which are considered as markers of sudden cardiac death risk. Three stages characterize the implemented method which performs a beat-to-beat processing of high-resolution electrocardiograms (HR-ECG). Fifteen lead HR-ECG signals are filtered and denoised for the improvement of signal-to-noise ratio. Five features were then extracted and used as inputs of a classifier based on a machine learning approach. For the performance evaluation of the proposed method, a HR-ECG database consisting of real ventricular late potential (VLP)-negative and semi-simulated VLP-positive patterns was used. Experimental results show that the implemented system reaches satisfactory performance in terms of sensitivity, specificity accuracy, and positive predictivity; in fact, the respective values equal to 98.33%, 98.36%, 98.35%, and 98.52% were achieved.
Improving Basic Natural Language Processing Tools for the Ainu Language
Authors: Nowakowski Karol , Ptaszynski Michal , Masui Fumito , Momouchi Yoshio
Published: October 2019

Ainu is a critically endangered language spoken by the native inhabitants of northern Japan. This paper describes our research aimed at the development of technology for automatic processing of text in Ainu. In particular, we improved the existing tools for normalizing old transcriptions, word segmentation, and part-of-speech tagging. In the experiments we applied two Ainu language dictionaries from different domains (literary and colloquial) and created a new data set by combining them. The experiments revealed that expanding the lexicon had a positive impact on the overall performance of our tools, especially with test data unrelated to any of the training sets used.
Population Dynamics of Six Major Insect Pests During Multiple Crop Growing Seasons in Northwestern New Mexico
Authors: Djaman Koffi , Higgins Charles , O’Neill Michael , Begay Shantel , Koudahe Komlan , Allen Samuel
Published: October 2019

This study was conducted to monitor the population dynamics of six major insect pests at the NMSU Agricultural Science Center at Farmington (ASC-Farmington) and within an adjacent commercial farm (Navajo Agricultural Products Industry, NAPI) for more effective and efficient pest management during the 2013–2019 period. Specific pheromone traps, sticky and net traps were used to collects moths of beet armyworm (Spodoptera exigua), cabbage looper (Trichoplusia ni), corn earworm (Helicoverpa zea), fall armyworm (Spodoptera frugiperda), potato psyllid (Bactericera cockerelli), and western bean cutworm (Striacosta albicosta). These insects generally appear in early June and their population decreases toward the end of August/early September with different peak times and magnitudes during July and August. Bactericera cockerelli was not substantially present in the commercial farm due to intensive insecticide application. Overall, all six insect species were present at ASC-Farmington, with relative abundance, in percent of the total collected moths by all traps, varying from 6.5 to 19% for Trichoplusia ni, 16 to 29.2% for Spodoptera exigua, 1.5 to 20.6% for Striacosta albicosta, 10 to 25% for Helicoverpa zea, 18.5 to 25.6% for Spodoptera frugiperda and 8.5 to 26.9% for Bactericera cockerelli. In NAPI’s commercial field, while the potato psyllid Bactericera cockerelli was not recorded, Trichoplusia ni and Spodoptera exigua showed decreasing rates that varied from 27.5 to 4.2% and from 49.3 to 7.8%, respectively. Striacosta albicosta, Helicoverpa zea and Spodoptera exigua showed increasing rates varying from 2.9 to 28%, from 7.8 to 25.3% and from 10.9 to 52%, respectively. The results of this study could serve as a guideline for sustainable management strategies for each of the six species for production profitability.
A Multiscale Review of Behavioral Variation in Collective Foraging Behavior in Honey Bees
Authors: Lemanski Natalie J. , Cook Chelsea N. , Smith Brian H. , Pinter-Wollman Noa
Published: October 2019

The emergence of collective behavior from local interactions is a widespread phenomenon in social groups. Previous models of collective behavior have largely overlooked the impact of variation among individuals within the group on collective dynamics. Honey bees (Apis mellifera) provide an excellent model system for exploring the role of individual differences in collective behavior due to their high levels of individual variation and experimental tractability. In this review, we explore the causes and consequences of individual variation in behavior for honey bee foraging across multiple scales of organization. We summarize what is currently known about the genetic, developmental, and neurophysiological causes of individual differences in learning and memory among honey bees, as well as the consequences of this variation for collective foraging behavior and colony fitness. We conclude with suggesting promising future directions for exploration of the genetic and physiological underpinnings of individual differences in behavior in this model system.
The Factors Predicting Concordant Epidermal Growth Factor Receptor (EGFR) Mutation Detected in Liquid/Tissue Biopsy and the Related Clinical Outcomes in Patients of Advanced Lung Adenocarcinoma with EGFR Mutations
Authors: Kuo Chia-Yu , Lee Mei-Hsuan , Tsai Ming-Ju , Yang Chih-Jen , Hung Jen-Yu , Chong Inn-Wen
Published: October 2019

Liquid biopsy to identify epidermal growth factor receptor (EGFR) gene mutations from circulating tumor DNA (ctDNA) for lung adenocarcinoma is less invasive than traditional tissue biopsy. Most patients have concordant results in liquid/tissue biopsy, while the clinical significance of concordant results remains unclear. Our study aimed to evaluate the predicting factors and clinical outcomes associated with concordant results in liquid/tissue biopsy in newly diagnosed lung adenocarcinoma patients with EGFR mutations. In the 80 patients of stage III or IV lung adenocarcinoma, 51 patients had EGFR mutations detected in tissue samples, while 33 (65%) of them had concordant results shown in liquid biopsy. Multivariable regression analysis showed that lymph node involvement (adjusted odds ratio (95% CI): 8.71 (1.88–40.35), p = 0.0057) and bone metastasis (adjusted odds ratio (95% CI): 9.65 (1.72–54.05), p = 0.0099) were the independent predicting factors for concordant results. Forty of these 51 patients were stage IV and were treated with EGFR tyrosine kinase inhibitors (TKIs). The concordant results in liquid/tissue samples were associated with significantly poorer progression-free survival (PFS) in univariate analysis. However, multivariable analysis showed that lymph node involvement was the only independent predicting factor for poorer PFS, while concordant results in liquid/tissue samples were excluded during variable selection. The concordant results in liquid/tissue samples might indicate a larger tumor burden, which actually contributes to poorer PFS.
Buffering Capacity in Sepsis: A Prospective Cohort Study in Critically Ill Patients
Authors: Vasileiadis Ioannis , Kompoti Maria , Rovina Nikoletta , Tripodaki Elli-Sophia , Filis Christos , Alevrakis Emmanouil , Kyriakoudi Anna , Kyriakopoulou Magdalini , Koulouris Nikolaos , Koutsoukou Antonia
Published: October 2019

Background: The concept of buffering generally refers to the ability of a system/organism to withstand attempted changes. For acid-base balance in particular, it is the body’s ability to limit pH aberrations when factors that potentially affect it change. Buffering is vital for maintaining homeostasis of an organism. The present study was undertaken in order to investigate the probable buffering capacity changes in septic patients. Materials and methods: This prospective cohort study included 113 ICU patients (96 septic and 17 critically-ill non-septic/controls). The buffering capacity indices were assessed upon ICU admission and reassessed only in septic patients, either at improvement or upon severe deterioration. Applying Stewart’s approach, the buffering capacity was assessed with indices calculated from the observed central venous-arterial gradients: a) ΔPCO2/Δ[H+] or ΔpH, b) ΔSID/Δ[H+] or ΔpH. Results: In a generalized estimating equation linear regression model, septic patients displayed significant differences in ΔPCO2/ΔpH [beta coefficient = –47.63, 95% CI (–80.09) – (–15.17), p = 0.004], compared to non-septic patients on admission. Lower absolute value of ΔPCO2/ΔpH (%) on admission was associated with a significant reduction in ICU mortality (HR 0.98, 95% CI: 0.97–0.99, p = 0.02). At septic-group reassessment (remission or deterioration), one-unit increase of ΔPCO2/Δ[H+] reduced the ICU death hazard by 44% (HR 0.56, 95% CI: 0.33–0.96, p = 0.03). Conclusions: In the particular cohort of patients studied, a difference in the buffering capacity was recorded between septic and non-septic patients on admission. Moreover, buffering capacity was an independent predictor of fatal ICU outcome at both assessments, ICU-admission and sepsis remission or deterioration.
Pilates Method Improves Cardiorespiratory Fitness: A Systematic Review and Meta-Analysis
Authors: Fernández-Rodríguez Rubén , Álvarez-Bueno Celia , Ferri-Morales Asunción , Torres-Costoso Ana I. , Cavero-Redondo Iván , Martínez-Vizcaíno Vicente
Published: October 2019

Cardiorespiratory fitness has been postulated as an independent predictor of several chronic diseases. We aimed to estimate the effect of Pilates on improving cardiorespiratory fitness and to explore whether this effect could be modified by a participant’s health condition or by baseline VO2 max levels. We searched databases from inception to September 2019. Data were pooled using a random effects model. The Cochrane risk of bias (RoB 2.0) tool and the Quality Assessment Tool for Quantitative Studies were performed. The primary outcome was cardiorespiratory fitness measured by VO2 max. The search identified 527 potential studies of which 10 studies were included in the systematic review and 9 in the meta-analysis. The meta-analysis showed that Pilates increased VO2 max, with an effect size (ES) = 0.57 (95% CI: 0.15–1; I2 = 63.5%, p = 0.018) for the Pilates group vs. the control and ES = 0.51 (95% CI: 0.26–0.76; I2 = 67%, p = 0.002) for Pilates pre-post effect. The estimates of the pooled ES were similar in both sensitivity and subgroup analyses; however, random-effects meta-regressions based on baseline VO2 max were significant. Pilates improves cardiorespiratory fitness regardless of the population’s health status. Therefore, it may be an efficacious alternative for both the healthy population and patients suffering from specific disorders to achieve evidenced-based results from cardiorespiratory and neuromotor exercises.
Opioid-Related Diagnoses and Concurrent Claims for HIV, HBV, or HCV among Medicare Beneficiaries, United States, 2015
Authors: Chang Man-Huei , Moonesinghe Ramal , Schieber Lyna Z. , Truman Benedict I.
Published: October 2019

Unsterile opioid injection increases risk for infection transmission, including HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV). We assess prevalence of and risk factors associated with opioid overdose and infections with HIV, HBV, or HCV among Medicare beneficiaries with opioid-related fee-for-service claims during 2015. We conducted a cross-sectional analysis to estimate claims for opioid use and overdose and HIV, HBV, or HCV infections, using data from US Medicare fee-for-service claims. Beneficiaries with opioid-related claims had increased odds for HIV (2.3; 95% confidence interval (CI), 2.3–2.4), acute HBV (6.7; 95% CI, 6.3–7.1), chronic HBV (5.0; 95% CI, 4.7–5.4), acute HCV (9.6; 95% CI, 9.2–10.0), and chronic HCV (8.9; 95% CI, 8.7–9.1). Beneficiaries with opioid-related claims and for HIV, HBV, or HCV infection, respectively, had a 1.1–1.9-fold odds for having a claim for opioid overdose. Independent risk factors for opioid overdose and each selected infection outcome included age, sex, race/ethnicity, region, and residence in a high-vulnerability county. Having opioid-related claims and selected demographic attributes were independent, significant risk factors for having HIV, HBV, or HCV claims among US Medicare beneficiaries. These results might help guide interventions intended to reduce incidences of HIV, HCV, and HBV infections among beneficiaries with opioid-related claims.
Best Evidence Rehabilitation for Chronic Pain Part 5: Osteoarthritis
Authors: Rice David , McNair Peter , Huysmans Eva , Letzen Janelle , Finan Patrick
Published: October 2019

Osteoarthritis (OA) is a leading cause of chronic pain and disability in older adults, which most commonly affects the joints of the knee, hip, and hand. To date, there are no established disease modifying interventions that can halt or reverse OA progression. Therefore, treatment is focused on alleviating pain and maintaining or improving physical and psychological function. Rehabilitation is widely recommended as first-line treatment for OA as, in many cases, it is safer and more effective than the best-established pharmacological interventions. In this article, we describe the presentation of OA pain and give an overview of its peripheral and central mechanisms. We then provide a state-of-the-art review of rehabilitation for OA pain—including self-management programs, exercise, weight loss, cognitive behavioral therapy, adjunct therapies, and the use of aids and devices. Next, we explore several promising directions for clinical practice, including novel education strategies to target unhelpful illness and treatment beliefs, methods to enhance the efficacy of exercise interventions, and innovative, brain-directed treatments. Finally, we discuss potential future research in areas, such as treatment adherence and personalized rehabilitation for OA pain.
Recovery from Anesthesia after Robotic-Assisted Radical Cystectomy: Two Different Reversals of Neuromuscular Blockade
Authors: Claroni Claudia , Covotta Marco , Torregiani Giulia , Marcelli Maria Elena , Tuderti Gabriele , Simone Giuseppe , Scotto di Uccio Alessandra , Zinilli Antonio , Forastiere Ester
Published: October 2019

During robot-assisted radical cystectomy (RARC), specific surgical conditions (a steep Trendelenburg position, prolonged pneumoperitoneum, effective myoresolution until the final stages of surgery) can seriously impair the outcomes. The aim of the study was to evaluate the incidence of postoperative nausea and vomiting (PONV) and ileus and the quality of cognitive function at the awakening in two groups of patients undergoing different reversals. In this randomized trial, patients that were American Society of Anesthesiologists physical status (ASA) ≤III candidates for RARC for bladder cancer were randomized into two groups: In the sugammadex (S) group, patients received 2 mg/kg of sugammadex as reversal of neuromuscolar blockade; in the neostigmine (N) group, antagonization was obtained with neostigmine 0.04 mg/kg + atropine 0.02 mg/kg. PONV was evaluated at 30 min, 6 and 24 h after anesthesia. Postoperative cognitive functions and time to resumption of intestinal transit were also investigated. A total of 109 patients were analyzed (54 in the S group and 55 in the N group). The incidence of early PONV was lower in the S group but not statistically significant (S group 25.9% vs. N group 29%; p = 0.711). The Mini-Mental State test mean value was higher in the S group vs. the N group (1 h after surgery: 29.3 (29; 30) vs. 27.6 (27; 30), p = 0.007; 4 h after surgery: 29.5 (30; 30) vs. 28.4 (28; 30), p = 0.05). We did not observe a significant decrease of the PONV after sugammadex administration versus neostigmine use. The Mini-Mental State test mean value was greater in the S group.
Development of a Minimum Data Set Registry for Chronic Venous Insufficiency of the Lower Limbs
Authors: Homs-Romero Erica , Romero-Collado Angel
Published: October 2019

The purpose of this study was to develop a minimum data set (MDS) registry for the prevention, diagnosis and treatment of chronic venous insufficiency (CVI) of the lower limbs. We designed the instrument in two phases, comprising a literature review and an e-Delphi study to validate the content. We obtained a total of 39 documents that we used to develop a registry with 125 items grouped in 7 categories, as follows: Patient examination, venous disease assessment methods, diagnostic tests to confirm the disease, ulcer assessment, treatments to manage the disease at all its stages, patient quality of life, and patient health education. The instrument content was validated by 25 experts, 88% of whom were primary healthcare and hospital nurses and 84% had more than 10 years’ experience in wound care. Using a two-round Delphi approach, we reduced the number of items in the MDS-CVI to 106 items. The categories remained unchanged. We developed an MDS for CVI with seven categories to assist healthcare professionals in the prevention, early detection, and treatment history of CVI. This tool will allow the creation of a registry in the primary care setting to monitor the venous health state of the population.
Hybrid Zoning Algorithm to Optimize Overhead in Smart Mobile Communication
Authors: Souidi Mohammed , Habbani Ahmed , Berradi Halim
Published: October 2019

With the increase of mobile terminals, routing protocols in wireless communications must provide better quality of service to meet bandwidth and reliability requirements. In networks without infrastructure, such as ad hoc and sensor networks, where a device performs as both a terminal and a router to forward data of other nodes, maintaining the network topology consumes considerable resources in terms of energy and bandwidth. These parameters need to be considered when designing routing protocols for wireless networks. To reduce the cost of the protocol overhead, some algorithms act on the forwarders, while others act on the transmission of messages. Finally, the hybrid ones are a combination of both. In this paper, we propose a new algorithm with two zoning strategies to enhance the performance of mobile network. The first strategy helps to select dispersive forwarders in order to reduce the collision in radio channel. The second strategy aims to reduce the transmission of redundant messages. Both strategies are based on the location information of nodes. We implemented our algorithm in the optimized link state routing protocol, the most used protocol in mobile ad hoc networks. We showed by simulations that our solution reduces drastically the cost of the overhead with no hindrance to the network topology.
Prospects for Agricultural Sustainable Intensification: A Review of Research
Authors: Xie Hualin , Huang Yingqian , Chen Qianru , Zhang Yanwei , Wu Qing
Published: October 2019

In recent years, as a way to achieve higher agricultural output while reducing the negative impact of agricultural production on the environment, agricultural sustainable intensification has attracted worldwide attention. Under the framework of "connotation definition-measuring method-influencing factor-implementation path", this paper systematically sorts out the main research results in the field of agricultural sustainable intensification. The results show that: (1) The connotation of agricultural sustainable intensification has not been clearly defined. It is widely believed that sustainable intensification has the characteristics of increasing production and reducing environmental damage, and is widely used in agricultural, biological and environmental sciences; (2) The measurement methods and indicators of agricultural sustainable intensification are diverse, and the measurement cases are mainly distributed in Europe, Asia, Africa and America; (3) The influencing factors of agricultural sustainable intensification can be roughly divided into four aspects: socio-economic factors, farmers’ own characteristics and natural factors, among which population pressure is the potential driving force for agricultural sustainable intensification; (4) The most obvious feature of agricultural sustainable intensification is the reduction of the yield gap. The strategy of implementing agricultural sustainable intensification can be attributed to the effective use of inputs and the adoption of sustainable practices and technologies. Therefore, the implementation path can be summarized as enhancing the effectiveness of external inputs to the agricultural system and optimizing the practice and technology mix within the crop production system. Finally, this paper concludes that research on connotation definition, influencing mechanism, different regional models, incentive mechanism for farmers, impact evaluation and system design of agricultural sustainable intensification should be strengthened in future.
Wheat Space Odyssey: “From Seed to Seed”. Kernel Morphology
Authors: Baranova Ekaterina N. , Levinskikh Margarita A. , Gulevich Alexander A.
Published: October 2019

The long-term autonomous existence of man in extraterrestrial conditions is associated with the need to cultivate plants—the only affordable and effective means for both providing oxygen and CO2 utilization, and providing one of the most habitual and energetically valuable products: plant food. In this study, we analyzed the results of the space odyssey of wheat and compared the morphological features of parental grains harvested from soil grown wheat plants, the grains obtained from plants grown in a specialized device for plant cultivation—the “Lada” space greenhouses during space flight in the ISS, and the grains obtained from plants in the same device on Earth. The seeds obtained under various conditions were studied using scanning electron microscopy. We studied the mutual location of the surface layers of the kernel cover tissues, the structural features of the tube and cross cells of the fruit coat (pericarp), and the birsh hairs of the kernels. It was found that the grains obtained under wheat plants cultivation on board of the ISS in near space had some specific differences from the parental, original grains, and the grains obtained from plants grown in the “Lada” greenhouse in ground conditions. These changes were manifested in a shortening of the birsh hairs, and a change in the size and relative arrangement of the cells of the kernel coat. We suggest that such changes are a manifestation of the sensitivity of the cytoskeleton reorganization systems and water exchange to the influence of particular physical conditions of space flight (microgravity, increased doses of radiation, etc.). Thus, the revealed changes did not hinder the wheat grains production “from seed to seed”, which allows the cultivation of this crop in stable life support systems in near earth orbit.
Characterization of Patients with Allergic Rhinitis to Ragweed Pollen in Two Distinct Regions of Romania
Authors: Bocsan Ioana Corina , Muntean Ioana Adriana , Ureche Corina , Pop Raluca Maria , Neag Maria Adriana , Sabin Octavia , Deleanu Diana , Buzoianu Anca Dana
Published: October 2019

Background and objectives: Ragweed pollen is a major source of allergen, which has rarely been observed in Romania until now. In this study, we evaluated the symptoms and associated factors in patients with allergic rhinitis to ragweed pollen in two distinct regions of Romania. Materials and Methods: We evaluated the records of patients newly diagnosed with allergic rhinitis induced by ragweed pollen in two allergological centers from North-West (NW) and Central parts of Romania between 2013 and 2015. The patients were clinically evaluated regarding disease length, presence, and severity of the allergic rhinitis symptoms and the association with other allergic manifestations (asthma and conjunctivitis). Results: The sensitization to ragweed was significantly higher in the NW part compared to the Central part (18.27% vs 4.1%, p < 0.001). More patients with monosensitization to ragweed pollen were observed in the NE center (27%) compared to the Central one (20.7%). Patients with monosensitization to ragweed pollen presented more severe forms of rhinitis (70% vs 31.5%, p = 0.02) in the NW part compared to polysensitized patients. The total symptoms score was significantly higher in patients from the Central part compared to the NW part (9.21 ± 2.01 vs 5.76 ±1.96, p < 0.001). Bronchial asthma was associated at a similar frequency to allergic rhinitis in both centers, but it was more frequently observed in monosensitized patients in the NW center. Allergic conjunctivitis was more frequently reported by patients from the Central part (75.86 vs 41.9, p = 0.02), while in the NW region it was noticed more commonly in monosensitized patients (65% vs 33.33, p = 0.02). Conclusions: Allergic rhinitis to ragweed pollen has been more frequently reported in the NW part of Romania. Patients with severe forms of rhinitis were observed in the central part, while in the NW the severe forms of disease were reported by patients with monosensitization. Ragweed pollen is intensely allergogenic and determines association of ocular and asthma symptoms. Co-sensitization increases the risk of asthma association.