bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Axial In-Situ Stress in Deep Tunnel Analysis Considering Strain Softening and Dilatancy
Authors: Yi Kang , Liu Zhenghe , Lu Zhiguo , Zhang Junwen , Dong Shuangyong
Published: March 2020

In many previous tunnel analyses, the axial in-situ stress was ignored. In this work, its effect on the deformation and failure of the surrounding rock of a deep tunnel was revealed, considering the objective strain softening and dilatancy behavior of the surrounding rock. Analysis based on the incremental plastic flow theory was conducted, and C++ was used to write a constitutive model for numerical simulation to verify and further analyze this effect. Then, the results were validated by the field monitoring data of a coal mine gateway. Results show that the effect of the axial in-situ stress σa0 is more significant when strain softening is considered, compared with the results of a perfectly elastoplastic model. When the axial stress σa is σ1 or σ3 at the initial yield, an increase or decrease in σa0 intensifies the deformation and failure of the surrounding rock. When σa is σ2 at the initial yield, 3D plastic flow partly controlled by σa may occur, and an increase in σa0 intensifies the deformation and failure of the surrounding rock. The effect of σa0 will be amplified by considering dilatancy. Considering both strain softening and dilatancy, when σa0 is close to the tangential in-situ stress σt0 or significantly greater than σt0 (1.5 times), σa will be σ2 or σ1 at the initial yield, and then 3D plastic flow will occur. In the deformation prediction and support design of a deep tunnel, σa0 should not be ignored, and the strain softening and dilatancy behavior of the surrounding rock should be accurately considered.
Camelina and Crambe Oil Crops for Bioeconomy—Straw Utilisation for Energy
Authors: Krzyżaniak Michał , Stolarski Mariusz J. , Graban Łukasz , Lajszner Waldemar , Kuriata Tomasz
Published: March 2020

Agriculture can provide biomass for bioproducts, biofuels and as energy feedstock with a low environmental impact, derived from carbohydrate, protein and oil annual crops, as well from lignocellulosic crops. This paper presents the thermophysical and chemical features of camelina and crambe straw depending on nitrogen fertilisation rate with a view to their further use in a circular bioeconomy. A two-factorial field experiment was set up in 2016, with camelina and crambe as the first factor and the N fertilizer rate (0, 60 and 120 kg·ha−1·N) as the second factor. Ash content in crambe straw (6.97% d.m.) was significantly higher than in camelina straw (4.79% d.m.). The higher heating value was higher for the camelina (18.50 MJ·kg−1·d.m.) than for the crambe straw (17.94 MJ·kg−1·d.m.). Sulphur content was also significantly higher in camelina than in crambe straw. An increase in nitrogen content with increasing fertilisation rate was visible in the straw of both species (from 1.19 to 1.33% d.m., for no fertilisation and for a rate of 120 kg·ha−1·N, respectively). Crambe straw contained more than five times more chlorine than camelina straw. In conclusion, despite certain adverse properties, camelina and crambe straw can be an alternative to other types of biomass, both for direct combustion, gasification and in the production of second-generation biofuels.
Short Legacy Effects of Growing Season Nitrogen Addition and Reduced Precipitation alter Soil Respiration during Nongrowing Season
Authors: Yan Guoyong , Xing Yajuan , Wang Qinggui , Mu Changcheng
Published: March 2020

The short legacy effects of growing season nitrogen (N) addition and reduced precipitation on nongrowing season soil respiration (Rs), autotrophic respiration (Ra), and heterotrophic respiration (Rh) are still unclear. Therefore, a field manipulative experiment to determine the responses of nongrowing season Rs and its components to growing season N addition and reduced precipitation was conducted in a temperate forest. The results show that growing season N addition and reduced precipitation significantly increased nongrowing season Rs by regulating the response of Ra and Rh. The combination of N addition and reduced precipitation also showed a much stronger effect on Rs and its components, but the magnitude and direction largely depended on the snowpack thickness. The effects of growing season N addition and reduced precipitation on nongrowing season Rs and its components were mediated by different sampling periods. N addition significantly decreased Rs by decreasing Rh in early winter and significantly increased Rs by increasing Ra in deep winter and late winter. All treatments decreased temperature sensitivity (Q10) of Rs and Rh. Our findings contribute to a better understanding of how nongrowing season Rs and its components will change under growing season N addition and reduced precipitation and could improve predictions of the future states of the soil C cycle in response to climate change.
Ectopic Expression of AhGLK1b (GOLDEN2-like Transcription Factor) in Arabidopsis Confers Dual Resistance to Fungal and Bacterial Pathogens
Authors: Ali Niaz , Chen Hua , Zhang Chong , Khan Shahid Ali , Gandeka Mamadou , Xie Dongyang , Zhuang Weijian
Published: March 2020

GOLDEN2-LIKE (GLK) is a member of the myeloblastosis (MYB) family transcription factor and it plays an important role in the regulation of plastid development and stress tolerance. In this study, a gene named AhGLK1b was identified from a cultivated peanut showing down-regulation in response to low calcium with a complete open reading frame (ORF) of 1212 bp. The AhGLK1b has 99.26% and 96.28% sequence similarities with its orthologs in Arachis ipaensis and A. duranensis, respectively. In the peanut, the AhGLK1b was localized in the nucleus and demonstrated the highest expression in the leaf, followed by the embryo. Furthermore, the expression of AhGLK1b was induced significantly in response to a bacterial pathogen, Ralstonia solanacearum infection. Ectopic expression of AhGLK1b in Arabidopsis showed stronger resistance against important phytopathogenic fungi S. sclerotiorum. It also exhibited high resistance to infection of the bacterial pathogen Pst DC3000. AhGLK1b-expressing Arabidopsis induced defense-related genes including PR10 and Phox/Bem 1 (PBI), which are involved in multiple disease resistance. Taken together, the results suggest that AhGLK1b might be useful in providing dual resistance to fungal and bacterial pathogens as well as tolerance to abiotic stresses.
Estimation of Avalanche Development and Frontal Velocities Based on the Spectrogram of the Seismic Signals Generated at the Vallée de la Sionne Test Site
Authors: Suriñach Emma , Flores-Márquez Elsa Leticia , Roig-Lafon Pere , Furdada Glòria , Tapia Mar
Published: March 2020

The changes in the seismic signals generated by avalanches recorded at three sites along a path at the Vallée de la Sionne (VdlS) experimental site are presented. We discuss and correlate the differences in the duration, signal amplitudes, and frequency content of the sections (Signal ONset (ON), Signal Body (SBO), and Signal TAil and Signal ENd STA-SEN) of the spectrograms with the evolution of the powder, transitional and wet snow avalanches along a path. The development of the avalanche front was quantified using the exponential function in time F (t) = K’ exp (β t) fitted to the shape of the signal ONset (SON section of the spectrogram. The speed of the avalanche front is contained in β. To this end, a new method was developed. The three seismic components were converted into one seismic component (FS), when expressing the vector in polar coordinates. We linked the theoretical function of the shape of the FS-SON section of the spectrogram to the numerical coefficients of its shape after considering the spectrogram as an image. This allowed us to obtain the coefficients K’ and β. For this purpose, the Hough Transform (HT) was applied to the image. The values of the resulting coefficients K’ and β are included in different ranges in accordance with the three types of avalanche. Curves created with these coefficients enable us to estimate the development of the different avalanche types along the path. Our results show the feasibility of classifying the type of avalanche through these coefficients. Average speeds of the avalanches approaching the recording sites were estimated. The speed values of wet and transitional avalanches are consistent with those derived from GEODAR (GEOphysical Doppler radAR) measurements, when available. The absence of agreement in the speed values obtained from seismic signals and GEODAR measurements for powder snow avalanches indicates, for this type of avalanche, a different source of the measured signal. Hence, the use of the two measuring systems proves to be complementary.
Effects of Earthquakes on Flood Hazards: A Case Study From Christchurch, New Zealand
Authors: Quigley Mark , Duffy Brendan
Published: March 2020

Earthquakes can influence flood hazards by altering the flux, volumes, and distributions of surface and/or subsurface waters and causing physical changes to natural and engineered environments (e.g., elevation, topographic relief, permeability) that affect surface and subsurface hydrologic regimes. This paper analyzes how earthquakes increased flood hazards in Christchurch, New Zealand, using empirical observations and seismological data. Between 4 September 2010 and 4 December 2017, this region hosted one moment magnitude (Mw) 7.1 earthquake, 3 earthquakes with Mw ≥ 6, and 31 earthquakes with local magnitude (ML) ≥ 5. Flooding related to liquefaction-induced groundwater pore-water fluid pressure perturbations and groundwater expulsion occurred in at least six earthquakes. Flooding related to shaking-induced ground deformations (e.g., subsidence) occurred in at least four earthquakes. Flooding related to tectonic deformations of the land surface (fault surface rupture and/or folding) occurred in at least two earthquakes. At least eight earthquakes caused damage to surface (e.g., buildings, bridges, roads) and subsurface (e.g., pipelines) infrastructure in areas of liquefaction and/or flooding. Severe liquefaction and associated groundwater-expulsion flooding in vulnerable sediments occurred at peak ground accelerations as low as 0.15 to 0.18 g (proportion of gravity). Expected return times of liquefaction-induced flooding in vulnerable sediments were estimated to be 100 to 500 years using the Christchurch seismic hazard curve, which is consistent with emerging evidence from paleo-liquefaction studies. Liquefaction-induced subsidence of 100 to 250 mm was estimated for 100-year peak ground acceleration return periods in parts of Christchurch.
COVID-19 Outbreak: An Overview on Dentistry
Authors: Spagnuolo Gianrico , De Vito Danila , Rengo Sandro , Tatullo Marco
Published: March 2020

Coronavirus disease 2019, also called COVID-19, is the latest infectious disease to rapidly develop worldwide [...]
Surface-Specific Caries Preventive Effect of an Intervention Comprising Fissure Sealant, Povidone-Iodine and Fluoride Varnish in a Remote Indigenous Community in Australia
Authors: Tadakamadla Santosh K. , Lalloo Ratilal , Kroon Jeroen , Johnson Newell W.
Published: March 2020

This study evaluates the effect of a topical intervention comprising of fissure sealant, povidone-iodine, and fluoride varnish in preventing caries on occlusal, approximal, and smooth surfaces. This three-year clinical trial was conducted in a remote Indigenous community of Australia. All schoolchildren (age range: 4–17) were invited to participate; those with parental consents to receive three-annual epidemiological examinations and interventions constituted the experimental group, while those with consents for only the epidemiological examination formed a comparison group. The intervention group received an annual application of fissure sealant, povidone–iodine and fluoride varnish for two consecutive years along with the restoration of any cavitated lesions, while the comparison group did not receive any intervention except for the usual care that included emergency treatment and restorations. Incipient and advanced caries were recorded in the permanent dentition while data on confounding variables were collected through questionnaires. Caries increment and progression were the outcome variables. A total of 408 children participated in the baseline examination, 208 finished the study. After adjusting for confounders, the prevented fraction (PF) on occlusal surfaces for advanced caries in the experimental group was 76.1% (mean difference- −0.35, 95% CI: −0.67–0.04), while the PF for progression from incipient to advanced caries was 100%(mean difference- −0.30, 95% CI: −0.52–0.09). The mean number of smooth surfaces that progressed from incipient to advanced caries in the comparison group was more than twice that of the experimental group, the mean difference was −0.25 (95% CI: −0.46–−0.03) with a PF of 61%. The intervention was only effective in preventing advanced caries on occlusal surfaces and in halting the progression of caries on occlusal and smooth surfaces but not on approximal caries.
The Potential Role of Migratory Birds in the Rapid Spread of Ticks and Tick-Borne Pathogens in the Changing Climatic and Environmental Conditions in Europe
Authors: Buczek Alicja M. , Buczek Weronika , Buczek Alicja , Bartosik Katarzyna
Published: March 2020

This opinion piece highlights the role of migratory birds in the spread of ticks and their role in the circulation and dissemination of pathogens in Europe. Birds with different lifestyles, i.e., non-migrants residing in a specific area, or short-, medium-, and long-distance migrants, migrating within one or several distant geographical regions are carriers of a number of ticks and tick-borne pathogens. During seasonal migrations, birds that cover long distances over a short time and stay temporarily in different habitats can introduce tick and pathogen species in areas where they have never occurred. An increase in the geographical range of ticks as well as the global climate changes affecting the pathogens, vectors, and their hosts increase the incidence and the spread of emerging tick-borne diseases worldwide. Tick infestations of birds varied between regions depends on the rhythms of tick seasonal activity and the bird migration rhythms determined by for example, climatic and environmental factors. In areas north of latitude ca. 58°N, immature Ixodes ricinus ticks are collected from birds most frequently, whereas ticks from the Hyalomma marginatum group dominate in areas below 42°N. We concluded that the prognosis of hazards posed by tick-borne pathogens should take into account changes in the migration of birds, hosts of many epidemiologically important tick species.
Adequacy of Parenteral Nutrition in Preterm Infants According to Current Recommendations: A Study in A Spanish Hospital
Authors: Sánchez-García Ana María , Zaragoza-Martí Ana , Murcia-López Ana Cristina , Navarro-Ruiz Andrés , Noreña-Peña Ana
Published: March 2020

Background: In preterm infants, it is important to ensure adequate nutritional intake to accomplish foetal growth requirements. This study evaluated clinical practice regarding the prescription of parenteral nutrition in preterm infants in the neonatology unit of a tertiary hospital. Methods: It was a retrospective observational study of a sample of preterm infants (n = 155) born between January 2015 and December 2017 who were prescribed parenteral nutrition. Compliance with the hospital’s protocol and with the guidelines of the scientific societies American Society for Parenteral and Enteral Nutrition (ASPEN), European Society for Clinical Nutrition and Metabolism (ESPEN) and Spanish Society of Clinical Nutrition and Metabolism (SENPE) was evaluated. The differences in macronutrient intake and total duration of parenteral nutrition were analysed according to gestational age and birth weight. Results: The established protocol was followed in a high percentage (95.5%–100%) except with respect to the initiation of supplying established trace elements (64.9%). Compliance with the recommendations set forth in the guidelines was between 82.1% and 100%, with the exception of the initial carbohydrate intake recommended by ASPEN and ESPEN, for which compliance was 8.3%. Lower gestational age and birth weight were correlated with longer duration of parenteral nutrition (p < 0.001). Conclusions: A lower gestational age and birth weight are related to a longer duration of parenteral nutrition. The results of this study demonstrate the importance of developing and evaluating protocols in clinical practice.
“Unworthy of Care and Treatment”: Cultural Devaluation and Structural Constraints to Healthcare-Seeking for Older People in Rural China
Authors: Zou Xiang , Fitzgerald Ruth , Nie Jing-Bao
Published: March 2020

This paper examines the experiences of seeking healthcare for rural Chinese older people, a population who experiences the multiple threats of socio-economic deprivation, marginalization, and lack of access to medical care, yet have been relatively overlooked within the existing scholarly literature. Based on ethnographical data collected from six-month fieldwork conducted in a rural primary hospital in Southern China, this paper identifies a widespread discouraging, dispiriting attitude regarding healthcare-seeking for rural older members despite the ongoing efforts of institutional reforms with a particular focus on addressing access to health services amongst rural populations. Such an attitude was expressed by older people’s families as well as the public in their narratives by devaluing older members’ health care demands as “unworthy of care and treatment” (“buzhide zhi” in Chinese). It was also internalized by older people, based on which they deployed a family-oriented health-seeking model and strategically downgraded their expectation on receiving medical care. Moreover, underpinning this discouragement and devaluation, as well as making them culturally legitimate, is the social expectation of rural older people to be enduring and restrained with health-seeking. Simultaneously, this paper highlights the sourc2e of institutional and structural impediments, as they intersect with unfavorable socio-cultural values that normalize discouragement and devaluation.
The Lack of Evidence for an Association between Cancer Biomarker Conversion Patterns and CTC-Status in Patients with Metastatic Breast Cancer
Authors: Stefanovic Stefan , Deutsch Thomas M. , Riethdorf Sabine , Fischer Chiara , Hartkopf Andreas , Sinn Peter , Feisst Manuel , Pantel Klaus , Golatta Michael , Brucker Sara Y. , Sütterlin Marc , Schneeweiss Andreas , Wallwiener Markus
Published: March 2020

Circulating tumor cell (CTC) detection is a prognostic factor in the metastatic breast cancer (MBC) setting. Discrepancies in primary (PT) and metastatic tumor (MT) genetic profiles are also of prognostic importance. Our study aimed to compare the CTC statuses and prognoses between those with subtype stable MBCs and MBCs with specific biomarker conversions. The study enrolled 261 MBC patients, treated at the National Center for Tumor Diseases, Heidelberg, Germany in a five-year period. All underwent PT and MT biopsies and subsequent CTC enumeration before the initiation of systemic therapy. ER and HER2 statuses of the PTs and MTs were determined and progression free survivals (PFSs) and overall survivals (OSs) were recorded. We compared CTC statuses, CTC counts, PFSs and OSs between subgroups of patients with different receptor change patterns. Patients who had tumors that converted to triple negative MTs had the shortest median OSs, while HER2 expression was not associated with a shorter median OS. No significant differences in PFSs and OSs have been demonstrated by Kaplan-Meier curve comparisons in any of the subgroup analyses. CTC counts were similar in all subgroups. CTCs were comparably less frequently detected in patients with a stable HER2 expression. Similar proportions of CTC positives were observed in all other subtype change pattern subgroups, barring the aforementioned HER2 stable subgroup. The detection of CTCs was of no appreciable prognostic value in different receptor change pattern subgroups in our cohort.
Bulked Segregant Analysis Coupled with Whole-Genome Sequencing (BSA-Seq) Mapping Identifies a Novel pi21 Haplotype Conferring Basal Resistance to Rice Blast Disease
Authors: Liang Tingmin , Chi Wenchao , Huang Likun , Qu Mengyu , Zhang Shubiao , Chen Zi-Qiang , Chen Zai-Jie , Tian Dagang , Gui Yijie , Chen Xiaofeng , Wang Zonghua , Tang Weiqi , Chen Songbiao
Published: March 2020

Basal or partial resistance has been considered race-non-specific and broad-spectrum. Therefore, the identification of genes or quantitative trait loci (QTLs) conferring basal resistance and germplasm containing them is of significance in breeding crops with durable resistance. In this study, we performed a bulked segregant analysis coupled with whole-genome sequencing (BSA-seq) to identify QTLs controlling basal resistance to blast disease in an F2 population derived from two rice varieties, 02428 and LiXinGeng (LXG), which differ significantly in basal resistance to rice blast. Four candidate QTLs, qBBR-4, qBBR-7, qBBR-8, and qBBR-11, were mapped on chromosomes 4, 7, 8, and 11, respectively. Allelic and genotypic association analyses identified a novel haplotype of the durable blast resistance gene pi21 carrying double deletions of 30 bp and 33 bp in 02428 (pi21-2428) as a candidate gene of qBBR-4. We further assessed haplotypes of Pi21 in 325 rice accessions, and identified 11 haplotypes among the accessions, of which eight were novel types. While the resistant pi21 gene was found only in japonica before, three Chinese indica varieties, ShuHui881, Yong4, and ZhengDa4Hao, were detected carrying the resistant pi21-2428 allele. The pi21-2428 allele and pi21-2428-containing rice germplasm, thus, provide valuable resources for breeding rice varieties, especially indica rice varieties, with durable resistance to blast disease. Our results also lay the foundation for further identification and functional characterization of the other three QTLs to better understand the molecular mechanisms underlying rice basal resistance to blast disease.
Thymosin β4-Enhancing Therapeutic Efficacy of Human Adipose-Derived Stem Cells in Mouse Ischemic Hindlimb Model
Authors: Kim Jong-Ho , Lim I-Rang , Park Chi-Yeon , Joo Hyung Joon , Noh Ji-Min , Choi Seung-Cheol , Hong Soon Jun , Lim Do-Sun
Published: March 2020

Thymosin β4 (Tβ4) is a G-actin sequestering protein that contributes to diverse cellular activities, such as migration and angiogenesis. In this study, the beneficial effects of combined cell therapy with Tβ4 and human adipose-derived stem cells (hASCs) in a mouse ischemic hindlimb model were investigated. We observed that exogenous treatment with Tβ4 enhanced endogenous TMSB4X mRNA expression and promoted morphological changes (increased cell length) in hASCs. Interestingly, Tβ4 induced the active state of hASCs by up-regulating intracellular signaling pathways including the PI3K/AKT/mTOR and MAPK/ERK pathways. Treatment with Tβ4 significantly increased cell migration and sprouting from microbeads. Moreover, additional treatment with Tβ4 promoted the endothelial differentiation potential of hASCs by up-regulating various angiogenic genes. To evaluate the in vivo effects of the Tβ4-hASCs combination on vessel recruitment, dorsal window chambers were transplanted, and the co-treated mice were found to have a significantly increased number of microvessel branches. Transplantation of hASCs in combination with Tβ4 was found to improve blood flow and attenuate limb or foot loss post-ischemia compared to transplantation with hASCs alone. Taken together, the therapeutic application of hASCs combined with Tβ4 could be effective in enhancing endothelial differentiation and vascularization for treating hindlimb ischemia.
Biofabrication of SDF-1 Functionalized 3D-Printed Cell-Free Scaffolds for Bone Tissue Regeneration
Authors: Lauer Alina , Wolf Philipp , Mehler Dorothea , Götz Hermann , Rüzgar Mehmet , Baranowski Andreas , Henrich Dirk , Rommens Pol Maria , Ritz Ulrike
Published: March 2020

Large segmental bone defects occurring after trauma, bone tumors, infections or revision surgeries are a challenge for surgeons. The aim of our study was to develop a new biomaterial utilizing simple and cheap 3D-printing techniques. A porous polylactide (PLA) cylinder was printed and functionalized with stromal-derived factor 1 (SDF-1) or bone morphogenetic protein 7 (BMP-7) immobilized in collagen type I. Biomechanical testing proved biomechanical stability and the scaffolds were implanted into a 6 mm critical size defect in rat femur. Bone growth was observed via x-ray and after 8 weeks, bone regeneration was analyzed with µCT and histological staining methods. Development of non-unions was detected in the control group with no implant. Implantation of PLA cylinder alone resulted in a slight but not significant osteoconductive effect, which was more pronounced in the group where the PLA cylinder was loaded with collagen type I. Addition of SDF-1 resulted in an osteoinductive effect, with stronger new bone formation. BMP-7 treatment showed the most distinct effect on bone regeneration. However, histological analyses revealed that newly formed bone in the BMP-7 group displayed a holey structure. Our results confirm the osteoinductive character of this 3D-biofabricated cell-free new biomaterial and raise new options for its application in bone tissue regeneration.
Expression Analyses of Soybean VOZ Transcription Factors and the Role of GmVOZ1G in Drought and Salt Stress Tolerance
Authors: Li Bo , Zheng Jia-Cheng , Wang Ting-Ting , Min Dong-Hong , Wei Wen-Liang , Chen Jun , Zhou Yong-Bin , Chen Ming , Xu Zhao-Shi , Ma You-Zhi
Published: March 2020

Vascular plant one-zinc-finger (VOZ) transcription factor, a plant specific one-zinc-finger-type transcriptional activator, is involved in regulating numerous biological processes such as floral induction and development, defense against pathogens, and response to multiple types of abiotic stress. Six VOZ transcription factor-encoding genes (GmVOZs) have been reported to exist in the soybean (Glycine max) genome. In spite of this, little information is currently available regarding GmVOZs. In this study, GmVOZs were cloned and characterized. GmVOZ genes encode proteins possessing transcriptional activation activity in yeast cells. GmVOZ1E, GmVOZ2B, and GmVOZ2D gene products were widely dispersed in the cytosol, while GmVOZ1G was primarily located in the nucleus. GmVOZs displayed a differential expression profile under dehydration, salt, and salicylic acid (SA) stress conditions. Among them, GmVOZ1G showed a significantly induced expression in response to all stress treatments. Overexpression of GmVOZ1G in soybean hairy roots resulted in a greater tolerance to drought and salt stress. In contrast, RNA interference (RNAi) soybean hairy roots suppressing GmVOZ1G were more sensitive to both of these stresses. Under drought treatment, soybean composite plants with an overexpression of hairy roots had higher relative water content (RWC). In response to drought and salt stress, lower malondialdehyde (MDA) accumulation and higher peroxidase (POD) and superoxide dismutase (SOD) activities were observed in soybean composite seedlings with an overexpression of hairy roots. The opposite results for each physiological parameter were obtained in RNAi lines. In conclusion, GmVOZ1G positively regulates drought and salt stress tolerance in soybean hairy roots. Our results will be valuable for the functional characterization of soybean VOZ transcription factors under abiotic stress.
XPA: DNA Repair Protein of Significant Clinical Importance
Authors: Borszéková Pulzová Lucia , Ward Thomas A. , Chovanec Miroslav
Published: March 2020

The nucleotide excision repair (NER) pathway is activated in response to a broad spectrum of DNA lesions, including bulky lesions induced by platinum-based chemotherapeutic agents. Expression levels of NER factors and resistance to chemotherapy has been examined with some suggestion that NER plays a role in tumour resistance; however, there is a great degree of variability in these studies. Nevertheless, recent clinical studies have suggested Xeroderma Pigmentosum group A (XPA) protein, a key regulator of the NER pathway that is essential for the repair of DNA damage induced by platinum-based chemotherapeutics, as a potential prognostic and predictive biomarker for response to treatment. XPA functions in damage verification step in NER, as well as a molecular scaffold to assemble other NER core factors around the DNA damage site, mediated by protein–protein interactions. In this review, we focus on the interacting partners and mechanisms of regulation of the XPA protein. We summarize clinical oncology data related to this DNA repair factor, particularly its relationship with treatment outcome, and examine the potential of XPA as a target for small molecule inhibitors.
Functional Divergence of Microtubule-Associated TPX2 Family Members in Arabidopsis thaliana
Authors: Dvořák Tomaštíková Eva , Rutten Twan , Dvořák Petr , Tugai Alisa , Ptošková Klara , Petrovská Beáta , van Damme Daniel , Houben Andreas , Doležel Jaroslav , Demidov Dmitri
Published: March 2020

TPX2 (Targeting Protein for Xklp2) is an evolutionary conserved microtubule-associated protein important for microtubule nucleation and mitotic spindle assembly. The protein was described as an activator of the mitotic kinase Aurora A in humans and the Arabidopsis AURORA1 (AUR1) kinase. In contrast to animal genomes that encode only one TPX2 gene, higher plant genomes encode a family with several TPX2-LIKE gene members (TPXL). TPXL genes of Arabidopsis can be divided into two groups. Group A proteins (TPXL2, 3, 4, and 8) contain Aurora binding and TPX2_importin domains, while group B proteins (TPXL1, 5, 6, and 7) harbor an Xklp2 domain. Canonical TPX2 contains all the above-mentioned domains. We confirmed using in vitro kinase assays that the group A proteins contain a functional Aurora kinase binding domain. Transient expression of Arabidopsis TPX2-like proteins in Nicotiana benthamiana revealed preferential localization to microtubules and nuclei. Co-expression of AUR1 together with TPX2-like proteins changed the localization of AUR1, indicating that these proteins serve as targeting factors for Aurora kinases. Taken together, we visualize the various localizations of the TPX2-LIKE family in Arabidopsis as a proxy to their functional divergence and provide evidence of their role in the targeted regulation of AUR1 kinase activity.
Attenuation of Pseudomonas aeruginosa Quorum Sensing by Natural Products: Virtual Screening, Evaluation and Biomolecular Interactions
Authors: Zhong Lin , Ravichandran Vinothkannan , Zhang Na , Wang Hailong , Bian Xiaoying , Zhang Youming , Li Aiying
Published: March 2020

Natural products play vital roles against infectious diseases since ancient times and most drugs in use today are derived from natural sources. Worldwide, multi-drug resistance becomes a massive threat to the society with increasing mortality. Hence, it is very crucial to identify alternate strategies to control these ‘super bugs’. Pseudomonas aeruginosa is an opportunistic pathogen reported to be resistant to a large number of critically important antibiotics. Quorum sensing (QS) is a cell–cell communication mechanism, regulates the biofilm formation and virulence factors that endow pathogenesis in various bacteria including P. aeruginosa. In this study, we identified and evaluated quorum sensing inhibitors (QSIs) from plant-based natural products against P. aeruginosa. In silico studies revealed that catechin-7-xyloside (C7X), sappanol and butein were capable of interacting with LasR, a LuxR-type quorum sensing regulator of P. aeruginosa. In vitro assays suggested that these QSIs significantly reduced the biofilm formation, pyocyanin, elastase, and rhamnolipid without influencing the growth. Especially, butein reduced the biofilm formation up to 72.45% at 100 µM concentration while C7X and sappanol inhibited the biofilm up to 66% and 54.26% respectively. Microscale thermophoresis analysis revealed that C7X had potential interaction with LasR (KD = 933±369 nM) and thermal shift assay further confirmed the biomolecular interactions. These results suggested that QSIs are able to substantially obstruct the P. aeruginosa QS. Since LuxR-type transcriptional regulator homologues are present in numerous bacterial species, these QSIs may be developed as broad spectrum anti-infectives in the future.
Pyoverdine-Mediated Killing of Caenorhabditis elegans by Pseudomonas syringae MB03 and the Role of Iron in Its Pathogenicity
Authors: Bashir Anum , Tian Tian , Yu Xun , Meng Cui , Ali Muhammad , Li Lin
Published: March 2020

The pathogenicity of the common phytopathogenic bacterium Pseudomonas syringae toward Caenorhabditis elegans has been recently demonstrated. However, the major virulence factors involved in this interaction remain unknown. In this study, we investigated the nematocidal activity of P. syringae against C. elegans under iron-sufficient/limited conditions, primarily focusing on the role of the ferric chelator pyoverdine in a P. syringae–C. elegans liquid-based pathogenicity model. Prediction-based analysis of pyoverdine-encoding genes in the genome of the wild-type P. syringae strain MB03 revealed that the genes are located in one large cluster. Two non-ribosomal peptide synthetase genes (pvdD and pvdJ) were disrupted via a Rec/TE recombination system, resulting in mutant strains with abrogated pyoverdine production and attenuated virulence against C. elegans. When used alone, pure pyoverdine also showed nematocidal activity. The role of iron used alone or with pyoverdine was further investigated in mutant and MB03-based bioassays. The results indicated that pyoverdine in P. syringae MB03 is a robust virulence factor that promotes the killing of C. elegans. We speculate that pyoverdine functions as a virulence determinant by capturing environmentally available iron for host bacterial cells, by limiting its availability for C. elegans worms, and by regulating and/or activating other intracellular virulence factors that ultimately kills C. elegans worms.
The Role of Extended CFTR Gene Sequencing in Newborn Screening for Cystic Fibrosis
Authors: Bergougnoux Anne , Lopez Maureen , Girodon Emmanuelle
Published: March 2020

There has been considerable progress in the implementation of newborn screening (NBS) programs for cystic fibrosis (CF), with DNA analysis being part of an increasing number of strategies. Thanks to advances in genomic sequencing technologies, CFTR-extended genetic analysis (EGA) by sequencing its coding regions has become affordable and has already been included as part of a limited number of core NBS programs, to the benefit of admixed populations. Based on results analysis of existing programs, the values and challenges of EGA are reviewed in the perspective of its implementation on a larger scale. Sensitivity would be increased at best by using EGA as a second tier, but this could be at the expense of positive predictive value, which improves, however, if EGA is applied after testing a variant panel. The increased detection of babies with an inconclusive diagnosis has proved to be a major drawback in programs using EGA. The lack of knowledge on pathogenicity and penetrance associated with numerous variants hinders the introduction of EGA as a second tier, but EGA with filtering for all known CF variants with full penetrance could be a solution. The issue of incomplete knowledge is a real challenge in terms of the implemention of NBS extended to many genetic diseases.
Analysis on the Relationship between Eating Behavior, Physical Activities and Youth Obesity: Based on the Korea Youth Risk Behavior Survey for High School Students in 2016~2018
Authors: Lee Seung-Hoo , Lee Jong-Ho
Published: March 2020

In this study, a total of 94,511 surveys were used for the analysis, using raw data from the recent 3 years (2016–2018) of the Korea Youth Risk Behavior Survey (KYRBS) to compare differences in obesity rates based on eating behavior and physical activity among high school students. The cross-analysis and logistic regression were performed in the composite sample design using the SPSS 25.0 statistical package. The results are as follows. First, the more physical activity male students have, the lower the obesity rate. Female students, however, showed a minor difference. Second, the group that drinks the soda was 1158 times more likely to be obese than the group that does not drink the soda, and third, the group that eats the fast food was 1129 times more likely to be obese than the group that does not. Fourth, students belonging to male or female schools had a 1230 times higher obesity rate than coeducational students. Fifth, the obesity rate was 1150 times higher for second grade and 1263 times higher for third grade compared to the first grade. Finally, there was no significant difference related to the nutrition education. It is suggested that, to fight youth obesity in high school students, institutions need to raise public awareness of this problem through information campaigns aimed at improving and fostering potentially existing educational measures.
Technology for Our Future? Exploring the Duty to Report and Processes of Subjectification Relating to Digitalized Suicide Prevention
Authors: Broer Tineke
Published: March 2020

Digital and networking technologies are increasingly used to predict who is at risk of attempting suicide. Such digitalized suicide prevention within and beyond mental health care raises ethical, social and legal issues for a range of actors involved. Here, I will draw on key literature to explore what issues (might) arise in relation to digitalized suicide prevention practices. I will start by reviewing some of the initiatives that are already implemented, and address some of the issues associated with these and with potential future initiatives. Rather than addressing the breadth of issues, however, I will then zoom in on two key issues: first, the duty of care and the duty to report, and how these two legal and professional standards may change within and through digitalized suicide prevention; and secondly a more philosophical exploration of how digitalized suicide prevention may alter human subjectivity. To end with the by now famous adagio, digitalized suicide prevention is neither good nor bad, nor is it neutral, and I will argue that we need sustained academic and social conversation about who can and should be involved in digitalized suicide prevention practices and, indeed, in what ways it can and should (not) happen.
Customer Loyalty Improves the Effectiveness of Recommender Systems Based on Complex Network
Authors: Bai Yun , Jia Suling , Wang Shuangzhe , Tan Binkai
Published: March 2020

Inferring customers’ preferences and recommending suitable products is a challenging task for companies, although recommender systems are constantly evolving. Loyalty is an indicator that measures the preference relationship between customers and products in the field of marketing. To this end, the aim of this study is to explore whether customer loyalty can improve the accuracy of the recommender system. Two algorithms based on complex networks are proposed: a recommendation algorithm based on bipartite graph and PersonalRank (BGPR), and a recommendation algorithm based on single vertex set network and DeepWalk (SVDW). In both algorithms, loyalty is taken as an attribute of the customer, and the relationship between customers and products is abstracted into the network topology. During the random walk among nodes in the network, product recommendations for customers are completed. Taking a real estate group in Malaysia as an example, the experimental results verify that customer loyalty can indeed improve the accuracy of the recommender system. We can also conclude that companies are more effective at recommending customers with moderate loyalty levels.
Evaluation of Proinflammatory, NF-kappaB Dependent Cytokines: IL-1α, IL-6, IL-8, and TNF-α in Tissue Specimens and Saliva of Patients with Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders
Authors: Babiuch Karolina , Kuśnierz-Cabala Beata , Kęsek Barbara , Okoń Krzysztof , Darczuk Dagmara , Chomyszyn-Gajewska Maria
Published: March 2020

Background: Oral squamous cell carcinoma (OSCC) is a life-threatening disease. It could be preceded by oral potentially malignant disorders (OPMDs). It was confirmed that chronic inflammation can promote carcinogenesis. Cytokines play a crucial role in this process. The aim of the study was to evaluate interleukin-1alpha (IL-1α), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α) in tissue specimens and saliva of patients with OSCC and OPMDs. Methods: Cytokines were evaluated in 60 tissue specimens of pathological lesions (OSCCs or OPMDs) and in 7 controls (normal oral mucosa, NOM) by immunohistochemistry and in saliva of 45 patients with OSCC or OPMDs and 9 controls (healthy volunteers) by enzyme-linked immunosorbent assays. Results: Immunohistochemical analysis revealed significantly higher expression of IL-8 in OSCC specimens and TNF-α in OSCCs and OPMDs with dysplasia as compared to NOM. Moreover, expression of TNF-α was significantly higher in oral leukoplakia and oral lichen planus without dysplasia, whereas expression of IL-8 only in oral leukoplakia without dysplasia in comparison with NOM. Salivary concentrations of all evaluated cytokines were significantly higher in patients with OSCC than in controls. Moreover, levels of IL-8 were significantly higher in saliva of patients with OPMDs with dysplasia as compared to controls and in OSCC patients as compared to patients with dysplastic lesions. There was also significant increase in salivary concentrations of IL-6, IL-8 and TNF-α in patients with OSCC as compared to patients with OPMDs without dysplasia. Conclusion: The study confirmed that proinflammatory, NF-kappaB dependent cytokines are involved in pathogenesis of OPMDs and OSCC. The most important biomarker of malignant transformation process within oral mucosa among all assessed cytokines seems to be IL-8. Further studies on a larger sample size are needed to corroborate these results.
Development and Validation of a Quick Sepsis-Related Organ Failure Assessment-Based Machine-Learning Model for Mortality Prediction in Patients with Suspected Infection in the Emergency Department
Authors: Kwon Young Suk , Baek Moon Seong
Published: March 2020

The quick sepsis-related organ failure assessment (qSOFA) score has been introduced to predict the likelihood of organ dysfunction in patients with suspected infection. We hypothesized that machine-learning models using qSOFA variables for predicting three-day mortality would provide better accuracy than the qSOFA score in the emergency department (ED). Between January 2016 and December 2018, the medical records of patients aged over 18 years with suspected infection were retrospectively obtained from four EDs in Korea. Data from three hospitals (n = 19,353) were used as training-validation datasets and data from one (n = 4234) as the test dataset. Machine-learning algorithms including extreme gradient boosting, light gradient boosting machine, and random forest were used. We assessed the prediction ability of machine-learning models using the area under the receiver operating characteristic (AUROC) curve, and DeLong’s test was used to compare AUROCs between the qSOFA scores and qSOFA-based machine-learning models. A total of 447,926 patients visited EDs during the study period. We analyzed 23,587 patients with suspected infection who were admitted to the EDs. The median age of the patients was 63 years (interquartile range: 43–78 years) and in-hospital mortality was 4.0% (n = 941). For predicting three-day mortality among patients with suspected infection in the ED, the AUROC of the qSOFA-based machine-learning model (0.86 [95% CI 0.85–0.87]) for three -day mortality was higher than that of the qSOFA scores (0.78 [95% CI 0.77–0.79], p < 0.001). For predicting three-day mortality in patients with suspected infection in the ED, the qSOFA-based machine-learning model was found to be superior to the conventional qSOFA scores.
Damage-Associated Molecular Patterns and Th-Cell-Related Cytokines Released after Progressive Effort
Authors: Kostrzewa-Nowak Dorota , Ciechanowicz Andrzej , Clark Jeremy S.C. , Nowak Robert
Published: March 2020

Inflammation-induced processes commence with the activation of signalling pathways at the cellular level, which mobilize inflammatory cells and stimulate the secretion of chemokines, cytokines, and damage-associated molecular pattern molecules (DAMPs). Physical effort stimulates inflammation, contributing to muscle repair and regeneration. We have examined the impact of different protocols of progressive-effort tests on T-cell DAMP levels, extracellular cleavage products (fibronectin and hyaluronan), and Th-cell-related cytokine levels among soccer players. Thirty male soccer players with a median age of 17 (16–22) years performed different defined protocols for progressive exercise until exhaustion: (1) YO-YO intermittent recovery test level 1 (YYRL1, n = 10); (2) maximal multistage 20 m shuttle run (Beep, n = 10); and mechanical treadmill (MT, n = 10); and (3) shuttle-run test (n = 10). Blood samples were taken three times as follows: at baseline, post effort, and in recovery. Significantly higher post-effort concentrations of IL-4, IL-6, IL-10, and IFN-γ were observed in the Beep group, IL-4 in the YYRL1 group, and IL-6 and IFN-γ in the MT group as compared with the baseline values. Recovery values were significantly higher for concentrations of IL-4, IL-10, and IFN-γ in the YYRL1 group, only for IFN-γ in the Beep group, and for IL-6, IL-10, and INF-γ in the MT group as compared with the baseline values. Post-effort concentrations of DEFβ2, Hsp27, Fn, and UA in the Beep group and Hsp27 and HA in the YYRL1 group were significantly higher as compared with the baseline values. It seems the performed efficiency test protocols caused a short-term imbalance in Th1/Th2 cytokine levels without giving common molecular patterns. The rapidity of these changes was apparently related to specific physical movements and the type of running surface.