bluuebunny/crossref_metadata_2025 huggingface dataset:
Biosynthesis of Phenylamide Phytoalexins in Pathogen-Infected Barley
Authors: Ube Naoki , Yabuta Yukinori , Tohnooka Takuji , Ueno Kotomi , Taketa Shin , Ishihara Atsushi
Published: November 2019

Phytoalexins are inducible antimicrobial metabolites in plants, and have been indicated to be important for the rejection of microbial infection. HPLC analysis detected the induced accumulation of three compounds 1–3 in barley (Hordeum vulgare) roots infected by Fusarium culmorum, the causal agent of Fusarium root rot. Compounds 1–3 were identified as cinnamic acid amides of 9-hydroxy-8-oxotryptamine, 8-oxotryptamine, and (1H-indol-3-yl)methylamine, respectively, by spectroscopic analysis. Compounds 1 and 2 had been previously reported from wheat, whereas 3 was an undescribed compound. We named 1–3 as triticamides A–C, respectively, because they were isolated from barley and wheat, which belong to the Triticeae tribe. These compounds showed antimicrobial activities, indicating that triticamides function as phytoalexins in barley. The administration of deuterium-labeled N-cinnamoyl tryptamine (CinTry) to barley roots resulted in the effective incorporation of CinTry into 1 and 2, which suggested that they were synthesized through the oxidation of CinTry. Nine putative tryptamine hydroxycinnamoyl transferase (THT)-encoding genes (HvTHT1–HvTHT9) were identified by database search on the basis of homology to known THT gene sequences from rice. Since HvTHT7 and HvTHT8 had the same sequences except one base, we measured their expression levels in total by RT-qPCR. HvTHT7/8 were markedly upregulated in response to infection by F. culmorum. The HvTHT7 and HvTHT8 enzymes preferred cinnamoyl- and feruloyl-CoAs as acyl donors and tryptamine as an acyl acceptor, and (1H-indol-3-yl)methylamine was also accepted as an acyl acceptor. These findings suggested that HvTHT7/8 are responsible for the induced accumulation of triticamides in barley.
Characterization of New TRPM8 Modulators in Pain Perception
Authors: De Caro Carmen , Cristiano Claudia , Avagliano Carmen , Bertamino Alessia , Ostacolo Carmine , Campiglia Pietro , Gomez-Monterrey Isabel , La Rana Giovanna , Gualillo Oreste , Calignano Antonio , Russo Roberto
Published: November 2019

Background: Transient Receptor Potential Melastatin-8 (TRPM8) is a non-selective cation channel activated by cold temperature and by cooling agents. Several studies have proved that this channel is involved in pain perception. Although some studies indicate that TRPM8 inhibition is necessary to reduce acute and chronic pain, it is also reported that TRPM8 activation produces analgesia. These conflicting results could be explained by extracellular Ca2+-dependent desensitization that is induced by an excessive activation. Likely, this effect is due to phosphatidylinositol 4,5-bisphosphate (PIP2) depletion that leads to modification of TRPM8 channel activity, shifting voltage dependence towards more positive potentials. This phenomenon needs further evaluation and confirmation that would allow us to understand better the role of this channel and to develop new therapeutic strategies for controlling pain. Experimental approach: To understand the role of TRPM8 in pain perception, we tested two specific TRPM8-modulating compounds, an antagonist (IGM-18) and an agonist (IGM-5), in either acute or chronic animal pain models using male Sprague-Dawley rats or CD1 mice, after systemic or topical routes of administration. Results: IGM-18 and IGM-5 were fully characterized in vivo. The wet-dog shake test and the body temperature measurements highlighted the antagonist activity of IGM-18 on TRPM8 channels. Moreover, IGM-18 exerted an analgesic effect on formalin-induced orofacial pain and chronic constriction injury-induced neuropathic pain, demonstrating the involvement of TRPM8 channels in these two pain models. Finally, the results were consistent with TRPM8 downregulation by agonist IGM-5, due to its excessive activation. Conclusions: TRPM8 channels are strongly involved in pain modulation, and their selective antagonist is able to reduce both acute and chronic pain.
GnRH Antagonists Produce Differential Modulation of the Signaling Pathways Mediated by GnRH Receptors
Authors: Sperduti Samantha , Limoncella Silvia , Lazzaretti Clara , Paradiso Elia , Riccetti Laura , Turchi Sara , Ferrigno Ilaria , Bertacchini Jessika , Palumbo Carla , Potì Francesco , Longobardi Salvatore , Millar Robert P. , Simoni Manuela , Newton Claire L. , Casarini Livio
Published: November 2019

Commercial gonadotropin-releasing hormone (GnRH) antagonists differ by 1–2 amino acids and are used to inhibit gonadotropin production during assisted reproduction technologies (ART). In this study, potencies of three GnRH antagonists, Cetrorelix, Ganirelix and Teverelix, in inhibiting GnRH-mediated intracellular signaling, were compared in vitro. GnRH receptor (GnRHR)-transfected HEK293 and neuroblastoma-derived SH-SY5Y cell lines, as well as mouse pituitary LβT2 cells endogenously expressing the murine GnRHR, were treated with GnRH in the presence or absence of the antagonist. We evaluated intracellular calcium (Ca2+) and cAMP increases, cAMP-responsive element binding-protein (CREB) and extracellular-regulated kinase 1 and 2 (ERK1/2) phosphorylation, β-catenin activation and mouse luteinizing-hormone β-encoding gene (Lhb) transcription by bioluminescence resonance energy transfer (BRET), Western blotting, immunostaining and real-time PCR as appropriate. The kinetics of GnRH-induced Ca2+ rapid increase revealed dose-response accumulation with potency (EC50) of 23 nM in transfected HEK293 cells, transfected SH-SY5Y and LβT2 cells. Cetrorelix inhibited the 3 × EC50 GnRH-activated calcium signaling at concentrations of 1 nM–1 µM, demonstrating higher potency than Ganirelix and Teverelix, whose inhibitory doses fell within the 100 nM–1 µM range in both transfected HEK293 and SH-SY5Y cells in vitro. In transfected SH-SY5Y, Cetrorelix was also significantly more potent than other antagonists in reducing GnRH-mediated cAMP accumulation. All antagonists inhibited pERK1/2 and pCREB activation at similar doses, in LβT2 and transfected HEK293 cells treated with 100 nM GnRH. Although immunostainings suggested that Teverelix could be less effective than Cetrorelix and Ganirelix in inhibiting 1 µM GnRH-induced β-catenin activation, Lhb gene expression increase occurring upon LβT2 cell treatment by 1 µM GnRH was similarly inhibited by all antagonists. To conclude, this study has demonstrated Cetrorelix-, Ganirelix- and Teverelix-specific biased effects at the intracellular level, not affecting the efficacy of antagonists in inhibiting Lhb gene transcription.
Comparatively Barcoded Chromosomes of Brachypodium Perennials Tell the Story of Their Karyotype Structure and Evolution
Authors: Lusinska Joanna , Betekhtin Alexander , Lopez-Alvarez Diana , Catalan Pilar , Jenkins Glyn , Wolny Elzbieta , Hasterok Robert
Published: November 2019

The Brachypodium genus is an informative model system for studying grass karyotype organization. Previous studies of a limited number of species and reference chromosomes have not provided a comprehensive picture of the enigmatic phylogenetic relationships in the genus. Comparative chromosome barcoding, which enables the reconstruction of the evolutionary history of individual chromosomes and their segments, allowed us to infer the relationships between putative ancestral karyotypes of extinct species and extant karyotypes of current species. We used over 80 chromosome-specific BAC (bacterial artificial chromosome) clones derived from five reference chromosomes of B. distachyon as probes against the karyotypes of twelve accessions representing five diploid and polyploid Brachypodium perennials. The results showed that descending dysploidy is common in Brachypodium and occurs primarily via nested chromosome fusions. Brachypodium distachyon was rejected as a putative ancestor for allotetraploid perennials and B. stacei for B. mexicanum. We propose two alternative models of perennial polyploid evolution involving either the incorporation of a putative x = 5 ancestral karyotype with different descending dysploidy patterns compared to B. distachyon chromosomes or hybridization of two x = 9 ancestors followed by genome doubling and descending dysploidy. Details of the karyotype structure and evolution in several Brachypodium perennials are revealed for the first time.
The Pathogenic TSH β-Subunit Variant C105Vfs114X Causes a Modified Signaling Profile at TSHR
Authors: Kalveram Laura , Kleinau Gunnar , Szymańska Kamila , Scheerer Patrick , Rivero-Müller Adolfo , Grüters-Kieslich Annette , Biebermann Heike
Published: November 2019

(1) Background: Central congenital hypothyroidism (CCH) is a rare endocrine disorder that can be caused by mutations in the β-subunit of thyrotropin (TSHB). The TSHB mutation C105Vfs114X leads to isolated thyroid-stimulating-hormone-(TSH)-deficiency and results in a severe phenotype. The aim of this study was to gain more insight into the underlying molecular mechanism and the functional effects of this mutation based on two assumptions: a) the three-dimensional (3D) structure of TSH should be modified with the C105V substitution, and/or b) whether the C-terminal modifications lead to signaling differences. (2) Methods: wild-type (WT) and different mutants of hTSH were generated in human embryonic kidney 293 cells (HEK293 cells) and TSH preparations were used to stimulate thyrotropin receptor (TSHR) stably transfected into follicular thyroid cancer cells (FTC133-TSHR cells) and transiently transfected into HEK293 cells. Functional characterization was performed by determination of Gs, mitogen activated protein kinase (MAPK) and Gq/11 activation. (3) Results: The patient mutation C105Vfs114X and further designed TSH mutants diminished cyclic adenosine monophosphate (cAMP) signaling activity. Surprisingly, MAPK signaling for all mutants was comparable to WT, while none of the mutants induced PLC activation. (4) Conclusion: We characterized the patient mutation C105Vfs114X concerning different signaling pathways. We identified a strong decrease of cAMP signaling induction and speculate that this could, in combination with diverse signaling regarding the other pathways, accounting for the patient’s severe phenotype.
Systematic Elucidation of the Mechanism of Genistein against Pulmonary Hypertension via Network Pharmacology Approach
Authors: Chen Yucai , Chen Di , Liu Sijia , Yuan Tianyi , Guo Jian , Fang Lianhua , Du Guanhua
Published: November 2019

: Numerous studies have shown that genistein has a good therapeutic effect on pulmonary hypertension (PH). However, there has been no systematic research performed yet to elucidate its exact mechanism of action in relation to PH. In this study, a systemic pharmacology approach was employed to analyze the anti-PH effect of genistein. Firstly, the preliminary predicted targets of genistein against PH were obtained through database mining, and then the correlation of these targets with PH was analyzed. After that, the protein-protein interaction network was constructed, and the functional annotation and cluster analysis were performed to obtain the core targets and key pathways involved in exerting the anti-PH effect of genistein. Finally, the mechanism was further analyzed via molecular docking of genistein with peroxisome proliferator-activated receptor γ (PPARγ). The results showed that the anti-PH effect of genistein may be closely related to PPARγ, apoptotic signaling pathway, and the nitric oxide synthesis process. This study not only provides new insights into the mechanism of genistein against PH, but also provides novel ideas for network approaches for PH-related research.
Investigation of the Moderating Effect of Culture on Users’ Susceptibility to Persuasive Features in Fitness Applications
Authors: Oyibo Kiemute , Vassileva Julita
Published: November 2019

Persuasive technologies have been identified as a potential motivational tool to tackle the rising problem of physical inactivity worldwide, with research showing they are more likely to be successful if tailored to the target audience. However, in the physical activity domain, there is limited research on how culture moderates users’ susceptibility to the various persuasive features employed in mobile health applications aimed to motivate behavior change. To bridge this gap, we conducted an empirical study among 256 participants from collectivist (n = 67) and individualist (n = 189) cultures to determine their culture-specific persuasion profiles with respect to six persuasive features commonly employed in fitness applications on the market. The persuasive features include two personal features (goal-setting/self-monitoring and reward) and four social features (competition, cooperation, social learning and social comparison). We based our study on the rating of storyboards (on which each of the six persuasive features is illustrated) and the ranking of the six persuasive features in terms of perceived persuasiveness. The results of our analysis showed that users from individualist and collectivist cultures significantly differ in their persuasion profiles. Based on our rating measure, collectivist users are more likely to be susceptible to all six persuasive features (personal and social) than individualist users, who are only likely to be susceptible to personal features. However, based on our ranking measure, individualist users are more likely to be susceptible to personal features (goal-setting/self-monitoring and reward) than collectivist users. In contrast, collectivist users are more likely to be susceptible to social features (cooperation and social learning) than individualist users. Based on these findings, we provide culture-specific persuasive technology design guidelines. Our study is the first to uncover the moderating effect of culture on users’ susceptibility to commonly employed persuasive features in fitness applications.
Combining Visual Contrast Information with Sound Can Produce Faster Decisions
Authors: Dresp-Langley Birgitta , Monfouga Marie
Published: November 2019

Pieron’s and Chocholle’s seminal psychophysical work predicts that human response time to information relative to visual contrast and/or sound frequency decreases when contrast intensity or sound frequency increases. The goal of this study is to bring to the forefront the ability of individuals to use visual contrast intensity and sound frequency in combination for faster perceptual decisions of relative depth (“nearer”) in planar (2D) object configurations based on physical variations in luminance contrast. Computer controlled images with two abstract patterns of varying contrast intensity, one on the left and one on the right, preceded or not by a pure tone of varying frequency, were shown to healthy young humans in controlled experimental sequences. Their task (two-alternative, forced-choice) was to decide as quickly as possible which of two patterns, the left or the right one, in a given image appeared to “stand out as if it were nearer” in terms of apparent (subjective) visual depth. The results showed that the combinations of varying relative visual contrast with sounds of varying frequency exploited here produced an additive effect on choice response times in terms of facilitation, where a stronger visual contrast combined with a higher sound frequency produced shorter forced-choice response times. This new effect is predicted by audio-visual probability summation.
Syntheses and Structures of Novel λ3,λ3-Phosphanylalumanes Fully Bearing Carbon Substituents and Their Substituent Effects
Authors: Yanagisawa Tatsuya , Mizuhata Yoshiyuki , Tokitoh Norihiro
Published: November 2019

The novel phosphanylalumanes, Al–P single-bond species, fully bearing carbon protecting groups on aluminum and phosphorus atoms, are synthesized by the reactions of aluminum monohalides [(t-Bu)2AlBr and (C6F5)2AlCl·0.5(toluene)] with Mes2PLi. Regarding the t-Bu system, λ3,λ3-phosphanylalumane is obtained. Concerning the C6F5 system, on the other hand, the corresponding LiCl complex, λ4,λ4-phosphanylalumane, is obtained. The Al–P bond lengths of C6F5-substituted λ3,λ4-, and λ4,λ4-derivatives are much shorter than those of the reported λ3,λ4-phosphanylalumane derivatives and comparable to that observed for the previously reported λ3,λ3-phosphanylalumanes. Theoretical calculations reveal that the binding of the C6F5 groups to Al results in a large contribution of Al and a large s-character in the Al–P bond of phosphanylalumanes. Considering t-Bu-substituted phosphanylalumanes, the Al–P bond lengths reflect the coordination number of Al, showing a longer Al–P bond length in the case of λ4-Al as compared with that of λ3-Al. Combining the structural, spectroscopic, and theoretical results, the t-Bu-substituted λ3,λ3-phosphanylalumane has well separated vacant p orbital and lone pairs, which is suitable for reactivity studies.
Do Host Plant and Associated Ant Species Affect Microbial Communities in Myrmecophytes?
Authors: Ruiz-González Mario X. , Leroy Céline , Dejean Alain , Gryta Hervé , Jargeat Patricia , Armijos Carrión Angelo D. , Orivel Jérôme
Published: November 2019

Ant-associated microorganisms can play crucial and often overlooked roles, and given the diversity of interactions that ants have developed, the study of the associated microbiomes is of interest. We focused here on specialist plant-ant species of the genus Allomerus that grow a fungus to build galleries on their host-plant stems. Allomerus-inhabited domatia, thus, might be a rich arena for microbes associated with the ants, the plant, and the fungus. We investigated the microbial communities present in domatia colonised by four arboreal ants: Allomerus decemarticulatus, A. octoarticulatus, A. octoarticulatus var. demerarae, and the non-fungus growing plant-ant Azteca sp. cf. depilis, inhabiting Hirtella physophora or Cordia nodosa in French Guiana. We hypothesized that the microbial community will differ among these species. We isolated microorganisms from five colonies of each species, sequenced the 16S rRNA or Internal TranscribedSpacer (ITS) regions, and described both the alpha and beta diversities. We identified 69 microbial taxa, which belong to five bacterial and two fungal phyla. The most diverse phyla were Proteobacteria and Actinobacteria. The microbial community of Azteca cf. depilis and Allomerus spp. differed in composition and richness. Geographical distance affected microbial communities and richness but plant species did not. Actinobacteria were only associated with Allomerus spp.
Gall-Colonizing Ants and Their Role as Plant Defenders: From ’Bad Job’ to ’Useful Service’
Authors: Giannetti Daniele , Castracani Cristina , Spotti Fiorenza A. , Mori Alessandra , Grasso Donato A.
Published: November 2019

Galls are neoformed structures on host plant tissues caused by the attack of insects or other organisms. They support different communities of specialized parasitic insects (the gall inducers), and can also provide refuge to other insects, such as moths, beetles and ants, referred to as secondary occupants. This study focuses on galls induced by the oak gall wasp Andricus quercustozae and secondarily colonized by ants in a mixed oak forest. A field survey and two experiments were carried out to a) study ant (species-specific) preferences for different features of the galls, b) describe differences in gall architecture due to ant activity, c) analyse the effects of the presence of gall-dwelling ants on plant health. The results show that there are differences between ant species in gall colonization and in the alteration of gall opening and inner structure. We verified that gall-dwelling ants protect their host plants efficiently, offering them an indirect defence mechanism against enemies (predators and pathogens). The data suggest a new paradigm in ant–plant relationships mediated by the presence of galls on the plants whose ecological and evolutionary implications are discussed.
Computed and Subjective Blue Scleral Color Analysis as a Diagnostic Tool for Iron Deficiency: A Pilot Study
Authors: Lobbes Hervé , Dehos Julien , Pereira Bruno , Le Guenno Guillaume , Sarry Laurent , Ruivard Marc
Published: November 2019

Iron deficiency (ID) is the most common nutritional deficiency. ID diagnosis requires ferritin measurement because clinical findings are poor and nonspecific. We studied the diagnostic value of blue sclera, which was scarcely reported as a specific and sensitive sign of ID. We enrolled 74 patients suspected of having ID. Pictures of their eyes were taken using a smartphone under similar daylight conditions. Three independent physicians graded the scleral color, and a computer analysis yielded the blue percentile of the sclera image. Final analysis included 67 patients (mean age 59.9 ± 20.1 years). Fifty-one had ID. Subjective blue scleral color was associated with ID for physician 1 (64.5% vs. 86.1%, p = 0.03). Sensitivity was 60.8% (CI95: 46.1%; 74.2%), specificity 68.8% (CI95: 41.3%; 89%), and positive predictive value 86.1% (CI95: 70.5%; 95.3%). A marginal difference was observed for other physicians (p = 0.05). Computer analysis showed higher blue in the ID group (p = 0.04). The area under the receiver operating characteristic (ROC) curve was 0.7 (0.54; 0.85). Sensitivity was 78.4% (CI95: 63.7%; 88.7%), specificity was 50% (CI95: 24.7%; 75.3%). Assessment of blue sclera was not influenced by iris color, sex, or anemia. We showed that blue sclera has good positive predictive value for ID diagnosis, and computer analysis was correlated to clinical assessment. Improvement of this innovative, non-invasive method could provide an easy handling and inexpensive diagnosis tool for ID.
CMR Tissue Characterization in Patients with HFmrEF
Authors: Doeblin Patrick , Hashemi Djawid , Tanacli Radu , Lapinskas Tomas , Gebker Rolf , Stehning Christian , Motzkus Laura Astrid , Blum Moritz , Tahirovic Elvis , Dordevic Aleksandar , Kraft Robin , Zamani Seyedeh Mahsa , Pieske Burkert , Edelmann Frank , Düngen Hans-Dirk , Kelle Sebastian
Published: November 2019

The characteristics and optimal management of heart failure with a moderately reduced ejection fraction (HFmrEF, LV-EF 40–50%) are still unclear. Advanced cardiac MRI offers information about function, fibrosis and inflammation of the myocardium, and might help to characterize HFmrEF in terms of adverse cardiac remodeling. We, therefore, examined 17 patients with HFpEF, 18 with HFmrEF, 17 with HFrEF and 17 healthy, age-matched controls with cardiac MRI (Phillips 1.5 T). T1 and T2 relaxation time mapping was performed and the extracellular volume (ECV) was calculated. Global circumferential (GCS) and longitudinal strain (GLS) were derived from cine images. GLS (−15.7 ± 2.1) and GCS (−19.9 ± 4.1) were moderately reduced in HFmrEF, resembling systolic dysfunction. Native T1 relaxation times were elevated in HFmrEF (1027 ± 40 ms) and HFrEF (1033 ± 54 ms) compared to healthy controls (972 ± 31 ms) and HFpEF (985 ± 32 ms). T2 relaxation times were elevated in HFmrEF (55.4 ± 3.4 ms) and HFrEF (56.0 ± 6.0 ms) compared to healthy controls (50.6 ± 2.1 ms). Differences in ECV did not reach statistical significance. HFmrEF differs from healthy controls and shares similarities with HFrEF in cardiac MRI parameters of fibrosis and inflammation.
Patient-Derived Head and Neck Cancer Organoids Recapitulate EGFR Expression Levels of Respective Tissues and Are Responsive to EGFR-Targeted Photodynamic Therapy
Authors: Driehuis Else , Spelier Sacha , Beltrán Hernández Irati , de Bree Remco , M. Willems Stefan , Clevers Hans , Oliveira Sabrina
Published: November 2019

Patients diagnosed with head and neck squamous cell carcinoma (HNSCC) are currently treated with surgery and/or radio- and chemotherapy. Despite these therapeutic interventions, 40% of patients relapse, urging the need for more effective therapies. In photodynamic therapy (PDT), a light-activated photosensitizer produces reactive oxygen species that ultimately lead to cell death. Targeted PDT, using a photosensitizer conjugated to tumor-targeting molecules, has been explored as a more selective cancer therapy. Organoids are self-organizing three-dimensional structures that can be grown from both normal and tumor patient-material and have recently shown translational potential. Here, we explore the potential of a recently described HNSCC–organoid model to evaluate Epidermal Growth Factor Receptor (EGFR)-targeted PDT, through either antibody- or nanobody-photosensitizer conjugates. We find that EGFR expression levels differ between organoids derived from different donors, and recapitulate EGFR expression levels of patient material. EGFR expression levels were found to correlate with the response to EGFR-targeted PDT. Importantly, organoids grown from surrounding normal tissues showed lower EGFR expression levels than their tumor counterparts, and were not affected by the treatment. In general, nanobody-targeted PDT was more effective than antibody-targeted PDT. Taken together, patient-derived HNSCC organoids are a useful 3D model for testing in vitro targeted PDT.
Quadriceps Neuromuscular Impairments after Arthroscopic Knee Surgery: Comparison between Procedures
Authors: Casartelli Nicola C. , Item-Glatthorn Julia F. , Friesenbichler Bernd , Bizzini Mario , Salzmann Gian M. , Maffiuletti Nicola A.
Published: November 2019

Quadriceps neuromuscular function remains impaired in the short- and long-term following knee arthroscopy for meniscal surgery and/or anterior cruciate ligament (ACL) reconstruction. The aim of this study was to compare quadriceps neuromuscular impairments in patients following meniscal surgery with and without ACL reconstruction. Thirty patients were tested six months after meniscal surgery with (n = 15) and without (n = 15) ACL reconstruction. We bilaterally assessed knee extension maximal voluntary contraction (MVC) torque using dynamometry, vastus lateralis thickness using ultrasound, quadriceps voluntary activation and evoked knee extension torque with transcutaneous electrical stimulation. Patient-reported outcomes were evaluated with the Knee Injury and Osteoarthritis Outcome Score (KOOS). Compared with meniscus patients, ACL patients demonstrated larger asymmetries in MVC torque (15% vs. 5%, p = 0.049) and vastus lateralis thickness (6% vs. 0%, p = 0.021). In ACL patients, asymmetries in MVC torque correlated with asymmetries in evoked torque (r = 0.622, p = 0.013). In meniscus patients, asymmetries in muscle activation correlated with KOOS quality of life (r = 0.619, p = 0.018). Patients demonstrated persistent quadriceps muscle weakness six months after ACL reconstruction, but not after isolated meniscal surgery. Quantitative and/or qualitative muscular changes likely underlie quadriceps muscle weakness in ACL patients, whereas activation failure is associated with poor quality of life in some meniscus patients.
The Reciprocal Association between Problem Gambling and Mental Health Symptoms/Substance Use: Cross-Lagged Path Modelling of Longitudinal Cohort Data
Authors: Dowling Nicki A. , Butera Carla A. , Merkouris Stephanie S. , Youssef George J. , Rodda Simone N. , Jackson Alun C.
Published: November 2019

To date, studies have highlighted cross-sectional and unidirectional prospective relationships between problem gambling and mental health symptoms or substance use. The current study aims to: (1) examine the reciprocal relationships between problem gambling and mental health symptoms (depression, generalized anxiety)/substance use variables (hazardous alcohol use, daily tobacco use, and drug use) using cross-lagged path models in a prospective general population cohort sample; and (2) determine whether these associations are moderated by age and gender. This study involved secondary data analysis from 1109 respondents who provided data during Wave 2 or 3 (12-months apart) of the Tasmanian Longitudinal Gambling Study (Australia). Depression (odds ratio (OR) = 2.164) and generalized anxiety (OR = 2.300) at Wave 2 were found to have cross-lagged associations with the subsequent development of any-risk gambling (low-risk, moderate-risk, or problem gambling) at Wave 3. Hazardous alcohol use, daily tobacco use, and drug use at Wave 2 were not associated with the development of any-risk gambling at Wave 3. Any-risk gambling at Wave 2 was not associated with the subsequent development of any mental health symptoms or substance use variables at Wave 3. Age and gender failed to be significant moderators in the associations between any-risk gambling and mental health symptoms or substance use variables. Future longitudinal and event-level research is required to further substantiate these prospective relationships, with a view to developing targeted preventions and interventions.
Molecular Scavengers, Oxidative Stress and Cardiovascular Disease
Authors: Di Minno Alessandro , Stornaiuolo Mariano , Novellino Ettore
Published: November 2019

Cardiovascular disease (CVD) is the number one cause of deaths worldwide, with yearly deaths due to atherothrombosis—i [...]
Impact of the Total Number of Carotid Plaques on the Outcome of Ischemic Stroke Patients with Atrial Fibrillation
Authors: Park Hyungjong , Han Minho , Kim Young Dae , Yoo Joonsang , Lee Hye Sun , Choi Jin Kyo , Heo Ji Hoe , Nam Hyo Suk
Published: November 2019

Background: Atrial fibrillation (AF) shares several risk factors with atherosclerosis. We investigated the association between total carotid plaque number (TPN) and long-term prognosis in ischemic stroke patients with AF. Methods: A total of 392 ischemic stroke patients with AF who underwent carotid ultrasonography were enrolled. TPN was assessed using B-mode ultrasound. The patients were categorized into two groups according to best cutoff values for TPN (TPN ≤ 4 vs. TPN ≥ 5). The long-term risk of major adverse cardiovascular events (MACE) and mortality according to TPN was investigated using a Cox hazard model. Results: After a mean follow-up of 2.42 years, 113 patients (28.8%) had developed MACE and 88 patients (22.4%) had died. MACE occurred more frequently in the TPN ≥ 5 group than in the TPN ≤ 4 group (adjusted hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.01–2.21; p < 0.05). Moreover, the TPN ≥ 5 group showed an increased risk of all-cause mortality (adjusted HR, 2.69; 95% CI, 1.40–5.17; p < 0.05). TPN along with maximal plaque thickness and intima media thickness showed improved prognostic utility when added to the variables of the CHAD2DS2-VASc score. Conclusion: TPN can predict the long-term outcome of ischemic stroke patients with AF. Adding TPN to the CHAD2DS2-VASc score increases the predictability of outcome after stroke.
Cross-Sectional and Longitudinal Associations between Peak Expiratory Flow and Frailty in Older Adults
Authors: Trevisan Caterina , Rizzuto Debora , Maggi Stefania , Sergi Giuseppe , Welmer Anna-Karin , Vetrano Davide Liborio
Published: November 2019

Peak expiratory flow (PEF) has been linked to several health-related outcomes in older people, but its association with frailty is still unclear. This study investigates the association between PEF and prevalent and incident frailty in older adults. Data come from 2559 community-dwelling participants (age ≥ 60 years) of the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K). Baseline PEF was expressed as standardized residual (SR) percentiles. Frailty was assessed at baseline and over six years, according to the Fried criteria. Associations between PEF and frailty were estimated cross-sectionally through logistic regressions, and longitudinally by multinomial logistic regression, considering death as alternative outcome. Obstructive respiratory diseases and smoking habits were treated as potential effect modifiers. Our cross-sectional results showed that the 10th–49th and <10th PEF SR percentile categories were associated with three- and five-fold higher likelihood of being frail than the 80th–100th category. Similar estimates were confirmed longitudinally, i.e., adjusted OR = 3.11 (95% CI: 1.61–6.01) for PEF SR percentiles < 10th, compared with 80th–100th percentiles. Associations were enounced in participants without physical deficits, and tended to be stronger among those with baseline obstructive respiratory diseases, and, longitudinally, also among former/current smokers. These findings suggest that PEF is a marker of general robustness in older adults, and its reduction exceeding that expected by age is associated with frailty development.
Early Post-Operative Intervention of Whole-Body Vibration in Patients After Total Knee Arthroplasty: A Pilot Study
Authors: Hsiao Yu-Hsuan , Chien Song-Hsiung , Tu Hung-Pin , Fu Jimmy Chun-Ming , Tsai Shih-Ting , Chen Ying-Shan , Chen Yi-Jen , Chen Chia-Hsin
Published: November 2019

(1) Background: Knee osteoarthritis causes pain, weakness, muscle atrophy, and disability. The application of whole-body vibration in patients with knee osteoarthritis can improve strength, balance, and functional activities. The purpose of the study is to evaluate the effects of early whole-body vibration intervention in patients after total knee arthroplasty. (2) Method: A single-blinded randomized control trial. Fifty-two patients with knee osteoarthritis post total knee replacement from a medical center in southern Taiwan were randomly assigned to either a whole-body vibration group or control group. Main outcome measures included pain severity, leg circumference, knee range of motion, knee extensor strength, a five-times sit to stand test, and a timed up and go test. (3) Results: Immediately post treatment, the patients in the vibration group showed a significant increase in knee extensor strength and improvement in calf swelling compared to the control group. A trend toward decrease in pain severity and improvement in functional performance were observed in both groups without a significant difference between the groups. There was no significant difference in knee range of motion (ROM) and functional performance between the groups. (4) Conclusions: The whole-body vibration intervention in patients early post total knee arthroplasty showed significant immediate effect in increasing knee extensor strength and decreasing calf swelling.
Expression of EEF1A1 Is Associated with Prognosis of Patients with Colon Adenocarcinoma
Authors: Joung Eun kyo , Kim Jiyoung , Yoon Nara , Maeng Lee-so , Kim Ji Hoon , Park Sungsoo , Kang Keunsoo , Kim Jeong Seon , Ahn Young-Ho , Ko Yoon Ho , Byun Jae Ho , Hong Ji Hyung
Published: November 2019

Background: The prognostic role of the translational factor, elongation factor-1 alpha 1 (EEF1A1), in colon cancer is unclear. Objectives: The present study aimed to investigate the expression of EEF1A in tissues obtained from patients with stage II and III colon cancer and analyze its association with patient prognosis. Methods: A total of 281 patients with colon cancer who underwent curative resection were analyzed according to EEF1A1 expression. Results: The five-year overall survival in the high-EEF1A1 group was 87.7%, whereas it was 65.6% in the low-EEF1A1 expression group (hazard ratio (HR) 2.47, 95% confidence interval (CI) 1.38–4.44, p = 0.002). The five-year disease-free survival of patients with high EEF1A1 expression was 82.5%, which was longer than the rate of 55.4% observed for patients with low EEF1A1 expression (HR 2.94, 95% CI 1.72–5.04, p < 0.001). Univariate Cox regression analysis indicated that age, preoperative carcinoembryonic antigen level, adjuvant treatment, total number of metastatic lymph nodes, and EEF1A1 expression level were significant prognostic factors for death. In multivariate analysis, expression of EEF1A1 was an independent prognostic factor associated with death (HR 3.01, 95% CI 1.636–5.543, p < 0.001). EEF1A1 expression was also an independent prognostic factor for disease-free survival in multivariate analysis (HR 2.54, 95% CI 1.459–4.434, p < 0.001). Conclusions: Our study demonstrated that high expression of EEF1A1 has a favorable prognostic effect on patients with colon adenocarcinoma.
Comment from the Editor on the Special Issue “Head and Neck Critical Illness: Basic and Clinical Research Implications”
Authors: Tomita Hiroyuki
Published: November 2019

While oncogenic mutations of head and neck squamous cell carcinomas (HNSCC) in head and neck malignancies are uncommon, analysis using next-generation sequencing (NGS) technologies is growing. Further, single-cell analysis is being developed to overcome cancer cell heterogeneity and improve the poor survival of patients. However, it is important for researchers to know how to use this information to improve patients’ survival.
Mortality Prediction of Septic Patients in the Emergency Department Based on Machine Learning
Authors: Perng Jau-Woei , Kao I-Hsi , Kung Chia-Te , Hung Shih-Chiang , Lai Yi-Horng , Su Chih-Min
Published: November 2019

In emergency departments, the most common cause of death associated with suspected infected patients is sepsis. In this study, deep learning algorithms were used to predict the mortality of suspected infected patients in a hospital emergency department. During January 2007 and December 2013, 42,220 patients considered in this study were admitted to the emergency department due to suspected infection. In the present study, a deep learning structure for mortality prediction of septic patients was developed and compared with several machine learning methods as well as two sepsis screening tools: the systemic inflammatory response syndrome (SIRS) and quick sepsis-related organ failure assessment (qSOFA). The mortality predictions were explored for septic patients who died within 72 h and 28 days. Results demonstrated that the accuracy rate of deep learning methods, especially Convolutional Neural Network plus SoftMax (87.01% in 72 h and 81.59% in 28 d), exceeds that of the other machine learning methods, SIRS, and qSOFA. We expect that deep learning can effectively assist medical staff in early identification of critical patients.
Predictive Validity of the qSOFA Score for Sepsis in Adults with Community-Onset Staphylococcal Infection in Thailand
Authors: Gupta Supaksh , Rudd Kristina E. , Tandhavanant Sarunporn , Suntornsut Pornpan , Chetchotisakd Ploenchan , Angus Derek C. , Peacock Sharon J. , Chantratita Narisara , West Timothy Eoin
Published: November 2019

The quick sequential organ failure assessment (qSOFA) score has had limited validation in lower resource settings and was developed using data from high-income countries. We sought to evaluate the predictive validity of the qSOFA score for sepsis within a low- and middle-income country (LMIC) population with culture-proven staphylococcal infection. This was a secondary analysis of a prospective multicenter cohort in Thailand with culture-positive infection due to Staphylococcus aureus or S. argenteus within 24 h of admission and positive (≥2/4) systemic inflammatory response syndrome (SIRS) criteria. Primary exposure was maximum qSOFA score within 48 h of culture collection and primary outcome was mortality at 28 days. Baseline risk of mortality was determined using a multivariable logistic regression model with age, gender, and co-morbidities significantly associated with the outcome. Predictive validity was assessed by discrimination of mortality using area under the receiver operating characteristic (AUROC) curve compared to a model using baseline risk factors alone. Of 253 patients (mean age 54 years (SD 16)) included in the analysis, 23 (9.1%) died by 28 days after enrollment. Of those who died, 0 (0%) had a qSOFA score of 0, 8 (35%) had a score of 1, and 15 (65%) had a score ≥2. The AUROC of qSOFA plus baseline risk was significantly greater than for the baseline risk model alone (AUROCqSOFA = 0.80 (95% CI, 0.70–0.89), AUROCbaseline = 0.62 (95% CI, 0.49–0.75); p < 0.001). Among adults admitted to four Thai hospitals with community-onset coagulase-positive staphylococcal infection and SIRS, the qSOFA score had good predictive validity for sepsis.
Efficacy and Feasibility of Salvage Re-Irradiation with CyberKnife for In-Field Neck Lymph Node Recurrence: A Retrospective Study
Authors: Kobayashi Daijiro , Sato Hiro , Saitoh Jun-ichi , Oike Takahiro , Nakajima Atsushi , Noda Shin-ei , Kato Shingo , Iwanaga Mototaro , Shimizu Tsuneo , Nakano Takashi
Published: November 2019

Neck lymph node (LN) recurrence in the irradiated field represents an important aspect of treatment failure after primary radiotherapy owing to the lack of a standard treatment. The aim of this study is to investigate the efficacy and safety of CyberKnife treatment for neck LN recurrence after radiotherapy. Between 2008 and 2016, 55 neck LN recurrences after radiotherapy in 16 patients were treated with CyberKnife. The median follow-up period was 17 months (range, 2–53 months). The median previous radiotherapy dose was 68 Gy (range, 50–70 Gy). The median marginal dose as equivalent dose delivered in 2-Gy fractions (α/β = 10) was 50 Gy (range, 40–58 Gy). The one-year local control (LC) and overall survival rates were 81% and 71%, respectively. The one-year LC was higher with a target volume ≤1.0 cm3 than that with a target volume >1.0 cm3 (p = 0.006). Fatal bleeding was observed in one patient who had large (91 cm3) and widespread tumor with invasion to the carotid artery before CyberKnife treatment. CyberKnife treatment for neck LN recurrence is safe and feasible in most cases. Indication for the treatment should be carefully considered for large and widespread tumors.
An Ex-Situ Immobilization Experiment with Zn, Pb, and Cu in Dredged Marine Sediments from Bohai Bay, China
Authors: Zhang Wensi , Wang Xiao , Liu Baolin
Published: November 2019

The remediation of dredged marine sediments contaminated by metals has drawn increasing attention globally. Immobilization was regarded as a promising method for reducing adverse impacts on marine ecosystems. In this study, kaolinite and limestone were used as amendments to immobilize Zn, Pb, and Cu in dredged marine sediments, which were collected from the coastal zone adjacent to Tianjin Port in Bohai Bay. The sequential extraction procedure was applied to identify the mobility of metals and, further, to evaluate the immobilization effect of the amendments. The physical–chemical properties of the sediments, such as the pH, electrical conductivity (EC), salinity, and total organic carbon (TOC), were also measured to better understand their influence on the three metals’ mobility. The results of the sequential extraction procedure indicated that the mobile fractions of the metals were converted into relatively stable fractions because of the two amendments. In addition, the EC, salinity, and TOC decreased moderately, while no obvious variations in the pH of the sediments were observed with the addition of kaolinite and limestone. It was confirmed that both kaolinite and limestone can effectively reduce the mobility and bioavailability of metals, particularly Zn, and limestone generally has a better immobilization effect, compared with kaolinite.
Simulation Techniques for Design and Control of a Waste Heat Recovery System in Marine Natural Gas Propulsion Applications
Authors: Altosole Marco , Campora Ugo , Donnarumma Silvia , Zaccone Raphael
Published: November 2019

Waste Heat Recovery (WHR) marine systems represent a valid solution for the ship energy efficiency improvement, especially in Liquefied Natural Gas (LNG) propulsion applications. Compared to traditional diesel fuel oil, a better thermal power can be recovered from the exhaust gas produced by a LNG-fueled engine. Therefore, steam surplus production may be used to feed a turbogenerator in order to increase the ship electric energy availability without additional fuel consumption. However, a correct design procedure of the WHR steam plant is fundamental for proper feasibility analysis, and from this point of view, numerical simulation techniques can be a very powerful tool. In this work, the WHR steam plant modeling is presented paying attention to the simulation approach developed for the steam turbine and its governor dynamics. Starting from a nonlinear system representing the whole dynamic behavior, the turbogenerator model is linearized to carry out a proper synthesis analysis of the controller, in order to comply with specific performance requirements of the power grid. For the considered case study, simulation results confirm the validity of the developed approach, aimed to test the correct design of the whole system in proper working dynamic conditions.
Offshore Wind Power Integration into Future Power Systems: Overview and Trends
Authors: Fernández-Guillamón Ana , Das Kaushik , Cutululis Nicolaos A. , Molina-García Ángel
Published: November 2019

Nowadays, wind is considered as a remarkable renewable energy source to be implemented in power systems. Most wind power plant experiences have been based on onshore installations, as they are considered as a mature technological solution by the electricity sector. However, future power scenarios and roadmaps promote offshore power plants as an alternative and additional power generation source, especially in some regions such as the North and Baltic seas. According to this framework, the present paper discusses and reviews trends and perspectives of offshore wind power plants for massive offshore wind power integration into future power systems. Different offshore trends, including turbine capacity, wind power plant capacity as well as water depth and distance from the shore, are discussed. In addition, electrical transmission high voltage alternating current (HVAC) and high voltage direct current (HVDC) solutions are described by considering the advantages and technical limitations of these alternatives. Several future advancements focused on increasing the offshore wind energy capacity currently under analysis are also included in the paper.
Tree Wind Breaks in Central Asia and Their Effects on Agricultural Water Consumption
Authors: Thevs Niels , Gombert Alina , Strenge Eva , Lleshi Roland , Aliev Kumar , Emileva Begaiym
Published: November 2019

Across Central Asia, agriculture largely depends on irrigation due to arid and semi-arid climatic conditions. Water is abstracted from rivers, which are largely fed by glacier melt. In the course of climate change, glaciers melt down so that a reduced glacier volume and reduced water runoffs are expected to be available for irrigation. Tree wind breaks are one option to reduce water consumption in irrigated agriculture and build resilience against climate change. This paper therefore assesses the water consumption of major crops in Kyrgyzstan and adjacent areas, i.e., cotton (Gossypium hirsutum L.), wheat (Triticum aestivum L.), corn (Zea mays L.), rice (Oryza sativa L.), potato (Solanum tuberosum L.), and barley (Hordeum vulgare L.) in combination with tree wind breaks. Crop water consumption was assessed through the Penman Monteith approach. Tree wind break types investigated were single rows from poplars (Populus spec.) and multiple rows with understory vegetation by elm (Ulmus minor L.) and poplar, respectively. Tree water consumption was determined through sapflow measurements. The seasonal reference evapotranspiration (ETo) for field crops was 876–995 mm without wind breaks and dropped to less than half through multiple row wind breaks with understory vegetation (50 m spacing). Tree water consumption was 1125–1558 mm for poplar and 435 mm for elm. Among the wind break crop systems, elm wind breaks resulted in the highest reductions of water consumption, followed by single row poplars, at spacing of 50 and 100 m, respectively. However, elm grows much slower than poplar, so poplars might be more attractive for farmers. Furthermore, single row wind breaks might by much easier to be integrated into the agrarian landscape as they consume less space.